PKE?dPhrefs.MYD g||7pGiatti, L. L. Rocha, A. A. de Toledo, R. F. Barreira, L. P. Rios, L. Pelicioni, M. C. Mutti, L. V. Cutolo, S. A.2007[Sanitary and socio-environmental conditions in the Iauarete indigenous area, Sao Gabriel da Cachoeira, Amazonas State, Brazil]1711-23Cien Saude Colet126 2008/09/25_Brazil *Environment Humans *Indians, South American Sanitation/*standards Socioeconomic FactorsNov-Dec!OBJECTIVE: To describe sanitary, social and environmental conditions that are significant for health of residents in the Iauarete Indigenous Area in Brazilian Amazonia, notable for its population concentration. METHOD: Qualitative and quantitative methodologies were used, with the action research method deployed mainly for qualitative approaches, through community meetings with tribespeople and researchers in the villages constituting the hub of the Area. Talking maps were prepared and interviews were conducted, together with studies of solid wastes disposal techniques, in addition to locating, sampling and analyzing the quality of water used for human consumption, in parallel to the use of geo-referencing techniques. RESULTS: Of the 65 water samples analyzed, 89.2% presented fecal coliforms, with no adequate sanitary solutions found for the disposal of solid wastes. From the public health standpoint, the sanitary practices of these indigenous peoples caused concern, clashing with their own relative knowledge. CONCLUSIONS: The specific set of problems associated with the way of life imposed by mainstream society requires the implementation of joint activities in the infra-structure and health education fields in order to solve collective health issues, stressing local community participation.+http://www.ncbi.nlm.nih.gov/pubmed/18813507<Giatti, Leandro Luiz Rocha, Aristides Almeida de Toledo, Renata Ferraz Barreira, Luciana Pranzetti Rios, Leonardo Pelicioni, Maria Cecilia Focesi Mutti, Luciane Viero Cutolo, Silvana Audra English Abstract Research Support, Non-U.S. Gov't Brazil Ciencia & saude coletiva Cien Saude Colet. 2007 Nov-Dec;12(6):1711-23.*1678-4561 (Electronic) 1413-8123 (Linking)18813507bCondicoes sanitarias e socioambientais em Iauarete, area indigena em Sao Gabriel da Cachoeira, AM.jCentro de Pesquisa Leonidas e Maria Deane, Fiocruz/Amazonia, Manaus, AM. leandrogiatti@amazonia.fiocruz.brS1413-81232007000600032 [pii]por||7"Scalabrino, G. Veber, D. Mutti, E.20076New pathogenesis of the cobalamin-deficient neuropathy9-18 Med Secoli191 2008/05/02Anemia, Pernicious/*etiology/history Animals History, 19th Century History, 20th Century Humans London Vitamin B 12 Deficiency/*complications/historySubacute combined degeneration (SCD) is considered the neurological counterpart of pernicious anaemia because it is the paradigmatic neurological manifestation of acquired vitamin B12 (cobalamin (Cbl)) deficiency in adulthood. Hitherto, the theories advanced to explain the pathogenesis of SCD have postulated a causal relationship between SCD lesions and the impairment of either or both of two Cbl-dependent reactions. We have identified a new experimental model, the totally gastrectomised (TGX) rat, to reproduce the key morphological features of the disease, and found new mechanisms responsible for the pathogenesis of SCD. We have demonstrated that the neuropathological lesions in TGX rats are not only due to mere vitamin withdrawal but also to the overproduction of the myelinolytic tumour necrosis factor (TNF)-alpha, nerve growth factor, the soluble(s) CD40:sCD40 ligand dyad, and the reduced synthesis of the neurotrophic agents, epidermal growth factor and interleukin-6. Cbl replacement treatments normalised all of these abnormalities.+http://www.ncbi.nlm.nih.gov/pubmed/18447164zScalabrino, Giuseppe Veber, Daniela Mutti, Elena Historical Article Italy Medicina nei secoli Med Secoli. 2007;19(1):9-18.0394-9001 (Print)18447164vInstitute of General Pathology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Milano, I.eng||7oPira, E. Discalzi, G. Manzari, M. Turbiglio, M. Apostoli, P. Mutti, A. Corradi, M. Giachino, G. M. Iavicoli, S.2007[Guidelines for the health surveillance of subjects exposed to carcinogenic and mutagenic agents at the workplace. First review]11-53G Ital Med Lav Ergon293 Suppl 2008/04/24=*Carcinogens Chromosome Aberrations Humans Lung Neoplasms/diagnosis/etiology Micronucleus Tests Mutagens/*adverse effects Neoplasms/blood/*diagnosis/etiology Occupational Diseases/blood/*diagnosis/etiology Occupational Exposure/*adverse effects *Population Surveillance Risk Assessment Tumor Markers, Biological/blood+http://www.ncbi.nlm.nih.gov/pubmed/18429364QPira, Enrico Discalzi, Gianluigi Manzari, Marco Turbiglio, Marco Apostoli, Pietro Mutti, Antonio Corradi, Massimo Giachino, Gian Mario Iavicoli, Sergio Societa Italiana di Medicina del Lavoro e Igiene Industriale Practice Guideline Italy Giornale italiano di medicina del lavoro ed ergonomia G Ital Med Lav Ergon. 2007;29(3 Suppl):11-53.%1592-7830 (Print) 1592-7830 (Linking)18429364Linee guida per la sorveglianza sanitaria degli esposti ad agenti cancerogeni e mutageni in ambiente di lavoro. Prima revisione.*Medicina del Lavoro, Universita di Torino.ita b||7Foddis, R. Vivaldi, A. Filiberti, R. Puntoni, R. Mutti, L. Ambrosino, N. Chella, A. Guglielmi, G. Gattini, V. Buselli, R. Perretta, S. Cristaudo, A.2007E[Serum mesothelin dosages in follow-up of previously exposed workers]342-5G Ital Med Lav Ergon293 Suppl 2008/04/16Adult Aged Asbestos/*adverse effects Female Follow-Up Studies GPI-Linked Proteins Humans Male Membrane Glycoproteins/*blood Mesothelioma/blood/diagnosis/etiology Middle Aged Occupational Exposure/*analysis Prospective StudiesJul-SepHigh dosages of Serum Mesothelin have been demonstrated to be significantly associated to Pleural Malignant Mesothelioma. We recently demonstrated that Serum Mesothelin may be clinically helpful both for diagnostic and prognostic purposes, with the best cut-off corresponding to 1 nM. We also discovered that high levels of Serum Mesothelin are significantly associated to Lung Cancer. The usefulness of this marker in secondary prevention has been suggested, though never demonstrated. We therefore started a long-term prospective cohort study including previously asbestos-exposed workers. These subjects periodically underwent both radiological tests and serum mesothelin dosages. As a mid-term goal of this longitudinal study we decided to check the variability of mesothelin dosages, comparing baseline and follow-up values, as well as the possible correlation with age, duration of exposure, smoking, any abnormality of respiratory functional tests (RFT) and/or radiological tests. At baseline, Mesothelin mean value was 0.66 +/- 0.4 (range 0.08-2.2 nM). Both age (p = 0.04) and abnormal thoracic TC (p = 0.04) were significantly correlated with increased serum mesothelin levels and increasing age. No association was found between baseline mesothelin levels and duration of asbestos exposure (p = 0.5), smoking habits (p = 0.2), abnormal RFT, DLCO (carbon monoxide diffusing capacity) or thoracic X-ray. No significant variation was observed between mesothelin values at baseline and at follow-up (p = 0.2).+http://www.ncbi.nlm.nih.gov/pubmed/18409716 Foddis, R Vivaldi, A Filiberti, R Puntoni, R Mutti, L Ambrosino, N Chella, A Guglielmi, G Gattini, V Buselli, R Perretta, S Cristaudo, A English Abstract Italy Giornale italiano di medicina del lavoro ed ergonomia G Ital Med Lav Ergon. 2007 Jul-Sep;29(3 Suppl):342-5.%1592-7830 (Print) 1592-7830 (Linking)18409716XIl dosaggio della mesotelina sierica nel follow-up dei lavoratori ex esposti ad amianto.Dipartimento di Endocrinologia e Metabolismo, Ortopedia e Traumatologia, Medicina del Lavoro, Universita di Pisa. r.foddis@med.unipi.itita #||7Simonini, S. Foddis, R. Filiberti, R. Puntoni, R. Mutti, L. Ambrosino, N. Chella, A. Guglielmi, G. Buselli, R. Iuzzolini, M. Mignani, A. Ottenga, F. Cristaudo, A.2007\[Evaluation of a series of serum mesothelin in patients with pleural malignant mesothelioma]339-42G Ital Med Lav Ergon293 Suppl 2008/04/16Aged Female GPI-Linked Proteins Humans Male Membrane Glycoproteins/*blood Mesothelioma/*blood Middle Aged Pleural Neoplasms/*bloodJul-SepPleural Malignant Mesothelioma (MM) is a highly aggressive neoplasm with a poor survival rate, hard diagnosis and treatment. The incidence of MM in Western Europe countries is expected to increase drammatically in the next 10-15 years. In spite of this drammatic scenario, at this time the only instruments for screening and early diagnosis are based on radiological tests with evident ethical and economical problems. For this reason, some authors are evaluating biological indicators with the significance of screening and early diagnosis markers. One of the most promising marker is serum mesothelin (SMRP). SMRP levels appeares to be significantly related to MM and its clinical (diagnostic/prognostic) usefulnes has been suggested. The purpose of this research is to show SMRP trend in relation both to the course of the disease and the response to therapies in some Epithelioid MM patients. The analysis of SMRP levels in these patients suggests that it may be a useful marker for monitoring the response to treatment. In fact, it was observed that SMRP increases in patients who did not respond to therapy, it tends to remain stable when therapies results into a clinical stabilization, while it decreases after surgical procedure and in case of clinical improvement.+http://www.ncbi.nlm.nih.gov/pubmed/18409715Simonini, S Foddis, R Filiberti, R Puntoni, R Mutti, L Ambrosino, N Chella, A Guglielmi, G Buselli, R Iuzzolini, M Mignani, A Ottenga, F Cristaudo, A English Abstract Italy Giornale italiano di medicina del lavoro ed ergonomia G Ital Med Lav Ergon. 2007 Jul-Sep;29(3 Suppl):339-42.%1592-7830 (Print) 1592-7830 (Linking)18409715mValutazione di dosaggi seriati di mesotelina sierica in pazienti affetti da mesotelioma maligno della pleura.OU.O. Medicina Preventiva del Lavoro, Azienda Ospedeliero- Universitaria Pisana.ita||7IGoldoni, M. Caglieri, A. Poli, D. Vettori, M. V. Ceccatelli, S. Mutti, A.2008~Methylmercury at low doses modulates the toxicity of PCB153 on PC12 neuronal cell line in asynchronous combination experiments808-11Food Chem Toxicol462 2007/11/06Animals Cell Survival Dose-Response Relationship, Drug Drug Antagonism Drug Combinations Food Contamination Methylmercury Compounds/administration & dosage/*toxicity PC12 Cells/*drug effects/metabolism Polychlorinated Biphenyls/*toxicity RatsFeb*Me-Hg and PCB153 are known neurotoxic contaminants which tend to accumulate in food, particularly in fish. Aim of this study was to perform asynchronous and combined exposure to Me-Hg and PCB153 in a neuronal rat cell line (PC12) to better characterise the antagonism observed at some combination concentrations. PC12 cells were treated with three concentrations of Me-Hg (0.1-0.5-1.0 microM) and PCB153 at one concentration (175 microM) in single and combined asynchronous exposures, using viability (MTT assay) as end-point. At all concentrations used, a statistically significant antagonistic effect was observed when Me-Hg preceded PCB153 exposure, while effect was additive when PCB153 preceded Me-Hg exposure. The antagonism is particularly evident at low concentrations of Me-Hg (0.1 microM). In conclusion, combined asynchronous exposure showed that whereas Me-Hg can modulate PCB153 toxicity, the opposite seems not to be true. Therefore, the use of asynchronous exposure could be a promising approach to study the mechanisms of toxicity of binary mixtures.+http://www.ncbi.nlm.nih.gov/pubmed/17980472$Goldoni, M Caglieri, A Poli, D Vettori, M V Ceccatelli, S Mutti, A Research Support, Non-U.S. Gov't England Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association Food Chem Toxicol. 2008 Feb;46(2):808-11. Epub 2007 Sep 29.%0278-6915 (Print) 0278-6915 (Linking)17980472Laboratory of Industrial Toxicology, Department of Clinical Medicine, Nephrology and Health Sciences, University of Parma, Via Gramsci 14, 43100 Parma, Italy. matteo.goldoni@nemo.unipr.it5S0278-6915(07)00442-5 [pii] 10.1016/j.fct.2007.09.104eng O||7Sartore-Bianchi, A. Gasparri, F. Galvani, A. Nici, L. Darnowski, J. W. Barbone, D. Fennell, D. A. Gaudino, G. Porta, C. Mutti, L.2007lBortezomib inhibits nuclear factor-kappaB dependent survival and has potent in vivo activity in mesothelioma5942-51Clin Cancer Res1319 2007/10/03Animals Antineoplastic Agents/pharmacology Boronic Acids/*pharmacology Cell Line, Tumor Cell Survival Cell Transformation, Neoplastic Enzyme Inhibitors/pharmacology Humans Male Mesothelioma/*drug therapy/*metabolism Mice Mice, Nude NF-kappa B/*metabolism Nitriles/pharmacology Proteasome Endopeptidase Complex/antagonists & inhibitors Pyrazines/*pharmacology Sulfones/pharmacology Tumor Necrosis Factor-alpha/metabolismOct 1PURPOSE: Purpose of this study has been the assessment of nuclear factor-kappaB (NF-kappaB) as a survival factor in human mesothelial cells (HMC), transformed HMC and malignant mesothelioma (MMe) cells. We aimed at verifying whether the proteasome inhibitor Bortezomib could abrogate NF-kappaB activity in MMe cells, leading to tumor cell death and may be established as a novel treatment for this aggressive neoplasm. EXPERIMENTAL DESIGN: In HMC and MMe cells, NF-kappaB nuclear translocation and DNA binding were studied by electrophoretic mobility shift assay, following treatment with tumor necrosis factor-alpha (TNF-alpha). The IKK inhibitor Bay11-7082 was also tested to evaluate its effects on HMC, transformed HMC, and MMe cell viability upon exposure to asbestos fibers. Following Bortezomib treatment, cytotoxicity of MMe cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, whereas apoptosis and cell-cycle blockade were investigated by high-content analysis. Bortezomib was also given to mice bearing i.p. xenografts of MMe cells, and its effects on tumor growth were evaluated. RESULTS: Here, we show that NF-kappaB activity is a constitutive survival factor in transformed HMC, MMe cells, and acts as a survival factor in HMC exposed to asbestos fibers. Bortezomib inhibits NF-kappaB activity in MMe cells and induces cell cycle blockade and apoptosis in vitro as well as tumor growth inhibition in vivo. CONCLUSIONS: Inhibition of NF-kappaB constitutive activation in MMe cells by Bortezomib resulted in in vitro cytotoxicity along with apoptosis and in vivo tumor regression. Our results support the use of Bortezomib in the treatment of MMe and has led to a phase II clinical trial currently enrolling in Europe.+http://www.ncbi.nlm.nih.gov/pubmed/17908991_Sartore-Bianchi, Andrea Gasparri, Fabio Galvani, Arturo Nici, Linda Darnowski, James W Barbone, Dario Fennell, Dean A Gaudino, Giovanni Porta, Camillo Mutti, Luciano Research Support, Non-U.S. Gov't United States Clinical cancer research : an official journal of the American Association for Cancer Research Clin Cancer Res. 2007 Oct 1;13(19):5942-51.%1078-0432 (Print) 1078-0432 (Linking)17908991Institute of Internal Medicine and Medical Oncology, IRCCS Policlinico San Matteo University Hospital, 1-27100 Pavia [corrected] Italy..13/19/5942 [pii] 10.1158/1078-0432.CCR-07-0536eng ||7Balbi, B. Pignatti, P. Corradi, M. Baiardi, P. Bianchi, L. Brunetti, G. Radaeli, A. Moscato, G. Mutti, A. Spanevello, A. Malerba, M.2007mBronchoalveolar lavage, sputum and exhaled clinically relevant inflammatory markers: values in healthy adults769-81 Eur Respir J304 2007/10/02Adolescent Adult Aged Aged, 80 and over Biological Markers/metabolism Breath Tests *Bronchoalveolar Lavage *Exhalation Female Humans Inflammation/*metabolism Male Middle Aged Nitric Oxide/metabolism Reference Values Sputum/*metabolismOctBronchoalveolar lavage (BAL), induced sputum and exhaled breath markers (exhaled nitric oxide and exhaled breath condensate) can each provide biological insights into the pathogenesis of respiratory disorders. Some of their biomarkers are also employed in the clinical management of patients with various respiratory diseases. In the clinical context, however, defining normal values and cut-off points is crucial. The aim of the present review is to investigate to what extent the issue of defining normal values in healthy adults has been pursued for the biomarkers with clinical value. The current authors reviewed data from literature that specifically addressed the issue of normal values from healthy adults for the four methodologies. Most studies have been performed for BAL (n = 9), sputum (n = 3) and nitric oxide (n = 3). There are no published studies for breath condensate, none of whose markers yet has clinical value. In healthy adult nonsmokers the cut-off points (mean+2sd) for biomarkers with clinical value were as follows. BAL: 16.7% lymphocytes, 2.3% neutrophils and 1.9% eosinophils; sputum: 7.7 x 10(6).mL(-1) total cell count and 2.2% eosinophils; nitric oxide: 20.2 ppb. The methodologies differ concerning the quantity and characteristics of available reference data. Studies focusing on obtaining reference values from healthy individuals are still required, more evidently for the new, noninvasive methodologies.+http://www.ncbi.nlm.nih.gov/pubmed/17906085!Balbi, B Pignatti, P Corradi, M Baiardi, P Bianchi, L Brunetti, G Radaeli, A Moscato, G Mutti, A Spanevello, A Malerba, M Review Switzerland The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology Eur Respir J. 2007 Oct;30(4):769-81.%0903-1936 (Print) 0903-1936 (Linking)17906085rDivision of Pneumology, Fondazione Salvatore Maugeri, IRCCS, Via Revislate 13, 28010, Veruno, Italy. bbalbi@fsm.it(30/4/769 [pii] 10.1183/09031936.00112306eng ||7 Ugolini, D. Neri, M. Ceppi, M. Cesario, A. Dianzani, I. Filiberti, R. Gemignani, F. Landi, S. Magnani, C. Mutti, L. Puntoni, R. Bonassi, S.2008oGenetic susceptibility to malignant mesothelioma and exposure to asbestos: the influence of the familial factor162-71 Mutat Res6583 2007/10/02Asbestos/*adverse effects Disease Outbreaks Environmental Exposure/adverse effects Family Family Health *Genetic Predisposition to Disease Humans Italy/epidemiology Mesothelioma/epidemiology/*etiology/*genetics Neoplasms/geneticsMar-AprBACKGROUND: Asbestos is the principal etiological factor of malignant mesothelioma (MM), accounting for more than 80% of all tumor cases. However, other co-factors, including genetic susceptibility may play a role in the etiology of this disease, possibly modulating the effects of exposure to asbestos and other carcinogenic mineral fibers. The frequent report of familial clustering was the first indication supporting the involvement of genetic factors. Therefore, we performed an extensive literature search to evaluate existing studies reporting familial cases of MM. METHODS: Published reports addressing the issue of familial susceptibility to MM have been searched through PubMed using keywords and free text tools. Eighty-two citations were retrieved and 20 of them actually reported a familial cluster of MM. Three more articles were identified through the references. The probability that the observed familial clusters of mesothelioma could have randomly occurred in exposed families was evaluated with the Family History Score Zi (FHSi). RESULTS: The result of this analysis suggested that clustering of MM cases in families exposed to asbestos may be explained with the additional contribution of other familial factors. The FHSi allowed to reject the hypothesis of random occurrence of these clusters with a probability of a first type error ranging between 1 per cent and 1 per billion. CONCLUSIONS: The evaluation of the published materials supports the hypothesis that - although familial clustering of MM is largely attributable to shared asbestos exposure - the additional contribution of factors dealing with genetic susceptibility may play a role in the etiology of MM.+http://www.ncbi.nlm.nih.gov/pubmed/17904414IUgolini, Donatella Neri, Monica Ceppi, Marcello Cesario, Alfredo Dianzani, Irma Filiberti, Rosangela Gemignani, Federica Landi, Stefano Magnani, Corrado Mutti, Luciano Puntoni, Riccardo Bonassi, Stefano Research Support, Non-U.S. Gov't Review Netherlands Mutation research Mutat Res. 2008 Mar-Apr;658(3):162-71. Epub 2007 Aug 10.%0027-5107 (Print) 0027-5107 (Linking)17904414RDipartimento di Oncologia, Biologia e Genetica, University of Genoa, Genoa, Italy.7S1383-5742(07)00029-4 [pii] 10.1016/j.mrrev.2007.08.001eng+||7 -Savenkov, S. N. Sydoruk, O. I. Muttiah, R. S.2007eEigenanalysis of dichroic, birefringent, and degenerate polarization elements: a Jones-calculus study6700-9Appl Opt4627 2007/09/21Sep 20A theoretical analysis of eigenpolarizations and eigenvalues pertaining to the Jones matrices of dichroic, birefringent, and degenerate polarization elements is presented. The analysis is carried out employing a general model of a polarization element. Expressions for the corresponding polarization elements are derived and analyzed. It is shown that, despite the presence of birefringence, a polarization element can, in a general case, demonstrate a totally dichroic behavior. Moreover, it is proved that birefringence necessarily accompanies dichroic elements with orthogonal eigenpolarizations. A transition between degenerate, dichroic, and birefringent eigenvalues is studied, and examples of synthesis of polarization elements are given.+http://www.ncbi.nlm.nih.gov/pubmed/17882290ySavenkov, Sergey N Sydoruk, Oleksiy I Muttiah, Ranjan S United States Applied optics Appl Opt. 2007 Sep 20;46(27):6700-9.%0003-6935 (Print) 0003-6935 (Linking)17882290lDepartment of Radiophysics, Taras Shevchenko Kiev National University, 01033 Kiev, Ukraine. sns@univ.kiev.ua 141252 [pii]engA||7 #Fennell, D. A. Chacko, A. Mutti, L.2008BBCL-2 family regulation by the 20S proteasome inhibitor bortezomib1189-97Oncogene279 2007/09/11AAnimals Boronic Acids/*pharmacology Gene Expression Regulation, Enzymologic/*drug effects Humans Multigene Family/*drug effects Protease Inhibitors/*pharmacology Proteasome Endopeptidase Complex/*antagonists & inhibitors/physiology Proto-Oncogene Proteins c-bcl-2/biosynthesis/*genetics/physiology Pyrazines/*pharmacologyFeb 21Bortezomib (Velcade, PS341) was licensed in 2003 as a first-in-class 20S proteasome inhibitor indicated for treatment of multiple myeloma, and is currently being evaluated clinically in a range of solid tumours. The mechanisms underlying its cancer cell toxicity are complex. A growing body of evidence suggests proteasome inhibition-dependent regulation of the BCL-2 family is a critical requirement. In particular, the stabilization of BH3-only proteins BIK, NOXA and BIM, appear to be essential for effecting BAX- and BAK-dependent cell death. These mechanisms are reviewed and the implications for favourable novel drug interactions are highlighted.+http://www.ncbi.nlm.nih.gov/pubmed/17828309Fennell, D A Chacko, A Mutti, L Research Support, Non-U.S. Gov't Review England Oncogene Oncogene. 2008 Feb 21;27(9):1189-97. Epub 2007 Sep 10.*1476-5594 (Electronic) 0950-9232 (Linking)17828309Thoracic Oncology Research Group, Centre for Cancer Research and Cell Biology, Queen's University Belfast, Northern Ireland, UK. d.fennell@qub.ac.uk$1210744 [pii] 10.1038/sj.onc.1210744eng 5||7 Cristaudo, A. Foddis, R. Vivaldi, A. Guglielmi, G. Dipalma, N. Filiberti, R. Neri, M. Ceppi, M. Paganuzzi, M. Ivaldi, G. P. Mencoboni, M. Canessa, P. A. Ambrosino, N. Chella, A. Mutti, L. Puntoni, R.2007WClinical significance of serum mesothelin in patients with mesothelioma and lung cancer5076-81Clin Cancer Res1317 2007/09/06Aged Female GPI-Linked Proteins Humans Lung Neoplasms/*blood/mortality Male Membrane Glycoproteins/*blood Mesothelioma/*blood/mortality Middle Aged Prognosis Respiratory Tract Diseases/bloodSep 1.PURPOSE: High levels of serum-soluble mesothelin family proteins (SMRP) have been found to be associated with malignant mesothelioma (MM), but not lung cancer (LC). To verify the clinical role of this marker for both these tumors, we tested serum SMRP in the largest population of thoracic cancers ever assembled. EXPERIMENTAL DESIGN: SMRP blood concentrations were measured in 107 patients with MM, 215 patients with LC, 130 patients with benign respiratory diseases (BRD), and 262 controls. Statistical comparison between mean serum SMRP levels in all groups was done and receiver operating characteristic curves were constructed to evaluate the performance of this marker. RESULTS: SMRP levels were significantly higher in patients with MM and LC than in patients with benign respiratory diseases and controls (P < 0.001). The area under the receiver operating characteristic curve for serum SMRP discriminating MM and controls was 0.77 (95% confidence interval, 0.71-0.83), with a best cutoff of 1.00 nmol/L (sensitivity, 68.2%; specificity, 80.5%). In both MM and LC, serum SMRP levels did not differ significantly between early and late stages. High SMRP levels proved to be an independent negative prognostic factor in patients with MM. CONCLUSIONS: Our data confirm that serum SMRP is a promising marker for the diagnosis, prognosis, and clinical monitoring of MM. We found that serum SMRP dosage may prove helpful in LC diagnosis as well. These data may also have positive repercussions on secondary preventive medical strategies for workers previously exposed to asbestos.+http://www.ncbi.nlm.nih.gov/pubmed/17785560Cristaudo, Alfonso Foddis, Rudy Vivaldi, Agnese Guglielmi, Giovanni Dipalma, Nicola Filiberti, Rosangela Neri, Monica Ceppi, Marcello Paganuzzi, Michela Ivaldi, Gian Paolo Mencoboni, Manlio Canessa, Pier Aldo Ambrosino, Nicolino Chella, Antonio Mutti, Luciano Puntoni, Riccardo Research Support, Non-U.S. Gov't United States Clinical cancer research : an official journal of the American Association for Cancer Research Clin Cancer Res. 2007 Sep 1;13(17):5076-81.%1078-0432 (Print) 1078-0432 (Linking)17785560eDepartment of Endocrinology and Metabolism, University of Pisa, Pisa, Italy. a.cristaudo@med.unipi.it.13/17/5076 [pii] 10.1158/1078-0432.CCR-07-0629eng ||7 PGoldoni, M. Caglieri, A. Corradi, M. Poli, D. Rusca, M. Carbognani, P. Mutti, A.2008aChromium in exhaled breath condensate and pulmonary tissue of non-small cell lung cancer patients487-93Int Arch Occup Environ Health814 2007/08/29Aged Biological Markers Breath Tests Carcinoma, Non-Small-Cell Lung/*metabolism Chromium/*metabolism Female Humans Lung/*chemistry Lung Neoplasms/*metabolism Male Middle AgedFebOBJECTIVE: Chromium in exhaled breath condensate (EBC) has recently been proposed as a biomarker of pulmonary exposure. The aim of this study was to measure the Cr levels in the EBC and pulmonary tissue of patients with early, operable non-small cell lung cancer (NSCLC) who had not been occupationally exposed to Cr before and after tumour resection and to correlate Cr in lung tissue with that in EBC. METHODS: Cr levels in the EBC and pulmonary tissue of 20 NSCLC patients were measured by means of electrothermal atomic absorption before and after tumour resection. Cr levels were also measured in the urine of 15 of these patients. RESULTS: The pre-surgery EBC Cr levels of the NSCLC patients were not different from those of the controls, but both EBC and urinary Cr levels increased after surgery. There was a significant correlation between Cr levels in EBC and pulmonary tissue (R = 0.55, P = 0.01), but not between these and urinary Cr levels. CONCLUSION: Cr levels in EBC and urine of NSCLC patients were increased after surgical intervention. Measured Cr EBC levels were by one order of magnitude lower than those observed in moderately exposed workers. This fact, together with the correlation between Cr in EBC and in pulmonary tissue, confirms that EBC is a promising biological fluid to test pulmonary exposure to Cr, giving complementary information to that provided by urinary Cr, not correlated with EBC and tissue.+http://www.ncbi.nlm.nih.gov/pubmed/17724608nGoldoni, Matteo Caglieri, Andrea Corradi, Massimo Poli, Diana Rusca, Michele Carbognani, Paolo Mutti, Antonio R01 HL72323/HL/NHLBI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Germany International archives of occupational and environmental health Int Arch Occup Environ Health. 2008 Feb;81(4):487-93. Epub 2007 Aug 28.%0340-0131 (Print) 0340-0131 (Linking)17724608Laboratory of Industrial Toxicology, Department of Clinical Medicine, Nephrology and Health Sciences, University of Parma, Via Gramsci 14, 43100 Parma, Italy.10.1007/s00420-007-0242-8eng ||7?Muttil, P. Kaur, J. Kumar, K. Yadav, A. B. Sharma, R. Misra, A.2007LInhalable microparticles containing large payload of anti-tuberculosis drugs140-50Eur J Pharm Sci322 2007/08/08Administration, Inhalation Animals Antitubercular Agents/*administration & dosage/blood/pharmacokinetics Calorimetry, Differential Scanning Chromatography, High Pressure Liquid Cytosol/metabolism Desiccation Drug Compounding Flow Cytometry Hydrogen-Ion Concentration Isoniazid/administration & dosage/blood/pharmacokinetics Macrophages, Alveolar/metabolism Mice Nanoparticles/*administration & dosage Particle Size Phagocytosis Rifabutin/administration & dosage/blood/pharmacokinetics Solubility TabletsOctMicroparticles containing large payloads of two anti-tuberculosis (TB) drugs were prepared and evaluated for suitability as a dry powder inhalation targeting alveolar macrophages. A solution containing one part each of isoniazid and rifabutin, plus two parts poly(lactic acid) (L-PLA) was spray-dried. Drug content and in vitro release were assayed by HPLC, and DSC was used to elucidate release behaviour. Particle size was measured by laser scattering and aerosol characteristics by cascade impaction using a Lovelace impactor. Microparticles were administered to mice using an in-house inhalation apparatus or by intra-tracheal instillation. Drugs in solution were administered orally and by intra-cardiac injection. Flow cytometry and HPLC were used to investigate the specificity and magnitude of targeting macrophages. Microparticles having drug content approximately 50% (w/w), particle size approximately 5 microm and satisfactory aerosol characteristics (median mass aerodynamic diameter, MMAD=3.57 microm; geometric standard deviation, GSD=1.41 microm; fine particle fraction, FPF(<4.6 microm)=78.91+/-8.4%) were obtained in yields of >60%. About 70% of the payload was released in vitro in 10 days. Microparticles targeted macrophages and not epithelial cells on inhalation. Drug concentrations in macrophages were approximately 20 times higher when microparticles were inhaled rather than drug solutions administered. Microparticles were thus deemed suitable for enhanced targeted drug delivery to lung macrophages.+http://www.ncbi.nlm.nih.gov/pubmed/17681458Muttil, Pavan Kaur, Jatinder Kumar, Kaushlendra Yadav, Awadh Bihari Sharma, Rolee Misra, Amit Netherlands European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences Eur J Pharm Sci. 2007 Oct;32(2):140-50. Epub 2007 Jul 4.%0928-0987 (Print) 0928-0987 (Linking)17681458OPharmaceutics Division, Central Drug Research Institute, Lucknow 226001, India.6S0928-0987(07)00264-3 [pii] 10.1016/j.ejps.2007.06.006eng ~t7\Mutti, D. O. Cooper, M. E. O'Brien, S. Jones, L. A. Marazita, M. L. Murray, J. C. Zadnik, K.2007+Candidate gene and locus analysis of myopia1012-9Mol Vis13 2007/07/27Alleles Brain-Derived Neurotrophic Factor/genetics Child *Chromosome Mapping Chromosomes, Human, Pair 12 Chromosomes, Human, Pair 18 Collagen Type II/genetics Collagen Type XVIII/genetics Eye Proteins/genetics Fibroblast Growth Factor 2/genetics Genetic Linkage Homeodomain Proteins/genetics Humans Microsatellite Repeats Myopia/*genetics Paired Box Transcription Factors/genetics Polymorphism, Single Nucleotide Repressor Proteins/geneticsMPURPOSE: A previous study has reported evidence of a strong linkage, but no association, between paired box gene 6 (PAX6) and myopia. We attempted to replicate these findings and to conduct a candidate gene and locus evaluation of genetic involvement in common forms of myopia. METHODS: Samples were collected from 517 individuals in 123 families with a myopic child participating in the Orinda Longitudinal Study of Myopia or the Contact Lens and Myopia Progression Study. Myopia in the proband children was defined as -0.75 D or more and as being present in both meridians on cycloplegic autorefraction (1% tropicamide). Affected status in parents and siblings was determined by survey. After DNA was extracted from buccal mucosal cells and genotyped using assays for microsatellite markers and single nucleotide polymorphisms (SNPs), DNA was analyzed for linkage disequilibrium. Markers on chromosomes 12 and 18 were selected as regions previously associated with pathological myopia. SNPs were also analyzed in genes where their expression pattern or their association with syndromes conveys myopia as part of the phenotype (FGF2, BDNF, COL2A1, COL18A1, and PAX6). RESULTS: The SNP rs1635529 for COL2A1 on 12q13.11 showed highly significant over-transmission to affected individuals (p=0.00007). No SNP for FGF2, BDNF, COL18A1, or PAX6 showed significant over-transmission to affected individuals after correction for multiple comparisons. Markers on chromosome 12 and 18 previously associated with pathological myopia also showed no significant associations with the more common form of myopia in this study. CONCLUSIONS: As reported previously by others, PAX6 showed no association with myopia. Associations in the current analysis are suggestive of involvement of COL2A1. Future studies should focus on replication in other samples and in genome-wide approaches.+http://www.ncbi.nlm.nih.gov/pubmed/17653045LMutti, Donald O Cooper, Margaret E O'Brien, Sarah Jones, Lisa A Marazita, Mary L Murray, Jeffrey C Zadnik, Karla K23 EY00383/EY/NEI NIH HHS/United States RR03655/RR/NCRR NIH HHS/United States U10 EY08893/EY/NEI NIH HHS/United States Research Support, N.I.H., Extramural United States Molecular vision Mol Vis. 2007 Jun 28;13:1012-9.*1090-0535 (Electronic) 1090-0535 (Linking)277654017653045^College of Optometry, The Ohio State University, Columbus, OH 43210-1240, USA. mutti.2@osu.eduv13/a110 [pii]eng |t7WJones, L. A. Sinnott, L. T. Mutti, D. O. Mitchell, G. L. Moeschberger, M. L. Zadnik, K.2007LParental history of myopia, sports and outdoor activities, and future myopia3524-32Invest Ophthalmol Vis Sci488 2007/07/27Adult Child Family Health Humans *Leisure Activities Logistic Models Longitudinal Studies *Motor Activity Myopia/*epidemiology/*genetics Parents Predictive Value of Tests ROC Curve Sports/*statistics & numerical dataAugPURPOSE: To identify whether parental history of myopia and/or parent-reported children's visual activity levels can predict juvenile-onset myopia. METHODS: Survey-based data from Orinda Longitudinal Study of Myopia subjects from 1989 to 2001 were used to predict future myopia. Univariate and multiple logistic regression analyses were performed, and receiver operator characteristic (ROC) curves were generated. Differences among the areas under the ROC curves were compared using the method of multiple comparison with the best. RESULTS: Of the 514 children eligible for this analysis, 111 (21.6%) became myopic. Differences in the third grade between eventual myopes and nonmyopes were seen for the number of myopic parents (P < 0.001) and for the number of sports and outdoor activity hours per week (11.65 +/- 6.97 hours for nonmyopes vs. 7.98 +/- 6.54 hours for future myopes, P < 0.001). Analysis of the areas under the ROC curves showed three variables with a predictive value better than chance: the number of myopic parents, the number of sports and outdoor activity hours per week, and the number of reading hours per week. After controlling for sports and outdoor hours per week and parental myopia history, reading hours per week was no longer a statistically significant factor. The area under the curve for the parental myopia history and sports and outdoor activities model was 0.73. A significant interaction in the logistic model showed a differential effect of sport and outdoor activity hours per week based on a child's number of myopic parents. CONCLUSIONS: Parental history of myopia was an important predictor in univariate and multivariate models, with a differential effect of sports and outdoor activity hours per week based on the number of myopic parents. Lower amounts of sports and outdoor activity increased the odds of becoming myopic in those children with two myopic parents more than in those children with either zero or one myopic parent. The chance of becoming myopic for children with no myopic parents appears lowest in the children with the highest amount of sports and outdoor activity, compared with those with two myopic parents.+http://www.ncbi.nlm.nih.gov/pubmed/17652719Jones, Lisa A Sinnott, Loraine T Mutti, Donald O Mitchell, Gladys L Moeschberger, Melvin L Zadnik, Karla R24-EY014792/EY/NEI NIH HHS/United States U10 EY008893-17/EY/NEI NIH HHS/United States U10-EY08893/EY/NEI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2007 Aug;48(8):3524-32.%0146-0404 (Print) 0146-0404 (Linking)287140317652719dCollege of Optometry, The Ohio State University, Columbus, Ohio 43210, USA. ljones@optometry.osu.edu$48/8/3524 [pii] 10.1167/iovs.06-1118eng||7Muttitt, S. C. Alvarez, R. C.2007BChronic disease management: it's time for transformational change!43-7; discussion 68-70 Healthc Pap74 2007/06/28Canada Chronic Disease/economics/*prevention & control/*therapy *Disease Management Health Care Rationing/organization & administration Humans Information Systems/economics/*organization & administration Medical Records Systems, Computerized/organization & administration National Health Programs/economics/*organization & administration Practice Guidelines as Topic Primary Health Care/organization & administration Quality of Health Care/organization & administration;The authors of the lead essay present a compelling case for the development and implementation of a national strategy on chronic disease prevention and management (CDPM). The literature demonstrates that the Chronic Care Model can improve quality and reduce costs. Substantial evidence supports the role of health information technologies such as electronic health records (EHRs) in achieving these goals. However, an interoperable pan-Canadian health infostructure does not exist; funding is required to establish this across the continuum of care. An investment of $350 per capita would provide a robust health technology platform to support a national CDPM strategy. Such an investment would deliver annual benefits of $6-$7.6 billion; this could be leveraged to support national healthcare priorities such as CDPM. EHRs will improve decisions about care, reduce system errors and increase efficiency. They will also improve our ability to measure, assess and manage care. We cannot run a high-performing health system without sound data. This was a key step to enabling progress on wait times management. Leadership is required if a national CDPM strategy is to become reality. The authors made a convincing case for the development of a national strategy; we need to turn their words into actionable events to gain necessary momentum.+http://www.ncbi.nlm.nih.gov/pubmed/17595551rMuttitt, Sarah C Alvarez, Richard C Comment Canada HealthcarePapers Healthc Pap. 2007;7(4):43-7; discussion 68-70.%1488-917X (Print) 1488-917X (Linking)17595551/Innovation and Adoption, Canada Health Infoway.eng E||7pRigamonti, D. Bolognini, D. Mutti, C. Zuccato, C. Tartari, M. Sola, F. Valenza, M. Kazantsev, A. G. Cattaneo, E.2007Loss of huntingtin function complemented by small molecules acting as repressor element 1/neuron restrictive silencer element silencer modulators24554-62 J Biol Chem28234 2007/06/15Animals Brain-Derived Neurotrophic Factor/metabolism Cell Survival Dose-Response Relationship, Drug Enzyme-Linked Immunosorbent Assay Gene Expression Regulation Gene Silencing Immunohistochemistry Luciferases/metabolism Models, Chemical Nerve Tissue Proteins/metabolism/*physiology Neurons/metabolism Nuclear Proteins/metabolism/*physiology Peptides/chemistry Rats Transcription Factors/metabolismAug 24Increased levels of the repressor element 1/neuron restrictive silencer element (RE1/NRSE) silencing activity promoter, and a consequent reduction in the transcription of many RE1/NRSE-bearing neuronal genes, including brain-derived neurotrophic factor (BDNF), have been demonstrated in Huntington disease (HD) and represent one possible effector of its selective neuronal vulnerability. Restoring the expression levels of neuronal genes in diseased neurons therefore seems to be an attractive therapeutic approach. To this end, we have developed a cell-based reporter assay for monitoring RE1/NRSE silencing activity and validated it by genetically inactivating the RE1/NRSE or pharmacologically stimulating global transcription. In a pilot compound screen, we identified three closely related structural analogues that up-regulate reporter expression at low nanomolar concentrations, and follow-up studies have shown that they efficaciously increase endogenous BDNF levels in HD cells. Moreover, one of the compounds increases the viability of HD cells. Our findings suggest a new avenue for the development of drugs for HD and other neurodegenerative disorders based on the pharmacological up-regulation of the production of the neuronal survival factor BDNF and of other RE1/NRSE-regulated neuronal genes.+http://www.ncbi.nlm.nih.gov/pubmed/17565993'Rigamonti, Dorotea Bolognini, Daniele Mutti, Cesare Zuccato, Chiara Tartari, Marzia Sola, Francesco Valenza, Marta Kazantsev, Aleksey G Cattaneo, Elena Research Support, Non-U.S. Gov't United States The Journal of biological chemistry J Biol Chem. 2007 Aug 24;282(34):24554-62. Epub 2007 Jun 12.%0021-9258 (Print) 0021-9258 (Linking)17565993Centre for Stem Cell Research and Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, Milan 20133, Italy.'M609885200 [pii] 10.1074/jbc.M609885200engV|t7Mutti, D. O. Hayes, J. R. Mitchell, G. L. Jones, L. A. Moeschberger, M. L. Cotter, S. A. Kleinstein, R. N. Manny, R. E. Twelker, J. D. Zadnik, K.2007mRefractive error, axial length, and relative peripheral refractive error before and after the onset of myopia2510-9Invest Ophthalmol Vis Sci486 2007/05/26Adolescent Age of Onset Child Eye/*pathology/ultrasonography Female Humans Hyperopia/ethnology/physiopathology Male Models, Biological Myopia/ethnology/*physiopathology Refraction, Ocular/*physiologyJun; PURPOSE: To evaluate refractive error, axial length, and relative peripheral refractive error before, during the year of, and after the onset of myopia in children who became myopic compared with emmetropes. METHODS: Subjects were 605 children 6 to 14 years of age who became myopic (at least -0.75 D in each meridian) and 374 emmetropic (between -0.25 D and +1.00 D in each meridian at all visits) children participating between 1995 and 2003 in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study. Axial length was measured annually by A-scan ultrasonography. Relative peripheral refractive error (the difference between the spherical equivalent cycloplegic autorefraction 30 degrees in the nasal visual field and in primary gaze) was measured using either of two autorefractors (R-1; Canon, Lake Success, NY [no longer manufactured] or WR 5100-K; Grand Seiko, Hiroshima, Japan). Refractive error was measured with the same autorefractor with the subjects under cycloplegia. Each variable in children who became myopic was compared to age-, gender-, and ethnicity-matched model estimates of emmetrope values for each annual visit from 5 years before through 5 years after the onset of myopia. RESULTS: In the sample as a whole, children who became myopic had less hyperopia and longer axial lengths than did emmetropes before and after the onset of myopia (4 years before through 5 years after for refractive error and 3 years before through 5 years after for axial length; P < 0.0001 for each year). Children who became myopic had more hyperopic relative peripheral refractive errors than did emmetropes from 2 years before onset through 5 years after onset of myopia (P < 0.002 for each year). The fastest rate of change in refractive error, axial length, and relative peripheral refractive error occurred during the year before onset rather than in any year after onset. Relative peripheral refractive error remained at a consistent level of hyperopia each year after onset, whereas axial length and myopic refractive error continued to elongate and to progress, respectively, although at slower rates compared with the rate at onset. CONCLUSIONS: A more negative refractive error, longer axial length, and more hyperopic relative peripheral refractive error in addition to faster rates of change in these variables may be useful for predicting the onset of myopia, but only within a span of 2 to 4 years before onset. Becoming myopic does not appear to be characterized by a consistent rate of increase in refractive error and expansion of the globe. Acceleration in myopia progression, axial elongation, and peripheral hyperopia in the year prior to onset followed by relatively slower, more stable rates of change after onset suggests that more than one factor may influence ocular expansion during myopia onset and progression.+http://www.ncbi.nlm.nih.gov/pubmed/17525178Mutti, Donald O Hayes, John R Mitchell, G Lynn Jones, Lisa A Moeschberger, Melvin L Cotter, Susan A Kleinstein, Robert N Manny, Ruth E Twelker, J Daniel Zadnik, Karla CLEERE Study Group R24-EY014792/EY/NEI NIH HHS/United States U10 EY008893-16/EY/NEI NIH HHS/United States U10-EY08893/EY/NEI NIH HHS/United States Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2007 Jun;48(6):2510-9.%0146-0404 (Print) 0146-0404 (Linking)265771917525178[Ohio State University College of Optometry, Columbus, Ohio 43210-1240, USA. mutti.2@osu.edu$48/6/2510 [pii] 10.1167/iovs.06-0562eng %~|7fMutti, E. Veber, D. Stampachiacchiere, B. Triaca, V. Gammella, E. Tacchini, L. Aloe, L. Scalabrino, G.2007lCobalamin deficiency-induced down-regulation of p75-immunoreactive cell levels in rat central nervous system92-9 Brain Res1157 2007/05/26Animals Central Nervous System/*metabolism/physiopathology Down-Regulation/*physiology Gastrectomy/adverse effects Homocysteine/blood Immunohistochemistry Male Methylmalonic Acid/blood Nerve Fibers, Myelinated/metabolism Nerve Growth Factor/metabolism Rats Rats, Sprague-Dawley Receptor, Nerve Growth Factor/*metabolism Recovery of Function/drug effects/physiology Septal Nuclei/metabolism/physiopathology Spinal Cord/metabolism/physiopathology Vitamin B 12/*metabolism/pharmacology Vitamin B 12 Deficiency/*metabolismJul 9"We investigated immunoreactivity for p75 neurotrophin receptor (NTR) in the spinal cord white matter and septum of rats made cobalamin-deficient (Cbl-D) by means of total gastrectomy or a Cbl-D diet. Cbl deficiency down-regulates p75NTR-immunoreactive cell levels in spinal cord white matter and septum with different time courses. On the whole, the spinal cord white matter seems to be more affected in terms of p75NTR-immunoreactive cells, most of which are astrocytes. The p75NTR-immunoreactive cell levels in the spinal cord white matter and septum normalized in rats treated with Cbl (scheme b) and killed 4 months after total gastrectomy. However, Western blot analysis of p75NTR in the spinal cords of Cbl-D rats shows increased p75NTR protein levels, which are resistant to Cbl replacement. These findings demonstrate that a neurotrophic vitamin (Cbl) positively regulates the levels of a neurotrophic receptor (p75NTR) (at least in terms of immunohistochemistry) in rat central nervous system, although the underlying mechanism(s) are still unknown.+http://www.ncbi.nlm.nih.gov/pubmed/17524373Mutti, Elena Veber, Daniela Stampachiacchiere, Barbara Triaca, Viviana Gammella, Elena Tacchini, Lorenza Aloe, Luigi Scalabrino, Giuseppe Netherlands Brain research Brain Res. 2007 Jul 9;1157:92-9. Epub 2007 Apr 25.%0006-8993 (Print) 0006-8993 (Linking)17524373]Institute of General Pathology, University of Milan, Via Mangiagalli 31, 20133 Milano, Italy.:S0006-8993(07)00919-5 [pii] 10.1016/j.brainres.2007.04.055eng ||t7Dick, F. D. De Palma, G. Ahmadi, A. Osborne, A. Scott, N. W. Prescott, G. J. Bennett, J. Semple, S. Dick, S. Mozzoni, P. Haites, N. Wettinger, S. B. Mutti, A. Otelea, M. Seaton, A. Soderkvist, P. Felice, A.2007]Gene-environment interactions in parkinsonism and Parkinson's disease: the Geoparkinson study673-80Occup Environ Med6410 2007/04/24Case-Control Studies Environmental Exposure/*statistics & numerical data Europe/epidemiology Female Genetic Predisposition to Disease/*epidemiology Genotype Humans Male Odds Ratio Parkinson Disease/*epidemiology/*genetics Polymorphism, Genetic Risk Factors Sex DistributionOct`OBJECTIVES: To investigate associations of Parkinson's disease (PD) and parkinsonian syndromes with polymorphic genes that influence metabolism of either foreign chemical substances or dopamine and to seek evidence of gene-environment interaction effects that modify risk. METHODS: A case-control study of 959 prevalent cases of parkinsonism (767 with PD) and 1989 controls across five European centres. Occupational hygienists estimated the average annual intensity of exposure to solvents, pesticides and metals, (iron, copper, manganese), blind to disease status. CYP2D6, PON1, GSTM1, GSTT1, GSTM3, GSTP1, NQO1, CYP1B1, MAO-A, MAO-B, SOD 2, EPHX, DAT1, DRD2 and NAT2 were genotyped. Results were analysed using multiple logistic regression adjusting for key confounders. RESULTS: There was a modest but significant association between MAO-A polymorphism in males and disease risk (G vs T, OR 1.30, 95% CI 1.02 to 1.66, adjusted). The majority of gene-environment analyses did not show significant interaction effects. There were possible interaction effects between GSTM1 null genotype and solvent exposure (which were stronger when limited to PD cases only). CONCLUSIONS: Many small studies have reported associations between genetic polymorphisms and PD. Fewer have examined gene-environment interactions. This large study was sufficiently powered to examine these aspects. GSTM1 null subjects heavily exposed to solvents appear to be at increased risk of PD. There was insufficient evidence that the other gene-environment combinations investigated modified disease risk, suggesting they contribute little to the burden of PD.+http://www.ncbi.nlm.nih.gov/pubmed/17449559xDick, F D De Palma, G Ahmadi, A Osborne, A Scott, N W Prescott, G J Bennett, J Semple, S Dick, S Mozzoni, P Haites, N Wettinger, S Bezzina Mutti, A Otelea, M Seaton, A Soderkvist, P Felice, A Geoparkinson Study Group Multicenter Study Research Support, Non-U.S. Gov't England Occupational and environmental medicine Occup Environ Med. 2007 Oct;64(10):673-80. Epub 2007 Apr 20.*1470-7926 (Electronic) 1351-0711 (Linking)207838317449559dDepartment of Environmental and Occupational Medicine, University of Aberdeen, UK. f.dick@abdn.ac.uk-oem.2006.032078 [pii] 10.1136/oem.2006.032078eng||7RKalra, S. Ahuja, R. Mutti, E. Veber, D. Seetharam, S. Scalabrino, G. Seetharam, B.2007MCobalamin-mediated regulation of transcobalamin receptor levels in rat organs128-32Arch Biochem Biophys4631 2007/04/20Animals Caco-2 Cells Duodenum/physiology Gastrectomy Humans Intestinal Mucosa/physiology Liver/physiology Male Rats Rats, Sprague-Dawley Receptors, Cell Surface/*physiology Spinal Cord/physiology Vitamin B 12/*physiology Vitamin B 12 Deficiency/physiopathologyJul 1Total gastrectomy (TG) causes cobalamin (Cbl) deficiency followed by increases in tumor necrosis factor (TNF)-alpha levels in the spinal cord (SC) of the rat. In order to understand how Cbl deficiency may influence cell Cbl transport, we have measured by immunoblotting protein levels of the receptor for the Cbl-transcobalamin (TC) complex (TC-R) in both animal and cell models. TC-R protein levels were elevated in the total membranes of duodenal mucosa, kidneys, liver, and SC of rats made Cbl-deficient (Cbl-D) by means of TG or feeding with a Cbl-D diet. Postoperative Cbl-replacement treatment normalized the TC-R protein levels in each of the tested organs, regardless of whether this treatment was given during the first two post-TG or during the third and fourth post-TG mo. In Caco-2 cells, progressively increasing TNF-alpha concentrations supplemented to culture medium induced an up-regulation of TC-R protein levels. We provide the first evidence of the regulation of a Cbl-specific receptor by the vitamin itself in some rat organs.+http://www.ncbi.nlm.nih.gov/pubmed/17442257Kalra, Seema Ahuja, Rajiv Mutti, Elena Veber, Daniela Seetharam, Shakuntla Scalabrino, Giuseppe Seetharam, Bellur United States Archives of biochemistry and biophysics Arch Biochem Biophys. 2007 Jul 1;463(1):128-32. Epub 2007 Apr 2.%0003-9861 (Print) 0003-9861 (Linking)17442257jDepartment of Medicine, Medical College of Wisconsin, 5000 West National Avenue, Milwaukee, 53295 WI, USA.5S0003-9861(07)00121-X [pii] 10.1016/j.abb.2007.03.011eng ||7Bertino, P. Marconi, A. Palumbo, L. Bruni, B. M. Barbone, D. Germano, S. Dogan, A. U. Tassi, G. F. Porta, C. Mutti, L. Gaudino, G.2007QErionite and asbestos differently cause transformation of human mesothelial cells12-20 Int J Cancer1211 2007/03/14Asbestos/*toxicity Cell Death/drug effects Cell Transformation, Neoplastic/*chemically induced Cells, Cultured Cytotoxins/toxicity DNA/biosynthesis/genetics DNA Damage/genetics Epithelium/*drug effects/*pathology Humans Microscopy, Electron, Scanning Time Factors Zeolites/*toxicityJul 1RMalignant mesothelioma (MM) is an aggressive tumor associated with environmental or occupational exposure to asbestos fibers. Erionite is a fibrous zeolite, morphologically similar to asbestos and it is assumed to be even more carcinogenic. Onset and progression of MM has been suggested as the result of the cooperation between asbestos and other cofactors, such as SV40 virus infection. Nevertheless, several cases of MM were associated with environmental exposure to erionite in Turkey, where SV40 was never isolated in MM specimens. We show here that erionite is poorly cytotoxic, induces proliferating signals and high growth rate in human mesothelial cells (HMC). Long term exposure to erionite, but not to asbestos fibers, transforms HMC in vitro, regardless of the presence of SV40 sequences, leading to foci formation in cultured monolayers. Cells derived from foci display constitutive activation of Akt, NF-kappaB and Erk1/2, show prolonged survival and a deregulated cell cycle, involving cyclin D1 and E overexpression. Our results reveal that erionite is able per se to turn HMC into transformed highly proliferating cells and disclose the carcinogenic properties of erionite, prompting for a careful evaluation of environmental exposure to these fibers. The genetic predisposition to the effect of erionite is a separate subject for investigation.+http://www.ncbi.nlm.nih.gov/pubmed/17354240 Bertino, P Marconi, A Palumbo, L Bruni, B M Barbone, D Germano, S Dogan, A U Tassi, G F Porta, C Mutti, L Gaudino, G Research Support, Non-U.S. Gov't United States International journal of cancer. Journal international du cancer Int J Cancer. 2007 Jul 1;121(1):12-20.%0020-7136 (Print) 0020-7136 (Linking)17354240bDepartment of DISCAFF and DFB Center, University of Piemonte Orientale A. Avogadro, Novara, Italy.10.1002/ijc.22687eng |t7Dick, F. D. De Palma, G. Ahmadi, A. Scott, N. W. Prescott, G. J. Bennett, J. Semple, S. Dick, S. Counsell, C. Mozzoni, P. Haites, N. Wettinger, S. B. Mutti, A. Otelea, M. Seaton, A. Soderkvist, P. Felice, A.2007[Environmental risk factors for Parkinson's disease and parkinsonism: the Geoparkinson study666-72Occup Environ Med6410 2007/03/03 Aged Anti-Anxiety Agents/therapeutic use Antidepressive Agents/therapeutic use Case-Control Studies Causality Comorbidity Craniocerebral Trauma/epidemiology Environmental Exposure/*statistics & numerical data Europe/epidemiology Female Genetic Predisposition to Disease/epidemiology Humans Hypnotics and Sedatives/therapeutic use Logistic Models Male Mental Disorders/drug therapy/epidemiology Middle Aged Odds Ratio Parkinson Disease/*epidemiology/genetics Pesticides Risk Factors Tobacco Use Disorder/epidemiology Unconsciousness/epidemiologyOctzOBJECTIVE: To investigate the associations between Parkinson's disease and other degenerative parkinsonian syndromes and environmental factors in five European countries. METHODS: A case-control study of 959 prevalent cases of parkinsonism (767 with Parkinson's disease) and 1989 controls in Scotland, Italy, Sweden, Romania and Malta was carried out. Cases were defined using the United Kingdom Parkinson's Disease Society Brain Bank criteria, and those with drug-induced or vascular parkinsonism or dementia were excluded. Subjects completed an interviewer-administered questionnaire about lifetime occupational and hobby exposure to solvents, pesticides, iron, copper and manganese. Lifetime and average annual exposures were estimated blind to disease status using a job-exposure matrix modified by subjective exposure modelling. Results were analysed using multiple logistic regression, adjusting for age, sex, country, tobacco use, ever knocked unconscious and family history of Parkinson's disease. RESULTS: Adjusted logistic regression analyses showed significantly increased odds ratios for Parkinson's disease/parkinsonism with an exposure-response relationship for pesticides (low vs no exposure, odds ratio (OR) = 1.13, 95% CI 0.82 to 1.57, high vs no exposure, OR = 1.41, 95% CI 1.06 to 1.88) and ever knocked unconscious (once vs never, OR = 1.35, 95% CI 1.09 to 1.68, more than once vs never, OR = 2.53, 95% CI 1.78 to 3.59). Hypnotic, anxiolytic or antidepressant drug use for more than 1 year and a family history of Parkinson's disease showed significantly increased odds ratios. Tobacco use was protective (OR = 0.50, 95% CI 0.42 to 0.60). Analyses confined to subjects with Parkinson's disease gave similar results. CONCLUSIONS: The association of pesticide exposure with Parkinson's disease suggests a causative role. Repeated traumatic loss of consciousness is associated with increased risk.+http://www.ncbi.nlm.nih.gov/pubmed/17332139fDick, F D De Palma, G Ahmadi, A Scott, N W Prescott, G J Bennett, J Semple, S Dick, S Counsell, C Mozzoni, P Haites, N Wettinger, S Bezzina Mutti, A Otelea, M Seaton, A Soderkvist, P Felice, A Geoparkinson study group Research Support, Non-U.S. Gov't England Occupational and environmental medicine Occup Environ Med. 2007 Oct;64(10):666-72. Epub 2007 Mar 1.*1470-7926 (Electronic) 1351-0711 (Linking)207840117332139Dr F Dick, Department of Environmental and Occupational Medicine, Aberdeen University Medical School, Foresterhill, Aberdeen AB25 2ZP, UK; f.dick@abdn.ac.uk.-oem.2006.027003 [pii] 10.1136/oem.2006.027003eng||7Lau, F. Hagens, S. Muttitt, S.2007QA proposed benefits evaluation framework for health information systems in Canada 112-6, 118 Healthc Q101 2007/03/01LCanada *Evaluation Studies as Topic *Medical Informatics Models, TheoreticalThis article describes a benefits evaluation framework for the health information systems currently being implemented across Canada through Canada Health Infoway with its jurisdictional partners and investment programs. This framework is based on the information systems success model by DeLone and McLean, the empirical analysis by van der Meijden on the use of this model in the health setting and our own review of evaluation studies and systematic review articles in health information systems. The current framework includes three dimensions of quality (system, information and service), two dimensions of system usage (use and user satisfaction) and three dimensions of net benefits (quality, access and productivity). Measures have been developed and work is under way to establish detailed evaluation plans and instruments for the individual investment programs to launch a series of benefits evaluation field studies across jurisdictions later this year.+http://www.ncbi.nlm.nih.gov/pubmed/17326376wLau, Francis Hagens, Simon Muttitt, Sarah Canada Healthcare quarterly (Toronto, Ont.) Healthc Q. 2007;10(1):112-6, 118.%1710-2774 (Print) 1710-2774 (Linking)17326376OSchool of Health Information Science, University of Victoria, British Columbia.eng |t7oBertino, P. Porta, C. Barbone, D. Germano, S. Busacca, S. Pinato, S. Tassi, G. Favoni, R. Gaudino, G. Mutti, L.2007Preliminary data suggestive of a novel translational approach to mesothelioma treatment: imatinib mesylate with gemcitabine or pemetrexed690-5Thorax628 2007/02/22?Antineoplastic Combined Chemotherapy Protocols/*therapeutic use Cell Death Deoxycytidine/administration & dosage/analogs & derivatives Genes, fms Glutamates/administration & dosage Guanine/administration & dosage/analogs & derivatives Humans Mesothelioma/*drug therapy/metabolism Piperazines/administration & dosage Pleural Neoplasms/*drug therapy/metabolism Proto-Oncogene Proteins c-akt/metabolism Proto-Oncogene Proteins c-kit/metabolism Pyrimidines/administration & dosage Receptor, Platelet-Derived Growth Factor beta/metabolism Signal Transduction Tumor Cells, CulturedAugBACKGROUND: Malignant mesothelioma is a cancer which is refractory to current treatments. Imatinib mesylate is a selective inhibitor of tyrosine kinases such as bcr-abl, c-Kit, c-Fms and platelet derived growth factor receptor beta (PDGFRbeta). PDGFRbeta is often overexpressed in mesothelioma cells and is a therapeutic target for imatinib in some solid tumours. A study was undertaken to assess whether imatinib alone or combined with chemotherapeutic agents may be effective for treating mesothelioma. METHODS: Cultures from mesothelioma MMP, REN and ISTMES2 cell lines were treated with imatinib alone or in combination with a chemotherapeutic agent. RESULTS: Imatinib induced cytotoxicity and apoptosis selectively on PDGFRbeta positive mesothelioma cells via blockade of receptor phosphorylation and interference with the Akt pathway. Of the chemotherapeutic agents tested in combination with imatinib, a synergistic effect was obtained with gemcitabine and pemetrexed. CONCLUSIONS: This study provides a rationale for a novel translational approach to the treatment of mesothelioma which relies on enhancement of tumour chemosensitivity by inhibition of Akt.+http://www.ncbi.nlm.nih.gov/pubmed/17311837Bertino, Pietro Porta, Camillo Barbone, Dario Germano, Serena Busacca, Sara Pinato, Sabrina Tassi, Giancarlo Favoni, Roberto Gaudino, Giovanni Mutti, Luciano Research Support, Non-U.S. Gov't England Thorax Thorax. 2007 Aug;62(8):690-5. Epub 2007 Feb 20.%0040-6376 (Print) 0040-6376 (Linking)211728717311837eDISCAFF Department and DFBC Center, University of Piemonte Orientale A Avogadro, 28100 Novara, Italy.-thx.2006.069872 [pii] 10.1136/thx.2006.069872eng||7 Mutti, D. O.2007LTo emmetropize or not to emmetropize? The question for hyperopic development97-102 Optom Vis Sci842 2007/02/15Accommodation, Ocular/*physiology Child Disease Progression Eye/*growth & development Humans Hyperopia/*physiopathology Refraction, Ocular/*physiologyFebhEmmetropization appears to be a rapid process, occurring in the first year of life. Failure to emmetropize leaves about 2 to 8% of children with potentially clinically significant hyperopia after infancy. Uncorrected hyperopia in childhood has a negative impact on distance acuity and the accuracy of the accommodative response for some unknown number of children. The clinical "gray zone" for these problems as judged by distance refractive error alone might begin somewhere around +2.00 to +3.00 D. Use of a refractive correction seems to improve distance acuity and the accuracy of accommodation. Clinicians' reluctance to prescribe hyperopic corrections to children to improve visual performance might be unwarranted. If emmetropization is largely complete, if defocus has only a minor effect on the development of refractive error in infancy or childhood, and if the hyperopic eye is already growing longer but not moving toward emmetropia, then there may be little reason to either wait or be concerned about interfering with emmetropization that may never happen. The immediate visual benefit may outweigh these concerns.+http://www.ncbi.nlm.nih.gov/pubmed/17299338]Mutti, Donald O R01-11,801/PHS HHS/United States R24-EY014792/EY/NEI NIH HHS/United States U10-EY08893/EY/NEI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review United States Optometry and vision science : official publication of the American Academy of Optometry Optom Vis Sci. 2007 Feb;84(2):97-102.%1040-5488 (Print) 1040-5488 (Linking)17299338DThe Ohio State University College of Optometry, Columbus, Ohio, USA.;10.1097/OPX.0b013e318031b079 00006324-200702000-00007 [pii]eng||7<Mutti, D. O. Candy, R. Cotter, S. A. Haegerstrom-Portnoy, G.2007Infant and child hyperopia80 Optom Vis Sci842 2007/02/15Child Child, Preschool Eyeglasses Humans *Hyperopia/epidemiology/physiopathology/therapy Infant Prevalence Prognosis Refraction, Ocular/physiologyFeb+http://www.ncbi.nlm.nih.gov/pubmed/17299334Mutti, Donald O Candy, Rowan Cotter, Susan A Haegerstrom-Portnoy, Gunilla Editorial United States Optometry and vision science : official publication of the American Academy of Optometry Optom Vis Sci. 2007 Feb;84(2):80.%1040-5488 (Print) 1040-5488 (Linking)17299334;10.1097/OPX.0b013e31803404bb 00006324-200702000-00003 [pii]eng R||7Landi, S. Gemignani, F. Neri, M. Barale, R. Bonassi, S. Bottari, F. Canessa, P. A. Canzian, F. Ceppi, M. Filiberti, R. Ivaldi, G. P. Mencoboni, M. Scaruffi, P. Tonini, G. P. Mutti, L. Puntoni, R.2007Polymorphisms of glutathione-S-transferase M1 and manganese superoxide dismutase are associated with the risk of malignant pleural mesothelioma2739-43 Int J Cancer12012 2007/02/109Aged Female Gene Frequency Genetic Predisposition to Disease Genotype Glutathione Transferase/*genetics Humans Logistic Models Male Mesothelioma/enzymology/genetics/*pathology Middle Aged Odds Ratio Pleural Neoplasms/genetics/*pathology *Polymorphism, Single Nucleotide Risk Factors Superoxide Dismutase/*geneticsJun 15 Individual response to oxidative stress, due to exposure to asbestos fibres plays a significant role in the malignant pleural mesothelioma (MPM) etiology. The differential impact on MPM risk of polymorphic alleles of glutathione-S-transferases (GSTs) and manganese superoxide dismutase (MnSOD/SOD2) genes involved in the defence against oxidative damage has been investigated. Ninety cases of MPM and 395 controls were genotyped using the arrayed-primer extension technique. Logistic regression analysis was applied to assess the predictive role of single nucleotide polymorphisms (SNPs) potentially involved in MPM carcinogenesis after adjustment for potential confounders. An increased risk of MPM was found in subjects bearing a GSTM1 null allele (OR = 1.69, 95% CI = 1.04-2.74; p = 0.034), and in those with the Ala/Ala genotypes at codon 16 within MnSOD (OR = 3.07, 95% CI = 1.55-6.05; p = 0.001). A stronger effect of MnSOD was observed among patients without a clear exposure to asbestos fibres. No effect was found for GSTA2, GSTA4, GSTM3, GSTP1 and GSTT1 genes. These findings, if replicated, contribute substantial evidence to the hypothesis that oxidative stress and cellular antireactive oxygen species systems are involved in the pathogenesis and in the natural history of MPM.+http://www.ncbi.nlm.nih.gov/pubmed/17290392Landi, Stefano Gemignani, Federica Neri, Monica Barale, Roberto Bonassi, Stefano Bottari, Fabio Canessa, Pier Aldo Canzian, Federico Ceppi, Marcello Filiberti, Rosangela Ivaldi, Gian Paolo Mencoboni, Manlio Scaruffi, Paola Tonini, Gian Paolo Mutti, Luciano Puntoni, Riccardo Research Support, Non-U.S. Gov't United States International journal of cancer. Journal international du cancer Int J Cancer. 2007 Jun 15;120(12):2739-43.%0020-7136 (Print) 0020-7136 (Linking)172903927Department of Biology, University of Pisa, Pisa, Italy.10.1002/ijc.22590eng ||7OSharma, R. Muttil, P. Yadav, A. B. Rath, S. K. Bajpai, V. K. Mani, U. Misra, A.2007zUptake of inhalable microparticles affects defence responses of macrophages infected with Mycobacterium tuberculosis H37Ra499-506J Antimicrob Chemother593 2007/01/24=Administration, Inhalation Animals Cytokines/biosynthesis Isoniazid/*administration & dosage Macrophages/*immunology/metabolism/microbiology Mice *Microspheres Mycobacterium tuberculosis/*immunology Phagocytosis Reactive Nitrogen Species/metabolism Reactive Oxygen Species/metabolism Rifampin/*administration & dosageMarOOBJECTIVES: To investigate whether inhalable microparticles containing two anti-tuberculosis agents, isoniazid and rifampicin, evoke host-defence strategies in macrophages in addition to targeting the incorporated drugs. METHODS: Microparticles were prepared by spray-drying a homogeneous solution of drugs and poly(lactic acid) (PLA; apparent viscosity 1.1 cP). Four parts PLA and three parts rifampicin were dissolved in dichloromethane. One part isoniazid was dissolved in methanol. The two solutions were mixed in the ratio 22 : 3 at which none of the solutes precipitated. These were administered as 'nose-only' inhalations to mice or exposed to cultured J774 mouse macrophages. Targeting to lung macrophages was investigated by transmission electron microscopy. Reactive oxygen species (ROS) were estimated by a cytochrome c assay and flow cytometry. Reactive nitrogen intermediates (RNI) were assayed using Griess reagent. Cytokines in culture supernatants were estimated by ELISA. RESULTS: Treatment with inhalable microparticles targeted lung macrophages in vivo and induced intense Golgi activity in the vicinity of microparticle-containing phagosomes. Microparticles induced a respiratory burst involving NADPH oxidase and enhanced NO production by infected macrophages. Microparticle-induced NADPH oxidase activation required optimal calcium ions. Microparticles efficiently induced tumour necrosis factor-alpha (TNF-alpha) secretion by macrophages recovered from infected mice. CONCLUSIONS: Microparticle phagocytosis induces responses in infected murine macrophages that are indicative of activation of innate bactericidal mechanisms, and are inimical to bacterial survival. It is likely that such responses augment straightforward drug action on the bacterium and contribute to the unexpectedly high efficacy of microparticles in experimental tuberculosis.+http://www.ncbi.nlm.nih.gov/pubmed/17242031 Sharma, Rolee Muttil, Pavan Yadav, Awadh Bihari Rath, Srikanta Kumar Bajpai, Virendra Kumar Mani, Uthirappan Misra, Amit Research Support, Non-U.S. Gov't England The Journal of antimicrobial chemotherapy J Antimicrob Chemother. 2007 Mar;59(3):499-506. Epub 2007 Jan 22.%0305-7453 (Print) 0305-7453 (Linking)17242031gPharmaceutics Division, Central Drug Research Institute, Chhattar Manzil Palace, Lucknow 226001, India.dkl533 [pii] 10.1093/jac/dkl533eng ||7kde Burbure, C. Pignatti, P. Corradi, M. Malerba, M. Clippe, A. Dumont, X. Moscato, G. Mutti, A. Bernard, A.2007kUteroglobin-related protein 1 and clara cell protein in induced sputum of patients with asthma and rhinitis172-9Chest1311 2007/01/16Adult Asthma/*immunology/*metabolism Case-Control Studies Female Humans Male Regression Analysis Respiratory Function Tests Rhinitis/*immunology/*metabolism Sputum/*immunology Uteroglobin/*metabolismJanRationale: Uteroglobin-related protein 1 (UGRP1) and Clara cell protein (CC16), members of the secretoglobin family, increasingly appear to play a role in airway inflammatory response. OBJECTIVE: To explore levels of UGRP1 and CC16 in induced sputum of patients with asthma and rhinitis. METHODS: Induced-sputum samples of patients with asthma or rhinitis (n = 32 each; atopic asthma, n = 24; atopic rhinitis, n = 20) and from 19 nonsmoking nonatopic control subjects were analyzed for cytology and levels of UGRP1, CC16, and albumin. Measurements and main results: Sputum UGRP1 increased in both asthma and rhinitis, most strikingly so in asthma, in which changes were most significant in atopic individuals. By contrast, sputum CC16 did not change significantly in either condition, although it was positively correlated with UGRP1 in patients and control subjects. Changes in sputum UGRP1 in atopic asthma were not linked to permeability changes reflected by increased albumin levels but correlated positively with sputum macrophages and negatively with eosinophils. The observed differences in UGRP1 and CC16 may be linked to different cell populations being responsible for their secretion; UGRP1 is mainly secreted in larger conducting airways, whereas CC16 is mainly secreted by the nasal and peripheral airways epithelium. CONCLUSIONS: The increase in UGRP1 but not of CC16 in asthma and rhinitis suggests that UGRP1 may play a role in these inflammatory diseases.+http://www.ncbi.nlm.nih.gov/pubmed/17218572de Burbure, Claire Pignatti, Patrizia Corradi, Massimo Malerba, Mario Clippe, Andre Dumont, Xavier Moscato, Gianna Mutti, Antonio Bernard, Alfred United States Chest Chest. 2007 Jan;131(1):172-9.%0012-3692 (Print) 0012-3692 (Linking)17218572Unit of Industrial Toxicology and Occupational Medicine, Universite Catholique de Louvain, Clos Chapelle-aux-Champs 30, bte 3054, B-1200 Brussels, Belgium.%131/1/172 [pii] 10.1378/chest.06-0835eng||7 !Manini, P. De Palma, G. Mutti, A.2007LExposure assessment at the workplace: implications of biological variability210-8 Toxicol Lett1683 2006/12/13Air Pollutants, Occupational/analysis Biological Markers/*analysis Environmental Monitoring/methods Humans Occupational Exposure/*analysis WorkplaceFeb 5ABiological monitoring (BM) and biomarkers are widely applied in occupational toxicology. BM is mainly aimed at (i) defining the existence of an occupational exposure; (ii) quantifying the level of internal dose; (iii) verifying that exposure limits (BEI((R)), BAT, BLV) are respected. As compared to ambient monitoring, BM is more expensive and complex. Several biomarkers are available for the same chemical and the meaning of the marker may depend on the sampling time. Therefore, practical issues, including cost and selection of an adequate sampling strategy, should be dealt with when planning a BM program for specific purposes. In addition, several biological and analytical sources of variability may influence biomarker levels, thus making the interpretation of BM data a difficult task. However, we should recognize that the main aim of BM is not to reduce, but to explain biological variance. The decreasing trend in occupational exposure levels highlighted the specificity problems of traditional biomarkers of exposure and prompted the research to the development of new biomarkers, e.g. unchanged volatile compounds in urine, minor metabolites, DNA and protein adducts. Depending on the scope and context (research or routine) different requirements of biomarkers can be envisaged in terms of validation and acceptable variability.+http://www.ncbi.nlm.nih.gov/pubmed/17157456Manini, Paola De Palma, Giuseppe Mutti, Antonio Review Netherlands Toxicology letters Toxicol Lett. 2007 Feb 5;168(3):210-8. Epub 2006 Nov 16.%0378-4274 (Print) 0378-4274 (Linking)17157456Laboratory of Industrial Toxicology, Department of Clinical Medicine, Nephrology and Health Sciences, University of Parma, via Gramsci 14, 43100 Parma, Italy. paola.manini@unipr.it8S0378-4274(06)01324-5 [pii] 10.1016/j.toxlet.2006.09.014eng||7!Porta, C. Mutti, L. Tassi, G.2007Negative results of an Italian Group for Mesothelioma (G.I.Me.) pilot study of single-agent imatinib mesylate in malignant pleural mesothelioma149-50Cancer Chemother Pharmacol591 2006/04/26Adult Aged Antineoplastic Agents/adverse effects/*therapeutic use Disease Progression Female Humans Male Mesothelioma/*drug therapy Middle Aged Pilot Projects Piperazines/adverse effects/*therapeutic use Pleural Neoplasms/*drug therapy Protein Kinase Inhibitors/adverse effects/*therapeutic use Pyrimidines/adverse effects/*therapeutic use Receptors, Platelet-Derived Growth Factor/drug effects Stem Cell Factor/metabolism Treatment FailureJan+http://www.ncbi.nlm.nih.gov/pubmed/16636799Porta, Camillo Mutti, Luciano Tassi, Gianfranco Clinical Trial Letter Germany Cancer chemotherapy and pharmacology Cancer Chemother Pharmacol. 2007 Jan;59(1):149-50. Epub 2006 Apr 25.%0344-5704 (Print) 0344-5704 (Linking)1663679910.1007/s00280-006-0243-4enga||7$Smith, E. L., 3rd Hung, L. F.1999RThe role of optical defocus in regulating refractive development in infant monkeys1415-35 Vision Res398 1999/05/27Animals Anisometropia/etiology/*physiopathology Biometry Cornea/anatomy & histology Eye/*growth & development Fixation, Ocular *Lenses Macaca mulatta Optics and Photonics Time Factors Vision, BinocularAprEarly in life, the two eyes of infant primates normally grow in a coordinated manner toward the ideal refractive state. We investigated the extent to which lens-induced changes in the effective focus of the eye affected refractive development in infant rhesus monkeys. The main finding was that spectacle lenses could predictably alter the growth of one or both eyes resulting in appropriate compensating refractive changes in both the hyperopic and myopic directions. Although the effective operating range of the emmetropization process in young monkeys is somewhat limited, the results demonstrate that emmetropization in this higher primate, as in a number of other species, is an active process that is regulated by optical defocus associated with the eye's effective refractive state.+http://www.ncbi.nlm.nih.gov/pubmed/10343811Smith, E L 3rd Hung, L F EY 03611/EY/NEI NIH HHS/United States EY 07551/EY/NEI NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. England Vision research Vision Res. 1999 Apr;39(8):1415-35.%0042-6989 (Print) 0042-6989 (Linking)10343811UCollege of Optometry, University of Houston, TX 77204-6052, USA. opto33@jetson.uh.eduS0042698998002296 [pii]eng||7#Smith, E. L., 3rd1998bSpectacle lenses and emmetropization: the role of optical defocus in regulating ocular development388-98 Optom Vis Sci756 1998/07/14Animals Animals, Newborn/*growth & development Anisometropia/etiology/physiopathology Eye/*growth & development *Eyeglasses Macaca mulatta Reference Values Refraction, Ocular/*physiology Refractive Errors/physiopathologyJunThe purpose of our investigation was to determine whether early ocular growth and refractive development was regulated by visual feedback in infant monkeys. Specifically, we examined the ability of infant monkeys to compensate for optically induced changes in the eye's refractive state and to recover from experimentally induced refractive errors. For moderate-powered anisometropic lenses, infants exhibited differential interocular axial growth rates that reduced the lens-induced refractive imbalance between the two eyes. Infants treated with equal-powered lenses over both eyes also showed compensating growth. For lens powers between approximately -3 and +6 D, the resulting refractive-error changes, which were primarily due to alterations in vitreous chamber growth rates, were well correlated with the effective refractive state produced by the treatment lenses. When the stimulus for altered eye growth was removed and the infants were provided unrestricted vision, monkey eyes consistently grew toward emmetropia. The remarkable degree of adaptability exhibited by the eyes of infant monkeys demonstrates that emmetropization in this higher primate is an active process that is regulated on a continuous basis by optical defocus. Consequently, early in life spectacle lenses by changing the eye's effective focus can predictably alter ocular growth and the refractive status of one or both eyes.*http://www.ncbi.nlm.nih.gov/pubmed/9661208-Smith, E L 3rd EY 03611/EY/NEI NIH HHS/United States EY 07551/EY/NEI NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states Optometry and vision science : official publication of the American Academy of Optometry Optom Vis Sci. 1998 Jun;75(6):388-98.%1040-5488 (Print) 1040-5488 (Linking)96612088College of Optometry, University of Houston, Texas, USA.eng ||7%+Irving, E. L. Sivak, J. G. Callender, M. G.19921Refractive plasticity of the developing chick eye448-56Ophthalmic Physiol Opt124 1992/10/01Accommodation, Ocular/physiology Animals Astigmatism/etiology Biometry Chickens Cornea/anatomy & histology Eye/*growth & development Lenses Optics and Photonics Refractive Errors/*etiology Sensory Deprivation Time FactorsOctWe have developed a lightweight plastic goggle with rigid contact lens inserts that can be applied to the eyes of newly hatched chicks to explore the range and accuracy of the developmental mechanism that responds to retinal defocus. Convex and concave lenses of 5, 10, 15, 20 and +30 D were applied to one eye on the day of hatching. The chick eye responds accurately to defocus between -10 and +15 D, although hyperopia develops more rapidly than myopia. Beyond this range there is first a levelling off of the response and then a decrease. The resulting refractive errors are caused mainly by increases and decreases in axial length, although high levels of hyperopia are associated with corneal flattening. If +/- 10 D defocusing lenses are applied nine days after hatching the resulting myopia and hyperopia are equal to about 80% of the inducing power. After one week of inducing myopia and hyperopia with +/- 10 D lenses, the inducing lenses were reversed. In this case, the refractive error did not reach the power of the second lens after another week of wear. Instead, astigmatism in varying amounts (0-12 D) was produced, being greater when reversal was from plus to minus. Finally, astigmatism can also be produced by applying 9 D toric inducing lenses on the day of hatching. The astigmatism produced varies from 2 to 6 D, and the most myopic meridian coincides with the power meridian of the inducing lens. This astigmatism appears to be primarily due to corneal toricity.(ABSTRACT TRUNCATED AT 250 WORDS)*http://www.ncbi.nlm.nih.gov/pubmed/1293533Irving, E L Sivak, J G Callender, M G Research Support, Non-U.S. Gov't England Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists) Ophthalmic Physiol Opt. 1992 Oct;12(4):448-56.%0275-5408 (Print) 0275-5408 (Linking)1293533=School of Optometry, University of Waterloo, Ontario, Canada.eng ||7&+Irving, E. L. Sivak, J. G. Callender, M. G.19921Refractive plasticity of the developing chick eye448-56Ophthalmic Physiol Opt124 1992/10/01Accommodation, Ocular/physiology Animals Astigmatism/etiology Biometry Chickens Cornea/anatomy & histology Eye/*growth & development Lenses Optics and Photonics Refractive Errors/*etiology Sensory Deprivation Time FactorsOctWe have developed a lightweight plastic goggle with rigid contact lens inserts that can be applied to the eyes of newly hatched chicks to explore the range and accuracy of the developmental mechanism that responds to retinal defocus. Convex and concave lenses of 5, 10, 15, 20 and +30 D were applied to one eye on the day of hatching. The chick eye responds accurately to defocus between -10 and +15 D, although hyperopia develops more rapidly than myopia. Beyond this range there is first a levelling off of the response and then a decrease. The resulting refractive errors are caused mainly by increases and decreases in axial length, although high levels of hyperopia are associated with corneal flattening. If +/- 10 D defocusing lenses are applied nine days after hatching the resulting myopia and hyperopia are equal to about 80% of the inducing power. After one week of inducing myopia and hyperopia with +/- 10 D lenses, the inducing lenses were reversed. In this case, the refractive error did not reach the power of the second lens after another week of wear. Instead, astigmatism in varying amounts (0-12 D) was produced, being greater when reversal was from plus to minus. Finally, astigmatism can also be produced by applying 9 D toric inducing lenses on the day of hatching. The astigmatism produced varies from 2 to 6 D, and the most myopic meridian coincides with the power meridian of the inducing lens. This astigmatism appears to be primarily due to corneal toricity.(ABSTRACT TRUNCATED AT 250 WORDS)*http://www.ncbi.nlm.nih.gov/pubmed/1293533Irving, E L Sivak, J G Callender, M G Research Support, Non-U.S. Gov't England Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists) Ophthalmic Physiol Opt. 1992 Oct;12(4):448-56.%0275-5408 (Print) 0275-5408 (Linking)1293533=School of Optometry, University of Waterloo, Ontario, Canada.enga||7'Smith, E. L., 3rd Hung, L. F.1999RThe role of optical defocus in regulating refractive development in infant monkeys1415-35 Vision Res398 1999/05/27Animals Anisometropia/etiology/*physiopathology Biometry Cornea/anatomy & histology Eye/*growth & development Fixation, Ocular *Lenses Macaca mulatta Optics and Photonics Time Factors Vision, BinocularAprEarly in life, the two eyes of infant primates normally grow in a coordinated manner toward the ideal refractive state. We investigated the extent to which lens-induced changes in the effective focus of the eye affected refractive development in infant rhesus monkeys. The main finding was that spectacle lenses could predictably alter the growth of one or both eyes resulting in appropriate compensating refractive changes in both the hyperopic and myopic directions. Although the effective operating range of the emmetropization process in young monkeys is somewhat limited, the results demonstrate that emmetropization in this higher primate, as in a number of other species, is an active process that is regulated by optical defocus associated with the eye's effective refractive state.+http://www.ncbi.nlm.nih.gov/pubmed/10343811Smith, E L 3rd Hung, L F EY 03611/EY/NEI NIH HHS/United States EY 07551/EY/NEI NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. England Vision research Vision Res. 1999 Apr;39(8):1415-35.%0042-6989 (Print) 0042-6989 (Linking)10343811UCollege of Optometry, University of Houston, TX 77204-6052, USA. opto33@jetson.uh.eduS0042698998002296 [pii]eng||7(Smith, E. L., 3rd1998bSpectacle lenses and emmetropization: the role of optical defocus in regulating ocular development388-98 Optom Vis Sci756 1998/07/14Animals Animals, Newborn/*growth & development Anisometropia/etiology/physiopathology Eye/*growth & development *Eyeglasses Macaca mulatta Reference Values Refraction, Ocular/*physiology Refractive Errors/physiopathologyJunThe purpose of our investigation was to determine whether early ocular growth and refractive development was regulated by visual feedback in infant monkeys. Specifically, we examined the ability of infant monkeys to compensate for optically induced changes in the eye's refractive state and to recover from experimentally induced refractive errors. For moderate-powered anisometropic lenses, infants exhibited differential interocular axial growth rates that reduced the lens-induced refractive imbalance between the two eyes. Infants treated with equal-powered lenses over both eyes also showed compensating growth. For lens powers between approximately -3 and +6 D, the resulting refractive-error changes, which were primarily due to alterations in vitreous chamber growth rates, were well correlated with the effective refractive state produced by the treatment lenses. When the stimulus for altered eye growth was removed and the infants were provided unrestricted vision, monkey eyes consistently grew toward emmetropia. The remarkable degree of adaptability exhibited by the eyes of infant monkeys demonstrates that emmetropization in this higher primate is an active process that is regulated on a continuous basis by optical defocus. Consequently, early in life spectacle lenses by changing the eye's effective focus can predictably alter ocular growth and the refractive status of one or both eyes.*http://www.ncbi.nlm.nih.gov/pubmed/9661208-Smith, E L 3rd EY 03611/EY/NEI NIH HHS/United States EY 07551/EY/NEI NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states Optometry and vision science : official publication of the American Academy of Optometry Optom Vis Sci. 1998 Jun;75(6):388-98.%1040-5488 (Print) 1040-5488 (Linking)96612088College of Optometry, University of Houston, Texas, USA.enga||7)Smith, E. L., 3rd Hung, L. F.1999RThe role of optical defocus in regulating refractive development in infant monkeys1415-35 Vision Res398 1999/05/27Animals Anisometropia/etiology/*physiopathology Biometry Cornea/anatomy & histology Eye/*growth & development Fixation, Ocular *Lenses Macaca mulatta Optics and Photonics Time Factors Vision, BinocularAprEarly in life, the two eyes of infant primates normally grow in a coordinated manner toward the ideal refractive state. We investigated the extent to which lens-induced changes in the effective focus of the eye affected refractive development in infant rhesus monkeys. The main finding was that spectacle lenses could predictably alter the growth of one or both eyes resulting in appropriate compensating refractive changes in both the hyperopic and myopic directions. Although the effective operating range of the emmetropization process in young monkeys is somewhat limited, the results demonstrate that emmetropization in this higher primate, as in a number of other species, is an active process that is regulated by optical defocus associated with the eye's effective refractive state.+http://www.ncbi.nlm.nih.gov/pubmed/10343811Smith, E L 3rd Hung, L F EY 03611/EY/NEI NIH HHS/United States EY 07551/EY/NEI NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. England Vision research Vision Res. 1999 Apr;39(8):1415-35.%0042-6989 (Print) 0042-6989 (Linking)10343811UCollege of Optometry, University of Houston, TX 77204-6052, USA. opto33@jetson.uh.eduS0042698998002296 [pii]eng ||7*pMutti, D. O. Mitchell, G. L. Jones, L. A. Friedman, N. E. Frane, S. L. Lin, W. K. Moeschberger, M. L. Zadnik, K.2005ZAxial growth and changes in lenticular and corneal power during emmetropization in infants3074-80Invest Ophthalmol Vis Sci469 2005/08/27 Accommodation, Ocular/physiology Cornea/*physiology Eye/*growth & development Female Humans Infant Lens, Crystalline/*physiology Male Ocular Physiological Phenomena Refraction, Ocular/*physiology Refractive Errors/physiopathology *Retinoscopy Vision, Ocular/*physiologySepPURPOSE: To evaluate the contribution made by the ocular components to the emmetropization of spherical equivalent refractive error in human infants between 3 and 9 months of age. METHODS: Keratophakometry in two meridians was performed on 222 normal-birthweight infant subjects at 3 and 9 months of age. The spherical equivalent refractive error was measured by cycloplegic retinoscopy (cyclopentolate 1%). Anterior chamber depth, lens thickness, and vitreous chamber depth were measured by A-scan ultrasonography over the closed eyelid. RESULTS: Both the mean and SD for spherical equivalent refractive error decreased between 3 and 9 months of age (+2.16 +/- 1.30 D at 3 months; +1.36 +/- 1.06 D at 9 months; P < 0.0001, for the change in both mean and SD). Average ocular component change was characterized by increases in axial length, thinning, and flattening of the crystalline lens, increases in lens equivalent refractive index, and decreases in lens and corneal power. Initial refractive error was associated in a nonlinear manner with the change in refractive error (R(2) = 0.41; P < 0.0001) and with axial growth (R(2) = 0.082; P = 0.0005). Reduction in hyperopia correlated significantly with increases in axial length (R(2) = 0.16; P < 0.0001), but not with changes in corneal and lenticular power. Decreases in lenticular and corneal power were associated with axial elongation (R(2) = 0.40, R(2) = 0.12, respectively; both P < 0.0001). CONCLUSIONS: Modulation in the amount of axial growth in relation to initial refractive error appeared to be the most influential factor in emmetropization of spherical equivalent refractive error. The associations between initial refractive error, subsequent axial growth, and change in refractive error were consistent with a visual basis for emmetropization. The cornea and crystalline lens lost substantial amounts of dioptric power in this phase of growth, but neither appeared to play a significant role in emmetropization.+http://www.ncbi.nlm.nih.gov/pubmed/16123404Mutti, Donald O Mitchell, G Lynn Jones, Lisa A Friedman, Nina E Frane, Sara L Lin, Wendy K Moeschberger, Melvin L Zadnik, Karla R01 EY 11801/EY/NEI NIH HHS/United States R21 EY 12273/EY/NEI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S. United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2005 Sep;46(9):3074-80.%0146-0404 (Print) 0146-0404 (Linking)16123404pOhio State University College of Optometry, 338 West Tenth Avenue, Columbus, OH 43210-1240, USA. mutti.2@osu.edu$46/9/3074 [pii] 10.1167/iovs.04-1040eng ||7+pMutti, D. O. Mitchell, G. L. Jones, L. A. Friedman, N. E. Frane, S. L. Lin, W. K. Moeschberger, M. L. Zadnik, K.2005ZAxial growth and changes in lenticular and corneal power during emmetropization in infants3074-80Invest Ophthalmol Vis Sci469 2005/08/27 Accommodation, Ocular/physiology Cornea/*physiology Eye/*growth & development Female Humans Infant Lens, Crystalline/*physiology Male Ocular Physiological Phenomena Refraction, Ocular/*physiology Refractive Errors/physiopathology *Retinoscopy Vision, Ocular/*physiologySepPURPOSE: To evaluate the contribution made by the ocular components to the emmetropization of spherical equivalent refractive error in human infants between 3 and 9 months of age. METHODS: Keratophakometry in two meridians was performed on 222 normal-birthweight infant subjects at 3 and 9 months of age. The spherical equivalent refractive error was measured by cycloplegic retinoscopy (cyclopentolate 1%). Anterior chamber depth, lens thickness, and vitreous chamber depth were measured by A-scan ultrasonography over the closed eyelid. RESULTS: Both the mean and SD for spherical equivalent refractive error decreased between 3 and 9 months of age (+2.16 +/- 1.30 D at 3 months; +1.36 +/- 1.06 D at 9 months; P < 0.0001, for the change in both mean and SD). Average ocular component change was characterized by increases in axial length, thinning, and flattening of the crystalline lens, increases in lens equivalent refractive index, and decreases in lens and corneal power. Initial refractive error was associated in a nonlinear manner with the change in refractive error (R(2) = 0.41; P < 0.0001) and with axial growth (R(2) = 0.082; P = 0.0005). Reduction in hyperopia correlated significantly with increases in axial length (R(2) = 0.16; P < 0.0001), but not with changes in corneal and lenticular power. Decreases in lenticular and corneal power were associated with axial elongation (R(2) = 0.40, R(2) = 0.12, respectively; both P < 0.0001). CONCLUSIONS: Modulation in the amount of axial growth in relation to initial refractive error appeared to be the most influential factor in emmetropization of spherical equivalent refractive error. The associations between initial refractive error, subsequent axial growth, and change in refractive error were consistent with a visual basis for emmetropization. The cornea and crystalline lens lost substantial amounts of dioptric power in this phase of growth, but neither appeared to play a significant role in emmetropization.+http://www.ncbi.nlm.nih.gov/pubmed/16123404Mutti, Donald O Mitchell, G Lynn Jones, Lisa A Friedman, Nina E Frane, Sara L Lin, Wendy K Moeschberger, Melvin L Zadnik, Karla R01 EY 11801/EY/NEI NIH HHS/United States R21 EY 12273/EY/NEI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S. United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2005 Sep;46(9):3074-80.%0146-0404 (Print) 0146-0404 (Linking)16123404pOhio State University College of Optometry, 338 West Tenth Avenue, Columbus, OH 43210-1240, USA. mutti.2@osu.edu$46/9/3074 [pii] 10.1167/iovs.04-1040eng |t7,HSmith, E. L., 3rd Kee, C. S. Ramamirtham, R. Qiao-Grider, Y. Hung, L. F.2005WPeripheral vision can influence eye growth and refractive development in infant monkeys3965-72Invest Ophthalmol Vis Sci4611 2005/10/27Animals Animals, Newborn Biometry Disease Models, Animal Eye/*growth & development/ultrasonography Laser Coagulation Macaca mulatta Refractive Errors/*physiopathology Retina/*physiopathology/surgery Retinoscopy Sensory Deprivation Vision, Ocular/*physiologyNov7PURPOSE: Given the prominence of central vision in humans, it has been assumed that visual signals from the fovea dominate emmetropization. The purpose of this study was to examine the impact of peripheral vision on emmetropization. METHODS: Bilateral, peripheral form deprivation was produced in 12 infant monkeys by rearing them with diffusers that had either 4- or 8-mm apertures centered on the pupils of each eye, to allow 24 degrees or 37 degrees of unrestricted central vision, respectively. At the end of the lens-rearing period, an argon laser was used to ablate the fovea in one eye of each of seven monkeys. Subsequently, all the animals were allowed unrestricted vision. Refractive error and axial dimensions were measured along the pupillary axis by retinoscopy and A-scan ultrasonography, respectively. Control data were obtained from 21 normal monkeys and 3 infants reared with binocular plano lenses. RESULTS: Nine of the 12 treated monkeys had refractive errors that fell outside the 10th- and 90th-percentile limits for the age-matched control subjects, and the average refractive error for the treated animals was more variable and significantly less hyperopic/more myopic (+0.03 +/- 2.39 D vs. +2.39 +/- 0.92 D). The refractive changes were symmetric in the two eyes of a given animal and axial in nature. After lens removal, all the treated monkeys recovered from the induced refractive errors. No interocular differences in the recovery process were observed in the animals with monocular foveal lesions. CONCLUSIONS: On the one hand, the peripheral retina can contribute to emmetropizing responses and to ametropias produced by an abnormal visual experience. On the other hand, unrestricted central vision is not sufficient to ensure normal refractive development, and the fovea is not essential for emmetropizing responses.+http://www.ncbi.nlm.nih.gov/pubmed/16249469Smith, Earl L 3rd Kee, Chea-Su Ramamirtham, Ramkumar Qiao-Grider, Ying Hung, Li-Fang P30 EY70551/EY/NEI NIH HHS/United States R01 EY003611-24A1/EY/NEI NIH HHS/United States R01 EY03611/EY/NEI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2005 Nov;46(11):3965-72.%0146-0404 (Print) 0146-0404 (Linking)176210016249469ICollege of Optometry, University of Houston, TX 77204, USA. esmith@uh.edu%46/11/3965 [pii] 10.1167/iovs.05-0445engD||7-Jiang, B. C. Ramamirtham, R.2005MThe adaptive effect of narrowing the interocular separation on the AC/A ratio2704-9 Vision Res4520 2005/05/14Accommodation, Ocular/*physiology Adaptation, Ocular/*physiology Adult Convergence, Ocular/*physiology Face/*anatomy & histology Humans Pupil Reaction Time Vision TestsSep^The purpose of this study was to determine whether the response AC/A ratio could be altered when the subject's interpupillary distance (IPD) was optically halved. We measured the changes in the AC/A ratio for 10 subjects after using the optical device for 30 min. Accommodative response was measured using a Canon R-1 optometer, and vergence response was measured with an ASL 210 Eye Movement Monitor. The average AC/A ratios were 1.20+/-0.35 (SD) (MA/D) and 0.84+/-0.39 (MA/D) before and after wearing the device, respectively. The decrease in AC/A ratio was statistically significant (p=0.01). This was mainly caused by a reduction in the slope of the accommodative vergence. The results of this study suggest that the AC/A ratio can be decreased if an IPD-narrowing device is used. A possible application of this mechanism in the study of myopia is discussed.+http://www.ncbi.nlm.nih.gov/pubmed/15890382bJiang, Bai-Chuan Ramamirtham, Ramkumar England Vision research Vision Res. 2005 Sep;45(20):2704-9.%0042-6989 (Print) 0042-6989 (Linking)15890382zCollege of Optometry, Nova Southeastern University, 3200 S. University Dr., Ft. Lauderdale, FL 33328, USA. bjiang@nova.edu8S0042-6989(05)00203-8 [pii] 10.1016/j.visres.2005.03.016eng `|t7.HKee, C. S. Hung, L. F. Qiao-Grider, Y. Ramamirtham, R. Smith, E. L., 3rd2005FAstigmatism in monkeys with experimentally induced myopia or hyperopia248-60 Optom Vis Sci824 2005/04/15Animals Astigmatism/*etiology/physiopathology Cornea/physiopathology Eye/growth & development Eyeglasses Hyperopia/*complications/etiology/physiopathology Macaca mulatta Myopia/*complications/etiology/physiopathology Refraction, OcularAprPURPOSE: Astigmatism is the most common ametropia found in humans and is often associated with large spherical ametropias. However, little is known about the etiology of astigmatism or the reason(s) for the association between spherical and astigmatic refractive errors. This study examines the frequency and characteristics of astigmatism in infant monkeys that developed axial ametropias as a result of altered early visual experience. METHODS: Data were obtained from 112 rhesus monkeys that experienced a variety of lens-rearing regimens that were intended to alter the normal course of emmetropization. These visual manipulations included form deprivation (n = 13); optically imposed defocus (n = 48); and continuous ambient lighting with (n = 6) or without optically imposed defocus (n = 6). In addition, data from 19 control monkeys and 39 infants reared with an optically imposed astigmatism were used for comparison purposes. The lens-rearing period started at approximately 3 weeks of age and ended by 4 to 5 months of age. Refractive development for all monkeys was assessed periodically throughout the treatment and subsequent recovery periods by retinoscopy, keratometry, and A-scan ultrasonography. RESULTS: In contrast to control monkeys, the monkeys that had experimentally induced axial ametropias frequently developed significant amounts of astigmatism (mean refractive astigmatism = 0.37 +/- 0.33 D [control] vs. 1.24 +/- 0.81 D [treated]; two-sample t-test, p < 0.0001), especially when their eyes exhibited relative hyperopic shifts in refractive error. The astigmatism was corneal in origin (Pearson's r; p < 0.001 for total astigmatism and the JO and J45 components), and the axes of the astigmatism were typically oblique and bilaterally mirror symmetric. Interestingly, the astigmatism was not permanent; the majority of the monkeys exhibited substantial reductions in the amount of astigmatism at or near the end of the lens-rearing procedures. CONCLUSIONS: In infant monkeys, visual conditions that alter axial growth can also alter corneal shape. Similarities between the astigmatic errors in our monkeys and some astigmatic errors in humans suggest that vision-dependent changes in eye growth may contribute to astigmatism in humans.+http://www.ncbi.nlm.nih.gov/pubmed/15829845Kee, Chea-Su Hung, Li-Fang Qiao-Grider, Ying Ramamirtham, Ramkumar Smith, Earl L 3rd EY 03,611/EY/NEI NIH HHS/United States EY 07,551/EY/NEI NIH HHS/United States R01 EY003611-24A1/EY/NEI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States Optometry and vision science : official publication of the American Academy of Optometry Optom Vis Sci. 2005 Apr;82(4):248-60.%1040-5488 (Print) 1040-5488 (Linking)181023315829845]College of Optometry, University of Houston, Houston, Texas 77204-2020, USA. ckee@mail.uh.edu00006324-200504000-00008 [pii]engF|7/'Huang, J. Hung, L. F. Smith, E. L., 3rd2011Effects of Foveal Ablation on the Pattern of Peripheral Refractive Errors in Normal and Form-deprived Infant Rhesus Monkeys (Macaca mulatta)Invest Ophthalmol Vis Sci 2011/06/23Jun 21Purpose: The purpose of this study was to determine whether visual signals from the fovea contribute to the changes in the pattern of peripheral refractions associated with form deprivation myopia in monkeys. Methods: Monocular form-deprivation was produced in 18 rhesus monkeys by securing diffusers in front of their treated eyes between 22 +/- 2 and 155 +/- 17 days of age. In 8 of these form-deprived monkeys, the fovea and most of the perifovea of the treated eye were ablated by laser photocoagulation at the start of the diffuser-rearing period. Each eye's refractive status was measured by retinoscopy along the pupillary axis and at 15 degrees intervals along the horizontal meridian to eccentricities of 45 degrees . Control data were obtained from 12 normal monkeys and 5 monkeys that had monocular foveal ablations and were subsequently reared with unrestricted vision. Results: Foveal ablation, by itself, did not produce systematic alterations in either the central or peripheral refractive errors of the treated eyes. In addition, foveal ablation did not alter the patterns of peripheral refractions in monkeys with form deprivation myopia. The patterns of peripheral refractive errors in the two groups of form-deprived monkeys, either with or without foveal ablation, were qualitatively similar (treated eyes: F = 0.31, P = 0.74; anisometropia: F = 0.61, P = 0.59), but significantly different from those found in the normal monkeys (F = 8.46 and 9.38 respectively, P < 0.05). Conclusions: Central retinal signals do not contribute in an essential way to the alterations in eye shape that occur during the development of vision-induced axial myopia.+http://www.ncbi.nlm.nih.gov/pubmed/21693598dJournal article Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2011 Jun 21.*1552-5783 (Electronic) 0146-0404 (Linking)216935989College of Optometry, University of Houston, Houston, TX;'iovs.10-6757 [pii] 10.1167/iovs.10-6757Eng |t70gSmith, E. L., 3rd Ramamirtham, R. Qiao-Grider, Y. Hung, L. F. Huang, J. Kee, C. S. Coats, D. Paysse, E.2007IEffects of foveal ablation on emmetropization and form-deprivation myopia3914-22Invest Ophthalmol Vis Sci489 2007/08/296Animals Animals, Newborn Biometry Disease Models, Animal Eye/growth & development/ultrasonography Fovea Centralis/*physiopathology/surgery Laser Coagulation Light Macaca mulatta Myopia/*physiopathology Refraction, Ocular Retinoscopy *Sensory Deprivation Tomography, Optical Coherence Vision, Ocular/*physiologySep|PURPOSE: Because of the prominence of central vision in primates, it has generally been assumed that signals from the fovea dominate refractive development. To test this assumption, the authors determined whether an intact fovea was essential for either normal emmetropization or the vision-induced myopic errors produced by form deprivation. METHODS: In 13 rhesus monkeys at 3 weeks of age, the fovea and most of the perifovea in one eye were ablated by laser photocoagulation. Five of these animals were subsequently allowed unrestricted vision. For the other eight monkeys with foveal ablations, a diffuser lens was secured in front of the treated eyes to produce form deprivation. Refractive development was assessed along the pupillary axis by retinoscopy, keratometry, and A-scan ultrasonography. Control data were obtained from 21 normal monkeys and three infants reared with plano lenses in front of both eyes. RESULTS: Foveal ablations had no apparent effect on emmetropization. Refractive errors for both eyes of the treated infants allowed unrestricted vision were within the control range throughout the observation period, and there were no systematic interocular differences in refractive error or axial length. In addition, foveal ablation did not prevent form deprivation myopia; six of the eight infants that experienced monocular form deprivation developed myopic axial anisometropias outside the control range. CONCLUSIONS: Visual signals from the fovea are not essential for normal refractive development or the vision-induced alterations in ocular growth produced by form deprivation. Conversely, the peripheral retina, in isolation, can regulate emmetropizing responses and produce anomalous refractive errors in response to abnormal visual experience. These results indicate that peripheral vision should be considered when assessing the effects of visual experience on refractive development.+http://www.ncbi.nlm.nih.gov/pubmed/17724167Smith, Earl L 3rd Ramamirtham, Ramkumar Qiao-Grider, Ying Hung, Li-Fang Huang, Juan Kee, Chea-su Coats, David Paysse, Evelyn P30 EY007551-15/EY/NEI NIH HHS/United States P30 EY70551/EY/NEI NIH HHS/United States R01 EY003611-25/EY/NEI NIH HHS/United States R01 EY03611/EY/NEI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2007 Sep;48(9):3914-22.%0146-0404 (Print) 0146-0404 (Linking)270992817724167ZCollege of Optometry, University of Houston, Houston, Texas 77204-2020, USA. esmith@uh.edu$48/9/3914 [pii] 10.1167/iovs.06-1264eng |t71gSmith, E. L., 3rd Ramamirtham, R. Qiao-Grider, Y. Hung, L. F. Huang, J. Kee, C. S. Coats, D. Paysse, E.2007IEffects of foveal ablation on emmetropization and form-deprivation myopia3914-22Invest Ophthalmol Vis Sci489 2007/08/296Animals Animals, Newborn Biometry Disease Models, Animal Eye/growth & development/ultrasonography Fovea Centralis/*physiopathology/surgery Laser Coagulation Light Macaca mulatta Myopia/*physiopathology Refraction, Ocular Retinoscopy *Sensory Deprivation Tomography, Optical Coherence Vision, Ocular/*physiologySep|PURPOSE: Because of the prominence of central vision in primates, it has generally been assumed that signals from the fovea dominate refractive development. To test this assumption, the authors determined whether an intact fovea was essential for either normal emmetropization or the vision-induced myopic errors produced by form deprivation. METHODS: In 13 rhesus monkeys at 3 weeks of age, the fovea and most of the perifovea in one eye were ablated by laser photocoagulation. Five of these animals were subsequently allowed unrestricted vision. For the other eight monkeys with foveal ablations, a diffuser lens was secured in front of the treated eyes to produce form deprivation. Refractive development was assessed along the pupillary axis by retinoscopy, keratometry, and A-scan ultrasonography. Control data were obtained from 21 normal monkeys and three infants reared with plano lenses in front of both eyes. RESULTS: Foveal ablations had no apparent effect on emmetropization. Refractive errors for both eyes of the treated infants allowed unrestricted vision were within the control range throughout the observation period, and there were no systematic interocular differences in refractive error or axial length. In addition, foveal ablation did not prevent form deprivation myopia; six of the eight infants that experienced monocular form deprivation developed myopic axial anisometropias outside the control range. CONCLUSIONS: Visual signals from the fovea are not essential for normal refractive development or the vision-induced alterations in ocular growth produced by form deprivation. Conversely, the peripheral retina, in isolation, can regulate emmetropizing responses and produce anomalous refractive errors in response to abnormal visual experience. These results indicate that peripheral vision should be considered when assessing the effects of visual experience on refractive development.+http://www.ncbi.nlm.nih.gov/pubmed/17724167Smith, Earl L 3rd Ramamirtham, Ramkumar Qiao-Grider, Ying Hung, Li-Fang Huang, Juan Kee, Chea-su Coats, David Paysse, Evelyn P30 EY007551-15/EY/NEI NIH HHS/United States P30 EY70551/EY/NEI NIH HHS/United States R01 EY003611-25/EY/NEI NIH HHS/United States R01 EY03611/EY/NEI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2007 Sep;48(9):3914-22.%0146-0404 (Print) 0146-0404 (Linking)270992817724167ZCollege of Optometry, University of Houston, Houston, Texas 77204-2020, USA. esmith@uh.edu$48/9/3914 [pii] 10.1167/iovs.06-1264eng |t72HSmith, E. L., 3rd Kee, C. S. Ramamirtham, R. Qiao-Grider, Y. Hung, L. F.2005WPeripheral vision can influence eye growth and refractive development in infant monkeys3965-72Invest Ophthalmol Vis Sci4611 2005/10/27Animals Animals, Newborn Biometry Disease Models, Animal Eye/*growth & development/ultrasonography Laser Coagulation Macaca mulatta Refractive Errors/*physiopathology Retina/*physiopathology/surgery Retinoscopy Sensory Deprivation Vision, Ocular/*physiologyNov7PURPOSE: Given the prominence of central vision in humans, it has been assumed that visual signals from the fovea dominate emmetropization. The purpose of this study was to examine the impact of peripheral vision on emmetropization. METHODS: Bilateral, peripheral form deprivation was produced in 12 infant monkeys by rearing them with diffusers that had either 4- or 8-mm apertures centered on the pupils of each eye, to allow 24 degrees or 37 degrees of unrestricted central vision, respectively. At the end of the lens-rearing period, an argon laser was used to ablate the fovea in one eye of each of seven monkeys. Subsequently, all the animals were allowed unrestricted vision. Refractive error and axial dimensions were measured along the pupillary axis by retinoscopy and A-scan ultrasonography, respectively. Control data were obtained from 21 normal monkeys and 3 infants reared with binocular plano lenses. RESULTS: Nine of the 12 treated monkeys had refractive errors that fell outside the 10th- and 90th-percentile limits for the age-matched control subjects, and the average refractive error for the treated animals was more variable and significantly less hyperopic/more myopic (+0.03 +/- 2.39 D vs. +2.39 +/- 0.92 D). The refractive changes were symmetric in the two eyes of a given animal and axial in nature. After lens removal, all the treated monkeys recovered from the induced refractive errors. No interocular differences in the recovery process were observed in the animals with monocular foveal lesions. CONCLUSIONS: On the one hand, the peripheral retina can contribute to emmetropizing responses and to ametropias produced by an abnormal visual experience. On the other hand, unrestricted central vision is not sufficient to ensure normal refractive development, and the fovea is not essential for emmetropizing responses.+http://www.ncbi.nlm.nih.gov/pubmed/16249469Smith, Earl L 3rd Kee, Chea-Su Ramamirtham, Ramkumar Qiao-Grider, Ying Hung, Li-Fang P30 EY70551/EY/NEI NIH HHS/United States R01 EY003611-24A1/EY/NEI NIH HHS/United States R01 EY03611/EY/NEI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2005 Nov;46(11):3965-72.%0146-0404 (Print) 0146-0404 (Linking)176210016249469ICollege of Optometry, University of Houston, TX 77204, USA. esmith@uh.edu%46/11/3965 [pii] 10.1167/iovs.05-0445engD||73Jiang, B. C. Ramamirtham, R.2005MThe adaptive effect of narrowing the interocular separation on the AC/A ratio2704-9 Vision Res4520 2005/05/14Accommodation, Ocular/*physiology Adaptation, Ocular/*physiology Adult Convergence, Ocular/*physiology Face/*anatomy & histology Humans Pupil Reaction Time Vision TestsSep^The purpose of this study was to determine whether the response AC/A ratio could be altered when the subject's interpupillary distance (IPD) was optically halved. We measured the changes in the AC/A ratio for 10 subjects after using the optical device for 30 min. Accommodative response was measured using a Canon R-1 optometer, and vergence response was measured with an ASL 210 Eye Movement Monitor. The average AC/A ratios were 1.20+/-0.35 (SD) (MA/D) and 0.84+/-0.39 (MA/D) before and after wearing the device, respectively. The decrease in AC/A ratio was statistically significant (p=0.01). This was mainly caused by a reduction in the slope of the accommodative vergence. The results of this study suggest that the AC/A ratio can be decreased if an IPD-narrowing device is used. A possible application of this mechanism in the study of myopia is discussed.+http://www.ncbi.nlm.nih.gov/pubmed/15890382bJiang, Bai-Chuan Ramamirtham, Ramkumar England Vision research Vision Res. 2005 Sep;45(20):2704-9.%0042-6989 (Print) 0042-6989 (Linking)15890382zCollege of Optometry, Nova Southeastern University, 3200 S. University Dr., Ft. Lauderdale, FL 33328, USA. bjiang@nova.edu8S0042-6989(05)00203-8 [pii] 10.1016/j.visres.2005.03.016eng `|t74HKee, C. S. Hung, L. F. Qiao-Grider, Y. Ramamirtham, R. Smith, E. L., 3rd2005FAstigmatism in monkeys with experimentally induced myopia or hyperopia248-60 Optom Vis Sci824 2005/04/15Animals Astigmatism/*etiology/physiopathology Cornea/physiopathology Eye/growth & development Eyeglasses Hyperopia/*complications/etiology/physiopathology Macaca mulatta Myopia/*complications/etiology/physiopathology Refraction, OcularAprPURPOSE: Astigmatism is the most common ametropia found in humans and is often associated with large spherical ametropias. However, little is known about the etiology of astigmatism or the reason(s) for the association between spherical and astigmatic refractive errors. This study examines the frequency and characteristics of astigmatism in infant monkeys that developed axial ametropias as a result of altered early visual experience. METHODS: Data were obtained from 112 rhesus monkeys that experienced a variety of lens-rearing regimens that were intended to alter the normal course of emmetropization. These visual manipulations included form deprivation (n = 13); optically imposed defocus (n = 48); and continuous ambient lighting with (n = 6) or without optically imposed defocus (n = 6). In addition, data from 19 control monkeys and 39 infants reared with an optically imposed astigmatism were used for comparison purposes. The lens-rearing period started at approximately 3 weeks of age and ended by 4 to 5 months of age. Refractive development for all monkeys was assessed periodically throughout the treatment and subsequent recovery periods by retinoscopy, keratometry, and A-scan ultrasonography. RESULTS: In contrast to control monkeys, the monkeys that had experimentally induced axial ametropias frequently developed significant amounts of astigmatism (mean refractive astigmatism = 0.37 +/- 0.33 D [control] vs. 1.24 +/- 0.81 D [treated]; two-sample t-test, p < 0.0001), especially when their eyes exhibited relative hyperopic shifts in refractive error. The astigmatism was corneal in origin (Pearson's r; p < 0.001 for total astigmatism and the JO and J45 components), and the axes of the astigmatism were typically oblique and bilaterally mirror symmetric. Interestingly, the astigmatism was not permanent; the majority of the monkeys exhibited substantial reductions in the amount of astigmatism at or near the end of the lens-rearing procedures. CONCLUSIONS: In infant monkeys, visual conditions that alter axial growth can also alter corneal shape. Similarities between the astigmatic errors in our monkeys and some astigmatic errors in humans suggest that vision-dependent changes in eye growth may contribute to astigmatism in humans.+http://www.ncbi.nlm.nih.gov/pubmed/15829845Kee, Chea-Su Hung, Li-Fang Qiao-Grider, Ying Ramamirtham, Ramkumar Smith, Earl L 3rd EY 03,611/EY/NEI NIH HHS/United States EY 07,551/EY/NEI NIH HHS/United States R01 EY003611-24A1/EY/NEI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States Optometry and vision science : official publication of the American Academy of Optometry Optom Vis Sci. 2005 Apr;82(4):248-60.%1040-5488 (Print) 1040-5488 (Linking)181023315829845]College of Optometry, University of Houston, Houston, Texas 77204-2020, USA. ckee@mail.uh.edu00006324-200504000-00008 [pii]eng |t75HSmith, E. L., 3rd Kee, C. S. Ramamirtham, R. Qiao-Grider, Y. Hung, L. F.2005WPeripheral vision can influence eye growth and refractive development in infant monkeys3965-72Invest Ophthalmol Vis Sci4611 2005/10/27Animals Animals, Newborn Biometry Disease Models, Animal Eye/*growth & development/ultrasonography Laser Coagulation Macaca mulatta Refractive Errors/*physiopathology Retina/*physiopathology/surgery Retinoscopy Sensory Deprivation Vision, Ocular/*physiologyNov7PURPOSE: Given the prominence of central vision in humans, it has been assumed that visual signals from the fovea dominate emmetropization. The purpose of this study was to examine the impact of peripheral vision on emmetropization. METHODS: Bilateral, peripheral form deprivation was produced in 12 infant monkeys by rearing them with diffusers that had either 4- or 8-mm apertures centered on the pupils of each eye, to allow 24 degrees or 37 degrees of unrestricted central vision, respectively. At the end of the lens-rearing period, an argon laser was used to ablate the fovea in one eye of each of seven monkeys. Subsequently, all the animals were allowed unrestricted vision. Refractive error and axial dimensions were measured along the pupillary axis by retinoscopy and A-scan ultrasonography, respectively. Control data were obtained from 21 normal monkeys and 3 infants reared with binocular plano lenses. RESULTS: Nine of the 12 treated monkeys had refractive errors that fell outside the 10th- and 90th-percentile limits for the age-matched control subjects, and the average refractive error for the treated animals was more variable and significantly less hyperopic/more myopic (+0.03 +/- 2.39 D vs. +2.39 +/- 0.92 D). The refractive changes were symmetric in the two eyes of a given animal and axial in nature. After lens removal, all the treated monkeys recovered from the induced refractive errors. No interocular differences in the recovery process were observed in the animals with monocular foveal lesions. CONCLUSIONS: On the one hand, the peripheral retina can contribute to emmetropizing responses and to ametropias produced by an abnormal visual experience. On the other hand, unrestricted central vision is not sufficient to ensure normal refractive development, and the fovea is not essential for emmetropizing responses.+http://www.ncbi.nlm.nih.gov/pubmed/16249469Smith, Earl L 3rd Kee, Chea-Su Ramamirtham, Ramkumar Qiao-Grider, Ying Hung, Li-Fang P30 EY70551/EY/NEI NIH HHS/United States R01 EY003611-24A1/EY/NEI NIH HHS/United States R01 EY03611/EY/NEI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2005 Nov;46(11):3965-72.%0146-0404 (Print) 0146-0404 (Linking)176210016249469ICollege of Optometry, University of Houston, TX 77204, USA. esmith@uh.edu%46/11/3965 [pii] 10.1167/iovs.05-0445eng %|t76Mutti, D. O. Sinnott, L. T. Mitchell, G. L. Jones-Jordan, L. A. Moeschberger, M. L. Cotter, S. A. Kleinstein, R. N. Manny, R. E. Twelker, J. D. Zadnik, K.2011`Relative peripheral refractive error and the risk of onset and progression of myopia in children199-205Invest Ophthalmol Vis Sci521 2010/08/27Axial Length, Eye Child Disease Progression Ethnic Groups Female Follow-Up Studies Humans Hyperopia/*complications/ethnology Male Myopia/*etiology/*physiopathology Risk FactorsJanEPURPOSE: To investigate whether relative peripheral hyperopia is a risk factor for either the onset of myopia in children or the rate of myopic progression. METHODS: The risk of myopia onset was assessed in 2043 nonmyopic third-grade children (mean age +/- SD = 8.8 +/- 0.52 years) participating in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study between 1995 and 2007, 324 of whom became myopic by the eighth grade. Progression analyses used data from 774 myopic children in grades 1 to 8. Foveal and relative peripheral refractive error 30 degrees in the nasal visual field was measured annually by using cycloplegic autorefraction. Axial length was measured by A-scan ultrasonography. RESULTS: The association between more hyperopic relative peripheral refractive error in the third grade and the risk of the onset of myopia by the eighth grade varied by ethnic group (Asian children odds ratio [OR] = 1.56, 95% confidence interval [CI] = 1.06-2.30; African-American children OR = 0.75, 95% CI = 0.58-0.96; Hispanics, Native Americans, and whites showed no significant association). Myopia progression was greater per diopter of more hyperopic relative peripheral refractive error, but only by a small amount (-0.024 D per year; P = 0.02). Axial elongation was unrelated to the average relative peripheral refractive error (P = 0.77), regardless of ethnicity. CONCLUSIONS: Relative peripheral hyperopia appears to exert little consistent influence on the risk of the onset of myopic refractive error, on the rate of myopia progression, or on axial elongation.+http://www.ncbi.nlm.nih.gov/pubmed/20739476Mutti, Donald O Sinnott, Loraine T Mitchell, G Lynn Jones-Jordan, Lisa A Moeschberger, Melvin L Cotter, Susan A Kleinstein, Robert N Manny, Ruth E Twelker, J Daniel Zadnik, Karla CLEERE Study Group R24-EY014792/EY/NEI NIH HHS/United States U10-EY08893/EY/NEI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2011 Jan 5;52(1):199-205. Print 2011 Jan.*1552-5783 (Electronic) 0146-0404 (Linking)305327520739476RThe Ohio State University College of Optometry, Columbus, OH, USA. mutti.2@osu.edu'iovs.09-4826 [pii] 10.1167/iovs.09-4826engV|t77Mutti, D. O. Hayes, J. R. Mitchell, G. L. Jones, L. A. Moeschberger, M. L. Cotter, S. A. Kleinstein, R. N. Manny, R. E. Twelker, J. D. Zadnik, K.2007mRefractive error, axial length, and relative peripheral refractive error before and after the onset of myopia2510-9Invest Ophthalmol Vis Sci486 2007/05/26Adolescent Age of Onset Child Eye/*pathology/ultrasonography Female Humans Hyperopia/ethnology/physiopathology Male Models, Biological Myopia/ethnology/*physiopathology Refraction, Ocular/*physiologyJun; PURPOSE: To evaluate refractive error, axial length, and relative peripheral refractive error before, during the year of, and after the onset of myopia in children who became myopic compared with emmetropes. METHODS: Subjects were 605 children 6 to 14 years of age who became myopic (at least -0.75 D in each meridian) and 374 emmetropic (between -0.25 D and +1.00 D in each meridian at all visits) children participating between 1995 and 2003 in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study. Axial length was measured annually by A-scan ultrasonography. Relative peripheral refractive error (the difference between the spherical equivalent cycloplegic autorefraction 30 degrees in the nasal visual field and in primary gaze) was measured using either of two autorefractors (R-1; Canon, Lake Success, NY [no longer manufactured] or WR 5100-K; Grand Seiko, Hiroshima, Japan). Refractive error was measured with the same autorefractor with the subjects under cycloplegia. Each variable in children who became myopic was compared to age-, gender-, and ethnicity-matched model estimates of emmetrope values for each annual visit from 5 years before through 5 years after the onset of myopia. RESULTS: In the sample as a whole, children who became myopic had less hyperopia and longer axial lengths than did emmetropes before and after the onset of myopia (4 years before through 5 years after for refractive error and 3 years before through 5 years after for axial length; P < 0.0001 for each year). Children who became myopic had more hyperopic relative peripheral refractive errors than did emmetropes from 2 years before onset through 5 years after onset of myopia (P < 0.002 for each year). The fastest rate of change in refractive error, axial length, and relative peripheral refractive error occurred during the year before onset rather than in any year after onset. Relative peripheral refractive error remained at a consistent level of hyperopia each year after onset, whereas axial length and myopic refractive error continued to elongate and to progress, respectively, although at slower rates compared with the rate at onset. CONCLUSIONS: A more negative refractive error, longer axial length, and more hyperopic relative peripheral refractive error in addition to faster rates of change in these variables may be useful for predicting the onset of myopia, but only within a span of 2 to 4 years before onset. Becoming myopic does not appear to be characterized by a consistent rate of increase in refractive error and expansion of the globe. Acceleration in myopia progression, axial elongation, and peripheral hyperopia in the year prior to onset followed by relatively slower, more stable rates of change after onset suggests that more than one factor may influence ocular expansion during myopia onset and progression.+http://www.ncbi.nlm.nih.gov/pubmed/17525178Mutti, Donald O Hayes, John R Mitchell, G Lynn Jones, Lisa A Moeschberger, Melvin L Cotter, Susan A Kleinstein, Robert N Manny, Ruth E Twelker, J Daniel Zadnik, Karla CLEERE Study Group R24-EY014792/EY/NEI NIH HHS/United States U10 EY008893-16/EY/NEI NIH HHS/United States U10-EY08893/EY/NEI NIH HHS/United States Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2007 Jun;48(6):2510-9.%0146-0404 (Print) 0146-0404 (Linking)265771917525178[Ohio State University College of Optometry, Columbus, Ohio 43210-1240, USA. mutti.2@osu.edu$48/6/2510 [pii] 10.1167/iovs.06-0562eng ||78QAtchison, D. A. Pritchard, N. Schmid, K. L. Scott, D. H. Jones, C. E. Pope, J. M.20055Shape of the retinal surface in emmetropia and myopia2698-707Invest Ophthalmol Vis Sci468 2005/07/27Adolescent Adult Anterior Eye Segment/anatomy & histology Body Weights and Measures Female Humans Magnetic Resonance Imaging Male Myopia/*etiology Retina/*anatomy & histology Sex FactorsAug#PURPOSE: To determine and compare the shapes of the retinas of emmetropic and myopic eyes. METHODS: Nonrotationally symmetrical ellipsoids were mathematically fitted to the retinal surfaces of 21 emmetropic and 66 myopic eyes (up to -12 D) of participants aged 18 to 36 years (mean, 25.5) using transverse axial and sagittal images derived from magnetic resonance imaging. RESULTS: The shapes of the ellipsoids varied considerably between subjects with similar refractive errors. The shapes were oblate (steepening toward the equator) in most of the emmetropic eyes (i.e., the axial dimensions of the ellipsoids were smaller than both the vertical and horizontal dimensions). As myopia increased, all ellipsoid dimensions increased with the axial dimension increasing more than the vertical dimension, which in turn increased more than the horizontal dimension (increases in approximate ratios 3:2:1). The relative difference in the increase of these dimensions meant that as the degree of myopia increased the retinal shape decreased in oblateness. However, few myopic eyes were prolate (flattening toward the equator). Independent of myopia, the ellipsoids were tilted about the vertical axis by 11 degrees +/- 13 degrees , and ellipsoid centers were decentered horizontally by 0.5 +/- 0.4 mm nasally and 0.2 +/- 0.5 mm inferiorly, relative to the fovea. CONCLUSIONS: In general both emmetropic and myopic retinas are oblate in shape, although myopic eyes less so. This finding may be relevant to theories implicating the peripheral retina in the development of myopia.+http://www.ncbi.nlm.nih.gov/pubmed/16043841Atchison, David A Pritchard, Nicola Schmid, Katrina L Scott, Dion H Jones, Catherine E Pope, James M Comparative Study Research Support, Non-U.S. Gov't United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2005 Aug;46(8):2698-707.%0146-0404 (Print) 0146-0404 (Linking)16043841Centre for Health Research-Optometry, Queensland University of Technology, Brisbane, Queensland, Australia. d.atchison@qut.edu.au$46/8/2698 [pii] 10.1167/iovs.04-1506eng ||79QAtchison, D. A. Pritchard, N. Schmid, K. L. Scott, D. H. Jones, C. E. Pope, J. M.20055Shape of the retinal surface in emmetropia and myopia2698-707Invest Ophthalmol Vis Sci468 2005/07/27Adolescent Adult Anterior Eye Segment/anatomy & histology Body Weights and Measures Female Humans Magnetic Resonance Imaging Male Myopia/*etiology Retina/*anatomy & histology Sex FactorsAug#PURPOSE: To determine and compare the shapes of the retinas of emmetropic and myopic eyes. METHODS: Nonrotationally symmetrical ellipsoids were mathematically fitted to the retinal surfaces of 21 emmetropic and 66 myopic eyes (up to -12 D) of participants aged 18 to 36 years (mean, 25.5) using transverse axial and sagittal images derived from magnetic resonance imaging. RESULTS: The shapes of the ellipsoids varied considerably between subjects with similar refractive errors. The shapes were oblate (steepening toward the equator) in most of the emmetropic eyes (i.e., the axial dimensions of the ellipsoids were smaller than both the vertical and horizontal dimensions). As myopia increased, all ellipsoid dimensions increased with the axial dimension increasing more than the vertical dimension, which in turn increased more than the horizontal dimension (increases in approximate ratios 3:2:1). The relative difference in the increase of these dimensions meant that as the degree of myopia increased the retinal shape decreased in oblateness. However, few myopic eyes were prolate (flattening toward the equator). Independent of myopia, the ellipsoids were tilted about the vertical axis by 11 degrees +/- 13 degrees , and ellipsoid centers were decentered horizontally by 0.5 +/- 0.4 mm nasally and 0.2 +/- 0.5 mm inferiorly, relative to the fovea. CONCLUSIONS: In general both emmetropic and myopic retinas are oblate in shape, although myopic eyes less so. This finding may be relevant to theories implicating the peripheral retina in the development of myopia.+http://www.ncbi.nlm.nih.gov/pubmed/16043841Atchison, David A Pritchard, Nicola Schmid, Katrina L Scott, Dion H Jones, Catherine E Pope, James M Comparative Study Research Support, Non-U.S. Gov't United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2005 Aug;46(8):2698-707.%0146-0404 (Print) 0146-0404 (Linking)16043841Centre for Health Research-Optometry, Queensland University of Technology, Brisbane, Queensland, Australia. d.atchison@qut.edu.au$46/8/2698 [pii] 10.1167/iovs.04-1506eng ||7:"Siegwart, J. T., Jr. Norton, T. T.1999VRegulation of the mechanical properties of tree shrew sclera by the visual environment387-407 Vision Res392 1999/05/18Animals Biomechanics Elasticity Environment Rheology Sclera/growth & development/*physiology Sensory Deprivation Tupaiidae/*physiology Vision, Monocular Visual Perception/*physiologyJan Experiments in several species have shown that the axial elongation rate of the developing eye can be increased or decreased by manipulating the visual environment, indicating that a visually guided emmetropization mechanism controls the enlargement of the vertebrate eye during postnatal development. Previous studies in tree shrews (Tupaia glis belangeri) suggest that regulation of the mechanical properties of the sclera may be an important part of the mechanism that controls the axial elongation rate in this mammal. To learn whether the mechanical properties of the sclera change when the axial elongation rate is increased or decreased under visual control, uniaxial mechanical tests were performed on 3-mm wide strips of tree shrew sclera. The creep rate was measured under 1, 3, and 5 g of tension, maintained for 30 min at each level. The modulus of elasticity was calculated from the elastic extension that occurred when the force was increased from 0 to 1 g, 1 to 3 g, and 3 to 5 g. Both were measured in the sclera of both eyes from animals exposed to four experimental conditions: (1) Normal development, at intervals from the day of natural eyelid opening (day 1 of visual experience [VE]) to greater than 5 years of age; (2) Monocular form deprivation (MD), for varying lengths of time; (3) Recovery from MD; (4) Monocular -5 D lens treatment. The creep rate was low in normal animals (1-2% elongation/h), did not change significantly between day 1 and day 75 of VE, and was not significantly different between the two eyes. Four days of MD produced a 200-300% increase in creep rate in the sclera from deprived eyes. Creep rate remained similarly elevated after 11 and 21 days of MD. After 2 days of recovery, which followed 11 days of MD, the creep rate of sclera from the recovering eyes was below normal levels. In animals that wore a monocular -5 D lens for up to 21 days, creep rate increased, and then decreased, in concert with the increase, and decrease, in axial elongation rate as the eyes compensated for the lens. The modulus of elasticity of the sclera was not significantly affected by any manipulation. The temporal correspondence between changes in axial elongation rate and changes in creep rate support the hypothesis that regulation of the time-dependent mechanical properties of fibrous mammalian sclera plays a role in controlling axial elongation rate during both normal emmetropization and the development of refractive errors.+http://www.ncbi.nlm.nih.gov/pubmed/10326144Siegwart, J T Jr Norton, T T EY03039/EY/NEI NIH HHS/United States EY05922/EY/NEI NIH HHS/United States RR05807/RR/NCRR NIH HHS/United States Research Support, U.S. Gov't, P.H.S. England Vision research Vision Res. 1999 Jan;39(2):387-407.%0042-6989 (Print) 0042-6989 (Linking)10326144tDepartment of Physiological Optics, University of Alabama at Birmingham 35294-4390, USA. jsiegwart@icare.opt.uab.eduS0042698998001503 [pii]eng ||7;"Siegwart, J. T., Jr. Norton, T. T.1999VRegulation of the mechanical properties of tree shrew sclera by the visual environment387-407 Vision Res392 1999/05/18Animals Biomechanics Elasticity Environment Rheology Sclera/growth & development/*physiology Sensory Deprivation Tupaiidae/*physiology Vision, Monocular Visual Perception/*physiologyJan Experiments in several species have shown that the axial elongation rate of the developing eye can be increased or decreased by manipulating the visual environment, indicating that a visually guided emmetropization mechanism controls the enlargement of the vertebrate eye during postnatal development. Previous studies in tree shrews (Tupaia glis belangeri) suggest that regulation of the mechanical properties of the sclera may be an important part of the mechanism that controls the axial elongation rate in this mammal. To learn whether the mechanical properties of the sclera change when the axial elongation rate is increased or decreased under visual control, uniaxial mechanical tests were performed on 3-mm wide strips of tree shrew sclera. The creep rate was measured under 1, 3, and 5 g of tension, maintained for 30 min at each level. The modulus of elasticity was calculated from the elastic extension that occurred when the force was increased from 0 to 1 g, 1 to 3 g, and 3 to 5 g. Both were measured in the sclera of both eyes from animals exposed to four experimental conditions: (1) Normal development, at intervals from the day of natural eyelid opening (day 1 of visual experience [VE]) to greater than 5 years of age; (2) Monocular form deprivation (MD), for varying lengths of time; (3) Recovery from MD; (4) Monocular -5 D lens treatment. The creep rate was low in normal animals (1-2% elongation/h), did not change significantly between day 1 and day 75 of VE, and was not significantly different between the two eyes. Four days of MD produced a 200-300% increase in creep rate in the sclera from deprived eyes. Creep rate remained similarly elevated after 11 and 21 days of MD. After 2 days of recovery, which followed 11 days of MD, the creep rate of sclera from the recovering eyes was below normal levels. In animals that wore a monocular -5 D lens for up to 21 days, creep rate increased, and then decreased, in concert with the increase, and decrease, in axial elongation rate as the eyes compensated for the lens. The modulus of elasticity of the sclera was not significantly affected by any manipulation. The temporal correspondence between changes in axial elongation rate and changes in creep rate support the hypothesis that regulation of the time-dependent mechanical properties of fibrous mammalian sclera plays a role in controlling axial elongation rate during both normal emmetropization and the development of refractive errors.+http://www.ncbi.nlm.nih.gov/pubmed/10326144Siegwart, J T Jr Norton, T T EY03039/EY/NEI NIH HHS/United States EY05922/EY/NEI NIH HHS/United States RR05807/RR/NCRR NIH HHS/United States Research Support, U.S. Gov't, P.H.S. England Vision research Vision Res. 1999 Jan;39(2):387-407.%0042-6989 (Print) 0042-6989 (Linking)10326144tDepartment of Physiological Optics, University of Alabama at Birmingham 35294-4390, USA. jsiegwart@icare.opt.uab.eduS0042698998001503 [pii]eng _||7<IRose, K. A. Morgan, I. G. Smith, W. Burlutsky, G. Mitchell, P. Saw, S. M.2008YMyopia, lifestyle, and schooling in students of Chinese ethnicity in Singapore and Sydney527-30Arch Ophthalmol1264 2008/04/17 Asian Continental Ancestry Group/*ethnology Child Cross-Sectional Studies *Education Female Humans Life Style/*ethnology Male Myopia/*ethnology New South Wales/epidemiology Prevalence Questionnaires Refraction, Ocular Risk Factors Singapore/epidemiology Visual AcuityApr_OBJECTIVE: To compare the prevalence and risk factors for myopia in 6- and 7-year-old children of Chinese ethnicity in Sydney and Singapore. METHODS: Two cross-sectional samples of age- and ethnicity-matched primary school children participated: 124 from the Sydney Myopia Study and 628 from the Singapore Cohort Study on the Risk Factors for Myopia. Cycloplegic autorefraction was used to determine myopia prevalence (spherical equivalent < or = -0.5 diopter). Lifestyle activities were ascertained by questionnaire. RESULTS: The prevalence of myopia in 6- and 7-year-old children of Chinese ethnicity was significantly lower in Sydney (3.3%) than in Singapore (29.1%) (P < .001). The prevalence of myopia in 1 or more parents was 68% in Sydney and 71% in Singapore. Children in Sydney read more books per week (P < .001) and did more total near-work activity (P = .002). Children in Sydney spent more time on outdoor activities (13.75 vs 3.05 hours per week; P < .001), which was the most significant factor associated with the differences in the prevalence of myopia between the 2 sites. CONCLUSIONS: The lower prevalence of myopia in Sydney was associated with increased hours of outdoor activities. We hypothesize that another factor contributing to the differences in the prevalence of myopia may be the early educational pressures found in Singapore but not in Sydney.+http://www.ncbi.nlm.nih.gov/pubmed/18413523Rose, Kathryn A Morgan, Ian G Smith, Wayne Burlutsky, George Mitchell, Paul Saw, Seang-Mei Comparative Study Research Support, Non-U.S. Gov't United States Archives of ophthalmology Arch Ophthalmol. 2008 Apr;126(4):527-30.*1538-3601 (Electronic) 0003-9950 (Linking)18413523Discipline of Applied Vision Sciences, Faculty of Health Sciences, University of Sydney, Lidcombe, Australia. k.rose@usyd.edu.au*126/4/527 [pii] 10.1001/archopht.126.4.527eng||7=Low, W. Dirani, M. Gazzard, G. Chan, Y. H. Zhou, H. J. Selvaraj, P. Au Eong, K. G. Young, T. L. Mitchell, P. Wong, T. Y. Saw, S. M.2010_Family history, near work, outdoor activity, and myopia in Singapore Chinese preschool children1012-6Br J Ophthalmol948 2010/05/18Child Child, Preschool Cross-Sectional Studies Exercise Female Genetic Predisposition to Disease Humans Infant Leisure Activities Male Myopia/epidemiology/*etiology/genetics *Reading Risk Factors Singapore/epidemiologyAug{AIMS: To investigate the risk factors for myopia, including near work and outdoor activity, in Singapore Chinese preschool children. METHODS: A cross-sectional study, with disproportionate random sampling by 6-month age groups, of 3009 Singapore Chinese children aged 6-72 months was performed. Information on family history, near work and outdoor activity was obtained. Spherical equivalent refraction (SER) was assessed. RESULTS: Children with two myopic parents were more likely to be myopic (adjusted OR=1.91; 95% CI 1.38 to 2.63) and to have a more myopic SER (regression coefficient=-0.35; 95% CI -0.47 to -0.22) than children without myopic parents. For each 1 cm taller height, the SER was more myopic by 0.01 dioptres. Neither near work nor outdoor activity was associated with preschool myopia. CONCLUSIONS: A family history of myopia was the strongest factor associated with preschool myopia. In contrast, neither near work nor outdoor activity was found to be associated with early myopia. These data suggest that genetic factors may play a more substantial role in the development of early-onset myopia than key environmental factors.+http://www.ncbi.nlm.nih.gov/pubmed/20472747Low, Wilson Dirani, Mohamed Gazzard, Gus Chan, Yiong-Huak Zhou, Hui-Jun Selvaraj, Prabakaran Au Eong, Kah-Guan Young, Terri L Mitchell, Paul Wong, Tien-Yin Saw, Seang-Mei England The British journal of ophthalmology Br J Ophthalmol. 2010 Aug;94(8):1012-6. Epub 2010 May 14.*1468-2079 (Electronic) 0007-1161 (Linking)20472747Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine, National University of Singapore, 16 Medical Drive (MD3), Singapore 117597.-bjo.2009.173187 [pii] 10.1136/bjo.2009.173187eng ||7>cDirani, M. Tong, L. Gazzard, G. Zhang, X. Chia, A. Young, T. L. Rose, K. A. Mitchell, P. Saw, S. M.20099Outdoor activity and myopia in Singapore teenage children997-1000Br J Ophthalmol938 2009/02/13Adolescent Age Factors Child Female Humans *Leisure Activities Male Myopia/epidemiology/*prevention & control Sex Factors Singapore/epidemiology Sports/*statistics & numerical data Time Factors Young AdultAugAIM: To investigate the relationship of outdoor activities and myopia in Singapore teenage children. METHODS: Teenage children (1249 participants), examined in the Singapore Cohort study Of Risk factors for Myopia (SCORM), during 2006 were included in analyses. Participants completed questionnaires that quantified total outdoor activity, and underwent an eye examination. RESULTS: The mean total time spent on outdoor activity was 3.24 h/day. The total outdoor activity (h/day) was significantly associated with myopia, odds ratio 0.90 (95% CI 0.84 to 0.96) (p = 0.004), after adjusting for age, gender, ethnicity, school type, books read per week, height, parental myopia, parental education and intelligence quotient. In addition, the total time spent outdoors was associated with significantly less myopic refraction (regression coefficient = 0.17; CI 0.10 to 0.25, p<0.001) and shorter axial length (regression coefficient -0.06 (CI -0.1 to -0.03, p<0.001). Total sports was also significantly negatively associated with myopia (p = 0.008) but not indoor sports (p = 0.16). CONCLUSIONS: Participants who spent more time outdoors were less likely to be myopic. Thus, outdoor activity may protect against development of myopia in children, supporting recent Australian data. As near work did not predict outdoor activity, this can be viewed as an independent factor and not merely the reciprocal of near work.+http://www.ncbi.nlm.nih.gov/pubmed/19211608Dirani, M Tong, L Gazzard, G Zhang, X Chia, A Young, T L Rose, K A Mitchell, P Saw, S-M Research Support, Non-U.S. Gov't England The British journal of ophthalmology Br J Ophthalmol. 2009 Aug;93(8):997-1000. Epub 2009 Feb 11.*1468-2079 (Electronic) 0007-1161 (Linking)19211608Singapore Eye Research Institute, and Department of Community, Occupational and Family Medicine, Yong Loo Lin School of Medicine, National University of Singapore, MD3, 16 Medical Drive, Singapore 117597. dirani@unimelb.edu.au-bjo.2008.150979 [pii] 10.1136/bjo.2008.150979eng ||7?cDirani, M. Tong, L. Gazzard, G. Zhang, X. Chia, A. Young, T. L. Rose, K. A. Mitchell, P. Saw, S. M.20099Outdoor activity and myopia in Singapore teenage children997-1000Br J Ophthalmol938 2009/02/13Adolescent Age Factors Child Female Humans *Leisure Activities Male Myopia/epidemiology/*prevention & control Sex Factors Singapore/epidemiology Sports/*statistics & numerical data Time Factors Young AdultAugAIM: To investigate the relationship of outdoor activities and myopia in Singapore teenage children. METHODS: Teenage children (1249 participants), examined in the Singapore Cohort study Of Risk factors for Myopia (SCORM), during 2006 were included in analyses. Participants completed questionnaires that quantified total outdoor activity, and underwent an eye examination. RESULTS: The mean total time spent on outdoor activity was 3.24 h/day. The total outdoor activity (h/day) was significantly associated with myopia, odds ratio 0.90 (95% CI 0.84 to 0.96) (p = 0.004), after adjusting for age, gender, ethnicity, school type, books read per week, height, parental myopia, parental education and intelligence quotient. In addition, the total time spent outdoors was associated with significantly less myopic refraction (regression coefficient = 0.17; CI 0.10 to 0.25, p<0.001) and shorter axial length (regression coefficient -0.06 (CI -0.1 to -0.03, p<0.001). Total sports was also significantly negatively associated with myopia (p = 0.008) but not indoor sports (p = 0.16). CONCLUSIONS: Participants who spent more time outdoors were less likely to be myopic. Thus, outdoor activity may protect against development of myopia in children, supporting recent Australian data. As near work did not predict outdoor activity, this can be viewed as an independent factor and not merely the reciprocal of near work.+http://www.ncbi.nlm.nih.gov/pubmed/19211608Dirani, M Tong, L Gazzard, G Zhang, X Chia, A Young, T L Rose, K A Mitchell, P Saw, S-M Research Support, Non-U.S. Gov't England The British journal of ophthalmology Br J Ophthalmol. 2009 Aug;93(8):997-1000. Epub 2009 Feb 11.*1468-2079 (Electronic) 0007-1161 (Linking)19211608Singapore Eye Research Institute, and Department of Community, Occupational and Family Medicine, Yong Loo Lin School of Medicine, National University of Singapore, MD3, 16 Medical Drive, Singapore 117597. dirani@unimelb.edu.au-bjo.2008.150979 [pii] 10.1136/bjo.2008.150979eng ||7@LRose, K. A. Morgan, I. G. Ip, J. Kifley, A. Huynh, S. Smith, W. Mitchell, P.2008=Outdoor activity reduces the prevalence of myopia in children1279-85 Ophthalmology1158 2008/02/26Child Cross-Sectional Studies Female Humans Hyperopia/epidemiology *Leisure Activities Male Myopia/*epidemiology/ethnology New South Wales/epidemiology Odds Ratio Prevalence Questionnaires Refraction, Ocular/physiology *Sports WorkAugOBJECTIVE: To assess the relationship of near, midworking distance, and outdoor activities with prevalence of myopia in school-aged children. DESIGN: Cross-sectional study of 2 age samples from 51 Sydney schools, selected using a random cluster design. PARTICIPANTS: One thousand seven hundred sixty-five 6-year-olds (year 1) and 2367 12-year-olds (year 7) participated in the Sydney Myopia Study from 2003 to 2005. METHODS: Children had a comprehensive eye examination, including cycloplegic refraction. Parents and children completed detailed questionnaires on activity. MAIN OUTCOME MEASURES: Myopia prevalence and mean spherical equivalent (SE) in relation to patterns of near, midworking distance, and outdoor activities. Myopia was defined as SE refraction < or = -0.5 diopters (D). RESULTS: Higher levels of outdoor activity (sport and leisure activities) were associated with more hyperopic refractions and lower myopia prevalence in the 12-year-old students. Students who combined high levels of near work with low levels of outdoor activity had the least hyperopic mean refraction (+0.27 D; 95% confidence interval [CI], 0.02-0.52), whereas students who combined low levels of near work with high levels of outdoor activity had the most hyperopic mean refraction (+0.56 D; 95% CI, 0.38-0.75). Significant protective associations with increased outdoor activity were seen for the lowest (P = 0.04) and middle (P = 0.02) tertiles of near-work activity. The lowest odds ratios for myopia, after adjusting for confounders, were found in groups reporting the highest levels of outdoor activity. There were no associations between indoor sport and myopia. No consistent associations between refraction and measures of activity were seen in the 6-year-old sample. CONCLUSIONS: Higher levels of total time spent outdoors, rather than sport per se, were associated with less myopia and a more hyperopic mean refraction, after adjusting for near work, parental myopia, and ethnicity.+http://www.ncbi.nlm.nih.gov/pubmed/18294691Rose, Kathryn A Morgan, Ian G Ip, Jenny Kifley, Annette Huynh, Son Smith, Wayne Mitchell, Paul Research Support, Non-U.S. Gov't United States Ophthalmology Ophthalmology. 2008 Aug;115(8):1279-85. Epub 2008 Feb 21.*1549-4713 (Electronic) 0161-6420 (Linking)18294691zSchool of Applied Vision Sciences, Faculty of Health Sciences, University of Sydney, Sydney, Australia. k.rose@usyd.edu.au8S0161-6420(07)01364-4 [pii] 10.1016/j.ophtha.2007.12.019eng ||7ALRose, K. A. Morgan, I. G. Ip, J. Kifley, A. Huynh, S. Smith, W. Mitchell, P.2008=Outdoor activity reduces the prevalence of myopia in children1279-85 Ophthalmology1158 2008/02/26Child Cross-Sectional Studies Female Humans Hyperopia/epidemiology *Leisure Activities Male Myopia/*epidemiology/ethnology New South Wales/epidemiology Odds Ratio Prevalence Questionnaires Refraction, Ocular/physiology *Sports WorkAugOBJECTIVE: To assess the relationship of near, midworking distance, and outdoor activities with prevalence of myopia in school-aged children. DESIGN: Cross-sectional study of 2 age samples from 51 Sydney schools, selected using a random cluster design. PARTICIPANTS: One thousand seven hundred sixty-five 6-year-olds (year 1) and 2367 12-year-olds (year 7) participated in the Sydney Myopia Study from 2003 to 2005. METHODS: Children had a comprehensive eye examination, including cycloplegic refraction. Parents and children completed detailed questionnaires on activity. MAIN OUTCOME MEASURES: Myopia prevalence and mean spherical equivalent (SE) in relation to patterns of near, midworking distance, and outdoor activities. Myopia was defined as SE refraction < or = -0.5 diopters (D). RESULTS: Higher levels of outdoor activity (sport and leisure activities) were associated with more hyperopic refractions and lower myopia prevalence in the 12-year-old students. Students who combined high levels of near work with low levels of outdoor activity had the least hyperopic mean refraction (+0.27 D; 95% confidence interval [CI], 0.02-0.52), whereas students who combined low levels of near work with high levels of outdoor activity had the most hyperopic mean refraction (+0.56 D; 95% CI, 0.38-0.75). Significant protective associations with increased outdoor activity were seen for the lowest (P = 0.04) and middle (P = 0.02) tertiles of near-work activity. The lowest odds ratios for myopia, after adjusting for confounders, were found in groups reporting the highest levels of outdoor activity. There were no associations between indoor sport and myopia. No consistent associations between refraction and measures of activity were seen in the 6-year-old sample. CONCLUSIONS: Higher levels of total time spent outdoors, rather than sport per se, were associated with less myopia and a more hyperopic mean refraction, after adjusting for near work, parental myopia, and ethnicity.+http://www.ncbi.nlm.nih.gov/pubmed/18294691Rose, Kathryn A Morgan, Ian G Ip, Jenny Kifley, Annette Huynh, Son Smith, Wayne Mitchell, Paul Research Support, Non-U.S. Gov't United States Ophthalmology Ophthalmology. 2008 Aug;115(8):1279-85. Epub 2008 Feb 21.*1549-4713 (Electronic) 0161-6420 (Linking)18294691zSchool of Applied Vision Sciences, Faculty of Health Sciences, University of Sydney, Sydney, Australia. k.rose@usyd.edu.au8S0161-6420(07)01364-4 [pii] 10.1016/j.ophtha.2007.12.019eng||7B3McCarthy, C. S. Megaw, P. Devadas, M. Morgan, I. G.2007kDopaminergic agents affect the ability of brief periods of normal vision to prevent form-deprivation myopia100-7 Exp Eye Res841 2006/11/11Animals Biometry Chickens Darkness Dopamine/*physiology Dopamine Agonists/pharmacology Dopamine Antagonists/pharmacology Eye/drug effects/growth & development/pathology Light Male Myopia/etiology/physiopathology/*prevention & control *Sensory DeprivationJanPlacing a translucent diffuser over the eye of a chick causes the eye to grow excessively, resulting in form-deprivation myopia. For chickens kept on a 12:12 h light/dark cycle, removing the diffuser for 3 h during the light period protects against the excessive growth, but if the bird is kept in the dark for this 3-h period, the protective effect is abolished. Injecting dopamine agonists into the eye during this 3-h dark period restores the protective effect, which can be blocked by dopamine antagonists injected just prior to diffuser removal in the light. These responses are mediated by D2 receptors, suggesting that the protective effect of normal vision against form-deprivation is mediated through the stimulation of dopamine release and activation of D2-dopamine receptors.+http://www.ncbi.nlm.nih.gov/pubmed/17094962McCarthy, C S Megaw, P Devadas, M Morgan, I G Research Support, Non-U.S. Gov't England Experimental eye research Exp Eye Res. 2007 Jan;84(1):100-7. Epub 2006 Nov 13.%0014-4835 (Print) 0014-4835 (Linking)17094962Visual Sciences Group, Research School of Biological Sciences, Centre for Visual Science and ARC Centre of Excellence in Vision Science, The Australian National University, Canberra, ACT 0200, Australia.6S0014-4835(06)00375-7 [pii] 10.1016/j.exer.2006.09.018eng~|7CSorsby, A. Leary, G. A.1969CA longitudinal study of refraction and its components during growth1-41 Spec Rep Ser Med Res Counc (G B)309 1969/01/01Age Factors Anthropometry Body Height Body Weight Child Child, Preschool Cornea/growth & development Eye/*growth & development Female Follow-Up Studies Humans Lens, Crystalline/growth & development Male Myopia/etiology *Refraction, Ocular Sex Factors*http://www.ncbi.nlm.nih.gov/pubmed/5397893Sorsby, A Leary, G A England Special report series (Medical Research Council (Great Britain)) Spec Rep Ser Med Res Counc (G B). 1969;309:1-41.0072-6575 (Print)5397893eng ||7DHMutti, D. O. Mitchell, G. L. Moeschberger, M. L. Jones, L. A. Zadnik, K.2002OParental myopia, near work, school achievement, and children's refractive error3633-40Invest Ophthalmol Vis Sci4312 2002/11/28Adolescent Adult Cross-Sectional Studies Educational Measurement *Educational Status Family Health Female Heredity/*genetics Humans Male Myopia/*epidemiology/etiology/*genetics Odds Ratio Ohio/epidemiology *Parents Prevalence Questionnaires Risk Factors Work/*statistics & numerical dataDec\PURPOSE: To quantify the degree of association between juvenile myopia and parental myopia, near work, and school achievement. METHODS: Refractive error, parental refractive status, current level of near activities (assumed working distance-weighted hours per week spent studying, reading for pleasure, watching television, playing video games or working on the computer), hours per week spent playing sports, and level of school achievement (scores on the Iowa Tests of Basic Skills [ITBS]) were assessed in 366 eighth grade children who participated in the Orinda Longitudinal Study of Myopia in 1991 to 1996. RESULTS: Children with myopia were more likely to have parents with myopia; to spend significantly more time studying, more time reading, and less time playing sports; and to score higher on the ITBS Reading and Total Language subtests than emmetropic children (chi(2) and Wilcoxon rank-sum tests; P < 0.024). Multivariate logistic regression models showed no substantial confounding effects between parental myopia, near work, sports activity, and school achievement, suggesting that each factor has an independent association with myopia. The multivariate odds ratio (95% confidence interval) for two compared with no parents with myopia was 6.40 (2.17-18.87) and was 1.020 (1.008-1.032) for each diopter-hour per week of near work. Interactions between parental myopia and near work were not significant (P = 0.67), indicating no increase in the risk associated with near work with an increasing number of parents with myopia. CONCLUSIONS: Heredity was the most important factor associated with juvenile myopia, with smaller independent contributions from more near work, higher school achievement, and less time in sports activity. There was no evidence that children inherit a myopigenic environment or a susceptibility to the effects of near work from their parents.+http://www.ncbi.nlm.nih.gov/pubmed/12454029ZMutti, Donald O Mitchell, G Lynn Moeschberger, Melvin L Jones, Lisa A Zadnik, Karla R21-EY12273/EY/NEI NIH HHS/United States U10-EY08893/EY/NEI NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2002 Dec;43(12):3633-40.%0146-0404 (Print) 0146-0404 (Linking)12454029POhio State University College of Optometry, Columbus 43210, USA. mutti.2@osu.edueng ||7EHMutti, D. O. Mitchell, G. L. Moeschberger, M. L. Jones, L. A. Zadnik, K.2002OParental myopia, near work, school achievement, and children's refractive error3633-40Invest Ophthalmol Vis Sci4312 2002/11/28Adolescent Adult Cross-Sectional Studies Educational Measurement *Educational Status Family Health Female Heredity/*genetics Humans Male Myopia/*epidemiology/etiology/*genetics Odds Ratio Ohio/epidemiology *Parents Prevalence Questionnaires Risk Factors Work/*statistics & numerical dataDec\PURPOSE: To quantify the degree of association between juvenile myopia and parental myopia, near work, and school achievement. METHODS: Refractive error, parental refractive status, current level of near activities (assumed working distance-weighted hours per week spent studying, reading for pleasure, watching television, playing video games or working on the computer), hours per week spent playing sports, and level of school achievement (scores on the Iowa Tests of Basic Skills [ITBS]) were assessed in 366 eighth grade children who participated in the Orinda Longitudinal Study of Myopia in 1991 to 1996. RESULTS: Children with myopia were more likely to have parents with myopia; to spend significantly more time studying, more time reading, and less time playing sports; and to score higher on the ITBS Reading and Total Language subtests than emmetropic children (chi(2) and Wilcoxon rank-sum tests; P < 0.024). Multivariate logistic regression models showed no substantial confounding effects between parental myopia, near work, sports activity, and school achievement, suggesting that each factor has an independent association with myopia. The multivariate odds ratio (95% confidence interval) for two compared with no parents with myopia was 6.40 (2.17-18.87) and was 1.020 (1.008-1.032) for each diopter-hour per week of near work. Interactions between parental myopia and near work were not significant (P = 0.67), indicating no increase in the risk associated with near work with an increasing number of parents with myopia. CONCLUSIONS: Heredity was the most important factor associated with juvenile myopia, with smaller independent contributions from more near work, higher school achievement, and less time in sports activity. There was no evidence that children inherit a myopigenic environment or a susceptibility to the effects of near work from their parents.+http://www.ncbi.nlm.nih.gov/pubmed/12454029ZMutti, Donald O Mitchell, G Lynn Moeschberger, Melvin L Jones, Lisa A Zadnik, Karla R21-EY12273/EY/NEI NIH HHS/United States U10-EY08893/EY/NEI NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2002 Dec;43(12):3633-40.%0146-0404 (Print) 0146-0404 (Linking)12454029POhio State University College of Optometry, Columbus 43210, USA. mutti.2@osu.edueng ]||7F,Hepsen, I. F. Evereklioglu, C. Bayramlar, H.2001The effect of reading and near-work on the development of myopia in emmetropic boys: a prospective, controlled, three-year follow-up study2511-20 Vision Res4119 2001/08/03Anterior Chamber/anatomy & histology Biometry Case-Control Studies Child Child Development/*physiology Corneal Topography Humans Longitudinal Studies Male Myopia/*etiology *Reading Refraction, Ocular Vitreous Body/anatomy & histologySep This study aimed to investigate the effect of reading and near work on myopic development in emmetropic boys in school age. It involved totally 114 children in two groups. Right eyes of 67 randomly selected students (mean age=12.93) with mean 6 h of reading and near work (Group 1) were compared with the right eyes of 47 apprentices (mean age=12.96) working as skilled laborers (Group 2). Cycloplegic refraction, keratometric readings and biometric measurements including anterior chamber depth (ACD), lens thickness (LT), vitreous chamber depth (VCD) and axial length (AL) were performed for 3 years at 18 month intervals. Two analyses were conducted: (1) for subjects in both groups with baseline refractive error from +0.50 to -0.50 D; (2) for all subjects in both groups with baseline refractive error from +1.00 to -1.00 D. For subjects with baseline refractive error of +/-0.50 D, myopic shift was present in 20 of 41 (48.8%) in group 1 and in seven of 37 (18.9%) in group 2 at the end of the study. The magnitude of the myopic shift was 0.56 and 0.07 D in group 1 and 2, respectively. For subjects with a baseline refractive error of +/-1.00 D, myopic progression was present in 40 of 67 (59.7%) in group 1 and in 10 of 47 (21.3%) in group 2 at the last readings. In this larger refractive range, the magnitude of the myopic shift was 0.61 and 0.12 D in group 1 and 2, respectively. The mean ACD, VCD and AL were significantly higher in the last readings after 36 months than in the first readings (for each, P=0.0001) in group 1. There was no statistically significant difference between two measurements of these parameters in group 2. The final keratometric dioptric readings were lower than the first values (for each, P=0.0001) in both groups at the end of the study. This prospective and controlled study suggested that reading and near work, important environmental factors, might cause refractive myopic shifts in emmetropic students. The myopic shift was primarily related to significant increases in ACD, VCD and AL in this young age group.+http://www.ncbi.nlm.nih.gov/pubmed/11483181eHepsen, I F Evereklioglu, C Bayramlar, H England Vision research Vision Res. 2001 Sep;41(19):2511-20.%0042-6989 (Print) 0042-6989 (Linking)11483181rInonu University Medical Faculty, Turgut Ozal Medical Center, Research Hospital, Malatya, Turkey. hepsenif@usa.netS0042-6989(01)00135-3 [pii]eng ]||7G,Hepsen, I. F. Evereklioglu, C. Bayramlar, H.2001The effect of reading and near-work on the development of myopia in emmetropic boys: a prospective, controlled, three-year follow-up study2511-20 Vision Res4119 2001/08/03Anterior Chamber/anatomy & histology Biometry Case-Control Studies Child Child Development/*physiology Corneal Topography Humans Longitudinal Studies Male Myopia/*etiology *Reading Refraction, Ocular Vitreous Body/anatomy & histologySep This study aimed to investigate the effect of reading and near work on myopic development in emmetropic boys in school age. It involved totally 114 children in two groups. Right eyes of 67 randomly selected students (mean age=12.93) with mean 6 h of reading and near work (Group 1) were compared with the right eyes of 47 apprentices (mean age=12.96) working as skilled laborers (Group 2). Cycloplegic refraction, keratometric readings and biometric measurements including anterior chamber depth (ACD), lens thickness (LT), vitreous chamber depth (VCD) and axial length (AL) were performed for 3 years at 18 month intervals. Two analyses were conducted: (1) for subjects in both groups with baseline refractive error from +0.50 to -0.50 D; (2) for all subjects in both groups with baseline refractive error from +1.00 to -1.00 D. For subjects with baseline refractive error of +/-0.50 D, myopic shift was present in 20 of 41 (48.8%) in group 1 and in seven of 37 (18.9%) in group 2 at the end of the study. The magnitude of the myopic shift was 0.56 and 0.07 D in group 1 and 2, respectively. For subjects with a baseline refractive error of +/-1.00 D, myopic progression was present in 40 of 67 (59.7%) in group 1 and in 10 of 47 (21.3%) in group 2 at the last readings. In this larger refractive range, the magnitude of the myopic shift was 0.61 and 0.12 D in group 1 and 2, respectively. The mean ACD, VCD and AL were significantly higher in the last readings after 36 months than in the first readings (for each, P=0.0001) in group 1. There was no statistically significant difference between two measurements of these parameters in group 2. The final keratometric dioptric readings were lower than the first values (for each, P=0.0001) in both groups at the end of the study. This prospective and controlled study suggested that reading and near work, important environmental factors, might cause refractive myopic shifts in emmetropic students. The myopic shift was primarily related to significant increases in ACD, VCD and AL in this young age group.+http://www.ncbi.nlm.nih.gov/pubmed/11483181eHepsen, I F Evereklioglu, C Bayramlar, H England Vision research Vision Res. 2001 Sep;41(19):2511-20.%0042-6989 (Print) 0042-6989 (Linking)11483181rInonu University Medical Faculty, Turgut Ozal Medical Center, Research Hospital, Malatya, Turkey. hepsenif@usa.netS0042-6989(01)00135-3 [pii]eng ||7HIJibaja, M. L. Kingery, P. Neff, N. E. Smith, Q. Bowman, J. Holcomb, J. D.2000YTailored, interactive soap operas for breast cancer education of high-risk Hispanic women237-42 J Cancer Educ154 2001/02/24Adult Age Factors Analysis of Variance Breast Neoplasms/*prevention & control *Computer-Assisted Instruction *Drama Female Health Education/*methods Health Knowledge, Attitudes, Practice *Hispanic Americans Humans Middle Aged Poverty Areas User-Computer InterfaceWinterBACKGROUND: While Hispanic women have lower rates of breast cancer than do women of other ethnic groups, they are the least likely to undergo screening examinations. This study evaluated a culturally sensitive and linguistically appropriate, tailored, computer-based, educational program for early detection of breast cancer aimed at high-risk Hispanic women. METHODS: Spanish-speaking Hispanic women from an inner-city community health clinic were recruited and randomly assigned either to a computer intervention with an interactive soap-opera format (n = 118) or to a comparison group (n = 60). Pre- and posttests were used to identify any change in breast-cancer-related knowledge and beliefs. RESULTS: Both younger (18-40 years old) and older (41-65 years old) women in the intervention group demonstrated significant increases in their breast cancer screening knowledge and beliefs as compared with the younger and older women in the comparison group (n < 0.05). CONCLUSIONS: Computer-based tailored and interactive soap operas that are linguistically and culturally appropriate are effective in increasing breast cancer screening knowledge and beliefs among underserved Spanish-speaking Hispanic women.+http://www.ncbi.nlm.nih.gov/pubmed/11199243SJibaja, M L Kingery, P Neff, N E Smith, Q Bowman, J Holcomb, J D CA70542-01/CA/NCI NIH HHS/United States Clinical Trial Randomized Controlled Trial Research Support, U.S. Gov't, P.H.S. United States Journal of cancer education : the official journal of the American Association for Cancer Education J Cancer Educ. 2000 Winter;15(4):237-42.%0885-8195 (Print) 0885-8195 (Linking)11199243vDepartment of Family and Community Medicine, Baylor College of Medicine, Houston, Texas 77005, USA. mariaj@bcm.tmc.edu10.1080/08858190009528705eng8||7I$Wu, P. B. Date, E. S. Kingery, W. S.2000:The lumbar multifidus muscle in polysegmentally innervated483-5Electromyogr Clin Neurophysiol408 2001/01/13Denervation Electromyography Humans Low Back Pain/physiopathology/surgery Lumbar Vertebrae/innervation Lumbosacral Region Male Middle Aged Muscle, Skeletal/*innervation Spinal Nerve Roots/physiopathologyDec?We conducted a prospective case study to determine whether the lumbar multifidus muscle is polysegmentally innervated. A 49-year-old man with chronic mechanical low back pain underwent bilateral percutaneous radiofrequency neurotomy of the medial branches of the L3 dorsal rami. Electromyography (EMG) examination was performed in the L2-5 multifidi both prior to and 3 weeks after the procedure. Positive sharp waves and fibrillations appeared in the L3-L5 multifidi after the neurotomy. This study provides electrophysiological evidence in the human lumbar spine that the medial branch of the lumbar root innervates the multifidus muscle at multiple levels, i.e., the lumbar multifidus muscle is polysegmentally innervated. As a result, electromyography of the multifidus cannot identify a specific level of lumbar radiculopathy.+http://www.ncbi.nlm.nih.gov/pubmed/11155540Wu, P B Date, E S Kingery, W S Case Reports Belgium Electromyography and clinical neurophysiology Electromyogr Clin Neurophysiol. 2000 Dec;40(8):483-5.%0301-150X (Print) 0301-150X (Linking)11155540iDepartment of Physical Medicine and Rehabilitation, Palo Alto Medical Clinic, Palo Alto, California, USA.eng||7JmVan Gelder, J. Deferme, S. Annaert, P. Naesens, L. De Clercq, E. Van den Mooter, G. Kinget, R. Augustijns, P.2000}Increased absorption of the antiviral ester prodrug tenofovir disoproxil in rat ileum by inhibiting its intestinal metabolism1394-6Drug Metab Dispos2812 2000/11/30cAdenine/*analogs & derivatives/pharmacokinetics Animals Antiviral Agents/*pharmacokinetics Biotransformation Chromatography, High Pressure Liquid Ileum/*metabolism Intestinal Absorption/*physiology Intestines/metabolism Mesenteric Arteries/metabolism Organophosphorus Compounds/*pharmacokinetics Perfusion *Phosphonic Acids Prodrugs/*pharmacokinetics RatsDecPrevious studies have shown that strawberry extract increases the transepithelial transport of tenofovir disoproxil, an esterase-sensitive prodrug of the antiviral compound tenofovir (formerly PMPA), across Caco-2 monolayers. This increase in transport was at least partially due to inhibition of its intestinal metabolism. To further study the feasibility of this absorption enhancing strategy, the influence of various concentrations of strawberry extract (0-2%) on the intestinal absorption of tenofovir disoproxil (100 microM) was assessed using an in situ perfusion model with immediate blood sampling from the mesenteric vein, a model closer to the in vivo situation than the in vitro Caco-2 system. Inclusion of strawberry extract (1%) resulted in a 7-fold increase in the appearance of tenofovir equivalents. The metabolism of tenofovir disoproxil in the intestinal perfusate was significantly lower in the presence of strawberry extract (1%), showing that the metabolism of tenofovir disoproxil is reduced by the flavoring extract.+http://www.ncbi.nlm.nih.gov/pubmed/11095573Van Gelder, J Deferme, S Annaert, P Naesens, L De Clercq, E Van den Mooter, G Kinget, R Augustijns, P Research Support, Non-U.S. Gov't United states Drug metabolism and disposition: the biological fate of chemicals Drug Metab Dispos. 2000 Dec;28(12):1394-6.%0090-9556 (Print) 0090-9556 (Linking)11095573wLaboratorium voor Farmacotechnologie en Biofarmacie, Campus Gasthuisberg O&N, Katholieke Universiteit, Leuven, Belgium.eng u||7KcVan Gelder, J. Shafiee, M. De Clercq, E. Penninckx, F. Van den Mooter, G. Kinget, R. Augustijns, P.2000KSpecies-dependent and site-specific intestinal metabolism of ester prodrugs93-100 Int J Pharm2051-2 2000/09/23Animals Caco-2 Cells Esters/*pharmacokinetics Humans Intestines/*metabolism Male Nitrophenols/pharmacokinetics Prodrugs/*pharmacokinetics Rats Species Specificity SwineSep 15In order to select a species for drug absorption studies of ester prodrugs and to identify a possible absorption window with low esterase activity and hence increased absorption of the ester prodrug, the esterase activity was investigated in homogenates from various intestinal segments of different species. p-Nitrophenyl acetate and tenofovir disoproxil [bis(POC)-PMPA] were used as substrates for esterases. p-Nitrophenyl acetate is a model substrate for esterase activity, while tenofovir disoproxil (fumarate salt) is an ester prodrug of the potent antiviral nucleoside phosphonate analogue tenofovir. As esterase-mediated degradation during transepithelial transport may be a limiting factor for its oral absorption, targeting the prodrug to a region of the intestine with lower esterase activity may lead to an increase in oral absorption of the prodrug. The results obtained with p-nitrophenyl acetate and tenofovir disoproxil showed both a site-specific (duodenum > or = jejunum > ileum > or = colon) and species-dependent (rat > man > pig) degradation in intestinal homogenates. Degradation of tenofovir disoproxil in homogenates from Caco-2 monolayers (0.016+/-0.003 nmol. s(-1). mg protein(-1)) was low compared to its degradation in homogenates from human ileum (0.177+/-0.052 nmol. s(-1). mg protein(-1)). Rat ileum appears to be a suitable model to evaluate the influence of esterase activity on the oral absorption of the ester prodrug, as the degradation rate for tenofovir disoproxil (0.245+/-0.054 nmol. s(-1). mg protein(-1)) in rat ileum was similar to degradation in human ileum. The results also suggest that colon targeting may be a useful strategy to reduce the esterase-mediated degradation of ester prodrugs, hence resulting in a possible increase in their oral absorption.+http://www.ncbi.nlm.nih.gov/pubmed/11000545Van Gelder, J Shafiee, M De Clercq, E Penninckx, F Van den Mooter, G Kinget, R Augustijns, P Research Support, Non-U.S. Gov't Netherlands International journal of pharmaceutics Int J Pharm. 2000 Sep 15;205(1-2):93-100.%0378-5173 (Print) 0378-5173 (Linking)11000545_Laboratorium voor Farmacotechnologie en Biofarmacie, Campus Gasthuisberg, K.U. Leuven, Belgium.S037851730000507X [pii]eng E||7LUUgwoke, M. I. Agu, R. U. Jorissen, M. Augustijns, P. Sciot, R. Verbeke, N. Kinget, R.2000Toxicological investigations of the effects carboxymethylcellulose on ciliary beat frequency of human nasal epithelial cells in primary suspension culture and in vivo on rabbit nasal mucosa43-51 Int J Pharm2051-2 2000/09/23Animals Carboxymethylcellulose Sodium/*toxicity Cells, Cultured Cilia/drug effects/pathology/physiology Humans Hyperplasia/*chemically induced Nasal Mucosa/*drug effects/pathology/physiology RabbitsSep 15>The objective of this study was to investigate the safety of a mucoadhesive carboxymethylcellulose (CMC) formulation for intranasal administration of apomorphine. The effect of different concentrations of CMC on ciliary beat frequency (CBF) was studied using a human nasal epithelial suspension cell culture system. The CBF was determined by computerized microscope photometry. The in vivo rabbit nasal mucosal tolerance of the mucoadhesive polymer was investigated using light microscopy. Twice daily, six rabbits received CMC powder in one nostril and CMC/apomorphine powder in the alternate nostril for 4 weeks. Two control rabbits received air puffs in one nostril and nothing in the alternate nostril. The rabbits were subsequently sacrificed and the stained nasal sections examined microscopically. CMC showed both concentration- and time-dependent inhibitory effects on the CBF. Only mild-to-moderate cilio-inhibition was recorded with the different concentrations of the polymer. CMC (both with and without apomorphine) caused mild-to-moderate inflammation after 4 weeks. Necrosis, squamous metaplasia or ciliary degeneration was not observed. Based on: (1) the mild-to-moderate cilio-inhibition induced by different concentrations of CMC; and (2) the mild-to-moderate nasal mucosal inflammation caused by CMC with and without apomorphine, we conclude that this polymer can be considered as a safe carrier for short-term intranasal administration. However, further investigations are required for its use in the treatment of chronic diseases such as with apomorphine in Parkinson's disease.+http://www.ncbi.nlm.nih.gov/pubmed/11000541Ugwoke, M I Agu, R U Jorissen, M Augustijns, P Sciot, R Verbeke, N Kinget, R Research Support, Non-U.S. Gov't Netherlands International journal of pharmaceutics Int J Pharm. 2000 Sep 15;205(1-2):43-51.%0378-5173 (Print) 0378-5173 (Linking)11000541Laboratorium voor Farmacotechnologie en Biofarmacie, Campus Gasthuisberg O&N, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.S0378-5173(00)00484-1 [pii]eng||7M_Stavem, K. Kloster, R. Rossberg, E. Larsson, P. G. Dahl, R. Kinge, E. Lossius, R. Nakken, K. O.2000UAcupuncture in intractable epilepsy: lack of effect on health-related quality of life422-6Seizure96 2000/09/14*Acupuncture Therapy/methods Adult Confidence Intervals Epilepsy/psychology/*therapy Female Humans Male Middle Aged *Quality of Life/psychology Statistics, NonparametricSep1The objective of this study was to assess the effect on health-related quality of life of acupuncture and sham acupuncture as adjunctive treatment in intractable epilepsy. We performed a randomized controlled trail with two parallel treatment arms at The National Center for Epilepsy in Norway, a comprehensive epilepsy center. Thirty-four patients with long-standing drug resistant epilepsy completed the study. The intervention consisted of 20 acupuncture treatments (bilateral needling of three acupoints plus one or two individually chosen points) or sham acupuncture (bilateral needling with smaller needles of three points outside the traditional meridians) over 8 weeks. The main outcome measures were changes in mean health-related quality of life scores for the two groups after 8 weeks, using the 89-item Quality of Life in Epilepsy (QOLIE-89) questionnaire. We found no difference between the acupuncture and sham acupuncture groups in score changes in any dimension of the QOLIE-89 questionnaire, despite testing a large number of dimensions. We also found no change in QOLIE-89 scores between baseline and 8 weeks in either groups. In conclusion, we could not demonstrate a significant effect of traditional acupuncture or sham acupuncture on the health-related quality of life of patients with intractable epilepsy.+http://www.ncbi.nlm.nih.gov/pubmed/10986000Stavem, K Kloster, R Rossberg, E Larsson, P G Dahl, R Kinge, E Lossius, R Nakken, K O Clinical Trial Randomized Controlled Trial England Seizure : the journal of the British Epilepsy Association Seizure. 2000 Sep;9(6):422-6.%1059-1311 (Print) 1059-1311 (Linking)10986000Foundation for Health Services Research (HELTEF), Central Hospital of Akershus, Nordbyhagen, Norway. knut.stavem@klinmed.uio.no210.1053/seiz.2000.0436 S1059-1311(00)90436-9 [pii]eng ||7NUgwoke, M. I. Agu, R. U. Vanbilloen, H. Baetens, J. Augustijns, P. Verbeke, N. Mortelmans, L. Verbruggen, A. Kinget, R. Bormans, G.2000yScintigraphic evaluation in rabbits of nasal drug delivery systems based on carbopol 971p((R)) and carboxymethylcellulose207-14J Control Release682 2000/08/05 Animals Apomorphine/pharmacology Carboxymethylcellulose Sodium/*administration & dosage/pharmacokinetics *Drug Delivery Systems Male Mucociliary Clearance Nasal Mucosa/*metabolism Polyvinyls/*administration & dosage/pharmacokinetics Rabbits Technetium/diagnostic useAug 10]The residence time of apomorphine mucoadhesive preparations incorporating 99mTc labeled colloidal albumin in rabbit nasal cavity was evaluated by gamma scintigraphy. This technique was used to compare the nasal clearance of preparations based either on Carbopol 971P((R)) or lactose (control), each with and without apomorphine, or carboxymethylcellulose with apomorphine. The planar 1-min images showed an excipient-dependent progressive migration of radioactivity with time from the nasal cavity to the stomach and intestine. Thirty minutes post insufflation, the percentages of the formulations cleared from the nasal cavity were 47% for lactose, 26% for lactose/apomorphine, 10% for Carbopol 971P((R)), and 3% for both Carbopol 971P((R))/apomorphine and carboxymethylcellulose/apomorphine. Three hours post insufflation, the percentages of the formulations cleared from the nasal cavity were 70% for lactose, 58% for lactose/apomorphine, 24% for Carbopol 971P((R)), 12% for Carbopol 971P((R))/apomorphine, and 27% for carboxymethylcellulose/apomorphine. Apomorphine inhibited nasal mucociliary clearance since migration of the radioactivity administered with apomorphine containing preparations was in all cases slower than that of the corresponding powder without apomorphine. The peak plasma concentration of apomorphine was attained while all the formulations were still within the nasal cavity. The use of mucoadhesive polymers such as Carbopol 971P((R)) or carboxymethylcellulose in nasal dosage forms increases their residence time within the nasal cavity and provides the opportunity for sustained nasal drug delivery.+http://www.ncbi.nlm.nih.gov/pubmed/10925129Ugwoke, M I Agu, R U Vanbilloen, H Baetens, J Augustijns, P Verbeke, N Mortelmans, L Verbruggen, A Kinget, R Bormans, G Netherlands Journal of controlled release : official journal of the Controlled Release Society J Control Release. 2000 Aug 10;68(2):207-14.%0168-3659 (Print) 0168-3659 (Linking)10925129Laboratorium voor Farmacotechnologie en Biofarmacie, Campus Gasthuisberg O&N, Katholieke Universiteit Leuven, B-3000, Leuven, Belgium.S0168-3659(00)00258-3 [pii]engH||7O2Kingetsu, I. Kurosaka, D. Hashimoto, N. Tajima, N.2000T[A case of systemic lupus erythematosus associated with superior vena cava syndrome]192-9!Nihon Rinsho Meneki Gakkai Kaishi233 2000/08/05eHumans Lupus Erythematosus, Systemic/*complications Middle Aged Superior Vena Cava Syndrome/*etiologyJuntWe report on a case of systemic lupus erythematosus associated with superior vena cava syndrome. A 46-year-old woman developed polyarthralgia in December 1994. She was treated with nonsteroidal anti-inflammatory drugs. In February 1995, she was admitted to our hospital with systemic convulsion and disturbance of consciousness (III-300/Japan coma scale). Severe facial edema was also present. Laboratory studies revealed the presence of anti-nuclear antibody, anti-DNA antibody, anti-Sm antibody, and proteinuria. An X-ray film of the chest showed pericardial effusion and bilateral pleural effusions. Computed tomography of the chest showed a severe swelling of mediastinal lymph nodes. A diagnosis of systemic lupus erythematosus was made according to the American Rheumatism Association criteria. Initial treatment with intravenous dexamethasone improved the level of consciousness and decreased the facial edema, mediastinal lymphadenopathy, and the effusions on computed tomography of the chest. We believe that the most likely explanation for the facial edema is superior vena cava syndrome due to severe mediastinal lymphadenopathy.+http://www.ncbi.nlm.nih.gov/pubmed/10917018Kingetsu, I Kurosaka, D Hashimoto, N Tajima, N English Abstract Japan Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology Nihon Rinsho Meneki Gakkai Kaishi. 2000 Jun;23(3):192-9.%0911-4300 (Print) 0911-4300 (Linking)10917018KDepartment of Internal Medicine (III), Jikei University School of Medicine.jpn||7P8Ikechukwu Ugwoke, M. Kaufmann, G. Verbeke, N. Kinget, R.2000aIntranasal bioavailability of apomorphine from carboxymethylcellulose-based drug delivery systems125-31 Int J Pharm2021-2 2000/08/01Administration, Intranasal Animals Apomorphine/administration & dosage/*pharmacokinetics Carboxymethylcellulose Sodium/administration & dosage/*pharmacokinetics Dopamine Agonists/administration & dosage/*pharmacokinetics Drug Delivery Systems/*methods Male Microspheres RabbitsJul 20*Carboxymethyl cellulose (CMC) powder formulation of apomorphine was prepared by lyophilization and characterized with respect to the in vitro and intranasal in vivo release of apomorphine in rabbits. This was compared to apomorphine release from degradable starch microspheres (DSM) and lactose, as well as in vivo absorption after subcutaneous injection. In vitro apomorphine release from CMC was sustained, unlike that of DSM and lactose. Changing the drug loading of CMC from 15 to 30% (w/w) influenced drug release rate, which increased with increased drug loading. In vivo absorption of apomorphine from lactose, DSM and subcutaneous injection were rapid and not sustained. Slower absorption rates of apomorphine occurred from CMC. The fastest absorption rate was obtained with lactose and the slowest with CMC of 15% (w/w) drug loading. The T(max) from the CMC dosage forms were significantly prolonged compared to the immediate release forms. Plasma drug levels were sustained with CMC. The plasma concentration was maintained within 50% of the C(max), longer (15% (w/w), 70 min; 30% (w/w), 40 min) compared to the rest (lactose, 20 min; DSM, 25 min, subcutaneous injection, 35 min). The sustained plasma level of apomorphine by CMC was achieved with relative bioavailabilities equivalent to subcutaneous injection.+http://www.ncbi.nlm.nih.gov/pubmed/10915935Ikechukwu Ugwoke, M Kaufmann, G Verbeke, N Kinget, R Netherlands International journal of pharmaceutics Int J Pharm. 2000 Jul 20;202(1-2):125-31.%0378-5173 (Print) 0378-5173 (Linking)10915935Laboratorium voor Farmacotechnologie en Biofarmacie, Campus Gasthuisberg O&N, Katholieke Universiteit Leuven, B-3000, Leuven, Belgium.S0378517300004348 [pii]eng v||7QoAnnaert, P. Tukker, J. J. van Gelder, J. Naesens, L. de Clercq, E. van Den Mooter, G. Kinget, R. Augustijns, P.2000vIn vitro, ex vivo, and in situ intestinal absorption characteristics of the antiviral ester prodrug adefovir dipivoxil1054-62 J Pharm Sci898 2000/07/25Adenine/*analogs & derivatives/pharmacokinetics Animals Antiviral Agents/*pharmacokinetics *Intestinal Absorption Male *Phosphonic Acids Prodrugs/*pharmacokinetics Rats Rats, Wistar Verapamil/pharmacologyAugCaco-2 monolayers (in vitro), rat intestinal sheets mounted in modified Ussing Chambers (ex vivo), and in situ intestinal perfusion of rat ileum were used as models to determine and compare the absorption characteristics of the antiviral agent 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA, adefovir) and its bis(pivaloyloxymethyl)-ester prodrug [bis(POM)-PMEA, adefovir dipivoxil]. Although metabolism of adefovir dipivoxil was more pronounced in the ex vivo and in situ models than in the Caco-2 system, the transport of 'total adefovir' [= adefovir dipivoxil and its metabolites mono(POM)-PMEA and adefovir] was comparable in the three models. Compared with transport of the parent compound (adefovir), use of adefovir dipivoxil resulted in a significant increase in transport of total adefovir in the in vitro ( approximately 100-fold) and the in situ ( approximately 10-fold) models; in contrast, the ex vivo method failed to demonstrate a remarkable transport enhancement when using the ester prodrug. Similar to the results obtained in the Caco-2 model, the inclusion of the P-glycoprotein inhibitor verapamil resulted in transport enhancement during in situ perfusion of rat ileum with adefovir dipivoxil; however, no effect of verapamil could be observed in the ex vivo model. The results of this study confirm the utility of both the in vitro and in situ models to assess intestinal transport and metabolism of adefovir dipivoxil. The ex vivo model appeared to be less appropriate because of its inability to discriminate transport following administration of adefovir or adefovir dipivoxil and because of the absence of an effect of verapamil on transport when using adefovir dipivoxil.+http://www.ncbi.nlm.nih.gov/pubmed/10906729Annaert, P Tukker, J J van Gelder, J Naesens, L de Clercq, E van Den Mooter, G Kinget, R Augustijns, P Research Support, Non-U.S. Gov't United states Journal of pharmaceutical sciences J Pharm Sci. 2000 Aug;89(8):1054-62.%0022-3549 (Print) 0022-3549 (Linking)10906729JLaboratory of Pharmacotechnology & Biopharmacy, KULeuven, Leuven, Belgium.>10.1002/1520-6017(200008)89:8<1054::AID-JPS10>3.0.CO;2-5 [pii]eng(||7R6Jibaja, M. L. Sebastian, R. Kingery, P. Holcomb, J. D.2000=The multicultural sensitivity of physician assistant students79-85J Allied Health292 2000/06/30}*Attitude of Health Personnel *Cultural Diversity Humans Physician Assistants/*psychology Questionnaires Students/*psychologySummerUsing a specially designed instrument, the authors examined physician assistant students' multicultural sensitivity at four points before, during, and after the 30 months of a master's degree program. The students (n = 19) were found to have become more multiculturally sensitive by the end of the program, even in the absence of specific relevant instruction. The greatest improvement followed the end of clerkship rotations, where the students had experiences with low-income patients of other racial/ethnic backgrounds. The authors suggest that increasing such experiences during training may enhance students' multicultural sensitivity.+http://www.ncbi.nlm.nih.gov/pubmed/10874334Jibaja, M L Sebastian, R Kingery, P Holcomb, J D United states Journal of allied health J Allied Health. 2000 Summer;29(2):79-85.%0090-7421 (Print) 0090-7421 (Linking)10874334sDepartment of Family and Community Medicine, Baylor College of Medicine, Houston, TX 77030, USA. mariaj@bcm.tmc.edueng:||7SIKingery, J. R. Sowinski, K. M. Kraus, M. A. Klaunig, J. E. Mueller, B. A.2000\Vancomycin assay performance in patients with end-stage renal disease receiving hemodialysis653-6Pharmacotherapy206 2000/06/15Anti-Bacterial Agents/*blood Enzyme Multiplied Immunoassay Technique Fluorescence Polarization Humans Immunoassay Vancomycin/*bloodJun4STUDY OBJECTIVE: To compare the performance of polyclonal fluorescence polarization immunoassay (pFPIA) with that of enzyme-multiplied immunoassay technique (EMIT) in patients receiving vancomycin and hemodialysis. SETTING: Outpatient hemodialysis center. PATIENTS: Seven subjects with end-stage renal disease treated with hemodialysis 3 times/week with a cellulose triacetate hemodialyzer. INTERVENTION: Subjects received vancomycin 1000 mg intradialytically during the first study session and 750 mg every other hemodialysis session thereafter for 4 weeks. MEASUREMENTS AND MAIN RESULTS: Blood samples were obtained throughout the study, and vancomycin serum concentrations were determined by pFPIA and EMIT. The mean +/- SD difference (estimate of bias) between assays was -1.10 +/- 1.35 mg/L. The limits of agreement (mean difference +/- 1.96 x SD) between them were -3.80-1.60 mg/L. CONCLUSION: Our data suggest that the manufacturer's changes in the vancomycin pFPIA eliminated overestimation of drug concentrations in patients undergoing high-permeability hemodialysis.+http://www.ncbi.nlm.nih.gov/pubmed/10853620Kingery, J R Sowinski, K M Kraus, M A Klaunig, J E Mueller, B A Comparative Study Research Support, Non-U.S. Gov't United states Pharmacotherapy Pharmacotherapy. 2000 Jun;20(6):653-6.%0277-0008 (Print) 0277-0008 (Linking)10853620fDepartment of Pharmacy, Clarian Health Partners, Inc., Indiana University Hospital, Indianapolis, USA.eng !||7T\Damian, F. Blaton, N. Naesens, L. Balzarini, J. Kinget, R. Augustijns, P. Van den Mooter, G.2000Physicochemical characterization of solid dispersions of the antiviral agent UC-781 with polyethylene glycol 6000 and Gelucire 44/14311-22Eur J Pharm Sci104 2000/06/06Anilides/*chemical synthesis Anti-HIV Agents/*chemical synthesis Chemistry, Pharmaceutical Drug Carriers Furans/*chemical synthesis Polyethylene Glycols/*chemical synthesisQThe purpose of this study was to prepare and characterize solid dispersions of the antiviral thiocarboxanilide UC-781 with PEG 6000 and Gelucire 44/14 with the intention of improving its dissolution properties. The solid dispersions were prepared by the fusion method. Evaluation of the properties of the dispersions was performed using dissolution studies, differential scanning calorimetry, Fourier-transform infrared spectroscopy and X-ray powder diffraction. To investigate the possible formation of solid solutions of the drug in the carriers, the lattice spacings [d] of PEG 6000 and Gelucire 44/14 were determined in different concentrations of UC-781. The results obtained showed that the rate of dissolution of UC-781 was considerably improved when formulated in solid dispersions with PEG 6000 and Gelucire 44/14 as compared to pure UC-781. From the phase diagrams of PEG 6000 and Gelucire 44/14 it could be noted that up to approximately 25% w/w of the drug was dissolved in the liquid phase in the case of PEG 6000 and Gelucire 44/14. The data from the X-ray diffraction showed that the drug was still detectable in the solid state below a concentration of 5% w/w in the presence of PEG 6000 and Gelucire 44/14, while no significant changes in the lattice spacings of PEG 6000 or Gelucire 44/14 were observed. Therefore, the possibility of UC-781 to form solid solutions with the carriers under investigation was ruled out. The results from infrared spectroscopy together with those from X-ray diffraction and differential scanning calorimetry showed the absence of well-defined drug-polymer interactions.+http://www.ncbi.nlm.nih.gov/pubmed/10838021Damian, F Blaton, N Naesens, L Balzarini, J Kinget, R Augustijns, P Van den Mooter, G Netherlands European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences Eur J Pharm Sci. 2000;10(4):311-22.%0928-0987 (Print) 0928-0987 (Linking)10838021sLaboratorium voor Farmacotechnologie en Biofarmacie, K.U. Leuven, Campus Gasthuisberg O+N, B-3000, Leuven, Belgium.S0928098700000841 [pii]eng I|t7UDKingetsu, I. Ohno, N. Hayashi, N. Sakaguchi, M. Inouye, S. Saito, S.2000Common antigenicity between Japanese cedar (Cryptomeria japonica) pollen and Japanese cypress (Chamaecyparis obtusa) pollen, I. H-2 complex affects cross responsiveness to Cry j 1 and Cha o 1 at the T- and B-cell level in mice625-9 Immunology994 2000/05/03RAllergens/*immunology Animals Antigens, Plant B-Lymphocytes/*immunology Blotting, Western Cell Division/immunology Cross Reactions Epitopes/*immunology H-2 Antigens/*immunology Humans Immunoglobulin G/immunology Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Plant Proteins/*immunology Pollen/*immunology T-Lymphocytes/*immunology TreesAprCommon antigenicity among two purified Japanese cedar pollen allergens (Cry j 1 and Cry j 2) and one Japanese cypress pollen allergen (Cha o 1) was explored at the T-cell and B-cell level in mice of different H-2 haplotypes. Cry j 2 did not show any common antigenicity with Cry j 1 or Cha o 1. B10.S (H-2S) mice immunized with Cry j 1 or Cha o 1 generated T cells and antibodies reactive to both antigens, indicating the common antigenicity of these antigens. C57BL/6 (H-2b) mice were non-responders to Cry j 1. BALB/c (H-2d) mice immunized with Cry j 1 or Cha o 1 and C57BL/6 mice immunized with Cha o 1 generated T cells that were only reactive with the respective immunogen, but produced antibody reactive to both Cry j 1 and Cha o 1, indicating that Cry j 1 and Cha o 1 share their B-cell epitope but not their T-cell epitope. This finding may provide a clue for the clarification of the T-cell and B-cell epitopes of Cry j 1 and Cha o 1, even though the data are influenced by H-2 complex restriction in mice. Considering that H-2 complex restriction affects cross responsiveness to Cry j 1 and Cha o 1 at the T- and B-cell level in mice, we assessed the possible situation in humans exposed sequentially to Japanese cedar pollen and Japanese cypress pollen.+http://www.ncbi.nlm.nih.gov/pubmed/10792511Kingetsu, I Ohno, N Hayashi, N Sakaguchi, M Inouye, S Saito, S Research Support, Non-U.S. Gov't England Immunology Immunology. 2000 Apr;99(4):625-9.%0019-2805 (Print) 0019-2805 (Linking)232719910792511xDepartment of Internal Medicine (III), Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan. imm020 [pii]eng ||7V<Kingery, W. S. Guo, T. Z. Davies, M. F. Limbird, L. Maze, M.2000The alpha(2A) adrenoceptor and the sympathetic postganglionic neuron contribute to the development of neuropathic heat hyperalgesia in mice345-58Pain853 2000/04/27jAdrenergic alpha-Agonists/pharmacology Adrenergic alpha-Antagonists/pharmacology Analgesics, Non-Narcotic/pharmacology Anesthetics, Inhalation/pharmacology Animals Brain Chemistry/drug effects Dexmedetomidine/pharmacology Hot Temperature Hyperalgesia/metabolism/*physiopathology Isoflurane/pharmacology Mice Mice, Inbred Strains Neurons/metabolism/*physiology Nociceptors/physiology Pain Measurement Peripheral Nerves/*injuries/metabolism Physical Stimulation Receptors, Adrenergic, alpha-2/metabolism/*physiology Sympathectomy Sympathetic Fibers, Postganglionic/metabolism/*physiology Tibial Nerve/injuries/metabolismAprWe have addressed the role of the sympathetic nervous system in the development and maintenance of neuropathic pain. Using a new neuropathic mouse model, we examined the development of hyperalgesia in transgenic mice lacking functional alpha(2A) adrenoceptors and in sympathectomized wild-type mice, to determine if sympathetic-sensory coupling generates hyperalgesia. The development of neuropathic heat hyperalgesia required the presence of both the alpha(2A) adrenoceptor and the sympathetic postganglionic neuron (SPGN), but the development of mechanical hyperalgesia did not require either the alpha(2A) adrenoceptor or the SPGN, indicating different mechanisms of sensitization. These results suggest that the development of neuropathic heat hyperalgesia, but not mechanical hyperalgesia, requires sympathetic-sensory coupling in the peripheral nervous system. Nerve injury enhanced the analgesic efficacy of the alpha(2) adrenoceptor agonist dexmedetomidine, and paradoxically also induced an analgesic response to alpha(2) adrenoceptor antagonists. The alpha(2) agonist-evoked analgesia to mechanical stimuli was mediated by activating central alpha(2A) adrenoceptors, possibly at the spinal level. The peripherally restricted alpha(2) antagonist L659,066 evoked analgesia for heat, but not for mechanical stimuli, findings which support the hypothesis that the peripheral alpha(2) adrenoceptor plays a role in both the development and the maintenance of neuropathic heat hyperalgesia. The alpha(2) antagonist-evoked analgesia for heat stimuli was mediated by blocking peripheral and probably central alpha(2) adrenoceptors, while the analgesia for mechanical stimuli was mediated by blocking central alpha(2A) adrenoceptors. Intradermal injections with an alpha(2) agonist or antagonist had no effect on nociceptive thresholds, indicating that sympathetic-sensory coupling at the level of the cutaneous nociceptor did not contribute to the maintenance of neuropathic hyperalgesia.+http://www.ncbi.nlm.nih.gov/pubmed/10781908Kingery, W S Guo, T Z Davies, M F Limbird, L Maze, M GM30232/GM/NIGMS NIH HHS/United States Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Netherlands Pain Pain. 2000 Apr;85(3):345-58.%0304-3959 (Print) 0304-3959 (Linking)10781908jDepartment of Functional Restoration, Stanford University, Stanford, CA, USA. wkingery@leland.stanford.eduS0304395999002869 [pii]eng U||7W/Kinge, B. Midelfart, A. Jacobsen, G. Rystad, J.2000The influence of near-work on development of myopia among university students. A three-year longitudinal study among engineering students in Norway26-9Acta Ophthalmol Scand781 2000/03/22Adult Disease Progression Engineering/*education Female Follow-Up Studies Humans Male Myopia/epidemiology/*etiology/*physiopathology Norway/epidemiology Occupational Exposure/*adverse effects Prevalence Prospective Studies Questionnaires Refraction, Ocular Risk Factors *Students *WorkFebPURPOSE: The aim of this study was to investigate the effect of near-work on development and progression of myopia among adults exposed to high educational demands. METHODS: A three-year longitudinal refraction study was performed among 224 Norwegian engineering students (mean age 20.6 years, 117 females and 107 males) measuring their refraction at the beginning and the end of the period. The examinations included automated and clinical refraction in cycloplegia and a questionnaire regarding time spent on different kinds of near-work was filled in by the participants. A total of 192 students (100 females and 92 males) completed the study. RESULTS: The mean refractive change of -0.51+/-0.49 D (n=192) during the three-year period was statistically significant (p=0.0001). A significant relationship between refractive change towards myopia and time spent on reading scientific literature (p< or =0.001) and on practical near-work (p< or =0.05), respectively, was found. Also, a significant relationship between refractive change towards myopia and time spent at lectures was revealed (p< or =0.001). No relationship was found between refractive change and time spent at working with video display terminals (VDT) or watching television, respectively. CONCLUSIONS: The results indicate that intensive near-work could initiate myopia or lead to its progression in young adults. The time spent on near-work seems to play a significant role in that process.+http://www.ncbi.nlm.nih.gov/pubmed/10726783Kinge, B Midelfart, A Jacobsen, G Rystad, J Comparative Study Denmark Acta ophthalmologica Scandinavica Acta Ophthalmol Scand. 2000 Feb;78(1):26-9.%1395-3907 (Print) 1395-3907 (Linking)10726783hDepartment of Ophthalmology, Norwegian University of Science and Technology, Trondheim. bkinge@online.noeng ||7XUUgwoke, M. I. Agu, R. U. Jorissen, M. Augustijns, P. Sciot, R. Verbeke, N. Kinget, R.2000Nasal toxicological investigations of Carbopol 971P formulation of apomorphine: effects on ciliary beat frequency of human nasal primary cell culture and in vivo on rabbit nasal mucosa387-96Eur J Pharm Sci94 2000/02/09Acrylates/administration & dosage/*toxicity Adhesives/administration & dosage/*toxicity Administration, Intranasal Animals Apomorphine/administration & dosage/*toxicity Cells, Cultured Cilia/drug effects/physiology Dopamine Agonists/administration & dosage/*toxicity Dose-Response Relationship, Drug Drug Carriers Epithelial Cells/drug effects/physiology Freeze Drying Glucose/administration & dosage Humans Male Nasal Mucosa/cytology/*drug effects/physiology RabbitsFebQOBJECTIVE: The objective of this study was to investigate the nasal toxicity of a mucoadhesive Carbopol 971P formulation of apomorphine. MATERIALS AND METHODS: The effects of different concentrations of Carbopol 971P and apomorphine on ciliary beat frequency (CBF) were studied in suspension cultures of human nasal epithelial cells. The rabbit nasal mucosal tolerance of the formulation and its components were investigated using light microscopy. Different groups of the rabbits received twice daily, air puffs, glucose, glucose/apomorphine, Carbopol 971P or Carbopol 971P/apomorphine for 1 week (glucose-treated rabbits) or 1, 2 and 4 weeks (other treatments). RESULTS: Both Carbopol 971P and apomorphine showed both concentration- and time-dependent inhibitory effects on the CBF. The effects on CBF were: apomorphine, 1.0% w/v, irreversible ciliostasis; 0.1 and 0.5% w/v, reversible cilio-inhibition; 0.01%w/v, irreversible cilio-stimulation; and Carbopol 971P, 0.1 and 0.25% w/v, partially-reversible cilio-inhibition. Glucose and glucose/apomorphine physical mixture caused mild inflammation. Carbopol 971P (both with and without apomorphine) caused severe inflammation, which increased with duration of treatment. Necrosis, squamous metaplasia or ciliary degeneration was not observed. CONCLUSIONS: Due to the severe inflammation caused by Carbopol 971P with and without apomorphine, we conclude that this polymer is not a suitable carrier for intranasal administration of apomorphine. This is in spite of the reversible effects of Carbopol 971P (0.1 and 0. 25% w/v) and apomorphine (0.1 and 0.5% w/v) on CBF.+http://www.ncbi.nlm.nih.gov/pubmed/10664479(Ugwoke, M I Agu, R U Jorissen, M Augustijns, P Sciot, R Verbeke, N Kinget, R Comparative Study Research Support, Non-U.S. Gov't Netherlands European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences Eur J Pharm Sci. 2000 Feb;9(4):387-96.%0928-0987 (Print) 0928-0987 (Linking)10664479Laboratorium voor Farmacotechnologie en Biofarmacie, Campus Gasthuisberg O&N, Katholieke Universiteit Leuven, B-3000, Leuven, Belgium.S0928098799000822 [pii]eng ||7YjSawamura, S. Kingery, W. S. Davies, M. F. Agashe, G. S. Clark, J. D. Kobilka, B. K. Hashimoto, T. Maze, M.2000Antinociceptive action of nitrous oxide is mediated by stimulation of noradrenergic neurons in the brainstem and activation of [alpha]2B adrenoceptors9242-51 J Neurosci2024 2000/01/119Analgesics/*pharmacology Animals Brain Stem/cytology/*drug effects/metabolism Immunotoxins/administration & dosage Injections, Intraventricular Locus Coeruleus/cytology/drug effects/metabolism Male Mice Mice, Knockout Neurons/cytology/*drug effects/metabolism Nitrous Oxide/*pharmacology Pain Measurement/drug effects Pons/cytology/drug effects/metabolism Proto-Oncogene Proteins c-fos/metabolism RNA, Messenger/metabolism Rats Rats, Sprague-Dawley Receptors, Adrenergic/metabolism Receptors, Adrenergic, alpha-2/genetics/*metabolism Tyrosine 3-Monooxygenase/metabolismDec 15Although nitrous oxide (N(2)O) has been used to facilitate surgery for >150 years, its molecular mechanism of action is not yet defined. Having established that N(2)O-induced release of norepinephrine mediates the analgesic action at alpha(2) adrenoceptors in the spinal cord, we now investigated whether activation of noradrenergic nuclei in the brainstem is responsible for this analgesic action and which alpha(2) adrenoceptor subtype mediates this property. In rats, Fos immunoreactivity was examined in brainstem noradrenergic nuclei after exposure to nitrous oxide. After selective lesioning of noradrenergic nuclei by intracerebroventricular application of the mitochondrial toxin saporin, coupled to the antibody directed against dopamine beta hydroxylase (DbetaH-saporin), the analgesic and sedative actions of N(2)O were determined. Null mice for each of the three alpha(2) adrenoceptor subtypes (alpha(2A), alpha(2B), and alpha(2C)), and their wild-type cohorts, were tested for their antinociceptive and sedative response to N(2)O. Exposure to N(2)O increased expression of Fos immunoreactivity in each of the pontine noradrenergic nuclei (A5, locus coeruleus, and A7). DbetaH-saporin treatment eliminated nearly all of the catecholamine-containing neurons in the pons and blocked the analgesic but not the sedative effects of N(2)O. Null mice for the alpha(2B) adrenoceptor subtype exhibited a reduced or absent analgesic response to N(2)O, but their sedative response to N(2)O was intact. Our results support a pivotal role for noradrenergic pontine nuclei and alpha(2B) adrenoceptors in the analgesic, but not the sedative effects of N(2)O. Previously we demonstrated that the analgesic actions of alpha(2) adrenoceptor agonists are mediated by the alpha(2A) subtype; taken together with these data we propose that exogenous and endogenous alpha(2) adrenoceptor ligands activate different alpha(2) adrenoceptor subtypes to produce their analgesic action.+http://www.ncbi.nlm.nih.gov/pubmed/11125002|Sawamura, S Kingery, W S Davies, M F Agashe, G S Clark, J D Kobilka, B K Hashimoto, T Maze, M GM30232/GM/NIGMS NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. United states The Journal of neuroscience : the official journal of the Society for Neuroscience J Neurosci. 2000 Dec 15;20(24):9242-51.*1529-2401 (Electronic) 0270-6474 (Linking)11125002bDepartment of Anesthesia, Stanford University School of Medicine, Stanford, California 94305, USA.20/24/9242 [pii]eng .||7ZaUchenna Agu, R. Jorissen, M. Willems, T. Van den Mooter, G. Kinget, R. Verbeke, N. Augustijns, P.2000Safety assessment of selected cyclodextrins - effect on ciliary activity using a human cell suspension culture model exhibiting in vitro ciliogenesis219-26 Int J Pharm1932 1999/12/22Cells, Cultured Cilia/*drug effects Cyclodextrins/*toxicity Epithelial Cells/drug effects Excipients/*toxicity Humans Microscopy, Electron, Scanning Mucociliary Clearance/drug effects Nasal Mucosa/cytology/drug effects Solutions Time FactorsJan 5The objective of this study was to assess the cilio-inhibitory effect of a series of cyclodextrins using a human cell suspension culture system exhibiting in vitro ciliogenesis. Enzymatically released human nasal epithelial cells were cultured as sequential monolayer-suspension culture showing in vitro ciliogenesis. Ciliary beat frequency (CBF) was determined by computerized microscope photometry. Among the cyclodextrins investigated (gamma-cyclodextrin, hydroxypropyl-beta-cyclodextrin, anionic-beta-cyclodextrin polymer, dimethyl-beta-cyclodextrin and alpha-cyclodextrin), it was shown that after 30 min of exposure, gamma-cyclodextrin (10% w/v), hydroxypropyl-beta-cyclodextrin (10.0% w/v) and anionic-beta-CD polymer (8.0% w/v) were not significantly cilio-inhibitory (P0.05). Similarly, CBF remained stable upon cell exposure to alpha-cyclodextrin (2.0% w/v) and dimethyl-beta-cyclodextrin (1.0% w/v). However, higher concentrations of alpha-cyclodextrin and dimethyl-beta-cyclodextrin resulted in mild to severe cilio-inhibition after 45 min of exposure. The effect of alpha-cyclodextrin (5.0% w/v; 54+/-4% cilio-inhibition) was partially reversible while dimethyl-beta-cyclodextrin (10% w/v; 36+/-4% cilio-inhibition) was irreversible. The cilio-inhibition observed in this model was lower than reported for chicken trachea model. Given the fact that (1) irreversible cilio-inhibition observed in this study occurred only at concentrations exceeding those used in pharmaceutical formulations and/or at an unusual exposure time (45 min) and that (2) in an in vivo situation, dilution and mucociliary clearance contribute to further decrease in local concentrations of the applied compound, the results of this study confirm the safety of the cyclodextrins investigated as nasal absorption enhancers.+http://www.ncbi.nlm.nih.gov/pubmed/10606785Uchenna Agu, R Jorissen, M Willems, T Van den Mooter, G Kinget, R Verbeke, N Augustijns, P Research Support, Non-U.S. Gov't Netherlands International journal of pharmaceutics Int J Pharm. 2000 Jan 5;193(2):219-26.%0378-5173 (Print) 0378-5173 (Linking)10606785Laboratorium voor Farmacotechnologie en Biofarmacie, K.U. Leuven, Campus Gasthuisberg O&N, Herestraat 49, B-3000, Leuven, Belgium.S0378-5173(99)00342-7 [pii]eng U||7[/Kinge, B. Midelfart, A. Jacobsen, G. Rystad, J.2000The influence of near-work on development of myopia among university students. A three-year longitudinal study among engineering students in Norway26-9Acta Ophthalmol Scand781 2000/03/22Adult Disease Progression Engineering/*education Female Follow-Up Studies Humans Male Myopia/epidemiology/*etiology/*physiopathology Norway/epidemiology Occupational Exposure/*adverse effects Prevalence Prospective Studies Questionnaires Refraction, Ocular Risk Factors *Students *WorkFebPURPOSE: The aim of this study was to investigate the effect of near-work on development and progression of myopia among adults exposed to high educational demands. METHODS: A three-year longitudinal refraction study was performed among 224 Norwegian engineering students (mean age 20.6 years, 117 females and 107 males) measuring their refraction at the beginning and the end of the period. The examinations included automated and clinical refraction in cycloplegia and a questionnaire regarding time spent on different kinds of near-work was filled in by the participants. A total of 192 students (100 females and 92 males) completed the study. RESULTS: The mean refractive change of -0.51+/-0.49 D (n=192) during the three-year period was statistically significant (p=0.0001). A significant relationship between refractive change towards myopia and time spent on reading scientific literature (p< or =0.001) and on practical near-work (p< or =0.05), respectively, was found. Also, a significant relationship between refractive change towards myopia and time spent at lectures was revealed (p< or =0.001). No relationship was found between refractive change and time spent at working with video display terminals (VDT) or watching television, respectively. CONCLUSIONS: The results indicate that intensive near-work could initiate myopia or lead to its progression in young adults. The time spent on near-work seems to play a significant role in that process.+http://www.ncbi.nlm.nih.gov/pubmed/10726783Kinge, B Midelfart, A Jacobsen, G Rystad, J Comparative Study Denmark Acta ophthalmologica Scandinavica Acta Ophthalmol Scand. 2000 Feb;78(1):26-9.%1395-3907 (Print) 1395-3907 (Linking)10726783hDepartment of Ophthalmology, Norwegian University of Science and Technology, Trondheim. bkinge@online.noeng||7\PSaw, S. M. Shankar, A. Tan, S. B. Taylor, H. Tan, D. T. Stone, R. A. Wong, T. Y.20069A cohort study of incident myopia in Singaporean children1839-44Invest Ophthalmol Vis Sci475 2006/04/28Child Cohort Studies Female Humans Incidence Intelligence Tests Male Myopia/*epidemiology Questionnaires Risk Risk Factors Singapore/epidemiologyMaySPURPOSE: To determine the risk factors of incident myopia in a school-based cohort study in Singaporean children. METHODS: A 3-year prospective cohort study was conducted in Singaporean school children aged 7 to 9 years in three schools at entry. Chinese children without myopia at baseline (n = 994) were included in the analysis. The main outcome was incident myopia, defined as spherical equivalent (SE) at least -0.75 D based on cycloplegic autorefraction. Other definitions of incident myopia, at least -0.5 D and at least -1.0 D, were also assessed. RESULTS: After controlling for school, age, gender, income, reading in books per week and intelligence quotient (IQ) test scores, we found the relative risk (RR) of incident myopia defined as -0.75 D to be 1.55 (95% confidence interval [CI] 1.18-2.04) for two versus no myopic parents. The multivariate RR of myopia for IQ in the third versus first tertile was 1.50 (95% CI, 1.19-1.89). However, the RR of incident myopia was 1.01 (95% CI, 0.97-1.05) for every unit increase in books read per week. Similar results were obtained with definitions of -0.5 and -1.0 D for incident myopia. CONCLUSIONS: These data provide new prospective evidence of essential links between parental myopia, IQ scores and subsequent myopia development. However, reading in books per week was not associated with incident myopia.+http://www.ncbi.nlm.nih.gov/pubmed/16638989 Saw, Seang-Mei Shankar, Anoop Tan, Say-Beng Taylor, Hugh Tan, Donald T H Stone, Richard A Wong, Tien-Yin Comparative Study Research Support, Non-U.S. Gov't United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2006 May;47(5):1839-44.%0146-0404 (Print) 0146-0404 (Linking)16638989|Department of Community, Occupational, and Family Medicine, National University of Singapore, Singapore. cofsawsm@nus.edu.sg$47/5/1839 [pii] 10.1167/iovs.05-1081eng||7]PSaw, S. M. Shankar, A. Tan, S. B. Taylor, H. Tan, D. T. Stone, R. A. Wong, T. Y.20069A cohort study of incident myopia in Singaporean children1839-44Invest Ophthalmol Vis Sci475 2006/04/28Child Cohort Studies Female Humans Incidence Intelligence Tests Male Myopia/*epidemiology Questionnaires Risk Risk Factors Singapore/epidemiologyMaySPURPOSE: To determine the risk factors of incident myopia in a school-based cohort study in Singaporean children. METHODS: A 3-year prospective cohort study was conducted in Singaporean school children aged 7 to 9 years in three schools at entry. Chinese children without myopia at baseline (n = 994) were included in the analysis. The main outcome was incident myopia, defined as spherical equivalent (SE) at least -0.75 D based on cycloplegic autorefraction. Other definitions of incident myopia, at least -0.5 D and at least -1.0 D, were also assessed. RESULTS: After controlling for school, age, gender, income, reading in books per week and intelligence quotient (IQ) test scores, we found the relative risk (RR) of incident myopia defined as -0.75 D to be 1.55 (95% confidence interval [CI] 1.18-2.04) for two versus no myopic parents. The multivariate RR of myopia for IQ in the third versus first tertile was 1.50 (95% CI, 1.19-1.89). However, the RR of incident myopia was 1.01 (95% CI, 0.97-1.05) for every unit increase in books read per week. Similar results were obtained with definitions of -0.5 and -1.0 D for incident myopia. CONCLUSIONS: These data provide new prospective evidence of essential links between parental myopia, IQ scores and subsequent myopia development. However, reading in books per week was not associated with incident myopia.+http://www.ncbi.nlm.nih.gov/pubmed/16638989 Saw, Seang-Mei Shankar, Anoop Tan, Say-Beng Taylor, Hugh Tan, Donald T H Stone, Richard A Wong, Tien-Yin Comparative Study Research Support, Non-U.S. Gov't United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2006 May;47(5):1839-44.%0146-0404 (Print) 0146-0404 (Linking)16638989|Department of Community, Occupational, and Family Medicine, National University of Singapore, Singapore. cofsawsm@nus.edu.sg$47/5/1839 [pii] 10.1167/iovs.05-1081eng ||7^RIp, J. M. Saw, S. M. Rose, K. A. Morgan, I. G. Kifley, A. Wang, J. J. Mitchell, P.2008ORole of near work in myopia: findings in a sample of Australian school children2903-10Invest Ophthalmol Vis Sci497 2008/06/27zAdolescent Asian Continental Ancestry Group/statistics & numerical data Biometry Child European Continental Ancestry Group/statistics & numerical data Eye/pathology Family Health Female Humans Male Multivariate Analysis Myopia/ethnology/*etiology/pathology/physiopathology Odds Ratio Parents Questionnaires *Reading Refraction, Ocular *Schools Sex Factors *Students Time FactorsJulvPURPOSE: To examine the association of time spent in near work and reading with spherical equivalent refraction (SER) in a population-based sample of 12-year-old Australian schoolchildren. METHODS: Data on the time spent in near-work or outdoor activities per week and estimates for the duration of continuous reading and reading distances, were collected in questionnaires (2353 participants, 75.3% response) in the Sydney Myopia Study between 2004 and 2005; 2339 children underwent a comprehensive eye examination, including cycloplegia. RESULTS: Longer time spent on reading for pleasure and reports of close reading distance (< 30 cm) were associated with a more myopic refraction after adjustment for age, sex, ethnicity, and school type (P(trend) = 0.02 and P = 0.0003, respectively). Time spent in individual near-work activities, however, correlated poorly with SER (all r < or = 0.2) and was not significant in multivariate analyses for myopia (SER < or = -0.50 D), with adjustment for age, sex, ethnicity, parental myopia, school type, and outdoor activity. Children of European Caucasian ethnicity reported spending marginally less time in near work than children of East Asian ethnicity (26.0 h/wk vs. 32.5 h/wk, P < 0.0001). East Asian ethnicity, however, was associated with substantially greater odds of having myopia (odds ratio [OR], 11.0; 95% confidence interval [CI], 7.0-17.4). Near work such as close reading distance (< 30 cm) and continuous reading (> 30 minutes) independently increased the odds of having myopia in this sample of children. CONCLUSIONS: Although myopia was not significantly associated with time spent in near work after adjustment for other factors, there were significant independent associations with close reading distance and continuous reading. These associations may indicate that the intensity rather than the total duration of near work is an important factor.+http://www.ncbi.nlm.nih.gov/pubmed/18579757Ip, Jenny M Saw, Seang-Mei Rose, Kathryn A Morgan, Ian G Kifley, Annette Wang, Jie Jin Mitchell, Paul Research Support, Non-U.S. Gov't United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2008 Jul;49(7):2903-10.*1552-5783 (Electronic) 0146-0404 (Linking)18579757Centre for Vision Research, Department of Ophthalmology and the Westmead Millennium Institute, University of Sydney, Sydney, Australia.$49/7/2903 [pii] 10.1167/iovs.07-0804eng ||7_RIp, J. M. Saw, S. M. Rose, K. A. Morgan, I. G. Kifley, A. Wang, J. J. Mitchell, P.2008ORole of near work in myopia: findings in a sample of Australian school children2903-10Invest Ophthalmol Vis Sci497 2008/06/27zAdolescent Asian Continental Ancestry Group/statistics & numerical data Biometry Child European Continental Ancestry Group/statistics & numerical data Eye/pathology Family Health Female Humans Male Multivariate Analysis Myopia/ethnology/*etiology/pathology/physiopathology Odds Ratio Parents Questionnaires *Reading Refraction, Ocular *Schools Sex Factors *Students Time FactorsJulvPURPOSE: To examine the association of time spent in near work and reading with spherical equivalent refraction (SER) in a population-based sample of 12-year-old Australian schoolchildren. METHODS: Data on the time spent in near-work or outdoor activities per week and estimates for the duration of continuous reading and reading distances, were collected in questionnaires (2353 participants, 75.3% response) in the Sydney Myopia Study between 2004 and 2005; 2339 children underwent a comprehensive eye examination, including cycloplegia. RESULTS: Longer time spent on reading for pleasure and reports of close reading distance (< 30 cm) were associated with a more myopic refraction after adjustment for age, sex, ethnicity, and school type (P(trend) = 0.02 and P = 0.0003, respectively). Time spent in individual near-work activities, however, correlated poorly with SER (all r < or = 0.2) and was not significant in multivariate analyses for myopia (SER < or = -0.50 D), with adjustment for age, sex, ethnicity, parental myopia, school type, and outdoor activity. Children of European Caucasian ethnicity reported spending marginally less time in near work than children of East Asian ethnicity (26.0 h/wk vs. 32.5 h/wk, P < 0.0001). East Asian ethnicity, however, was associated with substantially greater odds of having myopia (odds ratio [OR], 11.0; 95% confidence interval [CI], 7.0-17.4). Near work such as close reading distance (< 30 cm) and continuous reading (> 30 minutes) independently increased the odds of having myopia in this sample of children. CONCLUSIONS: Although myopia was not significantly associated with time spent in near work after adjustment for other factors, there were significant independent associations with close reading distance and continuous reading. These associations may indicate that the intensity rather than the total duration of near work is an important factor.+http://www.ncbi.nlm.nih.gov/pubmed/18579757Ip, Jenny M Saw, Seang-Mei Rose, Kathryn A Morgan, Ian G Kifley, Annette Wang, Jie Jin Mitchell, Paul Research Support, Non-U.S. Gov't United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2008 Jul;49(7):2903-10.*1552-5783 (Electronic) 0146-0404 (Linking)18579757Centre for Vision Research, Department of Ophthalmology and the Westmead Millennium Institute, University of Sydney, Sydney, Australia.$49/7/2903 [pii] 10.1167/iovs.07-0804eng-||7`7Nathan, J. Kiely, P. M. Crewther, S. G. Crewther, D. P.1985WDisease-associated visual image degradation and spherical refractive errors in children680-8Am J Optom Physiol Opt6210 1985/10/01Adolescent Age Factors Child Child, Preschool Eye Diseases/classification/*complications Humans Infant Refractive Errors/*complications Retrospective Studies Vision Disorders/*etiologyOct^Retrospective clinical data from 496 eyes of 256 children attending a low vision clinic were analyzed to determine the relation between disease states which involve visual image degradation and refractive error. Refractive data from 1023 normal vision children were used as a control. The low vision children were grouped according to their disease classification and the acknowledged age-of-onset of their visual disability. It was found that there was an overall inability to emmetropize and a trend towards myopia. It was also observed that the diseases which led to myopia were associated with a peripheral or peripheral plus central impairment of vision and that those conditions in which foveal vision was primarily impaired showed a mild hypermetropic trend. Eyes in which the visual impairment was not congenital but occurred before the age of 3 years tended to develop hypermetropia. The deviation from emmetropia decreased with increasing age-of-onset of the visual impairment, as did the variation about the mean refraction. The plastic period for emmetropization is estimated to end at 8 to 9 years of age.*http://www.ncbi.nlm.nih.gov/pubmed/4073201Nathan, J Kiely, P M Crewther, S G Crewther, D P Research Support, Non-U.S. Gov't United states American journal of optometry and physiological optics Am J Optom Physiol Opt. 1985 Oct;62(10):680-8.%0093-7002 (Print) 0093-7002 (Linking)4073201eng-||7a7Nathan, J. Kiely, P. M. Crewther, S. G. Crewther, D. P.1985WDisease-associated visual image degradation and spherical refractive errors in children680-8Am J Optom Physiol Opt6210 1985/10/01Adolescent Age Factors Child Child, Preschool Eye Diseases/classification/*complications Humans Infant Refractive Errors/*complications Retrospective Studies Vision Disorders/*etiologyOct^Retrospective clinical data from 496 eyes of 256 children attending a low vision clinic were analyzed to determine the relation between disease states which involve visual image degradation and refractive error. Refractive data from 1023 normal vision children were used as a control. The low vision children were grouped according to their disease classification and the acknowledged age-of-onset of their visual disability. It was found that there was an overall inability to emmetropize and a trend towards myopia. It was also observed that the diseases which led to myopia were associated with a peripheral or peripheral plus central impairment of vision and that those conditions in which foveal vision was primarily impaired showed a mild hypermetropic trend. Eyes in which the visual impairment was not congenital but occurred before the age of 3 years tended to develop hypermetropia. The deviation from emmetropia decreased with increasing age-of-onset of the visual impairment, as did the variation about the mean refraction. The plastic period for emmetropization is estimated to end at 8 to 9 years of age.*http://www.ncbi.nlm.nih.gov/pubmed/4073201Nathan, J Kiely, P M Crewther, S G Crewther, D P Research Support, Non-U.S. Gov't United states American journal of optometry and physiological optics Am J Optom Physiol Opt. 1985 Oct;62(10):680-8.%0093-7002 (Print) 0093-7002 (Linking)4073201eng|t7bSieving, P. A. Fishman, G. A.19782Refractive errors of retinitis pigmentosa patients163-7Br J Ophthalmol623 1978/03/01Adolescent Adult Age Factors Astigmatism/complications Child Child, Preschool Humans Infant Middle Aged Myopia/complications Refractive Errors/*complications Retinitis Pigmentosa/*complications/geneticsMarbA retinitis pigmentosa (RP) population (268 eyes) had predominantly myopic refractive errors. Whereas 12% of a normal population have myopic refractions, myopia was found in 75% of 268 eyes of RP patients and in 95% of 41 eyes of X-linked RP patients. The spherical errors describe a single-peaked, skewed distribution, with a mean of -1.86 dioptres that is significantly (P less than 0.001) more myopic, by -2.93 D, than that of a normal population. The X-linked genetic group has a spherical mean of -5.51 D that is significantly (P less than 0.01) more myopic than the non-X-linked RP population. This X-linked spherical error distribution may be composed of two separate subdistributions. Astigmatic refractive errors greater than 0.5 D are found in 47% of this RP population, considerably in excess of the 19% of a normal population with such astigmatic errors.)http://www.ncbi.nlm.nih.gov/pubmed/638108Sieving, P A Fishman, G A Research Support, U.S. Gov't, P.H.S. England The British journal of ophthalmology Br J Ophthalmol. 1978 Mar;62(3):163-7.%0007-1161 (Print) 0007-1161 (Linking)1043172638108eng|t7cSieving, P. A. Fishman, G. A.19782Refractive errors of retinitis pigmentosa patients163-7Br J Ophthalmol623 1978/03/01Adolescent Adult Age Factors Astigmatism/complications Child Child, Preschool Humans Infant Middle Aged Myopia/complications Refractive Errors/*complications Retinitis Pigmentosa/*complications/geneticsMarbA retinitis pigmentosa (RP) population (268 eyes) had predominantly myopic refractive errors. Whereas 12% of a normal population have myopic refractions, myopia was found in 75% of 268 eyes of RP patients and in 95% of 41 eyes of X-linked RP patients. The spherical errors describe a single-peaked, skewed distribution, with a mean of -1.86 dioptres that is significantly (P less than 0.001) more myopic, by -2.93 D, than that of a normal population. The X-linked genetic group has a spherical mean of -5.51 D that is significantly (P less than 0.01) more myopic than the non-X-linked RP population. This X-linked spherical error distribution may be composed of two separate subdistributions. Astigmatic refractive errors greater than 0.5 D are found in 47% of this RP population, considerably in excess of the 19% of a normal population with such astigmatic errors.)http://www.ncbi.nlm.nih.gov/pubmed/638108Sieving, P A Fishman, G A Research Support, U.S. Gov't, P.H.S. England The British journal of ophthalmology Br J Ophthalmol. 1978 Mar;62(3):163-7.%0007-1161 (Print) 0007-1161 (Linking)1043172638108eng ||7dEAristodemou, P. Knox Cartwright, N. E. Sparrow, J. M. Johnston, R. L.2011Formula choice: Hoffer Q, Holladay 1, or SRK/T and refractive outcomes in 8108 eyes after cataract surgery with biometry by partial coherence interferometry63-71J Cataract Refract Surg371 2010/12/25Axial Length, Eye Biometry/*methods Humans Interferometry *Lenses, Intraocular Light *Phacoemulsification Postoperative Period Pseudophakia/*physiopathology Refraction, Ocular/*physiology Retrospective Studies Treatment OutcomeJanPURPOSE: To assess how intraocular lens (IOL) formula choice affects refractive outcomes after cataract surgery using IOLMaster biometry. SETTING: Department of Ophthalmology, Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, United Kingdom. DESIGN: Database study. METHODS: Hypothetical prediction errors were retrospectively calculated on prospectively collected data from electronic medical records using optimized Hoffer Q, Holladay 1, and SRK/T formulas (Sofport AO and Akreos Fit IOLs) across a range of 0.5 mm or 1.0 mm axial length (AL) subgroups. RESULTS: In short eyes, the Hoffer Q had the lowest mean absolute error (MAE) for ALs from 20.00 to 20.99 mm. The Hoffer Q and Holladay 1 had a lower MAE than the SRK/T for ALs from 21.00 to 21.49 mm. There were no statistically significant differences in MAE for ALs from 21.50 to 21.99 mm. In medium eyes, there were no statistically significant differences in MAE for any IOL formula for ALs from 22.00 to 23.49 mm. For ALs from 23.50 to 25.99 mm, there was a trend toward lower MAEs for the Holladay 1, with statistically significant differences in 2 subgroups. In long eyes, the SRK/T had the lowest MAE, with statistically significant differences for ALs of 27.00 mm or longer. CONCLUSIONS: The Hoffer Q performed best for ALs from 20.00 to 20.99 mm, the Hoffer Q and Holladay 1 for ALs from 21.00 to 21.49 mm, and the SRK/T for ALs of 27.00 mm or longer. Using optimized constants, refractive outcomes of 40%, 75%, and 95% within +/-0.25 diopter (D), +/-0.50 D, and +/-1.00 D, respectively, were achievable. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. Additional disclosure is found in the footnotes.+http://www.ncbi.nlm.nih.gov/pubmed/21183100Aristodemou, Petros Knox Cartwright, Nathaniel E Sparrow, John M Johnston, Robert L Comparative Study United States Journal of cataract and refractive surgery J Cataract Refract Surg. 2011 Jan;37(1):63-71.*1873-4502 (Electronic) 0886-3350 (Linking)21183100ABristol Eye Hospital, Bristol, United Kingdom. topetros@yahoo.com6S0886-3350(10)01566-X [pii] 10.1016/j.jcrs.2010.07.032eng v||7eEAristodemou, P. Knox Cartwright, N. E. Sparrow, J. M. Johnston, R. L.2011Intraocular lens formula constant optimization and partial coherence interferometry biometry: Refractive outcomes in 8108 eyes after cataract surgery50-62J Cataract Refract Surg371 2010/12/25Aged Axial Length, Eye *Biometry Humans Interferometry Lens Implantation, Intraocular *Lenses, Intraocular Light *Phacoemulsification Prospective Studies Refraction, Ocular/*physiology Retrospective Studies Treatment Outcome Visual Acuity/*physiologyJanPURPOSE: To assess the benefits of intraocular lens (IOL)-constant optimization for IOLMaster biometry on refractive outcomes after cataract surgery for all surgeons and individual surgeons, define acceptable levels of error in IOL-constant optimization, and calculate the minimum number of eyes required for IOL-constant optimization. SETTING: Department of Ophthalmology, Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, United Kingdom. DESIGN: Database study. METHODS: Hypothetical prediction errors were retrospectively calculated on prospectively collected data extracted from electronic medical records using manufacturers' and optimized IOL constants with Hoffer Q, Holladay 1, and SRK/T formulas for 2 IOLs. The acceptable IOL-constant optimization error margins, personalized IOL constants for individual surgeons, and minimum sample sizes for IOL-constant optimization were evaluated. RESULTS: Optimization of IOL constants reduced the mean absolute errors from 0.66 diopters (D) and 0.52 D to 0.40 D and 0.42 D for the Sofport AO IOL and Akreos Fit IOL, respectively. The percentage of eyes within +/-0.25 D, +/-0.50 D, and +/-1.00 D of target refraction improved from for both IOL models. The IOL-constant errors exceeding 0.09 for the Hoffer Q, 0.09 for the Holladay 1, and 0.15 for the SRK/T produced inferior outcomes. Differences in personalized IOL constants between most surgeons were clinically insignificant. Calculating IOL constants to within 0.06, 0.06, and 0.10 for the Hoffer Q, Holladay 1, and SRK/T, respectively, required 148 to 257 eyes. CONCLUSIONS: Optimizing IOL constants for IOLMaster biometry substantially improved refractive outcomes, far exceeding any additional benefit of personalizing IOL constants for individual surgeons. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. Additional disclosure is found in the footnotes.+http://www.ncbi.nlm.nih.gov/pubmed/21183099Aristodemou, Petros Knox Cartwright, Nathaniel E Sparrow, John M Johnston, Robert L Comparative Study United States Journal of cataract and refractive surgery J Cataract Refract Surg. 2011 Jan;37(1):50-62.*1873-4502 (Electronic) 0886-3350 (Linking)21183099ABristol Eye Hospital, Bristol, United Kingdom. topetros@yahoo.com6S0886-3350(10)01584-1 [pii] 10.1016/j.jcrs.2010.07.037eng B||7fRSchild, A. M. Rosentreter, A. Hellmich, M. Lappas, A. Dinslage, S. Dietlein, T. S.2010QEffect of a capsular tension ring on refractive outcomes in eyes with high myopia2087-93J Cataract Refract Surg3612 2010/11/30Adult Aged Aged, 80 and over Female Humans Lens Capsule, Crystalline/*surgery Lens Implantation, Intraocular Male Middle Aged Myopia, Degenerative/*physiopathology/*surgery *Phacoemulsification *Prosthesis Implantation Pseudophakia/*physiopathology Refraction, Ocular/*physiologyDecCPURPOSE: To evaluate the effect of capsular tension ring (CTR) implantation on refractive outcomes in patients with high myopia. SETTING: University of Cologne, Department of Ophthalmology, Cologne, Germany. DESIGN: Comparative case series. METHODS: The refractive outcomes in myopic eyes were compared between phacoemulsification and IOL implantation with a CTR (CTR group) and without a CTR (control group). Optical biometry (IOLMaster) was obtained. The power of the IOL was used to calculate the predicted postoperative spherical equivalent using the Haigis and SRK/T formulas. The main outcome measures were the mean error and mean absolute error of the refractive prediction error. RESULTS: The mean axial length was 29.1 mm (range 26.5 to 34.1 mm) in the CTR group and 28.2 mm (range 25.6 to 31.1 mm) in the control group. There was no statistically significant difference in the mean absolute refractive prediction error between the CTR group and the control group with the Haigis formula (P = .921) or SRK/T formula (P = .693). However, there was lower variance in the absolute refractive prediction error in the CTR group with both formulas (P = .014 and P = .027, respectively). Intragroup differences between formulas were not statistically significant (CTR, P = .069; control P = .551). CONCLUSIONS: Implantation of a CTR had no consistent effect on refractive outcomes compared with routine phacoemulsification in highly myopic eyes. There was a tendency toward higher precision in outcomes with a CTR. Results indicate IOL power calculation does not have to be changed when a CTR is used.+http://www.ncbi.nlm.nih.gov/pubmed/21111311Schild, Andrea M Rosentreter, Andre Hellmich, Martin Lappas, Alexandra Dinslage, Sven Dietlein, Thomas S United States Journal of cataract and refractive surgery J Cataract Refract Surg. 2010 Dec;36(12):2087-93.*1873-4502 (Electronic) 0886-3350 (Linking)21111311hDepartment of Ophthalmology, University Hospital of Cologne, Cologne, Germany. andrea.schild@uk-koeln.de6S0886-3350(10)01287-3 [pii] 10.1016/j.jcrs.2010.06.065eng ||7g:Kamiya, K. Aizawa, D. Igarashi, A. Komatsu, M. Shimizu, K.2008vEffects of antiglaucoma drugs on refractive outcomes in eyes with myopic regression after laser in situ keratomileusis233-238Am J Ophthalmol1452 2007/12/07Administration, Topical Adrenergic beta-Antagonists/*administration & dosage Adult Astigmatism/physiopathology Cornea/*drug effects/physiopathology Female Humans Intraocular Pressure/drug effects *Keratomileusis, Laser In Situ Lasers, Excimer Male Middle Aged Myopia/*drug therapy/physiopathology Ophthalmic Solutions/administration & dosage *Postoperative Complications Propanolamines/*administration & dosage Prospective Studies Refraction, Ocular/drug effects Visual AcuityFebPURPOSE: To assess effects of antiglaucoma drugs on refractive outcomes in eyes with myopic regression after laser in situ keratomileusis (LASIK). DESIGN: Prospective, nonrandomized clinical trial. METHODS: We examined 27 eyes with mean myopic regression +/- standard deviation of -1.26 +/- 0.48 diopters (D; range, -0.50 to -2.25 D) after LASIK. Nipradilol 2.5% was administered topically twice daily to these regressive eyes. We obtained the refraction (spherical equivalent, astigmatism), intraocular pressure (IOP) measurements, pachymetry, geometry, and refractive power of the cornea before and three months after treatment. RESULTS: Mean manifest refraction was improved significantly from -1.02 +/- 0.52 D to -0.44 +/- 0.39 D (P < .001). However, mean manifest astigmatism was changed from -0.55 +/- 0.30 D to -0.49 +/- 0.22 D, but the difference was not significant (P = .23). The IOP was decreased significantly from 11.4 +/- 2.4 mm Hg to 9.4 +/- 1.3 mm Hg (P < .001). Central corneal thickness was not changed significantly from 505.2 +/- 39.3 microm to 503.6 +/- 38.7 microm (P = .61). The posterior corneal surface was shifted posteriorly by 9.1 +/- 8.2 microm, and the total refractive power of the cornea was decreased significantly, by 0.63 +/- 0.62 D (P < .001), at three months after application. CONCLUSIONS: The preliminary data show that antiglaucoma drugs are effective for the reduction of the refractive regression, especially of the spherical errors, after LASIK. It is suggested that backward movement of the cornea may occur, possibly flattening the corneal curvature by lowering the IOP. Reduction of the IOP may contribute to improving regression after keratorefractive surgery.+http://www.ncbi.nlm.nih.gov/pubmed/18054889Kamiya, Kazutaka Aizawa, Daisuke Igarashi, Akihito Komatsu, Mari Shimizu, Kimiya Clinical Trial United States American journal of ophthalmology Am J Ophthalmol. 2008 Feb;145(2):233-238. Epub 2007 Dec 11.%0002-9394 (Print) 0002-9394 (Linking)18054889Department of Ophthalmology, University of Kitasato School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa, Japan. kamiyak-tky@umin.ac.jp5S0002-9394(07)00861-6 [pii] 10.1016/j.ajo.2007.09.036eng ||7h)Koivula, A. Petrelius, A. Zetterstrom, C.2005XClinical outcomes of phakic refractive lens in myopic and hyperopic eyes: 1-year results1145-52J Cataract Refract Surg316 2005/07/26Jun*PURPOSE: To confirm the safety, efficacy, and predictability of the surgical correction of myopia and hyperopia with the phakic refractive lens (PRL) (Medennium Inc.). SETTING: St. Eriks Eye Hospital, Stockholm, Sweden. METHODS: This was a prospective clinical study of 20 eyes, 14 myopic and 6 hyperopic, that had PRL implantation at St. Eriks Eye Hospital from April to November 2002. Examinations were performed preoperatively and 1 day, 1 week, 3 months, and 1 year postoperatively. Follow-up included evaluation of the PRL rotation with retroillumination photography, evaluation of the distance between the PRL and the crystalline lens with Scheimpflug image, laser flare, endothelial cell count, uncorrected (UCVA) and best corrected (BCVA) visual acuity, residual refractive error, refractive stability, intraocular pressure, and induced cataract. RESULTS: Postoperatively, 11 eyes (55%) gained 1 or more lines, 5 eyes (25%) had no change, and 4 eyes (20%) lost 1 line of BCVA. No eye lost 2 or more lines. Mean UCVA was 0.87+/- 0.29 postoperatively. Laser flare values were highest 1 day after operation with normalization at 3 months and without changes at 1 year (P<.05). A rotation of 10 degrees or more was found in 15 eyes (75%) during the first year. The distance between the PRL and crystalline lens was considerably less at 1 year than at baseline (P<.05). There was no statistically significant endothelial cell loss induced by the PRL (P<.05). No induced cataract, glaucoma, or inflammation was observed. In 1 hyperopic eye, horizontal iris transillumination defects were noticed at 1 year. CONCLUSION: Safety and efficacy indexes were high at 1-year follow-up. The PRL rotated slightly in the posterior chamber. The distance between the PRL and the crystalline lens was considerably less at 1 year than at baseline.+http://www.ncbi.nlm.nih.gov/pubmed/16039488Koivula, Annemari Petrelius, Anders Zetterstrom, Charlotta United States Journal of cataract and refractive surgery J Cataract Refract Surg. 2005 Jun;31(6):1145-52.%0886-3350 (Print) 0886-3350 (Linking)16039488QSt. Eriks Eye Hospital, S-112 82 Stockholm, Sweden. annemari.koivula@sankterik.se6S0886-3350(05)00160-4 [pii] 10.1016/j.jcrs.2004.11.059eng ||7i.Van Gelder, R. N. Steger-May, K. Pepose, J. S.2003|Correlation of visual and refractive outcomes between eyes after same-session bilateral laser in situ keratomileusis surgery577-83Am J Ophthalmol1355 2003/04/30/Adult Aged Aged, 80 and over Cornea/physiopathology/*surgery Female Follow-Up Studies Humans *Keratomileusis, Laser In Situ Male Middle Aged Refraction, Ocular/*physiology Refractive Errors/physiopathology *Refractive Surgical Procedures Retrospective Studies Treatment Outcome Visual Acuity/*physiologyMayPURPOSE: To determine whether between-eye refractive and visual outcomes after same-session laser in situ keratomileusis (LASIK) surgery are correlated, and to determine whether suboptimal visual and refractive outcomes in one eye are predictive of poor results in the fellow eye. DESIGN: Observational case series. METHODS: Retrospective chart review. A total of 484 eyes of 242 patients met inclusion criteria of having undergone same-day LASIK surgery and having 3-month refractive and visual acuity outcomes. Statistical comparisons of outcomes were performed, including between-eye Pearson correlation analysis and logistic regression models for predicting second-eye outcome. Main outcome measures were 1-month, 3-month, and 6-month uncorrected visual acuity and manifest refraction. RESULTS: Refractive outcomes at 1, 3, and 6 months between first (right) and second eyes were not found to be significantly different. No difference in uncorrected or best spectacle-corrected visual acuity was observed between first and second eyes Refractive outcomes of spherical equivalent, sphere, and cylinder and visual outcomes of uncorrected and best spectacle-corrected visual acuity were highly correlated between the two eyes. Analysis of cases with suboptimal outcomes (> or =1 diopter from intended correction or uncorrected acuity equal to or worse than 20/40) suggests that a poor refractive or visual outcome in the first eye increases the risk of a poor outcome in the second eye by approximately 20-fold. CONCLUSIONS: Retrospective analysis of refractive and visual outcomes from patients undergoing same-session bilateral LASIK demonstrates a high correlation of refractive and visual outcome between the eyes.+http://www.ncbi.nlm.nih.gov/pubmed/12719062Van Gelder, Russell N Steger-May, Karen Pepose, Jay S Research Support, Non-U.S. Gov't United States American journal of ophthalmology Am J Ophthalmol. 2003 May;135(5):577-83.%0002-9394 (Print) 0002-9394 (Linking)12719062tDepartment of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, USA.S0002939402022286 [pii]eng|t7jKnight-Nanan, D. M. O'Keefe, M.1996tRefractive outcome in eyes with retinopathy of prematurity treated with cryotherapy or diode laser: 3 year follow up998-1001Br J Ophthalmol8011 1996/11/01Astigmatism/complications Child, Preschool Cryotherapy Follow-Up Studies Humans Infant Infant, Newborn Laser Coagulation Longitudinal Studies Myopia/complications/physiopathology Refraction, Ocular Retinopathy of Prematurity/complications/physiopathology/*therapy Treatment OutcomeNovAIMS: To compare the refractive error 1 to 3 years after cryotherapy or diode laser treatment for threshold retinopathy of prematurity. METHODS: Twenty six infants treated with diode laser and 17 infants treated with cryotherapy underwent cycloplegic refraction during follow up. RESULTS: After 3 years of follow up, 94.1% of patients had myopia (right eye if bilateral) following cryotherapy and 45.5% of patients had myopia following diode laser treatment. The difference between the two proportions was 48.7% (95% confidence interval 17.8 to 80.1, p = 0.004). In the cryotherapy group 55% of patients were highly myopic (> -6.00 dioptres) while in the laser group there were no high myopes. CONCLUSIONS: In the diode laser group there were significantly fewer myopes than in the cryotherapy group up to 3 years after the procedure. There was no trend towards increasing myopia in the laser treated group and the refraction in these eyes stabilised after 1 year. In the cryotherapy group there was a significant increase in the degree of myopia between year 1 and year 3 of follow up (p = 0.02). Diode laser treatment is thought to be as effective as cryotherapy, and has the added benefit of reducing myopia, in the treatment of ROP.*http://www.ncbi.nlm.nih.gov/pubmed/8976729tKnight-Nanan, D M O'Keefe, M England The British journal of ophthalmology Br J Ophthalmol. 1996 Nov;80(11):998-1001.%0007-1161 (Print) 0007-1161 (Linking)5056798976729%Children's Hospital, Dublin, Ireland.eng|t7kKnight-Nanan, D. M. O'Keefe, M.1996tRefractive outcome in eyes with retinopathy of prematurity treated with cryotherapy or diode laser: 3 year follow up998-1001Br J Ophthalmol8011 1996/11/01Astigmatism/complications Child, Preschool Cryotherapy Follow-Up Studies Humans Infant Infant, Newborn Laser Coagulation Longitudinal Studies Myopia/complications/physiopathology Refraction, Ocular Retinopathy of Prematurity/complications/physiopathology/*therapy Treatment OutcomeNovAIMS: To compare the refractive error 1 to 3 years after cryotherapy or diode laser treatment for threshold retinopathy of prematurity. METHODS: Twenty six infants treated with diode laser and 17 infants treated with cryotherapy underwent cycloplegic refraction during follow up. RESULTS: After 3 years of follow up, 94.1% of patients had myopia (right eye if bilateral) following cryotherapy and 45.5% of patients had myopia following diode laser treatment. The difference between the two proportions was 48.7% (95% confidence interval 17.8 to 80.1, p = 0.004). In the cryotherapy group 55% of patients were highly myopic (> -6.00 dioptres) while in the laser group there were no high myopes. CONCLUSIONS: In the diode laser group there were significantly fewer myopes than in the cryotherapy group up to 3 years after the procedure. There was no trend towards increasing myopia in the laser treated group and the refraction in these eyes stabilised after 1 year. In the cryotherapy group there was a significant increase in the degree of myopia between year 1 and year 3 of follow up (p = 0.02). Diode laser treatment is thought to be as effective as cryotherapy, and has the added benefit of reducing myopia, in the treatment of ROP.*http://www.ncbi.nlm.nih.gov/pubmed/8976729tKnight-Nanan, D M O'Keefe, M England The British journal of ophthalmology Br J Ophthalmol. 1996 Nov;80(11):998-1001.%0007-1161 (Print) 0007-1161 (Linking)5056798976729%Children's Hospital, Dublin, Ireland.eng||7l2Saw, S. M. Gazzard, G. Shih-Yen, E. C. Chua, W. H.20050Myopia and associated pathological complications381-91Ophthalmic Physiol Opt255 2005/08/17Adolescent Adult Aged Cataract/etiology Child Choroid Diseases/etiology Glaucoma/etiology Humans Macular Degeneration/etiology Middle Aged Myopia/*complications Myopia, Degenerative/complications Optic Disk/abnormalities Retinal Diseases/etiologySepBesides the direct economic and social burden of myopia, associated ocular complications may lead to substantial visual loss. In several population and clinic-based cohorts, case-control and cross-sectional studies, higher risks of posterior subcapsular cataract, cortical and nuclear cataract in myopic patients were reported. Patients with high myopia (spherical equivalent at least -6.0 D) are more susceptible to ocular abnormalities. The prevalent risks of glaucoma were higher in myopic adults, and risks of chorioretinal abnormalities such as retinal detachment, chorioretinal atrophy and lacquer cracks increased with severity of myopia and greater axial length. Myopic adults were more likely to have tilted, rotated, and larger discs as well as other optic disc abnormalities. Often, these studies support possible associations between myopia and specific ocular complications, but we cannot infer causality because of limitations in study methodology. The detection and treatment of possible pathological ocular complications is essential in the management of high myopia. The ocular risks associated with myopia should not be underestimated and there is a public health need to prevent the onset or progression of myopia.+http://www.ncbi.nlm.nih.gov/pubmed/16101943Saw, Seang-Mei Gazzard, Gus Shih-Yen, Edwin Chan Chua, Wei-Han Review England Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists) Ophthalmic Physiol Opt. 2005 Sep;25(5):381-91.%0275-5408 (Print) 0275-5408 (Linking)16101943Department of Community, Occupational and Family Medicine, National University of Singapore, 16 Medical Drive, Singapore 117597. cofsawsm@nus.edu.sg-OPO298 [pii] 10.1111/j.1475-1313.2005.00298.xengs|t7m6Berntsen, D. A. Sinnott, L. T. Mutti, D. O. Zadnik, K.2011aAccommodative lag and juvenile-onset myopia progression in children wearing refractive correction1039-46 Vision Res519 2011/02/24May 11#The relationship between accommodative lag and annual myopia progression was investigated using linear models in 592 myopic children wearing a full refractive correction in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study. The mean (+/- SD) age and spherical equivalent refractive error at baseline were 10.4 +/- 1.8 years and -2.13 +/- 1.24 D, respectively. The mean annual progression of myopia was -0.45 +/- 0.32 D, and the mean accommodative lag (for a 4-D Badal stimulus) was 1.59 +/- 0.63 D. Neither lag at the beginning nor at the end of a yearly progression interval was associated with annual myopia progression (all p >/= 0.12). These data suggest that foveal hyperopic retinal blur during near viewing may not drive juvenile-onset myopia progression.+http://www.ncbi.nlm.nih.gov/pubmed/21342658jBerntsen, David A Sinnott, Loraine T Mutti, Donald O Zadnik, Karla CLEERE Study Group K12-EY015447/EY/NEI NIH HHS/United States R24-EY014792/EY/NEI NIH HHS/United States U10-EY008893/EY/NEI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England Vision research Vision Res. 2011 May 11;51(9):1039-46. Epub 2011 Feb 20.*1878-5646 (Electronic) 0042-6989 (Linking)311195421342658GUniversity of Houston College of Optometry, Houston, TX, United States.8S0042-6989(11)00065-4 [pii] 10.1016/j.visres.2011.02.016engs|t7n6Berntsen, D. A. Sinnott, L. T. Mutti, D. O. Zadnik, K.2011aAccommodative lag and juvenile-onset myopia progression in children wearing refractive correction1039-46 Vision Res519 2011/02/24May 11#The relationship between accommodative lag and annual myopia progression was investigated using linear models in 592 myopic children wearing a full refractive correction in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study. The mean (+/- SD) age and spherical equivalent refractive error at baseline were 10.4 +/- 1.8 years and -2.13 +/- 1.24 D, respectively. The mean annual progression of myopia was -0.45 +/- 0.32 D, and the mean accommodative lag (for a 4-D Badal stimulus) was 1.59 +/- 0.63 D. Neither lag at the beginning nor at the end of a yearly progression interval was associated with annual myopia progression (all p >/= 0.12). These data suggest that foveal hyperopic retinal blur during near viewing may not drive juvenile-onset myopia progression.+http://www.ncbi.nlm.nih.gov/pubmed/21342658jBerntsen, David A Sinnott, Loraine T Mutti, Donald O Zadnik, Karla CLEERE Study Group K12-EY015447/EY/NEI NIH HHS/United States R24-EY014792/EY/NEI NIH HHS/United States U10-EY008893/EY/NEI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England Vision research Vision Res. 2011 May 11;51(9):1039-46. Epub 2011 Feb 20.*1878-5646 (Electronic) 0042-6989 (Linking)311195421342658GUniversity of Houston College of Optometry, Houston, TX, United States.8S0042-6989(11)00065-4 [pii] 10.1016/j.visres.2011.02.016eng||7o$Chung, K. Mohidin, N. O'Leary, D. J.2002JUndercorrection of myopia enhances rather than inhibits myopia progression2555-9 Vision Res4222 2002/11/26Adolescent Analysis of Variance Child Disease Progression Eyeglasses Female Humans Male Myopia/etiology/physiopathology/*therapy Patient Compliance Visual AcuityOctThe effect of myopic defocus on myopia progression was assessed in a two-year prospective study on 94 myopes aged 9-14 years, randomly allocated to an undercorrected group or a fully corrected control group. The 47 experimental subjects were blurred by approximately +0.75 D (blurring VA to 6/12), while the controls were fully corrected. Undercorrection produced more rapid myopia progression and axial elongation (ANOVA, F(1,374)=14.32, p<0.01). Contrary to animal studies, myopic defocus speeds up myopia development in already myopic humans. Myopia could be caused by a failure to detect the direction of defocus rather than by a mechanism exhibiting a zero-point error.+http://www.ncbi.nlm.nih.gov/pubmed/12445849Chung, Kahmeng Mohidin, Norhani O'Leary, Daniel J Clinical Trial Randomized Controlled Trial Research Support, Non-U.S. Gov't England Vision research Vision Res. 2002 Oct;42(22):2555-9.%0042-6989 (Print) 0042-6989 (Linking)12445849XDepartment of Optometry, National University of Malaysia, 50300, Kuala Lumpur, Malaysia.S0042698902002584 [pii]eng||7p Press, L. J.2000uA randomized trial of the effect of single-vision vs. bifocal lenses on myopia progression in children with esophoria630-2 Optom Vis Sci7712 2001/01/09Disease Progression Esotropia/*physiopathology/therapy *Eyeglasses Humans Myopia/*physiopathology/therapy Refraction, Ocular Visual AcuityDec+http://www.ncbi.nlm.nih.gov/pubmed/11147731Press, L J Clinical Trial Comment Comparative Study Letter Randomized Controlled Trial United States Optometry and vision science : official publication of the American Academy of Optometry Optom Vis Sci. 2000 Dec;77(12):630-2.%1040-5488 (Print) 1040-5488 (Linking)1114773100006324-200012000-00007 [pii]eng ||7q&Fulk, G. W. Cyert, L. A. Parker, D. E.2000uA randomized trial of the effect of single-vision vs. bifocal lenses on myopia progression in children with esophoria395-401 Optom Vis Sci778 2000/08/31Aging/physiology Child Disease Progression Equipment Design Esotropia/*complications/physiopathology Eye/growth & development *Eyeglasses Female Humans Male Myopia/complications/physiopathology/*therapy Patient Compliance Prognosis Refraction, Ocular/*physiologyAugvBACKGROUND: Bifocals have long been thought to reduce progression of childhood myopia. However, this hypothesis has not been definitively evaluated. METHODS: We conducted a randomized clinical trial to test the hypothesis that bifocals slow myopia progression in children with near-point esophoria. Eighty-two myopic children were randomized to single-vision glasses (n = 40) or to bifocals with a +1.50 D add (n = 42) and were followed for 30 months. Refraction was measured by an automated refractor after cycloplegia. The primary outcome was myopia progression defined as the difference between the spherical equivalent at baseline and at the 30-month examination, averaged over both eyes. RESULTS: Follow-up was incomplete for six children in the bifocal group and one child in the single-vision group. Among the children completing the 30 months of follow up, myopia progression (mean spherical equivalent of the two eyes) averaged 0.99 D for bifocals and 1.24 D for single vision (unadjusted, p = 0.106; adjusted for age, p = 0.046). Treatment groups differed in their cumulative distributions (Kolmogorov-Smirnov procedure, p = 0.031). Evidence for a treatment effect on growth in vitreous chamber depth was similar (p = 0.046 by K.S.). CONCLUSION: Use of bifocals, instead of single-vision glasses, by children with near-point esophoria seemed to slow myopia progression to a slight degree.+http://www.ncbi.nlm.nih.gov/pubmed/109660655Fulk, G W Cyert, L A Parker, D E EY10613/EY/NEI NIH HHS/United States Clinical Trial Comparative Study Randomized Controlled Trial Research Support, U.S. Gov't, P.H.S. United states Optometry and vision science : official publication of the American Academy of Optometry Optom Vis Sci. 2000 Aug;77(8):395-401.%1040-5488 (Print) 1040-5488 (Linking)10966065qCollege of Optometry, Northeastern State University, Tahlequah, Oklahoma 74464-7017, USA. fulk@cherokee.nsuok.edu00006324-200008000-00006 [pii]eng ||7r&Fulk, G. W. Cyert, L. A. Parker, D. E.2000uA randomized trial of the effect of single-vision vs. bifocal lenses on myopia progression in children with esophoria395-401 Optom Vis Sci778 2000/08/31Aging/physiology Child Disease Progression Equipment Design Esotropia/*complications/physiopathology Eye/growth & development *Eyeglasses Female Humans Male Myopia/complications/physiopathology/*therapy Patient Compliance Prognosis Refraction, Ocular/*physiologyAugvBACKGROUND: Bifocals have long been thought to reduce progression of childhood myopia. However, this hypothesis has not been definitively evaluated. METHODS: We conducted a randomized clinical trial to test the hypothesis that bifocals slow myopia progression in children with near-point esophoria. Eighty-two myopic children were randomized to single-vision glasses (n = 40) or to bifocals with a +1.50 D add (n = 42) and were followed for 30 months. Refraction was measured by an automated refractor after cycloplegia. The primary outcome was myopia progression defined as the difference between the spherical equivalent at baseline and at the 30-month examination, averaged over both eyes. RESULTS: Follow-up was incomplete for six children in the bifocal group and one child in the single-vision group. Among the children completing the 30 months of follow up, myopia progression (mean spherical equivalent of the two eyes) averaged 0.99 D for bifocals and 1.24 D for single vision (unadjusted, p = 0.106; adjusted for age, p = 0.046). Treatment groups differed in their cumulative distributions (Kolmogorov-Smirnov procedure, p = 0.031). Evidence for a treatment effect on growth in vitreous chamber depth was similar (p = 0.046 by K.S.). CONCLUSION: Use of bifocals, instead of single-vision glasses, by children with near-point esophoria seemed to slow myopia progression to a slight degree.+http://www.ncbi.nlm.nih.gov/pubmed/109660655Fulk, G W Cyert, L A Parker, D E EY10613/EY/NEI NIH HHS/United States Clinical Trial Comparative Study Randomized Controlled Trial Research Support, U.S. Gov't, P.H.S. United states Optometry and vision science : official publication of the American Academy of Optometry Optom Vis Sci. 2000 Aug;77(8):395-401.%1040-5488 (Print) 1040-5488 (Linking)10966065qCollege of Optometry, Northeastern State University, Tahlequah, Oklahoma 74464-7017, USA. fulk@cherokee.nsuok.edu00006324-200008000-00006 [pii]eng ||7s8Yang, Z. Lan, W. Ge, J. Liu, W. Chen, X. Chen, L. Yu, M.2009aThe effectiveness of progressive addition lenses on the progression of myopia in Chinese children41-8Ophthalmic Physiol Opt291 2009/01/22Adolescent Child China/epidemiology Disease Progression *Eyeglasses Female Humans Linear Models Male Myopia/ethnology/*physiopathology/*therapy Sex Factors Treatment OutcomeJanPURPOSE: To evaluate the effectiveness of progressive addition lenses (PALs), with a near addition of +1.50 D, on the progression of myopia in Chinese children. METHODS: We enrolled 178 Chinese juvenile-onset acquired myopes (aged 7-13 years, -0.50 to -3.00 D spherical refractive error), who did not have moderately or highly myopic parents, for a 2-year prospective study. They were randomly assigned to the PAL group or single vision (SV) group. Primary measurements, which included myopia progression and ocular biometry, were performed every 6 months. Treatment effect was adjusted for important covariates, by using a multiple linear regression model. RESULTS: One hundred and forty-nine subjects (75 in SV and 74 in PAL) completed the 2-year study. The myopia progression (mean +/- S.D.) in the SV and PAL groups was -1.50 +/- 0.67 and -1.24 +/- 0.56 D, respectively. This difference of 0.26 D over 2 years was statistically significant (p = 0.01). The lens type (p = 0.02) and baseline spherical equivalent refraction (p = 0.05) were significant contributing factors to myopia progression. Mean increase in the depth of vitreous chamber was 0.70 +/- 0.40 and 0.59 +/- 0.24 mm, respectively. This difference of 0.11 mm was statistically significant (p = 0.04). Age (p < 0.01) was the only contributing factor to the elongation of vitreous chamber. Different near phoria (p < 0.01) and gender (p = 0.02) caused different treatment effects when wearing SV lenses. However, there were no factors found to influence the treatment effect of wearing PALs. CONCLUSIONS: Compared with SV lenses, myopia progression was found to be retarded by PALs to some extent in Chinese children without moderately or highly myopic parents, especially for subjects with near esophoria or females.+http://www.ncbi.nlm.nih.gov/pubmed/191542791Yang, Zhikuan Lan, Weizhong Ge, Jian Liu, Wen Chen, Xiang Chen, Linxin Yu, Minbin Randomized Controlled Trial Research Support, Non-U.S. Gov't England Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists) Ophthalmic Physiol Opt. 2009 Jan;29(1):41-8.*1475-1313 (Electronic) 0275-5408 (Linking)19154279mState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.-OPO608 [pii] 10.1111/j.1475-1313.2008.00608.xeng ||7t8Yang, Z. Lan, W. Ge, J. Liu, W. Chen, X. Chen, L. Yu, M.2009aThe effectiveness of progressive addition lenses on the progression of myopia in Chinese children41-8Ophthalmic Physiol Opt291 2009/01/22Adolescent Child China/epidemiology Disease Progression *Eyeglasses Female Humans Linear Models Male Myopia/ethnology/*physiopathology/*therapy Sex Factors Treatment OutcomeJanPURPOSE: To evaluate the effectiveness of progressive addition lenses (PALs), with a near addition of +1.50 D, on the progression of myopia in Chinese children. METHODS: We enrolled 178 Chinese juvenile-onset acquired myopes (aged 7-13 years, -0.50 to -3.00 D spherical refractive error), who did not have moderately or highly myopic parents, for a 2-year prospective study. They were randomly assigned to the PAL group or single vision (SV) group. Primary measurements, which included myopia progression and ocular biometry, were performed every 6 months. Treatment effect was adjusted for important covariates, by using a multiple linear regression model. RESULTS: One hundred and forty-nine subjects (75 in SV and 74 in PAL) completed the 2-year study. The myopia progression (mean +/- S.D.) in the SV and PAL groups was -1.50 +/- 0.67 and -1.24 +/- 0.56 D, respectively. This difference of 0.26 D over 2 years was statistically significant (p = 0.01). The lens type (p = 0.02) and baseline spherical equivalent refraction (p = 0.05) were significant contributing factors to myopia progression. Mean increase in the depth of vitreous chamber was 0.70 +/- 0.40 and 0.59 +/- 0.24 mm, respectively. This difference of 0.11 mm was statistically significant (p = 0.04). Age (p < 0.01) was the only contributing factor to the elongation of vitreous chamber. Different near phoria (p < 0.01) and gender (p = 0.02) caused different treatment effects when wearing SV lenses. However, there were no factors found to influence the treatment effect of wearing PALs. CONCLUSIONS: Compared with SV lenses, myopia progression was found to be retarded by PALs to some extent in Chinese children without moderately or highly myopic parents, especially for subjects with near esophoria or females.+http://www.ncbi.nlm.nih.gov/pubmed/191542791Yang, Zhikuan Lan, Weizhong Ge, Jian Liu, Wen Chen, Xiang Chen, Linxin Yu, Minbin Randomized Controlled Trial Research Support, Non-U.S. Gov't England Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists) Ophthalmic Physiol Opt. 2009 Jan;29(1):41-8.*1475-1313 (Electronic) 0275-5408 (Linking)19154279mState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.-OPO608 [pii] 10.1111/j.1475-1313.2008.00608.xeng ||7ueGwiazda, J. E. Hyman, L. Norton, T. T. Hussein, M. E. Marsh-Tootle, W. Manny, R. Wang, Y. Everett, D.2004Accommodation and related risk factors associated with myopia progression and their interaction with treatment in COMET children2143-51Invest Ophthalmol Vis Sci457 2004/06/30*Accommodation, Ocular Child Disease Progression *Eyeglasses Female Humans Male Myopia/*physiopathology/*therapy Reading Refraction, Ocular Risk Factors Strabismus/physiopathology Visual Acuity WorkJulPURPOSE: To examine baseline measurements of accommodative lag, phoria, reading distance, amount of near work, and level of myopia as risk factors for progression of myopia and their interaction with treatment over 3 years, in children enrolled in the Correction of Myopia Evaluation Trial (COMET). METHODS: COMET enrolled 469 ethnically diverse children (ages, 6-11 years) with myopia between -1.25 and -4.50 D. They were randomly assigned to either progressive addition lenses (PALs) with a +2.00 addition (n = 235) or single vision lenses (SVLs; n = 234), the conventional spectacle treatment, and were observed for 3 years. The primary outcome measure was progression of myopia by autorefraction after cycloplegia with 2 drops of 1% tropicamide. Other measurements included accommodative response (by an open field of view autorefractor), phoria (by cover test), reading distance, and hours of near work. Independent and interaction analyses were based on the mean of the two eyes. Results were adjusted for important covariates with multiple linear regression. RESULTS: Children with larger accommodative lags (>0.43 D for a 33 cm target) wearing SVLs had the most progression at 3 years. PALs were effective in slowing progression in these children, with statistically significant 3-year treatment effects (mean +/- SE) for those with larger lags in combination with near esophoria (PAL - SVL progression = -1.08 D - [-1.72 D] = 0.64 +/- 0.21 D), shorter reading distances (0.44 +/- 0.20 D), or lower baseline myopia (0.48 +/- 0.15 D). The 3-year treatment effect for larger lags in combination with more hours of near work was 0.42 +/- 0.26 D, which did not reach statistical significance. Statistically significant treatment effects were observed in these four groups at 1 year and became larger from 1 to 3 years. CONCLUSIONS: The results support the COMET rationale (i.e., a role for retinal defocus in myopia progression). In clinical practice in the United States children with large lags of accommodation and near esophoria often are prescribed PALs or bifocals to improve visual performance. Results of this study suggest that such children, if myopic, may have an additional benefit of slowed progression of myopia.+http://www.ncbi.nlm.nih.gov/pubmed/15223788ZGwiazda, Jane E Hyman, Leslie Norton, Thomas T Hussein, Mohamed E M Marsh-Tootle, Wendy Manny, Ruth Wang, Ying Everett, Donald COMET Grouup EY11740/EY/NEI NIH HHS/United States EY11752/EY/NEI NIH HHS/United States EY11754/EY/NEI NIH HHS/United States EY11755/EY/NEI NIH HHS/United States EY11756/EY/NEI NIH HHS/United States EY11805/EY/NEI NIH HHS/United States Clinical Trial Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2004 Jul;45(7):2143-51.%0146-0404 (Print) 0146-0404 (Linking)15223788]New England College of Optometry, Boston, Massachusetts 02115, USA. gwiazdaj@ne-optometry.edueng ||7veGwiazda, J. E. Hyman, L. Norton, T. T. Hussein, M. E. Marsh-Tootle, W. Manny, R. Wang, Y. Everett, D.2004Accommodation and related risk factors associated with myopia progression and their interaction with treatment in COMET children2143-51Invest Ophthalmol Vis Sci457 2004/06/30*Accommodation, Ocular Child Disease Progression *Eyeglasses Female Humans Male Myopia/*physiopathology/*therapy Reading Refraction, Ocular Risk Factors Strabismus/physiopathology Visual Acuity WorkJulPURPOSE: To examine baseline measurements of accommodative lag, phoria, reading distance, amount of near work, and level of myopia as risk factors for progression of myopia and their interaction with treatment over 3 years, in children enrolled in the Correction of Myopia Evaluation Trial (COMET). METHODS: COMET enrolled 469 ethnically diverse children (ages, 6-11 years) with myopia between -1.25 and -4.50 D. They were randomly assigned to either progressive addition lenses (PALs) with a +2.00 addition (n = 235) or single vision lenses (SVLs; n = 234), the conventional spectacle treatment, and were observed for 3 years. The primary outcome measure was progression of myopia by autorefraction after cycloplegia with 2 drops of 1% tropicamide. Other measurements included accommodative response (by an open field of view autorefractor), phoria (by cover test), reading distance, and hours of near work. Independent and interaction analyses were based on the mean of the two eyes. Results were adjusted for important covariates with multiple linear regression. RESULTS: Children with larger accommodative lags (>0.43 D for a 33 cm target) wearing SVLs had the most progression at 3 years. PALs were effective in slowing progression in these children, with statistically significant 3-year treatment effects (mean +/- SE) for those with larger lags in combination with near esophoria (PAL - SVL progression = -1.08 D - [-1.72 D] = 0.64 +/- 0.21 D), shorter reading distances (0.44 +/- 0.20 D), or lower baseline myopia (0.48 +/- 0.15 D). The 3-year treatment effect for larger lags in combination with more hours of near work was 0.42 +/- 0.26 D, which did not reach statistical significance. Statistically significant treatment effects were observed in these four groups at 1 year and became larger from 1 to 3 years. CONCLUSIONS: The results support the COMET rationale (i.e., a role for retinal defocus in myopia progression). In clinical practice in the United States children with large lags of accommodation and near esophoria often are prescribed PALs or bifocals to improve visual performance. Results of this study suggest that such children, if myopic, may have an additional benefit of slowed progression of myopia.+http://www.ncbi.nlm.nih.gov/pubmed/15223788ZGwiazda, Jane E Hyman, Leslie Norton, Thomas T Hussein, Mohamed E M Marsh-Tootle, Wendy Manny, Ruth Wang, Ying Everett, Donald COMET Grouup EY11740/EY/NEI NIH HHS/United States EY11752/EY/NEI NIH HHS/United States EY11754/EY/NEI NIH HHS/United States EY11755/EY/NEI NIH HHS/United States EY11756/EY/NEI NIH HHS/United States EY11805/EY/NEI NIH HHS/United States Clinical Trial Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2004 Jul;45(7):2143-51.%0146-0404 (Print) 0146-0404 (Linking)15223788]New England College of Optometry, Boston, Massachusetts 02115, USA. gwiazdaj@ne-optometry.edueng ||7w]Fan, D. S. Lam, D. S. Lam, R. F. Lau, J. T. Chong, K. S. Cheung, E. Y. Lai, R. Y. Chew, S. J.2004PPrevalence, incidence, and progression of myopia of school children in Hong Kong1071-5Invest Ophthalmol Vis Sci454 2004/03/24Adolescent Age Distribution Asian Continental Ancestry Group/ethnology Child Child, Preschool Cross-Sectional Studies Disease Progression Female Hong Kong/epidemiology Humans Incidence Longitudinal Studies Male Myopia/*epidemiology/*physiopathology Prevalence Schools Sex DistributionAprPURPOSE: To determine the prevalence, incidence, and progression of myopia of Chinese children in Hong Kong. METHODS: A cross-sectional survey was initially conducted. A longitudinal follow-up study was then conducted 12 months later. RESULTS: A total of 7560 children of mean age 9.33 (95% confidence interval [CI] = 9.11-9.45; range, 5-16) participated in the study. Mean spherical equivalent refraction (SER) was -0.33 D (SD = 11.56; range, -13.13 to +14.25 D). Myopia (SER ||7}_Young, F. A. Leary, G. A. Grosvenor, T. Maslovitz, B. Perrigin, D. M. Perrigin, J. Quintero, S.1985eHouston Myopia Control Study: a randomized clinical trial. Part I. Background and design of the study605-13Am J Optom Physiol Opt629 1985/09/01Adolescent Child Clinical Trials as Topic Eyeglasses Female Follow-Up Studies Humans Male Myopia/diagnosis/*therapy Parents/education Patient Care Team Patient Education as Topic Texas Vision Tests Visual AcuitySepThe Houston Myopia Control Study is a 3-year randomized clinical trial in which each of 213 myopic children was placed in either a single vision (standard treatment) group, a +1.00 D add treatment group, or a +2.00 D add treatment group, on the basis of a randomized procedure. Subjects for the three treatment groups were matched on the basis of sex, age, and the initial amount of myopia. The study involves two groups of investigators: an evaluation team, whose task has been to evaluate candidates before entering the study and to reevaluate each subject on a yearly basis for the 3-year period, and a patient care team, whose task has been to prescribe glasses for each subject as well as to counsel subjects and their parents in the correct use of the glasses and to provide a follow-up examination every six months for the duration of the study. Once the glasses had been prescribed, members of the evaluation team were not permitted to know which subjects wore single vision lenses and which wore bifocals. In the interest of good patient care, members of the patient care team knew which subjects wore single vision lenses and which wore +1.00 D add or +2.00 D add bifocals. In this report, the authors discuss theories concerning the etiology of myopia, methods that have been used in an attempt to control the progression of myopia, and the design of the current study. Further reports will present the results of the study on the basis of the data collected by each of the two study teams.*http://www.ncbi.nlm.nih.gov/pubmed/3901772Young, F A Leary, G A Grosvenor, T Maslovitz, B Perrigin, D M Perrigin, J Quintero, S Clinical Trial Comparative Study Randomized Controlled Trial United states American journal of optometry and physiological optics Am J Optom Physiol Opt. 1985 Sep;62(9):605-13.%0093-7002 (Print) 0093-7002 (Linking)3901772eng||7~8Grosvenor, T. Maslovitz, B. Perrigin, D. M. Perrigin, J.1985OThe Houston myopia control study: a preliminary report by the patient care team636-43J Am Optom Assoc568 1985/08/01Accommodation, Ocular Adolescent Age Factors Child Clinical Trials as Topic *Eyeglasses Female Humans Male Myopia/*therapy Patient ComplianceAugkThe Houston Myopia Control Study is a 3-year randomized clinical trial designed to test the efficacy of bifocal lenses for the control of myopia. Each of 213 myopic subjects, between the ages of 6 and 15 years, was placed in either a single vision (standard treatment) group, a +1.00 D. add group, or a +2.00 D. add group, by means of a table of random numbers. Subjects in each of the 3 groups were matched on the basis of sex, age, and the amount of myopia. Subjects were accepted into the study during an 18-month period ending in September, 1982, so all subjects will have completed the study by September, 1985. The purpose of this preliminary report is to inform optometrists of the existence of the study and to discuss the factors that must be taken into consideration when designing a randomized clinical trial making use of bifocal lenses for the control of myopia.*http://www.ncbi.nlm.nih.gov/pubmed/3897351Grosvenor, T Maslovitz, B Perrigin, D M Perrigin, J Clinical Trial Randomized Controlled Trial United states Journal of the American Optometric Association J Am Optom Assoc. 1985 Aug;56(8):636-43.%0003-0244 (Print) 0003-0244 (Linking)3897351engk||78Grosvenor, T. Perrigin, D. M. Perrigin, J. Maslovitz, B.1987iHouston Myopia Control Study: a randomized clinical trial. Part II. Final report by the patient care team482-98Am J Optom Physiol Opt647 1987/07/01Adolescent Age Factors Astigmatism/physiopathology Child Clinical Trials as Topic *Eyeglasses Female Humans Male Myopia/physiopathology/*therapy *Patient Care Team Random Allocation Refraction, Ocular Sex Factors Statistics as Topic Strabismus/physiopathologyJul1In a randomized clinical trial designed to test the efficacy of bifocal lenses for the control of juvenile myopia, each of 207 children between the ages of 6 and 15 years wore single vision lenses, +1.00 D add bifocals, or +2.00 D add bifocals for a period of 3 years. For the 124 subjects who completed the study, the mean changes in refraction were found to be -0.34 D per year for subjects wearing single vision lenses, -0.36 D per year for those wearing +1.00 D add bifocals, and -0.34 D per year for those wearing +2.00 D add bifocals. These differences were not statistically significant. When subjects in all three treatment groups were combined, it was found that the rate of progression tended to be the most rapid for subjects who entered the study at an early age with a large amount of myopia, and tended to be the least rapid for subjects who entered the study at a later age with a small amount of myopia. It was also found that subjects having with-the-rule astigmatism progressed more slowly than those having no astigmatism or against-the-rule astigmatism.*http://www.ncbi.nlm.nih.gov/pubmed/3307440Grosvenor, T Perrigin, D M Perrigin, J Maslovitz, B Clinical Trial Randomized Controlled Trial United states American journal of optometry and physiological optics Am J Optom Physiol Opt. 1987 Jul;64(7):482-98.%0093-7002 (Print) 0093-7002 (Linking)3307440eng r|t7FKyyronen, P. Taskinen, H. Lindbohm, M. L. Hemminki, K. Heinonen, O. P.1989mSpontaneous abortions and congenital malformations among women exposed to tetrachloroethylene in dry cleaning346-51J Epidemiol Community Health434 1989/12/01Abnormalities, Drug-Induced/*etiology Abortion, Spontaneous/*chemically induced Case-Control Studies Female Finland Humans Infant, Newborn *Laundering Occupational Diseases/*chemically induced Pregnancy Pregnancy Outcome Registries Risk Factors Selection Bias *TetrachloroethyleneDecSTUDY OBJECTIVE: The aim of the study was to determine whether exposure to tetrachloroethylene during the first trimester of pregnancy has harmful effects on pregnancy outcome. DESIGN: The study used record linkage identification of cases and case-control comparison. SETTING: The study involved dry cleaner and laundry workers throughout Finland who had become pregnant during the study period. Controls were age matched but otherwise unselected women giving birth to normal babies in the study period. SUBJECTS: Cases were defined as women who had been treated for spontaneous abortion or had delivered a malformed child. Out of 5700 workers nearly half had been pregnant during the study period. One pregnancy only was randomly selected for study per worker, and the final study population was 247 women with spontaneous abortions and 33 with malformed infants. Three age matched controls were selected for each abortion case and five for each malformation case. MEASUREMENTS AND MAIN RESULTS: Three women out of four had worked in early pregnancy. Exposure information was collected from 1108 women by mailed questionnaires, with a 77% response, and was partly confirmed by biological monitoring data. Exposure to tetrachloroethylene was found to be significantly associated with spontaneous abortions (odds ratio 3.6, p less than 0.05). CONCLUSION: The findings, together with other available data, indicate that exposure of pregnant women to tetrachloroethylene needs to be minimised.*http://www.ncbi.nlm.nih.gov/pubmed/2614324Kyyronen, P Taskinen, H Lindbohm, M L Hemminki, K Heinonen, O P Research Support, Non-U.S. Gov't England Journal of epidemiology and community health J Epidemiol Community Health. 1989 Dec;43(4):346-51.%0143-005X (Print) 0143-005X (Linking)105287226143244Institute of Occupational Health, Helsinki, Finland.eng||7MSavela, K. Hemminki, K. Hewer, A. Phillips, D. H. Putman, K. L. Randerath, K.1989Interlaboratory comparison of the 32P-postlabelling assay for aromatic DNA adducts in white blood cells of iron foundry workers485-92 Mutat Res2244 1989/12/01Chromatography, Thin Layer *DNA Damage Finland Humans Iron Leukocytes/analysis Occupational Diseases/*genetics Phosphorus Radioisotopes *Polycyclic CompoundsDec8Analysis by nuclease P1-enhanced 32P-postlabelling assay of DNA isolated from the white blood cells of 53 iron foundry workers was carried out independently in 3 laboratories, and the presence of aromatic DNA adducts was detected. The mean adduct levels in foundry workers varied from 9.2 +/- 23 (laboratory 3) and 12 +/- 10 (laboratory 2) to 26 +/- 43 (laboratory 1) and for the controls from 1.7 +/- 0.7 (laboratory 3) to 3.1 +/- 1.7 (laboratory 1) adducts per 10(8) nucleotides. No effect of smoking was observed in the present study. Each laboratory observed large interindividual variations of adduct levels. Good correlations were found between the results of the 32P-postlabelling assays carried out in the 3 laboratories; the correlation coefficients between laboratories 1 and 2, 1 and 3, and 2 and 3 were 0.61, 0.62, and 0.45, respectively, all being statistically highly significant (p less than 0.01). This interlaboratory comparison of the 32P-postlabelling method indicates the reproducibility of the method and its applicability in occupational exposure monitoring.*http://www.ncbi.nlm.nih.gov/pubmed/2586545Savela, K Hemminki, K Hewer, A Phillips, D H Putman, K L Randerath, K CA 43263/CA/NCI NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Netherlands Mutation research Mutat Res. 1989 Dec;224(4):485-92.%0027-5107 (Print) 0027-5107 (Linking)25865454Institute of Occupational Health, Helsinki, Finland.engP||7*Hemminki, E. Hayden, C. L. Janerich, D. T.1989bRecent endometrial cancer trends in Connecticut and prescriptions for estrogen replacement therapy952-3 Int J Cancer445 1989/11/15iConnecticut Estrogens/*adverse effects Female Humans Middle Aged Uterine Neoplasms/*epidemiology/etiologyNov 15*http://www.ncbi.nlm.nih.gov/pubmed/2583873Hemminki, E Hayden, C L Janerich, D T Letter United states International journal of cancer. Journal international du cancer Int J Cancer. 1989 Nov 15;44(5):952-3.%0020-7136 (Print) 0020-7136 (Linking)2583873eng||7ATaskinen, H. Anttila, A. Lindbohm, M. L. Sallmen, M. Hemminki, K.1989tSpontaneous abortions and congenital malformations among the wives of men occupationally exposed to organic solvents345-52Scand J Work Environ Health155 1989/10/01Abnormalities, Drug-Induced/*etiology Abortion, Spontaneous/*chemically induced Female Humans Infant, Newborn Male Occupational Medicine Pregnancy Risk Factors Solvents/*adverse effects Spermatogenesis/*drug effectsOctA case-referent study nested in a cohort monitored biologically for exposure to six organic solvents (styrene, toluene, xylene, tetrachloroethylene, trichloroethylene, and 1,1,1-trichloroethane) was conducted to investigate the effects of paternal exposure on pregnancy outcome. The pregnancies were identified from medical registers. The exposures of the men during the spermatogenesis preceding the pregnancies and of the women during the first trimester of the pregnancies were obtained with questionnaires, and the available biological monitoring measurements were used in the exposure assessment. Factors which significantly increased the odds ratio of spontaneous abortion were paternal exposure to organic solvents in general, high/frequent exposure to toluene or miscellaneous organic solvents (including thinners), and maternal heavy lifting. No significant association between paternal or maternal exposure and congenital malformations was found, but because of the few cases no firm conclusions can be drawn.*http://www.ncbi.nlm.nih.gov/pubmed/2799322Taskinen, H Anttila, A Lindbohm, M L Sallmen, M Hemminki, K R01-OH01919/OH/NIOSH CDC HHS/United States Research Support, U.S. Gov't, P.H.S. Finland Scandinavian journal of work, environment & health Scand J Work Environ Health. 1989 Oct;15(5):345-52.%0355-3140 (Print) 0355-3140 (Linking)27993224Institute of Occupational Health, Helsinki, Finland.eng||7-Hemminki, E. Uski, A. Koponen, P. Rimpela, U.1989lIron supplementation during pregnancy--experiences of a randomized trial relying on health service personnel290-8Control Clin Trials103 1989/09/01*Clinical Protocols Female Finland Health Manpower Hemoglobins/analysis Humans Infant, Newborn Iron/*therapeutic use Medical Records Midwifery/manpower Pregnancy Pregnancy Outcome *Prenatal Care Questionnaires Randomized Controlled Trials as Topic/*methodsSepvThis article reports the design and feasibility of a randomized controlled trial of the benefits of routine iron prophylaxis during pregnancy. The multicenter trial, supported by a small budget, relied on health service personnel in Finnish maternity centers. Iron prophylaxis has had an established position in Finnish maternity care, and iron is freely available. This contributed to our decision to ask for informed consent after randomization. During a year, 2960 mothers were recruited by midwives in 27 maternity health centers and randomized into two groups: selective and routine iron supplementation. Mothers were followed until the postpartum checkup, and data were collected by five different questionnaires and abstracted from the infant's patient record. Adherence of the midwives to the study protocol was satisfactory, as was mothers' compliance with recommended treatments. However, because the study was designed to compare two treatment policies, problems of nonmasking hamper of the biologic effects of iron. This trial encourages the use of existing health services and their personnel in evaluation of medical technology.*http://www.ncbi.nlm.nih.gov/pubmed/2791561Hemminki, E Uski, A Koponen, P Rimpela, U Clinical Trial Comparative Study Randomized Controlled Trial Research Support, Non-U.S. Gov't United states Controlled clinical trials Control Clin Trials. 1989 Sep;10(3):290-8.%0197-2456 (Print) 0197-2456 (Linking)2791561=Department of Public Health, University of Helsinki, Finland.0197-2456(89)90069-X [pii]eng||78Hemminki, E. Ferdock, M. J. Rahkonen, O. McKinlay, S. S.1989CClustering and consistency of use of medicines among mid-aged women859-68Med Care279 1989/09/01 Analgesics/administration & dosage Cardiovascular Agents/administration & dosage Drug Therapy/*utilization Female Health Status Hormones/administration & dosage Humans Massachusetts *Middle Aged Nonprescription Drugs Psychotropic Drugs/administration & dosage Space-Time Clustering *WomenSepThis paper describes the use of drugs among middle-aged Massachusetts women from 1982 to 1986. Data were obtained from follow-up interviews of women (n = 2565) who were premenopausal in a baseline survey of a representative sample of women with an age range of 45-55. In the first follow-up interview, 92% of women had used nonprescribed drugs ("current use"), but most only sporadically, while 47% had used prescribed drugs. The use of different types of drugs was concentrated in the same women, and women who had used prescribed drugs had also used nonprescribed drugs more often than the other women. In the first follow-up, women were classified as nonusers (includes sporadic nonprescribed drug use), nonprescribed medicine users, prescribed drug users, and mixed users; 43% of the women were in a different class three years later. Comparison of individual drug groups also showed changes in the user status between the two surveys. With the exception of poorer health, users of nonprescribed and prescribed drugs were similar to nonusers. Because use of drugs is common, further research on both its determinants and appropriateness is needed.*http://www.ncbi.nlm.nih.gov/pubmed/2770369Hemminki, E Ferdock, M J Rahkonen, O McKinlay, S S AG03111/AG/NIA NIH HHS/United States Research Support, U.S. Gov't, P.H.S. United states Medical care Med Care. 1989 Sep;27(9):859-68.%0025-7079 (Print) 0025-7079 (Linking)27703699New England Research Institute, Watertown, Massachusetts.eng||7 Hemminki, K.1989{Ring-opened 7-methylguanine nucleotides are resistant to nuclease P1 digestion and good substrates to polynucleotide kinase1761-3Carcinogenesis109 1989/09/018Deoxyguanine Nucleotides/*chemical synthesis Micrococcal Nuclease/metabolism Nucleotidases/*metabolism Phosphoric Diester Hydrolases/metabolism Phosphotransferases/*metabolism Polynucleotide 5'-Hydroxyl-Kinase/*metabolism Single-Strand Specific DNA and RNA Endonucleases Substrate Specificity T-Phages/enzymologySepDimethyl sulfate was used to prepare 7-methyl-2'-deoxy-guanosine 3'-monophosphate (7-methyl-dGMP), which was ring-opened in alkali to 2'-deoxy-N5-methyl-N5-formyl-2,5,6-triamino-4-oxopyrimidine 3'-monophosphate (ROM-dGMP). ROM-dGMP was not dephosphorylated by nuclease P1 in contrast to normal deoxynucleotides. It was efficiently 5'-phosphorylated by T4 polynucleotide kinase. When methylated DNA was alkali-treated and digested with micrococcal nuclease, spleen phosphodiesterase and nuclease P1, ROM-dGMP was formed and this was labeled with [gamma-32P]-ATP in the presence of polynucleotide kinase. Ring-opening and P1 treatment appear methods of choice for 32P-post-labeling of 7-alkylguanines in DNA.*http://www.ncbi.nlm.nih.gov/pubmed/2548753pHemminki, K Research Support, Non-U.S. Gov't United states Carcinogenesis Carcinogenesis. 1989 Sep;10(9):1761-3.%0143-3334 (Print) 0143-3334 (Linking)25487534Institute of Occupational Health, Helsinki, Finland.eng |t7'Parssinen, O. Hemminki, E. Klemetti, A.1989Effect of spectacle use and accommodation on myopic progression: final results of a three-year randomised clinical trial among schoolchildren547-51Br J Ophthalmol737 1989/07/01*Accommodation, Ocular Child Clinical Trials as Topic *Eyeglasses Female Follow-Up Studies Humans Male Myopia/*therapy Random AllocationJulTwo hundred and forty mildly myopic schoolchildren aged 9-11 years were randomly allocated to three treatment groups and the progression of myopia was followed-up for three years. The treatment groups were: (1) minus lenses with full correction for continuous use (the reference group), (2) minus lenses with full correction to be used for distant vision only, and (3) bifocal lenses with +1.75 D addition. Three-year refraction values were received from 237 children. The differences in the increases of the spherical equivalents were not statistically significant in the right eye, but in the left eye the change in the distant use group was significantly higher (-1.87 D) than in the continuous use group (-1.46 D) (p = 0.02, Student's t test). There were no differences between the groups in regard to school achievement, accidents, or satisfaction with glasses. In all three groups the more the daily close work done by the children the faster was the rate of myopic progression (right eye: r = 0.253, p = 0.0001, left eye: r = 0.267, p = 0.0001). Myopic progression did not correlate positively with accommodation, but the shorter the average reading distance of the follow-up time the faster was the myopic progression (right eye: r = 0.222, p = 0.0001, left eye: r = 0.255, p = 0.001). It seems that myopic progression is connected with much use of the eyes in reading and close work and with short reading distance but that progression cannot be reduced by diminishing accommodation with bifocals or by reading without spectacles.*http://www.ncbi.nlm.nih.gov/pubmed/2667638Parssinen, O Hemminki, E Klemetti, A Clinical Trial Randomized Controlled Trial Research Support, Non-U.S. Gov't England The British journal of ophthalmology Br J Ophthalmol. 1989 Jul;73(7):547-51.%0007-1161 (Print) 0007-1161 (Linking)10417982667638LDepartment of Ophthalmology, Central Hospital of Central Finland, Jyvaskyla.eng||7Hemminki, K. Kyyronen, P.1989)Gastrointestinal atresias and borreliosis1395Lancet18651 1989/06/17Animals Borrelia Infections/*complications *Digestive System Abnormalities Fathers Humans Intestinal Atresia/*etiology Male OccupationsJun 17*http://www.ncbi.nlm.nih.gov/pubmed/2567414OHemminki, K Kyyronen, P Letter England Lancet Lancet. 1989 Jun 17;1(8651):1395.%0140-6736 (Print) 0140-6736 (Linking)2567414S0140-6736(89)92846-8 [pii]eng ~|7Vainio, H. Hemminki, K.1989OEpidemiological and experimental applications to occupational cancer prevention323-45J UOEH11 Suppl 1989/03/20Animals Benzo(a)pyrene/analysis Carcinogenicity Tests/methods Carcinogens Cohort Studies DNA/analysis *DNA Adducts Environmental Monitoring/methods Humans Maximum Allowable Concentration Mice Mutagenicity Tests/methods Neoplasms/chemically induced/epidemiology/*prevention & control Neoplasms, Experimental/chemically induced Occupational Diseases/chemically induced/epidemiology/*prevention & control Rats Risk FactorsMar 20 At present, there is a whole array of risk factors, such as industrial chemicals, drugs, pesticides, complex chemical mixtures, physical and biological agents, for which there is a proven causal relationship with human cancer. The epidemiological studies are essential in providing proof for a causal relationship in humans. However, the epidemiological approach to the identification of the etiology of cancer is limited for two main reasons: only relatively high risks can be detected; and, secondly, the epidemiological surveys are based on observations of the effects as a consequence of an exposure that took place many years before. It can be estimated that epidemiological cancer research on common types of tumours is able to detect risk levels ranging from 5 x 10(-2) to 10(-3). This is, of course, far from commonly defined "acceptable risk" of 10(-5) - 10(-6). Frequently, negative epidemiological studies are thought to provide evidence of non-carcinogenicity, even though the exposure levels were so low that no such effect could even be expected. While the epidemiological studies have their greatest limitation in not being able to detect a low risk, that is to produce "false negative" results, carcinogenicity tests in experimental animals have been criticized in producing "false positive" results, i.e., in picking up cancer risks at very high exposure levels. Some investigators hold that the relatively high exposure levels given to experimental animals often results in carcinogenicity because of compensatory cell proliferation from toxic effects of the chemical, and accordingly, they have questioned the use of the Maximum Tolerated Dose (MTD). However, most of the chemicals determined to be carcinogenic would exhibit carcinogenic effects at exposure levels below the level of target organ toxicity. All epidemiologically proven human carcinogens which have been adequately studied, are also carcinogenic in laboratory animals. This does not necessarily mean that all animal carcinogens are human carcinogens. A more comprehensive evaluation of interspecies correlation between humans and rodents is limited by the lack of known human non-carcinogens. Nevertheless, the high interspecies correlation shown between rats and mice supports the view that extrapolation of carcinogenicity outcomes to other species, including humans, is appropriate. There is now a range of short-term laboratory tests which have been used to predict the results of long-term tests of carcinogenicity in mammalian species. Prediction is not entirely accurate, mainly because a fraction of carcinogens is active via a mechanism not employed by the short-term tests.(ABSTRACT TRUNCATED AT 400 WORDS)*http://www.ncbi.nlm.nih.gov/pubmed/2664947WVainio, H Hemminki, K Review Japan Journal of UOEH J UOEH. 1989 Mar 20;11 Suppl:323-45.%0387-821X (Print) 0387-821X (Linking)26649474Institute of Occupational Health, Helsinki, Finland.eng||70Mustonen, R. Takala, M. Leppala, S. Hemminki, K.1989[Dose-dependence and stability of cisplatin binding to tissue DNA and blood proteins in rats365-8Carcinogenesis102 1989/02/01Animals Blood Proteins/*metabolism Cisplatin/*metabolism DNA/*metabolism Dose-Response Relationship, Drug Male Rats Rats, Inbred Strains Spectrophotometry, AtomicFeb$Two experiments were carried out by using atomic absorption spectroscopy on the stability and dose-dependence of cisplatin [cis-diamminedichloroplatinum (II)] binding to blood proteins and tissue DNA of male Han/Wistar rats. The dose-dependence was studied by injecting 17 rats i.p. either with cisplatin (4.4, 8.0 or 11.0 mg/kg) or 0.9% NaCl (controls). The Pt concentrations in blood proteins (plasma proteins and hemoglobin) and DNAs of different tissues (kidney, liver, lung and testis) were measured 24 h after the treatment. The binding of cisplatin to blood proteins and tissue DNAs correlated with each other and the dose. The stability was studied by treating 17 rats i.v. with 8.0 mg cisplatin/kg. The Pt concentrations in kidney, liver and lung DNA were determined 5 h, 1, 3 or 5 days after the treatment. The disappearance of Pt was faster in kidney DNA than in liver or lung DNA; in 5 days the Pt concentration in kidney DNA decreased by 63% while the Pt content in liver or lung decreased by 40%. Both of these experiments showed that the binding of cisplatin to kidney DNA exceeded the other tissue DNAs examined. Testicular DNA showed the lowest level of binding. The present animal data suggest that the platination level of blood proteins may be used as a measure of Pt concentration in tissue DNA.*http://www.ncbi.nlm.nih.gov/pubmed/2912587oMustonen, R Takala, M Leppala, S Hemminki, K United states Carcinogenesis Carcinogenesis. 1989 Feb;10(2):365-8.%0143-3334 (Print) 0143-3334 (Linking)2912587eDepartment of Industrial Hygiene and Toxicology, Institute of Occupational Health, Helsinki, Finland.eng||7=Mustonen, R. Hietanen, P. Leppala, S. Takala, M. Hemminki, K.1989gDetermination of cis-diamminedichloroplatinum (II) in plasma proteins and hemoglobin of cancer patients361-6 Arch Toxicol635 1989/01/01Adolescent Adult Aged Blood Proteins/*analysis Cisplatin/*blood Female Hemoglobins/*analysis Humans Male Middle Aged Neoplasms/*blood Platinum/bloodcA study was conducted to determine the levels of cis-diamminedichloroplatinum (II) (cisplatin) in plasma proteins and hemoglobin of cancer patients after cisplatin chemotherapy. Thirty-seven cancer patients with different type of cancers (lung, esophageal, urinary tract, and testicular cancer, melanoma, osteosarcoma etc) received cisplatin 32-110 mg/m2 either as a single intravenous infusion or as infusions given on 5 consecutive days. Blood samples were classified according to time from previous cisplatin infusion. They included a total of 103 samples taken before the cisplatin infusion, immediately after infusion, 1, 2 or 3-5 days after infusion or 2-3, 4, or 5-7 weeks after infusion. Platinum (Pt) concentration in plasma proteins and hemoglobin was measured by atomic absorption spectroscopy (AAS). The data showed a correlation between the dose of cisplatin and the concentrations of Pt in plasma proteins and hemoglobin of cancer patients. Plasma proteins bound more cisplatin than hemoglobin, the respective maxima in the patients receiving greater than 50 mg/m2 being 27.7 and 1.6 ng/mg protein in samples drawn immediately after treatment. The kinetics of disappearance of Pt from plasma proteins showed several components; the initial half-life was about 5-7 days. The disappearance of Pt from hemoglobin showed a single component of a half-life of 12-14 days.*http://www.ncbi.nlm.nih.gov/pubmed/2818200}Mustonen, R Hietanen, P Leppala, S Takala, M Hemminki, K Germany, west Archives of toxicology Arch Toxicol. 1989;63(5):361-6.%0340-5761 (Print) 0340-5761 (Linking)28182004Institute of Occupational Health, Helsinki, Finland.eng~|7=Mustonen, R. Hemminki, K. Hietanen, P. Leppala, S. Takala, M.1989FCisplatin binding to plasma proteins and hemoglobin in cancer patients262-4Arch Toxicol Suppl13 1989/01/01Blood Proteins/*metabolism Cisplatin/*blood Hemoglobins/*metabolism Humans Infusions, Intravenous Neoplasms/*blood Protein Binding Spectrophotometry, Atomic*http://www.ncbi.nlm.nih.gov/pubmed/2774942Mustonen, R Hemminki, K Hietanen, P Leppala, S Takala, M Germany, west Archives of toxicology. Supplement. = Archiv fur Toxikologie. Supplement Arch Toxicol Suppl. 1989;13:262-4.%0171-9750 (Print) 0171-9750 (Linking)2774942eInstitute of Occupational Health, Department of Industrial Hygiene and Toxicology, Helsinki, Finland.eng~|7#Savela, K. Leppala, S. Hemminki, K.1989H32P-postlabelling of DNA adducts in white blood cells of foundry workers101-3Arch Toxicol Suppl13 1989/01/01Autoradiography Chromatography, Thin Layer DNA/*blood *DNA Damage Finland Humans Isotope Labeling Leukocytes/*analysis Occupational Diseases/*blood Phosphorus Radioisotopes/diagnostic use*http://www.ncbi.nlm.nih.gov/pubmed/2774915Savela, K Leppala, S Hemminki, K Research Support, Non-U.S. Gov't Germany, west Archives of toxicology. Supplement. = Archiv fur Toxikologie. Supplement Arch Toxicol Suppl. 1989;13:101-3.%0171-9750 (Print) 0171-9750 (Linking)2774915eInstitute of Occupational Health, Department of Industrial Hygiene and Toxicology, Helsinki, Finland.engK||7>Forsti, A. Leppala, S. Takala, M. Laatikainen, R. Hemminki, K.1989AKinetics of reaction of cis-diamminedichloroplatinum(II) with DNA120-5Pharmacol Toxicol641 1989/01/01Chromatography, High Pressure Liquid Chromatography, Ion Exchange Cisplatin/*analysis DNA/*analysis Kinetics Magnetic Resonance Spectroscopy Nucleotides/*analysisJanA method based on cation exchange chromatography was developed to determine the adducts formed in the reaction of cis-diamminedichloroplatinum(II) (cis-Pt) with DNA. DNA was incubated with various concentrations of cis-Pt for various periods of time, ethanol precipitated, and enzymatically digested to nucleosides and Pt-containing oligonucleotides. The unmodified nucleosides were separated from the positively charged intra- and interstrand cis Pt adducts with a weak cation exchanger, CM-Sephadex C-25, and the adducts were further purified by HPLC. The main adduct was shown to be an intrastrand cross-link of cis-Pt bound to the N-7 atoms of two neighboring guanines. The minor adducts were intra- and interstrand cross-links of cis-Pt with adenine and guanine and an interstrand cross-link of cis-Pt with two guanines. At low levels of DNA-modification (cis-Pt:nucleotide = 1:50-1:1000) the intrastrand cross-link of cis-Pt with two guanines consisted of 60-70% of the total platination of DNA. At higher levels of DNA-modification (greater than 1:20), the amount of undigested products increased, indicating shielding of DNA by cis-Pt from nucleolytic enzymes.*http://www.ncbi.nlm.nih.gov/pubmed/2755902Forsti, A Leppala, S Takala, M Laatikainen, R Hemminki, K Research Support, Non-U.S. Gov't Denmark Pharmacology & toxicology Pharmacol Toxicol. 1989 Jan;64(1):120-5.%0901-9928 (Print) 0901-9928 (Linking)27559024Institute of Occupational Health, Helsinki, Finland.eng||7%Hemminki, K. Peltonen, K. Vodicka, P.1989cDepurination from DNA of 7-methylguanine, 7-(2-aminoethyl)-guanine and ring-opened 7-methylguanines289-303Chem Biol Interact703-4 1989/01/01Animals Chromatography, High Pressure Liquid DNA/*metabolism Gas Chromatography-Mass Spectrometry Guanine/*analogs & derivatives/analysis/metabolism Kinetics Models, Chemical Molecular StructureDNA was reacted with dimethyl sulphate and ethyleneimine to afford respective 7-methylguanine and 7-(2-aminoethyl)guanine derivatives. The substituted DNA was boiled in 0.1 M NaCl containing 10 mM phosphate buffer (pH 7.0), and the release of 7-alkylguanines, guanine and adenine was followed. The half-lives of depurination were 1.5 and 4.1 min for 7-(2-aminoethyl)guanine and 7-methylguanine, respectively. 7-Methylguanine was released some 60 times faster than guanine and adenine. When 7-methylguanine-containing DNA was treated in alkali to cause imidazole ring-opening, two products were liberated by boiling the DNA solution. These products were released with apparent half-lives of 69 and 34 min. These ring-opened products isomerized to each other completely within 1 h at 37 degrees C. The isomers had an identical ultraviolet spectrum and they displayed a pKa of 9.8. When silylated and analysed in gas chromatography-mass spectroscopy the two isomers had an identical molecular weight and fragmentation pattern, consistent with a structural assignment as N5-methyl-N5-formyl-2,5,6-triamino-4-oxopyrimidine. Only one of the isomers appeared to be present on DNA; the isomerization took place when the ring-opened product was released into solution.*http://www.ncbi.nlm.nih.gov/pubmed/2743474Hemminki, K Peltonen, K Vodicka, P Research Support, Non-U.S. Gov't Netherlands Chemico-biological interactions Chem Biol Interact. 1989;70(3-4):289-303.%0009-2797 (Print) 0009-2797 (Linking)27434744Institute of Occupational Health, Helsinki, Finland.eng |t7'Parssinen, O. Hemminki, E. Klemetti, A.1989Effect of spectacle use and accommodation on myopic progression: final results of a three-year randomised clinical trial among schoolchildren547-51Br J Ophthalmol737 1989/07/01*Accommodation, Ocular Child Clinical Trials as Topic *Eyeglasses Female Follow-Up Studies Humans Male Myopia/*therapy Random AllocationJulTwo hundred and forty mildly myopic schoolchildren aged 9-11 years were randomly allocated to three treatment groups and the progression of myopia was followed-up for three years. The treatment groups were: (1) minus lenses with full correction for continuous use (the reference group), (2) minus lenses with full correction to be used for distant vision only, and (3) bifocal lenses with +1.75 D addition. Three-year refraction values were received from 237 children. The differences in the increases of the spherical equivalents were not statistically significant in the right eye, but in the left eye the change in the distant use group was significantly higher (-1.87 D) than in the continuous use group (-1.46 D) (p = 0.02, Student's t test). There were no differences between the groups in regard to school achievement, accidents, or satisfaction with glasses. In all three groups the more the daily close work done by the children the faster was the rate of myopic progression (right eye: r = 0.253, p = 0.0001, left eye: r = 0.267, p = 0.0001). Myopic progression did not correlate positively with accommodation, but the shorter the average reading distance of the follow-up time the faster was the myopic progression (right eye: r = 0.222, p = 0.0001, left eye: r = 0.255, p = 0.001). It seems that myopic progression is connected with much use of the eyes in reading and close work and with short reading distance but that progression cannot be reduced by diminishing accommodation with bifocals or by reading without spectacles.*http://www.ncbi.nlm.nih.gov/pubmed/2667638Parssinen, O Hemminki, E Klemetti, A Clinical Trial Randomized Controlled Trial Research Support, Non-U.S. Gov't England The British journal of ophthalmology Br J Ophthalmol. 1989 Jul;73(7):547-51.%0007-1161 (Print) 0007-1161 (Linking)10417982667638LDepartment of Ophthalmology, Central Hospital of Central Finland, Jyvaskyla.eng||78Edwards, M. H. Li, R. W. Lam, C. S. Lew, J. K. Yu, B. S.2002SThe Hong Kong progressive lens myopia control study: study design and main findings2852-8Invest Ophthalmol Vis Sci439 2002/08/31Child Disease Progression Double-Blind Method *Eyeglasses Female Hong Kong Humans Male Myopia/*physiopathology/*therapy Quality Assurance, Health Care Refraction, Ocular Research Design Treatment OutcomeSepPURPOSE: To determine whether the use of progressive addition spectacle lenses reduced the progression of myopia, over a 2-year period, in Hong Kong children between the ages of 7 and 10.5 years. METHODS: A clinical trial was carried out to compare the progression in myopia in a treatment group of 138 (121 retained) subjects wearing progressive lenses (PAL; add +1.50 D) and in a control group of 160 (133 retained) subjects wearing single vision lenses (SV). The research design was masked with random allocation to groups. Primary measurements outcomes were spherical equivalent refractive error and axial length (both measured using a cycloplegic agent). RESULTS: There were no statistically significant differences between the PAL and the SV groups for of any of the baseline outcome measures. After 2 years there had been statistically significant increases in myopia and axial length in both groups; however, there was no difference in the increases that occurred between the two groups. CONCLUSIONS: The research design used resulted in matched treatment and control groups. There was no evidence that progression of myopia was retarded by wearing progressive addition lenses, either in terms of refractive error or axial length.+http://www.ncbi.nlm.nih.gov/pubmed/122025023Edwards, Marion Hastings Li, Roger Wing-Hong Lam, Carly Siu-Yin Lew, John Kwok-Fai Yu, Bibianna Sin-Ying Clinical Trial Comparative Study Randomized Controlled Trial Research Support, Non-U.S. Gov't United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2002 Sep;43(9):2852-8.%0146-0404 (Print) 0146-0404 (Linking)12202502kCentre for Myopia Research, The Hong Kong Polytechnic University, Kowloon, Hong Kong. ormarion@polyu.edu.hkeng||78Edwards, M. H. Li, R. W. Lam, C. S. Lew, J. K. Yu, B. S.2002SThe Hong Kong progressive lens myopia control study: study design and main findings2852-8Invest Ophthalmol Vis Sci439 2002/08/31Child Disease Progression Double-Blind Method *Eyeglasses Female Hong Kong Humans Male Myopia/*physiopathology/*therapy Quality Assurance, Health Care Refraction, Ocular Research Design Treatment OutcomeSepPURPOSE: To determine whether the use of progressive addition spectacle lenses reduced the progression of myopia, over a 2-year period, in Hong Kong children between the ages of 7 and 10.5 years. METHODS: A clinical trial was carried out to compare the progression in myopia in a treatment group of 138 (121 retained) subjects wearing progressive lenses (PAL; add +1.50 D) and in a control group of 160 (133 retained) subjects wearing single vision lenses (SV). The research design was masked with random allocation to groups. Primary measurements outcomes were spherical equivalent refractive error and axial length (both measured using a cycloplegic agent). RESULTS: There were no statistically significant differences between the PAL and the SV groups for of any of the baseline outcome measures. After 2 years there had been statistically significant increases in myopia and axial length in both groups; however, there was no difference in the increases that occurred between the two groups. CONCLUSIONS: The research design used resulted in matched treatment and control groups. There was no evidence that progression of myopia was retarded by wearing progressive addition lenses, either in terms of refractive error or axial length.+http://www.ncbi.nlm.nih.gov/pubmed/122025023Edwards, Marion Hastings Li, Roger Wing-Hong Lam, Carly Siu-Yin Lew, John Kwok-Fai Yu, Bibianna Sin-Ying Clinical Trial Comparative Study Randomized Controlled Trial Research Support, Non-U.S. Gov't United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2002 Sep;43(9):2852-8.%0146-0404 (Print) 0146-0404 (Linking)12202502kCentre for Myopia Research, The Hong Kong Polytechnic University, Kowloon, Hong Kong. ormarion@polyu.edu.hkeng||7zGwiazda, J. Hyman, L. Hussein, M. Everett, D. Norton, T. T. Kurtz, D. Leske, M. C. Manny, R. Marsh-Tootle, W. Scheiman, M.2003A randomized clinical trial of progressive addition lenses versus single vision lenses on the progression of myopia in children1492-500Invest Ophthalmol Vis Sci444 2003/03/27tChild *Eyeglasses Female Humans Male Myopia/*physiopathology/*therapy Prescriptions Refraction, Ocular Visual AcuityApr PURPOSE: The purpose of the Correction of Myopia Evaluation Trial (COMET) was to evaluate the effect of progressive addition lenses (PALs) compared with single vision lenses (SVLs) on the progression of juvenile-onset myopia. METHODS: COMET enrolled 469 children (ages 6-11 years) with myopia between -1.25 and -4.50 D spherical equivalent. The children were recruited at four colleges of optometry in the United States and were ethnically diverse. They were randomly assigned to receive either PALs with a +2.00 addition (n = 235) or SVLs (n = 234), the conventional spectacle treatment for myopia, and were followed for 3 years. The primary outcome measure was progression of myopia, as determined by autorefraction after cycloplegia with 2 drops of 1% tropicamide at each annual visit. The secondary outcome measure was change in axial length of the eyes, as assessed by A-scan ultrasonography. Child-based analyses (i.e., the mean of the two eyes) were used. Results were adjusted for important covariates, by using multiple linear regression. RESULTS: Of the 469 children (mean age at baseline, 9.3 +/- 1.3 years), 462 (98.5%) completed the 3-year visit. Mean (+/-SE) 3-year increases in myopia (spherical equivalent) were -1.28 +/- 0.06 D in the PAL group and -1.48 +/- 0.06 D in the SVL group. The 3-year difference in progression of 0.20 +/- 0.08 D between the two groups was statistically significant (P = 0.004). The treatment effect was observed primarily in the first year. The number of prescription changes differed significantly by treatment group only in the first year. At 6 months, 17% of the PAL group versus 30% of the SVL group needed a prescription change (P = 0.0007), and, at 1 year, 43% of the PAL group versus 59% of the SVL group required a prescription change (P = 0.002). Interaction analyses identified a significantly larger treatment effect of PALs in children with lower versus higher baseline accommodative response at near (P = 0.03) and with lower versus higher baseline myopia (P = 0.04). Mean (+/- SE) increases in the axial length of eyes of children in the PAL and SVL groups, respectively, were: 0.64 +/- 0.02 mm and 0.75 +/- 0.02 mm, with a statistically significant 3-year mean difference of 0.11 +/- 0.03 mm (P = 0.0002). Mean changes in axial length correlated with those in refractive error (r = 0.86 for PAL and 0.89 for SVL). CONCLUSIONS: Use of PALs compared with SVLs slowed the progression of myopia in COMET children by a small, statistically significant amount only during the first year. The size of the treatment effect remained similar and significant for the next 2 years. The results provide some support for the COMET rationale-that is, a role for defocus in progression of myopia. The small magnitude of the effect does not warrant a change in clinical practice.+http://www.ncbi.nlm.nih.gov/pubmed/12657584Gwiazda, Jane Hyman, Leslie Hussein, Mohamed Everett, Donald Norton, Thomas T Kurtz, Daniel Leske, M Cristina Manny, Ruth Marsh-Tootle, Wendy Scheiman, Mitch EY11740/EY/NEI NIH HHS/United States EY11752/EY/NEI NIH HHS/United States EY11754/EY/NEI NIH HHS/United States EY11755/EY/NEI NIH HHS/United States EY11756/EY/NEI NIH HHS/United States EY11805/EY/NEI NIH HHS/United States Clinical Trial Comparative Study Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2003 Apr;44(4):1492-500.%0146-0404 (Print) 0146-0404 (Linking)12657584]New England College of Optometry, Boston, Massachusetts 02115, USA. gwiazdaj@ne-optometry.edueng||7zGwiazda, J. Hyman, L. Hussein, M. Everett, D. Norton, T. T. Kurtz, D. Leske, M. C. Manny, R. Marsh-Tootle, W. Scheiman, M.2003A randomized clinical trial of progressive addition lenses versus single vision lenses on the progression of myopia in children1492-500Invest Ophthalmol Vis Sci444 2003/03/27tChild *Eyeglasses Female Humans Male Myopia/*physiopathology/*therapy Prescriptions Refraction, Ocular Visual AcuityApr PURPOSE: The purpose of the Correction of Myopia Evaluation Trial (COMET) was to evaluate the effect of progressive addition lenses (PALs) compared with single vision lenses (SVLs) on the progression of juvenile-onset myopia. METHODS: COMET enrolled 469 children (ages 6-11 years) with myopia between -1.25 and -4.50 D spherical equivalent. The children were recruited at four colleges of optometry in the United States and were ethnically diverse. They were randomly assigned to receive either PALs with a +2.00 addition (n = 235) or SVLs (n = 234), the conventional spectacle treatment for myopia, and were followed for 3 years. The primary outcome measure was progression of myopia, as determined by autorefraction after cycloplegia with 2 drops of 1% tropicamide at each annual visit. The secondary outcome measure was change in axial length of the eyes, as assessed by A-scan ultrasonography. Child-based analyses (i.e., the mean of the two eyes) were used. Results were adjusted for important covariates, by using multiple linear regression. RESULTS: Of the 469 children (mean age at baseline, 9.3 +/- 1.3 years), 462 (98.5%) completed the 3-year visit. Mean (+/-SE) 3-year increases in myopia (spherical equivalent) were -1.28 +/- 0.06 D in the PAL group and -1.48 +/- 0.06 D in the SVL group. The 3-year difference in progression of 0.20 +/- 0.08 D between the two groups was statistically significant (P = 0.004). The treatment effect was observed primarily in the first year. The number of prescription changes differed significantly by treatment group only in the first year. At 6 months, 17% of the PAL group versus 30% of the SVL group needed a prescription change (P = 0.0007), and, at 1 year, 43% of the PAL group versus 59% of the SVL group required a prescription change (P = 0.002). Interaction analyses identified a significantly larger treatment effect of PALs in children with lower versus higher baseline accommodative response at near (P = 0.03) and with lower versus higher baseline myopia (P = 0.04). Mean (+/- SE) increases in the axial length of eyes of children in the PAL and SVL groups, respectively, were: 0.64 +/- 0.02 mm and 0.75 +/- 0.02 mm, with a statistically significant 3-year mean difference of 0.11 +/- 0.03 mm (P = 0.0002). Mean changes in axial length correlated with those in refractive error (r = 0.86 for PAL and 0.89 for SVL). CONCLUSIONS: Use of PALs compared with SVLs slowed the progression of myopia in COMET children by a small, statistically significant amount only during the first year. The size of the treatment effect remained similar and significant for the next 2 years. The results provide some support for the COMET rationale-that is, a role for defocus in progression of myopia. The small magnitude of the effect does not warrant a change in clinical practice.+http://www.ncbi.nlm.nih.gov/pubmed/12657584Gwiazda, Jane Hyman, Leslie Hussein, Mohamed Everett, Donald Norton, Thomas T Kurtz, Daniel Leske, M Cristina Manny, Ruth Marsh-Tootle, Wendy Scheiman, Mitch EY11740/EY/NEI NIH HHS/United States EY11752/EY/NEI NIH HHS/United States EY11754/EY/NEI NIH HHS/United States EY11755/EY/NEI NIH HHS/United States EY11756/EY/NEI NIH HHS/United States EY11805/EY/NEI NIH HHS/United States Clinical Trial Comparative Study Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2003 Apr;44(4):1492-500.%0146-0404 (Print) 0146-0404 (Linking)12657584]New England College of Optometry, Boston, Massachusetts 02115, USA. gwiazdaj@ne-optometry.edueng||75Horner, D. G. Soni, P. S. Salmon, T. O. Swartz, T. S.1999NMyopia progression in adolescent wearers of soft contact lenses and spectacles474-9 Optom Vis Sci767 1999/08/13Adolescent Astigmatism/etiology Child *Contact Lenses, Hydrophilic Disease Progression *Eyeglasses/adverse effects Humans Infant Myopia/*physiopathology/*therapy Refraction, Ocular/physiologyJuloThe purpose of this 3-year, randomized clinical trial was to determine the difference in myopia progression in adolescents wearing soft contact lenses over a control group wearing spectacles. A total of 175 adolescents between the ages of 11 and 14 years were randomized into 2 groups, spectacle wearers and soft contact lens wearers. The main result was that the spherical equivalent change between the groups showed no clinical or statistically significant difference. However, when a power vector analysis was used, which uses all the refractive error data, a small but statistically significant (F test = 4.24, T2 = 17.35, p < 0.01) difference between the groups was found (i.e., the refractive error of the spectacle wearers had a slight increase in astigmatism). It can be concluded that soft contact lens wear does not lead to additional myopia progression in adolescents.+http://www.ncbi.nlm.nih.gov/pubmed/10445639Horner, D G Soni, P S Salmon, T O Swartz, T S Clinical Trial Randomized Controlled Trial Research Support, Non-U.S. Gov't United states Optometry and vision science : official publication of the American Academy of Optometry Optom Vis Sci. 1999 Jul;76(7):474-9.%1040-5488 (Print) 1040-5488 (Linking)10445639Borish Center for Ophthalmic Research, Indiana University, School of Optometry, Bloomington, Indiana 47405-3680, USA. hornerdg@indiana.edueng 7F|7XMarsh-Tootle, W. L. Dong, L. M. Hyman, L. Gwiazda, J. Weise, K. K. Dias, L. Fernp, K. D.2009QMyopia Progression in Children Wearing Spectacles vs. Switching to Contact Lenses Optom Vis Sci 2009/05/12May 7kPURPOSE.: To investigate myopia progression in Correction of Myopia Evaluation Trial (COMET) participants who switched to soft contact lenses (CLs) vs. remained in spectacles after the clinical trial ended. METHODS.: Four hundred sixty-nine ethnically diverse, 6- to 11-year-old myopic children were randomly assigned to wear single vision lenses (SVLs) or progressive addition spectacle lenses (PALs) for 5 years as part of COMET. Afterwards they could choose another lens type, including CLs. Data in this article are from 286 participants who wore their original spectacle lenses for 6 years (n = 199) or wore CLs most or all the time between the 5- and 6-year visits (n = 87). Refractive error and axial length (AL) were measured after cycloplegia with 1% Tropicamide. The primary outcome was myopia progression between the 5- and 6-year visits. Two-year myopia progression was evaluated in a subset of 183 participants who wore the same lens type for an additional year. Myopia progression and AL were compared between the two lens groups using multiple linear regression. RESULTS.: Participants in the two groups were similar with respect to age, ethnicity, myopia at 5-years, accommodation and phoria, but more girls switched to CLs than remained in spectacles (p < 0.0001). Mean (+/-SD) myopia progression was higher (p = 0.003) after 1 year in the CL group[-0.28+/- 0.33 diopter (D)] than the spectacle group (-0.14+/- 0.36 D), and remained higher after 2 years in the 2-year subset (-0.52+/- 0.46 D vs.-0.25+/- 0.39 D, p < 0.0001). Results were similar after adjustment for related factors. No significant differences in AL were found between groups after adjustment. Corneal curvature remained unchanged in both groups. CONCLUSIONS.: COMET children switching from glasses to CLs experienced a small, statistically significant but clinically inconsequential increase in myopia progression.+http://www.ncbi.nlm.nih.gov/pubmed/19430326The COMET Group Journal article Optometry and vision science : official publication of the American Academy of Optometry Optom Vis Sci. 2009 May 7.*1538-9235 (Electronic) 1040-5488 (Linking)19430326*OD, MS, FAAO daggerPhD double daggerPhD, FAAO section signOD, MBA, FAAO paragraph signOD, FAAO Department of Optometry, School of Optometry, University of Alabama at Birmingham, Birmingham, Alabama (WM-T, KW), Division of Epidemiology, Stony Brook University School of Medicine, Stony Brook, New York (LMD, LH, LD), New England College of Optometry, Boston, Massachusetts (JG), and University of Houston College of Optometry, Houston, Texas (KF).10.1097/OPX.0b013e3181a6a250Eng 7F|7XMarsh-Tootle, W. L. Dong, L. M. Hyman, L. Gwiazda, J. Weise, K. K. Dias, L. Fernp, K. D.2009QMyopia Progression in Children Wearing Spectacles vs. Switching to Contact Lenses Optom Vis Sci 2009/05/12May 7kPURPOSE.: To investigate myopia progression in Correction of Myopia Evaluation Trial (COMET) participants who switched to soft contact lenses (CLs) vs. remained in spectacles after the clinical trial ended. METHODS.: Four hundred sixty-nine ethnically diverse, 6- to 11-year-old myopic children were randomly assigned to wear single vision lenses (SVLs) or progressive addition spectacle lenses (PALs) for 5 years as part of COMET. Afterwards they could choose another lens type, including CLs. Data in this article are from 286 participants who wore their original spectacle lenses for 6 years (n = 199) or wore CLs most or all the time between the 5- and 6-year visits (n = 87). Refractive error and axial length (AL) were measured after cycloplegia with 1% Tropicamide. The primary outcome was myopia progression between the 5- and 6-year visits. Two-year myopia progression was evaluated in a subset of 183 participants who wore the same lens type for an additional year. Myopia progression and AL were compared between the two lens groups using multiple linear regression. RESULTS.: Participants in the two groups were similar with respect to age, ethnicity, myopia at 5-years, accommodation and phoria, but more girls switched to CLs than remained in spectacles (p < 0.0001). Mean (+/-SD) myopia progression was higher (p = 0.003) after 1 year in the CL group[-0.28+/- 0.33 diopter (D)] than the spectacle group (-0.14+/- 0.36 D), and remained higher after 2 years in the 2-year subset (-0.52+/- 0.46 D vs.-0.25+/- 0.39 D, p < 0.0001). Results were similar after adjustment for related factors. No significant differences in AL were found between groups after adjustment. Corneal curvature remained unchanged in both groups. CONCLUSIONS.: COMET children switching from glasses to CLs experienced a small, statistically significant but clinically inconsequential increase in myopia progression.+http://www.ncbi.nlm.nih.gov/pubmed/19430326The COMET Group Journal article Optometry and vision science : official publication of the American Academy of Optometry Optom Vis Sci. 2009 May 7.*1538-9235 (Electronic) 1040-5488 (Linking)19430326*OD, MS, FAAO daggerPhD double daggerPhD, FAAO section signOD, MBA, FAAO paragraph signOD, FAAO Department of Optometry, School of Optometry, University of Alabama at Birmingham, Birmingham, Alabama (WM-T, KW), Division of Epidemiology, Stony Brook University School of Medicine, Stony Brook, New York (LMD, LH, LD), New England College of Optometry, Boston, Massachusetts (JG), and University of Houston College of Optometry, Houston, Texas (KF).10.1097/OPX.0b013e3181a6a250Eng||7 Barnett, W. A. Rengstorff, R. H.1977^Adaptation to hydrogel contact lenses: variations in myopia and corneal curvature measurements363-6J Am Optom Assoc483 1977/03/01Adult Contact Lenses, Hydrophilic/*adverse effects Cornea/anatomy & histology Female Humans Male Myopia/*etiology/rehabilitation Time FactorsMarKForty patients wearing lenses (soflens) were examined regularly for 3 months. During the first month the mean myopia gradually increased to 0.12 D more myopia and increased linearly to 0.50 D more myopia at 3 months. The mean corneal curvature flattened during the first 3 weeks, but steepened to about 0.37 D at 3 months. The process of myopia changes are not attributed solely to the anterior corneal curvature, but may also be the result of variations in the posterior corneal curvature, corneal thickness and index refraction as well as a change in the depth of the anterior chamber.)http://www.ncbi.nlm.nih.gov/pubmed/864190Barnett, W A Rengstorff, R H United states Journal of the American Optometric Association J Am Optom Assoc. 1977 Mar;48(3):363-6.%0003-0244 (Print) 0003-0244 (Linking)864190eng||7 Barnett, W. A. Rengstorff, R. H.1977^Adaptation to hydrogel contact lenses: variations in myopia and corneal curvature measurements363-6J Am Optom Assoc483 1977/03/01Adult Contact Lenses, Hydrophilic/*adverse effects Cornea/anatomy & histology Female Humans Male Myopia/*etiology/rehabilitation Time FactorsMarKForty patients wearing lenses (soflens) were examined regularly for 3 months. During the first month the mean myopia gradually increased to 0.12 D more myopia and increased linearly to 0.50 D more myopia at 3 months. The mean corneal curvature flattened during the first 3 weeks, but steepened to about 0.37 D at 3 months. The process of myopia changes are not attributed solely to the anterior corneal curvature, but may also be the result of variations in the posterior corneal curvature, corneal thickness and index refraction as well as a change in the depth of the anterior chamber.)http://www.ncbi.nlm.nih.gov/pubmed/864190Barnett, W A Rengstorff, R H United states Journal of the American Optometric Association J Am Optom Assoc. 1977 Mar;48(3):363-6.%0003-0244 (Print) 0003-0244 (Linking)864190eng||7 Grosvenor, T.1975SChanges in corneal curvature and subjective refraction of soft contact lens wearers405-13Am J Optom Physiol Opt526 1975/06/01Astigmatism/physiopathology Contact Lenses, Hydrophilic/*adverse effects Cornea/*anatomy & histology/pathology Humans *Refraction, Ocular Refractive Errors/physiopathology Time FactorsJun9Changes in corneal curvature and subjective refraction were found to occur in some wearers of N & N lathe-cut soft contact lenses. These changes appear to be the result of any one of a number of factors, including a relatively steep lens-cornea relationship, over-wearing of lenses and inadequate blinking habits.*http://www.ncbi.nlm.nih.gov/pubmed/1163625Grosvenor, T United states American journal of optometry and physiological optics Am J Optom Physiol Opt. 1975 Jun;52(6):405-13.%0093-7002 (Print) 0093-7002 (Linking)1163625eng||7 Grosvenor, T.1975SChanges in corneal curvature and subjective refraction of soft contact lens wearers405-13Am J Optom Physiol Opt526 1975/06/01Astigmatism/physiopathology Contact Lenses, Hydrophilic/*adverse effects Cornea/*anatomy & histology/pathology Humans *Refraction, Ocular Refractive Errors/physiopathology Time FactorsJun9Changes in corneal curvature and subjective refraction were found to occur in some wearers of N & N lathe-cut soft contact lenses. These changes appear to be the result of any one of a number of factors, including a relatively steep lens-cornea relationship, over-wearing of lenses and inadequate blinking habits.*http://www.ncbi.nlm.nih.gov/pubmed/1163625Grosvenor, T United states American journal of optometry and physiological optics Am J Optom Physiol Opt. 1975 Jun;52(6):405-13.%0093-7002 (Print) 0093-7002 (Linking)1163625eng ||7Anstice, N. S. Phillips, J. R.2011SEffect of dual-focus soft contact lens wear on axial myopia progression in children1152-61 Ophthalmology1186 2011/02/01JunZ PURPOSE: To test the efficacy of an experimental Dual-Focus (DF) soft contact lens in reducing myopia progression. DESIGN: Prospective, randomized, paired-eye control, investigator-masked trial with cross-over. PARTICIPANTS: Forty children, 11-14 years old, with mean spherical equivalent refraction (SER) of -2.71+/-1.10 diopters (D). METHODS: Dual-Focus lenses had a central zone that corrected refractive error and concentric treatment zones that created 2.00 D of simultaneous myopic retinal defocus during distance and near viewing. Control was a single vision distance (SVD) lens with the same parameters but without treatment zones. Children wore a DF lens in 1 randomly assigned eye and an SVD lens in the fellow eye for 10 months (period 1). Lens assignment was then swapped between eyes, and lenses were worn for a further 10 months (period 2). MAIN OUTCOME MEASURES: Primary outcome was change in SER measured by cycloplegic autorefraction over 10 months. Secondary outcome was a change in axial eye length (AXL) measured by partial coherence interferometry over 10 months. Accommodation wearing DF lenses was assessed using an open-field autorefractor. RESULTS: In period 1, the mean change in SER with DF lenses (-0.44+/-0.33 D) was less than with SVD lenses (-0.69+/-0.38 D; P < 0.001); mean increase in AXL was also less with DF lenses (0.11+/-0.09 mm) than with SVD lenses (0.22+/-0.10 mm; P < 0.001). In 70% of the children, myopia progression was reduced by 30% or more in the eye wearing the DF lens relative to that wearing the SVD lens. Similar reductions in myopia progression and axial eye elongation were also observed with DF lens wear during period 2. Visual acuity and contrast sensitivity with DF lenses were not significantly different than with SVD lenses. Accommodation to a target at 40 cm was driven through the central distance-correction zone of the DF lens. CONCLUSIONS: Dual-Focus lenses provided normal acuity and contrast sensitivity and allowed accommodation to near targets. Myopia progression and eye elongation were reduced significantly in eyes wearing DF lenses. The data suggest that sustained myopic defocus, even when presented to the retina simultaneously with a clear image, can act to slow myopia progression without compromising visual function. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.+http://www.ncbi.nlm.nih.gov/pubmed/21276616xAnstice, Nicola S Phillips, John R United States Ophthalmology Ophthalmology. 2011 Jun;118(6):1152-61. Epub 2011 Jan 26.*1549-4713 (Electronic) 0161-6420 (Linking)21276616uDepartment of Optometry and Vision Science, New Zealand National Eye Centre, The University of Auckland, New Zealand.8S0161-6420(10)01154-1 [pii] 10.1016/j.ophtha.2010.10.035eng ||7Anstice, N. S. Phillips, J. R.2011SEffect of dual-focus soft contact lens wear on axial myopia progression in children1152-61 Ophthalmology1186 2011/02/01JunZ PURPOSE: To test the efficacy of an experimental Dual-Focus (DF) soft contact lens in reducing myopia progression. DESIGN: Prospective, randomized, paired-eye control, investigator-masked trial with cross-over. PARTICIPANTS: Forty children, 11-14 years old, with mean spherical equivalent refraction (SER) of -2.71+/-1.10 diopters (D). METHODS: Dual-Focus lenses had a central zone that corrected refractive error and concentric treatment zones that created 2.00 D of simultaneous myopic retinal defocus during distance and near viewing. Control was a single vision distance (SVD) lens with the same parameters but without treatment zones. Children wore a DF lens in 1 randomly assigned eye and an SVD lens in the fellow eye for 10 months (period 1). Lens assignment was then swapped between eyes, and lenses were worn for a further 10 months (period 2). MAIN OUTCOME MEASURES: Primary outcome was change in SER measured by cycloplegic autorefraction over 10 months. Secondary outcome was a change in axial eye length (AXL) measured by partial coherence interferometry over 10 months. Accommodation wearing DF lenses was assessed using an open-field autorefractor. RESULTS: In period 1, the mean change in SER with DF lenses (-0.44+/-0.33 D) was less than with SVD lenses (-0.69+/-0.38 D; P < 0.001); mean increase in AXL was also less with DF lenses (0.11+/-0.09 mm) than with SVD lenses (0.22+/-0.10 mm; P < 0.001). In 70% of the children, myopia progression was reduced by 30% or more in the eye wearing the DF lens relative to that wearing the SVD lens. Similar reductions in myopia progression and axial eye elongation were also observed with DF lens wear during period 2. Visual acuity and contrast sensitivity with DF lenses were not significantly different than with SVD lenses. Accommodation to a target at 40 cm was driven through the central distance-correction zone of the DF lens. CONCLUSIONS: Dual-Focus lenses provided normal acuity and contrast sensitivity and allowed accommodation to near targets. Myopia progression and eye elongation were reduced significantly in eyes wearing DF lenses. The data suggest that sustained myopic defocus, even when presented to the retina simultaneously with a clear image, can act to slow myopia progression without compromising visual function. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.+http://www.ncbi.nlm.nih.gov/pubmed/21276616xAnstice, Nicola S Phillips, John R United States Ophthalmology Ophthalmology. 2011 Jun;118(6):1152-61. Epub 2011 Jan 26.*1549-4713 (Electronic) 0161-6420 (Linking)21276616uDepartment of Optometry and Vision Science, New Zealand National Eye Centre, The University of Auckland, New Zealand.8S0161-6420(10)01154-1 [pii] 10.1016/j.ophtha.2010.10.035eng ||7!Cho, P. Cheung, S. W. Edwards, M.2005The longitudinal orthokeratology research in children (LORIC) in Hong Kong: a pilot study on refractive changes and myopic control71-80 Curr Eye Res301 2005/05/07Body Weights and Measures Child *Contact Lenses Disease Progression Eye/anatomy & histology Female Follow-Up Studies Hong Kong Humans Male Myopia/prevention & control/*therapy Pilot Projects Refraction, OcularJanPURPOSE: Myopia is a common ocular disorder, and progression of myopia in children is of increasing concern. Modern overnight orthokeratology (ortho-k) is effective for myopic reduction and has been claimed to be effective in slowing the progression of myopia (myopic control) in children, although scientific evidence for this has been lacking. This 2 year pilot study was conducted to determine whether ortho-k can effectively reduce and control myopia in children. METHODS: We monitored the growth of axial length (AL) and vitreous chamber depth (VCD) in 35 children (7-12 years of age), undergoing ortho-k treatment and compared the rates of change with 35 children wearing single-vision spectacles from an earlier study (control). For the ortho-k subjects, we also determined the changes in corneal curvature and the relationships with changes of refractive errors, AL and VCD. RESULTS: The baseline spherical equivalent refractive errors (SER), the AL, and VCD of the ortho-k and control subjects were not statistically different. All the ortho-k subjects found post-ortho-k unaided vision acceptable in the daytime. The residual SER at the end of the study was -0.18 +/- 0.69 D (dioptre) and the reduction (less myopic) in SER was 2.09 +/- 1.34 D (all values are mean +/- SD). At the end of 24 months, the increases in AL were 0.29 +/- 0.27 mm and 0.54 +/- 0.27 mm for the ortho-k and control groups, respectively (unpaired t test; p = 0.012); the increases in VCD were 0.23 +/- 0.25 mm and 0.48 +/- 0.26 mm for the ortho-k and control groups, respectively (p = 0.005). There was significant initial corneal flattening in the ortho-k group but no significant relationships were found between changes in corneal power and changes in AL and VCD. CONCLUSION: Ortho-k can have both a corrective and preventive/control effect in childhood myopia. However, there are substantial variations in changes in eye length among children and there is no way to predict the effect for individual subjects.+http://www.ncbi.nlm.nih.gov/pubmed/15875367Cho, Pauline Cheung, Sin Wan Edwards, Marion Research Support, Non-U.S. Gov't England Current eye research Curr Eye Res. 2005 Jan;30(1):71-80.%0271-3683 (Print) 0271-3683 (Linking)15875367yDepartment of Optometry & Radiography, The Hong Kong Polytechnic University, Hong Kong, SAR, China. orpaulin@polyu.edu.hkeng ||7!Cho, P. Cheung, S. W. Edwards, M.2005The longitudinal orthokeratology research in children (LORIC) in Hong Kong: a pilot study on refractive changes and myopic control71-80 Curr Eye Res301 2005/05/07Body Weights and Measures Child *Contact Lenses Disease Progression Eye/anatomy & histology Female Follow-Up Studies Hong Kong Humans Male Myopia/prevention & control/*therapy Pilot Projects Refraction, OcularJanPURPOSE: Myopia is a common ocular disorder, and progression of myopia in children is of increasing concern. Modern overnight orthokeratology (ortho-k) is effective for myopic reduction and has been claimed to be effective in slowing the progression of myopia (myopic control) in children, although scientific evidence for this has been lacking. This 2 year pilot study was conducted to determine whether ortho-k can effectively reduce and control myopia in children. METHODS: We monitored the growth of axial length (AL) and vitreous chamber depth (VCD) in 35 children (7-12 years of age), undergoing ortho-k treatment and compared the rates of change with 35 children wearing single-vision spectacles from an earlier study (control). For the ortho-k subjects, we also determined the changes in corneal curvature and the relationships with changes of refractive errors, AL and VCD. RESULTS: The baseline spherical equivalent refractive errors (SER), the AL, and VCD of the ortho-k and control subjects were not statistically different. All the ortho-k subjects found post-ortho-k unaided vision acceptable in the daytime. The residual SER at the end of the study was -0.18 +/- 0.69 D (dioptre) and the reduction (less myopic) in SER was 2.09 +/- 1.34 D (all values are mean +/- SD). At the end of 24 months, the increases in AL were 0.29 +/- 0.27 mm and 0.54 +/- 0.27 mm for the ortho-k and control groups, respectively (unpaired t test; p = 0.012); the increases in VCD were 0.23 +/- 0.25 mm and 0.48 +/- 0.26 mm for the ortho-k and control groups, respectively (p = 0.005). There was significant initial corneal flattening in the ortho-k group but no significant relationships were found between changes in corneal power and changes in AL and VCD. CONCLUSION: Ortho-k can have both a corrective and preventive/control effect in childhood myopia. However, there are substantial variations in changes in eye length among children and there is no way to predict the effect for individual subjects.+http://www.ncbi.nlm.nih.gov/pubmed/15875367Cho, Pauline Cheung, Sin Wan Edwards, Marion Research Support, Non-U.S. Gov't England Current eye research Curr Eye Res. 2005 Jan;30(1):71-80.%0271-3683 (Print) 0271-3683 (Linking)15875367yDepartment of Optometry & Radiography, The Hong Kong Polytechnic University, Hong Kong, SAR, China. orpaulin@polyu.edu.hkeng||7!Kakita, T. Hiraoka, T. Oshika, T.2011NInfluence of overnight orthokeratology on axial elongation in childhood myopia2170-4Invest Ophthalmol Vis Sci525 2011/01/08Adolescent Axial Length, Eye/*physiopathology Biometry Child Disease Progression Eyeglasses Female Humans Interferometry Male Myopia/physiopathology/*therapy *Orthokeratologic Procedures Prospective StudiesAprPURPOSE: This prospective study was conducted to assess the influence of overnight orthokeratology (OK) on axial elongation in children, with those wearing spectacles as controls. METHODS: One hundred five subjects (210 eyes) were enrolled in the study. The OK group comprised 45 patients (90 eyes, age 12.1 +/- 2.5 years, mean +/- SD; OK group) who matched the inclusion criteria for OK. The control group comprised 60 patients (120 eyes, 11.9 +/- 2.0 years) who also matched the inclusion criteria for OK but preferred spectacles for myopia correction. Axial length was measured at baseline and after 2 years using ocular biometry, and the changes were evaluated and compared between the groups. RESULTS: Ninety-two subjects (42 and 50 in the OK and control groups, respectively) completed the 2-year follow-up examinations. At baseline, the spherical equivalent refractive error was -2.55 +/- 1.82 and -2.59 +/- 1.66 D, and the axial length was 24.66 +/- 1.11 and 24.79 +/- 0.80 mm in the OK and control groups, respectively, with no significant differences between the groups. The increase in axial length during the 2-year study period was 0.39 +/- 0.27 and 0.61 +/- 0.24 mm, respectively, and the difference was significant (P < 0.0001, unpaired t-test). CONCLUSIONS: OK suppressed axial elongation in myopic children, suggesting that this treatment can slow the progression of myopia to a certain extent.+http://www.ncbi.nlm.nih.gov/pubmed/21212181Kakita, Tetsuhiko Hiraoka, Takahiro Oshika, Tetsuro United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2011 Apr 6;52(5):2170-4. Print 2011 Apr.*1552-5783 (Electronic) 0146-0404 (Linking)21212181pKakita Eye Clinic, Kakita Eye Clinic, 4-1-15 Minaminagareyama, Nagareyama, Chiba, Japan. kec@kakitaeyeclinic.com'iovs.10-5485 [pii] 10.1167/iovs.10-5485eng A||7VSiatkowski, R. M. Cotter, S. A. Crockett, R. S. Miller, J. M. Novack, G. D. Zadnik, K.2008Two-year multicenter, randomized, double-masked, placebo-controlled, parallel safety and efficacy study of 2% pirenzepine ophthalmic gel in children with myopia332-9J AAPOS124 2008/03/25Administration, Topical Child Double-Blind Method Follow-Up Studies Gels Humans Muscarinic Antagonists/*administration & dosage Myopia/*drug therapy/physiopathology Pirenzepine/*administration & dosage Refraction, Ocular/drug effects Retrospective Studies Time Factors Treatment OutcomeAugPURPOSE: To evaluate if the safety and efficacy of the relatively selective M1-antagonist, pirenzepine, in slowing the progression of myopia in children is sustained over a 2-year period. METHODS: This was a multicenter, parallel-group, placebo-controlled, double-masked, randomized clinical trial. Enrolled were children aged 8 to 12 years, with entry spherical equivalent refractive error of -0.75 to -4.00 D and astigmatism ||7DShih, Y. F. Chen, C. H. Chou, A. C. Ho, T. C. Lin, L. L. Hung, P. T.1999XEffects of different concentrations of atropine on controlling myopia in myopic children85-90J Ocul Pharmacol Ther151 1999/02/27Adolescent Atropine/administration & dosage/*therapeutic use Child Disease Progression Humans Myopia/physiopathology/*prevention & control Ophthalmic Solutions/administration & dosage/therapeutic use Visual AcuityFebVAlthough 1% atropine effectively slows myopia progression, it is associated with adverse effects, including photophobia, blurred near vision, and poor compliance. We investigated whether lower doses of atropine would control myopia progression. One hundred and eighty-six children, from 6 to 13 years of age, were treated each night with different concentrations of atropine eye drops or a control treatment for up to 2 years. The mean myopic progression in each of the groups was 0.04 +/-0.63 diopter per year (D/Y) in the 0.5% atropine group, 0.45+/-0.55 D/Y in the 0.25% atropine group, and 0.47+/-0.91 D/Y in the 0.1% atropine group. All atropine groups showed significantly less myopic progression than the control group (1.06+/-0.61 D/Y) (p<0.01). Our study also showed that 61% of students in the 0.5% atropine group, 49% in the 0.25% atropine group and 42% in the 0.1% atropine group had no myopic progression. However, 4% of children in the 0.5% atropine group, 17% in the 0.25% atropine group, and 33% in the 0.1% atropine group still had fast myopic progression (>-1.0 D/Y). In contrast, only 8% of the control group showed no myopic progression and 44% had fast myopic progression. These results suggest that all three concentrations of atropine had significant effects on controlling myopia; however, treatment with 0.5% atropine was the most effective.+http://www.ncbi.nlm.nih.gov/pubmed/10048351TShih, Y F Chen, C H Chou, A C Ho, T C Lin, L L Hung, P T Clinical Trial Comparative Study Randomized Controlled Trial Research Support, Non-U.S. Gov't United states Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics J Ocul Pharmacol Ther. 1999 Feb;15(1):85-90.%1080-7683 (Print) 1080-7683 (Linking)10048351\Department of Ophthalmology, National Taiwan University Hospital, Taipei, Republic of China.eng >||7DShih, Y. F. Chen, C. H. Chou, A. C. Ho, T. C. Lin, L. L. Hung, P. T.1999XEffects of different concentrations of atropine on controlling myopia in myopic children85-90J Ocul Pharmacol Ther151 1999/02/27Adolescent Atropine/administration & dosage/*therapeutic use Child Disease Progression Humans Myopia/physiopathology/*prevention & control Ophthalmic Solutions/administration & dosage/therapeutic use Visual AcuityFebVAlthough 1% atropine effectively slows myopia progression, it is associated with adverse effects, including photophobia, blurred near vision, and poor compliance. We investigated whether lower doses of atropine would control myopia progression. One hundred and eighty-six children, from 6 to 13 years of age, were treated each night with different concentrations of atropine eye drops or a control treatment for up to 2 years. The mean myopic progression in each of the groups was 0.04 +/-0.63 diopter per year (D/Y) in the 0.5% atropine group, 0.45+/-0.55 D/Y in the 0.25% atropine group, and 0.47+/-0.91 D/Y in the 0.1% atropine group. All atropine groups showed significantly less myopic progression than the control group (1.06+/-0.61 D/Y) (p<0.01). Our study also showed that 61% of students in the 0.5% atropine group, 49% in the 0.25% atropine group and 42% in the 0.1% atropine group had no myopic progression. However, 4% of children in the 0.5% atropine group, 17% in the 0.25% atropine group, and 33% in the 0.1% atropine group still had fast myopic progression (>-1.0 D/Y). In contrast, only 8% of the control group showed no myopic progression and 44% had fast myopic progression. These results suggest that all three concentrations of atropine had significant effects on controlling myopia; however, treatment with 0.5% atropine was the most effective.+http://www.ncbi.nlm.nih.gov/pubmed/10048351TShih, Y F Chen, C H Chou, A C Ho, T C Lin, L L Hung, P T Clinical Trial Comparative Study Randomized Controlled Trial Research Support, Non-U.S. Gov't United states Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics J Ocul Pharmacol Ther. 1999 Feb;15(1):85-90.%1080-7683 (Print) 1080-7683 (Linking)10048351\Department of Ophthalmology, National Taiwan University Hospital, Taipei, Republic of China.eng L||7EFan, D. S. Lam, D. S. Chan, C. K. Fan, A. H. Cheung, E. Y. Rao, S. K.2007Topical atropine in retarding myopic progression and axial length growth in children with moderate to severe myopia: a pilot study27-33Jpn J Ophthalmol511 2007/02/14fAdministration, Topical Atropine/*administration & dosage/adverse effects Biometry Case-Control Studies Child Child, Preschool Disease Progression Eye/*growth & development/ultrasonography Female Humans Male Mydriatics/*administration & dosage/adverse effects Myopia/*drug therapy/physiopathology Ointments Pilot Projects Refraction, Ocular Treatment OutcomeJan-FebPURPOSE: To study the safety and efficacy of topical 1% atropine eye ointment in retarding myopic progression in children with moderate to severe myopia. METHODS: This was an interventional control study. Children (aged 5-10 years) with myopia of -3.00 diopters (D) or more were treated with 1% atropine ointment once daily for 1 year. Baseline and regular assessments of refractive errors by cycloplegic autorefraction and of axial length were done by ultrasound biometry, and the results were compared with data of control subjects. RESULTS: Twenty-three children (mean age: 7.4 +/- 1.6 years) with moderate to severe myopia, being treated in the Hong Kong Eye Hospital of the Chinese University of Hong Kong, were recruited into the atropine group, and 23 children from the same eye clinic were matched with the study subjects with respect to age, sex, and initial spherical equivalent refraction, as controls. The initial refractive errors were -5.18 +/- 2.05 D and -5.12 +/- 2.33 D in the atropine and the control groups, respectively (P = 0.934). Myopic progression was significantly less (P = 0.005) in the atropine group (+0.06 +/- 0.79 D) than in the control group (-1.19 +/- 2.48 D). Axial length increase was also significantly smaller in the atropine group (0.09 +/- 0.19 mm) than in the control group (0.70 +/- 0.63 mm) (P = 0.004). One child (4.3%) developed an allergic reaction. No other major adverse effects related to the treatment were noted. CONCLUSION: Topical 1% atropine ointment is a safe and effective treatment for retarding myopic progression in moderate to severe myopia. Further large-scale randomised controlled study with longer follow-up seems warranted.+http://www.ncbi.nlm.nih.gov/pubmed/17295137Fan, Dorothy S P Lam, Dennis S C Chan, Carmen K M Fan, Alex H Cheung, Eva Y Y Rao, Srinivas K Clinical Trial Research Support, Non-U.S. Gov't Japan Japanese journal of ophthalmology Jpn J Ophthalmol. 2007 Jan-Feb;51(1):27-33. Epub 2007 Feb 9.%0021-5155 (Print) 0021-5155 (Linking)17295137Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, Kowloon, Hong Kong, People's Republic of China. dorothyfan@cuhk.edu.hk10.1007/s10384-006-0380-7eng L||7EFan, D. S. Lam, D. S. Chan, C. K. Fan, A. H. Cheung, E. Y. Rao, S. K.2007Topical atropine in retarding myopic progression and axial length growth in children with moderate to severe myopia: a pilot study27-33Jpn J Ophthalmol511 2007/02/14fAdministration, Topical Atropine/*administration & dosage/adverse effects Biometry Case-Control Studies Child Child, Preschool Disease Progression Eye/*growth & development/ultrasonography Female Humans Male Mydriatics/*administration & dosage/adverse effects Myopia/*drug therapy/physiopathology Ointments Pilot Projects Refraction, Ocular Treatment OutcomeJan-FebPURPOSE: To study the safety and efficacy of topical 1% atropine eye ointment in retarding myopic progression in children with moderate to severe myopia. METHODS: This was an interventional control study. Children (aged 5-10 years) with myopia of -3.00 diopters (D) or more were treated with 1% atropine ointment once daily for 1 year. Baseline and regular assessments of refractive errors by cycloplegic autorefraction and of axial length were done by ultrasound biometry, and the results were compared with data of control subjects. RESULTS: Twenty-three children (mean age: 7.4 +/- 1.6 years) with moderate to severe myopia, being treated in the Hong Kong Eye Hospital of the Chinese University of Hong Kong, were recruited into the atropine group, and 23 children from the same eye clinic were matched with the study subjects with respect to age, sex, and initial spherical equivalent refraction, as controls. The initial refractive errors were -5.18 +/- 2.05 D and -5.12 +/- 2.33 D in the atropine and the control groups, respectively (P = 0.934). Myopic progression was significantly less (P = 0.005) in the atropine group (+0.06 +/- 0.79 D) than in the control group (-1.19 +/- 2.48 D). Axial length increase was also significantly smaller in the atropine group (0.09 +/- 0.19 mm) than in the control group (0.70 +/- 0.63 mm) (P = 0.004). One child (4.3%) developed an allergic reaction. No other major adverse effects related to the treatment were noted. CONCLUSION: Topical 1% atropine ointment is a safe and effective treatment for retarding myopic progression in moderate to severe myopia. Further large-scale randomised controlled study with longer follow-up seems warranted.+http://www.ncbi.nlm.nih.gov/pubmed/17295137Fan, Dorothy S P Lam, Dennis S C Chan, Carmen K M Fan, Alex H Cheung, Eva Y Y Rao, Srinivas K Clinical Trial Research Support, Non-U.S. Gov't Japan Japanese journal of ophthalmology Jpn J Ophthalmol. 2007 Jan-Feb;51(1):27-33. Epub 2007 Feb 9.%0021-5155 (Print) 0021-5155 (Linking)17295137Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, Kowloon, Hong Kong, People's Republic of China. dorothyfan@cuhk.edu.hk10.1007/s10384-006-0380-7eng !||7ATong, L. Huang, X. L. Koh, A. L. Zhang, X. Tan, D. T. Chua, W. H.2009hAtropine for the treatment of childhood myopia: effect on myopia progression after cessation of atropine572-9 Ophthalmology1163 2009/01/27WAccommodation, Ocular/drug effects Administration, Topical Atropine/*administration & dosage Child Disease Progression Double-Blind Method Female Follow-Up Studies Humans Male Mydriatics/*administration & dosage Myopia/*drug therapy/*physiopathology Ophthalmic Solutions/administration & dosage Visual Acuity/drug effects Withholding TreatmentMarPURPOSE: The aim of this study was to assess the effect on myopia progression after cessation of topical atropine treatment. DESIGN: Parallel-group, placebo-controlled, randomized, double-masked study. PARTICIPANTS: Four hundred children aged 6 to 12 years with refractive error of spherical equivalent -1.00 to -6.00 diopters (D) and astigmatism of -1.50 D or less. INTERVENTION: No intervention was administered. Subjects were followed up for 12 months after stopping treatment, which consisted of either 1% atropine or vehicle eyedrops once nightly for 2 years. Only 1 eye of each subject was chosen through randomization for treatment. MAIN OUTCOME MEASURES: The main efficacy outcome measures were change in spherical equivalent refraction as measured by cycloplegic autorefraction and change in ocular axial length as measured by ultrasonography. RESULTS: After cessation of atropine drops, the mean progression in the atropine-treated group was -1.14+/-0.80 D over 1 year, whereas the progression in placebo-treated eyes was -0.38+/-0.39 D (P<0.0001). However, after 3 years of participation in the trial (with 2 years on atropine treatment), eyes randomized to atropine have less severe myopia than other eyes. Spherical equivalent was -4.29+/-1.67 D in the atropine-treated eyes compared with -5.22+/-1.38 D in the placebo-treated eyes (P<0.0001). Spherical equivalents in atropine-untreated and placebo-untreated eyes were -5.00+/-1.62 D and -5.28+/-1.43 D, respectively. Over the 3 years, the increase in axial length of the atropine-treated eyes was 0.29+/-0.37 mm compared with 0.52+/-0.45 mm in the placebo-treated eyes (P<0.0001). After cessation of atropine, the amplitude of accommodation and near visual acuity returned to pretreatment levels. CONCLUSIONS: After stopping treatment, eyes treated with atropine demonstrated higher rates of myopia progression compared with eyes treated with placebo. However, the absolute myopia progression after 3 years was significantly lower in the atropine group compared with placebo.+http://www.ncbi.nlm.nih.gov/pubmed/19167081Tong, Louis Huang, Xiao Ling Koh, Angeline L T Zhang, Xiaoe Tan, Donald T H Chua, Wei-Han Randomized Controlled Trial Research Support, Non-U.S. Gov't United States Ophthalmology Ophthalmology. 2009 Mar;116(3):572-9. Epub 2009 Jan 22.*1549-4713 (Electronic) 0161-6420 (Linking)19167081?Singapore National Eye Center, Singapore. Louistong@hotmail.com8S0161-6420(08)01079-8 [pii] 10.1016/j.ophtha.2008.10.020eng ||7NChua, W. H. Balakrishnan, V. Chan, Y. H. Tong, L. Ling, Y. Quah, B. L. Tan, D.2006.Atropine for the treatment of childhood myopia2285-91 Ophthalmology11312 2006/09/26Administration, Topical Astigmatism/drug therapy/physiopathology Atropine/*therapeutic use Child Double-Blind Method Female Humans Male Muscarinic Antagonists/*therapeutic use Myopia/*drug therapy/physiopathology Ophthalmic Solutions/therapeutic use Refraction, Ocular/physiologyDecPURPOSE: To evaluate the efficacy and safety of topical atropine, a nonselective muscarinic antagonist, in slowing the progression of myopia and ocular axial elongation in Asian children. DESIGN: Parallel-group, placebo-controlled, randomized, double-masked study. PARTICIPANTS: Four hundred children aged 6 to 12 years with refractive error of spherical equivalent -1.00 to -6.00 diopters (D) and astigmatism of -1.50 D or less. INTERVENTION: Participants were assigned with equal probability to receive either 1% atropine or vehicle eye drops once nightly for 2 years. Only 1 eye of each subject was chosen through randomization for treatment. MAIN OUTCOME MEASURES: The main efficacy outcome measures were change in spherical equivalent refraction as measured by cycloplegic autorefraction and change in ocular axial length as measured by ultrasonography. The primary safety outcome measure was the occurrence of adverse events. RESULTS: Three hundred forty-six (86.5%) children completed the 2-year study. After 2 years, the mean progression of myopia and of axial elongation in the placebo-treated control eyes was -1.20+/-0.69 D and 0.38+/-0.38 mm, respectively. In the atropine-treated eyes, myopia progression was only -0.28+/-0.92 D, whereas the axial length remained essentially unchanged compared with baseline (-0.02+/-0.35 mm). The differences in myopia progression and axial elongation between the 2 groups were -0.92 D (95% confidence interval, -1.10 to -0.77 D; P<0.001) and 0.40 mm (95% confidence interval, 0.35-0.45 mm; P<0.001), respectively. No serious adverse events related to atropine were reported. CONCLUSIONS: Topical atropine was well tolerated and effective in slowing the progression of low and moderate myopia and ocular axial elongation in Asian children.+http://www.ncbi.nlm.nih.gov/pubmed/16996612Chua, Wei-Han Balakrishnan, Vivian Chan, Yiong-Huak Tong, Louis Ling, Yvonne Quah, Boon-Long Tan, Donald Randomized Controlled Trial Research Support, Non-U.S. Gov't United States Ophthalmology Ophthalmology. 2006 Dec;113(12):2285-91. Epub 2006 Sep 25.*1549-4713 (Electronic) 0161-6420 (Linking)16996612;Singapore National Eye Centre, Singapore. eyesnec@gmail.com8S0161-6420(06)00759-7 [pii] 10.1016/j.ophtha.2006.05.062eng ||74Chiang, M. F. Kouzis, A. Pointer, R. W. Repka, M. X.2001KTreatment of childhood myopia with atropine eyedrops and bifocal spectacles209-15Binocul Vis Strabismus Q163 2001/08/21Adolescent Atropine/*therapeutic use Child Disease Progression *Eyeglasses Female Humans Male Muscarinic Antagonists/*therapeutic use Myopia/physiopathology/*therapy Patient Compliance Retrospective Studies Treatment OutcomeBACKGROUND: Animal and human studies have suggested that muscarinic antagonists and bifocal spectacles may decrease the progression of myopia in children. The purpose of this study is to report the largest known series of patients treated simultaneously with bifocals and topical atropine. DESIGN: Retrospective, interventional, non-comparative case series. METHODS: 706 myopic children (296 boys and 410 girls, ages 6 to 16 years) were prescribed full cycloplegic spectacle corrections, with photochromic lenses and +2.25 diopter (D) reading adds in each eye. Both eyes were treated with atropine 1% drops once daily. OUTCOME MEASURES: Annual change in cycloplegic refractions of right eyes. Compliance with therapy was monitored by patient and parental report. RESULTS: 496 (70%) of the 706 patients reported full compliance with the treatment regimen, whereas the remaining 210 (30%) patients were partially compliant. The median interval of treatment was 3.62 years (range, 21 days-10.1 years). The mean rate of myopic progression was significantly less (P<0.001) in patients who were fully compliant with atropine therapy and bifocals (0.08 D/year) than in patients who were partially compliant with the treatment regimen (0.23 D/per year). No serious adverse effects were associated with atropine therapy. CONCLUSIONS: Full compliance with topical atropine therapy and bifocal spectacles was associated with decreased progression of myopia compared to partial compliance with treatment. For each of the treated groups, the mean rate of myopic progression was significantly less (P<0.05) than the mean annual rates of myopic progression published for the pediatric population.+http://www.ncbi.nlm.nih.gov/pubmed/11511288Chiang, M F Kouzis, A Pointer, R W Repka, M X Research Support, Non-U.S. Gov't United States Binocular vision & strabismus quarterly Binocul Vis Strabismus Q. 2001;16(3):209-15.%1088-6281 (Print) 1088-6281 (Linking)11511288gThe Wilmer Ophthalmological Institute, The Johns Hopkins Hospital, Baltimore, Maryland 21287-9028, USA.eng ||7NChua, W. H. Balakrishnan, V. Chan, Y. H. Tong, L. Ling, Y. Quah, B. L. Tan, D.2006.Atropine for the treatment of childhood myopia2285-91 Ophthalmology11312 2006/09/26Administration, Topical Astigmatism/drug therapy/physiopathology Atropine/*therapeutic use Child Double-Blind Method Female Humans Male Muscarinic Antagonists/*therapeutic use Myopia/*drug therapy/physiopathology Ophthalmic Solutions/therapeutic use Refraction, Ocular/physiologyDecPURPOSE: To evaluate the efficacy and safety of topical atropine, a nonselective muscarinic antagonist, in slowing the progression of myopia and ocular axial elongation in Asian children. DESIGN: Parallel-group, placebo-controlled, randomized, double-masked study. PARTICIPANTS: Four hundred children aged 6 to 12 years with refractive error of spherical equivalent -1.00 to -6.00 diopters (D) and astigmatism of -1.50 D or less. INTERVENTION: Participants were assigned with equal probability to receive either 1% atropine or vehicle eye drops once nightly for 2 years. Only 1 eye of each subject was chosen through randomization for treatment. MAIN OUTCOME MEASURES: The main efficacy outcome measures were change in spherical equivalent refraction as measured by cycloplegic autorefraction and change in ocular axial length as measured by ultrasonography. The primary safety outcome measure was the occurrence of adverse events. RESULTS: Three hundred forty-six (86.5%) children completed the 2-year study. After 2 years, the mean progression of myopia and of axial elongation in the placebo-treated control eyes was -1.20+/-0.69 D and 0.38+/-0.38 mm, respectively. In the atropine-treated eyes, myopia progression was only -0.28+/-0.92 D, whereas the axial length remained essentially unchanged compared with baseline (-0.02+/-0.35 mm). The differences in myopia progression and axial elongation between the 2 groups were -0.92 D (95% confidence interval, -1.10 to -0.77 D; P<0.001) and 0.40 mm (95% confidence interval, 0.35-0.45 mm; P<0.001), respectively. No serious adverse events related to atropine were reported. CONCLUSIONS: Topical atropine was well tolerated and effective in slowing the progression of low and moderate myopia and ocular axial elongation in Asian children.+http://www.ncbi.nlm.nih.gov/pubmed/16996612Chua, Wei-Han Balakrishnan, Vivian Chan, Yiong-Huak Tong, Louis Ling, Yvonne Quah, Boon-Long Tan, Donald Randomized Controlled Trial Research Support, Non-U.S. Gov't United States Ophthalmology Ophthalmology. 2006 Dec;113(12):2285-91. Epub 2006 Sep 25.*1549-4713 (Electronic) 0161-6420 (Linking)16996612;Singapore National Eye Centre, Singapore. eyesnec@gmail.com8S0161-6420(06)00759-7 [pii] 10.1016/j.ophtha.2006.05.062eng ||7-McBrien, N. A. Moghaddam, H. O. Reeder, A. P.1993YAtropine reduces experimental myopia and eye enlargement via a nonaccommodative mechanism205-15Invest Ophthalmol Vis Sci341 1993/01/01U*Accommodation, Ocular Animals Anthropometry Atropine/*therapeutic use Chickens Choroid/pathology Disease Models, Animal Eye/*pathology Hypertrophy/pathology/physiopathology/prevention & control Injections Light Myopia/pathology/physiopathology/*prevention & control Pupil/drug effects Retina/ultrastructure Sensory Deprivation Vitreous BodyJanPURPOSE: To determine whether the muscarinic antagonist atropine effectively reduces or prevents experimentally induced myopia via a nonaccommodative mechanism. METHODS: Chicks were monocularly deprived (MD) of pattern vision by placement of a translucent occluder over the left eye. In two of the three MD groups, chicks received a series of intravitreal injections of atropine (n = 8) or saline vehicle (n = 8) with MD. Control groups (n = 8) of chicks were employed to assess the effects of MD, intravitreal injections, and drug effects. RESULTS: In sham-injected or saline-injected MD chicks, 8 days of MD produced -18.5 D and -20.9 D of experimental myopia, respectively. In atropine-injected MD chicks, 8 days of MD produced only -2.8 D of experimental myopia. This significant reduction in experimentally induced myopia in atropine-injected MD chicks was associated with a marked reduction in the relative axial elongation of the deprived eye (0.21 mm) when compared to saline-injected or sham-injected MD chicks (1.04 mm and 1.00 mm). This reduction in axial length in atropine-injected MD chicks was predominantly the result of a reduction in vitreous chamber elongation, although a reduction in anterior segment depth also was observed. Mean equatorial diameter was significantly reduced in atropine-injected MD chicks compared to saline-injected and sham-injected MD chicks, although to a lesser extent. Control experiments demonstrated that intravitreally injected atropine did not reduce carbachol-induced accommodation or light-induced pupil constriction in the skeletal intraocular muscles of the chick eye. CONCLUSIONS: These findings demonstrate that chronic administration of the muscarinic antagonist atropine prevents experimentally induced myopia in chick via a nonaccommodative mechanism.*http://www.ncbi.nlm.nih.gov/pubmed/8425826McBrien, N A Moghaddam, H O Reeder, A P Research Support, Non-U.S. Gov't United states Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 1993 Jan;34(1):205-15.%0146-0404 (Print) 0146-0404 (Linking)8425826cDepartment of Optometry & Vision Sciences, University of Wales, College of Cardiff, United Kingdom.eng5||76Duboust, A. Metivier, F. Bedrossian, J. Merland, J. J.1979{[Embolization of the renal arteries or "medical nephrectomy" in amyloidosis nephrotic syndromes. 2 cases (author's transl)]3325-7Nouv Presse Med841 1979/10/29Adult Amyloidosis/complications Embolization, Therapeutic/adverse effects/*methods Humans Male Nephrotic Syndrome/etiology/*therapy *Renal ArteryOct 29Some nephrotic syndroms have a very poor prognosis (life threatening) because of the protidic loss, even if the renal fonction is still normal. Only a binephrectomy can prevent this true protidic diabetes. In order, to avoid the inconvenients of surgery which can be a major problem with patients having cicatrization difficulties, a bilateral embolization of the renal arteries was done. This procedure was successfully used in two patients with nephroctic syndrom secondary to a renal amyloidosis, who where in a cachectic state.)http://www.ncbi.nlm.nih.gov/pubmed/534197Duboust, A Metivier, F Bedrossian, J Merland, J J Case Reports English Abstract France La Nouvelle presse medicale Nouv Presse Med. 1979 Oct 29;8(41):3325-7.%0301-1518 (Print) 0301-1518 (Linking)534197Embolisation des arteres renales, ou "nephrectomie medicale", au cours des syndromes nephrotiques de l'amyloidose. 2 observations.fre||7Bedrossian, R. H.19793Silicone intubation of the lacrimal drainage system39-44Ophthalmic Surg109 1979/09/01jHumans Intubation/instrumentation/*methods Lacrimal Apparatus Diseases/*surgery Methods *Silicones SplintsSep)http://www.ncbi.nlm.nih.gov/pubmed/523072WBedrossian, R H United states Ophthalmic surgery Ophthalmic Surg. 1979 Sep;10(9):39-44.%0022-023X (Print) 0022-023X (Linking)523072engr||7*Shultz, T. Miller, W. C. Bedrossian, C. W.1979JClinical application of measurement of angiotensin-converting enzyme level439-41JAMA2425 1979/08/03Adult *Clinical Enzyme Tests Evaluation Studies as Topic False Negative Reactions False Positive Reactions Female Humans Leprosy/diagnosis Male Middle Aged Peptidyl-Dipeptidase A/*blood Sarcoidosis/*diagnosis Sarcoma/diagnosis Tuberculosis/diagnosisAug 3Assay of angiotensin-converting enzyme (ACE) in the sera of 69 patients demonstrated elevated levels in 19 of 22 (86%) of those with clinically active, biopsy-proved sarcoidosis. Patients with dormant sarcoidosis and generally those with various other disorders had normal levels. Elevated levels were also seen in six cases possibly representing sarcoid variants and in one case each of leprosy, carcinoma, tuberculosis, lymphomatoid granulomatosis, and immunoblastic sarcoma. Although ACE is sensitive to active sarcoidosis, the presence of false-positive findings limits its diagnostic usefulness to an adjunctive role; the assay should be combined with medical evaluation and tissue biopsy in selected cases.)http://www.ncbi.nlm.nih.gov/pubmed/221694Shultz, T Miller, W C Bedrossian, C W United states JAMA : the journal of the American Medical Association JAMA. 1979 Aug 3;242(5):439-41.%0098-7484 (Print) 0098-7484 (Linking)221694eng||76Sack, K. E. Bekheit, S. Fadem, S. Z. Bedrossian, C. W.1979ASevere pulmonary vascular disease in systemic lupus erythematosus1016-8 South Med J728 1979/08/01Acute Disease Adult Autopsy Diagnosis, Differential Echocardiography Electrocardiography Female Humans Lupus Erythematosus, Systemic/*complications *Pulmonary Artery Pulmonary Embolism/diagnosis Pulmonary Heart Disease/etiology Vascular Diseases/complications/diagnosis/etiologyAugIA young woman with systemic lupus erythematosus (SLE) had clinical evidence of acute cor pulmonale. Autopsy disclosed vascular lesions in the lungs resembling those seen in advanced pulmonary hypertension. This case illustrates that severe pulmonary vascular disease may complicate SLE and mimic pulmonary thromboembolic disease.)http://www.ncbi.nlm.nih.gov/pubmed/472799Sack, K E Bekheit, S Fadem, S Z Bedrossian, C W Case Reports United states Southern medical journal South Med J. 1979 Aug;72(8):1016-8.%0038-4348 (Print) 0038-4348 (Linking)472799engy||7Bedrossian, R. H.1979 The effect of atropine on myopia713-9 Ophthalmology865 1979/05/01Adolescent Atropine/*therapeutic use Child Evaluation Studies as Topic Follow-Up Studies Humans Myopia/*drug therapy Statistics as TopicMaySixty-two children were treated with atropine in one eye for one year; the fellow eye was the control. The eyes were switched the second year. Twenty-eight patients were treated for four years on the same basis. Control eyes showed significant increases in myopia compared to treated eyes. Some treated eyes showed decreases in myopia; no decreases were seen in control eyes. Posttreatment data analysis indicates the effects are long-term.)http://www.ncbi.nlm.nih.gov/pubmed/545205PBedrossian, R H United states Ophthalmology Ophthalmology. 1979 May;86(5):713-9.%0161-6420 (Print) 0161-6420 (Linking)545205eng||7+Bedrossian, C. W. Miller, W. C. Luna, M. A.1979<Methotrexate-induced diffuse interstitial pulmonary fibrosis313-8 South Med J723 1979/03/01Aged Brain Neoplasms/drug therapy Carcinoma, Squamous Cell/drug therapy Diagnosis, Differential Humans Lung Neoplasms/drug therapy Male Methotrexate/*adverse effects/therapeutic use Middle Aged Psoriasis/drug therapy Pulmonary Fibrosis/*chemically induced/diagnosis/pathologyMarUThree patients received respectively 190 mg, 175 mg, and 196 mg of methotrexate and developed bilateral pulmonary infiltrates without evidence of peripheral blood eosinophilia. Sputum in the three cases failed to reveal acid-fast bacilli, pathogenic fungi, or opportunistic organisms by cultures and appropriate stains. Despite discontinuance of the drug and/or institution of corticosteroid therapy, progressive respiratory failure led to death. In all three cases, autopsy revealed gross and microscopic features indistinguishable from those seen in the Hamman-Rich syndrome, and methotrexate hepatotoxicity was present in one. Pulmonary eosinophilia or granulomas, classically seen in previously reported cases of methotrexate pneumonitis, were not observed. It is suggested therefore that methotrexate be added to the list of agents capable of inducing diffuse interstitial pulmonary fibrosis. Conversely, diffuse interstitial pulmonary fibrosis should be considered in the differential diagnosis of patients receiving methotrexate who develop bilateral pulmonary infiltrates seen on chest roentgenograms.)http://www.ncbi.nlm.nih.gov/pubmed/424824|Bedrossian, C W Miller, W C Luna, M A Case Reports United states Southern medical journal South Med J. 1979 Mar;72(3):313-8.%0038-4348 (Print) 0038-4348 (Linking)424824eng||7eFournier, A. Bordier, P. Gueris, J. Sebert, J. L. Marie, P. Ferriere, C. Bedrossian, J. DeLuca, H. F.1979Comparison of 1 alpha-hydroxycholecalciferol and 25-hydroxycholecalciferol in the treatment of renal osteodystrophy: greater effect of 25-hydroxycholecalciferol on bone mineralization196-204 Kidney Int152 1979/02/01DAdult Alkaline Phosphatase/blood Biopsy Bone and Bones/*drug effects/pathology Calcium/blood Drug Administration Schedule Humans Hydroxycholecalciferols/administration & dosage/*therapeutic use Male Middle Aged Parathyroid Hormone/blood Phosphates/blood Renal Dialysis Renal Osteodystrophy/*drug therapy/metabolism/pathologyFeb)http://www.ncbi.nlm.nih.gov/pubmed/513484Fournier, A Bordier, P Gueris, J Sebert, J L Marie, P Ferriere, C Bedrossian, J DeLuca, H F Germany, west Kidney international Kidney Int. 1979 Feb;15(2):196-204.%0085-2538 (Print) 0085-2538 (Linking)513484eng8||74Bedrossian, C. W. Verani, R. Unger, K. M. Salman, J.1979\Pulmonary malignant fibrous histiocytoma. Light and electron microscopic studies of one case186-9Chest752 1979/02/01WCytoplasm/metabolism/ultrastructure Endoplasmic Reticulum/ultrastructure Fibroblasts/ultrastructure Glycogen/metabolism Histiocytes/ultrastructure Histiocytoma, Benign Fibrous/metabolism/*pathology/ultrastructure Humans Lung Neoplasms/metabolism/*pathology/ultrastructure Lysosomes/ultrastructure Male Microscopy, Electron Middle Aged NecrosisFeb5A malignant fibrous histiocytoma (MFH) arising in the lungs of a 51-year-old man was studied by light and electron microscopy. Features observed were identical to those of MFHs which occur in the skin and subcutaneous tissue and less commonly in other deep locations. By light microscopy, a storiform pattern with admixture of fibroblasts and histiocytes, as well as xanthomatous and giant cells, was noted. Undifferentiated tumor cells along with fibroblasts and histiocytes in different degrees of differentiation were identified ultrastructurally. These findings lend support to the concept that MFH is a sarcoma of primitive mesenchymal cell origin. The addition of the lung as another primary site for the development of this tumor is consistent with the view that MFHs may potentially arise in any part of the body.)http://www.ncbi.nlm.nih.gov/pubmed/217571lBedrossian, C W Verani, R Unger, K M Salman, J Case Reports United states Chest Chest. 1979 Feb;75(2):186-9.%0012-3692 (Print) 0012-3692 (Linking)217571engy||7Bedrossian, R. H.1979 The effect of atropine on myopia713-9 Ophthalmology865 1979/05/01Adolescent Atropine/*therapeutic use Child Evaluation Studies as Topic Follow-Up Studies Humans Myopia/*drug therapy Statistics as TopicMaySixty-two children were treated with atropine in one eye for one year; the fellow eye was the control. The eyes were switched the second year. Twenty-eight patients were treated for four years on the same basis. Control eyes showed significant increases in myopia compared to treated eyes. Some treated eyes showed decreases in myopia; no decreases were seen in control eyes. Posttreatment data analysis indicates the effects are long-term.)http://www.ncbi.nlm.nih.gov/pubmed/545205PBedrossian, R H United states Ophthalmology Ophthalmology. 1979 May;86(5):713-9.%0161-6420 (Print) 0161-6420 (Linking)545205engZ||7IShapiro, B. K. Palmer, F. B. Antell, S. Bilker, S. Ross, A. Capute, A. J.1990:Precursors of reading delay: neurodevelopmental milestones416-20 Pediatrics853 Pt 2 1990/03/01RChild Dyslexia/*psychology Humans *Language Development *Motor Skills Risk FactorsMarThe relationship between current reading ability and the achievement of early language and motor developmental milestones was evaluated in 240 children, aged 7 1/2 years, whose language and motor achievement had been charted at each well baby visit during the first 2 years of life. Those children whose composite reading score was 6 months behind their chronologic age on the Woodcock-Johnson Psychoeducational Battery were classified as having reading delay. Relationships to reading outcome were assessed for individual infant milestones, for critical screening values, and by statistical techniques that characterized the developmental process rather than single milestones. Significant differences (P less than .05) were noted between children with and without reading delays for the following milestones: 4 to 6 words, 7 to 20 words, 50 words, 2-word sentences, and 5 and 8 body parts. The positive predictive value of slower milestone achievement ranged from 0% to 50%. Techniques that focused on the developmental process during the first 2 years (either rate of achievement of neurodevelopmental milestones or order of milestone acquisition) were better able to classify children with reading delay (sensitivity = .73, specificity = .78). Although the language milestone measures did not classify children sufficiently well to be diagnostic, the data served to determine whether a child would be at high risk based on performance rather than historical factors.*http://www.ncbi.nlm.nih.gov/pubmed/2304802Shapiro, B K Palmer, F B Antell, S Bilker, S Ross, A Capute, A J MCJ 240463/PHS HHS/United States Research Support, U.S. Gov't, P.H.S. United states Pediatrics Pediatrics. 1990 Mar;85(3 Pt 2):416-20.%0031-4005 (Print) 0031-4005 (Linking)2304802@Kennedy Institute for Handicapped Children, Baltimore, MD 21205.eng||7#Silva, P. A. McGee, R. Williams, S.1982The predictive significance of slow walking and slow talking: a report from the Dunedin Multidisciplinary Child Development Study133-9Br J Disord Commun173 1982/12/01|Age Factors Child *Child Development Child, Preschool Humans Intelligence Locomotion Longitudinal Studies New Zealand SpeechDec*http://www.ncbi.nlm.nih.gov/pubmed/7183330Silva, P A McGee, R Williams, S Research Support, Non-U.S. Gov't England The British journal of disorders of communication Br J Disord Commun. 1982 Dec;17(3):133-9.%0007-098X (Print) 0007-098X (Linking)7183330eng,|?$Scheiman, Mitchell Rouse, Michael W.19949Optometric management of learning-related vision problems xiv, 606 p. St. LouisMosbyVision disorders in children. Learning disabilities. Vision Disorders in infancy & childhood. Vision Disorders complications. Vision Disorders therapy. Learning physiology. Learning Disorders etiology.m94003010 Mitchell M. Scheiman, Michael W. Rouse. ill. ; 28 cm. Includes bibliographical references and index. 08016638573958596=Jefferson or Adams Building Reading Rooms RE48.2.C5; S34 1994||7ETaanila, A. Murray, G. K. Jokelainen, J. Isohanni, M. Rantakallio, P.20054Infant developmental milestones: a 31-year follow-up581-6Dev Med Child Neurol479 2005/09/06gAdolescent Adult Age Factors Child Child Development/*classification Child Welfare/statistics & numerical data Child, Preschool Cohort Studies *Educational Status Finland Follow-Up Studies Humans Infant Infant, Newborn Language Development Motor Skills/classification Reference Values Registries/statistics & numerical data Statistics as Topic Toilet TrainingSepThis study examined the association between infant developmental milestones and educational level at 31 years of age in the Northern Finland 1966 Birth Cohort (n = 12 058). Developmental data (age at standing, walking, speaking, and measures of bowel and bladder control) were gathered from children's welfare centres. Information on type of schooling at 14 years of age was reported by children and parents. School achievement at 16 years of age and educational level at 31 years were obtained from national registers. Those who reached infant developmental milestones sooner in their first year of life had significantly better (p < 0.05) mean scores in teacher ratings at 16 years, and at 31 years they were more likely to have achieved a better educational level than slower developers. The adjusted odds ratios for individuals who developed more slowly to remain at a basic educational level (7 to 16y) ranged significantly from 1.1 to 1.3. The possibility of advancing from secondary to tertiary level was 1.4 times greater in faster developers than in slow developers. In conclusion, those who develop faster during their first year of life tend to attain higher levels of education in adolescence and adulthood.+http://www.ncbi.nlm.nih.gov/pubmed/16138663Taanila, Anja Murray, Graham K Jokelainen, Jari Isohanni, Matti Rantakallio, Paula England Developmental medicine and child neurology Dev Med Child Neurol. 2005 Sep;47(9):581-6.%0012-1622 (Print) 0012-1622 (Linking)16138663University of Oulu, Department of Public Health Science and General Practice, PO Box 5000, 90014 Oulu, Finland. anja.taanila@oulu.fiengaF|71Karimi, M. Fallah, R. Dehghanpoor, A. Mirzaei, M.2011EDevelopmental status of 5-year-old moderate low birth weight children Brain Dev 2011/01/25Jan 20UBackground: Low birth weight (LBW or birth weight<2500g) is one of the most serious children problems in today's world. The purpose of this study was to evaluate and compare developmental status of moderately LBW (birth weight: 1500-2499g) children at the age of five to that of normal birth weight (NBW: birth weight: 2500-4000g) ones. Methods: In a case-control study, developmental status of five year old children referred for vaccination between December 2008 and June 2009 in Yazd-Iran, evaluated via Persian version of 60-month Ages and Stages Questionnaires (ASQ). NBW and MLBW children were selected as control and case groups, respectively. Results: Frequency of developmental delay in gross motor, fine motor and problem solving domains were significantly higher in MLBW group and mean score in all developmental domains was statistically significant lower in case group. Conclusion: LBW is one of risk factors for developmental delay. So, evaluation and monitoring of development status of LBW should be emphasized for early and timely diagnosis, investigation, management and also rehabilitation.+http://www.ncbi.nlm.nih.gov/pubmed/21256687;Journal article Brain & development Brain Dev. 2011 Jan 20.*1872-7131 (Electronic) 0387-7604 (Linking)21256687oShahid Sadoughi University of Medical Sciences-Yazd, Department of Pediatrics, Shaheed Sadoughi Hospital, Iran.:S0387-7604(10)00285-8 [pii] 10.1016/j.braindev.2010.10.022Eng -||7AChyi, L. J. Lee, H. C. Hintz, S. R. Gould, J. B. Sutcliffe, T. L.2008rSchool outcomes of late preterm infants: special needs and challenges for infants born at 32 to 36 weeks gestation25-31 J Pediatr1531 2008/06/24Child *Child Development Child, Preschool Cognition Education, Special Educational Status Female Follow-Up Studies Humans Infant, Newborn *Infant, Premature Male Outcome Assessment (Health Care) *Reading SchoolsJulzOBJECTIVE: Because limited long-term outcome data exist for infants born at 32 to 36 weeks gestation, we compared school outcomes between 32- to 33-week moderate preterm (MP), 34-36 week late preterm (LP) and full-term (FT) infants. STUDY DESIGN: A total of 970 preterm infants and 13 671 FT control subjects were identified from the Early Childhood Longitudinal Study-Kindergarten Cohort. Test scores, teacher evaluations, and special education enrollment from kindergarten (K) to grade 5 were compared. RESULTS: LP infants had lower reading scores than FT infants in K to first grade (P < .05). Adjusted risk for poor reading and math scores remained elevated in first grade (P < .05). Teacher evaluations of math skills from K to first grade and reading skills from K to fifth grade were worse for LP infants (P < .05). Adjusted odds for below average skills remained higher for math in K and for reading at all grades (P < .05). Special education participation was higher for LP infants at early grades (odds ratio, 1.4-2.1). MP infants had lower test and teacher evaluation scores than FT infants and twice the risk for special education at all grade levels. CONCLUSIONS: Persistent teacher concerns through grade 5 and greater special education needs among MP and LP infants suggest a need to start follow-up, anticipatory guidance, and interventions for infants born at 32 to 36 weeks gestation.+http://www.ncbi.nlm.nih.gov/pubmed/18571530Chyi, Lisa J Lee, Henry C Hintz, Susan R Gould, Jeffrey B Sutcliffe, Trenna L United States The Journal of pediatrics J Pediatr. 2008 Jul;153(1):25-31. Epub 2008 Mar 19.*1097-6833 (Electronic) 0022-3476 (Linking)18571530Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University, Palo Alto, CA, USA. lisachyi@stanford.edu7S0022-3476(08)00068-1 [pii] 10.1016/j.jpeds.2008.01.027eng ||7@van Baar, A. L. Vermaas, J. Knots, E. de Kleine, M. J. Soons, P.2009`Functioning at school age of moderately preterm children born at 32 to 36 weeks' gestational age251-7 Pediatrics1241 2009/07/01}Attention Deficit Disorder with Hyperactivity/epidemiology Child Child Behavior Disorders/*epidemiology Cognition Disorders/*epidemiology Developmental Disabilities/epidemiology Education, Special/statistics & numerical data Female Follow-Up Studies Gestational Age Humans Infant, Newborn *Infant, Premature Intelligence Logistic Models Male Netherlands/epidemiology QuestionnairesJulOBJECTIVE: To study outcome of low-risk moderately preterm birth between 32 and 36/7 weeks' gestation. METHODS: 377 Moderately preterm children (M: 34.7, SD: 1.2 complete weeks), without need for neonatal intensive care and without dysmaturity or congenital malformations, were compared with 182 term children and assessed at eight years (M: 8.9, SD: 0.54). School situation, IQ, sustained attention, behavior problems, and attention-deficit/hyperactivity characteristics were studied. RESULTS: Special education was attended by 7.7% of the moderately preterm children, more than twice the rate of 2.8% in the general Dutch population of this age. Additional exploration for two preterm subgroups of 32 to 33 versus 34 to 36 weeks' gestation showed a need for special education in 9.7% versus 7.3% and a significant difference in grade retention for 30% versus 17%, respectively. Of the children attending mainstream primary schools, grade retention was found in 19% of the preterm versus 8% of the comparison children. Adjusting for maternal education, a group difference of 3 points was found in IQ. The preterm children needed more time for the sustained attention task. The preterm children had more behavior problems (specifically internalizing problems with 27% scoring above the borderline cut-off), as well as more attention-deficit/hyperactivity disorder characteristics (specifically attention deficits). CONCLUSIONS: Cognitive and emotional regulation difficulties affect functioning of moderately preterm children, as school problems, a slightly lower IQ, attention and behavioral problems are found when they are compared with term-born children. Identification and monitoring of precursors of these problems at younger age is needed in view of prevention purposes.+http://www.ncbi.nlm.nih.gov/pubmed/19564307van Baar, Anneloes L Vermaas, John Knots, Edwin de Kleine, Martin J K Soons, Paul United States Pediatrics Pediatrics. 2009 Jul;124(1):251-7.*1098-4275 (Electronic) 0031-4005 (Linking)19564307_Department of Pediatric Psychology, Tilburg University, Tilburg, Netherlands. a.l.vanbaar@uu.nl&124/1/251 [pii] 10.1542/peds.2008-2315eng |t7$Huddy, C. L. Johnson, A. Hope, P. L.2001GEducational and behavioural problems in babies of 32-35 weeks gestationF23-8 Arch Dis Child Fetal Neonatal Ed851 2001/06/23Adult Case-Control Studies Child Child Behavior Cohort Studies Delivery, Obstetric/methods Developmental Disabilities/*etiology Educational Status Female Humans Infant, Newborn Infant, Premature/*physiology/psychology Intensive Care, Neonatal Length of Stay Logistic Models Male Mothers Multivariate Analysis Needs Assessment Pre-Eclampsia/complications Pregnancy Respiration Disorders/complications Risk Factors Sex Factors Socioeconomic Factors *SurvivorsJulAIM: To identify incidence of school and behaviour problems at age 7 years in children born between 32 and 35 weeks gestation, and investigate perinatal risk factors. METHOD: The study population consisted of all children born at 32-35 weeks gestation to mothers resident in Oxfordshire in 1990. General practitioners, parents, and teachers were asked about health, behaviour, and education by postal questionnaire. Teachers rated children on level of function in six areas using a five point scale. They also completed the Strengths and Difficulties behaviour questionnaire. Perinatal risk factors were identified for children with poor school performance using a univariate and multivariate analysis. RESULTS: Teacher responses were obtained for 117 (66%) of the 176 children in the cohort. Twenty nine (25%) required support from a non-teaching assistant, five (4%) had required a statement of special educational needs, and three (3%) were at special school. Poor outcome was reported for 32% in writing, 31% in fine motor skills, 29% in mathematics, 19% in speaking, 21% in reading, and 12% in physical education. On the behaviour questionnaire, 19% of the cohort achieved an abnormal hyperactivity score (population norm 10%). Multivariate analysis showed perinatal variables that remained significant, independent of other variables; they were discharge from the special care baby unit > 36 weeks postconceptional age (odds ratio 4.15; 95% confidence interval 1.43 to 12.05) and male sex (odds ratio 3.88; 95% confidence interval 1.42 to 10.6). CONCLUSION: Up to a third of children born between 32 and 35 weeks gestation may have school problems. As there are larger numbers in this gestational category compared with smaller babies, this finding has implications for educational services.+http://www.ncbi.nlm.nih.gov/pubmed/11420317Huddy, C L Johnson, A Hope, P L England Archives of disease in childhood. Fetal and neonatal edition Arch Dis Child Fetal Neonatal Ed. 2001 Jul;85(1):F23-8.%1359-2998 (Print) 1359-2998 (Linking)172128011420317iNeonatal Unit, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK. huddy@doctors.org.ukeng ||7(Morse, S. B. Zheng, H. Tang, Y. Roth, J.20091Early school-age outcomes of late preterm infantse622-9 Pediatrics1234 2009/04/02 Child Development Child, Preschool Continuity of Patient Care Developmental Disabilities/*epidemiology Disabled Children/statistics & numerical data Female Gestational Age Humans Infant Infant, Newborn *Infant, Premature Pregnancy *Pregnancy Outcome Risk AssessmentAprlOBJECTIVE: Late preterm infants represent a significant portion of preterm deliveries. Until recently, these infants have received little attention because of assumptions that they carry minimal risk for long-term morbidities. The purpose of this study was to compare prekindergarten and kindergarten outcomes among healthy late preterm infants, 34 0/7 to 36 6/7 weeks' gestation at birth, and healthy term infants, 37 0/7 to 41 6/7 weeks' gestation at birth. METHODS: The study sample consisted of singleton infants who were born in Florida between January 1, 1996, and August 31, 1997, with a gestational age between 34 and 41 weeks (N = 161804) with a length of stay < or =72 hours. Seven early school-age outcomes were analyzed. Outcomes were adjusted for 15 potential confounding maternal and infant variables. Unadjusted and adjusted relative risk with 95% confidence interval was estimated for each outcome by using Poisson regression modeling. RESULTS: Risk for developmental delay or disability was 36% higher among late preterm infants compared with term infants. Risk for suspension in kindergarten was 19% higher for late preterm infants. The remaining 4 outcomes, disability in prekindergarten at 3 and 4 years of age, exceptional student education, and retention in kindergarten, all carried a 10% to 13% increased risk among late preterm infants. The assessment "not ready to start school" was borderline significant. CONCLUSIONS: This study suggests that healthy late preterm infants compared with healthy term infants face a greater risk for developmental delay and school-related problems up through the first 5 years of life.+http://www.ncbi.nlm.nih.gov/pubmed/19336353Morse, Steven Benjamin Zheng, Hao Tang, Yiwei Roth, Jeffrey Comparative Study Research Support, U.S. Gov't, Non-P.H.S. United States Pediatrics Pediatrics. 2009 Apr;123(4):e622-9.*1098-4275 (Electronic) 0031-4005 (Linking)19336353fDepartment of Pediatrics, University of Florida, Gainesville, FL 32610-0296, USA. morsesb@peds.ufl.edu'123/4/e622 [pii] 10.1542/peds.2008-1405eng*|?#Levine, Linda Gould Waldman, Gloria1980DFeminismo ante el franquismo : entrevistas con feministas de España191 p.@Colección de estudios hispánicos = Hispanic studies collectionMiami, Fla., USAEdiciones UniversalHFeminism Spain Case studies. Women Spain Social conditions Case studies.y81159831 Linda Gould Levine y Gloria Feiman Waldman. ill. ; 21 cm. Bibliography: p. 159-160. Hispanic studies collection.0897292324 (pbk.)2322043LJefferson or Adams Building Reading Rooms - STORED OFFSITE HQ1692; .F45 19804O|?MKaganoff, Nathan M. Kaufman, Menahem Levine, Mira America-Holy Land Project.,1980"Guide to America-Holy Land studies v. <1-4 >New York Arno Press1stYAmericans Palestine History Sources Bibliography. Palestine History Sources Bibliography.79008575 edited by Nathan M. Kaganoff ; introd. by Moshe Davis. ill. ; 25 cm. Vols. <3-4 > have title: Guide to American-Holy Land studies, 1620-1948. "America-Holy Land Studies"--Vol. 2, p. opp. t.p. Vol. 4- edited by Menahem Kaufman and Mira Levine. Vols. 2-<4 > have imprint: New York : Praeger. Includes indexes. v. 1. American presence.--v. 2. Political relations and American Zionism.--v. 3. Economic relations and philanthropy.--v. 4. Resource material in British, Israeli, and Turkish repositories.0405127553 (v. 1)863758Jefferson or Adams Building Reading Rooms Z3479.A43; G84 Reference - Main Reading Room (Jefferson, LJ100) Z3479.A43; G84 Reference/Hebraic - African/Middle East RR (Jefferson LJ220) Z3479.A43; G84 Reference - Manuscript Reading Room (Madison, LM101) Z3479.A43; G84~?SCummins, Kathleen M. Levine, Barbara R. Michigan. State Appellate Defender Office.,19802Michigan criminal appeals : practice and procedurexxix, 316, 447 p.LansingState Appellate Defender Office:Appellate procedure Michigan. Criminal procedure Michigan.t81117512 Kathleen M. Cummins, project director ; Barbara R. Levine, executive editor. ill. ; 30 cm. "February 1980."46829647Law Library Reading Room (Madison, LM201) KFM4784; .M53gO|?%Greenberg, Sidney Levine, Jonathan D.1978YThe new Ma*hzor : for Rosh Hashanah and Yom Kippur = [Ma*hazor *hadash] = Ma*hzor *hadash xv, 884 p.Bridgeport, Conn.Prayer Book Press/Media JudaicaRev. and expandedPMahzorim Texts. High Holidays Liturgy Texts. Conservative Judaism Liturgy Texts.x77092171 Ma*hzor (Conservative, Greenberg). High Holidays. English & Hebrew. compiled and edited by Sidney Greenberg and Jonathan D. Levine ; consulting editors, Irwin Groner, Harold Kushner. Ma*hzor *hadash Ma*hazor *hadash 22 cm. Text includes Hebrew prayers, most with an English translation and some also in transliteration. Partially includes original prayers in English. 08767707582250370Jefferson or Adams Building Reading Rooms BM675.H5; Z64513 1978 Jefferson or Adams Building Reading Rooms - STORED OFFSITE BM675.H5; Z64513 1978~? Levine, Étan1979Torah, Neviʼim u-Khetuvim : ketav-yad *Va*ti*kan, Urbina*ti 2 = Pentateuch, Prophets, and Hagiographa : Vatican ms. Urbinati 26 YerushalayimHotsaʼat Ma*korManuscripts, Hebrew Facsimiles.81114221 Bible. O.T. Hebrew. Biblioteca apostolica vaticana. Manuscript. chiefly facsim. ; 31 cm. Introductory material in English. Vol. 2 has added half t.p.: Vatican ms. Urbinati 2. "Be-li*vyat mafte*hot u-mavo me-et Profesor Etan Le*vin"--Vol. 1, leaf following t.p. "Mahadurah bat 390 *ota*kim memusparim." Vols. 1-2 include bibliography. LC has copy no. 242. Pentateuch, Prophets, and Hagiographa. Vatican ms. Urbinati 2.2318472KAfrican & Middle Eastern Reading Room (Jefferson, LJ220) BS715.5; .U73 1979O|?&Barbach, Lonnie Garfield Levine, Linda1980.Shared intimacies : women's sexual experiences xxii, 360 p.Garden City, N.Y.Anchor Press/Doubleday1st_Women Sexual behavior United States. Women United States Interviews. Sex instruction for women.\80000917 Lonnie Barbach and Linda Levine. 22 cm. Bibliography: p. [343]-345. Includes index. 038517177327706614Jefferson or Adams Building Reading Rooms HQ29; .B32O|?Burros, Marian Fox Levine, Lois1980BThe summertime cookbook : elegant but easy dining--indoors and out224 p.New York Collier Books1st Collier BooksPicnics. Outdoor cooking.j79020799 by Marian Burros and Lois Levine ; ill. by Rosalie Petrash Schmidt. ill. ; 21 cm. Includes index. 00201119081809183:Jefferson or Adams Building Reading Rooms TX823; .B88 1980~?De Soto, Hugo Levine, Janet1980 The stone 16 leavess.l.s.n.d80119019 by Hugo de Soto, as told to Janet Levine. ill. ; 30 cm. One hundred and two copies printed.18302799Jefferson or Adams Building Reading Rooms PS3554.E843; S8|?King, David Levine, Karen1980The best way in the world for a woman to make money : the founder of Careers for Women tells how to get in and move up through executive sales x, 262 p.New York Warner BooksGWomen sales personnel Vocational guidance. Selling Vocational guidance.79021413 (David Windsor) David King and Karen Levine. 21 cm. Reprint of the ed. published by Rawson, Wade Publishers, New York. Includes index. 044697515X4172580|? Levine, Aaron1980BFree enterprise and Jewish law : aspects of Jewish business ethics xii, 224 p.*The Library of Jewish law and ethics [v 8]New York*Ktav Pub. House : Yeshiva University Press|Commercial law (Jewish law) Business ethics. Free enterprise Religious aspects Judaism. Economics Religious aspects Judaism.Q80014067 by Aaron Levine. 24 cm. Includes bibliographical references and indexes. 08706870262771356;Law Library Reading Room (Madison, LM201) KBM920; .L38 1980O|?GLevine, Arthur Carnegie Council on Policy Studies in Higher Education.,1980When dreams and heroes died : a portrait of today's college student : [prepared for the Carnegie Council on Policy Studies in Higher Education] xix, 157 p.The Carnegie Council series$San Francisco, Calif. New York, N.Y.AJossey-Bass ; Carnegie Foundation for the Advancement of Teaching1st5College students United States Attitudes. Narcissism.J80008005 Arthur Levine. 24 cm. Bibliography: p. [148]-152. Includes index. 087589481X881334|Jefferson or Adams Building Reading Rooms LA229; .L42 Jefferson or Adams Building Reading Rooms - STORED OFFSITE LA229; .L42O|?%Levine, Betty K. Jefferson, Louise E.1980 Hawk high104 p.New YorkAtheneum1st-Hawks Fiction. Fathers and daughters Fiction.}Toni's plan to climb to a hawk's nest to prove her maturity backfires when she is caught in a storm at night on the mountain.L79022668 by Betty K. Levine ; drawings by Louise E. Jefferson. ill. ; 22 cm. 0689307489392591NJefferson or Adams Building Reading Rooms - STORED OFFSITE PZ7.L5783; Haw 1980|?Levine, Daniel1980%Jane Addams and the liberal traditionxviii, 277 p., 1 leaf of platesWestport, Conn.Greenwood PressFAddams, Jane, 1860-1935. Women social workers United States Biography.80018807 Daniel Levine. ill. ; 24 cm. Reprint of the ed. published by the State Historical Society of Wisconsin, Madison. Bibliography: p. 265-272. Includes index.0313226911 (lib. bdg.)2771798|?Levine, Daniel1980Varieties of reform thought xiii, 149 p.Westport, Conn.Greenwood Press1United States Social conditions. Social problems.79028658 Daniel Levine. 23 cm. Reprint of the ed. published by the State Historical Society of Wisconsin Madison. "Began as a doctoral dissertation in the Department of History at Northwestern University." Bibliography: p. 134-143. Includes index.0313223459 (lib. bdg.)393137|?Levine, Donald Nathan1980;Simmel and Parsons : two approaches to the study of society lxxv, 239 p.Dissertations in sociologyNew York Arno PressiSociology Methodology. Simmel, Georg, 1858-1918. Parsons, Talcott, 1902-1979. Structure of social action.|79009011 Donald Nathan Levine. 24 cm. Reprint of the author's thesis, University of Chicago, 1957. Bibliography: p. 235-239. 04051297932280374~? Levine, Jack19606To an unknown German photographer in the Warsaw Ghetto,1 print : lithograph ; 58.9 x 76 cm. (sheet)Jews Punishment & torture Poland Warsaw 1940-1950. World War, 1939-1945 Jews Poland Warsaw. Soldiers German Poland Warsaw 1940-1950. Warsaw (Poland) History Warsaw Ghetto Uprising, 1943. Lithographs 1960-1980.graphic`Print shows German soldiers and Jews in the Warsaw Ghetto, possibly during the uprising in 1943.F2010643633 Title from item (inscribed on stone). Edition of 35/120. Signed in pencil "J. Levine" lower right. Publication may be restricted. For information see "Ben and Beatrice Goldstein Foundation Collection," Forms part of: Ben and Beatrice Goldstein Foundation collection. Ben and Beatrice Goldstein Foundation collection16882402fPrints and Photographs Division Prints & Photographs Reading Room (Madison, LM337) Goldstein,; no. 699-|?Levine, Jerome P.1980#Algebraic structure of knot modules xi, 104 p. Lecture notes in mathematics 772Berlin ; New YorkSpringer-Verlag*Knot theory. Modules (Algebra) Invariants.{http://www.loc.gov/catdir/enhancements/fy0907/80000246-d.html http://www.loc.gov/catdir/enhancements/fy0907/80000246-t.html80000246 Jerome P. Levine. 25 cm. Includes bibliographical references and index. Lecture notes in mathematics (Springer-Verlag) ; 772. 03870973923243327;Jefferson or Adams Building Reading Rooms QA3; .L28 no. 772ZO|? Levine, Louis1980Biology of the gene xvii, 542 p. St. LouisMosby3d Genetics.I80010730 Louis Levine. ill. ; 24 cm. Includes bibliographies and indexes. 08016298883716306Jefferson or Adams Building Reading Rooms QH430; .L48 1980 Jefferson or Adams Building Reading Rooms - STORED OFFSITE QH430; .L48 1980~?Levine, Mark Kravitz, Marjorie National Criminal Justice Reference Service (U.S.), National Institute of Justice (United States.), Aspen Systems Corporation.,1980[Standards of care in adult and juvenile correctional institutions : a selected bibliography vii, 40 p.CSelected bibliography - National Criminal Justice Reference ServiceWashington, D.C.iU.S. Dept. of Justice, National Institute of Justice : for sale by Supt. of Docs., U.S. Govt. Print. Off.Correctional institutions Standards United States Abstracts. Prisons Standards United States Abstracts. Juvenile detention homes Standards United States Abstracts.Q80602119 compiled by Mark Levine ; Marjorie Kravitz, supervising editor ; National Criminal Justice Reference Service. 29 cm. "NCJ 61443." "Prepared for the National Institute of Justice, U.S. Department of Justice, by Aspen Systems Corp. under contract number J-LEAA-023-77." Selected bibliography (National Institute of Justice (U.S.))1839951Jefferson or Adams Building Reading Rooms HV9304; .L44 Jefferson or Adams Building Reading Rooms - STORED OFFSITE HV9304; .L44 Online Electronic Resource6|?Levine, Michael1980 How to reach anyone who's anyone ca. 225 p. Los AngelesPrice/Stern/Sloan:United States Directories. Social registers United States."82104481 by Michael Levine. 26 cm.0843106573 (pbk.)2335449;Jefferson or Adams Building Reading Rooms E154.5; .L48 1980 O|?Levine, Nathan1980Typing for everyone160 p.New York, N.Y. Arco Pub.5th Typewriting.-80080741 by Nathan Levine. ill. ; 20 x 36 cm.20668049758 (easel back ed.) 0668049723 (lib. bdg.)23007738Jefferson or Adams Building Reading Rooms Z49; .L65 1980*|?#Levine, Linda Gould Waldman, Gloria1980DFeminismo ante el franquismo : entrevistas con feministas de España191 p.@Colección de estudios hispánicos = Hispanic studies collectionMiami, Fla., USAEdiciones UniversalHFeminism Spain Case studies. Women Spain Social conditions Case studies.y81159831 Linda Gould Levine y Gloria Feiman Waldman. ill. ; 21 cm. Bibliography: p. 159-160. Hispanic studies collection.0897292324 (pbk.)2322043LJefferson or Adams Building Reading Rooms - STORED OFFSITE HQ1692; .F45 19804O|?MKaganoff, Nathan M. Kaufman, Menahem Levine, Mira America-Holy Land Project.,1980"Guide to America-Holy Land studies v. <1-4 >New York Arno Press1stYAmericans Palestine History Sources Bibliography. Palestine History Sources Bibliography.79008575 edited by Nathan M. Kaganoff ; introd. by Moshe Davis. ill. ; 25 cm. Vols. <3-4 > have title: Guide to American-Holy Land studies, 1620-1948. "America-Holy Land Studies"--Vol. 2, p. opp. t.p. Vol. 4- edited by Menahem Kaufman and Mira Levine. Vols. 2-<4 > have imprint: New York : Praeger. Includes indexes. v. 1. American presence.--v. 2. Political relations and American Zionism.--v. 3. Economic relations and philanthropy.--v. 4. Resource material in British, Israeli, and Turkish repositories.0405127553 (v. 1)863758Jefferson or Adams Building Reading Rooms Z3479.A43; G84 Reference - Main Reading Room (Jefferson, LJ100) Z3479.A43; G84 Reference/Hebraic - African/Middle East RR (Jefferson LJ220) Z3479.A43; G84 Reference - Manuscript Reading Room (Madison, LM101) Z3479.A43; G84~?SCummins, Kathleen M. Levine, Barbara R. Michigan. State Appellate Defender Office.,19802Michigan criminal appeals : practice and procedurexxix, 316, 447 p.LansingState Appellate Defender Office:Appellate procedure Michigan. Criminal procedure Michigan.t81117512 Kathleen M. Cummins, project director ; Barbara R. Levine, executive editor. ill. ; 30 cm. "February 1980."46829647Law Library Reading Room (Madison, LM201) KFM4784; .M53gO|?%Greenberg, Sidney Levine, Jonathan D.1978YThe new Ma*hzor : for Rosh Hashanah and Yom Kippur = [Ma*hazor *hadash] = Ma*hzor *hadash xv, 884 p.Bridgeport, Conn.Prayer Book Press/Media JudaicaRev. and expandedPMahzorim Texts. High Holidays Liturgy Texts. Conservative Judaism Liturgy Texts.x77092171 Ma*hzor (Conservative, Greenberg). High Holidays. English & Hebrew. compiled and edited by Sidney Greenberg and Jonathan D. Levine ; consulting editors, Irwin Groner, Harold Kushner. Ma*hzor *hadash Ma*hazor *hadash 22 cm. Text includes Hebrew prayers, most with an English translation and some also in transliteration. Partially includes original prayers in English. 08767707582250370Jefferson or Adams Building Reading Rooms BM675.H5; Z64513 1978 Jefferson or Adams Building Reading Rooms - STORED OFFSITE BM675.H5; Z64513 1978~? Levine, Étan1979Torah, Neviʼim u-Khetuvim : ketav-yad *Va*ti*kan, Urbina*ti 2 = Pentateuch, Prophets, and Hagiographa : Vatican ms. Urbinati 26 YerushalayimHotsaʼat Ma*korManuscripts, Hebrew Facsimiles.81114221 Bible. O.T. Hebrew. Biblioteca apostolica vaticana. Manuscript. chiefly facsim. ; 31 cm. Introductory material in English. Vol. 2 has added half t.p.: Vatican ms. Urbinati 2. "Be-li*vyat mafte*hot u-mavo me-et Profesor Etan Le*vin"--Vol. 1, leaf following t.p. "Mahadurah bat 390 *ota*kim memusparim." Vols. 1-2 include bibliography. LC has copy no. 242. Pentateuch, Prophets, and Hagiographa. Vatican ms. Urbinati 2.2318472KAfrican & Middle Eastern Reading Room (Jefferson, LJ220) BS715.5; .U73 1979O|?&Barbach, Lonnie Garfield Levine, Linda1980.Shared intimacies : women's sexual experiences xxii, 360 p.Garden City, N.Y.Anchor Press/Doubleday1st_Women Sexual behavior United States. Women United States Interviews. Sex instruction for women.\80000917 Lonnie Barbach and Linda Levine. 22 cm. Bibliography: p. [343]-345. Includes index. 038517177327706614Jefferson or Adams Building Reading Rooms HQ29; .B32O|?Burros, Marian Fox Levine, Lois1980BThe summertime cookbook : elegant but easy dining--indoors and out224 p.New York Collier Books1st Collier BooksPicnics. Outdoor cooking.j79020799 by Marian Burros and Lois Levine ; ill. by Rosalie Petrash Schmidt. ill. ; 21 cm. Includes index. 00201119081809183:Jefferson or Adams Building Reading Rooms TX823; .B88 1980~?De Soto, Hugo Levine, Janet1980 The stone 16 leavess.l.s.n.d80119019 by Hugo de Soto, as told to Janet Levine. ill. ; 30 cm. One hundred and two copies printed.18302799Jefferson or Adams Building Reading Rooms PS3554.E843; S8Z||7IShapiro, B. K. Palmer, F. B. Antell, S. Bilker, S. Ross, A. Capute, A. J.1990:Precursors of reading delay: neurodevelopmental milestones416-20 Pediatrics853 Pt 2 1990/03/01RChild Dyslexia/*psychology Humans *Language Development *Motor Skills Risk FactorsMarThe relationship between current reading ability and the achievement of early language and motor developmental milestones was evaluated in 240 children, aged 7 1/2 years, whose language and motor achievement had been charted at each well baby visit during the first 2 years of life. Those children whose composite reading score was 6 months behind their chronologic age on the Woodcock-Johnson Psychoeducational Battery were classified as having reading delay. Relationships to reading outcome were assessed for individual infant milestones, for critical screening values, and by statistical techniques that characterized the developmental process rather than single milestones. Significant differences (P less than .05) were noted between children with and without reading delays for the following milestones: 4 to 6 words, 7 to 20 words, 50 words, 2-word sentences, and 5 and 8 body parts. The positive predictive value of slower milestone achievement ranged from 0% to 50%. Techniques that focused on the developmental process during the first 2 years (either rate of achievement of neurodevelopmental milestones or order of milestone acquisition) were better able to classify children with reading delay (sensitivity = .73, specificity = .78). Although the language milestone measures did not classify children sufficiently well to be diagnostic, the data served to determine whether a child would be at high risk based on performance rather than historical factors.*http://www.ncbi.nlm.nih.gov/pubmed/2304802Shapiro, B K Palmer, F B Antell, S Bilker, S Ross, A Capute, A J MCJ 240463/PHS HHS/United States Research Support, U.S. Gov't, P.H.S. United states Pediatrics Pediatrics. 1990 Mar;85(3 Pt 2):416-20.%0031-4005 (Print) 0031-4005 (Linking)2304802@Kennedy Institute for Handicapped Children, Baltimore, MD 21205.eng||7(Aram, D. M. Ekelman, B. L. Nation, J. E.19844Preschoolers with language disorders: 10 years later232-44J Speech Hear Res272 1984/06/01Achievement Adolescent Child Child, Preschool Follow-Up Studies Humans Intelligence Language Development Disorders/*psychology/therapy Language Disorders/*psychology Language Tests Social AdjustmentJunLanguage, intelligence, academic achievement, and behavioral adjustment were assessed in a group of 20 adolescents originally studied 10 years earlier as preschoolers with language disorders. At follow-up, 20% had WISC-R IQ scores in the mentally deficient range and were being educated in EMR classrooms. Of the remaining 16, 11 (69%) had required special tutoring, grade retention, or LD class placement. The majority of non-EMR subjects continued to evidence persistent deficits in language and academic achievement and were rated by their parents as being less socially competent and having more behavioral problems than their peers. Of the initial preschool measures available, the Leiter was found to be the best single predictor of intelligence, language, class placement, and reading achievement in adolescence, although the NSST: Expressive subtest also was a strong predictor of adolescent language.*http://www.ncbi.nlm.nih.gov/pubmed/6738035Aram, D M Ekelman, B L Nation, J E United states Journal of speech and hearing research J Speech Hear Res. 1984 Jun;27(2):232-44.%0022-4685 (Print) 0022-4685 (Linking)6738035engc||79Shapiro, B. K. Palmer, F. B. Wachtel, R. C. Capute, A. J.1984BIssues in the early identification of specific learning disability15-20J Dev Behav Pediatr51 1984/02/01Child *Child Development Child, Preschool Education, Special Humans Infant Infant, Newborn Language Development Learning Disorders/*diagnosis/prevention & control/psychology Psychological Tests UnderachievementFebCurrently the diagnosis of Specific Learning Disability (SLD) requires the demonstration of academic underachievement relative to cognitive potential. However, if the focus is shifted from academic underachievement to the detection of the deviant neurologic substrate, then the potential exists for diagnosing SLD prior to school. Circumstantial evidence from a variety of sources--studies of historical risk, the newborn examination, assessment of newborn behaviors, combination of newborn and subsequent examination, retrospective assessment of early development in SLD children, and aspects of infant development (motor or language) and SLD-suggests that the neurologic substrate for SLD can be identified in infancy. Early identification of SLD will permit early intervention when indicated, aid the assessment of therapeutic efficacy, and facilitate the evaluation of other interventions (e.g., neonatal care).*http://www.ncbi.nlm.nih.gov/pubmed/6699179Shapiro, B K Palmer, F B Wachtel, R C Capute, A J Research Support, Non-U.S. Gov't United states Journal of developmental and behavioral pediatrics : JDBP J Dev Behav Pediatr. 1984 Feb;5(1):15-20.%0196-206X (Print) 0196-206X (Linking)6699179eng ||7-Streissguth, A. P. Barr, H. M. Sampson, P. D.1990`Moderate prenatal alcohol exposure: effects on child IQ and learning problems at age 7 1/2 years662-9Alcohol Clin Exp Res145 1990/10/01GAchievement Alcohol Drinking/*adverse effects Child Child, Preschool Cohort Studies Delirium, Dementia, Amnestic, Cognitive Disorders/*diagnosis Dose-Response Relationship, Drug Female Fetal Alcohol Syndrome/*diagnosis Follow-Up Studies Humans Infant Infant, Newborn Learning Disorders/*diagnosis Male Pregnancy Wechsler ScalesOct&This longitudinal, prospective, population-based study examined the long-term effects of moderate prenatal alcohol exposure on 482 school aged children. Maternal reports of alcohol use obtained during pregnancy were significantly related to child IQ, achievement test scores, and classroom behaviors in second grade children, even after statistical adjustment for appropriate covariates. Consumption of two drinks per day or more on the average was related to a 7-point decrement in IQ in 7-year-old children even after statistically adjusting for appropriate covariates. Low paternal education and more children in the household were identified as environmental factors exacerbating the effect of prenatal alcohol exposure on child IQ. Learning problems were associated with the alcohol "BINGE" pattern of five or more drinks on at least one occasion. This study shows that alcohol use patterns within the social drinking range can have long lasting effects on IQ and learning problems in young school aged children. These patterns should not be interpreted as biologic thresholds. It should also be noted that these are group effects of prenatal alcohol exposure, not necessarily predictable in the individual child, and that for the most part these children were functioning within the normal range of intelligence.*http://www.ncbi.nlm.nih.gov/pubmed/2264594Streissguth, A P Barr, H M Sampson, P D AA01455-01-15/AA/NIAAA NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states Alcoholism, clinical and experimental research Alcohol Clin Exp Res. 1990 Oct;14(5):662-9.%0145-6008 (Print) 0145-6008 (Linking)2264594ZDepartment of Psychiatry and Behavioral Sciences, University of Washington, Seattle 98195.engO|?,Kaufman, Paul L. Alm, A. Adler, Francis Heed20034Adler's physiology of the eye : clinical application xvii, 876 p. St. LouisMosby10th"Eye Physiology. Ocular Physiology.2002071828 edited by Paul L. Kaufman, Albert Alm. Physiology of the eye ill. ; 27 cm. Includes bibliographical references and index. 0323011365127954569Jefferson or Adams Building Reading Rooms RE67; .A32 2003O|?$Adler, Francis Heed Moses, Robert A.19814Adler's Physiology of the eye : clinical application xii, 747 p. St. LouisC.V. Mosby Co.7thEye. Eye Physiology.80016862 Physiology of the eye edited by Robert A. Moses. ill. ; 26 cm. Includes bibliographies and index. Physiology of the eye. 080163541146627878Jefferson or Adams Building Reading Rooms RE67; .A3 1981}O|?$Adler, Francis Heed Moses, Robert A.19754Adler's Physiology of the eye : clinical application xiv, 702 p. Saint LouisC. V. Mosby Co.6thEye. Eye Physiology.k74028483 edited by Robert A. Moses. ill. ; 26 cm. Includes bibliographies and index. Physiology of the eye. 080163540340975128Jefferson or Adams Building Reading Rooms RE67; .A3 1975qO|?$Adler, Francis Heed Moses, Robert A.19703Adler's Physiology of the eye; clinical application xii, 713 p. Saint Louis,Mosby5thEye.y73104034 Physiology of the eye [Edited by] Robert A. Moses. illus. 21 cm. Includes bibliographies. Physiology of the eye. 080163539X12540378Jefferson or Adams Building Reading Rooms RE67; .A3 1970O|?5Adler, Francis Heed Moses, Robert A. Hart, William M.19874Adler's physiology of the eye : clinical application xiii, 709 p. St. LouisMosby8thEye. Eye physiology.86016180 Physiology of the eye edited by Robert A. Moses, William M. Hart, Jr. ill. ; 28 cm. Includes bibliographies and indexes. Physiology of the eye. 080163564038240368Jefferson or Adams Building Reading Rooms RE67; .A3 1987O|?$Adler, Francis Heed Hart, William M.19924Adler's physiology of the eye : clinical application xiv, 888 p. St. LouisMosby Year Book9thEye Physiology.92012791 Physiology of the eye edited by William M. Hart, Jr. ill. ; 28 cm. Includes bibliographical references and index. Physiology of the eye. 08016210702503605}Jefferson or Adams Building Reading Rooms RE67; .A32 1992 Reference - Science Reading Room (Adams, 5th Floor) RE67; .A32 1992|?Press, Leonard J.1997:Applied concepts in vision therapy, with accompanying disk xv, 381 p. St. LouisMosby>Visual training. Vision Disorders therapy. Orthoptics methods.96021428 edited by Leonard J. Press ; with nine contributors. ill. (some col.) ; 29 cm. + 1 computer disk (5 1/4 in.). Includes bibliographical references and index. System requirements for computer disk: IBM PC or compatible; DOS; Windows: 386 or later; Macintosh: 68020 or later. 0815167296690299See Reference Staff. By Appt in Jefferson Main RR (MRC) RE960; .A67 1997 Machine Readable Collections - STORED OFFSITE RE960; .A67 1997|?Hulme, Charles1981.Reading retardation and multi-sensory teaching200 p.#International library of psychologyLondon ; BostonRoutledge & Kegan PaulfReading disability. Perceptual-motor learning. Paired-association learning. Reading Remedial teaching.81189604 GB*** Charles Hulme. ill. ; 22 cm. Revision of thesis (doctoral)--University of Oxford. Bibliography: p. 177-193. Includes indexes. 07100076121380296=Jefferson or Adams Building Reading Rooms LB1050.5; .H84 1981m||7Blackman, S. Goldstein, K. M.1982*Cognitive styles and learning disabilities106-15J Learn Disabil152 1982/02/01Achievement Attention Attention Deficit Disorder with Hyperactivity/psychology Child *Field Dependence-Independence Functional Laterality Humans Impulsive Behavior/*psychology/therapy Learning Disorders/*psychology Motor Skills Teaching/methodsFeb*http://www.ncbi.nlm.nih.gov/pubmed/7035593xBlackman, S Goldstein, K M Review United states Journal of learning disabilities J Learn Disabil. 1982 Feb;15(2):106-15.%0022-2194 (Print) 0022-2194 (Linking)7035593eng|?)Burian, Hermann M. Von Noorden, Gunter K.1974IBinocular vision and ocular motility; theory and management of strabismus xv, 494 p. Saint Louis, C. V. Mosby@Strabismus. Binocular vision. Eye Movements. Strabismus Therapy.c74008611 [by] Hermann M. Burian [and] Gunter K. Von Noorden. illus. 27 cm. Includes bibliographies. 080160897X22048585Jefferson or Adams Building Reading Rooms RE771; .B87=O|?)Burian, Hermann M. Von Noorden, Gunter K.1980_Burian-von Noorden's Binocular vision and ocular motility : theory and management of strabismus xviii, 502 p. St. LouisMosby2d@Strabismus. Binocular vision. Eye Movements. Strabismus Therapy.79019275 Gunter K. von Noorden. ill. ; 26 cm. Rev. ed. of: Binocular vision and ocular motility / Herman M. Burian, Gunter K. von Noorden. 1974. Includes bibliographies and index. Binocular vision and ocular motility. 0801608988864739:Jefferson or Adams Building Reading Rooms RE771; .B87 1980IO|?Von Noorden, Gunter K.1996JBinocular vision and ocular motility : theory and management of strabismus xviii, 605 p. St. LouisMosby5th,Strabismus. Binocular vision. Eye Movements.\95031579 Gunter K. von Noorden. ill. ; 28 cm. Includes bibliographical references and index. 08151902632088234O|?Von Noorden, Gunter K.1990JBinocular vision and ocular motility : theory and management of strabismusxvii, 557 p., 1 leaf of plates St. LouisMosby4th@Strabismus. Binocular vision. Eye Movements. Strabismus therapy.89013929 Gunter K. von Noorden. ill. (some col.) ; 28 cm. Rev. ed. of: Burian-von Noorden's Binocular vision and ocular motility. 3rd ed. 1985. Includes bibliographical references. 08016582251980182:Jefferson or Adams Building Reading Rooms RE771; .V62 1990O|?$Von Noorden, Gunter K. Campos, E. C.2002JBinocular vision and ocular motility : theory and management of strabismus xvi, 653 p.St. Louis, Mo.Mosby6th,Strabismus. Binocular vision. Eye Movements.|2001042586 Gunter K. von Noorden, Emilio C. Campos. ill. (some col.) ; 27 cm. Includes bibliographical references and index. 032301129212433821:Jefferson or Adams Building Reading Rooms RE771; .V62 2002O|?Von Noorden, Gunter K.1985_Burian-von Noorden's Binocular vision and ocular motility : theory and management of strabismus xvii, 500 p. St. LouisMosby3rd@Strabismus. Binocular vision. Eye Movements. Strabismus therapy.z84025476 Gunter K. von Noorden. 498 ill. ; 28 cm. Includes bibliographies and index. Binocular vision and ocular motility. 08016089963315281||7-Eidukaitis, A. Varonetskas, G. Zhemaitite, D.2004k[Application of chaos theory in analyzing the cardiac rhythm in healthy subjects at different sleep stages]56-62Fiziol Cheloveka305 2004/11/06Adult Cardiovascular Physiological Phenomena Electrocardiography Female *Heart Rate Humans Male *Nonlinear Dynamics Sleep/*physiology Sleep StagesSep-Oct+http://www.ncbi.nlm.nih.gov/pubmed/15526446Eidukaitis, A Varonetskas, G Zhemaitite, D Comparative Study Russia Fiziologiia cheloveka Fiziol Cheloveka. 2004 Sep-Oct;30(5):56-62.%0131-1646 (Print) 0131-1646 (Linking)15526446ePrimenenie teorii khaosa dlia analiza serdechnogo ritma v razlichnykh stadiiakh sna u zdorovykh lits.rus||7Kakonge, J. O.2002bApplication of chaos theory to solving the problems of social and environmental decline in Lesotho63-78J Environ Manage651 2002/08/14*Agriculture Animals Animals, Domestic *Conservation of Natural Resources Environmental Pollutants/*analysis Humans Lesotho *Nonlinear Dynamics Social Conditions SoilMayThis paper examines the definition of chaos theory and its use in different circumstances. The paper explains that environmental crisis is complex, chaotic and unstable and will remain so unless actions are taken to reverse the trend. It further suggests that chaos theory could be used to interpret the crisis and help identify solutions. By recommending the application of chaos theory to the environmental problems in Lesotho, the paper explores some of the key issues that contribute to and perpetuate the environmental situation, for example, the current land tenure system and the problem of overgrazing. In addition, it identifies appropriate and realistic government policies that could be implemented to address the environmental degradation in the country. The paper concludes that the application of chaos theory may be unable to help solve the environmental crisis in Lesotho unless there is political will and commitment and collective effort from all stakeholders, coupled with an attitudinal change.+http://www.ncbi.nlm.nih.gov/pubmed/12173423cKakonge, John O England Journal of environmental management J Environ Manage. 2002 May;65(1):63-78.%0301-4797 (Print) 0301-4797 (Linking)12173423bUnited Nations Development Programme, UNDP Banjul, PO Box 553, The Gambia. john.o.kakonge@undp.orgeng7||78Priesmeyer, H. R. Sharp, L. F. Wammack, L. Mabrey, J. D.1996;Chaos theory and clinical pathways: a practical application63-72Qual Manag Health Care44 1997/02/016*Case Management Continuity of Patient Care *Critical Pathways Health Services Research/*methods Hip Prosthesis Hospital Bed Capacity, 500 and over Hospitals, Teaching/*economics/standards Humans *Knee Prosthesis Movement *Nonlinear Dynamics Outcome Assessment (Health Care) Pain, Postoperative Prognosis TexasSummerNonlinear analysis can improve the adaptive ability of clinical paths and aid in providing improved continuity of care. This article continues our exploration of the ways "chaos theory" can be applied in health care by focusing on clinical applications. It describes a specific application of nonlinear techniques to knee arthroplasty, but the generalized nature of the technique suggests it can be applied in many other settings. The approach offers an innovative means for both improved patient care and cost savings.+http://www.ncbi.nlm.nih.gov/pubmed/10159143Priesmeyer, H R Sharp, L F Wammack, L Mabrey, J D United states Quality management in health care Qual Manag Health Care. 1996 Summer;4(4):63-72.%1063-8628 (Print) 1063-8628 (Linking)10159143,St. Mary's University, San Antonio, TX, USA.eng ||7QSkinner, J. E. Wolf, S. G. Kresh, J. Y. Izrailtyan, I. Armour, J. A. Huang, M. H.1996Application of chaos theory to a model biological system: evidence of self-organization in the intrinsic cardiac nervous system122-46Integr Physiol Behav Sci312 1996/04/01Algorithms Animals Coronary Circulation/physiology Dogs Electrocardiography Heart/*innervation Heart Rate Male Microelectrodes Models, Biological Myocardial Contraction/physiology Neuronal Plasticity/physiology *Nonlinear Dynamics RabbitsApr-JunThe neutral organization that determines the specific beat-to-beat pattern of cardiac behavior is expected to be demonstrated in the independent regulation of the RR intervals (chronotropy) and the corresponding QT subintervals (inotropy), as the former defines the rate of contraction and the latter has a linear negative correlation with the peak pressure inside the contracting ventricular muscles. The neurons of the isolated cardiac nervous system, many of which are located in the fat-pads of the heart, exhibit the same types of mechanical and chemical receptors and the same types of cholinergic and noradrenergic effectors as those found in the neural superstructure. In the surgically isolated and perfused rabbit heart we studied the responses of the QT and RR intervals evoked by block of coronary blood flow. We found that if we separated each RR cycle into QT and RR-QT components, then the dynamics of variation for each subinterval series often had the same fractional number of degrees of freedom (i.e., chaotic dimensions), a finding which suggests they are both regulated by the same underlying system. The ischemia/anoxia evoked transient dimensional increases and separations between the two subinterval series that, after the temporary divergence, reconverged to having the same lower value. The dimensional fluctuations occurred repeatedly and preceded or coincided with alterations in the magnitude and sign of the slope of QT vs RR-QT. We interpret the dimensional fluctuations of the two subinterval series as correlates of adaptation-dependent self-organization and reorganization in the underlying intrinsic cardiac nervous system during accumulating ischemia/anoxia. Such attempts at functional reorganization in this simple neurocardiac system may explain the transient dimensional changes in the RR intervals that precedes by 24 hrs the occurrences of fatal ventricular fibrillation in high-risk cardiac patients.*http://www.ncbi.nlm.nih.gov/pubmed/8809596`Skinner, J E Wolf, S G Kresh, J Y Izrailtyan, I Armour, J A Huang, M H NS27745/NS/NINDS NIH HHS/United States In Vitro Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states Integrative physiological and behavioral science : the official journal of the Pavlovian Society Integr Physiol Behav Sci. 1996 Apr-Jun;31(2):122-46.%1053-881X (Print) 1053-881X (Linking)8809596*Totts Gap Institute, Bangor PA 18013, USA.engx~t7 Stomp, A. M.1994Genetic information and ecosystem health: arguments for the application of chaos theory to identify boundary conditions for ecosystem management71-4Environ Health Perspect 102 Suppl 12 1994/12/01*Ecosystem Environmental Monitoring Environmental Pollution/prevention & control *Genetics, Population Humans *Nonlinear DynamicsDecTo meet the demands for goods and services of an exponentially growing human population, global ecosystems will come under increasing human management. The hallmark of successful ecosystem management will be long-term ecosystem stability. Ecosystems and the genetic information and processes which underlie interactions of organisms with the environment in populations and communities exhibit behaviors which have nonlinear characteristics. Nonlinear mathematical formulations describing deterministic chaos have been used successfully to model such systems in physics, chemistry, economics, physiology, and epidemiology. This approach can be extended to ecotoxicology and can be used to investigate how changes in genetic information determine the behavior of populations and communities. This article seeks to provide the arguments for such an approach and to give initial direction to the search for the boundary conditions within which lies ecosystem stability. The identification of a theoretical framework for ecotoxicology and the parameters which drive the underlying model is a critical component in the formulation of a prioritized research agenda and appropriate ecosystem management policy and regulation.*http://www.ncbi.nlm.nih.gov/pubmed/7713038vStomp, A M Review United states Environmental health perspectives Environ Health Perspect. 1994 Dec;102 Suppl 12:71-4.%0091-6765 (Print) 0091-6765 (Linking)15667267713038NForestry Department, North Carolina State University, Raleigh 27695-8002, USA.eng ||7/Skinner, J. E. Molnar, M. Vybiral, T. Mitra, M.19923Application of chaos theory to biology and medicine39-53Integr Physiol Behav Sci271 1992/01/01\Animals Heart/*physiology Humans *Models, Biological *Nervous System Physiological PhenomenaJan-MarThe application of "chaos theory" to the physical and chemical sciences has resolved some long-standing problems, such as how to calculate a turbulent event in fluid dynamics or how to quantify the pathway of a molecule during Brownian motion. Biology and medicine also have unresolved problems, such as how to predict the occurrence of lethal arrhythmias or epileptic seizures. The quantification of a chaotic system, such as the nervous system, can occur by calculating the correlation dimension (D2) of a sample of the data that the system generates. For biological systems, the point correlation dimension (PD2) has an advantage in that it does not presume stationarity of the data, as the D2 algorithm must, and thus can track the transient non-stationarities that occur when the systems changes state. Such non-stationarities arise during normal functioning (e.g., during an event-related potential) or in pathology (e.g., in epilepsy or cardiac arrhythmogenesis). When stochastic analyses, such as the standard deviation or power spectrum, are performed on the same data they often have a reduced sensitivity and specificity compared to the dimensional measures. For example, a reduced standard deviation of heartbeat intervals can predict increased mortality in a group of cardiac subjects, each of which has a reduced standard deviation, but it cannot specify which individuals will or will not manifest lethal arrhythmogenesis; in contrast, the PD2 of the very same data can specify which patients will manifest sudden death. The explanation for the greater sensitivity and specificity of the dimensional measures is that they are deterministic, and thus are more accurate in quantifying the time-series. This accuracy appears to be significant in detecting pathology in biological systems, and thus the use of deterministic measures may lead to breakthroughs in the diagnosis and treatment of some medical disorders.*http://www.ncbi.nlm.nih.gov/pubmed/1576087GSkinner, J E Molnar, M Vybiral, T Mitra, M HL31164/HL/NHLBI NIH HHS/United States NS27745/NS/NINDS NIH HHS/United States Research Support, U.S. Gov't, P.H.S. Review United states Integrative physiological and behavioral science : the official journal of the Pavlovian Society Integr Physiol Behav Sci. 1992 Jan-Mar;27(1):39-53.%1053-881X (Print) 1053-881X (Linking)1576087.Baylor College of Medicine, Houston, TX 77030.eng||7EDenton, T. A. Diamond, G. A. Helfant, R. H. Khan, S. Karagueuzian, H.1990NFascinating rhythm: a primer on chaos theory and its application to cardiology1419-40 Am Heart J1206 Pt 1 1990/12/01Animals Arrhythmias, Cardiac/physiopathology Biophysical Phenomena Biophysics *Cardiology/methods Humans *Mathematics Systems TheoryDecNonlinear dynamics is an exciting new way of looking at peculiarities that in the past have been ignored or explained away. We have attempted to give a general introduction to the basics of the mathematics, applications to cardiology, and a brief review of the new tools needed to use the concepts of nonlinear mathematics. The careful mathematical approach to problems in cardiac electrical dynamics and blood flow is opening a window on behaviors and mechanisms previously inaccessible.*http://www.ncbi.nlm.nih.gov/pubmed/2248188Denton, T A Diamond, G A Helfant, R H Khan, S Karagueuzian, H 2T32HL07380/HL/NHLBI NIH HHS/United States Dictionary Research Support, U.S. Gov't, P.H.S. Review United states American heart journal Am Heart J. 1990 Dec;120(6 Pt 1):1419-40.%0002-8703 (Print) 0002-8703 (Linking)2248188KDivision of Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA 90048.eng~?Khanser, Marites A.1999ZDance of chaos : the application of chaos theory in the Philippine foreign exchange market65 p.Cagayan de Oro CityKhanser Pub. House98948052 Library of Congress -- Jakarta Field Office P350.00 Marites A. Khanser. Application of chaos theory in the Philippine foreign exchange market ill. ; 29 cm. Includes bibliographical references.11830834LJefferson or Adams Building Reading Rooms - STORED OFFSITE MLCM 98/00252 (H)y? Press, L. J.19908The application of chaos theory to behavioural optometry98-100 J Behav Optom1hO|?"Griffin, John R. Grisham, J. David20022Binocular anomalies : diagnosis and vision therapy xv, 607 p.BostonButterworth-Heinemann4thuBinocular vision disorders. Visual training. Vision Disorders diagnosis. Vision Disorders therapy. Vision, Binocular.2001052910 John R. Griffin, J. David Grisham ; with a foreword by Kenneth J. Ciuffreda. ill. ; 29 cm. + 1 computer optical laser disc (4 3/4 in.) Includes bibliographical references and index. Minimum system requirements: Windows 98 or newer. 075067369912584148>Machine Readable Collections - STORED OFFSITE RE735; .G74 2002O~?"Griffin, John R. Grisham, J. David19952Binocular anomalies : diagnosis and vision therapy xiii, 519 p.BostonButterworth-Heinemann3rddBinocular vision disorders. Vision Disorders diagnosis. Vision Disorders therapy. Vision, Binocular.95011233 John R. Griffin, J. David Grisham ; with a foreword by Kenneth J. Ciuffreda. ill. ; 29 cm. Includes bibliographical references and index.4450817P|?Griffin, John R.19763Binocular anomalies : procedures for vision therapy xiv, 384 p.ChicagoProfessional PressBinocular vision disorders.V75018293 John R. Griffin. ill. ; 27 cm. Includes bibliographical references and index. 087873020641073415Jefferson or Adams Building Reading Rooms RE735; .G74O|?LGriffin, John R. Borsting, Eric J. Optometric Extension Program Foundation.,2010/Binocular anomalies : theory, testing & therapyp. Santa Ana, CAOEP Foundation5thuBinocular vision disorders. Visual training. Vision Disorders diagnosis. Vision Disorders therapy. Vision, Binocular.`2010037068 John R. Griffin, Eric J. Borsting. cm. Includes bibliographical references and index. 978092978016016447459 |?Mosby-Year Books Inc.,Journal of AAPOSSt. Louis, MO.ussv 97027904 SERLOC variant entry: American Association for Pediatric Ophthalmology and Strabismus Quarterly Selection Decision based on v. 1, n. 2, june 1997 1091-853111121834N/AXJefferson or Adams Building Reading Rooms RE48.2.C5; W747 2003*|?Wright, Kenneth W.1995&Pediatric ophthalmology and strabismus xviii, 902 p. St. Louis, MOMosbyPediatric ophthalmology. Strabismus. Eye Diseases in infancy & childhood. Ocular Motility Disorders in infancy & childhood. Strabismus in infancy & childhood. Ophthalmology methods.94049098 editor, Kenneth W. Wright ; section editors, Edward G. Buckley ... [et al.]. ill. (some col.) ; 29 cm. Includes bibliographical references and index. 0815193599655360>Jefferson or Adams Building Reading Rooms RE48.2.C5; P434 1995|?8Crawford, John S. New Orleans Academy of Ophthalmology.,1986aPediatric ophthalmology and strabismus : transactions of the New Orleans Academy of Ophthalmology xi, 546 p.8Transactions of the New Orleans Academy of OphthalmologyNew York Raven PressPediatric ophthalmology Congresses. Vision disorders in children Congresses. Strabismus Congresses. Eye Diseases in infancy & childhood congresses. Strabismus in infancy & childhood congresses.86000553 John S. Crawford ... [et al.]. ill. ; 25 cm. Based on the 34th Annual session of the New Orleans Academy of Ophthalmology. Includes bibliographies and index. 08816716494295419T|?1Parrish, Richard K. Bascom Palmer Eye Institute.,1999JThe University of Miami Bascom Palmer Eye Institute atlas of ophthalmologyWoburn, Mass. Philadelphia, Pa.(Butterworth-Heinemann ; Current Medicine,Ophthalmology Atlases. Eye Diseases Atlases."2002564056 [electronic resource] / editor, Richard K. Parrish II. Atlas of ophthalmology 2 CD-ROMs : sd., col. ; 4 3/4 in. System requirements for Windows: IBM-compatible 386 PC or higher; 4MB of RAM; DOS 3.1 or higher, Windows 3.1 or higher; CD-ROM drive; VGA or EGA monitor. System requirements for Macintosh: 68020 or better; 6MB of RAM; System 7 or higher. Title from disc label. Diagnostic examination and technology in ophthamology -- Corneal disease and keratorefractive surgery -- Ocular surface and tear disorders -- Glaucoma -- The lens and cataract surgery -- Retinal diseases -- Intraocular inflammation -- Intraocular tumors -- Neuro-ophthalmology -- Pediatric ophthalmology and strabismus -- Oculoplastic surgery. See Reference Staff. By Appt in Jefferson Main RR (MRC) RE71; [2005 00342]0750670762 (set)12750424 |? %Del Monte, Monte A. Archer, Steven M.19937Atlas of pediatric ophthalmology and strabismus surgery viii, 232 p.New YorkChurchill LivingstonePediatric ophthalmology Atlases. Strabismus Surgery Atlases. Children Surgery Atlases. Eye surgery atlases. Eye Diseases in infancy & childhood atlases.92049969 Monte A. Del Monte, with contributions by Steven M. Archer ; illustrated by Jaye Schlesinger. ill. ; 26 cm. Includes bibliographical references (p. 223-226) and index. 04430870832034293vO|? "Friedman, Neil J. Kaiser, Peter K.2007Essentials of ophthalmology xii, 294 p. PhiladelphiaSaunders Elsevier1st!Ophthalmology. Eye Diseases. Eye.]2006052275 101293386 Neil J. Friedman, Peter K. Kaiser. ill. (some col.) ; 28 cm. Includes bibliographical references (p. 283-285) and index. Ch. 1 Ocular anatomy, physiology, and embryology -- Ch. 2 Basic optics -- Ch. 3 Ocular pharmacology -- Ch. 4 The eye exam -- Ch. 5 Neuro-ophthalmology -- Ch. 6 Pediatric ophthalmology and strabismus -- Ch. 7 Orbit -- Ch. 8 Lids and adnexa -- Ch. 9 Conjunctiva -- Ch. 10 Sclera -- Ch. 11 Cornea -- Ch. 12 Anterior chamber -- Ch. 13 Glaucoma -- Ch. 14 Iris -- Ch. 15 Lens -- Ch. 16 Vitreous -- Ch. 17 Retina -- App. Differential diagnosis of common ocular symptoms.9781416029076 141602907914636271;Jefferson or Adams Building Reading Rooms RE46; .F8435 2007|? International Strabismological Association. Meeting (7th : 1994 : Vancouver B.C.), Lennerstrand, Gunnar American Association for Pediatric Ophthalmology and Strabismus. Meeting,1995Update on strabismus and pediatric ophthalmology : proceedings of the joint congress, June 19 to 23, 1994, Vancouver, Canada : the VIIth meeting of the International Strabismological Association and the 20th Meeting of the American Association for Pediatric Ophthalmology and Strabismuslxxiii, 666 p.Boca Raton, FL CRC PressPediatric ophthalmology Congresses. Strabismus Congresses. Eye Movement disorders Congresses. Strabismus in infancy & childhood congresses. Eye Diseases in infancy & childhood congresses.=http://www.loc.gov/catdir/enhancements/fy0744/94046587-d.html94046587 edited by Gunnar Lennerstrand. ill. ; 25 cm. Includes bibliographical references and indexes. (20th : 1994 : Vancouver, B.C.)0849389615 (alk. paper)3017039=Jefferson or Adams Building Reading Rooms RE48.2.C5; I58 1994(|? Nelson, Leonard B.2012Pediatric ophthalmologyp.EColor atlas & synopsis of clinical ophthalmology--Wills Eye Institute Philadelphia3Wolters Kluwer Health/Lippincott Williams & WilkinsJPediatric ophthalmology Atlases. Eye Abnormalities Atlases. Child. Infant.2011025455 editor, Leonard B. Nelson ; section editors, Michael J. Bartiss ... [et al.]. cm. Includes bibliographical references and index. Abnormalities affecting the eye as a whole / Judith B. Lavrich -- Congenital corneal opacity / Bruce Michael Schnall and Michael J. Bartiss -- Glaucoma / Alex V. Levin and Anya A. Trumler -- Iris anomalies / Michael J. Bartiss and Bruce Michael Schnall -- Lens anomalies / Hillary Gordon and Jonathan H. Salvin -- Retinal anomalies / Barry N. Wasserman ... [et al.] -- Eyelid anomalies / Kammi B. Gunton -- Lacrimal anomalies / Leonard B. Nelson and Harold P. Koller -- Strabismus disorders / Scott E. Olitsky and Leonard B. Nelson. Color atlas and synopsis of clinical ophthalmology series.9781451110876 (alk. paper)16837886 O|? Crick, R. Pitts Khaw, P. T.2003fA textbook of clinical ophthalmology : a practical guide to disorders of the eyes and their management xvii, 649 p.River Edge, NJWorld Scientific3rdOphthalmology. Eye Diseases.2003278216 101181325 Ronald Pitts Crick, Peng Tee Khaw. Clinical ophthalmology ill. (some col.) ; 24 cm. Includes index. 1. Introduction -- 2. Practical anatomy and physiology of the eye and orbit -- 3. Formation of the eye -- 4. Optics and refraction -- 5. Simple methods of eye examination -- 6. Painless impairment of vision (in the white eye) -- 7. Painful impairment of vision (in the red eye) -- 8. Red sticky eyes (conjunctivitis) -- 9. Watering eyes -- 10. Dry eyes -- 11. Squinting eyes (strabismus) disorders of ocular motility -- 12. Examination of structure -- 13. Examination of function -- 14. Cardiovascular conditions -- 15. Blood diseases -- 16. Endocrine disorders -- 17. Infections and infestations and nutritional deficiencies -- 18. Systemic immune disorders (collagen diseases) -- 19. Neurology -- 20. Congenital abnormalities and genetic disorders -- 21. Functional disorders -- 22. Eyelids -- 23. Lacrimal apparatus -- 24. Conjunctiva -- 25. Cornea and sclera -- 26. Lens -- 27. Vitreous -- 28. Uvea -- 29. Retina -- 30. Orbit -- 31. Disorders associated with the level of intraocular pressure -- 32. Therapeutics pt. 1 -- 33. Therapeutics pt. 2 -- 34. Iatrogenic disorders.9812381503 (pbk.) 9812381287133577569Jefferson or Adams Building Reading Rooms RE46; .C77 2003|?Alexander, Randell Case, Mary2011kChild fatality review quick reference : for health care, social services, and law enforcement professionalsp. St. Louis STM LearningChildren Mortality Handbooks, manuals, etc. Death Causes Handbooks, manuals, etc. Child abuse Investigation Handbooks, manuals, etc. Forensic Medicine methods Handbooks. Cause of Death Handbooks. Child Abuse Handbooks. Child Welfare Handbooks. Child. Wounds and Injuries Handbooks."Child Fatality Review Quick Reference condenses into accessible bulleted points the most important information on establishing, maintaining, and improving Child Fatality Review teams"--Provided by publisher.2010008573 [edited by] Randell Alexander, Mary E. Case. cm. Includes bibliographical references and index. Fatality review teams -- Fatality review procedures -- Forensics -- Law enforcement, prosecutors, CPS, and mental health professionals -- Social and environmental issues -- Homicide -- Perinatal deaths -- Sudden infant death syndrome -- Physical abuse -- Neglect and safety issues -- Nonabusive injuries -- Suicide -- Burns -- Drownings -- Medical conditions -- Pediatric ophthalmology. 978187806059416115729p|?%Feman, Stephen S. Reinecke, Robert D.1978#Handbook of pediatric ophthalmology x, 196 p.New YorkGrune & StrattonPediatric ophthalmology.t78071861 editors, Stephen S. Feman, Robert D. Reinecke. ill. ; 24 cm. Includes bibliographical references and index. 080891115522664878Jefferson or Adams Building Reading Rooms RE48.2.C5; H36 |?Mosby-Year Books Inc.,Journal of AAPOSSt. Louis, MO.ussv 97027904 SERLOC variant entry: American Association for Pediatric Ophthalmology and Strabismus Quarterly Selection Decision based on v. 1, n. 2, june 1997 1091-853111121834N/AXJefferson or Adams Building Reading Rooms RE48.2.C5; W747 2003*|?Wright, Kenneth W.1995&Pediatric ophthalmology and strabismus xviii, 902 p. St. Louis, MOMosbyPediatric ophthalmology. Strabismus. Eye Diseases in infancy & childhood. Ocular Motility Disorders in infancy & childhood. Strabismus in infancy & childhood. Ophthalmology methods.94049098 editor, Kenneth W. Wright ; section editors, Edward G. Buckley ... [et al.]. ill. (some col.) ; 29 cm. Includes bibliographical references and index. 0815193599655360>Jefferson or Adams Building Reading Rooms RE48.2.C5; P434 1995|?8Crawford, John S. New Orleans Academy of Ophthalmology.,1986aPediatric ophthalmology and strabismus : transactions of the New Orleans Academy of Ophthalmology xi, 546 p.8Transactions of the New Orleans Academy of OphthalmologyNew York Raven PressPediatric ophthalmology Congresses. Vision disorders in children Congresses. Strabismus Congresses. Eye Diseases in infancy & childhood congresses. Strabismus in infancy & childhood congresses.86000553 John S. Crawford ... [et al.]. ill. ; 25 cm. Based on the 34th Annual session of the New Orleans Academy of Ophthalmology. Includes bibliographies and index. 08816716494295419Z|?#Wybar, Kenneth Cullen Taylor, David1983)Pediatric ophthalmology : current aspects xv, 484 p.New York, N.Y. M. Dekker?Pediatric ophthalmology. Eye diseases In infancy and childhood.n82023513 edited by Kenneth Wybar, David Taylor. ill. ; 26 cm. Includes bibliographical references and indexes. 08247184104224813|?#Metz, Henry S. Rosenbaum, Arthur L.1982Pediatric ophthalmology vii, 549 p.Medical outline seriesGarden City, N.Y.Medical Examination Pub. Co.?Pediatric ophthalmology. Eye diseases In infancy and childhood.g81011067 edited by Henry S. Metz, Arthur L. Rosenbaum. ill. ; 21 cm. Includes bibliographies and index. 087488586827878138Jefferson or Adams Building Reading Rooms RE48.2.C5; P43DK|? Harley, Robison D.1983Pediatric ophthalmology2 PhiladelphiaSaunders2d?Pediatric ophthalmology. Eye diseases In infancy and childhood.X80050561 [edited by] Robison D. Harley. ill. ; 27 cm. Includes bibliographies and index.40721645267 (set) 0721645143 (v. 1) 0721645151 (v. 2)2300105[|?!Harley, Robison D.1975Pediatric ophthalmologyxxxiv, 1112 p. PhiladelphiaSaundersPediatric ophthalmology.}73176207 edited by Robison D. Harley ; with contributions by 46 authorities. ill. ; 27 cm. Includes bibliographies and index. 072164525926740668Jefferson or Adams Building Reading Rooms RE48.2.C5; P42(|?"Nelson, Leonard B.2012Pediatric ophthalmologyp.EColor atlas & synopsis of clinical ophthalmology--Wills Eye Institute Philadelphia3Wolters Kluwer Health/Lippincott Williams & WilkinsJPediatric ophthalmology Atlases. Eye Abnormalities Atlases. Child. Infant.2011025455 editor, Leonard B. Nelson ; section editors, Michael J. Bartiss ... [et al.]. cm. Includes bibliographical references and index. Abnormalities affecting the eye as a whole / Judith B. Lavrich -- Congenital corneal opacity / Bruce Michael Schnall and Michael J. Bartiss -- Glaucoma / Alex V. Levin and Anya A. Trumler -- Iris anomalies / Michael J. Bartiss and Bruce Michael Schnall -- Lens anomalies / Hillary Gordon and Jonathan H. Salvin -- Retinal anomalies / Barry N. Wasserman ... [et al.] -- Eyelid anomalies / Kammi B. Gunton -- Lacrimal anomalies / Leonard B. Nelson and Harold P. Koller -- Strabismus disorders / Scott E. Olitsky and Leonard B. Nelson. Color atlas and synopsis of clinical ophthalmology series.9781451110876 (alk. paper)16837886|?#$Lorenz, B. Borruat, François-Xavier20086Pediatric ophthalmology, neuro-ophthalmology, genetics xix, 333 p.Essentials in ophthalmologyBerlin ; New YorkSpringerNeuroophthalmology. Pediatric ophthalmology. Eye Diseases Genetic aspects. Eye Diseases. Child. Eye Diseases genetics. Infant. Optic Nerve. Visual Pathways.http://www.loc.gov/catdir/enhancements/fy0824/2007936032-d.html http://www.loc.gov/catdir/enhancements/fy0824/2007936032-t.html2007936032 GBA731323 101322513 013731291 editors, Birgit Lorenz, François-Xavier Borruat. ill. ; 25 cm. Includes bibliographical references and index.29783540336785 (alk. paper) 3540336788 (alk. paper)14979046:Jefferson or Adams Building Reading Rooms RE725; .P43 20083|?$Lorenz, B. Brodsky, Michael C.2010Pediatric ophthalmology, neuro-ophthalmology, genetics : strabisdmus : new concepts in pathophysiology, diagnosis, and treatment xvi, 231 p.Essentials in ophthalmologyBerlinSpringerNeuroophthalmology. Pediatric ophthalmology. Eye Diseases Genetic aspects. Strabismus diagnosis. Child. Infant. Strabismus genetics. Strabismus therapy. Medicine.<http://public.eblib.com/EBLPublic/PublicView.do?ptiID=5711132009938957 GBA972576 101523636 015332752 Birgit Lorenz, Michael Brodsky, editors. ill. ; 27 cm. Includes bibliographical references and index. Essentials in ophthalmology.]9783540858508 (alk. paper) 3540858504 (alk. paper) 9783540858515 (e-ISBN) 3540858512 (e-ISBN)15938306;Jefferson or Adams Building Reading Rooms RE725; .P435 2010T|?%1Parrish, Richard K. Bascom Palmer Eye Institute.,1999JThe University of Miami Bascom Palmer Eye Institute atlas of ophthalmologyWoburn, Mass. Philadelphia, Pa.(Butterworth-Heinemann ; Current Medicine,Ophthalmology Atlases. Eye Diseases Atlases."2002564056 [electronic resource] / editor, Richard K. Parrish II. Atlas of ophthalmology 2 CD-ROMs : sd., col. ; 4 3/4 in. System requirements for Windows: IBM-compatible 386 PC or higher; 4MB of RAM; DOS 3.1 or higher, Windows 3.1 or higher; CD-ROM drive; VGA or EGA monitor. System requirements for Macintosh: 68020 or better; 6MB of RAM; System 7 or higher. Title from disc label. Diagnostic examination and technology in ophthamology -- Corneal disease and keratorefractive surgery -- Ocular surface and tear disorders -- Glaucoma -- The lens and cataract surgery -- Retinal diseases -- Intraocular inflammation -- Intraocular tumors -- Neuro-ophthalmology -- Pediatric ophthalmology and strabismus -- Oculoplastic surgery. See Reference Staff. By Appt in Jefferson Main RR (MRC) RE71; [2005 00342]0750670762 (set)12750424]~?& Apt, Leonard19630Diagnostic procedures in pediatric ophthalmology+xii, 697-1051 p., illus. (part col.) 24 cm.Boston, Little, Brown)Eye Examination. Pediatric ophthalmology.L63021084 International opthalmology clinics, v. 3, no. 4. [from old catalog]70412787Jefferson or Adams Building Reading Rooms RE48.2.C5; A6 |?'%Del Monte, Monte A. Archer, Steven M.19937Atlas of pediatric ophthalmology and strabismus surgery viii, 232 p.New YorkChurchill LivingstonePediatric ophthalmology Atlases. Strabismus Surgery Atlases. Children Surgery Atlases. Eye surgery atlases. Eye Diseases in infancy & childhood atlases.92049969 Monte A. Del Monte, with contributions by Steven M. Archer ; illustrated by Jaye Schlesinger. ill. ; 26 cm. Includes bibliographical references (p. 223-226) and index. 04430870832034293vO|?("Friedman, Neil J. Kaiser, Peter K.2007Essentials of ophthalmology xii, 294 p. PhiladelphiaSaunders Elsevier1st!Ophthalmology. Eye Diseases. Eye.]2006052275 101293386 Neil J. Friedman, Peter K. Kaiser. ill. (some col.) ; 28 cm. Includes bibliographical references (p. 283-285) and index. Ch. 1 Ocular anatomy, physiology, and embryology -- Ch. 2 Basic optics -- Ch. 3 Ocular pharmacology -- Ch. 4 The eye exam -- Ch. 5 Neuro-ophthalmology -- Ch. 6 Pediatric ophthalmology and strabismus -- Ch. 7 Orbit -- Ch. 8 Lids and adnexa -- Ch. 9 Conjunctiva -- Ch. 10 Sclera -- Ch. 11 Cornea -- Ch. 12 Anterior chamber -- Ch. 13 Glaucoma -- Ch. 14 Iris -- Ch. 15 Lens -- Ch. 16 Vitreous -- Ch. 17 Retina -- App. Differential diagnosis of common ocular symptoms.9781416029076 141602907914636271;Jefferson or Adams Building Reading Rooms RE46; .F8435 2007KO|?)&Helveston, Eugene M. Ellis, Forrest D.1984 Pediatric ophthalmology practice xiii, 361 p. St. LouisMosby2nd?Pediatric ophthalmology. Eye diseases In infancy and childhood.g83008255 Eugene M. Helveston, Forrest D. Ellis. ill. ; 29 cm. Bibliography: p. 339-341. Includes index. 0801621437933255|?*&Helveston, Eugene M. Ellis, Forrest D.1980 Pediatric ophthalmology practice xiii, 303 p. St. LouisMosby?Pediatric ophthalmology. Eye diseases In infancy and childhood.g79018469 Eugene M. Helveston, Forrest D. Ellis. ill. ; 29 cm. Bibliography: p. 289-291. Includes index. 080162129118089638Jefferson or Adams Building Reading Rooms RE48.2.C5; H45~?+Holt, Lawrence Byerly1964Pediatric ophthalmology403 p. Philadelphia, Lea & FebigerPediatric ophthalmology.64014491 illus. 25 cm.79849397Jefferson or Adams Building Reading Rooms RE48.2.C5; H6|?,International Strabismological Association. Meeting (7th : 1994 : Vancouver B.C.), Lennerstrand, Gunnar American Association for Pediatric Ophthalmology and Strabismus. Meeting,1995Update on strabismus and pediatric ophthalmology : proceedings of the joint congress, June 19 to 23, 1994, Vancouver, Canada : the VIIth meeting of the International Strabismological Association and the 20th Meeting of the American Association for Pediatric Ophthalmology and Strabismuslxxiii, 666 p.Boca Raton, FL CRC PressPediatric ophthalmology Congresses. Strabismus Congresses. Eye Movement disorders Congresses. Strabismus in infancy & childhood congresses. Eye Diseases in infancy & childhood congresses.=http://www.loc.gov/catdir/enhancements/fy0744/94046587-d.html94046587 edited by Gunnar Lennerstrand. ill. ; 25 cm. Includes bibliographical references and indexes. (20th : 1994 : Vancouver, B.C.)0849389615 (alk. paper)3017039=Jefferson or Adams Building Reading Rooms RE48.2.C5; I58 1994K|?-Nelson, Leonard B.1984Pediatric ophthalmology xiv, 268 p.%Major problems in clinical pediatrics25 PhiladelphiaSaunders?Pediatric ophthalmology. Eye diseases In infancy and childhood.X83020055 Leonard B. Nelson. ill. ; 27 cm. Includes bibliographical references and index. 0721611915934377>O|?.Wilson, M. Edward20089Pediatric ophthalmology : current thought and a practicalNew YorkSpringer1st2008940289 Wilson, M. Edward, Saunders, Richard, Trivedi, Rupal H. ; [edited by] Wilson, M. Edward, Saunders, Richard, Trivedi, Rupal H.%9783540686323 (hard cover alk. paper)15497159O|?/Wright, Kenneth W.1999)Pediatric ophthalmology for pediatricians xvi, 385 p. BaltimoreWilliams & Wilkins1stPediatric ophthalmology. Vision disorders in children Diagnosis. Eye Diseases in infancy & childhood. Eye Diseases diagnosis. Vision Tests in infancy & childhood.v98021740 (Kenneth Weston), Kenneth W. Wright. ill. (some col.) ; 22 cm. Includes bibliographical references and index. 06833048524033543 ||70Zou, Y. C. Liu, L.20114The management of childhood esotropia with hyperopia731-5Curr Med Res Opin274 2011/01/27@Accommodation, Ocular/physiology Age of Onset Child Child, Preschool Esotropia/*complications/epidemiology/*therapy Eyeglasses Female Follow-Up Studies Humans Hyperopia/*complications/epidemiology/*therapy Male Ophthalmologic Surgical Procedures/statistics & numerical data Retrospective Studies Visual Acuity/physiologyAprOPURPOSE: Esotropia, especially accommodative estropia (AE), is often seen in patients with hyperopia. In this paper, the authors aim to report the management methods of different types of esotropia in children with hypermetropia and to show the feasibility and efficacy of prismatic correction in the management of small angle of residual esotropia in accommodative estropia. METHODS: A total of 82 esotropes with hyperopia treated during a 2-year period from 2007 to 2009 were reviewed retrospectively. Data were collected from the medical records. RESULTS: A total of 25 patients showed pure accommodative esotropes, whereas 45 had partial AE and 12 non-AE. All 25 pure AE patients were corrected fully using glasses alone, and all 12 non-AE patients received surgery. Among the 45 partial AE cases, 35 patients with residual esodeviation of 30 PD received surgery. The most recent follow-up examination indicated that all the non-surgical children were orthotropia or esophoria or had residual esotropia or = 0.05), but they did differ significantly from U.S. ophthalmologists (p < 0.001). Prescribing fractional amounts of hyperopia or astigmatism was not a popular rule of thumb among the German ophthalmologists, and there was no statistical difference between the German and U.S. practitioners. German ophthalmologists would prescribe for anisometropia for all patient age groups in the same way as both U.S. optometrists and U.S. ophthalmologists. CONCLUSION: The prescribing philosophies of German ophthalmologists for pediatric patients did not differ from those of U.S. ophthalmologists and U.S. optometrists when prescribing for anisometropia; they did differ from those of U.S. ophthalmologists but not of those of the U.S. optometrists when prescribing for asymptomatic bilateral hyperopia.+http://www.ncbi.nlm.nih.gov/pubmed/17299343Reiter, Constantin Leising, Daniel Madsen, Ellis M Multicenter Study United States Optometry and vision science : official publication of the American Academy of Optometry Optom Vis Sci. 2007 Feb;84(2):131-6.%1040-5488 (Print) 1040-5488 (Linking)17299343MMedicalisches Kollegium, Julius-Maximilians Universitaet, Wuerzburg, Germany.;10.1097/OPX.0b013e318031b065 00006324-200702000-00012 [pii]eng L||76Lyons, S. A. Jones, L. A. Walline, J. J. Bartolone, A. G. Carlson, N. B. Kattouf, V. Harris, M. Moore, B. Mutti, D. O. Twelker, J. D.2004;A survey of clinical prescribing philosophies for hyperopia233-7 Optom Vis Sci814 2004/04/21Data Collection *Eyeglasses Humans Hyperopia/*therapy Ophthalmology/*methods Optometry/*methods *Prescriptions *Professional PracticeAprFBACKGROUND: Prescribing philosophies for hyperopic refractive error in symptom-free children vary widely because relatively little information is available regarding the natural history of hyperopic refractive error in children and because accommodation and binocular function closely related to hyperopic refractive error vary widely among children. We surveyed pediatric optometrists and ophthalmologists to evaluate typical prescribing philosophies for hyperopia. METHODS: Practitioners were selected from the American Academy of Optometry Binocular Vision, Perception, and Pediatric Optometry Section; the College of Vision Development; the pediatric and binocular vision faculty members of the colleges of optometry; and the American Association for Pediatric Ophthalmology and Strabismus. Surveys were mailed to 314 participants: 212 optometrists and 102 ophthalmologists. RESULTS: A total of 161 (75%) of the optometrists and 59 (57%) of the ophthalmologists responded. About one-third of optometrists surveyed prescribe optical correction for symptom-free 6-month-old infants with +3.00 D to +4.00 D hyperopia, but fewer than 5% of ophthalmologists prescribe at this level. Most eye care practitioners prescribe optical correction for symptom-free 2-year-old children with +5.00 D of hyperopia, and this criterion for hyperopia decreases with age. Most ophthalmologists (71.4%) prescribe the full amount of astigmatism and less than the full amount of cycloplegic spherical component, and most optometrists (71.6%) prescribe less than the full amount of both components. When prescribing less than the full amount of astigmatism, eye care practitioners do not tend to prescribe a specific proportion of the cycloplegic refractive error. CONCLUSION: Pediatric eye care providers show a lack of consensus on prescribing philosophies for hyperopic children.+http://www.ncbi.nlm.nih.gov/pubmed/15097764Lyons, Stacy Ayn Jones, Lisa A Walline, Jeffrey J Bartolone, Amelia G Carlson, Nancy B Kattouf, Valerie Harris, Monica Moore, Bruce Mutti, Donald O Twelker, J Daniel R21-EY12273/EY/NEI NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States Optometry and vision science : official publication of the American Academy of Optometry Optom Vis Sci. 2004 Apr;81(4):233-7.%1040-5488 (Print) 1040-5488 (Linking)15097764AThe New England College of Optometry, Boston, Massachusetts, USA.00006324-200404000-00008 [pii]eng||77kGrasela, T. H., Jr. Welage, L. S. Walawander, C. A. Timm, E. G. Pelter, M. A. Poirier, T. I. Walters, J. K.1990qA nationwide survey of antibiotic prescribing patterns and clinical outcomes in patients with bacterial pneumonia1220-5DICP2412 1990/12/01{Aminoglycosides Anti-Bacterial Agents/*therapeutic use Bacterial Infections/complications/*drug therapy Canada Drug Therapy, Combination/therapeutic use Drug Utilization/*statistics & numerical data Hospitalization Humans Lactams Physician's Practice Patterns/*statistics & numerical data Pneumonia/*drug therapy/microbiology Prospective Studies Sputum/microbiology United StatesDecAntibiotic prescribing information was prospectively collected on 1822 hospitalized patients treated for suspected or documented bacterial pneumonia. Antibacterial therapy with a single antibiotic was employed in more than 50 percent of the patients, with cefazolin, cefuroxime, ampicillin, and ceftriaxone sodium representing the most commonly employed agents. Combination therapy using two antibiotics was employed in approximately 30 percent of patients with the aminoglycosides, particularly gentamicin, used extensively. A satisfactory outcome was achieved in approximately 80 percent of patients with a community- or institutional-acquired pneumonia; only 66 percent of nosocomial pneumonias had a satisfactory outcome. An important observation was the apparently common practice of switching patients to an oral antibiotic regimen after an average of seven days of antibiotics and subsequently discharging the patient. No difference was observed in the patterns of clinical response or duration of therapy for culture-positive versus culture-negative patients. The results of this surveillance program can serve as a basis for comparison of institution-specific drug utilization evaluation programs.*http://www.ncbi.nlm.nih.gov/pubmed/2089835Grasela, T H Jr Welage, L S Walawander, C A Timm, E G Pelter, M A Poirier, T I Walters, J K Research Support, Non-U.S. Gov't United states DICP : the annals of pharmacotherapy DICP. 1990 Dec;24(12):1220-5.%1042-9611 (Print) 1042-9611 (Linking)2089835@School of Pharmacy, State University of New York, Buffalo 14260.eng ||78{Olsen, R. B. Gydesen, S. U. Kristensen, M. Eschen, F. T. Sorensen, C. Hasle, H. Lund, S. Baastrup, P. C. Gylding-Sabroe, J.1990TPsychotropic medication in the elderly. A survey of prescribing and clinical outcome455-9 Dan Med Bull375 1990/10/01Adjustment Disorders/drug therapy Aged Aged, 80 and over Antidepressive Agents/therapeutic use Antipsychotic Agents/therapeutic use Bipolar Disorder/drug therapy Dementia/drug therapy Female Humans Hypnotics and Sedatives/therapeutic use Male Mental Disorders/*drug therapy Neurotic Disorders/drug therapy Paranoid Disorders/drug therapy Prospective Studies Psychotropic Drugs/adverse effects/*therapeutic useOctDue to the increasing elderly population, an increased number of elderly patients requires treatment for mental and behavioural disorders. There are relatively few clinical studies of the prescribing of psychotropic drugs in patients over 65 years of age. A prospective study was undertaken at three centres caring for the elderly, encompassing patients from general nursing homes and a psychiatric department. Entry of patients into the survey was determined by the clinical decision to prescribe psychotropic medication and an age of 65 years or older. Included in the study were 160 patients. The main reasons for initiating psychotropic medication were indicated, and anamnestic data were collected. Initial and continuing dosages of psychotropic medication were recorded. The clinical condition was assessed at the start of treatment and after four and eight weeks, utilising the Clinical Global Impressions (CGI) scale. The patient's daily activity using an abbreviated Stockton Geriatric Rating Scale (SGRS) was assessed. Side effects were recorded using the UKU Scale. Clinical improvement was seen in about half of the patients with the best effect in patients with mainly psychotic symptoms. Patients with chronic dementia-related problems responded less well. Side effects were few and generally mild. This situation may relate to cautious introduction of the medication and adoption of low-dose regimens. All centres avoided, if possible, psychotropic polypharmacy.*http://www.ncbi.nlm.nih.gov/pubmed/1980241Olsen, R B Gydesen, S U Kristensen, M Eschen, F T Sorensen, C Hasle, H Lund, S Baastrup, P C Gylding-Sabroe, J Clinical Trial Multicenter Study Denmark Danish medical bulletin Dan Med Bull. 1990 Oct;37(5):455-9.%0907-8916 (Print) 0907-8916 (Linking)1980241JGeropsychiatric Department, Copenhagen County Hospital Nordvang, Glostrup.engI|t79Tommila, V. Tarkkanen, A.1981;Incidence of loss of vision in the healthy eye in amblyopia575-7Br J Ophthalmol658 1981/08/01Adolescent Adult Aged Amblyopia/*complications/epidemiology Blindness/complications Child Eye Diseases/complications Eye Injuries/complications Female Finland Humans Male Middle Aged Risk Vision Disorders/complications/*epidemiologyAugIn Finland during the 20-year period 1958-78 35 patients with amblyopia lost the vision of the healthy eye. In more than 50% the cause was traumatic. The incidence of the loss of the healthy eye was 1.75 +/- 0.30 per thousand. During the same period in Finland the overall blindness rate of children was 0.11 per thousand and of adults aged 15-64 years 0.66 per thousand. For the amblyopic patient the risk of becoming blind is markedly higher than for the general population.*http://www.ncbi.nlm.nih.gov/pubmed/7295619kTommila, V Tarkkanen, A England The British journal of ophthalmology Br J Ophthalmol. 1981 Aug;65(8):575-7.%0007-1161 (Print) 0007-1161 (Linking)10395847295619eng ||7:/Webber, A. L. Wood, J. M. Gole, G. A. Brown, B.20088The effect of amblyopia on fine motor skills in children594-603Invest Ophthalmol Vis Sci492 2008/02/01Amblyopia/*physiopathology Anisometropia/physiopathology Child Esotropia/physiopathology Female Humans Male Motor Skills/*physiology Motor Skills Disorders/*physiopathology Strabismus/physiopathologyFeb?PURPOSE: In an investigation of the functional impact of amblyopia in children, the fine motor skills of amblyopes and age-matched control subjects were compared. The influence of visual factors that might predict any decrement in fine motor skills was also explored. METHODS: Vision and fine motor skills were tested in a group of children (n = 82; mean age, 8.2 +/- 1.7 [SD] years) with amblyopia of different causes (infantile esotropia, n = 17; acquired strabismus, n = 28; anisometropia, n = 15; mixed, n = 13; and deprivation n = 9), and age-matched control children (n = 37; age 8.3 +/- 1.3 years). Visual motor control (VMC) and upper limb speed and dexterity (ULSD) items of the Bruininks-Oseretsky Test of Motor Proficiency were assessed, and logMAR visual acuity (VA) and Randot stereopsis were measured. Multiple regression models were used to identify the visual determinants of fine motor skills performance. RESULTS: Amblyopes performed significantly poorer than control subjects on 9 of 16 fine motor skills subitems and for the overall age-standardized scores for both VMC and ULSD items (P < 0.05). The effects were most evident on timed tasks. The etiology of amblyopia and level of binocular function significantly affected fine motor skill performance on both items; however, when examined in a multiple regression model that took into account the intercorrelation between visual characteristics, poorer fine motor skills performance was associated with strabismus (F(1,75) = 5.428; P = 0.022), but not with the level of binocular function, refractive error, or visual acuity in either eye. CONCLUSIONS: Fine motor skills were reduced in children with amblyopia, particularly those with strabismus, compared with control subjects. The deficits in motor performance were greatest on manual dexterity tasks requiring speed and accuracy.+http://www.ncbi.nlm.nih.gov/pubmed/18235004Webber, Ann L Wood, Joanne M Gole, Glen A Brown, Brian Research Support, Non-U.S. Gov't United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2008 Feb;49(2):594-603.%0146-0404 (Print) 0146-0404 (Linking)18235004School of Optometry and Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia. al.webber@qut.edu.au#49/2/594 [pii] 10.1167/iovs.07-0869eng|?;9Caloroso, Elizabeth E. Rouse, Michael W. Cotter, Susan A.1993!Clinical management of strabismus xv, 367 p.BostonButterworth-Heinemann=Strabismus. Amblyopia. Amblyopia therapy. Strabismus therapy.92049704 Elizabeth E. Caloroso, Michael W. Rouse ; with a contribution by Susan A. Cotter. ill. ; 29 cm. Includes bibliographical references and index.075069047X (case alk. paper)1562460:Jefferson or Adams Building Reading Rooms RE771; .C16 1993||7<+Donchin, M. Woolf, O. Kaplan, L. Floman, Y.19907Secondary prevention of low-back pain. A clinical trial1317-20Spine (Phila Pa 1976)1512 1990/12/01Back Pain/*prevention & control *Exercise Therapy Female *Gymnastics Humans Incidence Male Middle Aged Occupational Diseases/*prevention & control Patient Education as Topic *Personnel, Hospital Regression AnalysisDecA clinical trial, aimed at secondary prevention of low-back pain, was performed in 142 hospital employees reporting at least three annual episodes of this condition. Participants were randomly assigned to one of three groups: a calisthenics program (CAL) for 3 months with biweekly sessions of flexion exercises, a back school program (5 sessions), and a control group. The effectiveness of the two intervention programs was evaluated over a 1-year period. Baseline preintervention data and evaluation at the end of 3 months of intervention and after an additional 6 months were collected. A monthly surveillance for the whole year showed a mean of 4.5 "painful months" in the CAL group versus 7.3 and 7.4 months in the back school and control groups, respectively (P less than 0.0001). The superiority of the CAL group was achieved partly because of the significant increase in trunk forward flexion and to initial increment in abdominal muscle strength. The increased trunk flexion was associated with the rate of participation in the CAL sessions. Further research is needed to answer the question of "intensity versus type of exercise" by comparing different intervention programs, with similar intensity.*http://www.ncbi.nlm.nih.gov/pubmed/2149210Donchin, M Woolf, O Kaplan, L Floman, Y Clinical Trial Comparative Study Randomized Controlled Trial Research Support, Non-U.S. Gov't United states Spine Spine (Phila Pa 1976). 1990 Dec;15(12):1317-20.%0362-2436 (Print) 0362-2436 (Linking)2149210|Department of Social Medicine, Hebrew University Hadassah School of Public Health and Community Medicine, Jerusalem, Israel.eng ||7=USmall, T. N. Keever, C. A. Weiner-Fedus, S. Heller, G. O'Reilly, R. J. Flomenberg, N.1990B-cell differentiation following autologous, conventional, or T-cell depleted bone marrow transplantation: a recapitulation of normal B-cell ontogeny1647-56Blood768 1990/10/15Adult Aging Antigens, CD/analysis Antigens, CD20 Antigens, Differentiation, B-Lymphocyte/analysis B-Lymphocytes/*cytology/immunology *Bone Marrow Transplantation Cell Differentiation Child Child, Preschool Graft vs Host Disease/blood HLA-DR Antigens/analysis Humans Immunoglobulin G/biosynthesis Immunoglobulin M/biosynthesis Immunophenotyping Infant, Newborn Leukocyte Count Lymphocyte Activation Staphylococcus aureus/immunology T-Lymphocytes/*physiologyOct 15aThe circulating lymphocytes of 88 consecutive patients following autologous, conventional, or T-cell depleted bone marrow transplantation were serially analyzed for B-cell surface antigen expression and function. In the majority of patients, except for those who developed chronic graft-versus-host disease, the number of circulating CD20+ B cell normalized by the fourth posttransplant month. The earliest detectable B cells normally expressed HLA-DR, CD19, surface immunoglobulin (slg), CD21, Leu-8, and lacked expression of CD10 (CALLA). In addition, the circulating B cells expressed CD1c, CD38, CD5, and CD23 for the first year following transplant, antigens that are normally expressed on a small percentage of circulating B cells in normal adults, but highly expressed on cord blood B cells. Similar to cord blood B cells, patient B cells isolated during the first year following transplant, proliferated normally to Staphylococcus aureus Cowan strain I (SAC), and produced IgM, but minimal or no IgG when stimulated with pokeweed mitogen and SAC, unlike normal adult B cells that produce both. The similar phenotype and function of posttransplant and cord blood B cells, and their similar rate of decline in patients and normal children adds further evidence to support the hypothesis that B-cell differentiation posttransplant is recapitulating normal B-cell ontogeny.*http://www.ncbi.nlm.nih.gov/pubmed/1698484TSmall, T N Keever, C A Weiner-Fedus, S Heller, G O'Reilly, R J Flomenberg, N CA-23766/CA/NCI NIH HHS/United States CA-33050/CA/NCI NIH HHS/United States CT5T32CA09512-02/CT/CIT NIH HHS/United States Comparative Study Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states Blood Blood. 1990 Oct 15;76(8):1647-56.%0006-4971 (Print) 0006-4971 (Linking)1698484`Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY 10021.eng J||7>mKeever, C. A. Flomenberg, N. Gazzola, M. V. Pekle, K. Yang, S. Y. Small, T. N. Collins, N. H. O'Reilly, R. J.1990Cytotoxic and proliferative T-cell clones with antidonor reactivity from a patient transplanted for severe combined immunodeficiency disease42-55 Hum Immunol291 1990/09/01oAdult Antibodies, Monoclonal/diagnostic use Bone Marrow Transplantation/*immunology Clone Cells Cytotoxicity, Immunologic/immunology Female HLA-D Antigens/immunology Host vs Graft Reaction/immunology Humans Immune Tolerance/immunology Immunologic Deficiency Syndromes/*immunology/therapy Infant, Newborn Lymphocyte Activation/immunology Male T-Lymphocytes/*immunologySepIPatients who have become split lymphoid chimeras (T cells of donor origin, B cells and monocytes of host origin) following transplantation of HLA-haploidentical marrow for the treatment of severe combined immunodeficiency disease provide a unique model for the study of tolerance. One such patient, UPN 345, was transplanted with maternal marrow and was found to have antidonor proliferative reactivity without detectable donor-directed cytotoxicity when tested at 18, 23, and 66 mos following bone marrow transplantation. In bulk culture, the proliferation to donor cells could be blocked by monoclonal antibodies to HLA-DR and -DQ. Nine clones with antidonor reactivity were established by limiting dilution techniques from a mixed lymphocyte culture between engrafted T cells and irradiated donor E rosette-negative cells. All of the clones were of maternal donor origin, and all were CD3+CD4+CD8-. The clones were tested for proliferative and cytotoxic activity toward donor, host, and paternal B-lymphoblastoid cell lines (B-LCL). Six clones proliferated strongly to maternal B-LCL but not to host B-LCL. Six clones were found to exclusively lyse maternal B-LCL. Four of the clones had both antidonor cytotoxic and antidonor proliferative reactivity. Monoclonal antibody blocking studies were performed on five of the six clones with cytotoxic activity. The antidonor cytotoxicity was not inhibited by monoclonal antibodies to class I determinants; however, three clones were inhibited in the presence of monoclonal antibody to DR, one clone was inhibited by anti-DQ monoclonal antibody, and one clone was inhibited by anti-DP monoclonal antibody. The cytotoxicity of all five clones was inhibited by monoclonal antibody to CD4. These data indicate that antidonor reactivity may also include a cytotoxic component which is not apparent in bulk cultures and which, based on our limiting dilution studies, is probably controlled by regulatory cells. Both the antidonor cytotoxicity and the antidonor proliferation appear to be directed primarily toward donor HLA class II antigens that are not shared with the patient.*http://www.ncbi.nlm.nih.gov/pubmed/2211189aKeever, C A Flomenberg, N Gazzola, M V Pekle, K Yang, S Y Small, T N Collins, N H O'Reilly, R J CA-08748/CA/NCI NIH HHS/United States CA-33050/CA/NCI NIH HHS/United States CT5T32CA09512-02/CT/CIT NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states Human immunology Hum Immunol. 1990 Sep;29(1):42-55.%0198-8859 (Print) 0198-8859 (Linking)2211189`Bone Marrow Transplantation Service, Memorial Sloan-Kettering Cancer Center, New York, New York.0198-8859(90)90068-Z [pii]eng ||7?{Incefy, G. S. Flomenberg, N. Heller, G. Kernan, N. A. Brochstein, J. Kirkpatrick, D. Kapoor, N. Groshen, S. O'Reilly, R. J.1990Evidence that appearance of thymulin in plasma follows lymphoid chimerism and precedes development of immunity in patients with lethal combined immunodeficiency transplanted with T cell-depleted haploidentical marrow55-61Transplantation501 1990/07/01)Bone Marrow Transplantation/*methods Chimera Female Humans Immunologic Deficiency Syndromes/immunology/*therapy Infant Infant, Newborn *Lymphocyte Depletion Male Phytohemagglutinins/pharmacology Plant Lectins T-Lymphocytes/*immunology Thymic Factor, Circulating/*analysis Thymus Hormones/*analysisJulThymulin, a peptide secreted by human thymic epithelial cells, circulates in peripheral blood. Levels of plasma thymulin (FTS-Zn) activity were analyzed in 21 patients with lethal combined immunodeficiency disorders who were treated with transplantation of HLA-haplotype-mismatched parental bone marrow depleted of T cells by differential agglutination with soybean agglutinin and E-rosetting (SBA-E-BMT). Among these 21 infants, 15 were patients with severe combined immunodeficiency (SCID) and 6 had combined immunodeficiency (CID) with Omenn's syndrome or CID with T cell predominance (CIDTP). In contrast to normal infants who possess high levels of plasma thymulin activity, 20 of the 21 patients demonstrated undetectable or low plasma thymulin levels for their age at admission prior to transplantation. Following SBA-E-BMT, however, thymulin became detectable in the plasma of 17 of 18 evaluable patients and reached normal or near-normal levels between 21 and 125 days posttransplant. In patients in whom the timing of engraftment could be established by emergence of donor lymphocytes, thymulin appeared in the plasma at approximately the same time as lymphoid chimerism was detected, and in all patients who were engrafted and immunologically reconstituted, the increment in thymulin levels preceded development of immune functions. These studies support the concept that normal marrow-derived cells in the graft can provide a stimulus necessary for induction of thymic epithelial secretory function in patients with thymic dysplasia. Further, immunologic reconstitution in these patients was not seen following SBA-E-BMT unless and until recovery of thymus function had been observed.*http://www.ncbi.nlm.nih.gov/pubmed/2368151KIncefy, G S Flomenberg, N Heller, G Kernan, N A Brochstein, J Kirkpatrick, D Kapoor, N Groshen, S O'Reilly, R J AG 02814/AG/NIA NIH HHS/United States CA 33050/CA/NCI NIH HHS/United States CA 33168/CA/NCI NIH HHS/United States Research Support, U.S. Gov't, P.H.S. United states Transplantation Transplantation. 1990 Jul;50(1):55-61.%0041-1337 (Print) 0041-1337 (Linking)2368151aBone Marrow Transplant Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.eng/||7@(Ginsburg, M. J. Ellis, G. L. Flom, L. L.1990rDetection of soft-tissue foreign bodies by plain radiography, xerography, computed tomography, and ultrasonography701-3 Ann Emerg Med196 1990/06/01Evaluation Studies as Topic Foreign Bodies/diagnosis/*radiography Glass Humans Plastics Tomography, X-Ray Computed/*standards *Ultrasonography Wood *XeroradiographyJunBDetection of a soft-tissue foreign body is common yet often difficult, particularly when the foreign material is not radiopaque. Various imaging modalities have been advocated for detecting foreign bodies that are not revealed by plain radiography. The abilities of plain radiography, xerography, computed tomography, and ultrasonography to detect glass, wooden, and plastic foreign bodies in an in vitro preparation are compared. While all of these imaging techniques demonstrated a glass foreign body, only ultrasonography clearly identified wooden and plastic foreign bodies.*http://www.ncbi.nlm.nih.gov/pubmed/2188542Ginsburg, M J Ellis, G L Flom, L L Comparative Study United states Annals of emergency medicine Ann Emerg Med. 1990 Jun;19(6):701-3.%0196-0644 (Print) 0196-0644 (Linking)2188542PDepartment of Emergency Medicine, McKeesport Hospital, Pittsburgh, Pennsylvania.S0196-0644(05)82483-7 [pii]eng ||7A]Krown, S. E. Gold, J. W. Niedzwiecki, D. Bundow, D. Flomenberg, N. Gansbacher, B. Brew, B. J.1990Interferon-alpha with zidovudine: safety, tolerance, and clinical and virologic effects in patients with Kaposi sarcoma associated with the acquired immunodeficiency syndrome (AIDS)812-21Ann Intern Med11211 1990/06/01Acquired Immunodeficiency Syndrome/complications/*drug therapy/immunology Adult CD4-Positive T-Lymphocytes/drug effects Drug Evaluation Drug Therapy, Combination Gene Products, gag/drug effects HIV Core Protein p24 HIV-1/drug effects Humans Interferon Alfa-2a/*administration & dosage/adverse effects Interferon Type I/*administration & dosage/adverse effects Interferon Type I, Recombinant/*administration & dosage Leukocyte Count/drug effects Male Middle Aged Neutropenia/chemically induced Sarcoma, Kaposi/*drug therapy/etiology/immunology Statistics as Topic Viral Core Proteins/drug effects Zidovudine/*administration & dosage/adverse effectsJun 1_OBJECTIVE: To evaluate safety, tolerance, and potential efficacy of interferon-alpha and zidovudine combination therapy in patients with Kaposi sarcoma and the acquired immunodeficiency syndrome (AIDS). DESIGN: Open, phase-I study with randomization between two preparations of interferon-alpha. SETTING: Outpatient clinic of a cancer research center. PATIENTS: Forty-three patients with Kaposi sarcoma associated with AIDS. INTERVENTIONS: Patients were treated with interferon-alpha, 4.5, 9, or 18 million U/d, and zidovudine, 100 or 200 mg orally every 4 hours. MEASUREMENTS AND MAIN RESULTS: Neutropenia was the major dose-limiting toxicity. Fatigue, liver enzyme elevation, anemia, and thrombocytopenia were dose-limiting in some patients. Maximum tolerated dosages for interferon-alpha 2a with zidovudine, respectively, were 4.5 million U/d with 200 mg every 4 hours or 18 million U/d with 100 mg every 4 hours. An interferon-alpha n1 [corrected] dosage of 9 million U/d with zidovudine dosages of either 100 or 200 mg every 4 hours induced dose-limiting toxicity in most patients. Of 37 evaluable patients, 17 (46%; 95% CI, 30% to 62%) showed complete or partial tumor regression. Antitumor effects occurred more frequently in patients with baseline CD4 counts above 200 x 10(6) cells/L (65%) than in patients with lower baseline counts (30%, P = 0.05). Effects on CD4 cells were related to both initial CD4 count and interferon dose. Increased skin test reactivity and decreased serum human immunodeficiency virus (HIV) p24 antigen and virus recovery from blood cells were seen. CONCLUSIONS: Combined therapy with interferon-alpha and zidovudine can be safely administered to patients with AIDS and Kaposi sarcoma. The observed effects on tumor growth, HIV replication, and immune function support further studies of the combination in patients at various stages of HIV infection.*http://www.ncbi.nlm.nih.gov/pubmed/1971504 Krown, S E Gold, J W Niedzwiecki, D Bundow, D Flomenberg, N Gansbacher, B Brew, B J AI-27669/AI/NIAID NIH HHS/United States Clinical Trial Randomized Controlled Trial Research Support, U.S. Gov't, P.H.S. United states Annals of internal medicine Ann Intern Med. 1990 Jun 1;112(11):812-21.%0003-4819 (Print) 0003-4819 (Linking)1971504;Memorial Sloan-Kettering Cancer Center, New York, New York.engt||7B$Bedell, H. E. Yap, Y. L. Flom, M. C.1990OFixational drift and nasal-temporal pursuit asymmetries in strabismic amblyopes968-76Invest Ophthalmol Vis Sci315 1990/05/01Adult Amblyopia/complications/*physiopathology Eye Movements/*physiology Fixation, Ocular/*physiology Humans Strabismus/complications/*physiopathology Vision Disparity/physiology Visual Acuity/physiologyMay*This study evaluated to what extent inaccurate and asymmetric smooth pursuit in strabismic amblyopic eyes is attributable to abnormally high-velocity eye drifts that these eyes exhibit during monocular fixation. Smooth pursuit gains (peak eye velocity/peak target velocity) were determined in the amblyopic and nonamblyopic eyes of 11 strabismics for nasalward and temporalward motion; the target oscillated across 6 degrees of the horizontal meridian at frequencies ranging from 0.0625 to 1 Hz. In general, pursuit gains were higher for nasalward than temporalward motion, for both amblyopic and nonamblyopic eyes. Correction for each eye's mean velocity of fixational drift eliminated this nasal-temporal pursuit asymmetry for most of the nonamblyopic eyes, but not for the amblyopic eyes. Compared to the nonamblyopic eyes, corrected pursuit gains of the amblyopic eyes averaged about 0.2 lower nasalward and about 0.4 lower temporalward, but substantial variation occurred among individuals. We suggest that the overall reduction of pursuit gain in strabismic amblyopic eyes (after correction is made for fixational drift bias) stems from the use of a nonfoveal (eccentric fixation) locus for tracking; the further reduction of temporalward gain may result from a nasal-temporal asymmetry in processing motion signals.*http://www.ncbi.nlm.nih.gov/pubmed/2335458Bedell, H E Yap, Y L Flom, M C R01 EY-03694/EY/NEI NIH HHS/United States R01 EY-05068/EY/NEI NIH HHS/United States Research Support, U.S. Gov't, P.H.S. United states Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 1990 May;31(5):968-76.%0146-0404 (Print) 0146-0404 (Linking)2335458>College of Optometry, University of Houston, Texas 77204-6052.eng.|t7CVDiSanto, J. P. Keever, C. A. Small, T. N. Nicols, G. L. O'Reilly, R. J. Flomenberg, N.1990gAbsence of interleukin 2 production in a severe combined immunodeficiency disease syndrome with T cells1697-704 J Exp Med1715 1990/05/01eAntigens, CD/analysis Antigens, CD3 Antigens, Differentiation, T-Lymphocyte/analysis Cells, Cultured Female Humans Immunologic Deficiency Syndromes/genetics/*immunology Infant, Newborn Interleukin-2/biosynthesis/*deficiency/genetics Ionomycin/pharmacology Lymphocyte Activation Male Receptors, Antigen, T-Cell/analysis T-Lymphocytes/drug effects/*immunologyMay 1We have characterized a child with a severe combined immunodeficiency disease syndrome with increased numbers, but a normal distribution, of CD3+ T cells. This patient's immunological defect appears to be attributable to a selective deficiency in T cell production of IL-2, which may reflect a subtle abnormality in the IL-2 gene locus or a defect in a regulatory factor necessary for IL-2 transcription. The increased numbers of phenotypically normal T cells in this patient suggest that alternative pathways of T cell development exist in man or that IL-2 production intra- and extrathymically is controlled via distinct regulatory mechanisms.*http://www.ncbi.nlm.nih.gov/pubmed/2139699NDiSanto, J P Keever, C A Small, T N Nicols, G L O'Reilly, R J Flomenberg, N CA-22507/CA/NCI NIH HHS/United States CA-23766/CA/NCI NIH HHS/United States CA-33050/CA/NCI NIH HHS/United States etc. Case Reports Research Support, U.S. Gov't, P.H.S. United states The Journal of experimental medicine J Exp Med. 1990 May 1;171(5):1697-704.%0022-1007 (Print) 0022-1007 (Linking)21879052139699pEffector Lymphocyte Biology, Laboratory Sloan-Kettering Institute for Cancer Research, New York, New York 10021.eng ||7D3Pizov, R. Segal, E. Kaplan, L. Floman, Y. Perel, A.1990oThe use of systolic pressure variation in hemodynamic monitoring during deliberate hypotension in spine surgery96-100 J Clin Anesth22 1990/03/01Adolescent Adult *Blood Pressure Cardiac Output Central Venous Pressure Heart Rate *Hemodynamics Humans *Hypotension, Controlled Middle Aged *Monitoring, Physiologic Nitroprusside Pulmonary Wedge Pressure Spectrum Analysis *Spinal FusionMar-AprsThe systolic pressure variation (SPV), which is the difference between the maximal and minimal systolic blood pressure (SP) during one ventilatory cycle, was studied in ten patients during posterior spine fusion. To minimize the blood loss, deliberate hypotension to a mean blood pressure of 50 mmHg was introduced by a continuous infusion of sodium nitroprusside. SPV was further divided into two components, delta up and delta down, using SP during a short apnea as a reference point. All hemodynamic parameters were measured at the beginning of anesthesia, 15 minutes after induction of hypotension, before cessation of nitroprusside infusion, and 15 minutes after the end of the hypotensive period. During the hypotensive period (166 +/- 53 minutes), cardiac output (CO) decreased significantly from 4.83 +/- 1.36 L/min to 3.86 +/- 1.07 L/min (p less than 0.05). Heart rate (HR), central venous pressure (CVP), and pulmonary capillary wedge pressure (PCWP) did not change during this period and bore no correlation to the changes in CO. The only variables that changed during the hypotensive period, in addition to CO, were SPV (from 13.1 +/- 4.9 mmHg to 16.9 +/- 5.1 mmHg, p less than 0.02), and delta down (from 6.0 +/- 3.8 mmHg to 9.9 +/- 6.3 mmHg, p less than 0.05). The delta down segment was the only hemodynamic variable whose changes during the hypotensive period showed a significant (p less than 0.018) correlation with the changes in CO. delta down reflects the degree of decrease in left ventricular stroke output in response to a positive pressure breath, and thus is a sensitive indicator of preload.(ABSTRACT TRUNCATED AT 250 WORDS)*http://www.ncbi.nlm.nih.gov/pubmed/2346658Pizov, R Segal, E Kaplan, L Floman, Y Perel, A Research Support, Non-U.S. Gov't United states Journal of clinical anesthesia J Clin Anesth. 1990 Mar-Apr;2(2):96-100.%0952-8180 (Print) 0952-8180 (Linking)2346658eDepartment of Anesthesiology and Orthopedic Surgery, Hadassah University Hospital, Jerusalem, Israel.0952-8180(90)90061-7 [pii]eng E||7EhRosenkrantz, K. Keever, C. Bhimani, K. Horvath, A. Brochstein, J. O'Reilly, R. Dupont, B. Flomenberg, N.1990Both ongoing suppression and clonal elimination contribute to graft-host tolerance after transplantation of HLA mismatched T cell-depleted marrow for severe combined immunodeficiency1721-8 J Immunol1445 1990/03/01Bone Marrow Transplantation/*immunology Cell Survival Clone Cells Graft Survival HLA Antigens/analysis Histocompatibility Humans *Immune Tolerance Immunologic Deficiency Syndromes/*immunology/surgery Lymphocyte Activation MaleMar 1Lymphocytes from children with severe combined immunodeficiency who had been immunologically reconstituted with haploidentical T cell-depleted bone marrow were analyzed with regard to their immunologic recognition of donor, host, or third party alloantigens. When compared with freshly isolated donor lymphocytes, the engrafted donor cells exhibited markedly reduced to absent responses toward host Ag in primary or secondary MLC and cell-mediated lympholysis assays. However, under limiting dilution conditions, cytotoxic responses to host Ag could be demonstrated, indicating that small numbers of host reactive cells were present, although down-regulated at high responder cell doses. These results are consistent with prior observations in limiting dilution cultures that indicate that cells with the potential to lyse autologous target cells exist in the peripheral blood of all normal individuals. The number of host reactive cells present in these patients is significantly less than that present in cells isolated directly from the marrow donors, and is also less than the number of autocytotoxic cells normally seen in peripheral blood. Together, these observations indicate that two mechanisms contribute to donor host tolerance in these patients. The majority of host reactive cells appear to have undergone clonal deletion or inactivation, whereas the small residual host-reactive population appears to be under ongoing immunoregulatory control.*http://www.ncbi.nlm.nih.gov/pubmed/2307837Rosenkrantz, K Keever, C Bhimani, K Horvath, A Brochstein, J O'Reilly, R Dupont, B Flomenberg, N CA22507/CA/NCI NIH HHS/United States CA23766/CA/NCI NIH HHS/United States CA33050/CA/NCI NIH HHS/United States etc. Case Reports Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states Journal of immunology (Baltimore, Md. : 1950) J Immunol. 1990 Mar 1;144(5):1721-8.%0022-1767 (Print) 0022-1767 (Linking)2307837OImmunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.eng ||7FzRosenkrantz, K. Bhimani, K. Welte, K. Buck, J. DiSanto, J. Levi, E. DiMartino, J. Hammerling, U. Dupont, B. Flomenberg, N.1990ZA novel autoregulatory cytokine is required for the regulation of autoaggressive responses254-64 Hum Immunol273 1990/03/01$Biological Factors/isolation & purification/*physiology Cells, Cultured Chromatography, Gel Cytokines Cytotoxicity, Immunologic/*physiology Humans Interleukin-2/pharmacology Molecular Weight Recombinant Proteins T-Lymphocytes/drug effects/*immunology Tetradecanoylphorbol Acetate/pharmacologyMarLimiting dilution studies indicate that cells with the potential to lyse autologous target cells exist in the peripheral blood of all normal individuals. In contrast to allocytotoxic cells, autocytolytic cells are down-regulated by a second less frequent cell population. When recombinant interleukin 2 is substituted for crude lymphocyte conditioned medium in these limiting dilution experiments, autocytotoxicity develops normally. Under these conditions, however, the autocytotoxic response is not down-regulated. Mixing crude lymphocyte-conditioned medium together with recombinant interleukin 2 restores the regulation of autocytotoxicity normally seen at high responder cell dose. These findings indicate that a second soluble factor present in the conditioned medium is necessary either for the activation, growth, or differentiation of the regulatory cell population or alternatively, to render the cytotoxic population responsive to the activity of regulatory cells. Gel filtration studies indicate that the molecular weight of this factor is between 60 and 80 kd. This factor appears to be distinct from known immunologically active cytokines. It is conceivable that deficiencies of this cytokine may be relevant to the pathogenesis of autoimmune diseases or graft-versus-host reactions.*http://www.ncbi.nlm.nih.gov/pubmed/2187837mRosenkrantz, K Bhimani, K Welte, K Buck, J DiSanto, J Levi, E DiMartino, J Hammerling, U Dupont, B Flomenberg, N CA22507/CA/NCI NIH HHS/United States CA23766/CA/NCI NIH HHS/United States CA33050/CA/NCI NIH HHS/United States etc. Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states Human immunology Hum Immunol. 1990 Mar;27(3):254-64.%0198-8859 (Print) 0198-8859 (Linking)2187837mDepartment of Immunology and Cell Biology, Sloan-Kettering Institute for Cancer Research, New York, NY 10021.0198-8859(90)90055-T [pii]eng ||7G9Briehl, M. M. Flomerfelt, F. A. Wu, X. P. Miesfeld, R. L.1990;Transcriptional analyses of steroid-regulated gene networks287-94Mol Endocrinol42 1990/02/01Androgens/genetics/metabolism/pharmacology Animals Base Sequence DNA/genetics Gene Expression/physiology Glucocorticoids/genetics/metabolism/pharmacology Liver Neoplasms, Experimental/metabolism/pathology Lymphoma/metabolism/pathology Male Nucleic Acid Hybridization Orchiectomy Prostate/metabolism/pathology RNA, Messenger/genetics/metabolism Rats Rats, Inbred Strains Steroids/metabolism/*physiology *Transcription, GeneticFebIt has been proposed that cell-specific responses to steroid action are the result of coordinate expression of steroid gene networks. Using three different cell systems, we have performed transcriptional analyses to determine if the observed hormone-induced alterations in gene expression are consistent with a limited number of potential target genes in any one cell type. Our results indicate that greater than 95% of the transcripts in dexamethasone-treated rat hepatoma (HTC), or mouse lymphoma (WEH17) cells, are similar to the mRNAs in untreated cells based on subtraction hybridization. In addition, we find that although the castration-induced expression of androgen-regulated transcripts in the rat ventral prostate (RVP) is significantly different between normal and castrated rats (19%), the majority of these mRNAs are accounted for by the over abundance of sulfated glycoprotein-2 sequences. Specifically, analysis of an RVP subtracted cDNA library revealed that sulfated glycoprotein-2 mRNA masked the presence of less abundant differentially expressed sequences, confirming that the actual size of the RVP androgen gene network is small. We conclude that steroid-mediated changes in transcription accurately reflect the expression of a few cell-specific target genes, and thus support the model of steroid gene networks. The potential to characterize key elements which determine both the time course and magnitude of cell-specific hormone responses is discussed.*http://www.ncbi.nlm.nih.gov/pubmed/2330007"Briehl, M M Flomerfelt, F A Wu, X P Miesfeld, R L CA-09213/CA/NCI NIH HHS/United States GM-40738/GM/NIGMS NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states Molecular endocrinology (Baltimore, Md.) Mol Endocrinol. 1990 Feb;4(2):287-94.%0888-8809 (Print) 0888-8809 (Linking)2330007@Department of Biochemistry, University of Arizona, Tucson 85721.eng||7HXDean, B. L. Drayer, B. P. Bird, C. R. Flom, R. A. Hodak, J. A. Coons, S. W. Carey, R. G.1990'Gliomas: classification with MR imaging411-5 Radiology1742 1990/02/01|Anaplasia Astrocytes/pathology Astrocytoma/classification/pathology Biopsy Brain Diseases/diagnosis Brain Edema/diagnosis Cerebral Hemorrhage/diagnosis Cysts/diagnosis Glioblastoma/classification/pathology Glioma/*classification/pathology Humans *Magnetic Resonance Imaging/methods Necrosis Observer Variation Regression Analysis Supratentorial Neoplasms/*classification/pathologyFebThe findings at magnetic resonance (MR) imaging in a group of 36 pathologically verified supratentorial gliomas were analyzed and compared with the biopsy diagnoses (a) to determine whether MR imaging could be used to classify astrocytic-series tumors into a three-tiered system of low-grade astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme; and (b) to evaluate MR imaging features that may aid in this classification. The MR characteristics evaluated were crossing of the midline, edema, tumor signal heterogeneity, hemorrhage, border definition, cyst formation or necrosis, and mass effect. The statistically significant MR characteristics (positive predictors) were mass effect (P = .0000) and cyst formation or necrosis (P = .0512). The MR accuracy rate approached that of neuropathologic diagnosis, which is subject to sampling errors. MR imaging may serve as an adjunct in case management when the clinical course and MR findings appear to be at odds with the neuropathologic diagnosis.*http://www.ncbi.nlm.nih.gov/pubmed/2153310Dean, B L Drayer, B P Bird, C R Flom, R A Hodak, J A Coons, S W Carey, R G Comparative Study United states Radiology Radiology. 1990 Feb;174(2):411-5.%0033-8419 (Print) 0033-8419 (Linking)2153310vDivision of Neuroradiology, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, AZ 85013.eng Y||7I7Terry, L. A. DiSanto, J. P. Small, T. N. Flomenberg, N.1990QDifferential expression and regulation of the human CD8 alpha and CD8 beta chains82-91Tissue Antigens352 1990/02/01 Antigens, CD8 Antigens, Differentiation, T-Lymphocyte/*genetics/immunology/metabolism Cell Line Down-Regulation *Gene Expression Regulation Humans Leukemia, T-Cell/immunology/metabolism/pathology Neutrophils/immunology/metabolism T-Lymphocytes/immunology/metabolism Transcription, GeneticFebhThe CD8 glycoprotein is expressed by thymocytes, mature T cells and natural killer (NK) cells and has been implicated in the recognition of monomorphic determinants on major histocompatibility complex (MHC) Class I antigens, and in signal transduction during the course of T-cell activation. Both human and rodent CD8 antigens are comprised of two distinct polypeptide chains, alpha and beta. The majority of monoclonal antibodies (mAb) reactive with the human CD8 antigen bind the CD8 alpha chain, while a single mAb, T8/2T8-5H7, has been identified which binds to the CD8 alpha/beta heterodimer. While the two chains of CD8 have been presumed to be coordinately expressed in normal T cells, this is not always the case. Northern blot analysis of a panel of T-cell leukemias and normal cells demonstrate that CD8 alpha and CD8 beta are not invariably co-transcribed and phenotypic analysis of fresh and interleukin 2 (IL-2) expanded peripheral blood mononuclear cells (PBMC) confirm that the CD8 alpha and CD8 beta chains are differentially expressed at the cell surface. Four distinct subpopulations of CD8+ cells have been identified based on the expression of CD8 alpha/alpha or CD8 alpha/beta complexes: (1) T-cell receptor (TcR) alpha beta+ T cells which are CD8 alpha+/beta+; (2) TcR alpha beta+ T cells which are CD8 alpha+/beta-; (3) TcR gamma delta+ T cells which are CD8 alpha+/beta- and (4) natural killer (NK) cells which are CD8 alpha+/beta-. We also demonstrate the down-regulation of the CD8 alpha/beta heterodimers from the surface of a CD8+ T-cell clone following treatment with phorbol myristate acetate (PMA) while CD8 alpha/alpha homodimers remain on the cell surface. This observation demonstrates that a) a CD8+ T-cell clone can express both CD8 alpha/alpha homodimers and CD8 alpha/beta heterodimers and b) these two complexes do not have identical biological properties. Together, these data suggest that CD8 alpha/alpha and CD8 alpha/beta dimers may not subserve identical functions. The differential contribution of these two CD8 complexes should be considered in models of T-cell-mediated cytotoxicity and T-cell activation.*http://www.ncbi.nlm.nih.gov/pubmed/2111591;Terry, L A DiSanto, J P Small, T N Flomenberg, N CA22507/CA/NCI NIH HHS/United States CA23766/CA/NCI NIH HHS/United States CA33050/CA/NCI NIH HHS/United States etc. Comparative Study Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Denmark Tissue antigens Tissue Antigens. 1990 Feb;35(2):82-91.%0001-2815 (Print) 0001-2815 (Linking)2111591OEffector Lymphocyte Biology Laboratory, Memorial Sloan-Kettering Cancer Center.eng~|7J=Kreek, M. J. Khuri, E. Flomenberg, N. Albeck, H. Ochshorn, M.1990FImmune status of unselected methadone maintained former heroin addicts445-8Prog Clin Biol Res328 1990/01/01Adolescent Adult Female Heroin Dependence/blood/*immunology/rehabilitation Humans Immune System/drug effects/physiopathology Killer Cells, Natural/immunology Leukocyte Count Male Methadone/*therapeutic use Neuroimmunomodulation/drug effects/physiology T-Lymphocytes/immunology*http://www.ncbi.nlm.nih.gov/pubmed/2304962Kreek, M J Khuri, E Flomenberg, N Albeck, H Ochshorn, M United states Progress in clinical and biological research Prog Clin Biol Res. 1990;328:445-8.%0361-7742 (Print) 0361-7742 (Linking)2304962%Rockefeller University, New York, NY.eng ||7KmMotzer, R. J. Niedzwiecki, D. Isaacs, M. Menendez-Botet, C. Tong, W. P. Flombaum, C. Scher, H. I. Bosl, G. J.1990yCarboplatin-based chemotherapy with pharmacokinetic analysis for patients with hemodialysis-dependent renal insufficiency234-8Cancer Chemother Pharmacol273 1990/01/015Adult Antineoplastic Combined Chemotherapy Protocols/*therapeutic use Carboplatin/administration & dosage/*pharmacokinetics Carcinoma, Transitional Cell/drug therapy Humans Kidney Failure, Chronic/*metabolism Male Neoplasms, Germ Cell and Embryonal/drug therapy *Renal Dialysis Ureteral Neoplasms/drug therapyThree patients with renal insufficiency requiring hemodialysis were treated with carboplatin at 100 mg/m2 in combination with etoposide for advanced germ-cell tumor (GCT, two cases) or Adriamycin + vinblastine for a transitional-cell carcinoma of the ureter (one case). Hemodialysis was performed 24 h after the administration of carboplatin. Both patients with GCT achieved a complete response, and the patient with transitional-cell carcinoma of the ureter was inevaluable for response but his disease has not progressed. The dose of carboplatin was increased in one patient as renal function improved on therapy. In two patients, the pharmacokinetics of carboplatin were determined; the pre-dialysis half-lives, AUC, and total body clearances of free carboplatin-derived platinum were estimated to be 32 and 18.3 h, 4.93 and 6.17 mg ml-1 min, and 18.2 and 18.7 ml/min, respectively. The dialysis elimination half-lives (t1/2 beta) of 2 and 3 h, respectively, for these two patients were markedly lower than the predialysis values, indicating that carboplatin was dialyzed. In summary, carboplatin can be given to patients with severe renal insufficiency. Adequate AUCs were achieved and dialysis limited systemic exposure to free carboplatin.*http://www.ncbi.nlm.nih.gov/pubmed/2176133Motzer, R J Niedzwiecki, D Isaacs, M Menendez-Botet, C Tong, W P Flombaum, C Scher, H I Bosl, G J Case Reports Research Support, Non-U.S. Gov't Germany Cancer chemotherapy and pharmacology Cancer Chemother Pharmacol. 1990;27(3):234-8.%0344-5704 (Print) 0344-5704 (Linking)2176133[Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York.eng||7LDavis, M. R. Hoffman, L. G.1983VA three step method of the determination of fixation status and retinal correspondence807-9J Am Optom Assoc549 1983/09/01Afterimage Child Child, Preschool *Fixation, Ocular Humans Retina/*physiology Strabismus/*diagnosis/physiopathology Vision Tests/instrumentation/methodsSepIn examination and treatment of patients with strabismus one often encounters abnormal sensory adaptations such as eccentric fixation and anomalous retinal correspondence. Prognosis and treatment of strabismus are dependent on the presence or absence of these conditions. When eccentric fixation is present it becomes difficult to interpret the results of many tests used to determine retinal correspondence. This determination is further complicated when the patient is unable to give accurate responses. A technique utilizing visuoscopy and an afterimage has been performed on somewhat less cooperative patients. The results compare favorably to amblyoscopic measurements of the angle of anomaly.*http://www.ncbi.nlm.nih.gov/pubmed/6619483|Davis, M R Hoffman, L G United states Journal of the American Optometric Association J Am Optom Assoc. 1983 Sep;54(9):807-9.%0003-0244 (Print) 0003-0244 (Linking)6619483eng||7M Burian, H. M.19684Comment on "determination of retinal correspondence"146-7Arch Ophthalmol801 1968/07/01DFixation, Ocular Humans Retina/*physiopathology Strabismus/diagnosisJul*http://www.ncbi.nlm.nih.gov/pubmed/5660010ZBurian, H M United states Archives of ophthalmology Arch Ophthalmol. 1968 Jul;80(1):146-7.%0003-9950 (Print) 0003-9950 (Linking)5660010eng||7NFlom, M. C. Kerr, K. E.1967bDetermination of retinal correspondence. Multiple-testing results and the depth of anomaly concept200-13Arch Ophthalmol772 1967/02/01xAdolescent Amblyopia/*diagnosis Child Female Humans Male Strabismus/*diagnosis Vision Disorders/*diagnosis *Vision TestsFeb*http://www.ncbi.nlm.nih.gov/pubmed/6019013cFlom, M C Kerr, K E United states Archives of ophthalmology Arch Ophthalmol. 1967 Feb;77(2):200-13.%0003-9950 (Print) 0003-9950 (Linking)6019013engg||7O Wilczek, M.1967Q[Method of selective afterimages for the determination of retinal correspondence]107-10Klin Monbl Augenheilkd1501 1967/01/01Amblyopia/*physiopathology Child Fixation, Ocular Humans Methods Retina/*physiopathology Strabismus/*physiopathology Vision Tests/instrumentation*http://www.ncbi.nlm.nih.gov/pubmed/5598215oWilczek, M Germany, west Klinische Monatsblatter fur Augenheilkunde Klin Monbl Augenheilkd. 1967;150(1):107-10.%0023-2165 (Print) 0023-2165 (Linking)5598215LMethode der gezielten Nachbilder zur Feststellung der Netzhautkorrespondenz.ger||7PPur, S.19571[Aids in determination of retinal correspondence]404-5 Cesk Oftalmol135 1957/09/01Retina/*physiologySep+http://www.ncbi.nlm.nih.gov/pubmed/13489803UPur, s Not Available Ceskoslovenska oftalmologie Cesk Oftalmol. 1957 Sep;13(5):404-5.%0009-059X (Print) 0009-059X (Linking)13489803,Pomucka na urcovani retinalni korespondence.cze||7QFranklin, D. A.1951tDifferentiation of phi phenomenon and parallax. The use of phi phenomenon in determination of retinal correspondence77-87Am J Ophthalmol341 1951/01/01 *StrabismusJan+http://www.ncbi.nlm.nih.gov/pubmed/14799582dFranklin, d a Not Available American journal of ophthalmology Am J Ophthalmol. 1951 Jan;34(1):77-87.%0002-9394 (Print) 0002-9394 (Linking)14799582eng|?R)Rosenbloom, Alfred A. Morgan, Meredith W.1990.Principles and practice of pediatric optometry xxvi, 589 p. Philadelphia Lippincott~Pediatric optometry. Optometry. Vision Disorders diagnosis. Vision Disorders in infancy & childhood. Vision Disorders therapy.y90006079 edited by Alfred A. Rosenbloom, Meredith W. Morgan. ill. ; 25 cm. Includes bibliographical references and index. 039750917019960784||7S2011RRandomized trial to evaluate combined patching and atropine for residual amblyopia960-2Arch Ophthalmol1297 2011/07/13Jul+http://www.ncbi.nlm.nih.gov/pubmed/21746992Pediatric Eye Disease Investigator Group (PEDIG) Writing Committee United States Archives of ophthalmology Arch Ophthalmol. 2011 Jul;129(7):960-2.*1538-3601 (Electronic) 0003-9950 (Linking)21746992`c/o Jaeb Center for Health Research, 15310 Amberly Dr, Ste 350, Tampa, FL 33647. pedig@jaeb.org./129/7/960 [pii] 10.1001/archophthalmol.2011.174eng||7TSBaciarello, M. Cornini, A. Zasa, M. Pedrona, P. Scrofani, G. Venuti, F. Fanelli, G.2011xIntrathecal atropine to prevent postoperative nausea and vomiting after Cesarean section: a randomized, controlled trial781-8Minerva Anestesiol778 2011/07/07AugBACKGROUND: Postoperative nausea and vomiting (PONV) is a common adverse effect of intrathecal morphine, especially after Cesarean section. This randomized controlled trial investigated the effects of intrathecal administration of a small-dose of atropine on postoperative nausea and vomiting after Cesarean section. METHODS: Parturients with ASA physical status class I-II scheduled for elective Cesarean section and consenting to spinal anesthesia were enrolled. They received 0.5% hyperbaric bupivacaine 12.5 mg, morphine 200 microg and one of the following three solutions: atropine 100 microg intrathecally and saline intravenously; saline intrathecally and atropine 100 microg intravenously; saline only both intravenously and intrathecally. We examined the incidence and severity of PONV, pain ratings and the need for analgesics. RESULTS: We followed 204 parturients. The incidence of PONV was 15%, 37% and 49% in the three groups, respectively (P<0.001). The relative risk reduction for PONV when using intrathecal atropine was 69% vs. placebo and 59% vs. intravenous atropine. No differences were noted in terms of postoperative pain. CONCLUSION: Intrathecal atropine had a significant antiemetic effect, making it a useful adjunct for intrathecal opioid-related PONV.+http://www.ncbi.nlm.nih.gov/pubmed/21730925Baciarello, M Cornini, A Zasa, M Pedrona, P Scrofani, G Venuti, F Fanelli, G Italy Minerva anestesiologica Minerva Anestesiol. 2011 Aug;77(8):781-8.*1827-1596 (Electronic) 0375-9393 (Linking)21730925Department of Anesthesiology, Critical Care and Pain Medicine, University Hospital of Parma, Parma, Italy - mbaciarello@parmanesthesia.com.R02116664 [pii]enggF|7UVBaciarello, M. Cornini, A. Zasa, M. Pedrona, P. Scrofani, G. Venuti, F. S. Fanelli, G.2011xIntrathecal atropine to prevent postoperative nausea and vomiting after Cesarean section: a randomized, controlled trialMinerva Anestesiol 2011/05/11May 9BACKGROUND: Postoperative nausea and vomiting (PONV) is a common adverse effect of intrathecal morphine, especially after Cesarean section. This randomized controlled trial investigated the effects of intrathecal administration of a small-dose of atropine on postoperative nausea and vomiting after Cesarean section. METHODS: Parturients with ASA physical status class I-II scheduled for elective Cesarean section and consenting to spinal anesthesia were enrolled. They received 0.5% hyperbaric bupivacaine 12.5 mg, morphine 200 microg and one of the following three solutions: atropine 100 microg intrathecally and saline intravenously; saline intrathecally and atropine 100 microg intravenously; saline only both intravenously and intrathecally. We examined the incidence and severity of PONV, pain ratings and the need for analgesics. RESULTS: We followed 204 parturients. The incidence of PONV was 15%, 37% and 49% in the three groups, respectively (P<0.001). The relative risk reduction for PONV when using intrathecal atropine was 69% vs. placebo and 59% vs. intravenous atropine. No differences were noted in terms of postoperative pain. CONCLUSION: Intrathecal atropine had a significant antiemetic effect, making it a useful adjunct for intrathecal opioid-related PONV.+http://www.ncbi.nlm.nih.gov/pubmed/21555980GJournal article Minerva anestesiologica Minerva Anestesiol. 2011 May 9.*1827-1596 (Electronic) 0375-9393 (Linking)21555980Department of Anesthesiology, Critical Care and Pain Medicine, University Hospital of Parma, Parma, Italy - mbaciarello@parmanesthesia.com.R02116664 [pii]Eng ||7VpManganelli, F. Spadafora, M. Varrella, P. Peluso, G. Sauro, R. Di Lorenzo, E. Rosato, G. Daniele, S. Cuocolo, A.2011Addition of atropine to submaximal exercise stress testing in patients evaluated for suspected ischaemia with SPECT imaging: a randomized, placebo-controlled trial245-51Eur J Nucl Med Mol Imaging382 2010/11/10Adrenergic beta-Antagonists/therapeutic use Atropine/adverse effects/*pharmacology Calcium Channel Blockers/therapeutic use Coronary Angiography Coronary Artery Disease/drug therapy/*physiopathology/radiography/*radionuclide imaging Exercise Test/*methods Female Heart Rate/drug effects Humans Male Middle Aged Placebos *Tomography, Emission-Computed, Single-Photon Treatment OutcomeFebPURPOSE: To evaluate the effects of the addition of atropine to exercise testing in patients who failed to achieve their target heart rate (HR) during stress myocardial perfusion imaging with single-photon emission computed tomography (SPECT). METHODS: The study was a prospective, randomized, placebo-controlled design. Patients with suspected or known coronary artery disease who failed to achieve a target HR (>/=85% of maximal predicted HR) during exercise SPECT imaging were randomized to receive intravenous atropine (n=100) or placebo (n=101). RESULTS: The two groups of patients did not differ with respect to demographic or clinical characteristics. A higher proportion of patients in the atropine group achieved the target HR compared to the placebo group (60% versus 3%, p<0.0001). SPECT imaging was abnormal in a higher proportion of patients in the atropine group as compared to the placebo group (57% versus 42%, p<0.05). Stress-induced myocardial ischaemia was present in more patients in the atropine group as compared to placebo (47% versus 29%, p<0.01). In both groups of patients, no major side effects occurred. CONCLUSION: The addition of atropine at the end of exercise testing is more effective than placebo in raising HR to adequate levels, without additional risks of complications. The use of atropine in patients who initially failed to achieve their maximal predicted HR is associated with a higher probability of achieving a diagnostic myocardial perfusion study.+http://www.ncbi.nlm.nih.gov/pubmed/21061122-Manganelli, Fiore Spadafora, Marco Varrella, Paola Peluso, Giuseppina Sauro, Rosario Di Lorenzo, Emilio Rosato, Giuseppe Daniele, Stefania Cuocolo, Alberto Randomized Controlled Trial Germany European journal of nuclear medicine and molecular imaging Eur J Nucl Med Mol Imaging. 2011 Feb;38(2):245-51.*1619-7089 (Electronic) 1619-7070 (Linking)21061122[Department of Cardiology and Heart Surgery, San Giuseppe Moscati Hospital, Avellino, Italy.10.1007/s00259-010-1641-8eng ||7W4Aghamohammadi, H. Mehrabi, S. Mohammad Ali Beigi, F.2009sPrevention of bradycardia by atropine sulfate during urological laparoscopic surgery: a randomized controlled trial92-5Urol J62 2009/05/28Adolescent Adult Anesthesia, Intravenous/*adverse effects/methods Atropine/*administration & dosage Bradycardia/etiology/*prevention & control Chi-Square Distribution Double-Blind Method Female Fentanyl/administration & dosage Follow-Up Studies Heart Rate/drug effects Humans Infusions, Intravenous Intraoperative Complications/*prevention & control Laparoscopy/adverse effects/*methods Male Middle Aged Monitoring, Intraoperative Pneumoperitoneum, Artificial/adverse effects/methods Probability Reference Values Risk Assessment Surgical Procedures, Elective/adverse effects/methods Treatment Outcome Urologic Surgical Procedures/adverse effects/methodsSpringINTRODUCTION: Cardiac arrhythmias are a well-recognized complication of anesthesia for laparoscopy. The aim of this study was to evaluate the efficacy of atropine sulfate for prevention of bradyarrhythmia during laparoscopic surgery. MATERIALS AND METHODS: Sixty-four candidates for urological laparoscopic surgery were randomly assigned into 2 groups to receive either atropine sulfate or hypertonic saline solution (as placebo), intravenously 3 minutes before induction of anesthesia for the laparoscopic procedure. Then, all of the patients underwent anesthesia intravenous sodium thiopental and atracurium, followed by isoflurane or halothane inhalation. Heart rate and blood pressure were recorded preoperatively in the recovery room, preoperatively in the operation room, after induction of anesthesia, after induction of pneumoperitoneum, and postoperatively. RESULTS: A significant decreasing trend was seen in the heart rates during the operation in patients without atropine sulfate. Nine of 32 patients (28.1%) in this group developed bradycardia, while none of the patients with atropine sulfate prophylaxis had bradycardia perioperatively (P < .001). The mean decreases in systolic blood pressure between induction of anesthesia and pneumoperitoneum were 15.7 +/- 10.2 mm Hg in group 1 and 23.5 +/- 9.8 mm Hg in group 2 (P < .001). The mean decreases in diastolic blood pressure between these two measurements were 8.7 +/- 5.2 mm Hg in group 1 compared to 12.1 +/- 6.2 mm Hg in group 2 (P = .001). CONCLUSION: This study suggests that routine prophylaxis with an anticholinergic agent might be helpful in prevention of sinus bradycardia during urological laparoscopic surgery.+http://www.ncbi.nlm.nih.gov/pubmed/19472126Aghamohammadi, Homayun Mehrabi, Sadrollah Mohammad Ali Beigi, Faramarz Comparative Study Randomized Controlled Trial Iran Urology journal Urol J. 2009 Spring;6(2):92-5.*1735-546X (Electronic) 1735-1308 (Linking)19472126mDepartment of Anesthesiology,Shahid Labbafinejad MedicalCenter, Shahid Beheshti University(MC), Tehran, Iran.eng |t7XScheiman, M. M. Hertle, R. W. Kraker, R. T. Beck, R. W. Birch, E. E. Felius, J. Holmes, J. M. Kundart, J. Morrison, D. G. Repka, M. X. Tamkins, S. M.2008ZPatching vs atropine to treat amblyopia in children aged 7 to 12 years: a randomized trial1634-42Arch Ophthalmol12612 2008/12/10Amblyopia/drug therapy/physiopathology/*therapy Atropine/*therapeutic use Child Female Humans Male Mydriatics/*therapeutic use Ophthalmic Solutions/therapeutic use *Sensory Deprivation Treatment Outcome Vision, Binocular/physiology Visual Acuity/physiologyDecOBJECTIVE: To compare patching with atropine eyedrops in the treatment of moderate amblyopia (visual acuity, 20/40-20/100) in children aged 7 to 12 years. METHODS: In a randomized, multicenter clinical trial, 193 children with amblyopia were assigned to receive weekend atropine or patching of the sound eye 2 hours per day. Main Outcome Measure Masked assessment of visual acuity in the amblyopic eye using the electronic Early Treatment Diabetic Retinopathy Study testing protocol at 17 weeks. RESULTS: At 17 weeks, visual acuity had improved from baseline by an average of 7.6 letters in the atropine group and 8.6 letters in the patching group. The mean difference between groups (patching - atropine) adjusted for baseline acuity was 1.2 letters (ends of complementary 1-sided 95% confidence intervals for noninferiority, -0.7, 3.1 letters). This difference met the prespecified definition for equivalence (confidence interval <5 letters). Visual acuity in the amblyopic eye was 20/25 or better in 15 participants in the atropine group (17%) and 20 in the patching group (24%; difference, 7%; 95% confidence interval, -3% to 17%). CONCLUSIONS: Treatment with atropine or patching led to similar degrees of improvement among 7- to 12-year-olds with moderate amblyopia. About 1 in 5 achieved visual acuity of 20/25 or better in the amblyopic eye. CLINICAL RELEVANCE: Atropine and patching achieve similar results among older children with unilateral amblyopia. TRIAL REGISTRATION: (clinicaltrials.gov) Identifier: NCT00315328.+http://www.ncbi.nlm.nih.gov/pubmed/19064841iScheiman, Mitchell M Hertle, Richard W Kraker, Raymond T Beck, Roy W Birch, Eileen E Felius, Joost Holmes, Jonathan M Kundart, James Morrison, David G Repka, Michael X Tamkins, Susanna M Pediatric Eye Disease Investigator Group EY011751/EY/NEI NIH HHS/United States U10 EY011751-09/EY/NEI NIH HHS/United States U10 EY011751-10/EY/NEI NIH HHS/United States U10 EY011751-11/EY/NEI NIH HHS/United States Comparative Study Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Archives of ophthalmology Arch Ophthalmol. 2008 Dec;126(12):1634-42.*1538-3601 (Electronic) 0003-9950 (Linking)284677419064841EJaeb Center for Health Research, Tampa, FL 33647, USA. pedig@jaeb.org1126/12/1634 [pii] 10.1001/archophthalmol.2008.107eng ||7Y|Liang, C. K. Ho, T. Y. Li, T. C. Hsu, W. M. Li, T. M. Lee, Y. C. Ho, W. J. Cheng, J. T. Tzeng, C. Y. Liu, I. T. Chang, S. L.2008A combined therapy using stimulating auricular acupoints enhances lower-level atropine eyedrops when used for myopia control in school-aged children evaluated by a pilot randomized controlled clinical trial305-10Complement Ther Med166 2008/11/26Acupressure Acupuncture Points Acupuncture, Ear/*methods Adolescent Atropine/*therapeutic use Child Combined Modality Therapy Eye/drug effects Humans Intraocular Pressure Myopia/*therapy Ophthalmic Solutions/*therapeutic use Pilot Projects Refraction, Ocular Visual AcuityDecOBJECTIVE: This study was designed to compare the reduction in myopia progression in patients treated with atropine eyedrops alone with patients treated with a combined treatment of atropine and stimulation of the auricular acupoints. METHODS: This study was a randomized single-blind clinical controlled trial. A total of 71 school-aged children with myopia, who fulfilled the eligibility criteria, were recruited. They were randomly assigned into three groups. These were 22 treated with the 0.25% atropine (0.25A) only, 23 treated with the 0.5% atropine (0.5A) only and 26 treated with 0.25% atropine together with stimulation of the auricular acupoints (0.25A+E). The differences in the post-treatment effects among these three groups were statistically assessed. The primary outcome parameter was myopia progression, which was defined as diopter change per year (D/Y) after cycloplegic refraction measurement. RESULTS: The mean myopia progression of the 0.25A group was 0.38+/-0.32 D/Y. No significant difference in mean myopia progression was found between the 0.5A (0.15+/-0.15 D/Y) and 0.25A+E (0.21+/-0.23 D/Y) groups. However, there was a markedly reduced myopia progression in the 0.25A+E group compared to the 0.25A group (p<0.05). Furthermore, there was no statistical difference among these three groups in axial length elongation (ALE) of eye during this stage of the investigation. CONCLUSIONS: This study demonstrates that there was efficacy in stimulating the auricular acupoints and this enhanced the action of 0.25% atropine as a means of myopia control. The result was an effect almost equal to that of 0.5% atropine alone. There is also a need that the ALE of the eye should be further investigated over a longer period using the combined therapy.+http://www.ncbi.nlm.nih.gov/pubmed/19028329ELiang, Chih-Kai Ho, Tin-Yun Li, Tsai-Chung Hsu, Wen-Ming Li, Te-Mao Lee, Yu-Chen Ho, Wai-Jane Cheng, Juei-Tang Tzeng, Chung-Yuh Liu, I-Ting Chang, Shih-Liang Randomized Controlled Trial Research Support, Non-U.S. Gov't Scotland Complementary therapies in medicine Complement Ther Med. 2008 Dec;16(6):305-10. Epub 2008 May 29.*1873-6963 (Electronic) 0965-2299 (Linking)19028329`Graduate Institute of Integrated Medicine, China Medical University, Taichung City, Taiwan, ROC.6S0965-2299(08)00042-3 [pii] 10.1016/j.ctim.2008.04.007eng t||7Z_Arnulf, F. Monika, S. Herwig, S. Monika, H. Johannes, P. D. Gregor, U. Alfred, G. Markus, P. R.2009Atropine for prevention of cardiac dysrhythmias in patients with hepatocellular carcinoma undergoing percutaneous ethanol instillation: a randomized, placebo-controlled, double-blind trial715-20 Liver Int295 2008/11/21rAdministration, Cutaneous Adult Aged Anti-Arrhythmia Agents/*pharmacology Arrhythmias, Cardiac/*prevention & control Atropine/*pharmacology Carcinoma, Hepatocellular/*drug therapy Double-Blind Method Ethanol/administration & dosage/*adverse effects/*therapeutic use Female Humans Liver Neoplasms/*drug therapy Male Middle Aged Statistics, Nonparametric Treatment OutcomeMayCINTRODUCTION: Percutaneous ethanol injection (PEI) is an established method in the treatment of hepatocellular carcinoma (HCC). During this procedure, severe cardiac bradyarrhythmias can occur. A preemptive injection of atropine is recommended by professional guidelines to prevent these dysrhythmias. METHODS: Patients scheduled for PEI were randomized 1:1 to receive 0.5 mg atropinehydrochloride or placebo in a double-blind randomized placebo-controlled trial. Patients were electrocardiogram monitored, which were then analysed by an experienced rhythmologist blinded to the treatment arm. RESULTS: Patients in 40 consecutive PEI sessions were included. During PEI, a significant reduction in the mean heart rate (>15%) was seen in 15% of patients in the placebo group (median, -37%; range, 15-41%) and in 25% of patients receiving atropine (median, -20%; range, 16-64%). There was no significant difference between both groups. During PEI, two patients (10%) in the placebo group developed a sinuatrial block (SAB). Four patients in the atropine group (20%) developed arrhythmias: three patients SAB, one of them with escape rhythm and one AV-bundle block. Blood ethanol levels post-PEI, amount of instilled ethanol, tumour size and location were not different between patients with or without dysrhythmias. CONCLUSION: In this randomized-controlled trial, a preprocedure atropine injection did not prevent the occurrence of bradyarrhythmias. Prophylactic use of atropine might not be effective and therefore cannot be recommended as a routine procedure. Clinicaltrials.gov-identifier: NCT00575523.+http://www.ncbi.nlm.nih.gov/pubmed/19018977UArnulf, Ferlitsch Monika, Schmid Herwig, Schmidinger Monika, Homoncik Johannes, Pleiner-Duxneuner Gregor, Ulbrich Alfred, Gangl Markus, Peck-Radosavljevic Randomized Controlled Trial England Liver international : official journal of the International Association for the Study of the Liver Liver Int. 2009 May;29(5):715-20. Epub 2008 Oct 27.*1478-3231 (Electronic) 1478-3223 (Linking)19018977]Department of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria..LIV1905 [pii] 10.1111/j.1478-3231.2008.01905.xeng |t7[Repka, M. X. Kraker, R. T. Beck, R. W. Holmes, J. M. Cotter, S. A. Birch, E. E. Astle, W. F. Chandler, D. L. Felius, J. Arnold, R. W. Tien, D. R. Glaser, S. R.2008iA randomized trial of atropine vs patching for treatment of moderate amblyopia: follow-up at age 10 years1039-44Arch Ophthalmol1268 2008/08/13?Amblyopia/physiopathology/*therapy Atropine/administration & dosage/*therapeutic use Child Child, Preschool Female Follow-Up Studies Humans Male Mydriatics/administration & dosage/*therapeutic use Refraction, Ocular/physiology *Sensory Deprivation Treatment Outcome Vision, Binocular/physiology Visual Acuity/physiologyAugOBJECTIVE: To determine the visual acuity outcome at age 10 years for children younger than 7 years when enrolled in a treatment trial for moderate amblyopia. METHODS: In a multicenter clinical trial, 419 children with amblyopia (visual acuity, 20/40-20/100) were randomized to patching or atropine eyedrops for 6 months. Two years after enrollment, a subgroup of 188 children entered long-term follow-up. Treatment after 6 months was at the discretion of the investigator; 89% of children were treated. MAIN OUTCOME MEASURE: Visual acuity at age 10 years with the electronic Early Treatment Diabetic Retinopathy Study test. APPLICATION TO CLINICAL PRACTICE: Patching and atropine eyedrops produce comparable improvement in visual acuity that is maintained through age 10 years. RESULTS: The mean amblyopic eye acuity, measured in 169 patients, at age 10 years was 0.17 logMAR (logarithm of the minimum angle of resolution) (approximately 20/32), and 46% of amblyopic eyes had an acuity of 20/25 or better. Age younger than 5 years at entry into the randomized trial was associated with a better visual acuity outcome (P < .001). Mean amblyopic and sound eye visual acuities at age 10 years were similar in the original treatment groups (P = .56 and P = .80, respectively). CONCLUSIONS: At age 10 years, the improvement of the amblyopic eye is maintained, although residual amblyopia is common after treatment initiated at age 3 years to younger than 7 years. The outcome is similar regardless of initial treatment with atropine or patching.+http://www.ncbi.nlm.nih.gov/pubmed/18695096UPediatric Eye Disease Investigator Group Repka, Michael X Kraker, Raymond T Beck, Roy W Holmes, Jonathan M Cotter, Susan A Birch, Eileen E Astle, William F Chandler, Danielle L Felius, Joost Arnold, Robert W Tien, D Robbins Glaser, Stephen R EY011751/EY/NEI NIH HHS/United States U10 EY011751-08/EY/NEI NIH HHS/United States U10 EY011751-09/EY/NEI NIH HHS/United States U10 EY011751-10/EY/NEI NIH HHS/United States Comparative Study Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural United States Archives of ophthalmology Arch Ophthalmol. 2008 Aug;126(8):1039-44.*1538-3601 (Electronic) 0003-9950 (Linking)261435118695096,126/8/1039 [pii] 10.1001/archopht.126.8.1039eng !||7\?Ponduri, S. Turnbull, N. Birnie, D. Ireland, A. J. Sandy, J. R.2007UDoes atropine sulphate improve orthodontic bond survival? A randomized clinical trial663-70Am J Orthod Dentofacial Orthop1325 2007/11/17Adolescent *Atropine *Dental Bonding Female Humans Kaplan-Meier Estimate Male *Orthodontic Appliances *Parasympatholytics Patient Acceptance of Health Care Premedication Questionnaires Salivation/drug effects Statistics, NonparametricNovINTRODUCTION: The antisialagogue atropine sulphate has been used for many years as an adjunct to orthodontic bonding to reduce moisture contamination. The aims of this study were to investigate the effect of atropine sulphate premedication on orthodontic bond failures and to evaluate the attitudes of patients and parents toward its use in orthodontics. METHODS: After ethics committee approval, 51 patients (mean age, 14 years 7 months) were enrolled in this clinical trial. They were randomized to receive 2 interventions, atropine sulphate premedication (600 microg) or no premedication (control) with a Battenburg design (split-mouth). Overall, 852 brackets and 362 molar tubes were bonded. Bond failure data were collected over a 12-month period and analyzed with Kaplan-Meier survival probabilities and the log rank and Wilcoxon tests. Patient-centered outcome measures included a questionnaire relating to treatment with antisialagogues. RESULTS: The results showed no statistically significant difference in the bond survival rates between the 2 interventions--antisialagogue premedication or no premedication (P >.05). From the questionnaire, 94.1% of the subjects said they took the atropine sulphate before the bond appointment. Approximately 76% of them thought that taking medication before placement of orthodontic appliances was an acceptable part of treatment. CONCLUSIONS: Although the use of a premedication to induce hypo-salivation before orthodontic bonding appears to be an acceptable procedure to most patients and their parents, we did not find a statistically significant effect on the observed bond failure rates. There is no evidence to support the routine use of atropine sulphate before orthodontic bonding.+http://www.ncbi.nlm.nih.gov/pubmed/18005841xPonduri, Sirisha Turnbull, Nick Birnie, David Ireland, Anthony J Sandy, Jonathan R Randomized Controlled Trial United States American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics Am J Orthod Dentofacial Orthop. 2007 Nov;132(5):663-70.*1097-6752 (Electronic) 0889-5406 (Linking)18005841QDepartment of Orthodontics, Queen Alexandra Hospital, Portsmouth, United Kingdom.7S0889-5406(07)00564-1 [pii] 10.1016/j.ajodo.2006.10.022eng||7]%Meyer, S. Gottschling, S. Gortner, L.2007Propofol compared with the morphine, atropine, and suxamethonium regimen as induction agents for neonatal endotracheal intubation: a randomized, controlled trial932-3; author reply 933 Pediatrics1204 2007/10/03[Atropine/*administration & dosage Blood Pressure/drug effects Child Dose-Response Relationship, Drug Drug Approval Drug Therapy, Combination Humans Hypnotics and Sedatives/*administration & dosage Infant Intubation, Intratracheal/*methods Morphine/*administration & dosage Propofol/*administration & dosage Succinylcholine/*administration & dosageOct+http://www.ncbi.nlm.nih.gov/pubmed/17908787Meyer, Sascha Gottschling, Sven Gortner, Ludwig Comment Letter United States Pediatrics Pediatrics. 2007 Oct;120(4):932-3; author reply 933.*1098-4275 (Electronic) 0031-4005 (Linking)17908787&120/4/932 [pii] 10.1542/peds.2007-2083eng ||7^IGhanta, S. Abdel-Latif, M. E. Lui, K. Ravindranathan, H. Awad, J. Oei, J.2007Propofol compared with the morphine, atropine, and suxamethonium regimen as induction agents for neonatal endotracheal intubation: a randomized, controlled triale1248-55 Pediatrics1196 2007/05/09}Atropine/*administration & dosage Blood Pressure/drug effects/physiology Drug Therapy, Combination Female Humans Hypnotics and Sedatives/*administration & dosage Infant, Newborn Intubation, Intratracheal/*methods Male Morphine/*administration & dosage Muscle Relaxation/drug effects/physiology Propofol/*administration & dosage Succinylcholine/*administration & dosage Time FactorsJun^OBJECTIVES: The purpose of this work was to compare the efficacy of propofol, a hypnotic agent, to the regimen of morphine, atropine, and suxamethonium as an induction agent for nonemergency neonatal endotracheal intubation. We hypothesized that propofol aids intubation by allowing the continuation of spontaneous breathing. PATIENTS AND METHODS: We conducted a randomized, open-label, controlled trial of infants who required nonemergency endotracheal intubation. Primary outcome was successful intubation confirmed by chest auscultation and clinical examination of the infant. RESULTS: Infants randomly assigned to propofol (n = 33) and the morphine, atropine, and suxamethonium regimen (n = 30) were comparable in median gestational age (27 vs 28 weeks), birth weight (1020 vs 1095 g), weight at intubation (1068 vs 1275 g), and age at intubation (4 vs 3 days). Sleep or muscle relaxation were achieved within 60 seconds in both groups, but time to achieve successful intubation was more than twice as fast with propofol (120 vs 260 seconds). Blood pressure and heart rates were not different, but intraprocedural oxygen saturations were significantly lower in infants on the morphine, atropine, and suxamethonium regimen (trough arterial oxygen saturation: 60% vs 80%). Nasal/oral trauma was less common, and recovery time was shorter (780 vs 1425 seconds) in the propofol group. No significant adverse effects were seen in either group. CONCLUSIONS: Propofol is more effective than the morphine, atropine, and suxamethonium regimen as an induction agent to facilitate neonatal nasal endotracheal intubation. Importantly, hypoxemia was less severe, probably because of the maintenance of spontaneous breathing. A controlled environment may have promoted the ease of intubation, resulting in less trauma. The shorter duration of action would be advantageous in a compromised infant.+http://www.ncbi.nlm.nih.gov/pubmed/17485450Ghanta, Satish Abdel-Latif, Mohamed E Lui, Kei Ravindranathan, Hari Awad, John Oei, Julee Comparative Study Randomized Controlled Trial United States Pediatrics Pediatrics. 2007 Jun;119(6):e1248-55. Epub 2007 May 7.*1098-4275 (Electronic) 0031-4005 (Linking)17485450oDepartment of Newborn Care, Royal Hospital for Women, Barker Street, Randwick, New South Wales 2031, Australia.+peds.2006-2708 [pii] 10.1542/peds.2006-2708eng ||7_FFader, M. Glickman, S. Haggar, V. Barton, R. Brooks, R. Malone-Lee, J.2007Intravesical atropine compared to oral oxybutynin for neurogenic detrusor overactivity: a double-blind, randomized crossover trial208-13; discussion 213J Urol1771 2006/12/13DAdministration, Intravesical Administration, Oral Adult Aged Atropine/*administration & dosage Cross-Over Studies Double-Blind Method Humans Mandelic Acids/*administration & dosage Middle Aged Muscarinic Antagonists/*administration & dosage Urinary Bladder, Neurogenic/*drug therapy Urinary Bladder, Overactive/*drug therapyJanPURPOSE: We tested the efficacy and side effect profiles of intravesical atropine compared to oxybutynin immediate release when used by individuals with multiple sclerosis. MATERIALS AND METHODS: We performed a study to determine the most effective dose of atropine. Eight participants used increasing doses of intravesical atropine during a 12-day period. Bladder diary data showed that the instillation of 6 mg atropine 4 times daily was most effective for increasing bladder capacity (voided/catheter volumes). We then did a randomized, double-blind crossover trial. Participants received 14 days of treatment with oral oxybutynin or with intravesical atropine, followed by 14 days of alternative treatment. Participants recorded a bladder diary and rated side effects and quality of life. The primary outcome variable was bladder capacity. RESULTS: A total of 57 participants with multiple sclerosis completed the study. Average change in bladder capacity was higher in the atropine arm. The mean +/- SD oxybutynin change was 55.5 +/- 67.2 ml, the mean atropine change was 79.6 +/- 89.6 ml and the mean difference between arms was 24.1 ml (95% CI -0.4, 49.7; p = 0.053). Changes in incontinence events and voiding frequency were not statistically different between the arms. Changes in total side effect and dry mouth scores were significantly better in the atropine treatment arm. CONCLUSIONS: Intravesical atropine was as effective as oxybutynin immediate release for increasing bladder capacity and it was probably better with less antimuscarinic side effects. We recommend that intravesical atropine should be made available to patients with neurogenic detrusor overactivity and voiding problems requiring intermittent catheterization as an alternative to oral therapy, which often has troublesome side effects.+http://www.ncbi.nlm.nih.gov/pubmed/17162046Fader, Mandy Glickman, Scott Haggar, Veronica Barton, Rachel Brooks, Rodney Malone-Lee, James Comparative Study Randomized Controlled Trial Research Support, Non-U.S. Gov't United States The Journal of urology J Urol. 2007 Jan;177(1):208-13; discussion 213.%0022-5347 (Print) 0022-5347 (Linking)17162046lContinence and Skin Technology Group, University of Southampton, Southampton, United Kingdom. mf@soton.ac.uk6S0022-5347(06)02160-4 [pii] 10.1016/j.juro.2006.08.099eng ||7`EDe Simone, G. G. Eisenchlas, J. H. Junin, M. Pereyra, F. Brizuela, R.2006:Atropine drops for drooling: a randomized controlled trial665-71 Palliat Med207 2006/10/25 Administration, Sublingual Aged Aged, 80 and over Atropine/*therapeutic use Cross-Over Studies Digestive System Neoplasms/*complications Double-Blind Method Female Humans Male Middle Aged Placebos/therapeutic use Sialorrhea/complications/*drug therapy Treatment OutcomeOctINTRODUCTION: Drooling occasionally occurs in cancer patients, impairing their quality of life. Recommended treatment includes the use of anticholinergic drugs, but there is a lack of scientific evidence supporting it; some recent reports tested the use of sublingual atropine, and further controlled studies have been recommended. OBJECTIVE: To evaluate the effectiveness of sublingual atropine for the relief of drooling when compared with a placebo, in a population of patients with upper digestive cancer at the Gastroenterology 'Bonorino Udaondo' Hospital. POPULATION AND METHODOLOGY: From March 2002 to March 2003, 22 consecutive patients were enrolled in a prospective, randomized, placebo-controlled, double-blind, cross-over trial (gender: M/F=14/8; median age=66, range: 4887 years). Patients were randomly allocated to receive atropine or placebo for 48 hours (phase 1), followed by a wash-out period of 48 hours, and final cross-over during the next 48 hours (phase 2). We evaluated the impact on sialorrhoea, choking, interference with daily and social activities, and global impact from drooling by visual analogue scales (VAS) at the beginning and end of each phase, as well as patients' choice at the end of the study. RESULTS: Mean score for sialorrhoea was 59.6 (SD=28.5) at baseline and 34.9 (SD=27.7) after 48 hours of receiving atropine; 62.1 (SD=27.6) at baseline and 40.7 (SD=30.5) after 48 hours of placebo. Analysis of variance (ANOVA) for repeated measures and two factors was not significant for either the variable sialorrhoea (P=0.58) or any of the secondary outcomes measured. No severe toxicity was reported. CONCLUSIONS: This study failed to demonstrate the effectiveness of atropine over placebo in this population; we provide further discussion of results.+http://www.ncbi.nlm.nih.gov/pubmed/17060265De Simone, Gustavo G Eisenchlas, Jorge H Junin, Marta Pereyra, Facundo Brizuela, Rafael Comparative Study Randomized Controlled Trial England Palliative medicine Palliat Med. 2006 Oct;20(7):665-71.%0269-2163 (Print) 0269-2163 (Linking)17060265[Palliative Care Service, Hospital Bonorino Udaondo and Pallium Latinoamerica, Buenos Aires.'20/7/665 [pii] 10.1177/0269216306071702eng `||7aCRoberts, K. D. Leone, T. A. Edwards, W. H. Rich, W. D. Finer, N. N.2006Premedication for nonemergent neonatal intubations: a randomized, controlled trial comparing atropine and fentanyl to atropine, fentanyl, and mivacurium1583-91 Pediatrics1184 2006/10/04Adjuvants, Anesthesia/*therapeutic use Anoxia/etiology/prevention & control Atropine/*therapeutic use Blood Pressure Drug Therapy, Combination Female Fentanyl/*therapeutic use Heart Rate Humans Infant, Newborn Intubation/adverse effects/*methods Isoquinolines/*therapeutic use Male Neuromuscular Nondepolarizing Agents/*therapeutic use Oxygen/blood Prospective Studies Treatment OutcomeOctOBJECTIVE: The purpose of this work was to investigate whether using a muscle relaxant would improve intubation conditions in infants, thereby decreasing the incidence and duration of hypoxia and time and number of attempts needed to successfully complete the intubation procedure. PATIENTS/METHODS: This was a prospective, randomized, controlled, 2-center trial. Infants requiring nonemergent intubation were randomly assigned to receive atropine and fentanyl or atropine, fentanyl, and mivacurium before intubation. Incidence and duration of hypoxia were determined at oxygen saturation thresholds of < or = 85%, < or = 75%, < or = 60%, and < or = 40%. Videotape was reviewed to determine the time and number of intubation attempts and duration of action of mivacurium. RESULTS: Analysis of 41 infants showed that incidence of oxygen saturation < or = 60% of any duration was significantly less in the mivacurium group (55% vs 24%). The incidence of saturation level of any duration < or = 85%, 75%, and 40%; cumulative time > or = 30 seconds; and time below the thresholds were not significantly different. Total procedure time (472 vs 144 seconds) and total laryngoscope time (148 vs 61 seconds) were shorter in the mivacurium group. Successful intubation was achieved in < or = 2 attempts significantly more often in the mivacurium group (35% vs 71%). CONCLUSIONS: Premedication with atropine, fentanyl, and mivacurium compared with atropine and fentanyl without a muscle relaxant decreases the time and number of attempts needed to successfully intubate while significantly reducing the incidence of severe desaturation. Premedication including a short-acting muscle relaxant should be considered for all nonemergent intubations in the NICU.+http://www.ncbi.nlm.nih.gov/pubmed/17015550Roberts, Kari D Leone, Tina A Edwards, William H Rich, Wade D Finer, Neil N Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't United States Pediatrics Pediatrics. 2006 Oct;118(4):1583-91.*1098-4275 (Electronic) 0031-4005 (Linking)17015550jDivision of Neonatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA. rober694@umn.edu'118/4/1583 [pii] 10.1542/peds.2006-0590eng S||7bRepka, M. X. Wallace, D. K. Beck, R. W. Kraker, R. T. Birch, E. E. Cotter, S. A. Donahue, S. Everett, D. F. Hertle, R. W. Holmes, J. M. Quinn, G. E. Scheiman, M. M. Weakley, D. R.2005xTwo-year follow-up of a 6-month randomized trial of atropine vs patching for treatment of moderate amblyopia in children149-57Arch Ophthalmol1232 2005/02/16Amblyopia/physiopathology/*therapy Atropine/*therapeutic use Child Female Follow-Up Studies Humans Male Mydriatics/*therapeutic use Ophthalmic Solutions *Sensory Deprivation Treatment Outcome Vision, Binocular/physiology Visual Acuity/physiologyFebOBJECTIVE: To compare patching and atropine sulfate as treatments for moderate amblyopia in children 18 months after completion of a 6-month randomized trial. METHODS: In a randomized, multicenter (47 sites) clinical trial, 419 children younger than 7 years with amblyopia (20/40 to 20/100 in the affected eye) were assigned to receive either patching or atropine eye drops for 6 months. Between 6 months and 2 years, treatment was at the discretion of the investigator. Main Outcome Measure Visual acuity in the amblyopic eye and sound eye after 2 years. RESULTS: At 2 years, visual acuity in the amblyopic eye improved from baseline a mean of 3.7 lines in the patching group and 3.6 lines in the atropine group. The difference in visual acuity between treatment groups was small: 0.01 logMAR (95% confidence interval, -0.02 to 0.04). In both treatment groups, the mean amblyopic eye acuity was approximately 20/32, 1.8 lines worse than the mean sound eye acuity, which was approximately 20/20. CONCLUSIONS: Atropine or patching for 6 months followed by best clinical care until 2 years produced similar improvement of moderate amblyopia in children between 3 and 7 years of age at enrollment. However, on average the amblyopic eye acuity was still approximately 2 lines worse than the sound eye.+http://www.ncbi.nlm.nih.gov/pubmed/15710809Repka, Michael X Wallace, David K Beck, Roy W Kraker, Raymond T Birch, Eileen E Cotter, Susan A Donahue, Sean Everett, Donald F Hertle, Richard W Holmes, Jonathan M Quinn, Graham E Scheiman, Mitchell M Weakley, David R Pediatric Eye Disease Investigator Group EY11751/EY/NEI NIH HHS/United States Clinical Trial Comparative Study Multicenter Study Randomized Controlled Trial Research Support, U.S. Gov't, P.H.S. United States Archives of ophthalmology Arch Ophthalmol. 2005 Feb;123(2):149-57.%0003-9950 (Print) 0003-9950 (Linking)15710809EJaeb Center for Health Research, Tampa, FL 33647, USA. pedig@jaeb.org*123/2/149 [pii] 10.1001/archopht.123.2.149eng ||7cRepka, M. X. Cotter, S. A. Beck, R. W. Kraker, R. T. Birch, E. E. Everett, D. F. Hertle, R. W. Holmes, J. M. Quinn, G. E. Sala, N. A. Scheiman, M. M. Stager, D. R., Sr. Wallace, D. K.2004WA randomized trial of atropine regimens for treatment of moderate amblyopia in children2076-85 Ophthalmology11111 2004/11/04 Amblyopia/*drug therapy Atropine/*administration & dosage/adverse effects Child Child, Preschool Female Follow-Up Studies Humans Male Mydriatics/*administration & dosage/adverse effects Ophthalmic Solutions/administration & dosage Prospective Studies Visual Acuity/drug effects/physiologyNovOBJECTIVE: To compare daily atropine to weekend atropine as prescribed treatments for moderate amblyopia in children younger than 7 years. DESIGN: Prospective, randomized multicenter clinical trial (30 sites). PARTICIPANTS: One hundred sixty-eight children younger than 7 years with amblyopia in the range of 20/40 to 20/80 associated with strabismus, anisometropia, or both. INTERVENTION: Randomization either to daily atropine or to weekend atropine for 4 months. Partial responders were continued on the randomized treatment until no further improvement was noted. MAIN OUTCOME MEASURE: Visual acuity (VA) in the amblyopic eye after 4 months. RESULTS: The improvement in VA of the amblyopic eye from baseline to 4 months averaged 2.3 lines in each group. The VA of the amblyopic eye at study completion was either (1) at least 20/25 or (2) better than or equal to that of the sound eye in 39 children (47%) in the daily group and 45 children (53%) in the weekend group. The VA of the sound eye at the end of follow-up was reduced by 2 lines in one patient in each group. Stereoacuity outcomes were similar in the 2 groups. CONCLUSIONS: Weekend atropine provides an improvement in VA of a magnitude similar to that of the improvement provided by daily atropine in treating moderate amblyopia in children 3 to 7 years old. This article contains additional online-only material available at http://www.ophsource.com/periodicals/ophtha.+http://www.ncbi.nlm.nih.gov/pubmed/15522375Repka, Michael X Cotter, Susan A Beck, Roy W Kraker, Raymond T Birch, Eileen E Everett, Donald F Hertle, Richard W Holmes, Jonathan M Quinn, Graham E Sala, Nicholas A Scheiman, Mitchell M Stager, David R Sr Wallace, David K Pediatric Eye Disease Investigator Group EY11751/EY/NEI NIH HHS/United States Clinical Trial Comparative Study Multicenter Study Randomized Controlled Trial Research Support, U.S. Gov't, P.H.S. United States Ophthalmology Ophthalmology. 2004 Nov;111(11):2076-85.*1549-4713 (Electronic) 0161-6420 (Linking)15522375eJaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa, FL 33647, USA. rbeck@jaeb.org8S0161-6420(04)00930-3 [pii] 10.1016/j.ophtha.2004.04.032eng ||7d4Mader, T. J. Smithline, H. A. Durkin, L. Scriver, G.2003zA randomized controlled trial of intravenous aminophylline for atropine-resistant out-of-hospital asystolic cardiac arrest192-7Acad Emerg Med103 2003/03/05Advanced Cardiac Life Support Aged Aminophylline/pharmacology/*therapeutic use Blood Circulation/*drug effects Cardiotonic Agents/pharmacology/*therapeutic use Double-Blind Method Female Heart Arrest/*drug therapy/*physiopathology Humans Male Middle Aged Odds Ratio Prospective StudiesMarOBJECTIVES: Myocardial ischemia, during cardiopulmonary arrest, can lead to atropine-resistant bradyasystole from interstitial accumulation of endogenous adenosine. Aminophylline is a nonspecific adenosine receptor antagonist capable of reversing ischemia-induced bradyasystole in a variety of settings. The hypothesis of this study was that aminophylline improves the rate of return of spontaneous circulation (ROSC) in atropine-resistant asystolic out-of-hospital cardiac arrest when used early in the resuscitation effort. METHODS: This was a prospective, randomized, double-blinded, placebo-controlled trial set in an urban emergency medical services system serving a population of 250,000. All non-pregnant, normothermic adults suffering nontraumatic out-of-hospital cardiac arrest (February 1999 to August 2000) with asystole were eligible. Patients remaining in asystole after initial doses of epinephrine and atropine received either aminophylline 250 mg or matching placebo as a bolus injection through a peripheral intravenous line. All other aspects of the attempted resuscitation proceeded in accordance with standard Advanced Cardiac Life Support (ACLS) guidelines. A sample size of 102 patients was calculated to yield a power of 80% to show an absolute improvement of 25% in ROSC. The aminophylline and control groups were compared by calculating 95% confidence intervals (95% CIs) and the data were modeled using logistic regression. RESULTS: The investigators enrolled 112 consecutive patients. One subject was dropped prior to analysis because of missing data. Data for 111 patients were analyzed on an intention-to-treat basis. Baseline characteristics were similar for the two groups. Comparing the control and aminophylline groups, ROSC was achieved in 15.6% (95% CI = 6% to 29%) and 22.7% (95% CI = 13% to 35%), while reversal of asystole occurred in 26.7% (95% CI = 15% to 42%) and 40.9% (95% CI = 29% to 54%), respectively. Group allocation had an odds ratio of 1.8 (95% CI = 0.6 to 5.3) for ROSC. Witnessed arrest was an independent predictor of outcome with an odds ratio of 3.8 (95% CI = 1.3 to 11.2). CONCLUSIONS: Addition of aminophylline appears to be a promising new intervention in the ACLS treatment of atropine-resistant asystolic out-of-hospital cardiac arrest.+http://www.ncbi.nlm.nih.gov/pubmed/12615581 Mader, Timothy J Smithline, Howard A Durkin, Lou Scriver, Geoffrey Clinical Trial Randomized Controlled Trial Research Support, Non-U.S. Gov't United States Academic emergency medicine : official journal of the Society for Academic Emergency Medicine Acad Emerg Med. 2003 Mar;10(3):192-7.%1069-6563 (Print) 1069-6563 (Linking)12615581sDepartment of Emergency Medicine, Tufts University School of Medicine, Boston, MA 01199, USA. timothy.mader@bhs.orgeng \||7e2002[A randomized trial of atropine vs. patching for treatment of moderate amblyopia in children268-78Arch Ophthalmol1203 2002/03/15Amblyopia/*therapy Atropine/*therapeutic use Child Child, Preschool Female Follow-Up Studies Humans Male Mydriatics/*therapeutic use Ophthalmic Solutions Patient Compliance *Sensory Deprivation Treatment Outcome Visual Acuity/physiologyMarOBJECTIVE: To compare patching and atropine as treatments for moderate amblyopia in children younger than 7 years. METHODS: In a randomized clinical trial, 419 children younger than 7 years with amblyopia and visual acuity in the range of 20/40 to 20/100 were assigned to receive either patching or atropine at 47 clinical sites. MAIN OUTCOME MEASURE: Visual acuity in the amblyopic eye and sound eye after 6 months. RESULTS: Visual acuity in the amblyopic eye improved in both groups (improvement from baseline to 6 months was 3.16 lines in the patching group and 2.84 lines in the atropine group). Improvement was initially faster in the patching group, but after 6 months, the difference in visual acuity between treatment groups was small and clinically inconsequential (mean difference at 6 months, 0.034 logMAR units; 95% confidence interval, 0.005-0.064 logMAR units). The 6-month acuity was 20/30 or better in the amblyopic eye and/or improved from baseline by 3 or more lines in 79% of the patching group and 74% of the atropine group. Both treatments were well tolerated, although atropine had a slightly higher degree of acceptability on a parental questionnaire. More patients in the atropine group than in the patching group had reduced acuity in the sound eye at 6 months, but this did not persist with further follow-up. CONCLUSION: Atropine and patching produce improvement of similar magnitude, and both are appropriate modalities for the initial treatment of moderate amblyopia in children aged 3 to less than 7 years.+http://www.ncbi.nlm.nih.gov/pubmed/11879129Pediatric Eye Disease Investigator Group. EY11751/EY/NEI NIH HHS/United States Clinical Trial Comparative Study Multicenter Study Randomized Controlled Trial Research Support, U.S. Gov't, P.H.S. United States Archives of ophthalmology Arch Ophthalmol. 2002 Mar;120(3):268-78.%0003-9950 (Print) 0003-9950 (Linking)118791291Jaeb Center for Health Research, Tampa, Fla. USA.ecs10241 [pii]eng\||7f Gignac, E.1990Succinylcholine and atropine for premedication of the newborn infant before nasotracheal intubation: randomized, controlled trial1307-8 Crit Care Med1811 1990/11/01Atropine/*administration & dosage Humans Infant, Newborn Intubation, Intratracheal/*methods Nose Succinylcholine/*administration & dosageNov*http://www.ncbi.nlm.nih.gov/pubmed/2225909Gignac, E Clinical Trial Comment Letter Randomized Controlled Trial United states Critical care medicine Crit Care Med. 1990 Nov;18(11):1307-8.%0090-3493 (Print) 0090-3493 (Linking)2225909eng||7g,Barrington, K. J. Finer, N. N. Etches, P. C.1989Succinylcholine and atropine for premedication of the newborn infant before nasotracheal intubation: a randomized, controlled trial1293-6 Crit Care Med1712 1989/12/01Atropine/*administration & dosage Blood Gas Monitoring, Transcutaneous Blood Pressure/drug effects Cerebrovascular Circulation/drug effects Heart Rate/drug effects Hemodynamics/*drug effects Humans Infant, Newborn Intracranial Pressure/drug effects *Intubation, Intratracheal Randomized Controlled Trials as Topic Respiratory Insufficiency/physiopathology/*therapy Succinylcholine/*administration & dosageDecTwenty preterm newborn infants were randomized to receive either atropine alone (20 micrograms/kg) or atropine plus succinylcholine (2 mg/kg) before nasotracheal intubation. Heart rate, BP, transcutaneous PO2, and intracranial pressure were monitored continuously before, during, and after intubation. No infants developed bradycardia or hypoxia. Intracranial hypertension developed during intubation in the infants receiving atropine alone, but was prevented by premedication with succinylcholine and atropine (p less than .01). A 41% increase in systemic BP occurred immediately after the administration of succinylcholine (p less than .01). BP increased during intubation in both groups, and the overall peak BP was not significantly different between the groups. Intubation was significantly shorter in the infants receiving succinylcholine. Premedication with succinylcholine and atropine will facilitate intubation of neonates, and ameliorate the adverse physiologic consequences of this procedure.*http://www.ncbi.nlm.nih.gov/pubmed/2686934Barrington, K J Finer, N N Etches, P C Clinical Trial Randomized Controlled Trial United states Critical care medicine Crit Care Med. 1989 Dec;17(12):1293-6.%0090-3493 (Print) 0090-3493 (Linking)2686934MDivision of Newborn Medicine, Royal Alexandra Hospital, Edmonton, AB, Canada.eng||7hSchwartz, S. E. Fazio, T. L.1979qPre-endoscopic medication. A randomized double-blind trial of atropine and meperidine as a supplement to diazepam747-51Scand J Gastroenterol146 1979/01/01 Adult Aged Atropine/*therapeutic use Benzocaine/therapeutic use Clinical Trials as Topic Diazepam/*therapeutic use Double-Blind Method Female Fiber Optic Technology *Gastroscopy Humans Injections, Intramuscular Male Meperidine/*therapeutic use Middle Aged *Premedication Random AllocationThe effects of an intramuscular injection of atropine (0.6 mg) and meperidine (1 mg/kg body weight) 30 min before topical benzocaine and intravenous diazepam administration were compared with those of a control group that received only benzocaine and intravenous diazepam in a randomized double-blind controlled trial of premedication for upper gastrointestinal endoscopy in 100 consecutive patients. Atropine and meperidine decreased the amount of salivation and gastric secretion (p less than 0.001 and p less than 0.001, respectively) and increased the period of sedation (p less than 0.001). The patients' and examiners' evaluation of the procedure was the same with either premedication regimen. Neither regimen affected the success rate of the endoscopy. Regardless of the regimen used, every patient who underwent endoscopy stated that they would consent to another examination, if necessary. Patients judged before endoscopy to be most apprehensive tolerated the procedure least, and those judged to be least apprehensive tolerated the procedure best, irrespective of premedication. The addition of meperidine and atropine to a premedication regimen of diazepam and topical benzocaine does not appear to be beneficial.)http://www.ncbi.nlm.nih.gov/pubmed/394300Schwartz, S E Fazio, T L Clinical Trial Comparative Study Randomized Controlled Trial Norway Scandinavian journal of gastroenterology Scand J Gastroenterol. 1979;14(6):747-51.%0036-5521 (Print) 0036-5521 (Linking)394300eng4||7i2011RRandomized trial to evaluate combined patching and atropine for residual amblyopia960-2Arch Ophthalmol1297 2011/07/13Jul+http://www.ncbi.nlm.nih.gov/pubmed/21746992Pediatric Eye Disease Investigator Group (PEDIG) Writing Committee United States Archives of ophthalmology Arch Ophthalmol. 2011 Jul;129(7):960-2.*1538-3601 (Electronic) 0003-9950 (Linking)21746992`c/o Jaeb Center for Health Research, 15310 Amberly Dr, Ste 350, Tampa, FL 33647. pedig@jaeb.org./129/7/960 [pii] 10.1001/archophthalmol.2011.174eng ||7jqLam, D. S. Zhao, J. Chen, L. J. Wang, Y. Zheng, C. Lin, Q. Rao, S. K. Fan, D. S. Zhang, M. Leung, P. C. Ritch, R.2011Adjunctive effect of acupuncture to refractive correction on anisometropic amblyopia one-year results of a randomized crossover trial1501-11 Ophthalmology1188 2011/04/05AugOBJECTIVES: To evaluate the safety and adjunctive effect of acupuncture added to refractive correction for anisometropic amblyopia in younger children. DESIGN: Prospective, randomized, controlled, crossover trial. PARTICIPANTS: We included 83 children aged 3 to <7 years with untreated anisometropic amblyopia and baseline best-corrected visual acuity (BCVA) of 20/40 to 20/200 in the amblyopic eye. METHODS: Participants were randomized to receive spectacles alone (group 1; n = 42) or spectacles + acupuncture (group 2; n = 41) for 15 weeks, and were then crossed over to receive the other regimen for another 15 weeks. The BCVA in both eyes was measured at baseline and every 5 (+/-1) weeks for the initial 45 weeks and at 60 (+/-1) weeks. MAIN OUTCOME MEASURES: BCVA in the amblyopic eye at 15, 30, and 60 weeks. RESULTS: The mean baseline BCVA in the amblyopic eye was 0.50 and 0.49 logarithm of the minimum angle of resolution (logMAR) in groups 1 and 2, respectively. After 15 weeks of treatment, the BCVA had improved by a mean of 2.2 lines in group 1 and 2.9 lines in group 2. The mean difference in BCVA between groups was 0.77 lines (95% confidence interval (CI), 0.29-1.3; P = 0.0020) with baseline adjustment. BCVA of 1 line of VA decrease to 60 weeks. Acupuncture was well-tolerated by all children, and no severe adverse effect was encountered. CONCLUSIONS: Acupuncture is a potentially useful complementary treatment modality that may provide sustainable adjunctive effect to refractive correction for anisometropic amblyopia in young children. Further large-scale studies seem warranted. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.+http://www.ncbi.nlm.nih.gov/pubmed/21459451Lam, Dennis S C Zhao, Jianhao Chen, Li Jia Wang, Yunxiu Zheng, Chongren Lin, Qiaoer Rao, Srinivas K Fan, Dorothy S P Zhang, Mingzhi Leung, Ping Chung Ritch, Robert United States Ophthalmology Ophthalmology. 2011 Aug;118(8):1501-11. Epub 2011 Apr 3.*1549-4713 (Electronic) 0161-6420 (Linking)214594513Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong, China; Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou, China; Institute of Chinese Medicine, the Chinese University of Hong Kong, Hong Kong, China.8S0161-6420(11)00044-3 [pii] 10.1016/j.ophtha.2011.01.017eng D||7kqZhao, J. Lam, D. S. Chen, L. J. Wang, Y. Zheng, C. Lin, Q. Rao, S. K. Fan, D. S. Zhang, M. Leung, P. C. Ritch, R.2010qRandomized controlled trial of patching vs acupuncture for anisometropic amblyopia in children aged 7 to 12 years1510-7Arch Ophthalmol12812 2010/12/15*Acupuncture Therapy Amblyopia/physiopathology/*therapy Child Eyeglasses Female Follow-Up Studies Humans Male *Occlusive Dressings Treatment Outcome Visual Acuity/physiologyDecOBJECTIVE: To compare the effectiveness of 2-hour daily patching with the effectiveness of acupuncture in treating anisometropic amblyopia in children aged 7 to 12 years who have worn optimal spectacles for at least 16 weeks. METHODS: In a single-center randomized controlled trial, 88 eligible children with an amblyopic eye who had a best spectacle-corrected visual acuity (BSCVA) of 0.3 to 0.8 logMAR at baseline were randomly assigned to receive 2 hours of patching of the sound eye daily or 5 sessions of acupuncture weekly. All participants in our study received constant optical correction, plus 1 hour of near-vision activities daily, and were followed up at weeks 5, 10, 15, and 25. The main outcome measure was BSCVA in the amblyopic eye at 15 weeks. RESULTS: The mean BSCVA of the amblyopic eye at 15 weeks improved from baseline by 1.83 and 2.27 lines in the patching and acupuncture groups, respectively. After baseline adjustment, the mean difference of BSCVA between the 2 groups was 0.049 logMAR (95% confidence interval, 0.005-0.092; P = .03), meeting the definition of equivalence (difference within 1 line). The BSCVA had improved by 2 lines or more in 28 (66.7%) and 31 (75.6%) eyes in the patching and acupuncture groups, respectively. Amblyopia was resolved in 7 (16.7%) and 17 (41.5%) eyes in the patching and acupuncture groups, respectively. CONCLUSION: Acupuncture produced equivalent treatment effect for anisometropic amblyopia, compared with patching, and was statistically superior. Further studies are warranted to investigate its value in the treatment of amblyopia. CLINICAL RELEVANCE: Acupuncture could potentially become an alternative treatment to occlusion therapy for amblyopia. TRIAL REGISTRATION: Centers for Clinical Trials Registry Identifier: CUHK_CCT00248.+http://www.ncbi.nlm.nih.gov/pubmed/21149771DZhao, Jianhao Lam, Dennis S C Chen, Li Jia Wang, Yunxiu Zheng, Chongren Lin, Qiaoer Rao, Srinivas K Fan, Dorothy S P Zhang, Mingzhi Leung, Ping Chung Ritch, Robert Comparative Study Randomized Controlled Trial Research Support, Non-U.S. Gov't United States Archives of ophthalmology Arch Ophthalmol. 2010 Dec;128(12):1510-7.*1538-3601 (Electronic) 0003-9950 (Linking)21149771lJoint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, China.1128/12/1510 [pii] 10.1001/archophthalmol.2010.306eng ||7leWall, T. C. Marsh-Tootle, W. L. Crenshaw, K. Person, S. D. Datla, R. Kristofco, R. E. Hartmann, E. E.2011Design of a randomized clinical trial to improve rates of amblyopia detection in preschool aged children in primary care settings204-14Contemp Clin Trials322 2010/10/27zAmblyopia/*diagnosis Child, Preschool Education, Medical, Continuing/methods Female Humans Internet Male Mass Screening/methods/statistics & numerical data Middle Aged Outcome Assessment (Health Care) Patient Selection Physicians, Primary Care/education Primary Health Care/*methods Random Allocation Randomized Controlled Trials as Topic/*methods Vision Tests/methods/standardsMarPURPOSE: To present the design of a cluster randomized controlled trial (cRCT) to evaluate the effectiveness of a web-based intervention for improving provider knowledge about strabismus and amblyopia (S/A) and preschool vision screening (PVS), increase PVS rates, and improve rates of S/A diagnoses made by eye specialists. This is the first cRCT targeting amblyopia prevention. METHODS: Participants were Medicaid providers in AL, SC, or IL who had Internet access and had filed at least 8 claims for well child visits (WCV) for children ages 3 or 4 years old during a 12-month period before enrollment. Randomization to the Intervention (vision) or Control (blood pressure) arm occurred at the cluster level, defined as the provider (or group of providers) and his/her patients seen for WCVs. RESULTS: 65 Intervention providers (IPs) with 3547 children aged 3 or 4 years, and 71 Control providers (CPs) with 5053 children enrolled. The study will report measures of knowledge and self-reported vision screening behaviors from web-based data. The primary outcomes will be rates of PVS among PCPs, and rates of diagnosis of S/A by eye specialists among the children belonging to Control and Intervention practices. CONCLUSIONS: We had the same difficulty recruiting PCPs as reported by others. Baseline rates of PVS were low (14.1%), as were rates that S/A were diagnosed by eye providers (1.4%). Our data show a need to improve both primary outcome measures.+http://www.ncbi.nlm.nih.gov/pubmed/20974292LWall, Terry C Marsh-Tootle, Wendy L Crenshaw, Katie Person, Sharina D Datla, Raju Kristofco, Robert E Hartmann, E Eugenie R01EY015893/EY/NEI NIH HHS/United States Randomized Controlled Trial Research Support, N.I.H., Extramural United States Contemporary clinical trials Contemp Clin Trials. 2011 Mar;32(2):204-14. Epub 2010 Oct 23.*1559-2030 (Electronic) 1551-7144 (Linking)20974292FUniversity of Alabama at Birmingham, United States. twall@peds.uab.edu5S1551-7144(10)00202-8 [pii] 10.1016/j.cct.2010.10.009eng G|t7mRutstein, R. P. Quinn, G. E. Lazar, E. L. Beck, R. W. Bonsall, D. J. Cotter, S. A. Crouch, E. R. Holmes, J. M. Hoover, D. L. Leske, D. A. Lorenzana, I. J. Repka, M. X. Suh, D. W.2010oA randomized trial comparing Bangerter filters and patching for the treatment of moderate amblyopia in children 998-1004 e6 Ophthalmology1175 2010/02/19Amblyopia/physiopathology/*therapy Child Child, Preschool *Eyeglasses Female Humans Male *Occlusive Dressings *Sensory Deprivation Treatment Outcome Visual Acuity/*physiologyMayOBJECTIVE: To determine whether visual acuity improvement with Bangerter filters is similar to improvement with patching as initial therapy for children with moderate amblyopia. DESIGN: Randomized, clinical trial. PARTICIPANTS: We enrolled 186 children, 3 to <10 years old, with moderate amblyopia (20/40-20/80). METHODS: Children were randomly assigned to receive either daily patching or to use a Bangerter filter on the spectacle lens in front of the fellow eye. Study visits were scheduled at 6, 12, 18, and 24 weeks. MAIN OUTCOME MEASURES: Visual acuity in amblyopic eyes at 24 weeks. RESULTS: At 24 weeks, amblyopic eye improvement averaged 1.9 lines in the Bangerter group and 2.3 lines in the patching group (difference in mean visual acuities between groups adjusted for baseline acuity = 0.38 line). The upper limit of a 1-sided 95% confidence interval was 0.76 line, which slightly exceeded a prespecified noninferiority limit of <0.75 line. Similar percentages of subjects in each group improved > or =3 lines (Bangerter group 38% vs patching group 35%; P = 0.61) or had > or =20/25 amblyopic eye acuity (36% vs 31%, respectively; P = 0.86). There was a lower treatment burden in the Bangerter group as measured with the Amblyopia Treatment Index. With Bangerter filters, neither a fixation switch to the amblyopic eye nor induced blurring in the fellow eye to worse than that of the amblyopic eye was required for visual acuity improvement. CONCLUSIONS: Because the average difference in visual acuity improvement between Bangerter filters and patching was less than half a line, and there was lower burden of treatment on the child and family, Bangerter filter treatment is a reasonable option to consider for initial treatment of moderate amblyopia.+http://www.ncbi.nlm.nih.gov/pubmed/20163869OPediatric Eye Disease Investigator Group Writing Committee Rutstein, Robert P Quinn, Graham E Lazar, Elizabeth L Beck, Roy W Bonsall, Dean J Cotter, Susan A Crouch, Eric R Holmes, Jonathan M Hoover, Darren L Leske, David A Lorenzana, Ingryd J Repka, Michael X Suh, Donny W EY011751/EY/NEI NIH HHS/United States U10 EY011751-11/EY/NEI NIH HHS/United States U10 EY011751-12/EY/NEI NIH HHS/United States Comparative Study Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural United States Ophthalmology Ophthalmology. 2010 May;117(5):998-1004.e6. Epub 2010 Feb 16.*1549-4713 (Electronic) 0161-6420 (Linking)2864338201638695Jaeb Center for Health Research, Tampa, FL 33647, USA8S0161-6420(09)01185-3 [pii] 10.1016/j.ophtha.2009.10.014eng ?|t7n2009`Pharmacological plus optical penalization treatment for amblyopia: results of a randomized trial22-30Arch Ophthalmol1271 2009/01/14"Amblyopia/physiopathology/*therapy Atropine/*administration & dosage Child Child, Preschool Combined Modality Therapy *Eyeglasses Female Follow-Up Studies Humans Male Mydriatics/*administration & dosage Ophthalmic Solutions/administration & dosage Treatment Outcome Visual Acuity/physiologyJan7OBJECTIVE: To compare weekend atropine sulfate use augmented by a plano lens for the sound eye with weekend atropine use alone for moderate amblyopia in children aged 3 years to younger than 7 years. METHODS: In a multicenter clinical trial, 180 children with moderate amblyopia (visual acuities of 20/40-20/100) were randomized to weekend atropine use augmented by a plano lens or weekend atropine use alone. MAIN OUTCOME MEASURE: Masked assessment of amblyopic eye visual acuity using the Amblyopia Treatment Study HOTV testing protocol at 18 weeks. RESULTS: At 18 weeks, amblyopic eye improvement averaged 2.8 lines in the group that received atropine plus a plano lens and 2.4 lines in the group that received atropine alone (mean difference between groups adjusted for baseline acuity, 0.3 line; 95% confidence interval, -0.2 to 0.8 line). Amblyopic eye visual acuity was 20/25 or better in 24 patients (29%) in the group that received atropine only and 35 patients (40%) in the group that received atropine plus a plano lens (P = .03). More patients in the group that received atropine plus a plano lens had reduced sound eye visual acuity at 18 weeks; however, there were no cases of persistent reverse amblyopia. CONCLUSIONS: As an initial treatment for moderate amblyopia, the augmentation of weekend atropine use with a plano lens does not substantially improve amblyopic eye visual acuity when compared with weekend atropine use alone. Application to Clinical Practice Treatment of children with unilateral amblyopia. Trial Registration clinicaltrials.org Identifier: NCT00315302.+http://www.ncbi.nlm.nih.gov/pubmed/19139333Pediatric Eye Disease Investigator Group EY011751/EY/NEI NIH HHS/United States U10 EY011751-09/EY/NEI NIH HHS/United States U10 EY011751-10/EY/NEI NIH HHS/United States U10 EY011751-11/EY/NEI NIH HHS/United States Comparative Study Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural United States Archives of ophthalmology Arch Ophthalmol. 2009 Jan;127(1):22-30.*1538-3601 (Electronic) 0003-9950 (Linking)271310719139333.127/1/22 [pii] 10.1001/archophthalmol.2008.520eng |t7oScheiman, M. M. Hertle, R. W. Kraker, R. T. Beck, R. W. Birch, E. E. Felius, J. Holmes, J. M. Kundart, J. Morrison, D. G. Repka, M. X. Tamkins, S. M.2008ZPatching vs atropine to treat amblyopia in children aged 7 to 12 years: a randomized trial1634-42Arch Ophthalmol12612 2008/12/10Amblyopia/drug therapy/physiopathology/*therapy Atropine/*therapeutic use Child Female Humans Male Mydriatics/*therapeutic use Ophthalmic Solutions/therapeutic use *Sensory Deprivation Treatment Outcome Vision, Binocular/physiology Visual Acuity/physiologyDecOBJECTIVE: To compare patching with atropine eyedrops in the treatment of moderate amblyopia (visual acuity, 20/40-20/100) in children aged 7 to 12 years. METHODS: In a randomized, multicenter clinical trial, 193 children with amblyopia were assigned to receive weekend atropine or patching of the sound eye 2 hours per day. Main Outcome Measure Masked assessment of visual acuity in the amblyopic eye using the electronic Early Treatment Diabetic Retinopathy Study testing protocol at 17 weeks. RESULTS: At 17 weeks, visual acuity had improved from baseline by an average of 7.6 letters in the atropine group and 8.6 letters in the patching group. The mean difference between groups (patching - atropine) adjusted for baseline acuity was 1.2 letters (ends of complementary 1-sided 95% confidence intervals for noninferiority, -0.7, 3.1 letters). This difference met the prespecified definition for equivalence (confidence interval <5 letters). Visual acuity in the amblyopic eye was 20/25 or better in 15 participants in the atropine group (17%) and 20 in the patching group (24%; difference, 7%; 95% confidence interval, -3% to 17%). CONCLUSIONS: Treatment with atropine or patching led to similar degrees of improvement among 7- to 12-year-olds with moderate amblyopia. About 1 in 5 achieved visual acuity of 20/25 or better in the amblyopic eye. CLINICAL RELEVANCE: Atropine and patching achieve similar results among older children with unilateral amblyopia. TRIAL REGISTRATION: (clinicaltrials.gov) Identifier: NCT00315328.+http://www.ncbi.nlm.nih.gov/pubmed/19064841iScheiman, Mitchell M Hertle, Richard W Kraker, Raymond T Beck, Roy W Birch, Eileen E Felius, Joost Holmes, Jonathan M Kundart, James Morrison, David G Repka, Michael X Tamkins, Susanna M Pediatric Eye Disease Investigator Group EY011751/EY/NEI NIH HHS/United States U10 EY011751-09/EY/NEI NIH HHS/United States U10 EY011751-10/EY/NEI NIH HHS/United States U10 EY011751-11/EY/NEI NIH HHS/United States Comparative Study Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Archives of ophthalmology Arch Ophthalmol. 2008 Dec;126(12):1634-42.*1538-3601 (Electronic) 0003-9950 (Linking)284677419064841EJaeb Center for Health Research, Tampa, FL 33647, USA. pedig@jaeb.org1126/12/1634 [pii] 10.1001/archophthalmol.2008.107eng R|t7p2008zA randomized trial of near versus distance activities while patching for amblyopia in children aged 3 to less than 7 years2071-8 Ophthalmology11511 2008/09/16*Activities of Daily Living Amblyopia/physiopathology/*therapy Bandages Child Child, Preschool Depth Perception/physiology Distance Perception/*physiology Female Humans Male *Sensory Deprivation Visual Acuity/*physiologyNovWPURPOSE: To determine whether performing near activities while patching for amblyopia enhances improvement in visual acuity. DESIGN: Randomized clinical trial. PARTICIPANTS: A total of 425 children, aged 3 to <7 years, with amblyopia (20/40-20/400) that was caused by anisometropia, strabismus, or both, and that persisted after treatment with spectacles. METHODS: Children were randomized to 2 hours of patching per day with near activities or 2 hours of patching per day with distance activities. Instruction sheets describing common near and distance activities were given to the parents. Study visits were scheduled at 2, 5, 8, and 17 weeks. In weeks without a visit, weekly telephone calls were made to the parent to monitor and encourage compliance during the first 8 weeks. MAIN OUTCOME MEASURE: Masked assessment of visual acuity by isolated crowded HOTV optotypes at 8 weeks. RESULTS: At 8 weeks, improvement in amblyopic eye visual acuity averaged 2.6 lines in the distance activities group and 2.5 lines in the near activities group (mean difference in acuity between groups, adjusted for baseline acuity, 0.0 lines 95% confidence interval, -0.3 to 0.3). The 2 groups also appeared statistically similar at the 2-, 5-, and 17-week visits. At the 17-week examination, children with severe amblyopia improved a mean of 3.6 lines with 2 hours of daily patching. CONCLUSIONS: Performing common near activities does not improve visual acuity outcome when treating anisometropic, strabismic, or combined amblyopia with 2 hours of daily patching. Children with severe amblyopia may respond to 2 hours of daily patching.+http://www.ncbi.nlm.nih.gov/pubmed/18789533Pediatric Eye Disease Investigator Group EY011751/EY/NEI NIH HHS/United States U10 EY011751-09/EY/NEI NIH HHS/United States U10 EY011751-10/EY/NEI NIH HHS/United States U10 EY011751-11/EY/NEI NIH HHS/United States Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Ophthalmology Ophthalmology. 2008 Nov;115(11):2071-8. Epub 2008 Sep 11.*1549-4713 (Electronic) 0161-6420 (Linking)2615691187895338S0161-6420(08)00643-X [pii] 10.1016/j.ophtha.2008.06.031eng |t7qRepka, M. X. Kraker, R. T. Beck, R. W. Holmes, J. M. Cotter, S. A. Birch, E. E. Astle, W. F. Chandler, D. L. Felius, J. Arnold, R. W. Tien, D. R. Glaser, S. R.2008iA randomized trial of atropine vs patching for treatment of moderate amblyopia: follow-up at age 10 years1039-44Arch Ophthalmol1268 2008/08/13?Amblyopia/physiopathology/*therapy Atropine/administration & dosage/*therapeutic use Child Child, Preschool Female Follow-Up Studies Humans Male Mydriatics/administration & dosage/*therapeutic use Refraction, Ocular/physiology *Sensory Deprivation Treatment Outcome Vision, Binocular/physiology Visual Acuity/physiologyAugOBJECTIVE: To determine the visual acuity outcome at age 10 years for children younger than 7 years when enrolled in a treatment trial for moderate amblyopia. METHODS: In a multicenter clinical trial, 419 children with amblyopia (visual acuity, 20/40-20/100) were randomized to patching or atropine eyedrops for 6 months. Two years after enrollment, a subgroup of 188 children entered long-term follow-up. Treatment after 6 months was at the discretion of the investigator; 89% of children were treated. MAIN OUTCOME MEASURE: Visual acuity at age 10 years with the electronic Early Treatment Diabetic Retinopathy Study test. APPLICATION TO CLINICAL PRACTICE: Patching and atropine eyedrops produce comparable improvement in visual acuity that is maintained through age 10 years. RESULTS: The mean amblyopic eye acuity, measured in 169 patients, at age 10 years was 0.17 logMAR (logarithm of the minimum angle of resolution) (approximately 20/32), and 46% of amblyopic eyes had an acuity of 20/25 or better. Age younger than 5 years at entry into the randomized trial was associated with a better visual acuity outcome (P < .001). Mean amblyopic and sound eye visual acuities at age 10 years were similar in the original treatment groups (P = .56 and P = .80, respectively). CONCLUSIONS: At age 10 years, the improvement of the amblyopic eye is maintained, although residual amblyopia is common after treatment initiated at age 3 years to younger than 7 years. The outcome is similar regardless of initial treatment with atropine or patching.+http://www.ncbi.nlm.nih.gov/pubmed/18695096UPediatric Eye Disease Investigator Group Repka, Michael X Kraker, Raymond T Beck, Roy W Holmes, Jonathan M Cotter, Susan A Birch, Eileen E Astle, William F Chandler, Danielle L Felius, Joost Arnold, Robert W Tien, D Robbins Glaser, Stephen R EY011751/EY/NEI NIH HHS/United States U10 EY011751-08/EY/NEI NIH HHS/United States U10 EY011751-09/EY/NEI NIH HHS/United States U10 EY011751-10/EY/NEI NIH HHS/United States Comparative Study Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural United States Archives of ophthalmology Arch Ophthalmol. 2008 Aug;126(8):1039-44.*1538-3601 (Electronic) 0003-9950 (Linking)261435118695096,126/8/1039 [pii] 10.1001/archopht.126.8.1039eng||7r Wygnanski-Jaffe, T. Levin, A. V.2007The effect of the randomized trial of patching regimens for treatment of moderate amblyopia on pediatric ophthalmologists: 3-year outcome469-72J AAPOS115 2007/05/29Amblyopia/*therapy Child Follow-Up Studies Humans *Occlusive Dressings Practice Guidelines as Topic/*standards Prescriptions/*statistics & numerical data Questionnaires Randomized Controlled Trials as Topic/*methods Retrospective Studies *Sensory DeprivationOct+PURPOSE: To investigate whether the recommendations of the randomized trial of patching regimens for treatment of moderate amblyopia in children have been adopted by pediatric ophthalmologists 3 years after publication. METHODS: An identical questionnaire to that emailed 3 years ago (6 months after publication of the randomized trial) was emailed to 560 members of the American Association for Pediatric Ophthalmology and Strabismus. RESULTS: One hundred seven (20%) responses were received. Fifty-five percent of respondents had decreased their prescribed patching regimens at least sometimes as compared with 28% (p = 0.0005) in 2003. There was no significant increase in the prescription of near visual tasks or only 2 hour patching regimens. CONCLUSIONS: Our study suggests that pediatric ophthalmologists may be prescribing fewer patching hours in 2006 in comparison to 2003. However, the majority of ophthalmologists are still reluctant to patch for only 2 hours, and there has not been a significant increase in prescribing near visual tasks during patching.+http://www.ncbi.nlm.nih.gov/pubmed/17532241MWygnanski-Jaffe, Tamara Levin, Alex V Comparative Study Research Support, Non-U.S. Gov't United States Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus / American Association for Pediatric Ophthalmology and Strabismus J AAPOS. 2007 Oct;11(5):469-72. Epub 2007 May 29.%1091-8531 (Print) 1091-8531 (Linking)17532241|Department of Ophthalmology, The Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, Israel. twjaffe@hotmail.com8S1091-8531(07)00262-5 [pii] 10.1016/j.jaapos.2007.03.013eng |t7sWallace, D. K. Edwards, A. R. Cotter, S. A. Beck, R. W. Arnold, R. W. Astle, W. F. Barnhardt, C. N. Birch, E. E. Donahue, S. P. Everett, D. F. Felius, J. Holmes, J. M. Kraker, R. T. Melia, M. Repka, M. X. Sala, N. A. Silbert, D. I. Weise, K. K.2006oA randomized trial to evaluate 2 hours of daily patching for strabismic and anisometropic amblyopia in children904-12 Ophthalmology1136 2006/06/06:Amblyopia/etiology/physiopathology/*therapy Anisometropia/complications/physiopathology/*therapy Child Child, Preschool Eyeglasses Female Follow-Up Studies Humans Male Prospective Studies *Sensory Deprivation Strabismus/complications/physiopathology/*therapy Time Factors Treatment Outcome Visual Acuity/physiologyJunOBJECTIVE: To compare 2 hours of daily patching (combined with 1 hour of concurrent near visual activities) with a control group of spectacle wear alone (if needed) for treatment of moderate to severe amblyopia in children 3 to 7 years old. DESIGN: Prospective randomized multicenter clinical trial (46 sites). PARTICIPANTS: One hundred eighty children 3 to 7 years old with best-corrected amblyopic-eye visual acuity (VA) of 20/40 to 20/400 associated with strabismus, anisometropia, or both who had worn optimal refractive correction (if needed) for at least 16 weeks or for 2 consecutive visits without improvement. INTERVENTION: Randomization either to 2 hours of daily patching with 1 hour of near visual activities or to spectacles alone (if needed). Patients were continued on the randomized treatment (or no treatment) until no further improvement was noted. MAIN OUTCOME MEASURE: Best-corrected VA in the amblyopic eye after 5 weeks. RESULTS: Improvement in VA of the amblyopic eye from baseline to 5 weeks averaged 1.1 lines in the patching group and 0.5 lines in the control group (P = 0.006), and improvement from baseline to best measured VA at any visit averaged 2.2 lines in the patching group and 1.3 lines in the control group (P<0.001). CONCLUSION: After a period of treatment with spectacles, 2 hours of daily patching combined with 1 hour of near visual activities modestly improves moderate to severe amblyopia in children 3 to 7 years old.+http://www.ncbi.nlm.nih.gov/pubmed/16751033RWallace, David K Pediatric Eye Disease Investigator Group Edwards, Allison R Cotter, Susan A Beck, Roy W Arnold, Robert W Astle, William F Barnhardt, Carmen N Birch, Eileen E Donahue, Sean P Everett, Donald F Felius, Joost Holmes, Jonathan M Kraker, Raymond T Melia, Michele Repka, Michael X Sala, Nicholas A Silbert, David I Weise, Katherine K EY11751/EY/NEI NIH HHS/United States U10 EY011751-09/EY/NEI NIH HHS/United States Comparative Study Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural United States Ophthalmology Ophthalmology. 2006 Jun;113(6):904-12.*1549-4713 (Electronic) 0161-6420 (Linking)160919216751033eJaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa, FL 33647, USA. pedig@jaeb.org8S0161-6420(06)00386-1 [pii] 10.1016/j.ophtha.2006.01.069eng||7tWygnanski-Jaffe, T.2005yThe effect on pediatric ophthalmologists of the randomized trial of patching regimens for treatment of moderate amblyopia208-11J AAPOS93 2005/06/16Amblyopia/physiopathology/*therapy Bandages Child, Preschool *Diffusion of Innovation Humans *Ophthalmology *Pediatrics *Physician's Practice Patterns Questionnaires Randomized Controlled Trials as Topic *Sensory Deprivation Severity of Illness Index Societies, Medical United StatesJunPURPOSE: To investigate the implementation of the recommendations of the randomized trial of patching regimens for treatment of moderate amblyopia in children. METHODS: A questionnaire was e-mailed to 380 members of the American Association for Pediatric Ophthalmology and Strabismus. RESULTS: Ninety responses were received. The majority of questionnaire respondents did not alter their clinical practice of patching subsequent to publication of the results of the patching trial. Thirty-nine percent made no modification whatsoever; an additional 33% made rare adjustments, and only 12% claimed to have adapted the amount of patching hours to the recommendations of the study. CONCLUSIONS: It is evident from the questionnaire results that the majority of pediatric ophthalmologists that replied to the questionnaire did not alter their clinical practice of patching subsequent to publication of the results of the patching trial.+http://www.ncbi.nlm.nih.gov/pubmed/15956938Wygnanski-Jaffe, Tamara United States Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus / American Association for Pediatric Ophthalmology and Strabismus J AAPOS. 2005 Jun;9(3):208-11.%1091-8531 (Print) 1091-8531 (Linking)15956938Department of Ophthalmology, The Goldschleger Eye Institute, Sheba Medical Center, Sackler of Medicine, Tel-Aviv University, Israel. twjaffe@hotmail.com4S1091853104002228 [pii] 10.1016/j.jaapos.2004.11.012eng5||7uScheiman, M. M. Hertle, R. W. Beck, R. W. Edwards, A. R. Birch, E. Cotter, S. A. Crouch, E. R., Jr. Cruz, O. A. Davitt, B. V. Donahue, S. Holmes, J. M. Lyon, D. W. Repka, M. X. Sala, N. A. Silbert, D. I. Suh, D. W. Tamkins, S. M.2005IRandomized trial of treatment of amblyopia in children aged 7 to 17 years437-47Arch Ophthalmol1234 2005/04/13iAdolescent Amblyopia/*therapy Atropine/administration & dosage/adverse effects/*therapeutic use Child Combined Modality Therapy *Eyeglasses Female Follow-Up Studies Humans Male Mydriatics/administration & dosage/adverse effects/*therapeutic use Pilot Projects Reading *Sensory Deprivation Treatment Outcome Video Games Vision, Binocular Visual Acuity/physiologyAprxOBJECTIVE: To evaluate the effectiveness of treatment of amblyopia in children aged 7 to 17 years. METHODS: At 49 clinical sites, 507 patients with amblyopic eye visual acuity ranging from 20/40 to 20/400 were provided with optimal optical correction and then randomized to a treatment group (2-6 hours per day of prescribed patching combined with near visual activities for all patients plus atropine sulfate for children aged 7 to 12 years) or an optical correction group (optical correction alone). Patients whose amblyopic eye acuity improved 10 or more letters (> or =2 lines) by 24 weeks were considered responders. RESULTS: In the 7- to 12-year-olds (n = 404), 53% of the treatment group were responders compared with 25% of the optical correction group (P<.001). In the 13- to 17-year-olds (n = 103), the responder rates were 25% and 23%, respectively, overall (adjusted P = .22) but 47% and 20%, respectively, among patients not previously treated with patching and/or atropine for amblyopia (adjusted P = .03). Most patients, including responders, were left with a residual visual acuity deficit. CONCLUSIONS: Amblyopia improves with optical correction alone in about one fourth of patients aged 7 to 17 years, although most patients who are initially treated with optical correction alone will require additional treatment for amblyopia. For patients aged 7 to 12 years, prescribing 2 to 6 hours per day of patching with near visual activities and atropine can improve visual acuity even if the amblyopia has been previously treated. For patients 13 to 17 years, prescribing patching 2 to 6 hours per day with near visual activities may improve visual acuity when amblyopia has not been previously treated but appears to be of little benefit if amblyopia was previously treated with patching. We do not yet know whether visual acuity improvement will be sustained once treatment is discontinued; therefore, conclusions regarding the long-term benefit of treatment and the development of treatment recommendations for amblyopia in children 7 years and older await the results of a follow-up study we are conducting on the patients who responded to treatment.+http://www.ncbi.nlm.nih.gov/pubmed/15824215Scheiman, Mitchell M Hertle, Richard W Beck, Roy W Edwards, Allison R Birch, Eileen Cotter, Susan A Crouch, Earl R Jr Cruz, Oscar A Davitt, Bradley V Donahue, Sean Holmes, Jonathan M Lyon, Don W Repka, Michael X Sala, Nicholas A Silbert, David I Suh, Donny W Tamkins, Susanna M Pediatric Eye Disease Investigator Group Clinical Trial Multicenter Study Randomized Controlled Trial Research Support, U.S. Gov't, P.H.S. United States Archives of ophthalmology Arch Ophthalmol. 2005 Apr;123(4):437-47.%0003-9950 (Print) 0003-9950 (Linking)15824215EJaeb Center for Health Research, Tampa, FL 33647, USA. pedig@jaeb.org*123/4/437 [pii] 10.1001/archopht.123.4.437eng ||7v%Awan, M. Proudlock, F. A. Gottlob, I.2005}A randomized controlled trial of unilateral strabismic and mixed amblyopia using occlusion dose monitors to record compliance1435-9Invest Ophthalmol Vis Sci464 2005/03/26Amblyopia/*therapy Child, Preschool Female Humans Male Patient Compliance/*statistics & numerical data *Sensory Deprivation Strabismus/*therapy Time Factors Visual Acuity *Visual PerceptionAprBPURPOSE: To investigate compliance with patching therapy and the dose-effect relationship in occlusion therapy in amblyopia by recording the effective patching time using occlusion dose monitors (ODMs). METHODS: Fifty-two children with strabismic or mixed amblyopia (Snellen equivalent, 6/12-6/48) were given optimal refractive correction and randomly allocated for 12 weeks into three treatment groups: group 1, no patching; group 2, prescribed patching for 3 hours; and group 3, prescribed patching for 6 hours. The effective time of occlusion was monitored with ODMs continuously. Visual acuity (VA) was measured every 3 weeks with LogMAR (logarithm of the minimum angle of resolution) Crowded Tests. RESULTS: In the 3- and 6-hour groups, mean (SD) compliance was 57.5% (30.8%) and 41.2% (30.9%), respectively, and mean effective patching time per day was 1 hour 43 minutes (55 minutes) and 2 hours 33 minutes (1 hour 52 minutes), respectively. The mean (SD) improvement in logMAR VA of amblyopic eyes was 0.24 (0.17), 0.29 (0.14), and 0.34 (0.19) in groups 1, 2, and 3, respectively. There was no significant difference in compliance with the prescribed patching between the 3- and 6-hour groups. VA outcomes in the 3- and 6-hour groups were not significantly better than 0-hour patching. However, the VA of patients with eyes effectively patched for more than 3 hours improved significantly. A dose-effect relationship was observed. Age at treatment did not influence the visual outcome. CONCLUSIONS: Poor compliance with prescribed occlusion explains discrepancies in previous studies. No differences in the effect between the different prescribed patching periods were found. The dose-effect relationship observed should encourage development of methods such as educational intervention to improve visual outcome by increasing effective patching time.+http://www.ncbi.nlm.nih.gov/pubmed/15790912Awan, Musarat Proudlock, Frank A Gottlob, Irene Clinical Trial Comparative Study Randomized Controlled Trial Research Support, Non-U.S. Gov't United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1435-9.%0146-0404 (Print) 0146-0404 (Linking)15790912kDepartment of Ophthalmology, University of Leicester, Leicester Royal Infirmary, Leicester, United Kingdom.$46/4/1435 [pii] 10.1167/iovs.04-0971eng S||7wRepka, M. X. Wallace, D. K. Beck, R. W. Kraker, R. T. Birch, E. E. Cotter, S. A. Donahue, S. Everett, D. F. Hertle, R. W. Holmes, J. M. Quinn, G. E. Scheiman, M. M. Weakley, D. R.2005xTwo-year follow-up of a 6-month randomized trial of atropine vs patching for treatment of moderate amblyopia in children149-57Arch Ophthalmol1232 2005/02/16Amblyopia/physiopathology/*therapy Atropine/*therapeutic use Child Female Follow-Up Studies Humans Male Mydriatics/*therapeutic use Ophthalmic Solutions *Sensory Deprivation Treatment Outcome Vision, Binocular/physiology Visual Acuity/physiologyFebOBJECTIVE: To compare patching and atropine sulfate as treatments for moderate amblyopia in children 18 months after completion of a 6-month randomized trial. METHODS: In a randomized, multicenter (47 sites) clinical trial, 419 children younger than 7 years with amblyopia (20/40 to 20/100 in the affected eye) were assigned to receive either patching or atropine eye drops for 6 months. Between 6 months and 2 years, treatment was at the discretion of the investigator. Main Outcome Measure Visual acuity in the amblyopic eye and sound eye after 2 years. RESULTS: At 2 years, visual acuity in the amblyopic eye improved from baseline a mean of 3.7 lines in the patching group and 3.6 lines in the atropine group. The difference in visual acuity between treatment groups was small: 0.01 logMAR (95% confidence interval, -0.02 to 0.04). In both treatment groups, the mean amblyopic eye acuity was approximately 20/32, 1.8 lines worse than the mean sound eye acuity, which was approximately 20/20. CONCLUSIONS: Atropine or patching for 6 months followed by best clinical care until 2 years produced similar improvement of moderate amblyopia in children between 3 and 7 years of age at enrollment. However, on average the amblyopic eye acuity was still approximately 2 lines worse than the sound eye.+http://www.ncbi.nlm.nih.gov/pubmed/15710809Repka, Michael X Wallace, David K Beck, Roy W Kraker, Raymond T Birch, Eileen E Cotter, Susan A Donahue, Sean Everett, Donald F Hertle, Richard W Holmes, Jonathan M Quinn, Graham E Scheiman, Mitchell M Weakley, David R Pediatric Eye Disease Investigator Group EY11751/EY/NEI NIH HHS/United States Clinical Trial Comparative Study Multicenter Study Randomized Controlled Trial Research Support, U.S. Gov't, P.H.S. United States Archives of ophthalmology Arch Ophthalmol. 2005 Feb;123(2):149-57.%0003-9950 (Print) 0003-9950 (Linking)15710809EJaeb Center for Health Research, Tampa, FL 33647, USA. pedig@jaeb.org*123/2/149 [pii] 10.1001/archopht.123.2.149eng ||7xRepka, M. X. Cotter, S. A. Beck, R. W. Kraker, R. T. Birch, E. E. Everett, D. F. Hertle, R. W. Holmes, J. M. Quinn, G. E. Sala, N. A. Scheiman, M. M. Stager, D. R., Sr. Wallace, D. K.2004WA randomized trial of atropine regimens for treatment of moderate amblyopia in children2076-85 Ophthalmology11111 2004/11/04 Amblyopia/*drug therapy Atropine/*administration & dosage/adverse effects Child Child, Preschool Female Follow-Up Studies Humans Male Mydriatics/*administration & dosage/adverse effects Ophthalmic Solutions/administration & dosage Prospective Studies Visual Acuity/drug effects/physiologyNovOBJECTIVE: To compare daily atropine to weekend atropine as prescribed treatments for moderate amblyopia in children younger than 7 years. DESIGN: Prospective, randomized multicenter clinical trial (30 sites). PARTICIPANTS: One hundred sixty-eight children younger than 7 years with amblyopia in the range of 20/40 to 20/80 associated with strabismus, anisometropia, or both. INTERVENTION: Randomization either to daily atropine or to weekend atropine for 4 months. Partial responders were continued on the randomized treatment until no further improvement was noted. MAIN OUTCOME MEASURE: Visual acuity (VA) in the amblyopic eye after 4 months. RESULTS: The improvement in VA of the amblyopic eye from baseline to 4 months averaged 2.3 lines in each group. The VA of the amblyopic eye at study completion was either (1) at least 20/25 or (2) better than or equal to that of the sound eye in 39 children (47%) in the daily group and 45 children (53%) in the weekend group. The VA of the sound eye at the end of follow-up was reduced by 2 lines in one patient in each group. Stereoacuity outcomes were similar in the 2 groups. CONCLUSIONS: Weekend atropine provides an improvement in VA of a magnitude similar to that of the improvement provided by daily atropine in treating moderate amblyopia in children 3 to 7 years old. This article contains additional online-only material available at http://www.ophsource.com/periodicals/ophtha.+http://www.ncbi.nlm.nih.gov/pubmed/15522375Repka, Michael X Cotter, Susan A Beck, Roy W Kraker, Raymond T Birch, Eileen E Everett, Donald F Hertle, Richard W Holmes, Jonathan M Quinn, Graham E Sala, Nicholas A Scheiman, Mitchell M Stager, David R Sr Wallace, David K Pediatric Eye Disease Investigator Group EY11751/EY/NEI NIH HHS/United States Clinical Trial Comparative Study Multicenter Study Randomized Controlled Trial Research Support, U.S. Gov't, P.H.S. United States Ophthalmology Ophthalmology. 2004 Nov;111(11):2076-85.*1549-4713 (Electronic) 0161-6420 (Linking)15522375eJaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa, FL 33647, USA. rbeck@jaeb.org8S0161-6420(04)00930-3 [pii] 10.1016/j.ophtha.2004.04.032eng ||7y&Hrisos, S. Clarke, M. P. Wright, C. M.2004^The emotional impact of amblyopia treatment in preschool children: randomized controlled trial1550-6 Ophthalmology1118 2004/08/04Affective Symptoms Amblyopia/*psychology/*therapy Child Behavior/*psychology Child Development Child, Preschool *Emotions *Eyeglasses Family/psychology Female Humans Male Orthoptics/methods Prospective Studies Questionnaires *Sensory Deprivation Stress, Psychological/psychologyAug^PURPOSE: To investigate the emotional status of children undergoing active treatment for amblyopia. DESIGN: Postal survey, in the context of a prospective, multicenter, randomized controlled trial. PARTICIPANTS: Parents of 177 children with a unilateral visual impairment referred from preschool vision screening. The children had been recruited to a randomized controlled trial of treatment for unilateral visual impairment and randomly assigned to receive either glasses with or without patches, glasses alone, or treatment deferred for 1 year. METHODS: A self-completion questionnaire, including a psychometric behavioral scale, was sent to the parents of all children recruited to the trial at age 4 years, to 66 whose deferred treatment began at age 5 years, and finally to 151 remaining in the trial at the end of follow-up. MAIN OUTCOME MEASURES: Mean scores per treatment group on the Revised Rutter Parent Scale for Preschool Children. Comparison of parent responses to questions assessing the child's general well-being and difficulties associated with treatment. RESULTS: Completed questionnaires were returned for 144 of 177 (81%) children at a mean age (standard deviation) of 48 months (5.0), for 45 of 66 (68%) at a mean age of 61 months (5.8), and for 78 of 151 (52%) at a mean age of 67 months (5.0). Most parents reported having difficulty with patching their child regardless of age (77% at age 4 years and 73% at age 5 years), with fewer reporting difficulties with glasses alone (42% and 53%, respectively). Children were significantly more upset by patching than by glasses only (chi-square test, P = 0.03 for age 4 years and P = 0.01 for age 5 years), as were the parents of 4-year-olds (chi-square test, P = 0.01). Most parents thought their children were happy, cooperative, and good tempered, and behavioral scores did not differ between treatment groups. CONCLUSIONS: Treatment for unilateral visual impairment is not easy to implement and is commonly associated with some degree of distress. Despite this, no impact on the child's global well-being or behavior was seen either during or after the treatment period.+http://www.ncbi.nlm.nih.gov/pubmed/15288987Hrisos, S Clarke, M P Wright, C M Clinical Trial Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't United States Ophthalmology Ophthalmology. 2004 Aug;111(8):1550-6.%0161-6420 (Print) 0161-6420 (Linking)15288987ODepartment of Ophthalmology, University of Newcastle upon Tyne, United Kingdom.810.1016/j.ophtha.2003.12.059 S0161-6420(04)00352-5 [pii]eng||7zHolmes, J. M. Kraker, R. T. Beck, R. W. Birch, E. E. Cotter, S. A. Everett, D. F. Hertle, R. W. Quinn, G. E. Repka, M. X. Scheiman, M. M. Wallace, D. K.2003`A randomized trial of prescribed patching regimens for treatment of severe amblyopia in children2075-87 Ophthalmology11011 2003/11/05Amblyopia/physiopathology/*therapy Child Child, Preschool Double-Blind Method Female Humans Male Patient Compliance Prospective Studies Quality of Life Questionnaires *Sensory Deprivation Time Factors Visual Acuity/physiologyNov`OBJECTIVE: To compare full-time patching (all hours or all but 1 hour per day) to 6 hours of patching per day, as prescribed treatments for severe amblyopia in children younger than 7 years. DESIGN: Prospective, randomized multicenter clinical trial (32 sites). PARTICIPANTS: One hundred seventy-five children younger than 7 years with amblyopia in the range of 20/100 to 20/400. INTERVENTION: Randomization either to full-time patching or to 6 hours of patching per day, each combined with at least 1 hour of near-visual activities during patching. MAIN OUTCOME MEASURE: Visual acuity in the amblyopic eye after 4 months. RESULTS: Visual acuity in the amblyopic eye improved a similar amount in both groups. The improvement in the amblyopic eye acuity from baseline to 4 months averaged 4.8 lines in the 6-hour group and 4.7 lines in the full-time group (P = 0.45). CONCLUSION: Six hours of prescribed daily patching produces an improvement in visual acuity that is of similar magnitude to the improvement produced by prescribed full-time patching in treating severe amblyopia in children 3 to less than 7 years of age.+http://www.ncbi.nlm.nih.gov/pubmed/14597512Holmes, Jonathan M Kraker, Raymond T Beck, Roy W Birch, Eileen E Cotter, Susan A Everett, Donald F Hertle, Richard W Quinn, Graham E Repka, Michael X Scheiman, Mitchell M Wallace, David K Pediatric Eye Disease Investigator Group EY11751/EY/NEI NIH HHS/United States Clinical Trial Comparative Study Multicenter Study Randomized Controlled Trial Research Support, U.S. Gov't, P.H.S. United States Ophthalmology Ophthalmology. 2003 Nov;110(11):2075-87.%0161-6420 (Print) 0161-6420 (Linking)14597512eng (||7{Repka, M. X. Beck, R. W. Holmes, J. M. Birch, E. E. Chandler, D. L. Cotter, S. A. Hertle, R. W. Kraker, R. T. Moke, P. S. Quinn, G. E. Scheiman, M. M.2003WA randomized trial of patching regimens for treatment of moderate amblyopia in children603-11Arch Ophthalmol1215 2003/05/14Amblyopia/physiopathology/*therapy Bandages Child Child, Preschool Female Follow-Up Studies Humans Male Patient Compliance *Sensory Deprivation Time Factors Treatment Outcome Visual Acuity/physiologyMaypOBJECTIVE: To compare 2 hours vs 6 hours of daily patching as treatments for moderate amblyopia in children younger than 7 years. METHODS: In a randomized multicenter (35 sites) clinical trial, 189 children younger than 7 years with amblyopia in the range of 20/40 to 20/80 were assigned to receive either 2 hours or 6 hours of daily patching combined with at least 1 hour per day of near visual activities during patching.Main Outcome Measure Visual acuity in the amblyopic eye after 4 months. RESULTS: Visual acuity in the amblyopic eye improved a similar amount in both groups. The improvement in the visual acuity of the amblyopic eye from baseline to 4 months averaged 2.40 lines in each group (P =.98). The 4-month visual acuity was at least 20/32 and/or improved from baseline by 3 or more lines in 62% of patients in each group (P>.99). CONCLUSION: When combined with prescribing 1 hour of near visual activities, 2 hours of daily patching produces an improvement in visual acuity that is of similar magnitude to the improvement produced by 6 hours of daily patching in treating moderate amblyopia in children aged 3 to 7 years.+http://www.ncbi.nlm.nih.gov/pubmed/12742836Repka, Michael X Beck, Roy W Holmes, Jonathan M Birch, Eileen E Chandler, Danielle L Cotter, Susan A Hertle, Richard W Kraker, Raymond T Moke, Pamela S Quinn, Graham E Scheiman, Mitchell M Pediatric Eye Disease Investigator Group EY11751/EY/NEI NIH HHS/United States Clinical Trial Comparative Study Multicenter Study Randomized Controlled Trial Research Support, U.S. Gov't, P.H.S. United States Archives of ophthalmology Arch Ophthalmol. 2003 May;121(5):603-11.%0003-9950 (Print) 0003-9950 (Linking)12742836EJaeb Center for Health Research, Tampa, FL 33613, USA. rbeck@jaeb.org*10.1001/archopht.121.5.603 121/5/603 [pii]eng \||7|2002[A randomized trial of atropine vs. patching for treatment of moderate amblyopia in children268-78Arch Ophthalmol1203 2002/03/15Amblyopia/*therapy Atropine/*therapeutic use Child Child, Preschool Female Follow-Up Studies Humans Male Mydriatics/*therapeutic use Ophthalmic Solutions Patient Compliance *Sensory Deprivation Treatment Outcome Visual Acuity/physiologyMarOBJECTIVE: To compare patching and atropine as treatments for moderate amblyopia in children younger than 7 years. METHODS: In a randomized clinical trial, 419 children younger than 7 years with amblyopia and visual acuity in the range of 20/40 to 20/100 were assigned to receive either patching or atropine at 47 clinical sites. MAIN OUTCOME MEASURE: Visual acuity in the amblyopic eye and sound eye after 6 months. RESULTS: Visual acuity in the amblyopic eye improved in both groups (improvement from baseline to 6 months was 3.16 lines in the patching group and 2.84 lines in the atropine group). Improvement was initially faster in the patching group, but after 6 months, the difference in visual acuity between treatment groups was small and clinically inconsequential (mean difference at 6 months, 0.034 logMAR units; 95% confidence interval, 0.005-0.064 logMAR units). The 6-month acuity was 20/30 or better in the amblyopic eye and/or improved from baseline by 3 or more lines in 79% of the patching group and 74% of the atropine group. Both treatments were well tolerated, although atropine had a slightly higher degree of acceptability on a parental questionnaire. More patients in the atropine group than in the patching group had reduced acuity in the sound eye at 6 months, but this did not persist with further follow-up. CONCLUSION: Atropine and patching produce improvement of similar magnitude, and both are appropriate modalities for the initial treatment of moderate amblyopia in children aged 3 to less than 7 years.+http://www.ncbi.nlm.nih.gov/pubmed/11879129Pediatric Eye Disease Investigator Group. EY11751/EY/NEI NIH HHS/United States Clinical Trial Comparative Study Multicenter Study Randomized Controlled Trial Research Support, U.S. Gov't, P.H.S. United States Archives of ophthalmology Arch Ophthalmol. 2002 Mar;120(3):268-78.%0003-9950 (Print) 0003-9950 (Linking)118791291Jaeb Center for Health Research, Tampa, Fla. USA.ecs10241 [pii]eng ||7}Repka, M. X. Cotter, S. A. Beck, R. W. Kraker, R. T. Birch, E. E. Everett, D. F. Hertle, R. W. Holmes, J. M. Quinn, G. E. Sala, N. A. Scheiman, M. M. Stager, D. R., Sr. Wallace, D. K.2004WA randomized trial of atropine regimens for treatment of moderate amblyopia in children2076-85 Ophthalmology11111 2004/11/04 Amblyopia/*drug therapy Atropine/*administration & dosage/adverse effects Child Child, Preschool Female Follow-Up Studies Humans Male Mydriatics/*administration & dosage/adverse effects Ophthalmic Solutions/administration & dosage Prospective Studies Visual Acuity/drug effects/physiologyNovOBJECTIVE: To compare daily atropine to weekend atropine as prescribed treatments for moderate amblyopia in children younger than 7 years. DESIGN: Prospective, randomized multicenter clinical trial (30 sites). PARTICIPANTS: One hundred sixty-eight children younger than 7 years with amblyopia in the range of 20/40 to 20/80 associated with strabismus, anisometropia, or both. INTERVENTION: Randomization either to daily atropine or to weekend atropine for 4 months. Partial responders were continued on the randomized treatment until no further improvement was noted. MAIN OUTCOME MEASURE: Visual acuity (VA) in the amblyopic eye after 4 months. RESULTS: The improvement in VA of the amblyopic eye from baseline to 4 months averaged 2.3 lines in each group. The VA of the amblyopic eye at study completion was either (1) at least 20/25 or (2) better than or equal to that of the sound eye in 39 children (47%) in the daily group and 45 children (53%) in the weekend group. The VA of the sound eye at the end of follow-up was reduced by 2 lines in one patient in each group. Stereoacuity outcomes were similar in the 2 groups. CONCLUSIONS: Weekend atropine provides an improvement in VA of a magnitude similar to that of the improvement provided by daily atropine in treating moderate amblyopia in children 3 to 7 years old. This article contains additional online-only material available at http://www.ophsource.com/periodicals/ophtha.+http://www.ncbi.nlm.nih.gov/pubmed/15522375Repka, Michael X Cotter, Susan A Beck, Roy W Kraker, Raymond T Birch, Eileen E Everett, Donald F Hertle, Richard W Holmes, Jonathan M Quinn, Graham E Sala, Nicholas A Scheiman, Mitchell M Stager, David R Sr Wallace, David K Pediatric Eye Disease Investigator Group EY11751/EY/NEI NIH HHS/United States Clinical Trial Comparative Study Multicenter Study Randomized Controlled Trial Research Support, U.S. Gov't, P.H.S. United States Ophthalmology Ophthalmology. 2004 Nov;111(11):2076-85.*1549-4713 (Electronic) 0161-6420 (Linking)15522375eJaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa, FL 33647, USA. rbeck@jaeb.org8S0161-6420(04)00930-3 [pii] 10.1016/j.ophtha.2004.04.032eng||7~4Vinding, T. Gregersen, E. Jensen, A. Rindziunski, E.1991Prevalence of amblyopia in old people without previous screening and treatment. An evaluation of the present prophylactic procedures among children in Denmark796-8Acta Ophthalmol (Copenh)696 1991/12/01Aged Aged, 80 and over Amblyopia/*epidemiology/prevention & control Child Child, Preschool Denmark/epidemiology Evaluation Studies as Topic Female Humans Male Middle Aged Prevalence Random Allocation Vision ScreeningDecAn epidemiological study of amblyopia was performed among old people without previous screening and treatment. The study revealed a prevalence of 2.9% (strabismic in 2.3%, anisometropic in 0.6%). Present residual amblyopia among Danish school children is about 1% according to literature. The rate of cure of amblyopia by the present Danish system of prophylaxis and treatment is estimated to be 60-70%.*http://www.ncbi.nlm.nih.gov/pubmed/1789098Vinding, T Gregersen, E Jensen, A Rindziunski, E Comparative Study Denmark Acta ophthalmologica Acta Ophthalmol (Copenh). 1991 Dec;69(6):796-8.%0001-639X (Print) 0001-639X (Linking)1789098LDepartment of Ophthalmology, University State Hospital, Copenhagen, Denmark.eng}|7Grabovska, I. V. Mozga, V. A.1981_[Evaluation of the treatment effectiveness in obscuration and refractive amblyopia in children]57-60Vestn Oftalmol6 1981/11/01Adolescent Amblyopia/*therapy Astigmatism/therapy Child Child, Preschool Eyeglasses Humans Hyperopia/*therapy Infant Lens Diseases/therapy Myopia/*therapy *Orthoptics Visual AcuityNov-Dec*http://www.ncbi.nlm.nih.gov/pubmed/7324337mGrabovska, I V Mozga, V A Comparative Study Ussr Vestnik oftalmologii Vestn Oftalmol. 1981 Nov-Dec;(6):57-60.%0042-465X (Print) 0042-465X (Linking)7324337WOtsenka effektivnosti lecheniia pri obskuratsionnoi i refraktsionnoi ambliopii u detei.rus G|t7Rutstein, R. P. Quinn, G. E. Lazar, E. L. Beck, R. W. Bonsall, D. J. Cotter, S. A. Crouch, E. R. Holmes, J. M. Hoover, D. L. Leske, D. A. Lorenzana, I. J. Repka, M. X. Suh, D. W.2010oA randomized trial comparing Bangerter filters and patching for the treatment of moderate amblyopia in children 998-1004 e6 Ophthalmology1175 2010/02/19Amblyopia/physiopathology/*therapy Child Child, Preschool *Eyeglasses Female Humans Male *Occlusive Dressings *Sensory Deprivation Treatment Outcome Visual Acuity/*physiologyMayOBJECTIVE: To determine whether visual acuity improvement with Bangerter filters is similar to improvement with patching as initial therapy for children with moderate amblyopia. DESIGN: Randomized, clinical trial. PARTICIPANTS: We enrolled 186 children, 3 to <10 years old, with moderate amblyopia (20/40-20/80). METHODS: Children were randomly assigned to receive either daily patching or to use a Bangerter filter on the spectacle lens in front of the fellow eye. Study visits were scheduled at 6, 12, 18, and 24 weeks. MAIN OUTCOME MEASURES: Visual acuity in amblyopic eyes at 24 weeks. RESULTS: At 24 weeks, amblyopic eye improvement averaged 1.9 lines in the Bangerter group and 2.3 lines in the patching group (difference in mean visual acuities between groups adjusted for baseline acuity = 0.38 line). The upper limit of a 1-sided 95% confidence interval was 0.76 line, which slightly exceeded a prespecified noninferiority limit of <0.75 line. Similar percentages of subjects in each group improved > or =3 lines (Bangerter group 38% vs patching group 35%; P = 0.61) or had > or =20/25 amblyopic eye acuity (36% vs 31%, respectively; P = 0.86). There was a lower treatment burden in the Bangerter group as measured with the Amblyopia Treatment Index. With Bangerter filters, neither a fixation switch to the amblyopic eye nor induced blurring in the fellow eye to worse than that of the amblyopic eye was required for visual acuity improvement. CONCLUSIONS: Because the average difference in visual acuity improvement between Bangerter filters and patching was less than half a line, and there was lower burden of treatment on the child and family, Bangerter filter treatment is a reasonable option to consider for initial treatment of moderate amblyopia.+http://www.ncbi.nlm.nih.gov/pubmed/20163869OPediatric Eye Disease Investigator Group Writing Committee Rutstein, Robert P Quinn, Graham E Lazar, Elizabeth L Beck, Roy W Bonsall, Dean J Cotter, Susan A Crouch, Eric R Holmes, Jonathan M Hoover, Darren L Leske, David A Lorenzana, Ingryd J Repka, Michael X Suh, Donny W EY011751/EY/NEI NIH HHS/United States U10 EY011751-11/EY/NEI NIH HHS/United States U10 EY011751-12/EY/NEI NIH HHS/United States Comparative Study Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural United States Ophthalmology Ophthalmology. 2010 May;117(5):998-1004.e6. Epub 2010 Feb 16.*1549-4713 (Electronic) 0161-6420 (Linking)2864338201638695Jaeb Center for Health Research, Tampa, FL 33647, USA8S0161-6420(09)01185-3 [pii] 10.1016/j.ophtha.2009.10.014eng||7Holmes, J. M. Kraker, R. T. Beck, R. W. Birch, E. E. Cotter, S. A. Everett, D. F. Hertle, R. W. Quinn, G. E. Repka, M. X. Scheiman, M. M. Wallace, D. K.2003`A randomized trial of prescribed patching regimens for treatment of severe amblyopia in children2075-87 Ophthalmology11011 2003/11/05Amblyopia/physiopathology/*therapy Child Child, Preschool Double-Blind Method Female Humans Male Patient Compliance Prospective Studies Quality of Life Questionnaires *Sensory Deprivation Time Factors Visual Acuity/physiologyNov`OBJECTIVE: To compare full-time patching (all hours or all but 1 hour per day) to 6 hours of patching per day, as prescribed treatments for severe amblyopia in children younger than 7 years. DESIGN: Prospective, randomized multicenter clinical trial (32 sites). PARTICIPANTS: One hundred seventy-five children younger than 7 years with amblyopia in the range of 20/100 to 20/400. INTERVENTION: Randomization either to full-time patching or to 6 hours of patching per day, each combined with at least 1 hour of near-visual activities during patching. MAIN OUTCOME MEASURE: Visual acuity in the amblyopic eye after 4 months. RESULTS: Visual acuity in the amblyopic eye improved a similar amount in both groups. The improvement in the amblyopic eye acuity from baseline to 4 months averaged 4.8 lines in the 6-hour group and 4.7 lines in the full-time group (P = 0.45). CONCLUSION: Six hours of prescribed daily patching produces an improvement in visual acuity that is of similar magnitude to the improvement produced by prescribed full-time patching in treating severe amblyopia in children 3 to less than 7 years of age.+http://www.ncbi.nlm.nih.gov/pubmed/14597512Holmes, Jonathan M Kraker, Raymond T Beck, Roy W Birch, Eileen E Cotter, Susan A Everett, Donald F Hertle, Richard W Quinn, Graham E Repka, Michael X Scheiman, Mitchell M Wallace, David K Pediatric Eye Disease Investigator Group EY11751/EY/NEI NIH HHS/United States Clinical Trial Comparative Study Multicenter Study Randomized Controlled Trial Research Support, U.S. Gov't, P.H.S. United States Ophthalmology Ophthalmology. 2003 Nov;110(11):2075-87.%0161-6420 (Print) 0161-6420 (Linking)14597512eng ||7&Yamaguchi, M. Yokoyama, T. Shiraki, K.2010OSurgical procedure for correcting globe dislocation in highly myopic strabismus 341-346 e2Am J Ophthalmol1492 2009/11/277Adult Dislocations/etiology/*surgery Eye Movements Humans Magnetic Resonance Imaging Myopia/complications/*surgery Oculomotor Muscles/*surgery *Ophthalmologic Surgical Procedures Orbital Diseases/etiology/*surgery Prospective Studies Strabismus/complications/*surgery Visual Field Tests Visual Fields/physiologyFebPURPOSE: To design a surgical procedure for correcting globe dislocation in strabismus in high myopia (highly myopic strabismus). DESIGN: Prospective, interventional case series. METHODS: We examined 36 eyes of 21 patients with highly myopic strabismus and 27 eyes of 27 healthy volunteers as controls at Osaka City General Hospital between 2000 and 2006. Anatomic relationships between the muscle cone and globe were analyzed using magnetic resonance imaging. Ranges of globe movement and angles of ocular deviation were measured quantitatively as angles of maximum abduction and sursumduction and angles of ocular deviation, respectively, using the Goldmann perimeter and alternate prism cover tests. A surgical procedure involving muscle union of the superior rectus and lateral rectus muscles was performed in 23 eyes of 14 patients to restore the dislocated globe back to the muscle cone. RESULTS: After surgery, the angle of dislocation of the globe, defined as the angle formed by a line connecting the area centroid of the superior rectus muscle and the globe and a line connecting area centroid of the lateral rectus muscle and globe against the supertemporal wall of the orbit, was significantly decreased (P < .001), and angles of maximum abduction and sursumduction and the angle of ocular deviation improved significantly (P < .001). CONCLUSIONS: This surgical procedure to restore the dislocated globe back into the muscle cone by uniting muscle bellies of the superior rectus and lateral rectus muscles is effective for highly myopic strabismus.+http://www.ncbi.nlm.nih.gov/pubmed/19939345Yamaguchi, Makoto Yokoyama, Tsuranu Shiraki, Kunihiko United States American journal of ophthalmology Am J Ophthalmol. 2010 Feb;149(2):341-346.e2. Epub 2009 Nov 24.*1879-1891 (Electronic) 0002-9394 (Linking)19939345Department of Ophthalmology and Visual Sciences, Osaka City University, Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, OsakaCity, Japan. m2013569@med.osaka-cu.ac.jp5S0002-9394(09)00661-8 [pii] 10.1016/j.ajo.2009.08.035eng||7SSilverberg, M. Schuler, E. Veronneau-Troutman, S. Wald, K. Schlossman, A. Medow, N.1999INonsurgical management of binocular diplopia induced by macular pathology900-3Arch Ophthalmol1177 1999/07/17Adult Aged Aged, 80 and over Diplopia/etiology/*therapy Eyeglasses Female Humans *Macula Lutea Male Middle Aged Retinal Diseases/*complications *Sensory Deprivation Treatment Outcome *Vision, Binocular Visual AcuityJulOBJECTIVE: To treat binocular diplopia secondary to macular pathology. METHODS: Seven patients underwent evaluation and treatment. All had constant vertical diplopia caused by various maculopathies, including subretinal neovascularization, epiretinal membrane, and central serous retinopathy. Visual acuity ranged from 20/20 to 20/30 in the affected eye. All except 1 patient had a small-angle, comitant hyperdeviation with no muscle paresis. Sensory evaluation demonstrated peripheral fusion and reduced stereoacuity. Neither prism correction nor manipulation of the refractive errors corrected the diplopia. A partially occlusive foil (Bangerter) of density ranging from 0.4 to 1.0 was placed in front of the affected eye to restore stable, single vision. RESULTS: The Bangerter foil eliminated the diplopia in all patients. Two patients elected not to wear the foil; 1 patient was afraid of becoming dependent, and the other was bothered by the visual blur. Visual acuity in the affected eye was reduced on average by 3 lines. All patients maintained the same level of sensory fusion, with only 2 having reduced stereoacuity. Symptoms returned when the foil was removed or its density was reduced. CONCLUSION: Low-density Bangerter foils provide an effective, inexpensive, and aesthetically acceptable management for refractory binocular diplopia induced by macular pathology, allowing peripheral fusion to be maintained.+http://www.ncbi.nlm.nih.gov/pubmed/10408454Silverberg, M Schuler, E Veronneau-Troutman, S Wald, K Schlossman, A Medow, N Case Reports United states Archives of ophthalmology Arch Ophthalmol. 1999 Jul;117(7):900-3.%0003-9950 (Print) 0003-9950 (Linking)10408454jDepartment of Ophthalmology, Manhattan Eye, Ear, and Throat Hospital, New York, NY, USA. ebschuler@aol.comeng"||7 Barton, J. J.20044"Retinal diplopia" associated with macular wrinkling925-7 Neurology635 2004/09/15Aged Diplopia/etiology/*pathology/therapy Eyeglasses Female Humans Macula Lutea/*pathology Middle Aged Postoperative Complications/*pathology/therapy Retinal Detachment/surgery Retinal Diseases/complications/*pathology Stress, Mechanical Vitreous Body/pathologySep 14Binocular diplopia is usually due to misalignment from ocular motor dysfunction. Three patients with chronic binocular vertical diplopia and small comitant hypotropic deviations due to macular displacement (heterotopia) associated with monocular retinal wrinkling are described. This maculopathy was idiopathic in two and secondary to treated retinal detachment in the third. Displacement of the macula by vitreoretinal traction is an unusual cause of binocular diplopia that requires careful ophthalmoscopy to diagnose.+http://www.ncbi.nlm.nih.gov/pubmed/15365153ZBarton, Jason J S Case Reports United States Neurology Neurology. 2004 Sep 14;63(5):925-7.*1526-632X (Electronic) 0028-3878 (Linking)15365153Department of Neurology, KS-452, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave., Boston, MA 02215, USA. jbarton@bidmc.harvard.edu63/5/925 [pii]eng ||7Kawasaki, A. Purvin, V.2009'Giant cell arteritis: an updated review13-32Acta Ophthalmol871 2008/10/22)*Giant Cell Arteritis Humans Risk FactorsFebGiant cell arteritis (GCA) is the most common primary vasculitis of adults. The incidence of this disease is practically nil in the population under the age of 50 years, then rises dramatically with each passing decade. The median age of onset of the disease is about 75 years. As the ageing population expands, it is increasingly important for ophthalmologists to be familiar with GCA and its various manifestations, ophthalmic and non-ophthalmic. A heightened awareness of this condition can avoid delays in diagnosis and treatment. It is well known that prompt initiation of steroids remains the most effective means for preventing potentially devastating ischaemic complications. This review summarizes the current concepts regarding the immunopathogenetic pathways that lead to arteritis and the major phenotypic subtypes of GCA with emphasis on large vessel vasculitis, novel modalities for disease detection and investigative trials using alternative, non-steroid therapies.+http://www.ncbi.nlm.nih.gov/pubmed/18937808yKawasaki, Aki Purvin, Valerie Review England Acta ophthalmologica Acta Ophthalmol. 2009 Feb;87(1):13-32. Epub 2008 Oct 7.*1755-3768 (Electronic) 1755-375X (Linking)18937808tDepartment of Neuro-ophthalmology, Hopital Ophtalmique Jules Gonin, Lausanne, Switzerland. aki.kawasaki@ophtal.vd.ch.AOS1314 [pii] 10.1111/j.1755-3768.2008.01314.xengO||7+Friedman, D. I. Gordon, L. K. Quiros, P. A.2010-Headache attributable to disorders of the eye62-72Curr Pain Headache Rep141 2010/04/29Eye Diseases/*complications/physiopathology/therapy Headache/*etiology/physiopathology/therapy Humans Oculomotor Nerve Diseases/*complications/physiopathology/therapyFebSensory innervation to the eye and periocular area arises from the ophthalmic branch of the trigeminal nerve. Thus, ocular, orbital, and systemic disorders may produce head pain with ocular signs and symptoms. Whereas some of these entities have characteristic diagnostic features, others mimic primary headache disorders such as migraine and cluster headache. This article reviews common ocular and neuro-ophthalmic conditions that are accompanied by pain in or near the eye.+http://www.ncbi.nlm.nih.gov/pubmed/20425216Friedman, Deborah I Gordon, Lynn K Quiros, Peter A 1K23EY015525/EY/NEI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Current pain and headache reports Curr Pain Headache Rep. 2010 Feb;14(1):62-72.*1534-3081 (Electronic) 1534-3081 (Linking)20425216Flaum Eye Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. Deborah_Friedman@urmc.rochester.edu10.1007/s11916-009-0088-8eng~|7%Colombo, B. Dalla Libera, D. Comi, G.2010'Ocular pain: a neurological perspectiveS103-5 Neurol Sci 31 Suppl 1 2010/05/22jEye Diseases/*etiology Headache Disorders/*complications/*diagnosis Humans Pain/*etiology Pain MeasurementJunOcular pain and related symptoms are frequent manifestations of primary and secondary headache disorders. Neurologists are often the first physician to evaluate patients affected by these clinical features. The cause of eye pain may be attributed both to pathological disorders with abnormal neurologic and neuro-ophthalmologic findings and to diseases with no apparent eye disturbances. A thorough clinical approach is necessary for an appropriate diagnosis and a correct specific management.+http://www.ncbi.nlm.nih.gov/pubmed/20464596Colombo, Bruno Dalla Libera, Dacia Comi, Giancarlo Review Italy Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology Neurol Sci. 2010 Jun;31 Suppl 1:S103-5.*1590-3478 (Electronic) 1590-1874 (Linking)20464596Department of Neurology, Headache Center, IRCCS San Raffaele Hospital, via Olgettina 48, 20132, Milan, Italy. colombo.bruno@hsr.it10.1007/s10072-010-0298-1eng ||7NZada, G. Woodmansee, W. W. Ramkissoon, S. Amadio, J. Nose, V. Laws, E. R., Jr.2011RAtypical pituitary adenomas: incidence, clinical characteristics, and implications336-44 J Neurosurg1142 2010/09/28$Adenoma/epidemiology/metabolism/*pathology Adolescent Adult Aged Female Humans Immunohistochemistry Incidence Ki-67 Antigen Male Middle Aged Pituitary Gland/metabolism/pathology Pituitary Neoplasms/*epidemiology/metabolism/*pathology Retrospective Studies Tumor Markers, Biological/metabolismFeb1OBJECT: The 2004 WHO classification of pituitary adenomas now includes an "atypical" variant, defined as follows: MIB-1 proliferative index greater than 3%, excessive p53 immunoreactivity, and increased mitotic activity. The authors review the incidence of this atypical histopathological subtype and its correlation with tumor subtype, invasion, and surgical features. METHODS: The records of 121 consecutive patients who underwent transsphenoidal surgery for pituitary adenomas during an 18-month period were retrospectively reviewed for evidence of atypical adenomas. RESULTS: Eighteen adenomas (15%) met the criteria for atypical lesions; 17 (94%) of the 18 were macroadenomas. On imaging, 15 (83%) demonstrated imaging evidence of surrounding invasion, compared with 45% of typical adenomas (p = 0.004). Atypical tumors occurred in 12 female (67%) and 6 male (33%) patients. Patient age ranged from 16 to 70 years (mean 48 years). Nine patients (50%) had hormonally active tumors, and 9 had nonfunctional lesions. Four (22%) of the 18 patients presented to us with recurrent tumors. Immunohistochemical analysis demonstrated the following tumor subtypes: GH-secreting adenoma with plurihormonal staining (5 patients [28%]); null-cell adenoma (5 patients [28%]); silent ACTH tumor (3 patients [17%]), ACTH-staining tumor with Cushing's disease (2 patients [11%]), prolactinoma (2 patients [11%]), and silent FSH-staining tumor (1 patient [6%]). The MIB-1 labeling index ranged from 3% to 20% (mean 7%). CONCLUSIONS: Atypical tumors were identified in 15% of resected pituitary adenomas, and they tended to be aggressive, invasive macroadenomas. More longitudinal follow-up is required to determine whether surgical outcomes, potential for recurrence, or metastasis of atypical adenomas vary significantly from their typical counterparts.+http://www.ncbi.nlm.nih.gov/pubmed/20868211Zada, Gabriel Woodmansee, Whitney W Ramkissoon, Shakti Amadio, Jordan Nose, Vania Laws, Edward R Jr United States Journal of neurosurgery J Neurosurg. 2011 Feb;114(2):336-44. Epub 2010 Sep 24.*1933-0693 (Electronic) 0022-3085 (Linking)20868211Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. gzada@usc.edu10.3171/2010.8.JNS10290eng ,||7Tibussek, D. Schneider, D. T. Vandemeulebroecke, N. Turowski, B. Messing-Juenger, M. Willems, P. H. Mayatepek, E. Distelmaier, F.2010@Clinical spectrum of the pseudotumor cerebri complex in children313-21Childs Nerv Syst263 2009/11/11=Adolescent Cerebrospinal Fluid Pressure Child Child, Preschool Cohort Studies Comorbidity Female Follow-Up Studies Humans Infant Intracranial Pressure Male Papilledema/diagnosis/epidemiology/pathology/therapy Pseudotumor Cerebri/*diagnosis/epidemiology/pathology/*therapy Recurrence Reference Values Treatment OutcomeMarlPURPOSE: Our aim was to improve diagnosis and management of pseudotumor cerebri (PTC; also known as idiopathic intracranial hypertension) in children. METHODS: We performed a comprehensive analysis of epidemiology, diagnostic work-up, therapy, and clinical follow-up in 53 consecutive patients. RESULTS: We identified several important aspects to be considered in the management of these children. First, patients may present without obvious symptoms at diagnosis. Second, bilateral papilledema might not or not yet be present in symptomatic patients. Third, measurement of cerebrospinal fluid (CSF) opening pressure may not always be reliable due to drugs used for sedation, which may alter intracranial pressure. Fourth, normal CSF pressure values in childhood are not well established and diagnosis might even be justified if pressure is <20 cm H(2)O. Fifth, associated conditions are frequent (at least in our cohort); however, in most cases, a causative link cannot be proven. Finally, disease relapse is a serious problem (20% in our group), which stresses the importance of standardized follow-up programs. CONCLUSIONS: PTC constitutes an important and possibly underrecognized disorder in children and adolescents. Considering the high percentage of possibly associated conditions in our study, a detailed diagnostic work-up is crucial to identify treatable underlying conditions.+http://www.ncbi.nlm.nih.gov/pubmed/19902218MTibussek, Daniel Schneider, Dominik T Vandemeulebroecke, Nicola Turowski, Bernd Messing-Juenger, Martina Willems, Peter H G M Mayatepek, Ertan Distelmaier, Felix Germany Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery Childs Nerv Syst. 2010 Mar;26(3):313-21. Epub 2009 Nov 10.*1433-0350 (Electronic) 0256-7040 (Linking)19902218Department of General Pediatrics, University Children's Hospital, Heinrich-Heine-University Dusseldorf, Moorenstr. 5, 40225, Dusseldorf, Germany.10.1007/s00381-009-1018-0eng!|t7'Eva, P. R. Pascoe, P. T. Vaughan, D. G.1982:Refractive change in hyperglycaemia: hyperopia, not myopia500-5Br J Ophthalmol668 1982/08/01Adult Aged Diabetes Complications Diabetes Mellitus/metabolism Female Glucose/metabolism Humans Hyperglycemia/*complications/metabolism Hyperopia/*etiology Lens, Crystalline/metabolism Male Middle Aged Sorbitol/metabolismAugzSudden changes in refraction are well recognised feature of hyperglycaemia. A tendency towards myopia has always been associated with elevations in blood glucose. Twelve diabetic patients were found to have experienced such refractive changes. Review of their records demonstrates that hyperglycaemia produces hyperopia. A theoretical mechanism for this phenomenon is discussed.*http://www.ncbi.nlm.nih.gov/pubmed/7104266Eva, P R Pascoe, P T Vaughan, D G Case Reports Research Support, Non-U.S. Gov't England The British journal of ophthalmology Br J Ophthalmol. 1982 Aug;66(8):500-5.%0007-1161 (Print) 0007-1161 (Linking)10398357104266eng|t7,Ramos-Esteban, J. C. Goldberg, S. Danias, J.2002iDrug induced acute myopia with supraciliary choroidal effusion in a patient with Wegener's granulomatosis594-6Br J Ophthalmol865 2002/04/26Acute Kidney Injury/etiology Adult Female Humans Myopia/*chemically induced Sulfonamides/*adverse effects Wegener Granulomatosis/complications/*drug therapyMay+http://www.ncbi.nlm.nih.gov/pubmed/11973261Ramos-Esteban, J C Goldberg, S Danias, J Case Reports Letter Research Support, Non-U.S. Gov't England The British journal of ophthalmology Br J Ophthalmol. 2002 May;86(5):594-6.%0007-1161 (Print) 0007-1161 (Linking)177112311973261eng||7fFinken, M. J. Zwaveling-Soonawala, N. Walenkamp, M. J. Vulsma, T. van Trotsenburg, A. S. Rotteveel, J.2011Frequent occurrence of the triphasic response (diabetes insipidus/hyponatremia/diabetes insipidus) after surgery for craniopharyngioma in childhood22-6Horm Res Paediatr761 2011/06/28 Background/Aims: It is not exactly known how many children develop the triphasic response (diabetes insipidus (DI)/hyponatremia/DI) immediately after surgery for childhood craniopharyngioma; neither is it known which factors predict this. We studied the occurrence of the triphasic response after primary surgery for craniopharyngioma in children, and aimed to identify possible predictors. Methods: Patients <18 years old who had undergone a primary craniopharyngioma resection between January 1990 and February 2010 in either of the 2 academic centers in Amsterdam were studied retrospectively. Results: Twenty-one patients (5 males) fulfilled the inclusion criteria. Median age at surgery was 9.1 (range: 4.0-15.1) years. Six patients developed a triphasic response (29%). Of all factors, only the duration of surgery was found to be a predictor of a triphasic response: 8.5 (6.0-11.0) versus 4.6 (3.5-11.5) h in patients who did not develop a triphasic response (p = 0.03). Conclusion: After primary surgery for a craniopharyngioma, a considerable number of patients develop a triphasic response in the regulation of the sodium and water balance. This is predicted by (factors associated with) a longer duration of surgery. Other predictors could not be identified, which may be due to the small sample size.+http://www.ncbi.nlm.nih.gov/pubmed/21701131Finken, Martijn J J Zwaveling-Soonawala, Nitash Walenkamp, Marie J E Vulsma, Thomas van Trotsenburg, A S Paul Rotteveel, Joost Switzerland Hormone research in paediatrics Horm Res Paediatr. 2011;76(1):22-6. Epub 2011 Jun 23.1663-2826 (Electronic)21701131SDepartment of Pediatrics, VU University Medical Center, Amsterdam, The Netherlands.!000324115 [pii] 10.1159/000324115eng ||7KHolmer, H. Popovic, V. Ekman, B. Follin, C. Siversson, A. B. Erfurth, E. M.2011Hypothalamic involvement and insufficient sex steroid supplementation are associated with low bone mineral density in women with childhood onset craniopharyngioma25-31Eur J Endocrinol1651 2011/04/20JulcCONTEXT: Data on bone mineral density (BMD) are lacking in adults with childhood onset (CO)-craniopharyngioma (CP) with hypothalamic damage from the tumor. In patients with CO GH deficiency, BMD increases during GH treatment. OBJECTIVE: The aims were to evaluate BMD in adults with CO-CPs on complete hormone replacement, including long-term GH and to evaluate the impact of hypothalamic damage on these measures. DESIGN AND PARTICIPANTS: BMD (dual-energy X-ray absorptiometry), markers of bone turn over, physical activity and calcium intake were assessed in 39 CO-CP adults (20 women), with a median age of 28 (17-57) years, in comparison with matched population controls. RESULTS: Late puberty induction was recorded in both genders, but reduced androgen levels in females only. Only CP women had lower BMD (P=0.03) at L2-L4, and reduced Z-scores at femoral neck (P=0.004) and L2-L4 (P=0.004). Both genders had increased serum leptin levels (P=0.001), which significantly correlated negatively with BMD at L2-L4 (P=0.003; r=-0.5) and 45% of CP women had Z-score levels 0.005) at the last follow-up. DI was permanent in 9 of the 13 children, and multiple pituitary deficiencies were seen in all children. Treatment with growth hormone resulted in normalization of adult height from -1.27 +/- 1.52 SDS at the start of the treatment to -0.13 +/- 1.39 SDS at the last followup. The final height was not significantly lower than the genetic target height (P>0.005). The permanent deficit was visual impairment: blindness in one or both eyes in 4 children, bitemporal hemianopsia in 4, and other defects in 2. Recurrence of the disease was ruled out in one child after 31 months. No mortality was observed in the observation period of 104.92 +/- 76.11 months. CONCLUSIONS: the overall incidence of craniopharyngioma in the period of 1989-2008 in Macedonia was 1.43 per 1 000 000 person-years. Subtotal resection and systematic irradiation showed good life quality of survivors.+http://www.ncbi.nlm.nih.gov/pubmed/21191780 Gucev, Zoran S Danilovski, Dragan Tasic, Velibor Ugrinovski, Jovica Nastova, Vesna Jancevska, Aleksandra Krstevska-Konstantinova, Marina Pop-Jordanova, Nada Kirovski, Ilija China World journal of pediatrics : WJP World J Pediatr. 2011 Feb;7(1):74-8. Epub 2010 Dec 30.1867-0687 (Electronic)21191780PMedical Faculty Skopje, 50 Divizija BB, 1000 Skopje, Macedonia. gucevz@gmail.com10.1007/s12519-011-0250-3engO||7 Muller, H. L.2008RChildhood craniopharyngioma. Recent advances in diagnosis, treatment and follow-up193-202Horm Res694 2008/01/22Child Craniopharyngioma/complications/*diagnosis/*therapy Follow-Up Studies Humans Hypothalamus/physiopathology Obesity/etiology/physiopathology Pituitary Neoplasms/complications/*diagnosis/*therapy Prognosis Quality of Life Retrospective StudiesBACKGROUND: Craniopharyngioma are embryogenic malformations of the sellar area. With an overall incidence of 0.5-2 new cases per million population per year, 30-50% of all cases occur in childhood. Overall survival rates are high. However, quality of life (QoL) is substantially reduced in many survivors due to sequelae such as extreme obesity caused by hypothalamic lesions. METHODS: Based on retrospective analysis of 306 patients with childhood craniopharyngioma (HIT ENDO), we found that QoL was negatively related to hypothalamic involvement, tumor size and the number of neurosurgical interventions. RESULTS: Irradiation had no significant impact on long-term QoL. The prospective surveillance of 98 patients in KRANIOPHARYNGEOM 2000 revealed frequent and early events in terms of tumor relapse after apparently complete resection (EFS: 0.60 +/- 0.09 at 3 years) and tumor progression after incomplete resection (EFS: 0.22 +/- 0.09). CONCLUSION: We conclude that radical surgery in patients with hypothalamic involvement has a major negative impact on long-term QoL. Innovative treatment strategies are warranted to improve QoL in these patients at risk. Accordingly, the appropriate time point of irradiation after incomplete resection will be analyzed in KRANIOPHARYNGEOM 2007.+http://www.ncbi.nlm.nih.gov/pubmed/18204266Muller, Hermann L Research Support, Non-U.S. Gov't Review Switzerland Hormone research Horm Res. 2008;69(4):193-202. Epub 2008 Jan 21.*1423-0046 (Electronic) 0301-0163 (Linking)18204266Department of Pediatrics, Pediatric Hematology and Oncology, Klinikum Oldenburg GmbH, Oldenburg, Germany. mueller.hermann@klinikum-oldenburg.de!000113019 [pii] 10.1159/000113019eng ||7Berger, A. S. Kaplan, H. J.1992rClinical experience with the surgical removal of subfoveal neovascular membranes. Short-term postoperative results969-75; discussion 975-6 Ophthalmology996 1992/06/01`Adolescent Adult Aged Aging Cell Membrane Eye Infections, Parasitic/surgery Female Fluorescein Angiography Follow-Up Studies Fovea Centralis/parasitology/*surgery Fundus Oculi Histoplasmosis/surgery Humans Macular Degeneration/surgery Male Middle Aged Postoperative Complications Prognosis Retinal Neovascularization/parasitology/*surgery Visual AcuityJunBACKGROUND: Severe visual loss occurs in the presumed ocular histoplasmosis syndrome (POHS) and in age-related macular degeneration (ARMD) from subfoveal neovascularization. Although laser photocoagulation has recently been recommended for this complication in ARMD, treatment is inevitably associated with a loss of central vision. In an attempt to restore and/or preserve central vision, the authors undertook surgical removal of subfoveal neovascular membranes in these diseases. METHODS: Patients with POHS and ARMD with reduced Snellen visual acuity to 20/80 or less were selected if there was angiographic evidence of a neovascular membrane beneath the fovea. Modern vitreoretinal techniques were used to remove the subfoveal neovascular complex. RESULTS: The authors' first 15 patients with POHS and 19 patients with ARMD were followed for an average of 4 months postoperatively. Snellen visual acuity improved by 2 lines or more in 8 of 15 (53%) cases of POHS. Although similar improvements in Snellen visual acuity were not observed in cases of ARMD, 14 of 19 (74%) cases showed either slight improvement or stabilization of their vision postoperatively. Complications included recurrent neovascularization in 2 of 15 (13%) and 3 of 19 (16%) eyes with POHS and ARMD, respectively. No retinal detachment or preretinal proliferation was observed. CONCLUSIONS: These results suggest that subfoveal neovascularization can be successfully removed with preservation of foveal vision in POHS and stabilization in ARMD, at least for the short term. Visual improvement was observed in POHS even after 6 months of decreased vision. Finally, visual prognosis is most dependent on the integrity of the subfoveal RPE after removal of the membrane.*http://www.ncbi.nlm.nih.gov/pubmed/1630786Berger, A S Kaplan, H J Research Support, Non-U.S. Gov't United states Ophthalmology Ophthalmology. 1992 Jun;99(6):969-75; discussion 975-6.%0161-6420 (Print) 0161-6420 (Linking)1630786kDepartment of Ophthalmology and Visual Sciences, Washington University Medical Center, St. Louis, MO 63110.engp||7,Wykoff, C. C. Houston, S. K. Berrocal, A. M.2011MAnti-vascular endothelial growth factor agents for pediatric retinal diseases185-99Int Ophthalmol Clin511 2010/12/09Angiogenesis Inhibitors/*therapeutic use Antibodies, Monoclonal/*therapeutic use Child Humans Retinal Diseases/*drug therapy/metabolism Treatment Outcome Vascular Endothelial Growth Factor A/*antagonists & inhibitors/metabolismWinter+http://www.ncbi.nlm.nih.gov/pubmed/21139484Wykoff, Charles C Houston, Samuel K Berrocal, Audina M P30-EY014801/EY/NEI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review United States International ophthalmology clinics Int Ophthalmol Clin. 2011 Winter;51(1):185-99.*1536-9617 (Electronic) 0020-8167 (Linking)21139484;10.1097/IIO.0b013e318200df83 00004397-201105110-00011 [pii]eng|t7(Michaelides, M. Hunt, D. M. Moore, A. T.2004The cone dysfunction syndromes291-7Br J Ophthalmol882 2004/01/23iColor Vision Defects/*genetics Genotype Humans Mutation Phenotype Psychophysics Scotoma/genetics SyndromeFebThe cone dystrophies comprise a heterogeneous group of disorders characterised by visual loss, abnormalities of colour vision, central scotomata, and a variable degree of nystagmus and photophobia. They may be stationary or progressive. The stationary cone dystrophies are better described as cone dysfunction syndromes since a dystrophy often describes a progressive process. These different syndromes encompass a wide range of clinical and psychophysical findings. The aim is to review current knowledge relating to the cone dysfunction syndromes, with discussion of the various phenotypes, the currently mapped genes, and genotype-phenotype relations. The cone dysfunction syndromes that will be discussed are complete and incomplete achromatopsia, oligocone trichromacy, cone monochromatism, blue cone monochromatism, and Bornholm eye disease. Disorders with a progressive cone dystrophy phenotype will not be discussed.+http://www.ncbi.nlm.nih.gov/pubmed/14736794~Michaelides, M Hunt, D M Moore, A T Review England The British journal of ophthalmology Br J Ophthalmol. 2004 Feb;88(2):291-7.%0007-1161 (Print) 0007-1161 (Linking)177198914736794^Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.eng 8||7)Kelly, J. P. Crognale, M. A. Weiss, A. H.2003_ERGs, cone-isolating VEPs and analytical techniques in children with cone dysfunction syndromes289-304Doc Ophthalmol1063 2003/05/10Adolescent Child Child, Preschool Color Perception Tests Color Vision Defects/diagnosis/*physiopathology Electroretinography/*methods *Evoked Potentials, Visual Female Humans Male Retinal Cone Photoreceptor Cells/*physiology Retinal Diseases/diagnosis/*physiopathology SyndromeMayPhotoreceptor and post-receptoral function in children with congenital and acquired cone disorders was measured by full-field electroretinogram (ERG) and transient visual evoked potentials (VEPs). Subjects were five rod monochromats (RM), five with cone dystrophy (CD), and 30 controls. Patients were diagnosed by clinical findings, ERGs, and standard color vision tests. VEP stimuli were check reversals and color grating onsets that stimulated each photoreceptor type (L-, M-, or S-cones) or post-receptoral pathways (L-M, white/black). VEP signal-to-noise ratios (S/N) were calculated by Fourier analysis of VEP epochs. All RM patients showed extinguished cone ERGs. A near normal S-cone VEP was recorded from a blue-cone rod monochromat without any signal from the L- or M-cone stimuli. Two other RM patients were classified as incomplete RM based on a low-level VEP signal from either L- or M-cone stimuli. CD patients had mildly to severely reduced ERGs and VEPs were abnormal to all cone-isolating stimuli. The VEP S/N ratio was not significantly correlated with the amount of rod contrast in the color stimuli. Color VEPs provide an objective assessment of macular cone function in children with cone dysfunction syndromes that is more sensitive to residual central cone function than standard full-field ERGs. VEP techniques may be useful in the early detection of cone loss in children, especially in children who do not tolerate ERG testing.+http://www.ncbi.nlm.nih.gov/pubmed/12737507Kelly, John P Crognale, Michael A Weiss, Avery H Research Support, Non-U.S. Gov't Netherlands Documenta ophthalmologica. Advances in ophthalmology Doc Ophthalmol. 2003 May;106(3):289-304.%0012-4486 (Print) 0012-4486 (Linking)12737507qDivision of Ophthalmology, Children's Hospital & Regional Medical Center, Seattle, WA 98105, USA. jkelly@chmc.orgeng !||7Zervas, J. P. Smith, J. L.1987HNeuro-ophthalmic presentation of cone dysfunction syndromes in the adult202-18J Clin Neuroophthalmol74 1987/12/01aAdult Aged Electroretinography Eye Diseases/*complications/physiopathology Female Fundus Oculi Humans Male Nervous System Diseases/*complications/physiopathology *Photoreceptor Cells Retinal Diseases/complications/physiopathology Scotoma/complications/physiopathology Syndrome Vision Disorders/*complications/physiopathology Visual Acuity *Visual FieldsDecCone dysfunction syndromes are probably part of the spectrum of cone-rod degenerations and can present with widely varying clinical pictures. Thus, although the age of onset is usually before the third decade, patients can present at any age, and, although family history is usually positive, in typical cases it may be quite negative. Patients can have initially very subtle, bizarre, or poorly described visual complaints so that numerous examiners may label them "functional" or "malingering." They can present with the classic symptoms of hemeralopia, poor acuity, and reduced color vision, but these complaints may be absent. Visual acuity and color vision can be normal or severely reduced and the fundi may show classic changes such as bulls-eye maculopathy, macular choroidal atrophy, pigment clumping in the maculae, mild peripheral pigmentary changes, or a fundus flavimaculata-like change. The patients here reported were considered as having normal fundi by several competent ophthalmologists as a rule, however. Visual fields can vary from normal to ring scotomas, central scotomas, and other interesting types of defects, even simulating a hemianopia. Although involvement is usually symmetrical between the two eyes, this is not always the case, and one of our patients had a strictly uniocular cone dystrophy. Cone dysfunction can be considered in a patient of any age even with normal acuity, good color vision, and a normal ophthalmoscopic examination. A high index of suspicion should prompt specific questioning about hemeralopia, or reduced visual function in brightly illuminated situations, and better vision in twilight or under dim illumination. Patients may falsely describe hemeralopia as "glare" or "photophobia." Careful testing of color vision, a meticulous tangent screen examination, and specifically looking for diffuse narrowing of retinal arterioles in a patient with an otherwise normal fundus appearance will usually suffice to prompt the clinician to order electroretinography, which is the definitive diagnostic criterion for the cone dystrophies. It is important to consider this diagnosis before embarking on an otherwise fruitless and expensive neuroimaging investigation.*http://www.ncbi.nlm.nih.gov/pubmed/2963026Zervas, J P Smith, J L Case Reports United states Journal of clinical neuro-ophthalmology J Clin Neuroophthalmol. 1987 Dec;7(4):202-18.%0272-846X (Print) 0272-846X (Linking)2963026kBascom Palmer Eye Institute, Department of Ophthalmology, University of Miami School of Medicine, FL 33101.eng=||7 Nakano, H.1976[Comparative electrophysiological studies in cone dysfunction syndromes. Part III. Electroretinogram in total color blind (author's transl)]1694-700Nihon Ganka Gakkai Zasshi8012 1976/12/10^Child Color Vision Defects/*physiopathology Dark Adaptation *Electroretinography Female HumansDec 10*http://www.ncbi.nlm.nih.gov/pubmed/1088059Nakano, H Case Reports English Abstract Japan Nihon Ganka Gakkai zasshi Nihon Ganka Gakkai Zasshi. 1976 Dec 10;80(12):1694-700.%0029-0203 (Print) 0029-0203 (Linking)1088059jpn ||7 Hirose, T.1969 [Cone-rod dysfunction syndromes]556-76Nihon Ganka Gakkai Zasshi734 1969/04/01Adolescent Adult Blindness/complications Child Child, Preschool Color Vision Defects/complications Electroretinography Female Humans Male Pedigree *Photoreceptor Cells *Vision Disorders/diagnosisApr*http://www.ncbi.nlm.nih.gov/pubmed/5306075[Hirose, T Japan Nihon Ganka Gakkai zasshi Nihon Ganka Gakkai Zasshi. 1969 Apr;73(4):556-76.%0029-0203 (Print) 0029-0203 (Linking)5306075jpn~|7#Goodman, G. Ripps, H. Siegel, I. M.1963Cone Dysfunction Syndromes214-31Arch Ophthalmol70 1963/08/01*Adaptation, Ocular *Adolescent *Amblyopia *Child *Color Vision Defects *Electroretinography *Genetics, Medical *Infant *RetinaAug+http://www.ncbi.nlm.nih.gov/pubmed/14060101lGoodman, g Ripps, h Siegel, i m United states Archives of ophthalmology Arch Ophthalmol. 1963 Aug;70:214-31.%0003-9950 (Print) 0003-9950 (Linking)14060101eng ~t7<Querques, G. Prato, R. Coscas, G. Soubrane, G. Souied, E. H.2009In vivo visualization of photoreceptor layer and lipofuscin accumulation in stargardt's disease and fundus flavimaculatus by high resolution spectral-domain optical coherence tomography693-9Clin Ophthalmol3 2010/01/08 INTRODUCTION: To assess photoreceptor (PR) layer morphology in patients with Stargardt's disease (STGD) and fundus flavimaculatus (FFM) using high resolution spectral domain optical coherence tomography (HD-OCT; OCT 4000 Cirrus, Humphrey-Zeiss, San Leandro, CA). METHODS: This was a prospective observational case series. Sixteen consecutive patients with STGD and FFM underwent a complete ophthalmologic examination. Optical coherence tomography examination was performed with HD-OCT, a high-speed (27,000 axial scans per second) OCT system using spectral/Fourier domain detection, with an axial image resolution of 5 mum. RESULTS: A total of 31 eyes were included in the study. Transverse loss of the PR layer in the foveal region was shown by HD-OCT. Twenty eyes with clinically evident central atrophy had a disruption of either the Verhoeff's membrane (VM) or the layer corresponding to the interface of inner segment (IS) and outer segment (OS) of PR in the foveal region. Among these eyes, 12/20 eyes had a loss of the PR layer (loss of both VM and IS-OS interface) in the foveal region. Eleven eyes (11/31) without clinically evident central atrophy had an intact interface of IS and OS of PR centrally. Moreover, we observed hyperreflective deposits: type 1 lesions located within the retinal pigment epithelium (RPE) layer and at the level of the outer segments of PR, and type 2 lesions located at the level of the outer nuclear layer and clearly separated from the RPE layer. Type 1 lesions alone were associated with absence of loss of the PR layer in the foveal region in all eyes; type 2 lesions were always associated with presence of type 1 lesions, and often (8/12 eyes) associated with loss of the PR layer within the foveal region. Mean best-corrected visual acuity (BCVA) was significantly correlated with loss of the PR layer in the foveal region (P < 0.001), as well as to presence of type 2 flecks (P = 0.03). CONCLUSION: Type 2 deposits in STGD/FFM patients seem to represent a marker of the possible evolution towards foveal atrophy.+http://www.ncbi.nlm.nih.gov/pubmed/20054419Querques, Giuseppe Prato, Rosy Coscas, Gabriel Soubrane, Gisele Souied, Eric H New Zealand Clinical ophthalmology (Auckland, N.Z.) Clin Ophthalmol. 2009;3:693-9. Epub 2009 Dec 29.*1177-5483 (Electronic) 1177-5467 (Linking)280164020054419\Department of Ophthalmology, Hopital Intercommunal de Creteil, University Paris XII, France.engZ||7zErgun, E. Hermann, B. Wirtitsch, M. Unterhuber, A. Ko, T. H. Sattmann, H. Scholda, C. Fujimoto, J. G. Stur, M. Drexler, W.2005Assessment of central visual function in Stargardt's disease/fundus flavimaculatus with ultrahigh-resolution optical coherence tomography310-6Invest Ophthalmol Vis Sci461 2004/12/30Adult *Diagnostic Techniques, Ophthalmological Female Fluorescein Angiography Fluorescence Humans Male Middle Aged Photoreceptor Cells, Vertebrate/*pathology Prospective Studies Retinal Diseases/*diagnosis Tomography, Optical Coherence/*methods *Visual AcuityJank PURPOSE: To assess photoreceptor morphology in patients with Stargardt's disease and fundus flavimaculatus using ultrahigh-resolution optical coherence tomography (UHR-OCT) and correlate it with visual acuity (VA). METHODS: This was a prospective observational case series. Fourteen patients with Stargardt's disease (nine women, five men; average age, 39 years; range, 27-53) were examined. A clinically viable UHR-OCT system employing a new, compact titanium sapphire laser was used, enabling a 3-microm axial resolution in the retina. All patients received a full ophthalmic examination, including fluorescein angiography. Outcome was judged by central transverse photoreceptor loss, central foveal thickness, VA, central atrophy according to fluorescein angiography, and fundus autofluorescence. RESULTS: UHR-OCT was capable of visualizing and quantifying regions of central transverse photoreceptor (PR) loss. All Stargardt patients with central atrophy had a complete loss of the central photoreceptor layer in the foveal region (mean transverse photoreceptor loss, 4390 +/- 2270 microm; range, 530-9240 microm). Patients without clinically evident central atrophy had an intact photoreceptor layer centrally, but had small, focal parafoveal defects. A correlation was detected between VA and transverse PR loss (Spearman rho=-0.60, P=0.03), which was confirmed on logistic regression analysis (R2=0.49, P=0.0001). Central foveal thickness was reduced in patients with Stargardt's disease (85 +/- 40 microm; range, 58-280 microm). The correlation was statistically significant with VA (Spearman rho=0.43, P=0.04), but not with transverse PR loss (Spearman rho=-0.23, P >>0.05). Linear regression analysis showed a statistically significant association of central foveal thickness with VA (R2=0.51, P=0.0001), but not with transverse PR loss (P >>0.05). The extent of atrophy seen in fluorescein angiography correlated with VA and transverse PR loss (Spearman rho=-0.51, P=0.007; Spearman rho=0.77, P=0.0001). Similar correlations were found with the maximum transverse diameter of fundus autofluorescence (Spearman rho=-0.72, P=0.008; Spearman rho=0.77, P=0.003). CONCLUSIONS: Ultrahigh-resolution OCT demonstrates excellent visualization of intraretinal morphology and enables quantification of the photoreceptor layer. Thus, for the first time, an in vivo visualization and quantification of transverse, central photoreceptor loss and correlation with visual function is possible. Lower VA corresponds to a greater transverse photoreceptor loss, which also correlates with the extent of changes seen in fluorescein angiography and in fundus autofluorescence. Furthermore, reduced retinal thickness (i.e., atrophy of retinal layers) does not correlate with the transverse extent of PR loss. Thus, it seems that although there may be progressive atrophy of intraretinal layers, an intact photoreceptor layer leads to better VA. UHR-OCT may present a viable alternative to the assessment of central visual function, due to the easy, objective, and noninvasive data acquisition. Therefore, UHR-OCT could be of future use in judging patients' prognoses in Stargardt's disease.+http://www.ncbi.nlm.nih.gov/pubmed/15623790Ergun, Erdem Hermann, Boris Wirtitsch, Matthias Unterhuber, Angelika Ko, Tony H Sattmann, Harald Scholda, Christoph Fujimoto, James G Stur, Michael Drexler, Wolfgang R01-CA75289-04/CA/NCI NIH HHS/United States R01-EY11289-14/EY/NEI NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2005 Jan;46(1):310-6.%0146-0404 (Print) 0146-0404 (Linking)15623790IDepartment of Ophthalmology, General Hospital of Vienna, Vienna, Austria.#46/1/310 [pii] 10.1167/iovs.04-0212eng ||74Parisi, V. Canu, D. Iarossi, G. Olzi, D. Falsini, B.2002wAltered recovery of macular function after bleaching in Stargardt's disease-fundus flavimaculatus: pattern VEP evidence2741-8Invest Ophthalmol Vis Sci438 2002/07/31Adult Electroretinography Evoked Potentials, Visual/*physiology Female Fluorescein Angiography Humans Macula Lutea/*physiology Macular Degeneration/genetics/*physiopathology Male Middle Aged Phenotype *Photic Stimulation Visual AcuityAug PURPOSE: To evaluate recovery of pattern visual evoked potentials (VEPs) after macular bleaching in patients with Stargardt's disease-fundus flavimaculatus (STD/FF). METHODS: Sixteen unrelated patients with STD/FF (age, 26-52 years; visual acuity, 0.2-1.0; phenotype I, n = 6; phenotype II, n = 8; or phenotype III, n = 2) and 15 age-matched control subjects were evaluated. VEPs were recorded in response to counterphased (two reversals per second) checkerboards (check size, 15 minutes; mean luminance, 80 cd/m(2); contrast, 80%; stimulus field size, 18 degrees ) in baseline condition and at 20, 40, and 60 seconds after a 30-second exposure to a bleaching light (3.58 log photopic trolands), presented to the central (6 degrees field) retina. In all patients, macular focal electroretinograms (FERGs) to an 18 degrees uniform field, flickering at 41 Hz, were also recorded in separate sessions. RESULTS: At every postbleaching time, VEPs were delayed and suppressed in amplitude, compared with prebleaching values, in both patients and control subjects. However, the amount of delay and suppression was, on average, more pronounced (P < 0.001) in patients than in control subjects. This difference was not accounted for by eccentric fixation in patients (n = 8) with central scotoma and was still substantial when only patients (n = 8) with normal visual field and acuity were considered. In individual patients, baseline FERG amplitudes correlated (r = -0.6, P < 0.01) with the suppression of VEP amplitude at 40-seconds after bleaching. CONCLUSIONS: The results indicate an altered recovery of pattern VEPs after macular bleaching in STD/FF and suggest adaptation abnormalities in macular cone photoreceptors, occurring at disease stages with relatively preserved central visual field and acuity.+http://www.ncbi.nlm.nih.gov/pubmed/12147611Parisi, Vincenzo Canu, Doriana Iarossi, Giancarlo Olzi, Diego Falsini, Benedetto Research Support, Non-U.S. Gov't United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2002 Aug;43(8):2741-8.%0146-0404 (Print) 0146-0404 (Linking)12147611LCattedra di Clinica Oculistica, Universita di Roma Tor Vergata, Roma, Italy.engm~t7 Sharma, S.1999XOphthaproblem. Juvenile macular dystrophy (fundus flavimaculatus or Stargardt's disease) 2057, 2064Can Fam Physician45 1999/10/06Adult Age Factors Diagnosis, Differential Fluorescein Angiography Fundus Oculi Humans Macular Degeneration/*diagnosis/genetics MaleSep+http://www.ncbi.nlm.nih.gov/pubmed/10509215~Sharma, S Case Reports Canada Canadian family physician Medecin de famille canadien Can Fam Physician. 1999 Sep;45:2057, 2064.%0008-350X (Print) 0008-350X (Linking)232854010509215?Department of Ophthalmology, Queen's University, Kingston, Ont.eng~|77Stavrou, P. Good, P. A. Misson, G. P. Kritzinger, E. E.1998JElectrophysiological findings in Stargardt's-fundus flavimaculatus disease953-8 Eye (Lond) 12 ( Pt 6) 1999/05/18Adolescent Adult Child Electrooculography Electroretinography/methods Female Fundus Oculi Humans Macular Degeneration/*physiopathology Male Middle Aged Reaction Time Retrospective Studies PURPOSE: To determine the incidence of electrophysiological abnormalities in patients with Stargardt's-fundus flavimaculatus (STGD/FFM) disease. METHODS: A retrospective review was carried out of the hospital records of 46 patients who had undergone a scotopic, single flash photopic and 30 Hz electroretinogram (ERG), pattern ERG (PERG) and electro-oculogram (EOG). RESULTS: Patients were classified in two groups: those with flecks (n = 26) and those without flecks (n = 20). The incidence of abnormalities (amplitude and/or latency) for the two groups was: PERG, 90% and 98%; 30 Hz ERG, 55.8% and 50%; scotopic ERG, 38.5% and 27.5%; and single flash photopic ERG, 26% and 16%, respectively. EOG abnormalities occurred significantly more frequently in the group with flecks compared with the group without flecks: 69% and 42.5% respectively (p < 0.025). Furthermore, in the group with flecks the group mean scotopic ERG b-wave, 30 Hz ERG b-wave and PERG (P50) amplitude were significantly lower than in the group without flecks (p < 0.01). CONCLUSIONS: The most consistent electrophysiological abnormality in STGD/ FFM is the reduction of the PERG. However, EOG, 30 Hz ERG, scotopic and photopic ERG abnormalities can also frequently occur. ERG and EOG abnormalities occur more often in the presence of flecks.+http://www.ncbi.nlm.nih.gov/pubmed/10325994qStavrou, P Good, P A Misson, G P Kritzinger, E E England Eye (London, England) Eye (Lond). 1998;12 ( Pt 6):953-8.%0950-222X (Print) 0950-222X (Linking)10325994$Birmingham & Midland Eye Centre, UK.eng ||71Armstrong, J. D. Meyer, D. Xu, S. Elfervig, J. L.1998DLong-term follow-up of Stargardt's disease and fundus flavimaculatus448-57; discussion 457-8 Ophthalmology1053 1998/03/21Adolescent Adult Child Child, Preschool Color Perception/physiology Electrooculography Electroretinography Female Fluorescein Angiography Follow-Up Studies *Fundus Oculi Humans Macula Lutea/*pathology Macular Degeneration/*etiology/pathology/physiopathology Male Middle Aged Photography Retina/physiopathology Retinal Degeneration/*etiology/pathology/physiopathology Retrospective Studies Visual Acuity/physiology Visual Fields/physiologyMarOBJECTIVE: To understand better the shared characteristics of Stargardt's macular dystrophy (SMD) and fundus flavimaculatus (FF) by reviewing the clinical morphologic and retinal function changes in a large group of affected patients. DESIGN: The study design was a retrospective case review. PARTICIPANTS: Fifty-two patients with SMD and 48 patients with FF were observed from 1 to 22 years. INTERVENTION: Visual acuity (VA), visual fields (VFs), fundus photographs (FPs), fluorescein angiography (FA), electro-oculography (EOG), and electroretinography (ERG) were studied at various intervals. MAIN OUTCOME MEASURES: Changes of VA, VF, FP, FA, EOG ratio, and ERG amplitudes and implicit time at different periods in patients with SMD and patients with FF were measured. RESULTS: Visual acuity decreased gradually in both the SMD and FF groups, and once the 20/200 level was reached, little further change occurred. The yellowish flecks associated with these entities faded with time, and areas of retinal pigment epithelial (RPE) and choriocapillary atrophy developed. In advanced longstanding disease, retinal vessel attenuation and peripheral pigmentary changes were noted. Ninety-four percent of patients with FF were noted to have macular dystrophy at their last visit. Patients who had only central lesions did not have peripheral lesions develop. Intrafamilial variation in the funduscopic pattern was shown in four families. The EOG ratio was abnormal in 2.6% of the patients with SMD and in 48.6% of the patients with FF. An abnormal scotopic ERG was noted in 21.1% of the patients with FF and in none of the patients with SMD. The photopic ERG was abnormal in 32.4% of the patients with FF and in 5.4% of the patients with SMD. In patients with FF, a statistical dependence was noted between the duration of the disease and the ERG results, but no such correlation was seen in the SMD group. CONCLUSIONS: Morphologic changes and retinal function deterioration are more severe in patients with FF than in patients with SMD. The duration of the disease has a greater effect on patients with FF than on patients with SMD. These clinical morphologic and physiologic data may be used to supplement laboratory molecular biologic studies and aid in the further classification of these entities.*http://www.ncbi.nlm.nih.gov/pubmed/9499775Armstrong, J D Meyer, D Xu, S Elfervig, J L United states Ophthalmology Ophthalmology. 1998 Mar;105(3):448-57; discussion 457-8.%0161-6420 (Print) 0161-6420 (Linking)94997758Vitreoretinal Foundation, Memphis, Tennessee 38120, USA.9S0161-6420(98)93026-3 [pii] 10.1016/S0161-6420(98)93026-3eng||7Suzuki, R. Hirose, T.1996=[A special form of Stargardt's disease/fundus flavimaculatus]562-7Nihon Ganka Gakkai Zasshi1007 1996/07/01Child Child, Preschool Choroid/pathology Family Health Female Fluorescein Angiography Fundus Oculi Humans Macula Lutea/pathology Macular Degeneration/*diagnosis/genetics MaleJulStargardt's disease is a bull's-eye macular dystrophy with the characteristic appearance of a perifoveal lesion. We have observed four cases of an autosomal recessive disease with fundus features undistinguishable from Stargardt's disease, but with a different nature and much poorer prognosis. One case typical of Stargardt's disease characterized with macular degeneration showed a bull's-eye with dark choroid. Sixteen years later, the same eye developed bone corpuscle pigmentation in the periphery with non-recordable electroretinogram. The other three cases were members of a single family. They showed typical macular degeneration consistent with Stargardt's disease but had peripheral degeneration as well. Taking into account that there is a great diversity of retinal functions in Stargardt's disease, these features are different from those reported previously. Stargardt's disease should not be considered as a single clinical entity with a fair prognosis.*http://www.ncbi.nlm.nih.gov/pubmed/8741342Suzuki, R Hirose, T Case Reports English Abstract Research Support, Non-U.S. Gov't Japan Nihon Ganka Gakkai zasshi Nihon Ganka Gakkai Zasshi. 1996 Jul;100(7):562-7.%0029-0203 (Print) 0029-0203 (Linking)8741342LDepartment of Ophthalmology, Yamaguchi University School of Medicine, Japan.jpn ||7NDelori, F. C. Staurenghi, G. Arend, O. Dorey, C. K. Goger, D. G. Weiter, J. J.1995OIn vivo measurement of lipofuscin in Stargardt's disease--Fundus flavimaculatus2327-31Invest Ophthalmol Vis Sci3611 1995/10/01Adolescent Adult Aged Child Female Fundus Oculi Humans Lipofuscin/*analysis Macular Degeneration/genetics/*metabolism Male Middle Aged Pigment Epithelium of Eye/*chemistry Spectrometry, FluorescenceOctPURPOSE: Several histopathologic studies have concluded that Stargardt's disease (Fundus flavimaculatus) is associated with abnormally high levels of lipofuscin-like material in the retinal pigment epithelium. The purpose of this study was to determine whether this material has the same fluorescence characteristics as lipofuscin in vivo and whether noninvasive measurements identify a significant elevation in this material. METHODS: Five patients with autosomal recessive Stargardt's disease were included in this study, as were 45 healthy controls. All patients had the angiographic dark choroid sign. The intensity and emission spectra of lipofuscin fluorescence were measured by noninvasive fundus spectrophotometry at 7 degrees temporal to the fovea. RESULTS: The fluorescence intensities in the five patients with Stargardt's disease were significantly higher (P < 0.0001) than those observed in normal subjects of the same age. The emission spectra in the patients are similar in shape to those measured in normals, but flecks appear to shift the spectra toward shorter wavelengths. CONCLUSIONS: The spectral characteristics of the fluorophore observed in patients with Stargardt's disease are consistent with those of retinal pigment epithelial lipofuscin. These patients have abnormally high levels of lipofuscin, confirming previous histopathologic observations. Noninvasive retinal pigment epithelial lipofuscin measurements may be a useful adjunct in the diagnosis of Stargardt's disease.-F. flavimaculatus.*http://www.ncbi.nlm.nih.gov/pubmed/75587295Delori, F C Staurenghi, G Arend, O Dorey, C K Goger, D G Weiter, J J EYO-RO1-8511/EY/NEI NIH HHS/United States Comparative Study Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 1995 Oct;36(11):2327-31.%0146-0404 (Print) 0146-0404 (Linking)7558729OSchepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USA.eng||7+Lafaut, B. A. van Egmond, J. De Laey, J. J.1995WAsymmetric fundus flavimaculatus/Stargardt's disease, associated with unilateral myopia253-5Int Ophthalmol194 1995/01/01Adult Electroretinography Female Fluorescein Angiography Fundus Oculi Humans Macular Degeneration/*complications/pathology/physiopathology Myopia/*complications/pathology/physiopathology Ophthalmoscopy Visual FieldsAn unusual asymmetric pattern of fundus flavimaculatus was observed in a unilateral myopic patient. Although electrophysiologic testing was similar for both eyes, fundus lesions were different and less pronounced in the myopic eye.*http://www.ncbi.nlm.nih.gov/pubmed/8737707Lafaut, B A van Egmond, J De Laey, J J Case Reports Netherlands International ophthalmology Int Ophthalmol. 1995-1996;19(4):253-5.%0165-5701 (Print) 0165-5701 (Linking)8737707@Department of Ophthalmology, University Hospital Ghent, Belgium.eng||7Kaplan, J. Gerber, S. Larget-Piet, D. Rozet, J. M. Dollfus, H. Dufier, J. L. Odent, S. Postel-Vinay, A. Janin, N. Briard, M. L. et al.,1993\A gene for Stargardt's disease (fundus flavimaculatus) maps to the short arm of chromosome 1308-11 Nat Genet53 1993/11/01Child Chromosome Mapping *Chromosomes, Human, Pair 1 Female Genes, Recessive Genetic Linkage Haplotypes Humans Male Recombination, Genetic Retinal Diseases/*geneticsNovvStargardt's disease (fundus flavimaculatus) is one of the most frequent causes of macular degeneration in childhood and accounts for 7% of all retinal dystrophies. It is an autosomal recessive condition characterized by a bilateral loss of central vision occurring at age 7-12 years. Genetic linkage analysis of eight families has assigned the disease locus to chromosome 1p21-p13. Multipoint linkage analysis and haplotype analysis has allowed us to establish the best estimate for location of the gene over the locus D1S435 (maximum lod score of 12.66). Our results are consistent with the genetic homogeneity of this condition.*http://www.ncbi.nlm.nih.gov/pubmed/8275096Kaplan, J Gerber, S Larget-Piet, D Rozet, J M Dollfus, H Dufier, J L Odent, S Postel-Vinay, A Janin, N Briard, M L Research Support, Non-U.S. Gov't United states Nature genetics Nat Genet. 1993 Nov;5(3):308-11.%1061-4036 (Print) 1061-4036 (Linking)8275096NService de Genetique, INSERM U-12, Hopital des Enfants-Malades, Paris, France.10.1038/ng1193-308engS||7EItabashi, R. Katsumi, O. Mehta, M. C. Wajima, R. Tamai, M. Hirose, T.1993XStargardt's disease/fundus flavimaculatus: psychophysical and electrophysiologic results555-62 Graefes Arch Clin Exp Ophthalmol23110 1993/10/01 Adolescent Adult Aged Child Electroretinography Female Fluorescein Angiography Follow-Up Studies Fundus Oculi Humans Macular Degeneration/classification/genetics/*physiopathology Male Middle Aged Prognosis Psychophysics Retina/*physiology Visual Acuity Visual FieldsOctRetinal functions were analyzed psychophysically and electrophysiologically in 73 patients (146 eyes) with Stargardt's disease/fundus flavimaculatus. Patients were classified into types 1, 2, 3, and 4; patients with type 3 were subdivided into 3E and 3L (early and late onset of initial symptoms). Most had visual acuity (VA) of 20/200 or greater at initial testing. VA declined 0.25 octave/year during follow-up (mean, 6.1 years). Four of 16 patients (25%) older than 40 years had VA of 20/200 or less in the stronger eye. Psychophysical tests (flicker profile, central scotoma, dark adaptation) showed variable degrees of abnormalities. Electrophysiological tests showed significant photopic b-wave amplitude decreases, particularly in type 3E (42.2% of normal). The electro-oculogram light peak/dark trough ratio was abnormal in 60 of 132 eyes (45.5%), especially in type 3E (25 of 34 eyes, 73.5%). Visual prognosis and overall visual function varied depending upon disease type, location of retinal lesions, and age of onset. In Type 3E, overall retinal function was poorest and accompanied by the most severe decline of central vision and function in the surrounding macula.*http://www.ncbi.nlm.nih.gov/pubmed/8224929 Itabashi, R Katsumi, O Mehta, M C Wajima, R Tamai, M Hirose, T Germany Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie Graefes Arch Clin Exp Ophthalmol. 1993 Oct;231(10):555-62.%0721-832X (Print) 0721-832X (Linking)82249292Schepens Eye Research Institute, Boston, MA 02114.eng||7'Lachapelle, P. Little, J. M. Roy, M. S.1989FThe electroretinogram in Stargardt's disease and fundus flavimaculatus395-404Doc Ophthalmol734 1989/12/010Adolescent Adult Child Diagnosis, Differential Double-Blind Method *Electroretinography Female Fluorescein Angiography Fundus Oculi Humans Macular Degeneration/diagnosis/pathology/*physiopathology Male Oscillometry Retinal Diseases/diagnosis/pathology/*physiopathology Retrospective Studies Visual AcuityDecZA retrospective study was performed comparing the ERG results of 15 patients with Stargardt's disease and fundus flavimaculatus. Patients with fundus flavimaculatus had "fish-tail" lesions with or without macular changes, while the Stargardt's group had macular atrophy without fish-tail flecks. The mean visual acuity was 20/200 for the Stargardt's patients compared with a mean of 20/80 for the fundus flavimaculatus patients. The Stargardt's photopic and scotopic amplitudes were respectively 33% and 34% of normal, while the fundus flavimaculatus values were less impaired at 58% and 64% of normal.*http://www.ncbi.nlm.nih.gov/pubmed/2637122Lachapelle, P Little, J M Roy, M S Comparative Study Research Support, Non-U.S. Gov't Netherlands Documenta ophthalmologica. Advances in ophthalmology Doc Ophthalmol. 1989 Dec;73(4):395-404.%0012-4486 (Print) 0012-4486 (Linking)2637122\Department of Ophthalmology, McGill University-Montreal Children's Hospital, Quebec, Canada.eng~t7 Aaberg, T. M.1986sStargardt's disease and fundus flavimaculatus: evaluation of morphologic progression and intrafamilial co-existence453-87Trans Am Ophthalmol Soc84 1986/01/01Adaptation, Ocular Adolescent Adult Aged Child Color Perception Electrooculography Electroretinography Female Fluorescein Angiography *Fundus Oculi Humans Macular Degeneration/*genetics/physiopathology Male Middle Aged Pedigree Prospective Studies Visual Fields*http://www.ncbi.nlm.nih.gov/pubmed/3590477xAaberg, T M United states Transactions of the American Ophthalmological Society Trans Am Ophthalmol Soc. 1986;84:453-87.%0065-9533 (Print) 0065-9533 (Linking)12987473590477eng[||7Gelisken, O. De Laey, J. J.1985TA clinical review of Stargardt's disease and/or fundus flavimaculatus with follow-up225-35Int Ophthalmol84 1985/11/01Adolescent Adult Child Color Perception Dark Adaptation Electrooculography Electroretinography Female Fluorescein Angiography Fundus Oculi Humans Macular Degeneration/*genetics/pathology/physiopathology Male Vision, Ocular/physiology Visual FieldsNovOut of 49 patients diagnosed as having Stargardt's disease that have been clinically reviewed, 22 of these cases have been followed for a period up to 13 years. The cases have been studied in three subgroups, according to their fundus appearance. Patients from group I were those whose lesions were confined to the macula, showing no flecks in the retina. In group II the macular lesion was surrounded by perimacular flecks and in group III fundus flavimaculatus flecks were seen, diffusely scattered in the posterior pole. It appears that the prognosis of group I is better than the other groups, where surrounding flecks are seen in addition to the macular lesion. The follow-up indicates that the disease evolves with a rather large spectrum of expressivity. Assessment of a predictive factor for the evolution of the disease is not yet possible. However, the observation of a dark choroid appears to be strongly suggestive for a further centrifugal progression of the disease.*http://www.ncbi.nlm.nih.gov/pubmed/4086170fGelisken, O De Laey, J J Netherlands International ophthalmology Int Ophthalmol. 1985 Nov;8(4):225-35.%0165-5701 (Print) 0165-5701 (Linking)4086170eng||7)Wakabayashi, K. Yonemura, D. Kawasaki, K.1985PElectrophysiological analysis of Stargardt's disease fundus flavimaculatus group141-7Doc Ophthalmol602 1985/08/30Adolescent Adult Child *Electrooculography *Electroretinography Female Fluorescein Angiography Fundus Oculi Humans Male Retinal Diseases/classification/pathology/*physiopathologyAug 30Stargardt's disease-fundus flavimaculatus has four general distribution patterns in fundus appearance: (1) macular degeneration without flecks; (2) macular degeneration with perifoveal flecks; (3) macular degeneration with diffuse flecks; and (4) diffuse flecks without macular degeneration (Noble and Carr, 1979). Four cases corresponding each to the four subgroups were studied electrophysiologically by our new tests for the cone receptor cell (rapid off-response in the ERG) and for the retinal pigment epithelium (the hyperosmolarity response and the Diamox response). The results of our electrophysiological tests appear consistent with the histological findings by Klien and Krill (1967) and by Eagle et al. (1980), showing that the primary defect of fundus flavimaculatus is in the retinal pigment epithelium. Electrophysiologically, the severity of the disease correlated well with each fundus pattern.*http://www.ncbi.nlm.nih.gov/pubmed/4042820Wakabayashi, K Yonemura, D Kawasaki, K Case Reports Netherlands Documenta ophthalmologica. Advances in ophthalmology Doc Ophthalmol. 1985 Aug 30;60(2):141-7.%0012-4486 (Print) 0012-4486 (Linking)4042820engE||7,Moloney, J. B. Mooney, D. J. O'Connor, M. A.1983ARetinal function in Stargardt's disease and fundus flavimaculatus57-65Am J Ophthalmol961 1983/07/01Adolescent Adult Aging Diagnosis, Differential Female Fundus Oculi Humans Macular Degeneration/diagnosis/*genetics/physiopathology Male Psychophysiology Retina/*physiopathology Retinal Diseases/diagnosis/*physiopathology Syndrome Time FactorsJulzTen patients with Stargardt's disease and 14 with fundus flavimaculatus underwent thorough ophthalmic examinations, retinal photography, and, when possible, fluorescein angiography. Retinal function was also assessed by static and kinetic perimetry, the Farnsworth-Munsell 100-hue test, electro-oculography, and electroretinography. Visual acuity and color discrimination were reduced in all patients (mean visual acuity, 20/120; mean error score, 365). On electroretinography all patients had some significant abnormality of cone function and 24 eyes had abnormal rod function (mean Vmax, 298.3). Electrooculographic findings were abnormal in 24 eyes and borderline in ten others. These abnormalities were similar in both groups but more severe in fundus flavimaculatus. Stargardt's disease and fundus flavimaculatus did not co-exist in any family studied and the mean duration of disease was similar in both, indicating that Stargardt's disease did not progress to fundus flavimaculatus. Both the age of onset and duration significantly affected the severity of fundus flavimaculatus but neither had a significant effect on Stargardt's disease.*http://www.ncbi.nlm.nih.gov/pubmed/6869480Moloney, J B Mooney, D J O'Connor, M A Comparative Study Research Support, Non-U.S. Gov't United states American journal of ophthalmology Am J Ophthalmol. 1983 Jul;96(1):57-65.%0002-9394 (Print) 0002-9394 (Linking)6869480eng||7Ajamian, P. C. Wallace, W.1982-Stargardt's disease and fundus flavimaculatus1005-6J Am Optom Assoc5312 1982/12/01Electrooculography Electroretinography Female Fundus Oculi Humans *Macula Lutea Middle Aged Retinal Diseases/*diagnosis Visual AcuityDec*http://www.ncbi.nlm.nih.gov/pubmed/7153442Ajamian, P C Wallace, W Case Reports United states Journal of the American Optometric Association J Am Optom Assoc. 1982 Dec;53(12):1005-6.%0003-0244 (Print) 0003-0244 (Linking)7153442engC||7 van Meel, G. J. Winkelman, J. E.1982ZDystrophia retinae pigmentosa, fundus flavimaculatus and Stargardt's disease in one family13-20Ophthalmologica1841 1982/01/01Adolescent Adult Aged Child Fluorescein Angiography *Fundus Oculi Humans Macular Degeneration/complications/diagnosis/*genetics Male Middle Aged Pedigree Retinitis Pigmentosa/complications/diagnosis/*geneticsjThis paper describes a family, the propositus of which suffers from dystrophia retinae pigmentosa combined with fundus flavimaculatus and Stargardt's disease. The patient's mother and a maternal uncle suffer from a dystrophia retinae pigmentosa, whereas a sister shows peripheral degenerations. A further sister has a scotopic b wave of the ERG of low amplitude.*http://www.ncbi.nlm.nih.gov/pubmed/7054737van Meel, G J Winkelman, J E Case Reports Switzerland Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde Ophthalmologica. 1982;184(1):13-20.%0030-3755 (Print) 0030-3755 (Linking)7054737eng||7Noble, K. G. Carr, R. E.1979-Stargardt's disease and fundus flavimaculatus1281-5Arch Ophthalmol977 1979/07/01Adolescent Adult Atrophy Child Color Perception Tests Electrooculography Electroretinography Eye Diseases/diagnosis/genetics Female *Fundus Oculi Humans Macula Lutea Macular Degeneration/diagnosis/*genetics/physiopathology Male Middle Aged Visual Acuity Visual Field TestsJulaA study of 67 patients with a diagnosis of Stargardt's disease (juvenile macular degeneration) or fundus flavimaculatus showed that, apart from the ophthalmoscopic appearance, there is no clear distinction between these two disorders. The disease is an autosomal recessive macular degeneration that is bilateral and symmetrical in appearance, with diminished central vision as the hallmark symptom. The onset of symptoms usually occurred in the first or second decade, but a substantial number of patients were asymptomatic until the fourth or fifth decade. Psychophysical and electrophysiologic tests indicated that this is a localized and not a generalized retinal dystrophy. While the initial vision in the better eye was 6/12 (20/40) or better in one third of the patients, follow-up studies showed progression to levels between 6/30 (20/100) and 6/60 (20/400).)http://www.ncbi.nlm.nih.gov/pubmed/454263Noble, K G Carr, R E Research Support, U.S. Gov't, P.H.S. United states Archives of ophthalmology Arch Ophthalmol. 1979 Jul;97(7):1281-5.%0003-9950 (Print) 0003-9950 (Linking)454263eng(||7Streicher, T. Krcmery, K.1977/[Stargardt's disease and fundus flavimaculatus]141-6 Cesk Oftalmol332 1977/03/01Adolescent Child Fluorescein Angiography *Fundus Oculi Humans Retinal Degeneration/*congenital Retinal Detachment/diagnosis SyndromeMar)http://www.ncbi.nlm.nih.gov/pubmed/849613xStreicher, T Krcmery, K English Abstract Czechoslovakia Ceskoslovenska oftalmologie Cesk Oftalmol. 1977 Mar;33(2):141-6.%0009-059X (Print) 0009-059X (Linking)849613,Stargardtova choroba a fundus flavimaculatussloE||7Hadden, O. B. Gass, J. D.1976-Fundus flavimaculatus and Stargardt's disease527-39Am J Ophthalmol824 1976/10/01EAdolescent Adult Atrophy/complications Child Electrooculography Electroretinography Female Fluorescein Angiography *Fundus Oculi Humans Macula Lutea/pathology Male Middle Aged Night Blindness/etiology Retinal Degeneration/*congenital/diagnosis/genetics Retinal Diseases/diagnosis/genetics Syndrome Visual Acuity Visual FieldsOctkOf 42 patients studied who had fundus flavimaculatus and Stargardt's disease, most had reduced visual acuity due to an atrophic macular lesion. Family histories were consistent with autosomal-recessive inheritance. In some young patients, the yellow-white flecks developed with time, while in some older patients the flecks faded, pari passau with increasing retinal pigment epithelial atrophy. Fluorescein angiography showed that most white flecks were largely or totally nonfluorescent. Even after the flecks had faded from view, the sites where they had been usually remained nonfluorescent. In patients with lesions confined to the posterior pole, the electroretinogram and electro-oculogram were usually normal; in patients with widespread lesions, one or both tests were usually abnormal. Affected members of any one family had a similar distribution of fundus lesions.*http://www.ncbi.nlm.nih.gov/pubmed/1086060Hadden, O B Gass, J D Research Support, U.S. Gov't, P.H.S. United states American journal of ophthalmology Am J Ophthalmol. 1976 Oct;82(4):527-39.%0002-9394 (Print) 0002-9394 (Linking)1086060eng||7-Puech, B. Turut, P. Francois, P. Hache, J. C.1976a[Stargardt's incipient flavimaculatus disease (apropos of 2 cases of pure fundus flavimaculatus)]739-44Bull Soc Ophtalmol Fr767-8 1976/07/01Child Female *Fundus Oculi Humans Macular Degeneration/*congenital Retinal Degeneration/*congenital Retinal Diseases/pathology Syndrome Visual Field TestsJul-Aug*http://www.ncbi.nlm.nih.gov/pubmed/1029569Puech, B Turut, P Francois, P Hache, J C Case Reports English Abstract France Bulletin des societes d'ophtalmologie de France Bull Soc Ophtalmol Fr. 1976 Jul-Aug;76(7-8):739-44.%0081-1270 (Print) 0081-1270 (Linking)1029569,Maladie de Stargardt flavimaculee incipiens.freh||7-Francois, P. Turut, P. Puech, B. Hache, J. C.1975/[Stargardt's disease and fundus flavimaculatus]817-46 Arch Ophtalmol Rev Gen Ophtalmol3511 1975/11/01Adolescent Child Female Fluorescein Angiography *Fundus Oculi Genes, Recessive Humans Macular Degeneration/diagnosis/*genetics Male Ophthalmoscopy Retinal Degeneration/*genetics Retinal Vessels Visual Acuity Visual Fields Visual PerceptionNovkFrom their sixty two personnal observations and a study of literature cases, the authors demonstrate that the ophthalmoscopic fluoroscopic and functionnal aspects of macular lesions are strictly identical in Stargardt disease and in Fundus Flavimaculatus. Their transmission is also identical, generally autosomal and recessive, more rarely dominant. Flavimaculate lesions situated in perimacular or inperipheric area may coexist in the same family, and certainly correspond to variable forms of expressivity of a unique gene. The authors discuss the nosologic problems brought by these two affections and other juvenile macular degenerations. Their conclusions are as follows: The same disease may present three different forms: -- Pure Stargardt disease; -- Stargardt disease with perimacular flavimaculate crown; -- Stargardt disease with peripheric Fundus Flavimaculatus.)http://www.ncbi.nlm.nih.gov/pubmed/131535Francois, P Turut, P Puech, B Hache, J C English Abstract France Archives d'ophtalmologie et revue generale d'ophtalmologie Arch Ophtalmol Rev Gen Ophtalmol. 1975 Nov;35(11):817-46.%0003-973X (Print) 0003-973X (Linking)131535-Maladie de Stargardt et fundus flavimaculatusfre ||7-Turut, P. Puech, B. Francois, P. Hache, J. C.1975w[Fundus flavimaculatus of dominant heredity (apropos of 2 families). Nosological considerations on Stargardt's disease]309-15Bull Soc Ophtalmol Fr753 1975/03/01Adolescent Adult Aged Child Female Genes, Dominant Humans Macular Degeneration/classification/*genetics Male Retinal Degeneration/*geneticsMar*http://www.ncbi.nlm.nih.gov/pubmed/1204180Turut, P Puech, B Francois, P Hache, J C Case Reports France Bulletin des societes d'ophtalmologie de France Bull Soc Ophtalmol Fr. 1975 Mar;75(3):309-15.%0081-1270 (Print) 0081-1270 (Linking)1204180"Fundus flavimaculatus" a heredite dominante (a propos de deux familles) Considerations nosologiques sur la maladie de Stargardtfre 4||7%Kellner, U. Kraus, H. Foerster, M. H.2000SMultifocal ERG in chloroquine retinopathy: regional variance of retinal dysfunction94-7 Graefes Arch Clin Exp Ophthalmol2381 2000/02/09QAdaptation, Ocular Aged Antirheumatic Agents/*adverse effects Chloroquine/*adverse effects Color Vision Defects/chemically induced/physiopathology *Electroretinography Female Humans Middle Aged Retina/drug effects/*physiopathology Retinal Diseases/chemically induced/*physiopathology Severity of Illness Index Visual Acuity Visual FieldsJanBACKGROUND: A study was carried out to evaluate the regional variance of retinal dysfunction in chloroquine retinopathy. METHODS: In three patients with different stages of chloroquine retinopathy, ophthalmologic evaluations including recording of full-field electroretinogram (ISCEV standard) and multifocal electroretinogram were performed. RESULTS: In one patient with mild chloroquine retinopathy the visual acuity, visual fields and full-field electroretinogram were normal, but retinal dysfunction was indicated by color vision disturbances. The second patient had moderate chloroquine retinopathy with normal visual acuity, visual fields and dark-adapted full-field electroretinogram; light-adapted and flicker full-field electroretinogram responses were, however, borderline and color vision was abnormal. The third patient had severe chloroquine retinopathy with reduced visual acuity, visual field and color vision defects, and a reduced full-field electroretinogram. In the multifocal electroretinogram, recorded with 61 hexagons, amplitudes and implicit times were evaluated in rings surrounding the center. In all three patients severe dysfunction (either amplitudes or implicit times) was found in the parafoveal and perifoveal areas. In the fovea and towards the periphery the function was normal or only moderately reduced. CONCLUSION: Chloroquine retinopathy of different severity presents with characteristic alterations in the multifocal electroretinogram. Regional distribution of cone dysfunction is in agreement with previously reported histologic findings. The multifocal electroretinogram can detect retinal dysfunction in chloroquine retinopathy even when the full-field electroretinogram is normal and retinal alterations are subtle.+http://www.ncbi.nlm.nih.gov/pubmed/10664060Kellner, U Kraus, H Foerster, M H Comparative Study Germany Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie Graefes Arch Clin Exp Ophthalmol. 2000 Jan;238(1):94-7.%0721-832X (Print) 0721-832X (Linking)10664060Department of Ophthalmology, Universitats-Klinikum Benjamin Franklin, Freie Universitat Berlin, Hindenburgdamm 30, D-12200 Berlin, Germany. kellneru@zedat.fu-berlin.de02380094.417 [pii]eng 9||7cMa, K. Yang, X. F. Han, C. Zhang, N. Xu, J. Liu, S. B. Lu, H. Snellingen, T. Wang, N. L. Liu, N. P.2009wClinical features and linkage analysis for a Chinese family with autosomal dominant central areolar choroidal dystrophy2686-90Chin Med J (Engl)12222 2009/12/03Adolescent Adult Child Choroid Diseases/*genetics Electroretinography Female Fluorescein Angiography *Genetic Linkage Humans Male Middle AgedNov 20BACKGROUND: A Chinese family with autosomal dominant central areolar choroidal dystrophy (CACD) was identified. The purpose of this study was to collect the clinical findings from the family and to identify the genetic entity by linkage analysis. METHODS: Forty-three individuals from 3 generations of the family underwent ophthalmologic examinations, including best-corrected visual acuity, examination of the anterior segments, and inspection of the ocular fundus after pharmacologic mydriasis. Affected family members further underwent color vision test, color fundus photography, fluorescein angiography, automated perimetry, and electroretinography. The family was followed up for 30 months. Peripheral venous blood or buccal swabs were collected from each family member and genomic DNA was extracted. Linkage analysis was performed for candidate genes or loci using microsatellite markers. RESULTS: Seven family members in 3 continuous generations were diagnosed as having autosomal dominant CACD. The family showed progressive development of the disease, affecting both male and female. Age of onset of visual disturbances varied between 11 and 50 years. Phenotypic variability among affected individuals was apparent and ranged from relatively normal-appearing fundus with mild parafoveal pigment mottling to geographic atrophy of the macula. Fluorescein angiography showed hyperfluorescent parafoveal changes in early stage or well-demarcated area of chorioretinal atrophy with enhanced visibility of the residual underlying choroidal vessels in the late stage. Peripheral retina and visual fields were normal in affected individuals. Electroretinogram showed normal or mild reduction in the photopic amplitude. Eight candidate genes (STGD4, RCD1, peripherin/RDS, GUCA1A, RIMS1, UNC119, GUCY2D, and AIPL1) and two genetic loci (4p15.2 - 16.3, and 17p13) were excluded to be responsible for the disease by linkage analysis. CONCLUSIONS: The clinical findings of this Chinese family with CACD shared similarities with previously reported families of other ethnicities. Linkage analysis excluded the known genes and genetic loci, indicating genetic heterogeneity of the disease.+http://www.ncbi.nlm.nih.gov/pubmed/19951596Ma, Kai Yang, Xiu-fen Han, Cui Zhang, Ning Xu, Jun Liu, Shou-bin Lu, Hai Snellingen, Torkel Wang, Ning-li Liu, Ning-pu Research Support, Non-U.S. Gov't China Chinese medical journal Chin Med J (Engl). 2009 Nov 20;122(22):2686-90.%0366-6999 (Print) 0366-6999 (Linking)19951596Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing, China.engO||7zOuechtati, F. Belhadj Tahar, O. Mhenni, A. Chakroun, S. Chouchene, I. Oueslati, S. Rebai, A. Abdelhak, S. Jeddi-Blouza, A.2009Central areolar choroidal dystrophy associated with inherited drusen in a multigeneration Tunisian family: exclusion of the PRPH2 gene and the 17p13 locus589-94 J Hum Genet5410 2009/08/22Adult Aged Aged, 80 and over Choroid Diseases/complications/*genetics *Chromosomes, Human, Pair 17 Consanguinity Eye Diseases, Hereditary/*genetics *Family Family Characteristics Female Humans Intermediate Filament Proteins/*genetics/physiology Male Membrane Glycoproteins/*genetics/physiology Middle Aged Nerve Tissue Proteins/*genetics/physiology Pedigree Retinal Drusen/complications/*genetics TunisiaOctMCentral areolar choroidal dystrophy (CACD) is a rare inherited disease, which causes progressive profound loss of vision in patients during their fourth decade. It is characterized by atrophy of retinal pigment epithelium, photoreceptors and choriocapillaris. The disease showed a genetic heterogeneity. Previously, mutations in the peripherin/RDS gene and a linkage to the CACD locus in the 17p13 region have been reported in CACD families. In this study, we report on a clinical and genetic investigation of CACD in a large Tunisian consanguineous family with 21 affected individuals in three living generations. CACD has been associated with drusen in some of them. Linkage analysis and mutational screening exclude linkage to the PRPH2/RDS gene and to the CACD locus. These data provide further evidence of the genetic heterogeneity of CACD.+http://www.ncbi.nlm.nih.gov/pubmed/19696794Ouechtati, Farah Belhadj Tahar, Olfa Mhenni, Amin Chakroun, Sonia Chouchene, Ibtissem Oueslati, Souad Rebai, Ahmed Abdelhak, Sonia Jeddi-Blouza, Amel Case Reports Research Support, Non-U.S. Gov't Japan Journal of human genetics J Hum Genet. 2009 Oct;54(10):589-94. Epub 2009 Aug 21.*1435-232X (Electronic) 1434-5161 (Linking)19696794VMolecular Investigation of Genetic Orphan Diseases, Pasteur Institute, Tunis, Tunisia.#jhg200982 [pii] 10.1038/jhg.2009.82eng ||7sBoon, C. J. Klevering, B. J. Cremers, F. P. Zonneveld-Vrieling, M. N. Theelen, T. Den Hollander, A. I. Hoyng, C. B.2009#Central areolar choroidal dystrophy771-82, 782 e1 Ophthalmology1164 2009/02/27Adult Age of Onset Aged Choroid Diseases/diagnosis/*genetics/physiopathology Color Perception Tests DNA Mutational Analysis Electrooculography Electroretinography Female Fluorescein Angiography Follow-Up Studies Founder Effect Haplotypes Humans Intermediate Filament Proteins/*genetics Male Membrane Glycoproteins/*genetics Microsatellite Repeats Middle Aged *Mutation Nerve Tissue Proteins/*genetics Photography Polymerase Chain Reaction Polymorphism, Single Nucleotide Retinal Cone Photoreceptor Cells/pathology Retinal Degeneration/diagnosis/*genetics/physiopathology Retinal Pigment Epithelium/pathology Retrospective Studies Tomography, Optical CoherenceAprjOBJECTIVE: To describe the clinical characteristics, follow-up data and molecular genetic background in a large group of patients with central areolar choroidal dystrophy (CACD). DESIGN: Retrospective case series study. PARTICIPANTS: One hundred three patients with CACD from the Netherlands. METHODS: Ophthalmologic examination, including color vision testing, fundus photography, fluorescein angiography, fundus autofluorescence (FAF) imaging, optical coherence tomography, full-field electroretinography (ERG), multifocal ERG, and electrooculography. Blood samples were obtained for DNA extraction and subsequent analysis of the peripherin/RDS gene, as well as haplotype analysis. MAIN OUTCOME MEASURES: Clinical characteristics, phenotypic range, clinical follow-up data, and FAF findings. RESULTS: The mean age at onset of visual loss was 46 years, with subsequent gradual deterioration in visual acuity. Ninety-eight patients carried a p.Arg142Trp mutation in peripherin/RDS, whereas 5 affected members of a CACD family carried a p.Arg172Gln peripherin/RDS mutation. A remarkable variation in disease severity was observed, and nonpenetrance was seen up to the age of 64 years, in up to 21% of mutation carriers. However, most macular lesions in mutation carriers displayed a typical stage of CACD. Substantial changes were seen on FAF imaging after a mean follow-up period of 11 months. Electrophysiologic data were consistent with a central cone dystrophy. The age at onset and phenotypic characteristics of CACD show considerable overlap with atrophic age-related macular degeneration (AMD). The great majority of p.Arg142Trp-carrying CACD patients originated from the southeast region of the Netherlands, and haplotype analysis strongly suggested a common founder mutation. CONCLUSIONS: When caused by a p.Arg142Trp mutation in the peripherin/RDS gene, CACD causes a central cone dystrophy phenotype. This mutation, which most likely originates from a common founder in most patients, is associated with a significant degree of nonpenetrance. In the elderly patient, CACD may be confused with AMD, especially in cases with decreased penetrance.+http://www.ncbi.nlm.nih.gov/pubmed/19243827 Boon, Camiel J F Klevering, B Jeroen Cremers, Frans P M Zonneveld-Vrieling, Marijke N Theelen, Thomas Den Hollander, Anneke I Hoyng, Carel B Research Support, Non-U.S. Gov't United States Ophthalmology Ophthalmology. 2009 Apr;116(4):771-82, 782.e1. Epub 2009 Feb 25.*1549-4713 (Electronic) 0161-6420 (Linking)19243827cDepartment of Ophthalmology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.8S0161-6420(08)01270-0 [pii] 10.1016/j.ophtha.2008.12.019eng||7Riveiro-Alvarez, R. Trujillo-Tiebas, M. J. Gimenez, A. Cantalapiedra, D. Vallespin, E. Aguirre-Lamban, J. Villaverde, C. Ayuso, C.2007^Novel human pathological mutations. Gene symbol: RS1. Disease: X-linked juvenile retinoschisis647 Hum Genet1215 2007/09/20[Eye Proteins/*genetics *Genetic Diseases, X-Linked Humans *Mutation Retinoschisis/*geneticsJun+http://www.ncbi.nlm.nih.gov/pubmed/17879437Riveiro-Alvarez, Rosa Trujillo-Tiebas, M J Gimenez, A Cantalapiedra, D Vallespin, E Aguirre-Lamban, J Villaverde, C Ayuso, C Germany Human genetics Hum Genet. 2007 Jun;121(5):647.%0340-6717 (Print) 0340-6717 (Linking)17879437KFundacion Jimenez Diaz, Department Genetics, Madrid, Spain. rriveiro@fjd.eseng||7:Zeng, M. Yi, C. Guo, X. Jia, X. Deng, Y. Wang, J. Shen, H.2007lIdentification of novel mutations in the XLRS1 gene in Chinese patients with X-linked juvenile retinoschisis685-91 Curr Eye Res327-8 2007/09/14Asian Continental Ancestry Group/genetics Child Child, Preschool DNA Mutational Analysis Exons/genetics Eye Proteins/*genetics *Frameshift Mutation Humans Male *Mutation, Missense Pedigree Polymerase Chain Reaction Polymorphism, Single-Stranded Conformational Retinoschisis/*geneticsJul-AugX-linked juvenile retinoschisis (XLRS) is a major cause of macular degeneration in young men. In this study we analyzed all six exons of the XLRS1 gene in four sporadic XLRS patients and in an affected family in China who were recently diagnosed. We found there are five different mutations with four containing missense point mutations and one having a frame-shift deletion. Among these mutations both c.644A>T and c.520delC are novel and have not been previously reported. Moreover all the second-generation offsprings and most of the third-generation ones in the affected family were found to carry the mutations bearing X chromosome. The discovery of novel mutations in the XLRS1 gene would increase the available information about the spectrum of genetic abnormalities causing XLRS. Although the limited data failed to reveal a correlation between mutations and disease phenotypes our identification of novel mutations in the XLRS1 gene will facilitate early and correct diagnosis and genetic counseling regarding the prognosis of XLRS disease.+http://www.ncbi.nlm.nih.gov/pubmed/17852193Zeng, Meizhen Yi, Changxian Guo, Xiangming Jia, Xiaoyun Deng, Yan Wang, Juan Shen, Huangxuan Research Support, Non-U.S. Gov't England Current eye research Curr Eye Res. 2007 Jul-Aug;32(7-8):685-91.%0271-3683 (Print) 0271-3683 (Linking)17852193mState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China.)781953239 [pii] 10.1080/02713680701486410eng ~t7Li, X. Ma, X. Tao, Y.2007xClinical features of X linked juvenile retinoschisis in Chinese families associated with novel mutations in the RS1 gene804-12Mol Vis13 2007/07/07-Adolescent Adult Aged Asian Continental Ancestry Group/*genetics Base Sequence Child China DNA Mutational Analysis Exons/genetics Eye Proteins/*genetics Female Fundus Oculi Humans Male Middle Aged Molecular Sequence Data Mutation/*genetics Pedigree Refractive Errors Retinoschisis/*genetics/*pathologyzPURPOSE: To describe the clinical phenotype of X linked juvenile retinoschisis (XLRS) in 12 Chinese families with 11 different mutations in the XLRS1 (RS1) gene. METHODS: Complete ophthalmic examinations were carried out in 29 affected males (12 probands), 38 heterozygous females carriers, and 100 controls. The coding regions of the RS1 gene that encodes retinoschisin were amplified by polymerase chain reaction and directly sequenced. RESULTS: Of the 29 male participants, 28 (96.6%) displayed typical foveal schisis. Eleven different RS1 mutations were identified in 12 families; four of these mutations, two frameshift mutations (26 del T of exon 1 and 488 del G of exon 5), and two missense mutations (Asp145His and Arg156Gly) of exon 5, had not been previously described. One non-disease-related polymorphism (NSP): 576C to T (Pro192Pro) change was also newly reported herein. We compared genotypes and observed more severe clinical features in families with the following mutations: frameshift mutation (26 del T) of exon 1, the splice donor site mutation (IVS1+2T to C),or Arg102Gln, Arg209His, and Arg213Gln mutations. CONCLUSIONS: Severe XLRS phenotypes are associated with the frameshift mutation 26 del T, splice donor site mutation (IVS1+2T to C), and Arg102Gln, Asp145His, Arg209His, and Arg213Gln mutations. The wide variability in the phenotype in Chinese patients with XLRS and different mutations in the RS1 gene is described. Identification of mutations in the RS1 gene and expanded information on clinical manifestations will facilitate early diagnosis, appropriate early therapy, and genetic counseling regarding the prognosis of XLRS.+http://www.ncbi.nlm.nih.gov/pubmed/17615541~Li, Xiaoxin Ma, Xiang Tao, Yong Research Support, Non-U.S. Gov't United States Molecular vision Mol Vis. 2007 Jun 7;13:804-12.*1090-0535 (Electronic) 1090-0535 (Linking)276875617615541Department of Ophthalmology, People's Hospital, Peking University, Beijing, PR China. drlixiaoxin@vip.sina.com v13/a88 [pii]eng I~t7SSuganthalakshmi, B. Shukla, D. Rajendran, A. Kim, R. Nallathambi, J. Sundaresan, P.2007lGenetic variations in the hotspot region of RS1 gene in Indian patients with juvenile X-linked retinoschisis611-7Mol Vis13 2007/05/23Adolescent Adult Asian Continental Ancestry Group/*genetics Child Codon, Nonsense DNA Mutational Analysis Electrophoresis, Polyacrylamide Gel Exons Eye Proteins/*genetics *Genetic Variation Humans India Male Mutation, Missense Polymerase Chain Reaction Polymorphism, Restriction Fragment Length Polymorphism, Single-Stranded Conformational Protein Structure, Tertiary Retinoschisis/*geneticsPURPOSE: X-linked juvenile retinoschisis (XLRS) is the leading cause of macular degeneration in males. This condition is caused by mutations in the RS1 gene and is, characterized by schisis within the retina. The purpose of this study was to identify the mutations in the RS1 gene associated with XLRS in an Indian cohort. METHODS: The coding region of RS1 was analyzed for mutations by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and restriction fragment length polymorphism (RFLP) analysis in six unrelated subjects clinically diagnosed as having XLRS and in their available family members. Direct sequencing was performed for all samples that displayed an electrophoretic mobility shift in SSCP gel. RESULTS: Mutation analysis of RS1 gene revealed five mutations in exon 6 like c.574C>T, c.583A>G, c.608C>T, c.617G>A, and c.637C>T, respectively, among them four missense mutations, one nonsense mutation, and two novel sequence variations. These mutations were found in individuals who exhibited clinical features of bilateral foveal and peripheral retinoschisis consistent with XLRS. The mutations were absent in the 100 age matched control samples analyzed. CONCLUSIONS: This is the first report of mutations in RS1 to be associated with XLRS in the Indian population. The identified genetic variations, phenotype and genotype correlations were consistent with other studies. Identification of the causative mutation in patients with XLRS is helpful in confirming the diagnosis and in counseling of family members.+http://www.ncbi.nlm.nih.gov/pubmed/17515881Suganthalakshmi, Balasubbu Shukla, Dhananjay Rajendran, Anand Kim, Ramasamy Nallathambi, Jeyabalan Sundaresan, Periasamy Research Support, Non-U.S. Gov't United States Molecular vision Mol Vis. 2007 Apr 19;13:611-7.*1090-0535 (Electronic) 1090-0535 (Linking)266950717515881LDepartment of Genetics, Aravind Medical Research Foundation, Madurai, India. v13/a66 [pii]eng||7Agarwal, A. Rao, U. S.2007=Outer retinal corrugations in x-linked juvenile retinoschisis278-9Arch Ophthalmol1252 2007/02/14Adult Child Fluorescein Angiography Humans Male Retina/*pathology Retinoschisis/*diagnosis Siblings Tomography, Optical CoherenceFeb+http://www.ncbi.nlm.nih.gov/pubmed/17296908Agarwal, Anita Rao, Usha Sathish Case Reports Research Support, Non-U.S. Gov't United States Archives of ophthalmology Arch Ophthalmol. 2007 Feb;125(2):278-9.%0003-9950 (Print) 0003-9950 (Linking)17296908Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USA. anita.agarwal@vanderbilt.edu*125/2/278 [pii] 10.1001/archopht.125.2.278eng||7Jin, Z. B. Nao, I. N.2007OA novel truncating Rs1 mutation associated with X-linked juvenile retinoschisis71-3Jpn J Ophthalmol511 2007/02/14Adolescent Adult Child Child, Preschool *Codon, Nonsense DNA Mutational Analysis Electroretinography Eye Proteins/*genetics Female Humans Male Pedigree Polymerase Chain Reaction Retinoschisis/*genetics Tomography, Optical CoherenceJan-Feb+http://www.ncbi.nlm.nih.gov/pubmed/17295148Jin, Zi-Bing Nao-I, Nobuhisa Case Reports Letter Japan Japanese journal of ophthalmology Jpn J Ophthalmol. 2007 Jan-Feb;51(1):71-3. Epub 2007 Feb 9.%0021-5155 (Print) 0021-5155 (Linking)1729514810.1007/s10384-006-0387-0eng>||7MKraus, D. Karlstetter, M. Walczak, Y. Hilfinger, D. Langmann, T. Weber, B. H.2011Retinal expression of the X-linked juvenile retinoschisis (RS1) gene is controlled by an upstream CpG island and two opposing CRX-bound regions245-54Biochim Biophys Acta18094-6 2011/03/12Apr-Jun"X-linked juvenile retinoschisis (XLRS) is an orphan retinal disease in males caused by mutations in the RS1 gene. Previously we have characterized cone-rod homeobox (CRX)-responsive elements in the promoter region of RS1 driving selective gene expression in the retina. Here, we expanded our identification and functional analysis of cis-regulatory elements controlling quantitative expression of RS1 in vitro and in vivo. Sequence analysis identified a CpG island 3kb upstream of the transcription start site (TSS). In addition, chromatin immunoprecipitation coupled to microarrays (ChIP-Chip) targeting the retinal transcription factor CRX was performed. Thereby, we identified a second CRX-bound region (CBR2) in the first intron of RS1 which contains six evolutionarily conserved CRX binding motifs. In vitro luciferase reporter gene assays and dsRed reporter electroporation of mouse retinal organ cultures demonstrated a strong constitutive and orientation-independent enhancing effect of the upstream CpG island. The intronic CBR2 potently suppressed CBR1-driven RS1 promoter activity in vitro but failed to regulate a CBR1-reporter in short-term cultured mouse retinae. We conclude that a CpG island enhancer and two CBRs may act in a combinatorial fashion to fine-tune RS1 transcript levels in the retina.+http://www.ncbi.nlm.nih.gov/pubmed/21392589Kraus, Dominik Karlstetter, Marcus Walczak, Yana Hilfinger, Daniela Langmann, Thomas Weber, Bernhard H F Research Support, Non-U.S. Gov't Netherlands Biochimica et biophysica acta Biochim Biophys Acta. 2011 Apr-Jun;1809(4-6):245-54. Epub 2011 Mar 23.%0006-3002 (Print) 0006-3002 (Linking)21392589?Institute of Human Genetics, University of Regensburg, Germany.8S1874-9399(11)00051-4 [pii] 10.1016/j.bbagrm.2011.03.001eng =||7[Friedrich, U. Stohr, H. Hilfinger, D. Loenhardt, T. Schachner, M. Langmann, T. Weber, B. H.2011The Na/K-ATPase is obligatory for membrane anchorage of retinoschisin, the protein involved in the pathogenesis of X-linked juvenile retinoschisis1132-42 Hum Mol Genet206 2011/01/05Adenosine Triphosphatases/genetics/*metabolism Animals Cation Transport Proteins/genetics/*metabolism Cell Adhesion Molecules/*deficiency/genetics Cell Adhesion Molecules, Neuronal/genetics/*metabolism Cell Line Cell Membrane/genetics/*metabolism Eye Proteins/genetics Female HEK293 Cells Humans Male Mice Mice, Inbred C57BL Mice, Knockout Phospholipids/metabolism Protein Binding Protein Transport Retinoschisis/*enzymology/genetics/metabolism Sodium-Potassium-Exchanging ATPase/genetics/*metabolismMar 15 Mutations in the RS1 gene that encodes the discoidin domain containing retinoschisin cause X-linked juvenile retinoschisis (XLRS), a common macular degeneration in males. Disorganization of retinal layers and electroretinogram abnormalities are hallmarks of the disease and are also found in mice deficient for the orthologous murine protein, indicating that retinoschisin is important for the maintenance of retinal cell integrity. Upon secretion, retinoschisin associates with plasma membranes of photoreceptor and bipolar cells, although the components by which the protein is linked to membranes in vivo are still unclear. Here, we show that retinoschisin fails to bind to phospholipids or unilamellar lipid vesicles. A recent proteomic approach identified the Na/K-ATPase subunits ATP1A3 and ATP1B2 as binding partners of retinoschisin. We analyzed mice deficient for retinoschisin (Rs1h(-/Y)) and ATP1B2 (Atp1b2(-/-)) to characterize the role of Na/K-ATPase interaction in the organization of retinoschisin on cellular membranes. We demonstrate that both the Na/K-ATPase and retinoschisin are significantly reduced in Atp1b2(-/-) retinas, suggesting that retinoschisin membrane association is severely impaired in the absence of ATP1A3 and ATP1B2 subunits. Conversely, the presence of ATP1A3 and ATP1B2 are obligatory for binding of exogenously applied retinoschisin to crude membranes. Also, co-expression of ATP1A3 and ATP1B2 is required for retinoschisin binding to intact Hek293 cells. Taken together, our data support a predominant role of Na/K-ATPase in anchoring retinoschisin to retinal cell surfaces. Furthermore, altered localization of ATP1A3 and ATP1B2 is a notable consequence of retinoschisin deficiency and thus may be an important downstream aspect of cellular pathology in XLRS.+http://www.ncbi.nlm.nih.gov/pubmed/21196491Friedrich, Ulrike Stohr, Heidi Hilfinger, Daniela Loenhardt, Thomas Schachner, Melitta Langmann, Thomas Weber, Bernhard H F Research Support, Non-U.S. Gov't England Human molecular genetics Hum Mol Genet. 2011 Mar 15;20(6):1132-42. Epub 2010 Dec 31.*1460-2083 (Electronic) 0964-6906 (Linking)21196491oInstitute of Human Genetics, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.ddq557 [pii] 10.1093/hmg/ddq557eng |t7_Langmann, T. Lai, C. C. Weigelt, K. Tam, B. M. Warneke-Wittstock, R. Moritz, O. L. Weber, B. H.2008QCRX controls retinal expression of the X-linked juvenile retinoschisis (RS1) gene6523-34Nucleic Acids Res3620 2008/10/18Acetylation Animals Base Sequence Binding Sites Cell Line Dogs Eye Proteins/biosynthesis/*genetics Histones/metabolism Homeodomain Proteins/*metabolism Humans Mice Molecular Sequence Data Photoreceptor Cells, Vertebrate/metabolism *Promoter Regions, Genetic Response Elements Retina/*metabolism Retinal Bipolar Cells/metabolism Trans-Activators/*metabolism Transcriptional Activation Xenopus laevis p300-CBP Transcription Factors/metabolismNovX-linked juvenile retinoschisis is a heritable condition of the retina in males caused by mutations in the RS1 gene. Still, the cellular function and retina-specific expression of RS1 are poorly understood. To address the latter issue, we characterized the minimal promoter driving expression of RS1 in the retina. Binding site prediction, site-directed mutagenesis, and reporter assays suggest an essential role of two nearby cone-rod homeobox (CRX)-responsive elements (CRE) in the proximal -177/+32 RS1 promoter. Chromatin immunoprecipitation associates the RS1 promoter in vivo with CRX, the coactivators CBP, P300, GCN5 and acetylated histone H3. Transgenic Xenopus laevis expressing a green fluorescent protein (GFP) reporter under the control of RS1 promoter sequences show that the -177/+32 fragment drives GFP expression in photoreceptors and bipolar cells. Mutating either of the two conserved CRX binding sites results in strongly decreased RS1 expression. Despite the presence of sequence motifs in the promoter, NRL and NR2E3 appear not to be essential for RS1 expression. Together, our in vitro and in vivo results indicate that two CRE sites in the minimal RS1 promoter region control retinal RS1 expression and establish CRX as a key factor driving this expression.+http://www.ncbi.nlm.nih.gov/pubmed/18927113Langmann, Thomas Lai, Christine C L Weigelt, Karin Tam, Beatrice M Warneke-Wittstock, Regina Moritz, Orson L Weber, Bernhard H F Research Support, U.S. Gov't, Non-P.H.S. England Nucleic acids research Nucleic Acids Res. 2008 Nov;36(20):6523-34. Epub 2008 Oct 16.*1362-4962 (Electronic) 0305-1048 (Linking)258261618927113KInstitute of Human Genetics, University of Regensburg, Regensburg, Germany.gkn737 [pii] 10.1093/nar/gkn737eng ||7Min, S. H. Molday, L. L. Seeliger, M. W. Dinculescu, A. Timmers, A. M. Janssen, A. Tonagel, F. Tanimoto, N. Weber, B. H. Molday, R. S. Hauswirth, W. W.2005Prolonged recovery of retinal structure/function after gene therapy in an Rs1h-deficient mouse model of x-linked juvenile retinoschisis644-51Mol Ther124 2005/07/20XAnimals Cell Adhesion Molecules/*genetics Dependovirus/genetics Disease Models, Animal Electroretinography Eye Proteins/*genetics/metabolism *Gene Therapy Genetic Linkage Genetic Vectors Humans Male Mice Mice, Knockout Retina/pathology/*physiopathology Retinal Degeneration/*genetics Retinoschisis/genetics/physiopathology/*therapy TransfectionOct X-linked juvenile retinoschisis (RS) is a common cause of juvenile macular degeneration in males. RS is characterized by cystic spoke-wheel-like maculopathy, peripheral schisis, and a negative (b-wave more reduced than a-wave) electroretinogram (ERG). These symptoms are due to mutations in the RS1 gene in Xp22.2 leading to loss of functional protein. No medical treatment is currently available. We show here that in an Rs1h-deficient mouse model of human RS, delivery of the human RS1 cDNA with an AAV vector restored expression of retinoschisin to both photoreceptors and the inner retina essentially identical to that seen in wild-type mice. More importantly, unlike an earlier study with a different AAV vector and promoter, this work shows for the first time that therapeutic gene delivery using a highly specific AAV5-opsin promoter vector leads to progressive and significant improvement in both retinal function (ERG) and morphology, with preservation of photoreceptor cells that, without treatment, progressively degenerate.+http://www.ncbi.nlm.nih.gov/pubmed/16027044Min, Seok H Molday, Laurie L Seeliger, Mathias W Dinculescu, Astra Timmers, Adrian M Janssen, Andreas Tonagel, Felix Tanimoto, Naoyuki Weber, Bernhard H F Molday, Robert S Hauswirth, William W EY02422/EY/NEI NIH HHS/United States EY11123/EY/NEI NIH HHS/United States NS36302/NS/NINDS NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Molecular therapy : the journal of the American Society of Gene Therapy Mol Ther. 2005 Oct;12(4):644-51.%1525-0016 (Print) 1525-0016 (Linking)16027044qDepartment of Ophthalmology, University of Florida College of Medicine, Gainesville, 32610, USA. smin@eye.ufl.edu7S1525-0016(05)00225-X [pii] 10.1016/j.ymthe.2005.06.002eng||7fMooy, C. M. Van Den Born, L. I. Baarsma, S. Paridaens, D. A. Kraaijenbrink, T. Bergen, A. Weber, B. H.2002PHereditary X-linked juvenile retinoschisis: a review of the role of Muller cells979-84Arch Ophthalmol1207 2002/07/06Adult Eye Diseases, Hereditary/genetics/metabolism/*pathology Eye Proteins/metabolism Fibronectins/metabolism *Genetic Linkage Glial Fibrillary Acidic Protein/metabolism Humans Immunoenzyme Techniques Male Neurofilament Proteins/metabolism Neurons/metabolism/*ultrastructure Pedigree Photoreceptor Cells, Vertebrate/metabolism/*pathology Retinal Degeneration/genetics/metabolism/*pathology Vimentin/metabolism *X ChromosomeJul+http://www.ncbi.nlm.nih.gov/pubmed/12096974Mooy, Cornelia M Van Den Born, L Ingeborgh Baarsma, Seerp Paridaens, Dion A Kraaijenbrink, Thea Bergen, Arthur Weber, Bernhard H F Case Reports United States Archives of ophthalmology Arch Ophthalmol. 2002 Jul;120(7):979-84.%0003-9950 (Print) 0003-9950 (Linking)12096974tPathology Laboratory Dordrecht, Jkvr Van den Santheuvelweg 2A, 3317NL Dordrecht, the Netherlands. cmooy@paldordt.comecr0702-3 [pii]eng|t7Weber, B. H. Schrewe, H. Molday, L. L. Gehrig, A. White, K. L. Seeliger, M. W. Jaissle, G. B. Friedburg, C. Tamm, E. Molday, R. S.2002Inactivation of the murine X-linked juvenile retinoschisis gene, Rs1h, suggests a role of retinoschisin in retinal cell layer organization and synaptic structure6222-7Proc Natl Acad Sci U S A999 2002/05/02"Animals Blotting, Northern Blotting, Western Cells, Cultured Electrophysiology Electroretinography Eye Proteins/*genetics/*physiology Genetic Vectors Mice Mice, Knockout Microscopy, Electron Microscopy, Fluorescence *Mutation Ophthalmoscopy Retina/*cytology/*metabolism Synapses/*metabolismApr 30Deleterious mutations in RS1 encoding retinoschisin are associated with X-linked juvenile retinoschisis (RS), a common form of macular degeneration in males. The disorder is characterized by a negative electroretinogram pattern and by a splitting of the inner retina. To gain further insight into the function of the retinoschisin protein and its role in the cellular pathology of RS, we have generated knockout mice deficient in Rs1h, the murine ortholog of the human RS1 gene. We show that pathologic changes in hemizygous Rs1h(-/Y) male mice are evenly distributed across the retina, apparently contrasting with the macula-dominated features in human. Similar functional anomalies in human and Rs1h(-/Y) mice, however, suggest that both conditions are a disease of the entire retina affecting the organization of the retinal cell layers as well as structural properties of the retinal synapse.+http://www.ncbi.nlm.nih.gov/pubmed/11983912Weber, Bernhard H F Schrewe, Heinrich Molday, Laurie L Gehrig, Andrea White, Karen L Seeliger, Mathias W Jaissle, Gesine B Friedburg, Christoph Tamm, Ernst Molday, Robert S EY 2422/EY/NEI NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6222-7.%0027-8424 (Print) 0027-8424 (Linking)12293011983912{Institute of Human Genetics, Biocenter, University of Wurzburg, D-97074 Wurzburg, Germany. bweb@biozentrum.uni-wuerzburg.de&10.1073/pnas.092528599 99/9/6222 [pii]eng|t7/Gehrig, A. Weber, B. H. Lorenz, B. Andrassi, M.1999nFirst molecular evidence for a de novo mutation in RS1 (XLRS1) associated with X linked juvenile retinoschisis932-4 J Med Genet3612 2000/01/15Child, Preschool Eye Proteins/*genetics Female Glaucoma, Neovascular/etiology Humans Male Pedigree Retinal Degeneration/complications/*genetics Retinal Detachment/*genetics *X ChromosomeDec+http://www.ncbi.nlm.nih.gov/pubmed/10636740Gehrig, A Weber, B H Lorenz, B Andrassi, M Letter Research Support, Non-U.S. Gov't England Journal of medical genetics J Med Genet. 1999 Dec;36(12):932-4.%0022-2593 (Print) 0022-2593 (Linking)173428010636740eng||7EGehrig, A. White, K. Lorenz, B. Andrassi, M. Clemens, S. Weber, B. H.1999VAssessment of RS1 in X-linked juvenile retinoschisis and sporadic senile retinoschisis461-5 Clin Genet556 1999/08/18jAdult Eye Proteins/*genetics Female Humans Male Mutation Pedigree Retinal Diseases/*genetics *X ChromosomeJunThe RS1 gene is the causative gene in X-linked juvenile retinoschisis (RS). We have screened this gene for mutations in 13 patients with RS and in 7 probands with senile retinoschisis, a sporadic, later-onset form of retinoschisis. Mutations were detected in all RS patients. Of the 11 different mutations identified, six have been reported previously and live are novel. We did not find mutations in any of the senile retinoschisis patients and conclude that senile retinoschisis is not the result of germline mutations in the RS1 gene.+http://www.ncbi.nlm.nih.gov/pubmed/10450864Gehrig, A White, K Lorenz, B Andrassi, M Clemens, S Weber, B H Research Support, Non-U.S. Gov't Denmark Clinical genetics Clin Genet. 1999 Jun;55(6):461-5.%0009-9163 (Print) 0009-9163 (Linking)10450864EInstitut fur Humangenetik, Biozentrum, Universitat Wurzburg, Germany.eng '||7=Gehrig, A. E. Warneke-Wittstock, R. Sauer, C. G. Weber, B. H.1999XIsolation and characterization of the murine X-linked juvenile retinoschisis (Rs1h) gene303-7 Mamm Genome103 1999/03/021Amino Acid Sequence Animals Base Sequence Blotting, Northern Cloning, Molecular DNA Primers DNA, Complementary *Genetic Linkage Humans Mice Molecular Sequence Data Regulatory Sequences, Nucleic Acid Retinal Degeneration/*genetics Sequence Homology, Amino Acid Sequence Homology, Nucleic Acid *X ChromosomeMariX-linked juvenile retinoschisis (RS) is a vitreoretinal degeneration affecting only males. Recently, the RS1 gene underlying this common cause of early vision loss was identified and shown to encode a 224-amino acid precursor protein including a 23-residue leader sequence as well as a highly conserved discoidin motif at the C-terminus. Functional studies in other proteins with discoidin motifs have implicated this domain in phospholipid binding and cell-cell interactions on membrane surfaces. Thus, similar functional properties may exist for RS1 and may be related to the histopathological findings in RS. In order to further pursue the pathophysiology of RS and to understand RS1 function in early eye development, we now report the identification and characterization of the complete murine Rs1h gene. The full-length Rs1h cDNA was isolated by RT-PCR with degenerate oligonucleotide primers designed from human RS1 cDNA sequences. Subsequently, the exon/intron structure was determined in genomic DNA from mouse strain 129/SvJ. We show that human and murine RS1 coding sequences, exon/intron boundaries, as well as retina-specific expression, are highly conserved between the two species. The conceptual human and murine protein sequences reveal 96% amino acid identity with no amino acid changes within the discoidin domain. In addition, alignment of 5'-flanking sequences upstream of the human and mouse RS1 translation initiation sites identified putative binding sites for several transcription factors including CRX, a homeodomain transcription factor known to activate the transcription of several photoreceptor-specific genes.+http://www.ncbi.nlm.nih.gov/pubmed/10051329Gehrig, A E Warneke-Wittstock, R Sauer, C G Weber, B H Research Support, Non-U.S. Gov't United states Mammalian genome : official journal of the International Mammalian Genome Society Mamm Genome. 1999 Mar;10(3):303-7.%0938-8990 (Print) 0938-8990 (Linking)10051329aInstitut fur Humangenetik, Biozentrum, Am Hubland, Universitat Wurzburg, 97074 Wurzburg, Germany.eng||7xSauer, C. G. Gehrig, A. Warneke-Wittstock, R. Marquardt, A. Ewing, C. C. Gibson, A. Lorenz, B. Jurklies, B. Weber, B. H.1997NPositional cloning of the gene associated with X-linked juvenile retinoschisis164-70 Nat Genet172 1997/11/05wAmino Acid Sequence Base Sequence Child Cloning, Molecular DNA Mutational Analysis DNA Primers/genetics DNA, Complementary/genetics Exons Eye Proteins/*genetics Female Fungal Proteins/genetics *Genetic Linkage Humans Introns *Lectins Macular Degeneration/*genetics Male Molecular Sequence Data Pedigree *Protozoan Proteins Sequence Homology, Amino Acid X Chromosome/*geneticsOctX-linked juvenile retinoschisis(RS) is a recessively inherited vitreo-retinal degeneration characterized by macular pathology and intraretinal splitting of the retina. The RS gene has been localized to Xp22.2 to an approximately 1 Mb interval between DXS418 and DXS999/DXS7161. Mapping and expression analysis of expressed sequence tags have identified a novel transcript, designated XLRS1, within the centromeric RS locus that is exclusively expressed in retina. The predicted XLRS1 protein contains a highly conserved motif implicated in cell-cell interaction and thus may be active in cell adhesion processes during retinal development. Mutational analyses of XLRS1 in affected individuals from nine unrelated RS families revealed one nonsense, one frameshift, one splice acceptor and six missense mutations segregating with the disease phenotype in the respective families. These data provide strong evidence that the XLRS1 gene, when mutated, causes RS.*http://www.ncbi.nlm.nih.gov/pubmed/9326935Sauer, C G Gehrig, A Warneke-Wittstock, R Marquardt, A Ewing, C C Gibson, A Lorenz, B Jurklies, B Weber, B H Research Support, Non-U.S. Gov't United states Nature genetics Nat Genet. 1997 Oct;17(2):164-70.%1061-4036 (Print) 1061-4036 (Linking)93269359Institut fur Humangenetik, Universitat Wurzburg, Germany.10.1038/ng1097-164eng||7OWeber, B. H. Janocha, S. Vogt, G. Sander, S. Ewing, C. C. Roesch, M. Gibson, A.1995CX-linked juvenile retinoschisis (RS) maps between DXS987 and DXS44335-7Cytogenet Cell Genet691-2 1995/01/01Base Sequence Chromosome Mapping Crossing Over, Genetic DNA Primers DNA, Satellite/*genetics Female Genetic Markers Haplotypes/genetics Humans Male Molecular Sequence Data Pedigree *Polymorphism, Genetic *Repetitive Sequences, Nucleic Acid Retinal Diseases/*genetics *X ChromosomeX-linked juvenile retinoschisis (RS) has previously been localized to a 7-8 cM interval between markers at (DXS43, DXS207) and (DXS274, DXS41). Our analysis of more than 300 meioses in two multigeneration RS families identified eight recombinant RS chromosomes and narrowed the RS locus to an interval between DXS987 and DXS443. Our data suggest the following order of loci: Xpter-DXS207-DXS987-([DXS418-DXS999], RS)-DXS443-DXS365-DXS274-Xcen.*http://www.ncbi.nlm.nih.gov/pubmed/7835082Weber, B H Janocha, S Vogt, G Sander, S Ewing, C C Roesch, M Gibson, A Research Support, Non-U.S. Gov't Switzerland Cytogenetics and cell genetics Cytogenet Cell Genet. 1995;69(1-2):35-7.%0301-0171 (Print) 0301-0171 (Linking)78350829Institut fur Humangenetik, Biozentrum, Wurzburg, Germany.eng|t7'George, N. D. Yates, J. R. Moore, A. T.1995X linked retinoschisis697-702Br J Ophthalmol797 1995/07/01Diagnosis, Differential Electrophysiology Female *Genetic Linkage Heterozygote Humans Male Retinal Degeneration/*genetics/pathology/physiopathology *X ChromosomeJul*http://www.ncbi.nlm.nih.gov/pubmed/7662639George, N D Yates, J R Moore, A T Research Support, Non-U.S. Gov't Review England The British journal of ophthalmology Br J Ophthalmol. 1995 Jul;79(7):697-702.%0007-1161 (Print) 0007-1161 (Linking)5052027662639IDepartment of Ophthalmology, Addenbrooke's NHS Hospital Trust, Cambridge.eng|t75Bergen, A. A. ten Brink, J. B. van Schooneveld, M. J.1995BEfficient DNA carrier detection in X linked juvenile retinoschisis683-6Br J Ophthalmol797 1995/07/01Base Sequence Blotting, Southern DNA/*genetics Female *Genetic Linkage Genetic Markers Heterozygote Detection/*methods Humans Molecular Sequence Data Pedigree Polymerase Chain Reaction Retinal Degeneration/diagnosis/*genetics *X ChromosomeJulJuvenile retinoschisis is a rare, X linked hereditary vitroretinal degeneration. Female carriers of the disease do not develop any ocular abnormalities. Therefore, carrier detection by DNA analysis is extremely useful for these females. In order to evaluate the usefulness of a new class of DNA markers for carrier detection in X linked juvenile retinoschisis, DNA carrier detection or carrier exclusion was carried out in four possible carriers for X linked juvenile retinoschisis. The use of these highly polymorphic CA repeats, closely linked to the RS gene, greatly enhances both the reliability and feasibility of carrier detection in X linked juvenile retinoschisis.*http://www.ncbi.nlm.nih.gov/pubmed/7662636Bergen, A A ten Brink, J B van Schooneveld, M J Research Support, Non-U.S. Gov't England The British journal of ophthalmology Br J Ophthalmol. 1995 Jul;79(7):683-6.%0007-1161 (Print) 0007-1161 (Linking)50519976626369The Netherlands Ophthalmic Research Institute, Amsterdam.eng|t74George, N. D. Yates, J. R. Bradshaw, K. Moore, A. T.19950Infantile presentation of X linked retinoschisis653-7Br J Ophthalmol797 1995/07/01Electroretinography Fundus Oculi *Genetic Linkage Humans Infant Macular Degeneration/complications/diagnosis/*genetics Male Nystagmus, Pathologic/etiology Prognosis Strabismus/etiology *X ChromosomeJul Five infants who presented with nystagmus and/or strabismus were found to have bilateral highly elevated bullous retinoschisis involving the macula. Haemorrhage was present within the schisis cavity or the vitreous in four patients. The bullous retinoschisis eventually reattached spontaneously leaving pigment demarcation lines. A family history of X linked retinoschisis (XLRS) was known in two of the patients but in the other three subsequent investigation showed other male family members to be affected. It is important to recognise this uncommon presentation of XLRS so that the correct diagnosis is made and appropriate genetic counselling is given. Surgical treatment is not usually indicated and the visual prognosis is better than the initial appearance may suggest.*http://www.ncbi.nlm.nih.gov/pubmed/7662629George, N D Yates, J R Bradshaw, K Moore, A T Case Reports Research Support, Non-U.S. Gov't England The British journal of ophthalmology Br J Ophthalmol. 1995 Jul;79(7):653-7.%0007-1161 (Print) 0007-1161 (Linking)5051927662629@Department of Ophthalmology, Addenbrooke's NHS Trust, Cambridge.eng#||7RDumur, V. Trivier, E. Puech, B. Peugnet, F. Zanlonghi, X. Hache, J. C. Hanauer, A.1995Genetic analysis of new French X-linked juvenile retinoschisis kindreds using microsatellite markers closely linked to the RS locus: further narrowing of the RS candidate region79-82 Hum Genet961 1995/07/01Chromosome Mapping DNA, Satellite/*analysis Female France *Genetic Linkage Genetic Markers Humans Lod Score Male Pedigree Recombination, Genetic Repetitive Sequences, Nucleic Acid Retinal Degeneration/*genetics *Vitreous Body *X ChromosomeJulkThe gene involved in juvenile retinoschisis (RS) has previously been localized, by genetic linkage analyses, to Xp22.1-p22.2, between DXS274 and DXS43/DXS207; it is closely linked to the latter markers. From our recent data, this interval represents a genetic distance of approximately 10 cM. In the present study, we have studied 14 French families with X-linked juvenile RS by using four CA polymorphisms that are closely linked to the RS locus and that have recently been included in an Xp22.1-p22.2 high-resolution map. Complete cosegregation with the disease locus was observed for three of them, DXS207, DXS418, and DXS999, which further confirms the locus homogeneity for RS and the close linkage to this region. One recombinant was found with the most proximal marker, AFM291wf5, thereby defining this marker as the new proximal boundary of the candidate region for RS. Under the assumption that DXS207 and DXS43 constitute the distal boundary, the present study further reduces the region containing the disease gene to a interval of 3-4 cM. The results reported here should facilitate the eventual cloning of the RS gene.*http://www.ncbi.nlm.nih.gov/pubmed/7607659Dumur, V Trivier, E Puech, B Peugnet, F Zanlonghi, X Hache, J C Hanauer, A Research Support, Non-U.S. Gov't Germany Human genetics Hum Genet. 1995 Jul;96(1):79-82.%0340-6717 (Print) 0340-6717 (Linking)7607659jDepartment de Biochimie et d'Ophtalmologie, Centre Hospitalier Regional et Universitaire de Lille, France.eng5||7\Pawar, H. Bingham, E. L. Lunetta, K. L. Segal, M. Richards, J. E. Boehnke, M. Sieving, P. A.1995:Refined genetic mapping of juvenile X-linked retinoschisis206-10 Hum Hered454 1995/07/01*Chromosome Mapping Female *Genetic Linkage Humans Male Microsatellite Repeats Pedigree Recombination, Genetic Retinal Degeneration/*genetics X ChromosomeJul-AugJuvenile X-linked retinoschisis (RS) is an eye disease that causes acuity reduction and peripheral visual field loss typically beginning early in life. In further work towards positional cloning of the RS gene, we restudied our previously reported seven large American families and one additional new family, with a total of 63 affected males. RS linkage analysis using microsatellite repeat markers gave the following results: DXS207 (Z = 24.89, theta = 0.01), DXS987 (Z = 24.04, theta 0.01) and DXS999 (Z = 14.70, theta = 0.00). Recombination events in four individuals were studied further with additional markers (AFM291wf5, DXS443, DXS1052, DXS274 and DXS1226), and a flanking interval was obtained (DXS43, DXS207, DXS987)-RS-(AFM291wf5, DXS443). This study moves the RS centromeric boundary to (AFM291wf5, DXS443), about 5.5 cM closer than the previously reported boundary at DXS274 and narrows the RS inclusion interval to about 3.7 cM (using distances from CEPH family data).*http://www.ncbi.nlm.nih.gov/pubmed/7558052,Pawar, H Bingham, E L Lunetta, K L Segal, M Richards, J E Boehnke, M Sieving, P A P30-HG00209/HG/NHGRI NIH HHS/United States R01-EY10250/EY/NEI NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Switzerland Human heredity Hum Hered. 1995 Jul-Aug;45(4):206-10.%0001-5652 (Print) 0001-5652 (Linking)7558052DDepartment of Ophthalmology, University of Michigan, Ann Arbor, USA.eng||7OWeber, B. H. Janocha, S. Vogt, G. Sander, S. Ewing, C. C. Roesch, M. Gibson, A.1995CX-linked juvenile retinoschisis (RS) maps between DXS987 and DXS44335-7Cytogenet Cell Genet691-2 1995/01/01Base Sequence Chromosome Mapping Crossing Over, Genetic DNA Primers DNA, Satellite/*genetics Female Genetic Markers Haplotypes/genetics Humans Male Molecular Sequence Data Pedigree *Polymorphism, Genetic *Repetitive Sequences, Nucleic Acid Retinal Diseases/*genetics *X ChromosomeX-linked juvenile retinoschisis (RS) has previously been localized to a 7-8 cM interval between markers at (DXS43, DXS207) and (DXS274, DXS41). Our analysis of more than 300 meioses in two multigeneration RS families identified eight recombinant RS chromosomes and narrowed the RS locus to an interval between DXS987 and DXS443. Our data suggest the following order of loci: Xpter-DXS207-DXS987-([DXS418-DXS999], RS)-DXS443-DXS365-DXS274-Xcen.*http://www.ncbi.nlm.nih.gov/pubmed/7835082Weber, B H Janocha, S Vogt, G Sander, S Ewing, C C Roesch, M Gibson, A Research Support, Non-U.S. Gov't Switzerland Cytogenetics and cell genetics Cytogenet Cell Genet. 1995;69(1-2):35-7.%0301-0171 (Print) 0301-0171 (Linking)78350829Institut fur Humangenetik, Biozentrum, Wurzburg, Germany.eng||7Blodi, C. F. Stone, E. M.1990Best's vitelliform dystrophy49-59Ophthalmic Paediatr Genet111 1990/03/01 Electrooculography Fluorescein Angiography Fundus Oculi Genetic Linkage Humans Macular Degeneration/complications/diagnosis/*genetics/pathology Pigment Epithelium of Eye/pathology Prognosis Retinal Hemorrhage/etiology Retinal Neovascularization/etiology Visual AcuityMar2Best's vitelliform dystrophy is an autosomal dominant disease that pathologically affects the retinal pigment epithelium and symmetrically affects the macula of patients at a very young age. Visual acuity tends to remain quite good for long periods of time. In the later stages of the disease, atrophic changes of the retinal pigment epithelium or scarring secondary to subretinal neovascular membranes with hemorrhage may cause a loss of central visual acuity. An abnormal diminished light to dark ratio of the electrooculogram is the hallmark of the disease. No other significant ocular abnormalities or systemic problems have been associated with this genetic disorder. No therapy exists for halting the progression of the disease with the possible exception of laser photocoagulation treatment used to ablate subretinal neovascular membranes in an attempt to avoid complications of subretinal hemorrhages. However, an accurate diagnosis and pedigree analysis is important for allowing the physician to perform adequate family and genetic counseling to affected patients.*http://www.ncbi.nlm.nih.gov/pubmed/2190134Blodi, C F Stone, E M Research Support, Non-U.S. Gov't Review Netherlands Ophthalmic paediatrics and genetics Ophthalmic Paediatr Genet. 1990 Mar;11(1):49-59.%0167-6784 (Print) 0167-6784 (Linking)2190134ADepartment of Ophthalmology, University of Iowa, Iowa City 52242.eng||7"Schotthoefer, E. O. Wallace, D. K.2007.Strabismus associated with thyroid eye disease361-5Curr Opin Ophthalmol185 2007/08/19dGraves Ophthalmopathy/*complications/diagnosis/therapy Humans Strabismus/diagnosis/*etiology/therapySepPURPOSE OF REVIEW: We discuss the evaluation and treatment of strabismus related to thyroid eye disease with special attention to the literature published in 2006. RECENT FINDINGS: The etiology of thyroid eye disease is complex, although a recent review article evaluated the causative relationship between smoking and thyroid eye disease. The treatment of thyroid eye disease is also complex and involves a multidisciplinary approach including endocrinology and ophthalmology. Several recent articles have evaluated the role of medications in the treatment of thyroid eye disease. We discuss the current surgical strategies for the treatment of strabismus related to thyroid eye disease, including the use of adjustable suture techniques. New techniques in nonadjustable surgery are also examined. SUMMARY: Strabismus related to thyroid eye disease presents many challenges to the ophthalmologist. Successful treatment of strabismus is rewarding however, and has a significant impact on improving a patient's quality of life.+http://www.ncbi.nlm.nih.gov/pubmed/17700227Schotthoefer, Erin O Wallace, David K Review United States Current opinion in ophthalmology Curr Opin Ophthalmol. 2007 Sep;18(5):361-5.%1040-8738 (Print) 1040-8738 (Linking)17700227[Department of Ophthalmology, Duke University Eye Center, Durham, North Carolina 27710, USA.;10.1097/ICU.0b013e32827038f2 00055735-200709000-00003 [pii]engZ||7/Mullaney, P. Vajsar, J. Smith, R. Buncic, J. R.2000oThe natural history and ophthalmic involvement in childhood myasthenia gravis at the hospital for sick children504-10 Ophthalmology1073 2000/03/11\Adolescent Blepharoptosis/*diagnosis/drug therapy/etiology Child Child, Preschool Cholinesterase Inhibitors/therapeutic use Disease Progression Female Glucocorticoids/therapeutic use Hospitals, Pediatric Humans Infant Infant, Newborn Male Myasthenia Gravis/*diagnosis/drug therapy/etiology Myasthenia Gravis, Neonatal/diagnosis/drug therapy/etiology Myasthenic Syndromes, Congenital/*diagnosis/drug therapy/etiology Ontario Ophthalmoplegia/*diagnosis/drug therapy/etiology Prednisone/therapeutic use Pyridostigmine Bromide/therapeutic use Retrospective Studies Strabismus/*diagnosis/drug therapy/etiologyMar OBJECTIVE: To characterize signs, symptoms, and the natural history of myasthenic syndromes in pediatric patients. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Thirty-four patients with a diagnosis of myasthenia were identified from either the hospital's or treating physician's database. METHODS: Retrospective chart review, clinical examination, and telephone interview. MAIN OUTCOME MEASURES: Information pertaining to the ophthalmologic and neurologic examination, diagnostic interventions, and treatment was noted. Patients with active disease, attending during the study period, were examined at their outpatient visits. Those who no longer attended the hospital were contacted by means of a telephone interview to complete their follow-up. RESULTS: Thirty-four children were found to have myasthenia. Two had transient neonatal myasthenia, which resolved quickly. Seven (20.6%) patients had congenital myasthenic syndromes (CMS) and 25 (73.5%, 19 females) were affected with autoimmune myasthenia gravis (AMG). In those patients with severe CMS, three showed signs of generalized weakness, including failure to thrive, frequent apneas, and aspirations. In four patients with mild CMS, eye signs were relatively more prominent. In all patients with CMS, strabismus, ophthalmoplegia, and ptosis were the main ophthalmologic signs and remained relatively constant. Fourteen (56%) patients with AMG had ocular signs and symptoms, and five of them progressed to systemic involvement in 7.8 months on average (range, 1-23). The remaining nine patients with ocular AMG had either strabismus or ptosis and were treated with pyridostigmine (nine patients) and prednisone (two patients). Patients with ocular AMG were seen at 78 months on average, those with systemic AMG at 85.6 months. Systemic AMG was seen in 16 patients. No thymomas were found in 14 patients who underwent thymectomy. Of the 25 patients with AMG, 8 are still being treated, 8 are in remission for an average of 65.2 months and are asymptomatic, 4 patients are receiving long-term immunosuppressants (1 has likely sustained permanent damage to her extraocular muscles with complete ophthalmoplegia and ptosis), and 4 have been lost to follow-up. Finally, one patient died after aspiration because of bulbar weakness. CONCLUSIONS: Patients with CMS varied in the degree of severity. Apneic attacks, aspiration, and failure to thrive may obscure the diagnosis. Compared with AMG, their ophthalmologic signs and symptoms were usually permanent. Visual signs and symptoms were usually prominent in those patients with active AMG, but those in remission were asymptomatic. More than half of the patients with juvenile AMG had ocular symptoms. Generalization occurred in a minority in an average of 7.8 months. Patients entered remission after approximately 2 years of treatment and were visually asymptomatic. This study suggests that long-term permanent damage to the extraocular muscles as a result of juvenile AMG is rare. Myasthenia gravis is a life-threatening disease as evidenced by the death of one of our patients. Many of these patients are first seen by the ophthalmologist who can aid the diagnosis, screen for amblyopia, and monitor the patient's response to therapy.+http://www.ncbi.nlm.nih.gov/pubmed/10711889mMullaney, P Vajsar, J Smith, R Buncic, J R United states Ophthalmology Ophthalmology. 2000 Mar;107(3):504-10.%0161-6420 (Print) 0161-6420 (Linking)10711889VDepartment of Ophthalmology, The Hospital for Sick Children, Toronto, Ontario, Canada.S0161-6420(99)00138-4 [pii]eng||7Silverberg, M. Demer, J.2001JDuane's syndrome with compressive denervation of the lateral rectus muscle146-8Am J Ophthalmol1311 2001/02/13wAbducens Nerve Diseases/*complications/diagnosis Atrophy Duane Retraction Syndrome/*complications/diagnosis Esotropia/etiology Female Humans Magnetic Resonance Imaging Meningeal Neoplasms/*complications/diagnosis Meningioma/*complications/diagnosis Middle Aged *Muscle Denervation Nerve Compression Syndromes/*complications/diagnosis Oculomotor Muscles/*innervation/pathologyJanPURPOSE: To describe an unusual case of Duane's syndrome. METHODS: Individual case report. RESULTS: A skull base meningioma was discovered in a woman with Duane's syndrome who presented with recurrent, large-angle esotropia and uncharacteristic atrophy of the lateral rectus muscle on magnetic resonance image (MRI) scan. CONCLUSION: Neuroimaging may be useful in unusual cases of Duane's syndrome.+http://www.ncbi.nlm.nih.gov/pubmed/11162999 Silverberg, M Demer, J EY-00331/EY/NEI NIH HHS/United States EY-08313/EY/NEI NIH HHS/United States Case Reports Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States American journal of ophthalmology Am J Ophthalmol. 2001 Jan;131(1):146-8.%0002-9394 (Print) 0002-9394 (Linking)11162999FJules Stein Eye Institute, University of California, Los Angeles, USA.S0002939400007145 [pii]eng||7SRoss, R. D. Stec, L. A. Werner, J. C. Blumenkranz, M. S. Glazer, L. Williams, G. A.20016Presumed acquired ocular toxoplasmosis in deer hunters226-9Retina213 2001/06/26Adolescent Adult Animals Antibodies, Protozoan/analysis Antiprotozoal Agents/therapeutic use Deer/*parasitology *Food Parasitology Humans Male Meat/*parasitology Middle Aged Retinal Necrosis Syndrome, Acute/diagnosis/drug therapy/*parasitology Toxoplasma/immunology Toxoplasmosis, Ocular/diagnosis/drug therapy/*etiology Vision Disorders/diagnosis/drug therapy/parasitology Visual AcuityxPURPOSE: To describe acquired ocular toxoplasmosis in deer hunters. METHODS AND RESULTS: The authors describe five young men presenting with flu-like symptoms followed by visual loss due to a unilateral, focal necrotizing retinitis. All five men gave a history of ingesting undercooked or uncooked venison. All five had elevated toxoplasma serology, and all five improved clinically with an antitoxoplasma regimen. CONCLUSION: In previously healthy young men, flu-like symptoms associated with visual loss and retinitis should prompt questioning about hunting and raw game meat ingestion, especially when toxoplasmosis is suspected.+http://www.ncbi.nlm.nih.gov/pubmed/11421011Ross, R D Stec, L A Werner, J C Blumenkranz, M S Glazer, L Williams, G A Case Reports United States Retina (Philadelphia, Pa.) Retina. 2001;21(3):226-9.%0275-004X (Print) 0275-004X (Linking)114210113Retina Vitreous Center, Grand Blanc, Michigan, USA.eng||7"Mehta, D. Fergie, N. Narula, A. A.2002<Re: Conservative Management of Gradenigo Syndrome in a Child81-3Int J Pediatr Otorhinolaryngol621 2002/02/08Abducens Nerve Diseases/complications/*diagnosis/drug therapy Amoxicillin/administration & dosage Child Combined Modality Therapy Diplopia/complications/diagnosis Drug Therapy, Combination/*administration & dosage Female Floxacillin/administration & dosage Follow-Up Studies Humans Magnetic Resonance Imaging Mastoiditis/complications/*diagnosis/*drug therapy Middle Ear Ventilation/methods Syndrome Tomography, X-Ray ComputedJan 11+http://www.ncbi.nlm.nih.gov/pubmed/11831196Mehta, D Fergie, N Narula, A A Case Reports Comment Letter Ireland International journal of pediatric otorhinolaryngology Int J Pediatr Otorhinolaryngol. 2002 Jan 11;62(1):81-3.%0165-5876 (Print) 0165-5876 (Linking)11831196eng||7MMarianowski, R. Rocton, S. Ait-Amer, J. L. Morisseau-Durand, M. P. Manach, Y.20018Conservative management of Gradenigo syndrome in a child79-83Int J Pediatr Otorhinolaryngol571 2001/02/138Abducens Nerve Diseases/complications/*drug therapy Anti-Bacterial Agents Anti-Inflammatory Agents/therapeutic use Child Drug Therapy, Combination/therapeutic use Facial Pain/complications/*drug therapy Humans Male Methylprednisolone/therapeutic use Otitis Media/complications/*drug therapy Petrous Bone SyndromeJanGradenigo syndrome consists of the association of otitis media, facial pain in regions innervated by the first and second division of trigeminal nerve and abducens nerve paralysis. It is caused by osteitis of the petrous apex (PA) and is a very rare complication of otitis media. Its treatment usually consists in mastoidectomy and antibiotics. We report a case of a 6-year-old child, which was managed medically with a positive outcome.+http://www.ncbi.nlm.nih.gov/pubmed/11165646Marianowski, R Rocton, S Ait-Amer, J L Morisseau-Durand, M P Manach, Y Case Reports Ireland International journal of pediatric otorhinolaryngology Int J Pediatr Otorhinolaryngol. 2001 Jan;57(1):79-83.%0165-5876 (Print) 0165-5876 (Linking)11165646Department of Pediatric Otorhinolaryngology, Hopital Necker-Enfants Malades, 11 avenue Franco-Russe, Paris 75007, France. remimarian@aol.comS0165-5876(00)00442-0 [pii]eng||7Bashuk, R. G. Krendel, D. A.1990GMyasthenia gravis presenting as weakness after magnesium administration708-12 Muscle Nerve138 1990/08/01Adult Diagnosis, Differential Electrophysiology Female Humans Infusions, Parenteral Lambert-Eaton Myasthenic Syndrome/complications/diagnosis Magnesium Deficiency/blood Magnesium Sulfate/administration & dosage/*adverse effects Myasthenia Gravis/complications/*diagnosis Paralysis/*chemically induced/diagnosis/drug therapy Pre-Eclampsia/*drug therapy Pregnancy Pyridostigmine Bromide/therapeutic useAugWe studied a patient with no prior history of neuromuscular disease who became virtually quadriplegic after parenteral magnesium administration for preeclampsia. The serum magnesium concentration was 3.0 mEq/L, which is usually well tolerated. The magnesium was stopped and she recovered over a few days. While she was weak, 2-Hz repetitive stimulation revealed a decrement without significant facilitation at rapid rates or after exercise, suggesting postsynaptic neuromuscular blockade. After her strength returned, repetitive stimulation was normal, but single fiber EMG revealed increased jitter and blocking. Her acetylcholine receptor antibody level was markedly elevated. Although paralysis after magnesium administration has been described in patients with known myasthenia gravis, it has not previously been reported to be the initial or only manifestation of the disease. Patients who are unusually sensitive to the neuromuscular effects of magnesium should be suspected of having an underlying disorder of neuromuscular transmission.*http://www.ncbi.nlm.nih.gov/pubmed/2385256gBashuk, R G Krendel, D A Case Reports United states Muscle & nerve Muscle Nerve. 1990 Aug;13(8):708-12.%0148-639X (Print) 0148-639X (Linking)2385256OEmory University School of Medicine, Department of Neurology, Atlanta, Georgia.10.1002/mus.880130808eng|t7Mier, A. Laroche, C. Green, M.1990?Unsuspected myasthenia gravis presenting as respiratory failure422-3Thorax455 1990/05/01Azathioprine/therapeutic use Humans Male Middle Aged Myasthenia Gravis/*complications/drug therapy/physiopathology Prednisolone/therapeutic use Respiratory Insufficiency/drug therapy/*etiology/physiopathologyMayA patient developed respiratory failure after surgical removal of a recurrent thymoma, which necessitated removal of part of the diaphragm. The respiratory failure was due to previously undiagnosed myasthenia gravis, which had selectively affected the respiratory muscles.*http://www.ncbi.nlm.nih.gov/pubmed/2382251UMier, A Laroche, C Green, M Case Reports England Thorax Thorax. 1990 May;45(5):422-3.%0040-6376 (Print) 0040-6376 (Linking)4625032382251GDepartment of Respiratory Muscle Physiology, Brompton Hospital, London.eng||7)Dushay, K. M. Zibrak, J. D. Jensen, W. A.1990<Myasthenia gravis presenting as isolated respiratory failure232-4Chest971 1990/01/01vHumans Male Middle Aged Myasthenia Gravis/complications/*diagnosis/therapy Respiratory Insufficiency/*etiology/therapyJanjA patient with myasthenia gravis presenting as respiratory failure was unusual in his lack of peripheral neuromuscular involvement, negative results on many commonly used diagnostic tests, and lack of response to firstline therapeutic measures. Review of the pertinent literature revealed no previously described presentation of myasthenia gravis in this manner.*http://www.ncbi.nlm.nih.gov/pubmed/2295244aDushay, K M Zibrak, J D Jensen, W A Case Reports United states Chest Chest. 1990 Jan;97(1):232-4.%0012-3692 (Print) 0012-3692 (Linking)2295244^Section of Pulmonary and Critical Care Medicine, New England Deaconess Hospital, Boston 02215.engY||7Uddin, J. M. Davies, P. D.2002wTreatment of upper eyelid retraction associated with thyroid eye disease with subconjunctival botulinum toxin injection1183-7 Ophthalmology1096 2002/06/05Adult Aged Botulinum Toxins, Type A/*therapeutic use Conjunctiva/*drug effects Eyelid Diseases/*drug therapy/etiology Female Graves Disease/complications/*drug therapy Humans Injections Male Middle Aged Neuromuscular Agents/*therapeutic use Prospective Studies Treatment OutcomeJun-OBJECTIVE: To study the effectiveness of botulinum toxin injections, via a subconjunctival approach, in the management of upper eyelid retraction associated with thyroid eye disease. DESIGN: Prospective, non-comparative, interventional case series. PARTICIPANTS: Eleven patients with upper scleral exposure associated with thyroid eye disease who declined conservative or conventional surgical management. INTERVENTION: One or more treatments with injections of botulinum toxin into the subconjunctival space at the superior margin of the tarsal plate, via a conjunctival approach. MAIN OUTCOME MEASURES: Upper eyelid position in relation to the upper limbus, patient satisfaction, and complications. RESULTS: All patients experienced some improvement in the amount of lid retraction after injections. The amount of lid lowering varied between patients and lasted between 1 and 40 months. A lid position acceptable to the patient was obtained in 10 patients. Four patients had ptosis lasting from 1 to 3 weeks, and three patients had transient diplopia lasting 1 day to 3 weeks. CONCLUSIONS: This subconjunctival method of botulinum toxin injection provides an effective treatment for upper eyelid retraction associated with thyroid eye disease that is easy to administer and well tolerated by patients with few side effects.+http://www.ncbi.nlm.nih.gov/pubmed/12045064aUddin, Jimmy M Davies, Peter D United States Ophthalmology Ophthalmology. 2002 Jun;109(6):1183-7.%0161-6420 (Print) 0161-6420 (Linking)12045064EDepartment of Ophthalmology, West Norwich Hospital, Norwich, England.S0161-6420(02)01041-2 [pii]engK~|78Halmagyi, G. M. Curthoys, I. S. Brandt, T. Dieterich, M.19918Ocular tilt reaction: clinical sign of vestibular lesion47-50Acta Otolaryngol Suppl481 1991/01/01NEye Movements/*physiology Humans *Posture Vestibular Diseases/*physiopathology*http://www.ncbi.nlm.nih.gov/pubmed/1927445Halmagyi, G M Curthoys, I S Brandt, T Dieterich, M Review Sweden Acta oto-laryngologica. Supplementum Acta Otolaryngol Suppl. 1991;481:47-50.%0365-5237 (Print) 0365-5237 (Linking)1927445FNeurology Department, Royal Prince Alfred Hospital, Sydney, Australia.engi||7+Banna, M. Hoare, R. D. Stanley, P. Till, K.1973Craniopharyngioma in children781-5 J Pediatr835 1973/11/01Adolescent Blindness/etiology Brain Neoplasms/complications/diagnosis/*epidemiology/radiography Child Child, Preschool Craniopharyngioma/complications/diagnosis/*epidemiology/radiography Diabetes Insipidus/etiology Diplopia/etiology Extremities Eye Manifestations Eye Movements Female Growth Disorders/etiology Headache/etiology Humans Intracranial Pressure London Male Mental Disorders/etiology Muscles/physiopathology Optic Atrophy/etiology Retrospective Studies Vision, Ocular Visual Fields Vomiting/etiologyNov*http://www.ncbi.nlm.nih.gov/pubmed/4742571oBanna, M Hoare, R D Stanley, P Till, K United states The Journal of pediatrics J Pediatr. 1973 Nov;83(5):781-5.%0022-3476 (Print) 0022-3476 (Linking)4742571eng||7.Artarian, A. A. Polianker, Z. N. Motsnaia, MIa1973K[Modern x-ray contrast methods of diagnosing craniopharyngioma in children]53-7Vopr Neirokhir374 1973/07/01Adolescent Cerebral Angiography Cerebral Ventriculography Child Child, Preschool *Contrast Media Craniopharyngioma/*radiography Humans Hydrocephalus/radiography Methods Pneumoencephalography Sella TurcicaJul-Aug*http://www.ncbi.nlm.nih.gov/pubmed/4544058pArtarian, A A Polianker, Z N Motsnaia, M Ia Ussr Voprosy neirokhirurgii Vopr Neirokhir. 1973 Jul-Aug;37(4):53-7.%0042-8817 (Print) 0042-8817 (Linking)4544058KSovremennye rentgenokontrastnye metody diagnostiki kraniofaringiom u detei.rus|t7-Pacheco-Cutillas, M. Edgar, D. F. Sahraie, A.1999TAcquired colour vision defects in glaucoma-their detection and clinical significance1396-402Br J Ophthalmol8312 1999/11/27Aging/psychology Color Perception Tests Color Vision Defects/*diagnosis/*etiology Glaucoma/*complications Humans Quality of Life Visual Field Tests/methodsDec+http://www.ncbi.nlm.nih.gov/pubmed/10574822Pacheco-Cutillas, M Edgar, D F Sahraie, A Research Support, Non-U.S. Gov't Review England The British journal of ophthalmology Br J Ophthalmol. 1999 Dec;83(12):1396-402.%0007-1161 (Print) 0007-1161 (Linking)172289210574822gAVRC, Department of Optometry and Visual Science, City University, Northampton Square, London EC1V 0HB.eng4||7 Austin, D. J.1974QAcquired colour vision defects in patients suffering from chronic simple glaucoma880-3Trans Ophthalmol Soc U K944 1974/01/01Chronic Disease *Color Perception Female Glaucoma/*complications Humans Intraocular Pressure Male Middle Aged Vision Disorders/*etiology Visual Fields*http://www.ncbi.nlm.nih.gov/pubmed/4534140Austin, D J England Transactions of the ophthalmological societies of the United Kingdom Trans Ophthalmol Soc U K. 1974;94(4):880-3.%0078-5334 (Print) 0078-5334 (Linking)4534140eng|t7-Pacheco-Cutillas, M. Edgar, D. F. Sahraie, A.1999TAcquired colour vision defects in glaucoma-their detection and clinical significance1396-402Br J Ophthalmol8312 1999/11/27Aging/psychology Color Perception Tests Color Vision Defects/*diagnosis/*etiology Glaucoma/*complications Humans Quality of Life Visual Field Tests/methodsDec+http://www.ncbi.nlm.nih.gov/pubmed/10574822Pacheco-Cutillas, M Edgar, D F Sahraie, A Research Support, Non-U.S. Gov't Review England The British journal of ophthalmology Br J Ophthalmol. 1999 Dec;83(12):1396-402.%0007-1161 (Print) 0007-1161 (Linking)172289210574822gAVRC, Department of Optometry and Visual Science, City University, Northampton Square, London EC1V 0HB.eng4||7 Austin, D. J.1974QAcquired colour vision defects in patients suffering from chronic simple glaucoma880-3Trans Ophthalmol Soc U K944 1974/01/01Chronic Disease *Color Perception Female Glaucoma/*complications Humans Intraocular Pressure Male Middle Aged Vision Disorders/*etiology Visual Fields*http://www.ncbi.nlm.nih.gov/pubmed/4534140Austin, D J England Transactions of the ophthalmological societies of the United Kingdom Trans Ophthalmol Soc U K. 1974;94(4):880-3.%0078-5334 (Print) 0078-5334 (Linking)4534140eng|?,Dartnall, Herbert J. A. Abrahamson, Edwin W.1972Photochemistry of vision xi, 810 p.Handbook of sensory physiology,7/1Berlin, New York,Springer-VerlagVision. Physiological optics.y71182440 GDB*** by E. W. Abrahamson [and others] Edited by Herbert J. A. Dartnall. illus. 26 cm. Includes bibliographies.0387051457 (New York)3603552>Jefferson or Adams Building Reading Rooms QP351; .H34 vol. 7/1|?,Fuortes, Michelangelo G. F. Abramov Israel.,1972"Physiology of photoreceptor organs x, 765 p.Handbook of sensory physiology,VII/2Berlin, New York,Springer-VerlagRetina. Photoreceptors.m73189455 GDB*** by I. Abramov [and others] Edited by M. G. F. Fuortes. illus. 26 cm. Includes bibliographies.0387057439 (New York)785200CJefferson or Adams Building Reading Rooms QP351; .H34 vol. 7, no. 2|?5Jameson, Dorothea Hurvich, Leo Maurice Alpern, Mathew1972Visual psychophysics x, 812 p.Handbook of sensory physiology,7/4Berlin, New York,Springer-VerlagPhysiological optics.79186275 GDB*** by M. Alpern [and others] Edited by Dorothea Jameson and Leo M. Hurvich. illus. 26 cm. Includes bibliographies.0387051465 (New York)870186CJefferson or Adams Building Reading Rooms QP351; .H34 vol. 7, no. 4~|?Neil, Eric Andersson, Bengt1972 Enteroceptors233 p.Handbook of sensory physiology,3/1Berlin, New York,Springer-VerlagNeural receptors.f72181433 GDB*** by B. Andersson [and others] Edited by E. Neil. illus. 26 cm. Includes bibliographies.0387055231 (New York)4082035CJefferson or Adams Building Reading Rooms QP351; .H34 vol. 3, no. 1~?<Spitler, Harry Riley College of syntonic optometry Eaton O.,1941BThe syntonic principle, its relation to health and ocular problemsviii p., 21., 3-217 p. Eaton, O.,Light Physiological effect.!42008639 by Harry Riley Spitler ... illus., diagrs. 24 cm. "In part an abridgement and in part an amplification of a thesis in part fulfillment of academic requirements for the doctor of philosophy degree."--p. viii. Bibliographical foot-notes. "References" at end of some of the chapters.7385992zJefferson or Adams Building Reading Rooms QH651; .S7 Jefferson or Adams Building Reading Rooms - STORED OFFSITE QH651; .S7||7#Casati, S. Ottria, R. Ciuffreda, P.2009h17alpha- and 17beta-boldenone 17-glucuronides: synthesis and complete characterization by 1H and 13C NMR250-5Steroids742 2008/12/17xGlucuronides/*chemical synthesis/chemistry Magnetic Resonance Spectroscopy Testosterone/*analogs & derivatives/chemistryFebBoldenone is an androgenic anabolic steroid intensively used for growth promoting purposes in animals destined for meat production and as a performance enhancer in athletics. Therefore its use is officially banned either in animals intended for consumption or in humans. Because most anabolic steroids are completely metabolized and usually no parent steroid is excreted, metabolite identification is crucial to detect the illegal use of anabolic steroids either in humans or in livestock. 17alpha- and 17beta-boldenone 17-glucuronides were synthesized, purified and characterized in order to provide suitable standards for the identification and quantification of these metabolites.+http://www.ncbi.nlm.nih.gov/pubmed/19071152Casati, Silvana Ottria, Roberta Ciuffreda, Pierangela Research Support, Non-U.S. Gov't United States Steroids Steroids. 2009 Feb;74(2):250-5. Epub 2008 Nov 24.%0039-128X (Print) 0039-128X (Linking)19071152{Dipartimento di Scienze Precliniche LITA Vialba, Universita degli Studi di Milano, Via G.B. Grassi, 74-20157 Milano, Italy.:S0039-128X(08)00297-3 [pii] 10.1016/j.steroids.2008.11.012eng ||7Ciuffreda, D. Comte, D. Cavassini, M. Giostra, E. Buhler, L. Perruchoud, M. Heim, M. H. Battegay, M. Genne, D. Mulhaupt, B. Malinverni, R. Oneta, C. Bernasconi, E. Monnat, M. Cerny, A. Chuard, C. Borovicka, J. Mentha, G. Pascual, M. Gonvers, J. J. Pantaleo, G. Dutoit, V.2008ePolyfunctional HCV-specific T-cell responses are associated with effective control of HCV replication2665-77 Eur J Immunol3810 2008/10/30yCD4-Positive T-Lymphocytes/*immunology CD8-Positive T-Lymphocytes/*immunology HIV/immunology HIV Infections/complications/*immunology/virology Hepacivirus/*immunology/physiology Hepatitis C, Chronic/complications/*immunology/virology Humans Interferon-gamma/immunology/metabolism Interleukin-2/immunology/metabolism Liver Transplantation/immunology Viral Load Virus ReplicationOctHCV infection has a severe course of disease in HIV/HCV co-infection and in liver transplant recipients. However, the mechanisms involved remain unclear. Here, we evaluated functional profiles of HCV-specific T-cell responses in 86 HCV mono-infected patients, 48 HIV/HCV co-infected patients and 42 liver transplant recipients. IFN-gamma and IL-2 production and ability of CD4 and CD8 T cells to proliferate were assessed after stimulation with HCV-derived peptides. We observed that HCV-specific T-cell responses were polyfunctional in HCV mono-infected patients, with presence of proliferating single IL-2-, dual IL-2/IFN-gamma and single IFN-gamma-producing CD4+ and dual IL-2/IFN-gamma and single IFN-gamma-producing CD8+ cells. In contrast, HCV-specific T-cell responses had an effector profile in HIV/HCV co-infected individuals and liver transplant recipients with absence of single IL-2-producing HCV-specific CD4+ and dual IL-2/IFN-gamma-producing CD8+ T cells. In addition, HCV-specific proliferation of CD4+ and CD8+ T cells was severely impaired in HIV/HCV co-infected patients and liver transplant recipients. Importantly, "only effector" T-cell responses were associated with significantly higher HCV viral load and more severe liver fibrosis scores. Therefore, the present results suggest that immune-based mechanisms may contribute to explain the accelerated course of HCV infection in conditions of HIV-1 co-infection and liver transplantation.+http://www.ncbi.nlm.nih.gov/pubmed/18958874Ciuffreda, Donatella Comte, Denis Cavassini, Matthias Giostra, Emiliano Buhler, Leo Perruchoud, Monika Heim, Markus H Battegay, Manuel Genne, Daniel Mulhaupt, Beat Malinverni, Raffaele Oneta, Carl Bernasconi, Enos Monnat, Martine Cerny, Andreas Chuard, Christian Borovicka, Jan Mentha, Gilles Pascual, Manuel Gonvers, Jean-Jacques Pantaleo, Giuseppe Dutoit, Valerie Research Support, Non-U.S. Gov't Germany European journal of immunology Eur J Immunol. 2008 Oct;38(10):2665-77.%0014-2980 (Print) 0014-2980 (Linking)18958874Laboratory of AIDS Immunopathogenesis, Division of Immunology and Allergy, Department of Medicine, CHUV, Lausanne, Switzerland.10.1002/eji.200838336engo||7ULentini, S. Gaeta, R. Tancredi, F. Savasta, M. La Monaca, M. Ciuffreda, F. Monaco, F.2009\Transposition of the left carotid artery to the ascending aorta to repair aortic arch injury57-8 J Card Surg241 2008/09/175Aorta, Thoracic/*injuries/surgery Carotid Arteries/*surgery Carotid Stenosis/etiology/prevention & control/ultrasonography Humans Male Middle Aged Thoracic Injuries/complications/diagnosis/*surgery Ultrasonography, Doppler Vascular Surgical Procedures/*methods Wounds, Gunshot/complications/diagnosis/*surgeryJan-FebUWe present a case where we repaired the aortic arch, by the transposition of the left carotid artery to the ascending aorta. A 52-year-old man presented to our department with a penetrating chest wound by a gunshot in the attempt of suicide. The aortic arch and the insertion of the left carotid artery were involved in the lesion. Through sternotomic approach, the aortic arch was repaired in extracorporeal circulation. Left carotid artery was transected to allow easier repair of the arch posterior wall involved in the lesion, and to reduce the danger of residual stenosis. Then, it was translocated to the ascending aorta by interposing a 7-mm Gore-Tex (W.L. Gore & Associates, Flagstaff, AZ, USA) conduit. The patient complicated renal failure and pneumonia in the postoperative period, but eventually he was discharged in good general conditions.+http://www.ncbi.nlm.nih.gov/pubmed/18793235Lentini, Salvatore Gaeta, Roberto Tancredi, Fabrizio Savasta, Marcello La Monaca, Marco Ciuffreda, Francesco Monaco, Francesco Case Reports United States Journal of cardiac surgery J Card Surg. 2009 Jan-Feb;24(1):57-8. Epub 2008 Sep 12.*1540-8191 (Electronic) 0886-0440 (Linking)18793235SCardiac Surgery Unit, Policlinico G. Martino University of Messina, Messina, Italy.-JCS722 [pii] 10.1111/j.1540-8191.2008.00722.xeng ||7,Vasudevan, B. Ciuffreda, K. J. Gilmartin, B.2009gSympathetic inhibition of accommodation after sustained nearwork in subjects with myopia and emmetropia114-20Invest Ophthalmol Vis Sci501 2008/07/05Accommodation, Ocular/*physiology Adrenergic beta-Antagonists/*pharmacology Adult Betaxolol/pharmacology Ciliary Body/*physiopathology Female Humans Male Muscle, Smooth/*innervation Myopia/*physiopathology *Reading Sympathetic Nervous System/*drug effects Timolol/pharmacologyJanPURPOSE: The purposes of the present study were to assess the effect of a sympathetic inhibitory pharmacologic agent, timolol maleate, on the magnitude of nearwork-induced transient myopia (NITM) and its decay in different refractive groups for an extended near task duration and to determine the proportion of the young adult population manifesting effective sympathetic access under naturalistic closed-loop viewing conditions. METHODS: Ten subjects with emmetropia and 10 with myopia were tested. They read binocularly for 1 hour at a distance of 35 to 40 cm. NITM was calculated as the difference in distance refractive state after task as compared with before task immediately after reading. All subjects received timolol maleate to block the sympathetic nervous system and betaxolol as a control agent in independent test sessions separated by at least 3 days. Forty minutes after drug instillation, the NITM measurement procedure was repeated. RESULTS: Initial NITM magnitude was larger in subjects with myopia than in subjects with emmetropia before and after timolol instillation. Furthermore, NITM magnitude in subjects with sympathetic access was increased after timolol instillation. In contrast, with the control agent betaxolol, there was no increase. NITM decay duration to baseline was increased after timolol instillation in the subjects with myopia only. Only 15% of the subjects (n = 3 subjects with myopia) demonstrated effective and significant access to sympathetic facility. CONCLUSIONS: Subjects with myopia demonstrated an increase in decay duration with timolol, thus suggesting impaired sympathetic inhibition of accommodation. This may be a precursor for myopia progression in some persons.+http://www.ncbi.nlm.nih.gov/pubmed/18599570Vasudevan, Balamurali Ciuffreda, Kenneth J Gilmartin, Bernard United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2009 Jan;50(1):114-20. Epub 2008 Jul 3.*1552-5783 (Electronic) 0146-0404 (Linking)18599570oState University of New York, State College of Optometry, New York, New York 10036, USA. bvasudevan@sunyopt.edu'iovs.08-1762 [pii] 10.1167/iovs.08-1762engH||7qAlvarez, T. L. Beck, K. D. Ciuffreda, K. J. Chua, F. B. Daftari, A. DeMarco, R. M. Bergen, M. T. Servatius, R. J.2008IBrief intermittent light stimulation disrupts saccadic oculomotor control354-64Ophthalmic Physiol Opt284 2008/06/21Adult Analysis of Variance Attention Calibration Fixation, Ocular/physiology Humans Perceptual Masking *Photic Stimulation Reaction Time Saccades/*physiology Visual Perception/*physiologyJulPURPOSE: This study sought to determine the effect of very brief, single and multiple pulses of light on spatial and temporal aspects of saccadic eye movements. METHODS: Twelve visually normal, young adult subjects participated in the experiments. Horizontal eye position was monitored as subjects attempted to track target step displacements in the presence of either single or multiple brief flashes of light in the visual field. RESULTS: Three primary findings were observed: (1) increased saccadic latency, (2) increased time for target acquisition and (3) increased initial saccadic error. CONCLUSION: The present findings suggest the influence of attentional processes and/or visual masking effects on saccadic eye movement control.+http://www.ncbi.nlm.nih.gov/pubmed/18565091lAlvarez, Tara L Beck, Kevin D Ciuffreda, Kenneth J Chua, Florence B Daftari, Anuj DeMarco, Robert M Bergen, Michael T Servatius, Richard J Randomized Controlled Trial Research Support, Non-U.S. Gov't England Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists) Ophthalmic Physiol Opt. 2008 Jul;28(4):354-64.%0275-5408 (Print) 0275-5408 (Linking)18565091Department of Biomedical Engineering, New Jersey Institute of Technology, University Heights, Newark, NJ 07102, USA. tara.l.alvarez@njit.edu-OPO569 [pii] 10.1111/j.1475-1313.2008.00569.xeng||7*Bulson, R. C. Ciuffreda, K. J. Hung, G. K.2008-The effect of retinal defocus on golf putting334-44Ophthalmic Physiol Opt284 2008/06/21CAccommodation, Ocular/*physiology Adult Analysis of Variance Equipment Design Eye Movements/physiology Female Fixation, Ocular/physiology *Golf Head Movements/physiology Humans Male Movement Optometry/instrumentation/methods Psychomotor Performance Refraction, Ocular/physiology Retina/*physiology Software Sports EquipmentJulThe purpose of this experiment was to determine the effect of type and magnitude of retinal defocus on golf putting accuracy, and on the related eye, head, and putter movements. Eye, head, and putter movements were assessed objectively along with putting accuracy in 16 young adult, visually normal inexperienced golfers during a fixed 9-foot golf putt. Convex spherical (+0.50 D, +1.00 D, +1.50 D, +2.00 D, +10.00 D) and cylindrical (+1.00 D x 90, +2.00 D x 90) lenses were added binocularly to create various types and magnitudes of retinal defocus. Putting accuracy was significantly reduced only under the highest spherical blur lens condition (+10.00 D). No significant differences were found between any other lens conditions for eye, head or putter movements. Small amounts of spherical and astigmatic retinal defocus had a minimal impact on overall golf putting performance, except for putting accuracy under the highest blur condition. This is consistent with the findings of related studies. For a fixed putting distance, factors other than quality of the retinal image, such as blur adaptation and motor learning, appeared to be sufficient to maintain a high level of motor performance.+http://www.ncbi.nlm.nih.gov/pubmed/18565089Bulson, Ryan C Ciuffreda, Kenneth J Hung, George K Clinical Trial Research Support, Non-U.S. Gov't England Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists) Ophthalmic Physiol Opt. 2008 Jul;28(4):334-44.%0275-5408 (Print) 0275-5408 (Linking)18565089gDepartment of Vision Sciences, State University of New York, State College of Optometry, New York, USA.-OPO575 [pii] 10.1111/j.1475-1313.2008.00575.xeng ||76Scaramuzzi, G. Murgo, R. M. Cuttitta, A. Ciuffreda, L.2008s[Neuroendocrine carcinoma of the breast. Our experience and a proposal of a therapeutic algorithm for a rare tumor]203-6G Chir295 2008/05/30Aged Aged, 80 and over Algorithms Antineoplastic Agents, Hormonal/*therapeutic use Biopsy Breast Neoplasms/diagnosis/metabolism/*therapy Carcinoma, Neuroendocrine/diagnosis/metabolism/*therapy Female Humans Mastectomy/methods Middle Aged Neoplasm Staging Octreotide/analogs & derivatives/diagnostic use Radionuclide Imaging Receptors, Somatostatin/analysis Retrospective Studies Somatostatin/*analogs & derivatives/diagnostic use/*therapeutic use Treatment Outcome Tumor Markers, Biological/analysis Yttrium Radioisotopes/diagnostic useMay The neuroendocrine carcinoma of the breast is a very rare tumor. In this paper we describe our experience in 10 cases of neuroendocrine carcinoma of the breast, and an integrated diagnostic-therapeutic proposal for this tumor. Since no positive association has been shown between neuroendocrine differentiation and tumor size, staging, grading, survival and therefore prognosis, we consider that surgical therapy for neuroendocrine tumors of the breast should be the same as that performed in common invasive histotypes. Due to the presence of specific cellular receptors in neuroendocrine tumors of the breast, somatostatin has been claimed as a useful tool both for diagnostic (Octreoscan) and therapy (for metastatic disease). As for therapy, synthetic analogs show advantages versus native somatostatin, because of a longer half-life, and data from literature report encouraging results obtained by using radiolabelled somatostatin analogs. One of these is 90 Y-Dotatoc; we have already used it in patients with neuroendocrine tumors of the lung. Our algorithm for neuroendocrine tumors of the breast includes diagnostic scintigraphy with Octreoscan and receptor-mediated radiolabelled therapy with 90 Y-Dotatoc in patients with confirmed scintigraphic expression of somatostatin receptors in tumoral tissue.+http://www.ncbi.nlm.nih.gov/pubmed/18507954Scaramuzzi, G Murgo, R M Cuttitta, A Ciuffreda, L English Abstract Italy Il Giornale di chirurgia G Chir. 2008 May;29(5):203-6.%0391-9005 (Print) 0391-9005 (Linking)18507954xIl carcinoma neuroendocrino della mammella. Nostra esperienza e proposta di un algoritmo terapeutico per un tumore raro.LOspedale IRCCS "Casa Sollievo della Sofferenza" San Giovanni Rotondo, Italy. 2852 [pii]ita ||7Barone, C. Grillo, R. Dongiovanni, D. Birocco, N. Rampino, M. Redda, M. G. Garibaldi, E. Munoz, F. Pecorari, G. Cavalot, A. Garzinodemo, P. Buffoni, L. Ciuffreda, L. Ricardi, U. Cortesina, G. Giordano, C. Fasolis, M. Berrone, S. Bertetto, O. Schena, M.2008qInduction chemotherapy followed by concurrent chemoradiotherapy in advanced head and neck squamous cell carcinoma1285-91Anticancer Res282B 2008/05/29Adult Aged Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use Carcinoma, Squamous Cell/*drug therapy/pathology/*radiotherapy Cisplatin/administration & dosage/adverse effects Combined Modality Therapy Female Head and Neck Neoplasms/*drug therapy/pathology/*radiotherapy Humans Male Middle Aged Neoplasm Staging Paclitaxel/administration & dosage/adverse effects Remission Induction Treatment OutcomeMar-Apr-BACKGROUND: A phase II study was carried out to investigate an induction regimen with cisplatin, paclitaxel followed by radiotherapy concurrent with weekly cisplatin for locally advanced squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: Stage III-IV disease patients were eligible. Two cisplatin (100 mg/m2) and paclitaxel (175 mg/m2) courses were administered every 21 days followed by standard fractionated external beam radiotherapy (approximately 70 Gy), concomitant to weekly cisplatin (30 mg/m2). RESULTS: Thirty-five patients were enrolled: over 70% had unresectable disease with bulky lesions. Grade 3-4 neutropenia developed in 14% and G3 mucositis in 23%. Locoregional control was achieved in 51%. Median time to progression and overall survival were 10,7 and 17 months respectively; 2- and 3-year survival rates were 30% and 25% respectively. CONCLUSION: Our induction two-drug regimen followed by chemoradiotherapy with concurrent weekly cisplatin was well tolerated with low acute toxicity and good locoregional control and survival rate.+http://www.ncbi.nlm.nih.gov/pubmed/18505067LBarone, C Grillo, R Dongiovanni, D Birocco, N Rampino, M Redda, M G Ruo Garibaldi, E Munoz, F Pecorari, G Cavalot, A Garzinodemo, P Buffoni, L Ciuffreda, L Ricardi, U Cortesina, G Giordano, C Fasolis, M Berrone, S Bertetto, O Schena, M Clinical Trial, Phase II Greece Anticancer research Anticancer Res. 2008 Mar-Apr;28(2B):1285-91.%0250-7005 (Print) 0250-7005 (Linking)18505067mUOA Oncologia Medica, COES, Azienda Ospedaliera San Giovanni Battista, Torino, Italy. carla.barone@hotmail.iteng n||7McCormack, S. Stohr, W. Barber, T. Bart, P. A. Harari, A. Moog, C. Ciuffreda, D. Cellerai, C. Cowen, M. Gamboni, R. Burnet, S. Legg, K. Brodnicki, E. Wolf, H. Wagner, R. Heeney, J. Frachette, M. J. Tartaglia, J. Babiker, A. Pantaleo, G. Weber, J.2008pEV02: a Phase I trial to compare the safety and immunogenicity of HIV DNA-C prime-NYVAC-C boost to NYVAC-C alone3162-74Vaccine2625 2008/05/27AIDS Vaccines/administration & dosage/immunology/*therapeutic use Adult Antigens, Viral/biosynthesis/genetics/*immunology Drug Design Female HIV Infections/immunology/*prevention & control HIV-1/classification/genetics/immunology Humans Immunization, Secondary Injections, Intramuscular Male Safety Viral Vaccines/administration & dosage/*chemistry/*immunology env Gene Products, Human Immunodeficiency Virus/geneticsJun 13The aim of this randomised controlled trial was to see if the addition of 4 mg/ml DNA-C priming given by the intramuscular route at weeks 0 and 4 to NYVAC-C at weeks 20 and 24, safely increased the proportion of participants with HIV-specific T-cell responses measured by the interferon (IFN)-gamma ELISpot assay at weeks 26 and/or 28 compared to NYVAC-C alone. Although 2 individuals discontinued after the first DNA-C due to adverse events (1 vaso-vagal; 1 transient, asymptomatic elevation in alanine transaminase), the vaccines were well tolerated. Three others failed to complete the regimen (1 changed her mind; 2 lost to follow-up). Of the 35 that completed the regimen 90% (18/20) in the DNA-C group had ELISpot responses compared to 33% (5/15) that received NYVAC-C alone (p=0.001). Responses were to envelope in the majority (21/23). Of the 9 individuals with responses to envelope and other peptides, 8 were in the DNA-C group. These promising results suggest that DNA-C was an effective priming agent, that merits further investigation.+http://www.ncbi.nlm.nih.gov/pubmed/18502003McCormack, Sheena Stohr, Wolfgang Barber, Tristan Bart, Pierre-Alexandre Harari, Alexandre Moog, Christiane Ciuffreda, Donatella Cellerai, Cristina Cowen, Miranda Gamboni, Romilda Burnet, Severine Legg, Ken Brodnicki, Elizabeth Wolf, Hans Wagner, Ralf Heeney, Jonathan Frachette, Marie-Joelle Tartaglia, Jim Babiker, Abdel Pantaleo, Giuseppe Weber, Jonathan Clinical Trial, Phase I Randomized Controlled Trial Research Support, Non-U.S. Gov't Netherlands Vaccine Vaccine. 2008 Jun 13;26(25):3162-74. Epub 2008 May 6.%0264-410X (Print) 0264-410X (Linking)18502003PMRC Clinical Trials Unit, 222 Euston Road, London NW1 2DA, UK. smc@ctu.mrc.ac.uk9S0264-410X(08)00139-4 [pii] 10.1016/j.vaccine.2008.02.072eng ~t7Beano, A. Signorino, E. Evangelista, A. Brusa, D. Mistrangelo, M. Polimeni, M. A. Spadi, R. Donadio, M. Ciuffreda, L. Matera, L.2008`Correlation between NK function and response to trastuzumab in metastatic breast cancer patients25 J Transl Med6 2008/05/20kAntibodies, Monoclonal/chemistry/*therapeutic use Antineoplastic Agents/therapeutic use Breast Neoplasms/*drug therapy/*metabolism Cell Line, Tumor Disease-Free Survival Female Humans Interleukin-2/chemistry K562 Cells Killer Cells, Natural/*cytology Leukocytes, Mononuclear/metabolism Neoplasm Metastasis Receptor, erbB-2/chemistry Recombinant Proteins/chemistry~BACKGROUND: Trastuzumab is a monoclonal antibody selectively directed against Her2 and approved for the treatment of Her2 overexpressing breast cancer patients. Its proposed mechanisms of action include mediation of antibody-dependent cellular cytotoxicity (ADCC) by triggering FcgammaRIII on natural killer (NK) cells. This study addresses the correlation between overall NK function and trastuzumab's clinical activity. SUBJECTS AND METHODS: Clinical and immunological responses were assessed in 26 patients receiving trastuzumab monotherapy as maintenance management after chemotherapy (8 mg/kg load and then standard doses of 6 mg/kg every 3 weeks). Cytotoxic activity against the MHC class I-negative standard NK target K562 cell line and HER2-specific ADCC against a trastuzumab-coated Her2-positive SKBR3 cell line were assessed in peripheral blood mononuclear cells (PBMC) harvested after the first standard dose. After six months, seventeen patients were scored as responders and nine as non-responders according to the RECIST criteria, while Progression-Free Survival (PFS) was calculated during a 12 months follow-up. RESULTS: The responders had significantly higher levels of both NK and ADCC activities (p < 0.05) that were not different from those of eleven normal controls. The NK activity of the non-responders was significantly (p < 0.05) lower than that of the normal controls. At twelve months, there was a marked correlation between PFS and NK activity only. PFS was significantly longer in patients with high levels of NK activity, whereas its pattern was unrelated to high or low ADCC activity. CONCLUSION: One of the mechanisms of action of trastuzumab is NK cell-mediated ADCC lysis of the Her2-positve target cell. We show here that its potency is correlated with the short-term response to treatment, whereas longer protection against tumor expansion seems to be mediated by pure NK activity.+http://www.ncbi.nlm.nih.gov/pubmed/18485193'Beano, Alessandra Signorino, Elena Evangelista, Andrea Brusa, Davide Mistrangelo, Marinella Polimeni, Maria Antonia Spadi, Rosella Donadio, Michela Ciuffreda, Libero Matera, Lina Editorial Research Support, Non-U.S. Gov't England Journal of translational medicine J Transl Med. 2008 May 16;6:25.*1479-5876 (Electronic) 1479-5876 (Linking)241503118485193Dept of Medical Oncology, Molinette's Hospital, Turin, Italy, 2Laboratory of Tumour Immunology, Dept of Internal Medicine, Universityof Turin, Italy. gv.beano@accademiaservice.it+1479-5876-6-25 [pii] 10.1186/1479-5876-6-25eng ||7GSuchoff, I. B. Kapoor, N. Ciuffreda, K. J. Rutner, D. Han, E. Craig, S.2008The frequency of occurrence, types, and characteristics of visual field defects in acquired brain injury: a retrospective analysis259-65 Optometry795 2008/04/26Adolescent Adult Aged Aged, 80 and over Brain Injuries/*physiopathology Child Humans Middle Aged Retrospective Studies Stroke/*physiopathology Vision Disorders/*physiopathology Visual Fields/*physiologyMay BACKGROUND: The purpose of this retrospective study was to determine the frequency of occurrence of visual field defects in a sample of visually symptomatic, ambulatory outpatients who have acquired brain injury (ABI), either traumatic brain injury (TBI) or cerebral vascular accident (CVA). METHODS: The medical records of 220 individuals with TBI (n=160) or CVA (n=60) were reviewed retrospectively. This was determined by a computer-based query spanning the years 2000 through 2003. The individuals' records were reviewed to determine the frequency of targeted visual field defects that were classified as scattered, restricted, homonymous, nonhomonymous, and visual neglect. The altitudinal and lateral characteristics of these defects were also determined. RESULTS: In the total ABI sample of 220, some 102 (46.36%) individuals had 1 of the targeted defects diagnosed. These defects were present in 62 (38.75%) of the TBI subgroup and in 40 (66.67%) of the CVA subgroup. The most frequent defects in the TBI group were scattered (58.06%) followed by homonymous (22.58%). In the CVA group, the most numerous were homonymous (47.5%), with scattered and nonhomonymous accounting for 20% each. CONCLUSION: The uniqueness of the current study is that it reports the frequency of occurrence of specified visual field defects in the total ABI sample and in the TBI and CVA subgroups. This enabled comparisons with other studies that generally have reported on just 1 of these groupings. The current results are in accord with most of the other studies that are reviewed. The findings of this study should alert the reader to the high frequency of occurrence of visual field defects in the ABI population, and make the reader aware of the adverse effects they can have on quality of life and rehabilitation.+http://www.ncbi.nlm.nih.gov/pubmed/18436166Suchoff, Irwin B Kapoor, Neera Ciuffreda, Kenneth J Rutner, Daniella Han, Esther Craig, Shoshana United States Optometry (St. Louis, Mo.) Optometry. 2008 May;79(5):259-65.%1529-1839 (Print) 1558-1527 (Linking)18436166State University of New York, State College of Optometry, Raymond J. Greenwald Rehabilitation Center, New York, New York, USA. idrga@aol.com6S1529-1839(07)00757-9 [pii] 10.1016/j.optm.2007.10.012eng ||7MHan, M. H. Craig, S. B. Rutner, D. Kapoor, N. Ciuffreda, K. J. Suchoff, I. B.2008IMedications prescribed to brain injury patients: a retrospective analysis252-8 Optometry795 2008/04/265Adolescent Adult Aged Aged, 80 and over Anti-Anxiety Agents/therapeutic use Anticonvulsants/therapeutic use Antidepressive Agents/therapeutic use Brain Injuries/complications/*drug therapy Child Female Humans Male Middle Aged Retrospective Studies Stroke/complications/*drug therapy Vision Disorders/*etiologyMayBACKGROUND: The purposes of this study were to retrospectively evaluate the frequency of medications used by individuals with either traumatic brain injury (TBI) or cerebrovascular accident (CVA) and to consider the possible relationship between vision symptoms and diagnoses in this sample and the established visual and ocular side effects of the prescribed medications. METHODS: Charts of patients examined in the Raymond J. Greenwald Rehabilitation Center at the SUNY State College of Optometry from the years 2000 to 2003 were reviewed. Only TBI (n=160) or CVA (n=60) patients were included. Prescribed medications from 12 possible categories were identified. Patients experiencing blurred vision, diplopia, asthenopia, poor depth perception, and/or light sensitivity were identified. Patients with accommodative dysfunction, vergence dysfunction, versional dysfunction, dry eyes, and/or ptosis were also identified. RESULTS: The 4 most common medication categories taken by TBI patients were anti-anxiety/antidepressants (42.5%), anticonvulsants (26.9%), opiate/combination analgesics (23.8%), and cardiac/antihypertensives (23.1%). For the CVA patients, the medications were cardiac/antihypertensives (66.7%), anti-anxiety/antidepressants (31.7%), vitamins/mineral supplements (26.7%), and anticonvulsants (23.3%). Frequency of vision symptoms and diagnoses in the TBI and CVA patients appeared not to be related to medication use in most cases. CONCLUSIONS: Anti-anxiety drugs, antidepressants, and anticonvulsants were the overlapping medication categories between the TBI and CVA groups. Medication intake did not affect the frequency of the reported vision symptoms and diagnoses in most cases, suggesting the symptoms and diagnoses were primarily related to either the TBI or CVA itself.+http://www.ncbi.nlm.nih.gov/pubmed/18436165Han, M H Esther Craig, Shoshana B Rutner, Daniella Kapoor, Neera Ciuffreda, Kenneth J Suchoff, Irwin B United States Optometry (St. Louis, Mo.) Optometry. 2008 May;79(5):252-8.%1529-1839 (Print) 1558-1527 (Linking)18436165hState University of New York State College of Optometry, New York, New York 10036, USA. mhan@synuopt.edu6S1529-1839(08)00003-1 [pii] 10.1016/j.optm.2008.01.001eng||7Ciuffreda, K. J. Vasudevan, B.2008ONearwork-induced transient myopia (NITM) and permanent myopia--is there a link?103-14Ophthalmic Physiol Opt282 2008/03/15Accommodation, Ocular/*physiology Adolescent Adult Child Child, Preschool Disease Progression Eyeglasses Female Humans Male Myopia/*etiology/physiopathology Reading Visual Acuity/physiologyMar{Myopia is a worldwide public health problem. However, its understanding is incomplete, and many of its preventative and therapeutic aspects remain controversial. Nearwork is a primary, environmentally based factor in the aetiology of permanent myopia (PM), with nearwork-induced transient myopia (NITM) being a possible contributory component. A relationship between PM and NITM has been suggested, but that connection has remained somewhat indirect and elusive. However, based on recent converging evidence from clinical, laboratory and modelling studies, a five-fold argument will be advanced for a possible link between PM and NITM.+http://www.ncbi.nlm.nih.gov/pubmed/18339041Ciuffreda, Kenneth J Vasudevan, Balamurali Review England Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists) Ophthalmic Physiol Opt. 2008 Mar;28(2):103-14.%0275-5408 (Print) 0275-5408 (Linking)18339041oDepartment of Vision Sciences, SUNY/State College of Optometry, New York, NY 10036, USA. kciuffreda@sunyopt.edu-OPO550 [pii] 10.1111/j.1475-1313.2008.00550.xeng ||7Racca, P. Fanchini, L. Caliendo, V. Ritorto, G. Evangelista, W. Volpatto, R. Milanesi, E. Ciorba, A. Paris, M. Facilissimo, I. Macripo, G. Clerico, M. Ciuffreda, L.2008Efficacy and skin toxicity management with cetuximab in metastatic colorectal cancer: outcomes from an oncologic/dermatologic cooperation48-54Clin Colorectal Cancer71 2008/02/19IAnti-Infective Agents, Local/therapeutic use Antibodies, Monoclonal/*adverse effects Antineoplastic Combined Chemotherapy Protocols/*adverse effects Camptothecin/analogs & derivatives/therapeutic use Colorectal Neoplasms/*drug therapy/pathology Humans Neoplasm Metastasis Skin Diseases/*chemically induced/drug therapy/*pathologyJanPURPOSE: The aim of this study was to investigate the efficacy of the combination of irinotecan/cetuximab and to plan related skin toxicity management with an oncologic/dermatologic team. PATIENTS AND METHODS: Thirty-four patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer received cetuximab 400 mg/m2 as an initial dose and 250 mg/m2 weekly thereafter. In addition, patients received irinotecan 180 mg/m2 every 2 weeks. RESULTS: Thirty-two patients were evaluated for response rate (RR) and skin toxicity to establish the best management. In our study, the responses observed with cetuximab treatment were complete response in 1 patient (3%), partial response in 11 patients (34%), disease stabilization in 6 patients (19%), and progressive disease in 14 patients (44%). Of 34 patients evaluable for cutaneous toxicity, 10 patients (29%) presented with grade 1 eruption, 13 (38%) with grade 2 eruption, and 4 (12%) with grade 3 eruption. Allergic reactions such as flushing and urticaria (grade 2) were seen in 2 patients (6%). CONCLUSION: Cutaneous reactions consisted of follicular rash, xerosis, painful fissures in palms and soles, alterations in hair growth, and mucositis. In the majority of patients (80%-90%), the worst recorded skin effects were mild (grade 1) to moderate (grade 2). The incidence of severe cases (grade 3) was approximately 15%. All dermatologic effects were reversible and generally without sequelae within 4 weeks after treatment discontinuation. We observed significant correlations between degree of cutaneous toxicity and increased RR. Correct identification and treatment by oncologic/dermatologic cooperation of EGFR cutaneous side effects help to improve quality of life.+http://www.ncbi.nlm.nih.gov/pubmed/18279577`Racca, Patrizia Fanchini, Laura Caliendo, Virginia Ritorto, Giuliana Evangelista, Walter Volpatto, Roberta Milanesi, Enrica Ciorba, Angelica Paris, Myriam Facilissimo, Ivan Macripo, Giuseppe Clerico, Mario Ciuffreda, Libero Clinical Trial, Phase II Multicenter Study United States Clinical colorectal cancer Clin Colorectal Cancer. 2008 Jan;7(1):48-54.%1533-0028 (Print) 1533-0028 (Linking)18279577Centro Universitario di Ricerca Oncologica, Oncologia Medica I, ASO San Giovanni Battista Ospedale Molinette, Torino, Italy. p.racca@tin.iteng #||7Dongiovanni, D. Daniele, L. Barone, C. Dongiovanni, V. Fissore, C. Sapino, A. Macri, L. Bussolati, G. Buffoni, L. Gaspari, F. Grillo, R. Birocco, N. Addeo, A. Ciuffreda, L. Schena, M.2008YGefitinib (ZD1839): therapy in selected patients with non-small cell lung cancer (NSCLC)?73-81 Lung Cancer611 2008/02/05Adult Aged Aged, 80 and over Antineoplastic Agents/*therapeutic use Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics Female Gene Dosage Humans Immunohistochemistry In Situ Hybridization, Fluorescence Lung Neoplasms/*drug therapy/genetics Male Middle Aged Mutation Polymerase Chain Reaction Prognosis Quinazolines/*therapeutic use Receptor, Epidermal Growth Factor/*genetics Treatment OutcomeJulPURPOSE: To evaluate response rate, toxicity and epidermal growth factor (EGFR) mutations and gene copy number as outcome predictive factors in Italian patients with non-small cell lung cancer (NSCLC) treated with gefitinib (Iressa) in an expanded access program (EAP). PATIENTS AND METHODS: A total of 137 patients with advanced NSCLC received gefitinib as first line treatment or after failure of chemotherapy. In 43 cases, tissue specimens were available for EGFR status evaluation: immunohistochemical (IHC) for EGFR, fluorescence in situ hybridisation (FISH) or Chromogenic in situ hybridisation (CISH)-(ISH) analysis for EGFR and HER2 gene copy number, and PCR-DNA sequencing for mutational analysis of EGFR were performed. RESULTS: In the study population, response rate (PR) was 13%; disease stabilization (DS) 26%; overall disease control rate 39%; median survival 6.3 months and time to progression 2.7 months. Toxicity was mild (G3 skin toxicity in 3% and G3 liver toxicity in 4% of patients). An EGFR-mutation was detected in 9/43 patients: Eight deletions in exon 19 and 1 missense mutation in exon 21. Increased gene copy number for EGFR and/or HER2 was detected in 17/43 patients. Response rate was significantly higher in women, non-smokers, in mutation carriers than in wild type carriers, in EGFR-trisomy/polysomy carriers and HER2-trisomy/polysomy carriers. CONCLUSIONS: In this study, response rate and toxicity to gefitinib treatment were consistent with previously reported data for whites. Female gender, absence of smoking history, EGFR-mutations, EGFR and HER2-polysomy were significantly associated with response to gefitinib therapy in NSCLC patients.+http://www.ncbi.nlm.nih.gov/pubmed/18243402gDongiovanni, Diego Daniele, Lorenzo Barone, Carla Dongiovanni, Vincenzo Fissore, Camilla Sapino, Anna Macri, Luigia Bussolati, Giovanni Buffoni, Lucio Gaspari, Fabio Grillo, Raffaella Birocco, Nadia Addeo, Alfredo Ciuffreda, Libero Schena, Marina Clinical Trial Ireland Lung cancer (Amsterdam, Netherlands) Lung Cancer. 2008 Jul;61(1):73-81. Epub 2008 Feb 19.%0169-5002 (Print) 0169-5002 (Linking)18243402Medical Oncology, Centro Oncologico Ematologico Subalpino (C.O.E.S.), Azienda Ospedaliera S. Giovanni Battista, Turin, Italy. diego.dongiovanni@libero.it9S0169-5002(07)00721-0 [pii] 10.1016/j.lungcan.2007.12.007eng ||7Vasudevan, B. Ciuffreda, K. J.2008mAdditivity of near work-induced transient myopia and its decay characteristics in different refractive groups836-41Invest Ophthalmol Vis Sci492 2008/02/01j*Accommodation, Ocular Adult Humans Myopia/*etiology/physiopathology *Reading Vision, Binocular/physiologyFebPURPOSE: To determine the additive effect, if any, of NITM after 1 and 2 hours of reading in different refractive groups. METHODS: Fifteen early-onset myopes (EOMs), 14 late-onset myopes (LOMs), and 15 emmetropes (EMMs), as well as progressive myopes (PMs) and stable myopes (SMs), were tested. Subjects read binocularly for 2 hours at a distance of 35 to 40 cm. Distance refractive state of the right eye was assessed every 2 seconds for 30 seconds after the first hour of reading, and then every 2 seconds for 120 seconds after the second hour of reading. NITM was calculated as the difference in posttask distance refractive state compared with the pretask distance refractive state after each hour. RESULTS: Initial NITM values (mean +/- SE) recorded at the end of the near work tasks were 0.22 +/- 0.03 D and 0.29 +/- 0.03 D for the EOMs, 0.14 +/- 0.02 D and 0.20 +/- 0.03 D for the LOMs, 0.14 +/- 0.02 D and 0.15 +/- 0.02 D for the EMMs, 0.20 +/- 0.03 D and 0.27 +/- 0.03 D for the PMs, and 0.09 +/- 0.04 D and 0.20 +/- 0.05 D for the SMs, after the first and second hours of reading, respectively. After the second hour, only in the EOMs and LOMs was NITM significantly greater than that found after the first hour. Seventy percent of the myopes (EOMs and LOMs) but only 47% of the EMMs exhibited increased NITM in the second hour compared with the first hour. Only EOMs exhibited longer decay duration after the second hour of reading. NITM was increased in progressive myopes (PMs), but not in stable myopes (SMs), after the first hour of reading only. Within the PMs, NITM was increased after the second hour compared with the first hour. The time constant for decay was greater in the PMs than in the SMs. Lastly, many myopes (up to 46%) did not experience decay to baseline after the near task over the 120-second posttask period. CONCLUSIONS: EOMs and LOMs demonstrated larger NITM than the EMMs and exhibited NITM additivity, but the EOMs also exhibited prolonged decay of NITM compared with the EMMs and LOMs. PMs, but not SMs, exhibited additivity of NITM. These findings may be attributed to impaired sympathetic function in the subjects with myopia. It is speculated that with repeated cycles of near work, residual NITM may contribute to the progression of permanent myopia.+http://www.ncbi.nlm.nih.gov/pubmed/18235035Vasudevan, Balamurali Ciuffreda, Kenneth J Research Support, Non-U.S. Gov't United States Investigative ophthalmology & visual science Invest Ophthalmol Vis Sci. 2008 Feb;49(2):836-41.%0146-0404 (Print) 0146-0404 (Linking)18235035hState University of New York/State College of Optometry, New York, NY 10036, USA. bvasudevan@sunyopt.edu#49/2/836 [pii] 10.1167/iovs.07-0197eng ||7;Alessandrini, L. Ciuffreda, P. Pavlovic, R. Santaniello, E.2008Activity of adenosine deaminase and adenylate deaminase on adenosine and 2', 3(')-isopropylidene adenosine: role of the protecting group at different pH values31-6%Nucleosides Nucleotides Nucleic Acids271 2008/01/12AMP Deaminase/chemistry/*metabolism Adenosine/*chemistry Adenosine Deaminase/chemistry/*metabolism Aspergillus/enzymology Catalysis Deamination Hydrogen-Ion ConcentrationJanDThe deamination rate of 2',3'-isopropylidene adenosine catalyzed by adenosine deaminase (ADA) from calf intestine and adenylate deaminase (AMPDA) from Aspergillus species has been evaluated and compared with that of the enzymatic reactions of adenosine, to elucidate the influence of the protecting group on enzyme activity.+http://www.ncbi.nlm.nih.gov/pubmed/18188767Alessandrini, Laura Ciuffreda, Pierangela Pavlovic, Radmila Santaniello, Enzo Research Support, Non-U.S. Gov't United States Nucleosides, nucleotides & nucleic acids Nucleosides Nucleotides Nucleic Acids. 2008 Jan;27(1):31-6.%1525-7770 (Print) 1525-7770 (Linking)18188767aDipartimento di Scienze Precliniche LITA Vialba, Universita degli Studi di Milano, Milano, Italy.)789467216 [pii] 10.1080/15257770701571776eng ||7JCiuffreda, K. J. Rutner, D. Kapoor, N. Suchoff, I. B. Craig, S. Han, M. E.2008]Vision therapy for oculomotor dysfunctions in acquired brain injury: a retrospective analysis18-22 Optometry791 2007/12/25Adolescent Adult Aged Aged, 80 and over Brain Injuries/*complications/diagnosis Child Eye Movements Female Humans Male Middle Aged Ocular Motility Disorders/diagnosis/etiology/*therapy Orthoptics/*methods Quality of Life Reading Retrospective Studies Stroke/*complications/diagnosisJanBACKGROUND: Oculomotor dysfunctions are among the most common abnormalities found in the brain-injured population. The purpose of the current study was to determine retrospectively the effectiveness of conventional optometric vision therapy for oculomotor disorders of vergence and version in a sample of ambulatory, visually symptomatic, predominantly adult outpatients who had either mild traumatic brain injury (TBI) or cerebrovascular accident (CVA). METHODS: A computer-based query for acquired brain injury patients examined between the years of 2000 and 2003 was conducted in our clinic. This yielded 160 individuals with mild TBI and 60 with CVA. Of these patients, only those for whom vision therapy was prescribed and who completed an optometric vision therapy program for remediation of their oculomotor dysfunctions were selected. This included 33 with TBI and 7 with CVA. The criterion for treatment success was denoted by marked/total improvement in at least 1 primary symptom and at least 1 primary sign. RESULTS: Ninety percent of those with TBI and 100% of those with CVA were deemed to have treatment success. These improvements remained stable at retesting 2 to 3 months later. CONCLUSION: Nearly all patients in the current clinic sample exhibited either complete or marked reduction in their oculomotor-based symptoms and improvement in related clinical signs, with maintenance of the symptom reduction and sign improvements at the 2- to 3-month follow-up. These findings show the efficacy of optometric vision therapy for a range of oculomotor abnormalities in the primarily adult, mild brain-injured population. Furthermore, it shows considerable residual neural plasticity despite the presence of documented brain injury.+http://www.ncbi.nlm.nih.gov/pubmed/18156092Ciuffreda, Kenneth J Rutner, Daniella Kapoor, Neera Suchoff, Irwin B Craig, Shoshana Han, M E United States Optometry (St. Louis, Mo.) Optometry. 2008 Jan;79(1):18-22.%1529-1839 (Print) 1558-1527 (Linking)18156092State University of New York State College of Optometry, Raymond J Greenwald Rehabilitation Center, New York, NY 10036, USA. kciuffreda@sunyopt.edu6S1529-1839(07)00605-7 [pii] 10.1016/j.optm.2007.10.004eng s||7wRoato, I. Gorassini, E. Buffoni, L. Lyberis, P. Ruffini, E. Bonello, L. Baldi, I. Ciuffreda, L. Mussa, A. Ferracini, R.2008iSpontaneous osteoclastogenesis is a predictive factor for bone metastases from non-small cell lung cancer109-16 Lung Cancer611 2007/12/07Aged Aged, 80 and over Bone Neoplasms/metabolism/mortality/*secondary Bone Resorption Carcinoma, Non-Small-Cell Lung/metabolism/mortality/*secondary Enzyme-Linked Immunosorbent Assay Flow Cytometry Gene Expression Humans Interleukin-17/blood/genetics Kaplan-Meier Estimate Lung Neoplasms/metabolism/mortality/*pathology Male Middle Aged Osteoclasts/*cytology Prognosis Reverse Transcriptase Polymerase Chain ReactionJulLung cancer is a widespread disease and its incidence is growing. Since therapies have increased the life expectancy of lung cancer patients, the development of bone osteolytic metastases is becoming a common cause of morbidity. Osteolysis is caused by an increased osteoclast activity and may be reduced by inhibiting their formation and activity. We studied 60 male patients affected by NSCLC, divided in early and advanced stage disease. Patients' blood and urinary samples were collected at tumor diagnosis and at follow-up. PBMCs were cultured to investigate the spontaneous osteoclastogenesis. IL-7 was dosed in serum and its quantitative gene expression was evaluated on tumor and healthy tissues by RQ-PCR. Both at diagnosis and follow-up, osteolytic bone patients showed high spontaneous osteoclastogenesis level compared to non-bone metastatic and healthy controls. The presence of spontaneous osteoclastogenesis correlated with urinary crosslinks increase. Serum IL-7 levels were higher in bone metastatic patients than in patients without bone lesions and healthy controls. The serum IL-7 increase correlated with the osteoclastogenesis and, at least in part, depended on an increased IL-7 production by tumor cells. At follow-up, patients with increased osteoclastogenesis and serum IL-7 levels, were subjected to standard clinical analysis, which showed early secondary bone lesions. The in vitro assay for spontaneous osteoclastogenesis and serum IL-7 dosage could be useful for diagnostic purposes and it might be able to monitor cancer patients with a high risk to develop osteolytic metastases at follow-up, especially after a curative treatment.+http://www.ncbi.nlm.nih.gov/pubmed/18061306Roato, I Gorassini, E Buffoni, L Lyberis, P Ruffini, E Bonello, L Baldi, I Ciuffreda, L Mussa, A Ferracini, R Research Support, Non-U.S. Gov't Ireland Lung cancer (Amsterdam, Netherlands) Lung Cancer. 2008 Jul;61(1):109-16. Epub 2007 Dec 3.%0169-5002 (Print) 0169-5002 (Linking)18061306CeRMS (Center for Experimental Research and Medical Studies) University and A.S.O. San Giovanni Battista, Turin, Italy. roato78@libero.it9S0169-5002(07)00617-4 [pii] 10.1016/j.lungcan.2007.10.016eng?=Gonzales, SR. Ciufredda, KJ. Hernandez, LC. Escalante, JB. 2008The Correlation between Primitive Refexes and Saccadic Eye Movements in 5th Grade Children with Teacher-Reported Reading Problems140 Opt Vis Dev393 ||7Abdi, S. Rydberg, A.2005SAsthenopia in schoolchildren, orthoptic and ophthalmological findings and treatment65-72Doc Ophthalmol1112 2006/03/04Accommodation, Ocular/*physiology Adolescent Asthenopia/*diagnosis/physiopathology/*therapy Child Diagnosis, Differential Eye Movements/*physiology *Eyeglasses Female Humans Male Refraction, Ocular Treatment Outcome Vision Tests Visual AcuitySepThe aim of this study was to describe the orthoptic and ophthalmological findings in schoolchildren with asthenopia, to correlate them with asthenopic symptoms and to evaluate the effect of treatment. One hundred and twenty schoolchildren, aged 6-16 years, were included in the study. They were all referred by school nurses, for asthenopic symptoms. An orthoptic and ophthalmological assessment was performed. The main diagnoses were accommodative insufficiency, convergence insufficiency, refractive errors, and latent strabismus. Reading glasses could help 98% of the schoolchildren with reduced accommodation, and 94% of the children with refractive errors and heterophorias were helped with appropriate spherical, cylindrical and prism correction. Convergence exercise reduced the symptoms in all patients with convergence insufficiency. Ninety-three percent of all 120 schoolchildren were symptom free 3-6 month after treatment had started. By an orthoptic and ophthalmological examination abnormalities in schoolchildren with asthenopia related to visual problems can be identified. Most of the children were relieved from their symptoms by giving adequate glasses, convergence exercises and surgery.+http://www.ncbi.nlm.nih.gov/pubmed/16514487Abdi, Saber Rydberg, Agneta Comparative Study Research Support, Non-U.S. Gov't Netherlands Documenta ophthalmologica. Advances in ophthalmology Doc Ophthalmol. 2005 Sep;111(2):65-72. Epub 2006 Feb 28.%0012-4486 (Print) 0012-4486 (Linking)16514487WKarolinska Institutet, St. Erik's Eye Hospital, Stockholm, Sweden. saber.abdi@ste.ki.se10.1007/s10633-005-4722-4engG||7YMiller, L. J. Mittenberg, W. Carey, V. M. McMorrow, M. A. Kushner, T. E. Weinstein, J. M.1999,Astereopsis caused by traumatic brain injury537-43Arch Clin Neuropsychol146 2003/11/01AugyImpaired depth perception (astereopsis) has been observed in a variety of cerebral pathologies affecting the posterior parietal lobe. In the current study of 93 consecutive head trauma admissions, 24% had complete astereopsis and 41% performed more than 2 SDs below the orthopedic control group mean. Degree of impairment was related to Glascow Coma Scale score, length of posttraumatic amnesia, reduced visuospatial and memory abilities, and the presence of intracranial pathology of the parietal lobes. Impairment was also related to trauma severity in patients without any visualized intracranial pathology, presumably due to diffuse axonal shearing. Clinically meaningful impairment was observed in 25% of this group; 10% had complete astereopsis. Stereoacuity screening requires 1 to 2 minutes. Undetected astereopsis may increase risk for subsequent motor vehicle accidents or falls.+http://www.ncbi.nlm.nih.gov/pubmed/14590581Miller, L J Mittenberg, W Carey, V M McMorrow, M A Kushner, T E Weinstein, J M United States Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists Arch Clin Neuropsychol. 1999 Aug;14(6):537-43.%0887-6177 (Print) 0887-6177 (Linking)14590581tDepartment of Psychiatry, College of Medicine, Health Sciences Center, University of Arizona, Tucson, AZ 85724, USA.S0887617798000481 [pii]eng||7'Alpert, B. Engelstad, M. Kushner, G. M.1999IInvited review: small versus large plate fixation of mandibular fractures33-9; discussion 40J Craniomaxillofac Trauma53 2002/04/16Bone Plates/*classification Bone Screws Bone Wires Equipment Design Fracture Fixation, Internal/adverse effects/*instrumentation/methods Fracture Healing Humans Mandibular Fractures/classification/*surgery Surface PropertiesFalloBACKGROUND AND OBJECTIVES: Since the introduction of antibiotics in the late 1940s, open reduction and internal fixation (ORIF) gradually replaced various dental splints and devices as a means of providing additional reduction and fixation of mandibular fractures. Stainless steel wire has been recently replaced by plate-and-screw fixation. When properly utilized, this method provides convalescent function without maxillomandibular fixation (MMF). The purpose of this article is to review the evolution of small versus large plate fixation of mandibular fractures. METHODS AND MATERIALS: In the context of reports in the literature and 26 years of clinical experience, the authors review the types of mandibular rigid fixation, healing of fractures, morbidity of fracture repair, indications for rigid fixation, and evolution of techniques of treatment. RESULTS AND/OR CONCLUSIONS: Although numerous devices and techniques--bone clamps, intra- and extramedullary K-wires, metallic mesh, and other means--have been used and abandoned, modern plate and screw systems, if not the standard of care, have become widely accepted and used.+http://www.ncbi.nlm.nih.gov/pubmed/11951257Alpert, B Engelstad, M Kushner, G M Review United States The Journal of cranio-maxillofacial trauma J Craniomaxillofac Trauma. 1999 Fall;5(3):33-9; discussion 40.%1074-3219 (Print) 1074-3219 (Linking)11951257kDepartment of Surgical and Hospital Dentistry, University of Louisville School of Dentistry, KY 40292, USA.eng||7&Kushner, H. I. Luzzatti, C. Finger, S.1999A perplexing document in the early history of Gilles de la Tourette Syndrome: Melotti's rendition of a "Lecture of Charcot" (including a complete translation from the Italian with commentary)5-20J Hist Neurosci81 2001/10/20zFrance History, 19th Century History, 20th Century Humans Italy Neurology/*history Tourette Syndrome/*history TranslationsAprIn 1885, Dr. Guilio Melotti published an Italian translation of a lecture on "Convulsive Tics with Coprolalia and Echolalia" given by Jean-Martin Charcot. Although this lecture often has been cited as an authoritative statement of Charcot's view, until now it has not been translated into English. The lecture presents a number of statements that appear nowhere else in Charcot's published corpus, including some that seem to contradict Charcot's other pronouncements on maladie des tics. Although the Melotti-Charcot lecture may portray Charcot's position accurately in many passages, the article most likely is a compilation from a variety of sources.+http://www.ncbi.nlm.nih.gov/pubmed/11624136Kushner, H I Luzzatti, C Finger, S Biography Historical Article Portraits Netherlands Journal of the history of the neurosciences J Hist Neurosci. 1999 Apr;8(1):5-20.%0964-704X (Print) 0964-704X (Linking)116241369History of Medicine, San Diego State University, CA, USA.10.1076/jhin.8.1.5.1779eng2||7Kushner, B. J.1999Hemangiomas in children2018; author reply 2018-9 N Engl J Med34126 2000/01/05Adrenal Cortex Hormones/*adverse effects/therapeutic use Child Eye Neoplasms/*drug therapy Hemangioma/*drug therapy Humans Injections, IntralesionalDec 23+http://www.ncbi.nlm.nih.gov/pubmed/10617397Kushner, B J Comment Letter United states The New England journal of medicine N Engl J Med. 1999 Dec 23;341(26):2018; author reply 2018-9.%0028-4793 (Print) 0028-4793 (Linking)1061739710.1056/NEJM199912233412614eng~|7BRazi, K. Greene, K. P. Sakuma, M. Ge, S. Kushner, M. DeLisi, L. E.1999aReduction of the parahippocampal gyrus and the hippocampus in patients with chronic schizophrenia512-9Br J Psychiatry174 2000/01/05Adult Analysis of Variance Brain Diseases/*pathology Female Hippocampus/*pathology Humans Magnetic Resonance Imaging/methods Male Schizophrenia/*pathologyJunHBACKGROUND: There have been many studies reporting reduced volume of the hippocampus or other limbic structures in patients with schizophrenia, but the literature is inconsistent. AIMS: To compare patients with either first-episode or chronic schizophrenia with controls using high-resolution volumetric magnetic resonance imaging (MRI) scans. METHOD: Thirteen patients with first-episode schizophrenia, 27 with chronic schizophrenia and 31 controls had 1.5 mm coronal slices taken through the whole brain using a spoiled-grass MRI acquisition protocol. RESULTS: The parahippocampal gyrus was reduced significantly on the left side in patients with chronic schizophrenia compared with controls for both male and female patients, whereas the hippocampus was reduced significantly on both sides only in female patients. There were no significant reductions in any structure between patients with first-episode schizophrenia and controls. CONCLUSIONS: Volumetric reduction seen in patients with chronic schizophrenia may be due to an active degenerative process occurring after the onset of illness.+http://www.ncbi.nlm.nih.gov/pubmed/10616629Razi, K Greene, K P Sakuma, M Ge, S Kushner, M DeLisi, L E R0I-44233/PHS HHS/United States Clinical Trial Controlled Clinical Trial Research Support, U.S. Gov't, P.H.S. Review England The British journal of psychiatry : the journal of mental science Br J Psychiatry. 1999 Jun;174:512-9.%0007-1250 (Print) 0007-1250 (Linking)106166297Department of Psychiatry, SUNY, Stony Brook 11794, USA.eng||7FLynch, W. J. Kushner, M. G. Rawleigh, J. M. Fiszdon, J. Carroll, M. E.1999HThe effects of restraint stress on voluntary ethanol consumption in rats318-23Exp Clin Psychopharmacol74 1999/12/28Alcohol Drinking/*psychology Animals Drinking Glucose/pharmacology Male Rats Rats, Wistar Restraint, Physical Stress, Psychological/*psychologyNovSixty Wistar rats (Rattus norvegicus) were assigned to 4 groups of 15 rats each: ethanol stress (ES), ethanol no-stress (EN), isocaloric stress (IS) and isocaloric no-stress (IN). The effect of restraint stress on daily intake of ethanol and a 0.72% solution of glucose was examined in an ABA design (stress-no stress-stress). During the stress phases, 2 groups were subjected to daily 15-min restraint stress, whereas 2 groups were placed in different cages for 15 min as a control. All 4 groups were then given 6-hr access to their assigned liquid alone for 4 days followed by a choice between their assigned liquid and water on the 5th day. The ES group significantly increased their ethanol intake (g/kg) compared to the EN group on choice days but not on forced days. Percentage preference for ethanol was significantly greater and increased at a faster rate over the 75-day testing period compared with the EN group. However, total ethanol consumption (g/kg) and percentage preference did not vary as a function of phase. It is notable that the effects of restraint stress on ethanol self-administration persisted even after the stress schedule was removed.+http://www.ncbi.nlm.nih.gov/pubmed/10609966KLynch, W J Kushner, M G Rawleigh, J M Fiszdon, J Carroll, M E F31 DA05650/DA/NIDA NIH HHS/United States R37 DA03240/DA/NIDA NIH HHS/United States T32 DA07097/DA/NIDA NIH HHS/United States Research Support, U.S. Gov't, P.H.S. United states Experimental and clinical psychopharmacology Exp Clin Psychopharmacol. 1999 Nov;7(4):318-23.%1064-1297 (Print) 1064-1297 (Linking)10609966KDepartment of Psychiatry, University of Minnesota, Minneapolis, 55455, USA.eng w|t7\An, J. Ribeiro, R. C. Webb, P. Gustafsson, J. A. Kushner, P. J. Baxter, J. D. Leitman, D. C.1999Estradiol repression of tumor necrosis factor-alpha transcription requires estrogen receptor activation function-2 and is enhanced by coactivators15161-6Proc Natl Acad Sci U S A9626 1999/12/28]Adaptor Proteins, Signal Transducing Binding Sites Estradiol/*pharmacology Estrogen Receptor Modulators/pharmacology Estrogen Receptor alpha Estrogen Receptor beta Gene Expression Regulation Ligands Mutation Nuclear Proteins/metabolism Nuclear Receptor Coactivator 2 Receptors, Estrogen/genetics/*metabolism *Response Elements Selective Estrogen Receptor Modulators/metabolism Simplexvirus/enzymology/genetics Thymidine Kinase/genetics Transcription Factor AP-1/metabolism Transcription Factors/metabolism Transcription, Genetic/drug effects Tumor Necrosis Factor-alpha/biosynthesis/*genetics/pharmacologyDec 21The tumor necrosis factor-alpha (TNF-alpha) promoter was used to explore the molecular mechanisms of estradiol (E(2))-dependent repression of gene transcription. E(2) inhibited basal activity and abolished TNF-alpha activation of the TNF-alpha promoter. The E(2)-inhibitory element was mapped to the -125 to -82 region of the TNF-alpha promoter, known as the TNF-responsive element (TNF-RE). An AP-1-like site in the TNF-RE is essential for repression activity. Estrogen receptor (ER) beta is more potent than ERalpha at repressing the -1044 TNF-alpha promoter and the TNF-RE upstream of the herpes simplex virus thymidine kinase promoter, but weaker at activating transcription through an estrogen response element. The activation function-2 (AF-2) surface in the ligand-binding domain is required for repression, because anti-estrogens and AF-2 mutations impair repression. The requirement of the AF-2 surface for repression is probably due to its capacity to recruit p160 coactivators or related coregulators, because overexpressing the coactivator glucocorticoid receptor interacting protein-1 enhances repression, whereas a glucocorticoid receptor interacting protein-1 mutant unable to interact with the AF-2 surface is ineffective. Furthermore, receptor interacting protein 140 prevents repression by ERbeta, probably by interacting with the AF-2 surface and blocking the binding of endogenous coactivators. These studies demonstrate that E(2)-mediated repression requires the AF-2 surface and the participation of coactivators or other coregulatory proteins.+http://www.ncbi.nlm.nih.gov/pubmed/10611355xAn, J Ribeiro, R C Webb, P Gustafsson, J A Kushner, P J Baxter, J D Leitman, D C DK51083/DK/NIDDK NIH HHS/United States DK51281/DK/NIDDK NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15161-6.%0027-8424 (Print) 0027-8424 (Linking)2479010611355Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.eng||7Mohanty, B. K. Kushner, S. R.1999Residual polyadenylation in poly(A) polymerase I (pcnB ) mutants of Escherichia coli does not result from the activity encoded by the f310 gene1109-19 Mol Microbiol345 1999/12/14Adenosine Triphosphate/metabolism Amino Acid Sequence Bacterial Proteins/chemistry/*genetics/metabolism Base Sequence Carrier Proteins/metabolism Escherichia coli/*enzymology/genetics/growth & development *Escherichia coli Proteins Hot Temperature Molecular Sequence Data *Mutation Poly A/genetics/*metabolism Polynucleotide Adenylyltransferase/chemistry/*genetics/metabolism Promoter Regions, Genetic RNA, Messenger/metabolism Transcription, GeneticDecPAs extracts of poly(A) polymerase I (PAP I) deficient strains of Escherichia coli appeared to contain considerable residual polyadenylating activity, efforts were undertaken to identify a second poly(A) polymerase. Recently, a gene (f310 ) encoding the putative second poly(A) polymerase was cloned and sequenced. Here we have tested the ability of the F310 protein to add poly(A) tails in vivo by measuring total poly(A) levels in both f310 mutants and strains that overproduce F310. In addition, we have visualized poly(A) tails and examined ColE1 plasmid copy number in various genetic backgrounds. We also carried out direct biochemical measurements of AMP incorporation, using cell extracts after amplification of F310. All the data obtained indicate that F310 is not a poly(A) polymerase. Although the presence of two potential ATP binding domains in the F310 protein may account for its apparent ATP binding activity, its true biochemical function remains to be identified. In addition, we show that the f310 gene is transcribed, almost exclusively, during stationary phase from a sigmas promoter.+http://www.ncbi.nlm.nih.gov/pubmed/10594834Mohanty, B K Kushner, S R GM28760/GM/NIGMS NIH HHS/United States Research Support, U.S. Gov't, P.H.S. England Molecular microbiology Mol Microbiol. 1999 Dec;34(5):1109-19.%0950-382X (Print) 0950-382X (Linking)10594834EDepartment of Genetics, University of Georgia, Athens, GA 30602, USA. mmi1674 [pii]eng ||7Mohanty, B. K. Kushner, S. R.1999SAnalysis of the function of Escherichia coli poly(A) polymerase I in RNA metabolism1094-108 Mol Microbiol345 1999/12/14Blotting, Southern Colony Count, Microbial Enzyme Induction Escherichia coli/*enzymology/growth & development *Escherichia coli Proteins Isopropyl Thiogalactoside/metabolism Lac Operon/genetics Plasmids/genetics Poly A/metabolism Polynucleotide Adenylyltransferase/*metabolism Promoter Regions, Genetic RNA, Bacterial/*metabolism RNA, Messenger/genetics/metabolism RNA, Ribosomal, 16S/genetics/metabolism RNA, Ribosomal, 23S/genetics/metabolism Reverse Transcriptase Polymerase Chain Reaction Ribonucleases/metabolism Transcription, GeneticDecTo help understand the role of polyadenylation in Escherichia coli RNA metabolism, we constructed an IPTG-inducible pcnB [poly(A) polymerase I, PAP I] containing plasmid that permitted us to vary poly(A) levels without affecting cell growth or viability. Increased polyadenylation led to a decrease in the half-life of total pulse-labelled RNA along with decreased half-lives of the rpsO, trxA, lpp and ompA transcripts. In contrast, the transcripts for rne (RNase E) and pnp (polynucleotide phosphorylase, PNPase), enzymes involved in mRNA decay, were stabilized. rnb (RNase II) and rnc (RNase III) transcript levels were unaffected in the presence of increased polyadenylation. Long-term overproduction of PAP I led to slower growth and irreversible cell death. Differential display analysis showed that new RNA species were being polyadenylated after PAP I induction, including the mature 3'-terminus of 23S rRNA, a site that was not tailed in wild-type cells. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated an almost 20-fold variation in the level of polyadenylation among three different transcripts and that PAP I accounted for between 94% and 98.6% of their poly(A) tails. Cloning and sequencing of cDNAs derived from lpp, 23S and 16S rRNA revealed that, during exponential growth, C and U residues were polymerized into poly(A) tails in a transcript-dependent manner.+http://www.ncbi.nlm.nih.gov/pubmed/10594833Mohanty, B K Kushner, S R GM28760/GM/NIGMS NIH HHS/United States Research Support, U.S. Gov't, P.H.S. England Molecular microbiology Mol Microbiol. 1999 Dec;34(5):1094-108.%0950-382X (Print) 0950-382X (Linking)10594833EDepartment of Genetics, University of Georgia, Athens, GA 30602, USA. mmi1673 [pii]eng||7+Rosenstein, E. D. Kushner, L. J. Kramer, N.1999Rheumatoid arthritis 1424, 1426J Am Dent Assoc13010 1999/11/26zAnti-Inflammatory Agents, Non-Steroidal/administration & dosage/adverse effects Antirheumatic Agents/administration & dosage Arthritis, Rheumatoid/*drug therapy Aurothioglucose/administration & dosage Blood Loss, Surgical *Dental Care for Chronically Ill Humans Methotrexate/administration & dosage Pyrazoles Sjogren's Syndrome/*drug therapy Sulfonamides/administration & dosageOct+http://www.ncbi.nlm.nih.gov/pubmed/10570586Rosenstein, E D Kushner, L J Kramer, N Comment Letter United states Journal of the American Dental Association (1939) J Am Dent Assoc. 1999 Oct;130(10):1424, 1426.%0002-8177 (Print) 0002-8177 (Linking)10570586eng ||7aKushner, B. H. LaQuaglia, M. P. Cheung, N. K. Kramer, K. Hamelin, A. C. Gerald, W. L. Ladanyi, M.1999QClinically critical impact of molecular genetic studies in pediatric solid tumors530-5Med Pediatr Oncol336 1999/11/26Adolescent Carcinoma/*diagnosis/genetics/metabolism Child Diagnosis, Differential Female Humans Immunohistochemistry Infant Leukemia/*diagnosis/genetics/metabolism Male Neuroectodermal Tumors, Primitive/*diagnosis/genetics/metabolism Predictive Value of Tests Reverse Transcriptase Polymerase Chain Reaction Rhabdomyosarcoma, Alveolar/*diagnosis/genetics/metabolism Sarcoma, Small Cell/*diagnosis/genetics/metabolism Translocation, Genetic/*genetics Tumor Markers, Biological/biosynthesisDecBACKGROUND: Standard cytogenetic techniques are time-consuming and often not informative with solid tumors. In contrast, the reverse transcriptase-polymerase chain reaction (RT-PCR) is a readily available technique that can rapidly detect tumor-specific chromosomal rearrangements, even in small biopsy specimens. We present cases depicting the importance of including molecular diagnostic studies in the routine evaluation of pediatric solid tumors. PROCEDURE: We used RT-PCR to detect chimeric transcripts specific for major pediatric solid tumors, including peripheral primitive neuroectodermal tumor (pPNET), alveolar rhabdomyosarcoma (ARMS), and desmoplastic small round-cell tumor (DSRCT). We reviewed six recent cases in which the initial diagnosis was changed by the results of RT-PCR. RESULTS: Highly unusual or nonspecific clinical and/or histopathologic findings led to the initial diagnoses of neuroblastoma in three patients and DSRCT, leukemia, and carcinoma in one patient each. The final diagnoses after RT-PCR studies were pPNET in three patients, ARMS in two patients, and DSRCT in one patient. RT-PCR results led to early corrections in the diagnosis in two patients, but four patients received treatment not considered optimal for the neoplasms ultimately diagnosed, including three who, despite presenting with localized tumors that have a >70% cure rate with standard therapy, have died or are dying of disease. CONCLUSIONS: Molecular genetic studies on solid tumors can clarify the diagnosis in seemingly straightforward as well as in overtly problematic cases. These diagnostic distinctions are now critical as disease-specific and risk-directed therapies have emerged.+http://www.ncbi.nlm.nih.gov/pubmed/10573575Kushner, B H LaQuaglia, M P Cheung, N K Kramer, K Hamelin, A C Gerald, W L Ladanyi, M Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states Medical and pediatric oncology Med Pediatr Oncol. 1999 Dec;33(6):530-5.%0098-1532 (Print) 0098-1532 (Linking)10573575Department of Human Genetics, Pathology, Pediatrics, and Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. kushnerb@mskcc.orgB10.1002/(SICI)1096-911X(199912)33:6<530::AID-MPO2>3.0.CO;2-J [pii]eng ||70Falkner, B. Sherif, K. Sumner, A. E. Kushner, H.1999VBlood pressure increase with impaired glucose tolerance in young adult american blacks1086-90 Hypertension345 1999/11/24Adult *African Continental Ancestry Group Blood Glucose/metabolism *Blood Pressure Body Mass Index Diabetes Mellitus/ethnology/*physiopathology Female Glucose Tolerance Test Humans Insulin Resistance Lipids/blood MaleNovxHypertension and non-insulin-dependent diabetes mellitus are more prevalent in blacks than whites. The convergence of these 2 disorders augments the expression and severity of cardiovascular disease. The purpose of this study was to determine whether alterations in glucose metabolism are related to an increase in blood pressure (BP). This study was conducted on 304 nondiabetic blacks (mean age=32 years). Measurements in all subjects included BP, anthropometric measures, oral glucose tolerance test, insulin clamp to measure insulin sensitivity, and plasma lipids. The sample was stratified according to plasma glucose on oral glucose tolerance test to normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus (DM). A 2-way ANOVA was performed to determine differences between the metabolic groups. With the use of American Diabetic Association criteria, 20.4% of the samples were classified as IGT and 5.9% were diabetic. A significant increase in BP existed from NGT to IGT to DM, which was stronger in women than men (systolic blood pressure in women: NGT=122, IGT=127, and DM=140 mm Hg, P<0.001) with a significant linear trend (P<0.001). With the use of body mass index as a covariate, the group difference in BP remained significant (P=0.006). Measures of insulin sensitivity demonstrated significant metabolic group differences (P<0.001) with a linear trend (P<0.001) of decreasing insulin sensitivity from NGT to DM. These results indicate that early alterations in glucose metabolism effects an upward shift in BP. The higher BP in IGT and DM may be due to vascular endothelial cell resistance to insulin action.+http://www.ncbi.nlm.nih.gov/pubmed/10567186Falkner, B Sherif, K Sumner, A E Kushner, H DK461070/DK/NIDDK NIH HHS/United States HL51547/HL/NHLBI NIH HHS/United States Research Support, U.S. Gov't, P.H.S. United states Hypertension Hypertension. 1999 Nov;34(5):1086-90.*1524-4563 (Electronic) 0194-911X (Linking)10567186aDepartment of Medicine, MCP Hahnemann University, Philadelphia, PA 19129, USA. falknerb@mcphu.edueng||7hKushner, B. J. Sondhi, N. Reich-D'Almeida, F. Pollard, Z. F. de Faber, J. T. Davitt, B. V. Buncic, J. R.1999{A case of bilateral inferior rectus restriction after previous unilateral inferior rectus recession for thyroid eye disease208-14Binocul Vis Strabismus Q143 1999/11/11Diplopia/etiology Esotropia/*etiology/surgery Exotropia/prevention & control Eye Movements Female Follow-Up Studies Graves Disease/*complications Humans Middle Aged Oculomotor Muscles/*pathology/surgery *Postoperative Complications Visual Acuity+http://www.ncbi.nlm.nih.gov/pubmed/10553114Kushner, B J Sondhi, N Reich-D'Almeida, F Pollard, Z F de Faber, J T Davitt, B V Buncic, J R Case Reports Clinical Conference United states Binocular vision & strabismus quarterly Binocul Vis Strabismus Q. 1999;14(3):208-14.%1088-6281 (Print) 1088-6281 (Linking)105531143University Station Clinics, Madison, WI 53705, USA.eng||7Kushner, I. Ballou, S. P.19997Treatment of rheumatoid arthritis--we're getting closer2291-3 J Rheumatol2611 1999/11/118Antirheumatic Agents/*therapeutic use Arthritis, Rheumatoid/*drug therapy Cyclooxygenase 1 Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors/*therapeutic use Humans Isoenzymes/drug effects/metabolism Membrane Proteins Prostaglandin-Endoperoxide Synthases/drug effects/metabolism Social ClassNov+http://www.ncbi.nlm.nih.gov/pubmed/10555878pKushner, I Ballou, S P Comment Editorial Canada The Journal of rheumatology J Rheumatol. 1999 Nov;26(11):2291-3.%0315-162X (Print) 0315-162X (Linking)10555878eng ||7Corbett, T. H. Panchapor, C. Polin, L. Lowichik, N. Pugh, S. White, K. Kushner, J. Meyer, J. Czarnecki, J. Chinnukroh, S. Edelstein, M. LoRusso, P. Heilbrun, L. Horwitz, J. P. Grieshaber, C. Perni, R. Wentland, M. Coughlin, S. Elenbaas, S. Philion, R. Rake, J.1999iPreclinical efficacy of thioxanthone SR271425 against transplanted solid tumors of mouse and human origin17-27Invest New Drugs171 1999/11/11YAnimals Antineoplastic Agents/chemistry/*therapeutic use Doxorubicin/therapeutic use Drug Resistance, Multiple/physiology Drug Resistance, Neoplasm/physiology Drug Screening Assays, Antitumor Drug Stability Humans Mice Mice, Inbred ICR Mice, Transgenic Neoplasm Transplantation Paclitaxel/therapeutic use Thioxanthenes/chemistry/*therapeutic use%A highly active and broadly active thioxanthone has been identified: N-[[1-[[2-(Diethylamino)ethyl]amino]-7-methoxy-9-oxo-9H-thioxanthen++ +-4-yl] methylformamide (SR271425, BCN326862, WIN71425). In preclinical testing against a variety of subcutaneously growing solid tumors, the following %T/C and Log10 tumor cell kill (LK) values were obtained: Panc-03 T/C = 0, 5/5 cures; Colon-38 (adv. stage) T/C = 0, 3/5 cures, 4.9 LK; Mam-16/C T/C = 0, 3.5 LK; Mam-17/0 T/C = 0, 2.8 LK; Colon-26 T/C = 0, 1/5 cures, 3.2 LK; Colon-51 T/C = 0, 2.7 LK; Panc-02 T/C = 0, 3.1 LK; B16 Melanoma T/C = 13%, 4.0 LK; Squamous Lung-LC12 (adv. stage) T/C = 14%, 4.9 LK; BG-1 human ovarian T/C = 16%, 1.3 LK; WSU-Brl human breast T/C = 25%, 0.8 LK. The agent was modestly active against doxorubicin (Adr)-resistant solid tumors: Mam-17/AdrT/C =23%, 0.8 LK; and Mam-16/C/Adr T/C = 25%, 1.0 LK, but retained substantial activity against a taxol-resistant tumor: Mam-16/C/taxol T/C = 3%, 2.4 LK. SR271425 was highly active against IV implanted leukemias, L1210 6.3 LK and AML1498 5.3 LK. The agent was equally active both by the IV and oral routes of administration, although requiring approximately 30% higher dose by the oral route. Based on its preclinical antitumor profile, it may be appropriate to evaluate SR271425 in clinical trials.+http://www.ncbi.nlm.nih.gov/pubmed/10555119Corbett, T H Panchapor, C Polin, L Lowichik, N Pugh, S White, K Kushner, J Meyer, J Czarnecki, J Chinnukroh, S Edelstein, M LoRusso, P Heilbrun, L Horwitz, J P Grieshaber, C Perni, R Wentland, M Coughlin, S Elenbaas, S Philion, R Rake, J CA45962/CA/NCI NIH HHS/United States CA46560/CA/NCI NIH HHS/United States Research Support, U.S. Gov't, P.H.S. United states Investigational new drugs Invest New Drugs. 1999;17(1):17-27.%0167-6997 (Print) 0167-6997 (Linking)10555119WKarmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA.eng!||7Heymsfield, S. B. Greenberg, A. S. Fujioka, K. Dixon, R. M. Kushner, R. Hunt, T. Lubina, J. A. Patane, J. Self, B. Hunt, P. McCamish, M.1999lRecombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial1568-75JAMA28216 1999/11/05AAdult Antibodies/blood Body Composition Body Mass Index Double-Blind Method Drug Administration Schedule Energy Intake Female Humans Leptin/administration & dosage/*analogs & derivatives/immunology/pharmacokinetics/therapeutic use Linear Models Male Obesity/*drug therapy Recombinant Proteins/therapeutic use *Weight LossOct 273 CONTEXT: The protein hormone leptin is important to the homeostatic regulation of body weight. Treatment with exogenous leptin may affect weight loss. OBJECTIVE: To determine the relationship between increasing doses of exogenous leptin administration and weight loss in both lean and obese adults. DESIGN: A randomized, double-blind, placebo-controlled, multicenter, escalating dose cohort trial conducted from April 1997 to October 1998. SETTING: Four university nutrition and obesity clinics and 2 contract clinical research clinics. PARTICIPANTS: Fifty-four lean (body mass index, 20.0-27.5 kg/m2; mean [SD] body weight, 72.0 [9.7] kg) and 73 obese (body mass index, 27.6-36.0 kg/m2; mean [SD] body weight, 89.8 [11.4] kg) predominantly white (80%) men (n = 67) and women (n = 60) with mean (SD) age of 39 (10.3) years. INTERVENTIONS: Recombinant methionyl human leptin self-administered by daily morning subcutaneous injection (0 [placebo], 0.01, 0.03, 0.10, or 0.30 mg/kg). In part A, lean and obese subjects were treated for 4 weeks; in part B, obese subjects were treated for an additional 20 weeks. Lean subjects consumed a eucaloric diet to maintain body weight at the current value, and obese subjects were prescribed a diet that reduced their daily energy intake by 2100 kJ/d (500-kcal/d) from the amount needed to maintain a stable weight. MAIN OUTCOME MEASURES: Body weight, body fat, and incidence of adverse events. RESULTS: Weight loss from baseline increased with increasing dose of leptin among all subjects at 4 weeks (P = .02) and among obese subjects at 24 weeks (P = .01) of treatment. Mean (SD) weight changes at 4 weeks ranged from -0.4 (2.0) kg for placebo (n = 36) to -1.9 kg (1.6) kg for the 0.1 mg/kg dose (n = 29). Mean (SD) weight changes at 24 weeks ranged from -0.7 (5.4) kg for the 0.01 mg/kg dose (n = 6) to -7.1 (8.5) kg for the 0.30 mg/kg dose (n = 8). Fat mass declined from baseline as dose increased among all subjects at 4 weeks (P = .002) and among obese subjects at 24 weeks of treatment (P = .004); more than 95% of weight loss was fat loss in the 2 highest dose cohorts at 24 weeks. Baseline serum leptin concentrations were not related to weight loss at week 4 (P = .88) or at week 24 (P = .76). No clinically significant adverse effects were observed on major organ systems. Mild-to-moderate reactions at the injection site were the most commonly reported adverse effects. CONCLUSIONS: A dose-response relationship with weight and fat loss was observed with subcutaneous recombinant leptin injections in both lean and obese subjects. Based on this study, administration of exogenous leptin appears to induce weight loss in some obese subjects with elevated endogenous serum leptin concentrations. Additional research into the potential role for leptin and related hormones in the treatment of human obesity is warranted.+http://www.ncbi.nlm.nih.gov/pubmed/10546697Heymsfield, S B Greenberg, A S Fujioka, K Dixon, R M Kushner, R Hunt, T Lubina, J A Patane, J Self, B Hunt, P McCamish, M MO1-RR00054/RR/NCRR NIH HHS/United States Clinical Trial Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states JAMA : the journal of the American Medical Association JAMA. 1999 Oct 27;282(16):1568-75.%0098-7484 (Print) 0098-7484 (Linking)10546697]Weight Control Unit, St Luke's-Roosevelt Hospital, New York, NY 10025, USA. SBH2@Columbia.edujpc90045 [pii]engi||7 (Kushner, D. J. Baker, A. Dunstall, T. G.1999MPharmacological uses and perspectives of heavy water and deuterated compounds79-88Can J Physiol Pharmacol772 1999/10/27Animals Bacteria/drug effects Deuterium/*pharmacology/therapeutic use Deuterium Oxide/*pharmacology/therapeutic use Humans Insecticides/pharmacology Mice RatsFeb Since the discovery of D20 (heavy water) and its use as a moderator in nuclear reactors, its biological effects have been extensively, although seldom deeply, studied. This article reviews these effects on whole animals, animal cells, and microorganisms. Both "solvent isotope effects," those due to the special properties of D20 as a solvent, and "deuterium isotope effects" (DIE), which result when D replaces H in many biological molecules, are considered. The low toxicity of D20 toward mammals is reflected in its widespread use for measuring water spaces in humans and other animals. Higher concentrations (usually >20% of body weight) can be toxic to animals and animal cells. Effects on the nervous system and the liver and on formation of different blood cells have been noted. At the cellular level, D20 may affect mitosis and membrane function. Protozoa are able to withstand up to 70% D20. Algae and bacteria can adapt to grow in 100% D2O and can serve as sources of a large number of deuterated molecules. D2O increases heat stability of macromolecules but may decrease cellular heat stability, possibly as a result of inhibition of chaperonin formation. High D2O concentrations can reduce salt- and ethanol-induced hypertension in rats and protect mice from gamma irradation. Such concentrations are also used in boron neutron capture therapy to increase neutron penetration to boron compounds bound to malignant cells. D2O is more toxic to malignant than normal animal cells, but at concentrations too high for regular therapeutic use. D2O and deuterated drugs are widely used in studies of metabolism of drugs and toxic substances in humans and other animals. The deuterated forms of drugs often have different actions than the protonated forms. Some deuterated drugs show different transport processes. Most are more resistant to metabolic changes, especially those changes mediated by cytochrome P450 systems. Deuteration may also change the pathway of drug metabolism (metabolic switching). Changed metabolism may lead to increased duration of action and lower toxicity. It may also lead to lower activity, if the drug is normally changed to the active form in vivo. Deuteration can also lower the genotoxicity of the anticancer drug tamoxifen and other compounds. Deuteration increases effectiveness of long-chain fatty acids and fluoro-D-phenylalanine by preventing their breakdown by target microorganisms. A few deuterated antibiotics have been prepared, and their antimicrobial activity was found to be little changed. Their action on resistant bacteria has not been studied, but there is no reason to believe that they would be more effective against such bacteria. Insect resistance to insecticides is very often due to insecticide destruction through the cytochrome P450 system. Deuterated insecticides might well be more effective against resistant insects, but this potentially valuable possibility has not yet been studied.+http://www.ncbi.nlm.nih.gov/pubmed/10535697Kushner, D J Baker, A Dunstall, T G Research Support, Non-U.S. Gov't Review Canada Canadian journal of physiology and pharmacology Can J Physiol Pharmacol. 1999 Feb;77(2):79-88.%0008-4212 (Print) 0008-4212 (Linking)10535697SDepartment of Botany, University of Toronto, ON, Canada. kushner@botany.utoronto.caeng m||7 Webb, P. Nguyen, P. Valentine, C. Lopez, G. N. Kwok, G. R. McInerney, E. Katzenellenbogen, B. S. Enmark, E. Gustafsson, J. A. Nilsson, S. Kushner, P. J.1999The estrogen receptor enhances AP-1 activity by two distinct mechanisms with different requirements for receptor transactivation functions1672-85Mol Endocrinol1310 1999/10/12Binding Sites Estradiol/metabolism/pharmacology Estrogen Receptor alpha Estrogen Receptor beta Hela Cells/drug effects Humans Phenotype Receptors, Estrogen/drug effects/*genetics/*metabolism Recombinant Proteins/genetics/metabolism Response Elements Selective Estrogen Receptor Modulators/pharmacology Sequence Deletion Serine Tamoxifen/pharmacology Transcription Factor AP-1/genetics/*metabolism Transcriptional ActivationOctEstrogen receptors (ERs alpha and beta) enhance transcription in response to estrogens by binding to estrogen response elements (EREs) within target genes and utilizing transactivation functions (AF-1 and AF-2) to recruit p160 coactivator proteins. The ERs also enhance transcription in response to estrogens and antiestrogens by modulating the activity of the AP-1 protein complex. Here, we examine the role of AF-1 and AF-2 in ER action at AP-1 sites. Estrogen responses at AP-1 sites require the integrity of the ERalpha AF-1 and AF-2 activation surfaces and the complementary surfaces on the p160 coactivator GRIP1 (glucocorticoid receptor interacting protein 1), the NID/AF-1 region, and NR boxes. Thus, estrogen-liganded ERalpha utilizes the same protein-protein contacts to transactivate at EREs and AP-1 sites. In contrast, antiestrogen responses are strongly inhibited by ERalpha AF-1 and weakly inhibited by AF-2. Indeed, ERalpha truncations that lack AF-1 enhance AP-1 activity in the presence of antiestrogens, but not estrogens. This phenotype resembles ERbeta, which naturally lacks constitutive AF-1 activity. We conclude that the ERs enhance AP-1 responsive transcription by distinct mechanisms with different requirements for ER transactivation functions. We suggest that estrogen-liganded ER enhances AP-1 activity via interactions with p160s and speculate that antiestrogen-liganded ER enhances AP-1 activity via interactions with corepressors.+http://www.ncbi.nlm.nih.gov/pubmed/10517669Webb, P Nguyen, P Valentine, C Lopez, G N Kwok, G R McInerney, E Katzenellenbogen, B S Enmark, E Gustafsson, J A Nilsson, S Kushner, P J CA-18119/CA/NCI NIH HHS/United States CA-80210/CA/NCI NIH HHS/United States DK-51083/DK/NIDDK NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. United states Molecular endocrinology (Baltimore, Md.) Mol Endocrinol. 1999 Oct;13(10):1672-85.%0888-8809 (Print) 0888-8809 (Linking)10517669_Metabolic Research Unit, University of California School of Medicine, San Francisco 94143, USA.eng e||7 'Kushner, B. H. Kramer, K. Cheung, N. K.19998Oral etoposide for refractory and relapsed neuroblastoma3221-5 J Clin Oncol1710 1999/10/03rAdministration, Oral Antineoplastic Agents, Phytogenic/*administration & dosage/adverse effects Bone Marrow Neoplasms/*drug therapy/pathology Child Child, Preschool Drug Administration Schedule Etoposide/*administration & dosage/adverse effects Female Humans Male Neoplasm Recurrence, Local/*drug therapy/pathology Neuroblastoma/*drug therapy/pathology Treatment OutcomeOctPURPOSE: To describe the efficacy of oral etoposide against resistant stage 4 neuroblastoma. PATIENTS AND METHODS: Patients with refractory or recurrent stage 4 neuroblastoma were treated with etoposide 50 mg/m(2) taken orally each day, in two or three divided doses, for 21 consecutive days. Treatment could be repeated after a 1-week period. Extent-of-disease studies included imaging with 131-iodine-metaiodobenzylguanidine and extensive bone marrow (BM) sampling. RESULTS: Oral etoposide was used in 20 children between the ages of 2 and 11 years (median, 6 years). Prior treatment included high doses of alkylating agents and a median of 4.5 cycles of etoposide-containing chemotherapy, with cumulative etoposide doses of 1,800 mg/m(2) to 3,935 mg/m(2) (median, 2,300 mg/m(2)). Oral etoposide produced antineuroblastoma effects in four of four children with disease refractory to intensive induction treatment; sampling variability could account for resolution (n = 3) or reduction (n = 1) of BM involvement, but improvement in other markers also occurred. Antineuroblastoma effects were also evident in five of five children with asymptomatic relapses after a long chemotherapy-free interval: BM disease resolved and all other disease markers significantly improved in two patients, and disease markers improved or stabilized in three patients on treatment for more than 6 months. In these nine patients, extramedullary toxicity was absent, neutropenia did not occur, transfusional support was not needed, and preliminary data suggested little immunosuppression (phytohemagglutinin responses). Oral etoposide was ineffective in all (11 of 11) patients with rapidly growing tumor masses. CONCLUSION: Given the absence of toxicity to major organs, the minimal myelosuppression or immunosuppression, and the antineoplastic activity in patients with low tumor burdens after high-dose chemotherapy, limited use of low-dose oral etoposide should be considered for inclusion in postinduction consolidative treatment programs aimed at eradicating minimal residual disease.+http://www.ncbi.nlm.nih.gov/pubmed/10506622RKushner, B H Kramer, K Cheung, N K CA61017/CA/NCI NIH HHS/United States CA72868/CA/NCI NIH HHS/United States Clinical Trial Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states Journal of clinical oncology : official journal of the American Society of Clinical Oncology J Clin Oncol. 1999 Oct;17(10):3221-5.%0732-183X (Print) 0732-183X (Linking)10506622lDepartment of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. kusherb@mskcc.orgeng ||7 FHuang, A. Palmer, L. S. Hom, D. Anderson, A. E. Kushner, L. Franco, I.1999eIbuprofen combined with antibiotics suppresses renal scarring due to ascending pyelonephritis in rats1396-8J Urol1624 1999/09/24LAnimals Anti-Bacterial Agents/*administration & dosage Anti-Inflammatory Agents, Non-Steroidal/*administration & dosage Cicatrix/*etiology/*prevention & control Drug Therapy, Combination Female Ibuprofen/*administration & dosage Kidney Diseases/*etiology/*prevention & control Pyelonephritis/*complications Rats Rats, Sprague-DawleyOct(PURPOSE: In acute pyelonephritis renal scarring may be decreased by immediate antibiotic therapy. Unfortunately in children there is often a delay in starting treatment, which increases the likelihood of renal scarring. In rodents immediate antibiotic therapy is effective for preventing renal scar formation resulting from experimentally induced pyelonephritis. However, the same treatment beginning 72 hours after infection does not prevent renal scarring in this paradigm. We examined whether delayed administration of the nonsteroidal anti-inflammatory agent ibuprofen only or combined with antibiotics suppresses renal scarring in a model of ascending pyelonephritis in rats. MATERIALS AND METHODS: An inoculum of 5x10(9) organisms per ml. of Escherichia coli strain BH-5 was instilled into the bladder of rats and the urethra was occluded for 4 hours. Groups of animals were and were not treated with 15 mg./kg. cefadroxil or 10 mg./kg. ibuprofen given twice daily for 5 days, or the 2 drugs combined. Treatment began 72 hours after inoculation. In an additional group of rats sterile phosphate buffered saline was instilled into the bladder. In each rat the kidneys were examined grossly and microscopically 6 weeks later. RESULTS: Combined antibiotics and ibuprofen significantly inhibited gross renal scarring compared with no treatment or antibiotics only (p<0.05). No difference in renal scarring was detected in animals that received no treatment versus those that received antibiotics or ibuprofen only (p>0.05). CONCLUSIONS: Renal scarring resulting from acute pyelonephritis in this rat model is not decreased by delayed treatment with antibiotics only. The addition of ibuprofen to antibiotic therapy is effective for decreasing renal scarring due to acute pyelonephritis even when treatment is delayed for 72 hours.+http://www.ncbi.nlm.nih.gov/pubmed/10492222Huang, A Palmer, L S Hom, D Anderson, A E Kushner, L Franco, I Research Support, Non-U.S. Gov't United states The Journal of urology J Urol. 1999 Oct;162(4):1396-8.%0022-5347 (Print) 0022-5347 (Linking)10492222LDivision of Pediatric Urology, Schneider Children's Hospital, New York, USA.S0022-5347(05)68319-X [pii]eng ||7 FHoff, A. L. Sakuma, M. Wieneke, M. Horon, R. Kushner, M. DeLisi, L. E.1999\Longitudinal neuropsychological follow-up study of patients with first-episode schizophrenia1336-41Am J Psychiatry1569 1999/09/15-Adult Brain/anatomy & histology Cognition Disorders/*diagnosis/psychology Female Follow-Up Studies Hospitalization Humans Longitudinal Studies Magnetic Resonance Imaging Male Memory Neuropsychological Tests/*statistics & numerical data Schizophrenia/*diagnosis Schizophrenic Psychology Verbal LearningSepOBJECTIVE: The primary purpose of this article was to determine if cognitive abilities decline, remain unchanged, or modestly improve throughout the course of schizophrenic illness. METHOD: Forty-two patients with a first hospitalization for schizophrenia or schizophreniform disorder and 16 normal comparison subjects had a battery of neuropsychological tests and a magnetic resonance imaging (MRI) brain scan at approximate yearly intervals for the first 2 to 5 years of illness. Summary rating scales for language, executive, memory, processing speed, and sensory-perceptual functions were constructed. RESULTS: Patients with schizophrenia scored 1 to 2 standard deviations below normal comparison subjects on neuropsychological test measures during the course of the study. Patients exhibited less improvement than comparison subjects on measures of verbal memory. In general, improvement in positive symptoms over the time interval was associated with improvement in cognition. No changes in regional brain measurements were correlated with cognitive change in the patient group. CONCLUSIONS: Patients with schizophrenia have considerable cognitive dysfunction in the first 4 to 5 years of illness, which is stable at a level of 1 to 2 standard deviations below that of comparison subjects. There is little evidence for deterioration of cognitive abilities over the first few years of illness, with the exception of verbal memory, which shows significantly less improvement in patients over time relative to that of comparison subjects.+http://www.ncbi.nlm.nih.gov/pubmed/10484942Hoff, A L Sakuma, M Wieneke, M Horon, R Kushner, M DeLisi, L E MH-44233/MH/NIMH NIH HHS/United States Comparative Study Research Support, U.S. Gov't, P.H.S. United states The American journal of psychiatry Am J Psychiatry. 1999 Sep;156(9):1336-41.%0002-953X (Print) 0002-953X (Linking)10484942Stony Brook First-Episode Schizophrenia Project, Department of Psychiatry, State University of New York, USA. alhoff@ucdavis.edueng||78Gudivaka, R. Schoeller, D. A. Kushner, R. F. Bolt, M. J.1999aSingle- and multifrequency models for bioelectrical impedance analysis of body water compartments1087-96J Appl Physiol873 1999/09/14Adult Algorithms Body Fluid Compartments/drug effects/*physiology Body Water/*physiology Diuretics/pharmacology *Electric Impedance Extracellular Space/physiology Female Humans Male Models, BiologicalSep The 1994 National Institutes of Health Technology Conference on bioelectrical impedance analysis (BIA) did not support the use of BIA under conditions that alter the normal relationship between the extracellular (ECW) and intracellular water (ICW) compartments. To extend applications of BIA to these populations, we investigated the accuracy and precision of seven previously published BIA models for the measurement of change in body water compartmentalization among individuals infused with lactated Ringer solution or administered a diuretic agent. Results were compared with dilution by using deuterium oxide and bromide combined with short-term changes of body weight. BIA, with use of proximal, tetrapolar electrodes, was measured from 5 to 500 kHz, including 50 kHz. Single-frequency, 50-kHz models did not accurately predict change in total body water, but the 50-kHz parallel model did accurately measure changes in ICW. The only model that accurately predicted change in ECW, ICW, and total body water was the 0/infinity-kHz parallel (Cole-Cole) multifrequency model. Use of the Hanai correction for mixing was less accurate. We conclude that the multifrequency Cole-Cole model is superior under conditions in which body water compartmentalization is altered from the normal state.+http://www.ncbi.nlm.nih.gov/pubmed/10484581iGudivaka, R Schoeller, D A Kushner, R F Bolt, M J DK-26678/DK/NIDDK NIH HHS/United States RR-00055/RR/NCRR NIH HHS/United States Clinical Trial Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. United states Journal of applied physiology (Bethesda, Md. : 1985) J Appl Physiol. 1999 Sep;87(3):1087-96.%8750-7587 (Print) 0161-7567 (Linking)10484581VClinical Nutrition Research Unit, University of Chicago, Chicago, Illinois 60637, USA.eng ||7%Humphries, S. Kushner, H. Falkner, B.1999mLow dietary magnesium is associated with insulin resistance in a sample of young, nondiabetic Black Americans747-56Am J Hypertens128 Pt 1 1999/09/10xAdult *African Americans Blood Glucose/metabolism Calcium, Dietary/administration & dosage *Diet Female Glucose Tolerance Test Humans Insulin Resistance/*physiology Magnesium/*administration & dosage Magnesium Deficiency/epidemiology/*physiopathology Male Potassium/administration & dosage Sex Characteristics Sodium, Dietary/administration & dosage United States/epidemiologyAugIn both humans and experimental animals, dietary induced magnesium deficiency is correlated with insulin resistance. The purpose of this study was to determine whether dietary magnesium intake is associated with insulin sensitivity or blood pressure in a sample of nondiabetic, young adult black Americans. We also examined dietary calcium, potassium, and sodium intake. The study was conducted on a sample (n = 179) of young adults aged 30 +/- 3.4 years who had been followed longitudinally. Nutrient intake was assessed by obtaining a 24-h recall interview of dietary intake. Intake data were entered in a nutrient analysis program (Nutritionist III), which quantitated micronutrients, macronutrients, and minerals. We classified the sample into insulin-sensitive (IS) and insulin-resistant (IR) groups, according to insulin-stimulated glucose use (M) measured during insulin clamp. M correlated positively with magnesium intake in mg/kg of fat-free mass (r = 0.15, P < .05 overall; in men, r = 0.25, P < .02). There was a significant negative correlation of total dietary magnesium intake with the sum of insulin levels measured during an oral glucose tolerance test (OGTT) (r = -0.13, P < .05). When corrected for body fat, in men there was also a significant correlation of dietary magnesium intake, measured in mg/kg of fat-free mass, with the sum of insulin concentrations on the OGTT (r = -0.22, P < .05). When cases were categorically classified as IS versus IR, magnesium intake in mg/kg of fat-free mass was lower in IR (2.97 +/- 1.4) than in IS (3.68 +/- 2.2; P = .022). These results suggest a possible role for dietary magnesium in insulin resistance.+http://www.ncbi.nlm.nih.gov/pubmed/10480466Humphries, S Kushner, H Falkner, B DK 46107/DK/NIDDK NIH HHS/United States HL 51547/HL/NHLBI NIH HHS/United States Research Support, U.S. Gov't, P.H.S. United states American journal of hypertension Am J Hypertens. 1999 Aug;12(8 Pt 1):747-56.%0895-7061 (Print) 0895-7061 (Linking)10480466AMCP Hahnemann University, Philadelphia, Pennsylvannia 19129, USA.S0895-7061(99)00041-2 [pii]eng}|7RRakhmanin Iu, A. Fomenko, S. E. Kushnerova, N. F. Gordeleichuk, T. N. Fokin, M. V.1999h[Effects of a plant preparation Korrda-K on metabolic reactions in the liver of rats exposed to acetone]41-4 Gig Sanit4 1999/08/31Acetone/*toxicity Animals Blood Glucose/analysis/drug effects Carbohydrate Metabolism Fatty Acids/metabolism Flavonoids/*pharmacology Lipid Metabolism Liver/*drug effects/metabolism Male *Plants, Medicinal Rats Solvents/*toxicityJul-Aug5The paper deals with the study of the preventive effect of the plant drug Korrda-K on lipid and carbohydrate metabolism in the liver of the rat exposed to acetone inhalation. The agent was found to have hepatic and membranous protective effects. On exposure to acetone, Korrda-K promotes the normalization of blood glucose levels and other biochemical parameters. The magnitude of changes in the composition of lipids and fatty acids suggests that the preventive use of the agent favours the preservation of the membrane structure of hepatocytes changed by acetone.+http://www.ncbi.nlm.nih.gov/pubmed/10465877Rakhmanin, Iu A Fomenko, S E Kushnerova, N F Gordeleichuk, T N Fokin, M V Comparative Study English Abstract Russia Gigiena i sanitariia Gig Sanit. 1999 Jul-Aug;(4):41-4.%0016-9900 (Print) 0016-9900 (Linking)10465877qVliianie rastitel'nogo preparata Korrda-K na metabolicheskie reaktsii v pecheni krys pri intoksikatsii atsetonom.rus |t7aMa, H. Hong, H. Huang, S. M. Irvine, R. A. Webb, P. Kushner, P. J. Coetzee, G. A. Stallcup, M. R.1999dMultiple signal input and output domains of the 160-kilodalton nuclear receptor coactivator proteins6164-73 Mol Cell Biol199 1999/08/24Animals Binding Sites Cell Line Histone Acetyltransferases Humans Molecular Weight Nuclear Proteins/chemistry/*metabolism Nuclear Receptor Coactivator 1 Nuclear Receptor Coactivator 2 Receptors, Androgen/chemistry/metabolism Receptors, Cytoplasmic and Nuclear/chemistry/*metabolism Receptors, Steroid/chemistry/metabolism Receptors, Thyroid Hormone/chemistry/metabolism Recombinant Fusion Proteins/chemistry/metabolism Signal Transduction Trans-Activators/chemistry/metabolism Transcription Factors/chemistry/*metabolismSepqMembers of the 160-kDa nuclear receptor coactivator family (p160 coactivators) bind to the conserved AF-2 activation function found in the hormone binding domains of nuclear receptors (NR) and are potent transcriptional coactivators for NRs. Here we report that the C-terminal region of p160 coactivators glucocorticoid receptor interacting protein 1 (GRIP1), steroid receptor coactivator 1 (SRC-1a), and SRC-1e binds the N-terminal AF-1 activation function of the androgen receptor (AR), and p160 coactivators can thereby enhance transcriptional activation by AR. While they all interact efficiently with AR AF-1, these same coactivators have vastly different binding strengths with and coactivator effects on AR AF-2. p160 activation domain AD1, which binds secondary coactivators CREB binding protein (CBP) and p300, was previously implicated as the principal domain for transmitting the activating signal to the transcription machinery. We identified a new highly conserved motif in the AD1 region which is important for CBP/p300 binding. Deletion of AD1 only partially reduced p160 coactivator function, due to signaling through AD2, another activation domain located at the C-terminal end of p160 coactivators. C-terminal coactivator fragments lacking AD1 but containing AD2 and the AR AF-1 binding site served as efficient coactivators for full-length AR and AR AF-1. The two signal input domains (one that binds NR AF-2 domains and one that binds AF-1 domains of some but not all NRs) and the two signal output domains (AD1 and AD2) of p160 coactivators played different relative roles for two different NRs: AR and thyroid hormone receptor.+http://www.ncbi.nlm.nih.gov/pubmed/10454563dMa, H Hong, H Huang, S M Irvine, R A Webb, P Kushner, P J Coetzee, G A Stallcup, M R CA/OD72821/CA/NCI NIH HHS/United States DK43093/DK/NIDDK NIH HHS/United States DK51083/DK/NIDDK NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states Molecular and cellular biology Mol Cell Biol. 1999 Sep;19(9):6164-73.%0270-7306 (Print) 0270-7306 (Linking)8454810454563`Departments of Pathology, University of Southern California, Los Angeles, California 90033, USA.eng||7Kushner, A. Cobey, J.19996Helping victims of landmines. A public health approach30-1Minn Med827 1999/08/04Adult Blast Injuries/*epidemiology/prevention & control/rehabilitation Cambodia Child *Developing Countries Female Humans Male Medical Missions, Official *Public Health *WarJul+http://www.ncbi.nlm.nih.gov/pubmed/10431543SKushner, A Cobey, J United states Minnesota medicine Minn Med. 1999 Jul;82(7):30-1.%0026-556X (Print) 0026-556X (Linking)10431543eng t||7)Kushner, S. A. Dewey, S. L. Kornetsky, C.1999The irreversible gamma-aminobutyric acid (GABA) transaminase inhibitor gamma-vinyl-GABA blocks cocaine self-administration in rats797-802J Pharmacol Exp Ther2902 1999/07/20[4-Aminobutyrate Transaminase/*antagonists & inhibitors Animals Cocaine/*antagonists & inhibitors/pharmacology Conditioning, Operant/drug effects Enzyme Inhibitors/metabolism/*pharmacology Food Male Rats Rats, Wistar Reinforcement Schedule Reward Self Administration Vigabatrin gamma-Aminobutyric Acid/*analogs & derivatives/metabolism/pharmacologyAuggamma-Vinyl gamma-aminobutyric acid (GABA) (GVG) is an irreversible inhibitor of GABA transaminase, the primary enzyme involved in GABA metabolism. Acute administration of GVG increases brain GABA levels and blocks cocaine-induced locomotor activity, cocaine-induced lowering of brain stimulation reward thresholds, and cocaine-induced conditioned place preference. To further evaluate the effects of GVG on cocaine-induced reward, we examined its effects on cocaine self-administration in male Wistar rats on fixed ratio 5 and progressive ratio schedules of reinforcement. Additionally, the effects of GVG on operant responding for a food reward were examined on the same two schedules to determine whether the effects of GVG were specific to cocaine reward or generalized to other types of reward. GVG dose dependently decreased responding for cocaine on both schedules of reinforcement, suggesting that GVG attenuated the reward value of the cocaine. Responding for food was also decreased by GVG, suggesting that the effects of increased GABA levels induced by GVG may have a general effect on central reward systems. Data from this and other studies indicate that GVG does not induce motor impairment, decrease spontaneous locomotor activity, or induce catalepsy. Taken together, these data suggest that increases in GABAergic activity induced by GVG have an attenuating effect on centrally mediated reward systems and that the GABA system may be a useful target in the development of new therapeutic strategies for cocaine addiction.+http://www.ncbi.nlm.nih.gov/pubmed/10411594Kushner, S A Dewey, S L Kornetsky, C DA-02326/DA/NIDA NIH HHS/United States KO5-DA-00099/DA/NIDA NIH HHS/United States Research Support, U.S. Gov't, P.H.S. United states The Journal of pharmacology and experimental therapeutics J Pharmacol Exp Ther. 1999 Aug;290(2):797-802.%0022-3565 (Print) 0022-3565 (Linking)10411594Laboratory of Behavioral Pharmacology, Department of Pharmacology, Boston University School of Medicine, Boston, Massachusetts. sk53@is7.nyu.edueng F||75Benegas, N. M. Egbert, J. Engel, W. K. Kushner, B. J.1999ADiplopia secondary to aniseikonia associated with macular disease896-9Arch Ophthalmol1177 1999/07/17XAdult Aged Aged, 80 and over Aniseikonia/*complications/physiopathology Diplopia/*etiology/physiopathology Epiretinal Membrane/complications Eye Diseases/complications Humans *Macula Lutea/physiopathology Male Middle Aged Retinal Diseases/*complications/physiopathology Retrospective Studies Strabismus/complications Visual Acuity Vitreous BodyJulOBJECTIVE: To provide an explanation for diplopia and the inability to fuse in some patients with macular disease. METHODS: We identified 7 patients from our practices who had binocular diplopia concurrent with epiretinal membranes or vitreomacular traction. A review of the medical records of all patients was performed. In addition to complete ophthalmologic and orthoptic examinations, evaluation of aniseikonia using the Awaya New Aniseikonia Tests (Handaya Co Ltd, Tokyo, Japan) was performed on all patients. RESULTS: All patients were referred for troublesome diplopia. Six of the patients had epiretinal membranes and 1 had vitreomacular traction. All 7 patients had aniseikonia, ranging from 5% to 18%. In 5 of the patients the image in the involved eye was larger, and in the other 2 patients it was smaller than in the fellow eye. All patients had concomitant small-angle strabismus and at least initially did not fuse when the deviation was offset with a prism. Response to optical management and retinal surgery was variable. CONCLUSIONS: Aniseikonia caused by separation or compression of photoreceptors can be a contributing factor to the existence of diplopia and the inability to fuse in patients with macular disease. Concomitant small-angle strabismus and the inability to fuse with prisms may lead the clinician to the incorrect diagnosis of central disruption of fusion. Surgical intervention does not necessarily improve the aniseikonia.+http://www.ncbi.nlm.nih.gov/pubmed/10408453Benegas, N M Egbert, J Engel, W K Kushner, B J Case Reports Research Support, Non-U.S. Gov't United states Archives of ophthalmology Arch Ophthalmol. 1999 Jul;117(7):896-9.%0003-9950 (Print) 0003-9950 (Linking)10408453WDepartment of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, USA.eng ||7JJabbour, M. E. Goldfischer, E. R. Anderson, A. E. Kushner, L. Smith, A. D.1999jFailed endopyelotomy: low expression of TGF beta regardless of the presence or absence of crossing vessels295-8 J Endourol134 1999/07/16Adult Biological Markers *Endoscopy Female Humans Kidney Pelvis/*blood supply/metabolism/surgery Male Muscle, Smooth/blood supply/metabolism Renal Artery/*anatomy & histology Renal Veins/*anatomy & histology Transforming Growth Factor beta/*biosynthesis Treatment Failure Ureter/blood supply/metabolism/surgery Ureteral Obstruction/metabolism/pathology/*surgery *Urologic Surgical Procedures Wound HealingMayBACKGROUND AND OBJECTIVE: Endopyelotomy relies on Davis' intubated ureterotomy principle of healing by secondary intention and smooth-muscle regeneration. Approximately 15% of endopyelotomies fail, and the restrictured segment almost always shows evidence of reactive fibrosis with little smooth-muscle regeneration. Previous data suggests that an elevation of TGF beta in obstructed ureteropelvic junctures may be necessary for successful tissue repair following endopyelotomy. The role of crossing vessels in endopyelotomy failure is very controversial. To better understand the pathophysiology of endopyelotomy failure, the expression of transforming growth factor-beta (TBG beta) in patients with a failed endopyelotomy and crossing vessels was compared with that in patients without crossing vessels, as well as those having primary pyeloplasty or a normal ureteropelvic junction (UPJ). MATERIALS AND METHODS: The expression of TGF beta was detected immunohistochemically in slide-mounted thin sections (4 microns) cut from paraffin-blocked adult UPJ segments obtained during primary pyeloplasty (N = 11), secondary pyeloplasty after failed endopyelotomy with documented crossing vessels (N = 10), secondary pyeloplasty after failed endopyelotomy without crossing vessels (N = 11), and normal UPJs removed during nephrectomy for purposes unrelated to obstruction (N = 11). Expression was graded on a scale of 0 to 4. RESULTS: The combined failed endopyelotomy group had a significantly (P < 0.05) lower level of TGF beta (1.9 +/- 0.7) than did primary obstructed UPJs (2.6 +/- 0.7). The TGF beta level in the crossing vessels group (1.9 +/- 0.7) did not differ from that in the group without crossing vessels (1.8 +/- 0.7), nor did it differ from that in the group with normal UPJs (1.6 +/- 0.7). As expected, primary obstructed UPJs had a significantly higher level of TGF beta than normal ones (P < 0.02). CONCLUSIONS: Obstructed UPJs that had failed endopyelotomy had a similarly reduced level of TGF beta whether or not crossing vessels were present. These data suggest that an elevation of TGF beta in obstructed UPJs may be necessary for successful tissue repair after endopyelotomy and that the presence of crossing vessels is probably not relevant.+http://www.ncbi.nlm.nih.gov/pubmed/10405909Jabbour, M E Goldfischer, E R Anderson, A E Kushner, L Smith, A D Comparative Study United states Journal of endourology / Endourological Society J Endourol. 1999 May;13(4):295-8.%0892-7790 (Print) 0892-7790 (Linking)10405909|Department of Urology, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, New York, USA.eng ||7IMerchant, T. E. Kushner, B. H. Sheldon, J. M. LaQuaglia, M. Healey, J. H.1999\Effect of low-dose radiation therapy when combined with surgical resection for Ewing sarcoma65-70Med Pediatr Oncol332 1999/07/09qAdolescent Adult Antineoplastic Combined Chemotherapy Protocols/therapeutic use Bone Neoplasms/drug therapy/pathology/*radiotherapy/surgery Child Child, Preschool Combined Modality Therapy Female Humans Male Middle Aged Prognosis Radiotherapy Dosage Retrospective Studies Sarcoma, Ewing's/drug therapy/*radiotherapy/secondary/surgery Survival Analysis Treatment OutcomeAugBACKGROUND: As an alternative to high-dose irradiation, limited surgery and low-dose irradiation have been investigated as a means to achieve local control. We retrospectively examined the clinical characteristics, treatment, and outcome for 25 patients with Ewing sarcoma treated with limited surgery and low-dose irradiation. PROCEDURE: The records of 25 patients (age 4-48 years) were reviewed who were treated between 1979 and 1996 at Memorial Sloan-Kettering Cancer Center. At the time of diagnosis, 21 of the 25 patients had prognostically unfavorable tumors including the presence of metastatic disease (n = 12), an axial primary (n = 17), and a tumor measuring greater than 8 cm (n = 18). The primary tumor was completely resected (wide local excision) in 13 patients, incompletely resected (marginal excision) in 7 patients, and biopsied only in the remaining 5 patients. The median dose of irradiation to the primary site was 30 Gy. RESULTS: With a median follow-up of 67 months (range 16-189 months) for the surviving patients, 28% failed distantly, and an additional 28% suffered from the progression of previously established metastatic disease. No patient failed locally. The median overall survival was 43 months. The actuarial overall survival at 5 years was 39% (+/-11%) for all patients and 60% (+/-14%) for patients with localized disease. CONCLUSIONS: Limited surgery and postoperative irradiation are one strategy that promises to balance the goal of achieving local control with the goal of diminishing late effects. Apart from the scenario in which radiation therapy is absolutely unnecessary, low-dose irradiation may be appropriate after considering the risk for local recurrence and overall prognosis.+http://www.ncbi.nlm.nih.gov/pubmed/10398178Merchant, T E Kushner, B H Sheldon, J M LaQuaglia, M Healey, J H United states Medical and pediatric oncology Med Pediatr Oncol. 1999 Aug;33(2):65-70.%0098-1532 (Print) 0098-1532 (Linking)10398178}Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA. thomas.merchant@stjude.orgA10.1002/(SICI)1096-911X(199908)33:2<65::AID-MPO1>3.0.CO;2-L [pii]engl||7LActon, P. D. Kushner, S. A. Kung, M. P. Mozley, P. D. Plossl, K. Kung, H. F.1999Simplified reference region model for the kinetic analysis of [99mTc]TRODAT-1 binding to dopamine transporters in nonhuman primates using single-photon emission tomography518-26Eur J Nucl Med265 1999/06/26Animals Brain/metabolism/*radionuclide imaging Carrier Proteins/*metabolism Dopamine/*metabolism Dopamine Plasma Membrane Transport Proteins Female *Membrane Glycoproteins *Membrane Transport Proteins *Nerve Tissue Proteins Organotechnetium Compounds/*diagnostic use/pharmacokinetics Papio Radiopharmaceuticals/*diagnostic use/pharmacokinetics *Tomography, Emission-Computed, Single-Photon Tropanes/*diagnostic use/pharmacokineticsMay< Accurate quantification of neuroreceptors requires full kinetic modeling of the dynamic single-photon emission tomography (SPET) or positron emission tomography (PET) images, with highly invasive arterial blood sampling. This study investigated the application of a reference region kinetic model to the dynamics of [99mTc]TRODAT-1 in nonhuman primates, obviating the need for blood sampling. A series of dynamic SPET scans were performed on two baboons following the injection of approximately 700 MBq of [99mTc]TRODAT-1. Rapid arterial blood samples were taken automatically during scanning. Reconstructed SPET images were coregistered with magnetic resonance imaging (MRI) scans of the baboons, and regions of interest (ROIs) placed on the striatum, cerebellum and cerebral hemispheres. The ROI data were combined with metabolite-corrected blood data, and fitted to a three-compartment kinetic model using nonlinear least squares techniques. The same data were also used in a simplified reference region model, in which the input function was derived from the nondisplaceable tissue compartment. In addition, semiquantitative blinded analysis was performed by three raters to determine the point of transient equilibrium in the specific binding curves. All methods generated values for the ratio of the kinetic rate constants k3/k4, which gives an estimate of the binding potential, BP. These were compared with the full kinetic model. The mean values of k3/k4 for the three different analysis techniques for each baboon were: 1.17 +/- 0.21 and 1.12 +/- 0.13 (full kinetic model), 0.93 +/- 0.13 and 0.90 +/- 0.07 (reference region model), and 0.97 +/- 0.18 and 0.92 +/- 0.08 (equilibrium method). The reference region method gave significantly lower results than the full kinetic model (P = 0.01), but it also produced a much smaller spread and better quality fits to the kinetic data. The reference region model results for k3/k4 correlated very strongly with the full kinetic analysis (r2 = 0.992, P < 0.001), and with the equilibrium model (r2 = 0.88, P = 0.002). The subjectivity inherent in the equilibrium method produces inferior results compared with both kinetic analyses. It is suggested that the self-consistency of the reference region model, which requires no arterial blood sampling, provides a more precise and reliable estimate of the binding of [99mTc]TRODAT-1 to dopamine transporters than full kinetic modeling. The reference region method is also better suited to a routine clinical environment, and would be able to distinguish smaller differences in dopaminergic function between patient groups.+http://www.ncbi.nlm.nih.gov/pubmed/10382097|Acton, P D Kushner, S A Kung, M P Mozley, P D Plossl, K Kung, H F 3GM08042/GM/NIGMS NIH HHS/United States NS-18509/NS/NINDS NIH HHS/United States NS-24538/NS/NINDS NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Germany European journal of nuclear medicine Eur J Nucl Med. 1999 May;26(5):518-26.%0340-6997 (Print) 0340-6997 (Linking)10382097MDepartment of Radiology, University of Pennsylvania, Philadelphia 19104, USA.eng ||7PLopez, G. N. Webb, P. Shinsako, J. H. Baxter, J. D. Greene, G. L. Kushner, P. J.1999eTitration by estrogen receptor activation function-2 of targets that are downstream from coactivators897-909Mol Endocrinol136 1999/06/24UAdaptor Proteins, Signal Transducing Binding, Competitive CREB-Binding Protein Carrier Proteins/metabolism Chloramphenicol O-Acetyltransferase/genetics/metabolism Estradiol/metabolism/pharmacology Gene Expression Regulation Genes, Reporter Histone Acetyltransferases Humans Nuclear Proteins/genetics/metabolism Nuclear Receptor Coactivator 1 Nuclear Receptor Coactivator 2 Nucleocytoplasmic Transport Proteins Receptors, Estrogen/drug effects/genetics/*metabolism Receptors, Glucocorticoid/metabolism Receptors, Progesterone/metabolism Receptors, Thyroid Hormone/drug effects/genetics/metabolism Recombinant Proteins/genetics/metabolism Tamoxifen/metabolism/pharmacology Titrimetry Trans-Activators/genetics/*metabolism Transcription Factor TFIIB Transcription Factors/genetics/*metabolism Transcription, Genetic Triiodothyronine/metabolism/pharmacologyJun|Cross-interference (squelching) among nuclear receptors has been proposed to reflect the titration of coactivators that bind the receptors in a hormone-dependent manner. We have tested whether the coactivators are the only target titrated during squelching of one receptor by another, or whether proteins needed for coactivator function are titrated as well. That the coactivators are indeed one target of squelching is apparent. The isolated ligand-binding domain of the estrogen receptor (ER-LBD) squelches transcriptional activation by the thyroid hormone receptor (TR) only when the LBD is bound to ligands that promote coactivator interactions and only when regions of the LBD that promote coactivator interactions are undisturbed. Furthermore, the ER-LBD and the TR compete in vitro for the related p160 coactivators, SRC1a and GRIP1 (glucocorticoid receptor interacting protein 1), or the putative corepressor, RIP140. Finally TR action becomes more potent when coactivator levels are raised. Nonetheless, supplying excess SRC1a or GRIP1 does not abolish squelching by the ER. In fact, squelching becomes even more severe when coactivators are abundant. Supplying combinations of coactivators from the p160 class and the CREB-binding protein (CBP)/p300 class makes squelching most severe. Elevated RIP140 inhibits TR action, but also protects the residual TR action from squelching by the ER-LBD. We conclude that ER-LBD squelches TR both by titrating p160-CBP coactivators and additionally by cooperating with the coactivators to titrate a second factor. The second factor would be needed by the TR for coactivator-mediated transcriptional stimulation.+http://www.ncbi.nlm.nih.gov/pubmed/10379889Lopez, G N Webb, P Shinsako, J H Baxter, J D Greene, G L Kushner, P J DK-51083/DK/NIDDK NIH HHS/United States Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. United states Molecular endocrinology (Baltimore, Md.) Mol Endocrinol. 1999 Jun;13(6):897-909.%0888-8809 (Print) 0888-8809 (Linking)10379889LMetabolic Research Unit, University of California, San Francisco 94143, USA.eng ||7OSumner, A. E. Kushner, H. Sherif, K. D. Tulenko, T. N. Falkner, B. Marsh, J. B.1999qSex differences in African-Americans regarding sensitivity to insulin's glucoregulatory and antilipolytic actions71-7 Diabetes Care221 1999/05/20Adult *African Continental Ancestry Group Analysis of Variance Blood Glucose/drug effects/*metabolism Cohort Studies Female Glucose Clamp Technique Glucose Tolerance Test Homeostasis Humans Hyperinsulinism Infusions, Intravenous Insulin/administration & dosage/*pharmacology/physiology Lipolysis/*drug effects Longitudinal Studies Male Metabolic Clearance Rate Philadelphia Regression Analysis Sex CharacteristicsJanM OBJECTIVE: The purpose of this study was to determine if there are sex differences in African-Americans regarding the effect of obesity on sensitivity to insulin as a glucoregulatory and antilipolytic hormone. RESEARCH DESIGN AND METHODS: Data from study participants, 127 nondiabetic African-Americans (mean age 32 +/- 4 years), included anthropometric measurements, an oral glucose tolerance test (OGTT), a 2-h euglycemic-hyperinsulinemic clamp, and a fasting triglyceride level. Sensitivity to insulin as a glucoregulatory hormone was determined by M/FFM, where M is the mean glucose infusion rate during the second hour of the clamp and FFM is fat-free mass. Sensitivity to insulin's antilipolytic action was assessed during the OGTT by the percent suppression of free fatty acid (FFA) concentrations between 0 and 120 min. The higher the suppression of FFAs, the greater the sensitivity to insulin's antilipolytic action. RESULTS: The participants were classified by BMI into three groups: nonobese (31 men, 24 women), obese (17 men, 14 women), and severely obese (12 men, 29 women). The women had higher percentages of body fat (P < 0.001), and the men had greater FFM (P < 0.001). The M/FFM values for men versus women in each BMI group were nonobese, 8.8 +/- 2.8 vs. 10.8 +/- 4.4; obese, 7.2 +/- 3.4 vs. 8.5 +/- 3.4; and severely obese, 4.7 +/- 2.1 vs. 6.1 +/- 2.2. The difference between the BMI groups was significant (P < 0.001), as was the difference between men and women (P < 0.01). In addition, there was a significant sex difference in percent suppression of FFAS (P < 0.001). The men and women had similar fasting insulin and FFA concentrations; however, in the men only, the percent suppression of FFA declined with increasing obesity (nonobese, 83 +/- 15%; obese, 73 +/- 18%; and severely obese, 69 +/- 19%; P = 0.02). The women in all three BMI groups had lower FFA levels of 86-88%. CONCLUSIONS: Obese African-American men and women are resistant to insulin as a glucoregulatory hormone, but only obese men are resistant to insulin's antilipolytic action; obese African-American women are sensitive to insulin's antilipolytic action. The combined presence of sensitivity to insulin's antilipolytic action with resistance to insulin's glucoregulatory action in obese African-American women may contribute to their high prevalence of obesity and type 2 diabetes.+http://www.ncbi.nlm.nih.gov/pubmed/10333906Sumner, A E Kushner, H Sherif, K D Tulenko, T N Falkner, B Marsh, J B HL-51536/HL/NHLBI NIH HHS/United States HL-51547/HL/NHLBI NIH HHS/United States Research Support, U.S. Gov't, P.H.S. United states Diabetes care Diabetes Care. 1999 Jan;22(1):71-7.%0149-5992 (Print) 0149-5992 (Linking)10333906Institute for Women's Health, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania, USA. annes@intra.niddk.nih.goveng ||7*Kushner, M. G. Sher, K. J. Erickson, D. J.1999`Prospective analysis of the relation between DSM-III anxiety disorders and alcohol use disorders723-32Am J Psychiatry1565 1999/05/18Alcohol-Related Disorders/diagnosis/*epidemiology/psychology Anxiety Disorders/diagnosis/*epidemiology/psychology Causality Comorbidity Cross-Sectional Studies Family Female Follow-Up Studies Humans Logistic Models Male Multivariate Analysis Odds Ratio Prevalence Prospective Studies Psychiatric Status Rating Scales/statistics & numerical data Sex Factors Students/statistics & numerical data UniversitiesMayOBJECTIVE: Cross-sectional studies show a robust association between anxiety disorders and alcohol use disorders (comorbidity); however, this methodology does not allow for the testing of causal models. The authors attempted to overcome this limitation by examining comorbid relationships prospectively. METHOD: Male and female college students were assessed as freshmen (year 1), and then again at years 4 and 7, for selected 12-month anxiety disorders (generalized anxiety disorder, agoraphobia, and social phobia or panic) diagnosed according to the National Institute of Mental Health Diagnostic Interview Schedule (DIS) and DSM-III and for 12-month DIS/DSM-III alcohol use disorders (alcohol dependence alone and alcohol abuse or dependence). RESULTS: Cross-sectionally, the odds of having either an anxiety disorder or an alcohol use disorder were two- to fivefold greater when the other condition was present. Prospectively, the odds of developing a new alcohol dependence diagnosis at year 7 increased from 3.5 to five times for those diagnosed with an anxiety disorder at years 1 or 4. Conversely, the odds of developing a new anxiety disorder at year 7 increased by about four times for those diagnosed with alcohol dependence at years 1 or 4. When alcohol abuse and dependence were combined, the pattern of findings was similar, albeit weaker. Multivariate path models provide similar results and highlight the reciprocal influence of alcohol use disorders and anxiety disorders. CONCLUSIONS: Alcohol use disorders (especially alcohol dependence) and anxiety disorders demonstrate a reciprocal causal relationship over time, with anxiety disorders leading to alcohol dependence and vice versa.+http://www.ncbi.nlm.nih.gov/pubmed/10327905Kushner, M G Sher, K J Erickson, D J AA-07231/AA/NIAAA NIH HHS/United States Research Support, U.S. Gov't, P.H.S. United states The American journal of psychiatry Am J Psychiatry. 1999 May;156(5):723-32.%0002-953X (Print) 0002-953X (Linking)10327905*University of Minnesota, Minneapolis, USA.eng ||7Kushner, B. J.1999ODoes overcorrecting minus lens therapy for intermittent exotropia cause myopia?638-42Arch Ophthalmol1175 1999/05/18Accommodation, Ocular Child Child, Preschool Exotropia/physiopathology/*therapy Eyeglasses/*adverse effects Female Follow-Up Studies Humans Infant Male Myopia/*etiology/physiopathology Retrospective StudiesMay~BACKGROUND: Overcorrecting minus lens therapy has been used as a treatment for intermittent exotropia. It is based on the principle that an exotropic deviation will be decreased by stimulating accommodative convergence with additional minus power in spectacles. Because excessive accommodation has been implicated as a cause of myopia, there is theoretical concern that overcorrecting minus lens therapy for exotropia may cause myopia. OBJECTIVE: To investigate the effect of overcorrecting minus lens therapy for exotropia on the progression of myopia. DESIGN: A retrospective chart review. SUBJECTS AND METHODS: Seventy-four patients with intermittent exotropia were treated with overcorrecting minus lens therapy for at least 6 months (6-month treatment group), and a 34-patient subset of them received overcorrecting minus lens therapy for 5 years (5-year treatment group). The mean change in refractive error (spherical equivalent of the fixing eye) of these 2 groups 5 years after initial examination was compared with the mean change in refractive error of a control group of 45 patients with intermittent exotropia who did not receive overcorrecting minus lens therapy. RESULTS: At the time of initial examination, the mean (+/-SD) refractive error was 0.00 +/- 1.40 diopters (D) in the control group, 0.00 +/- 1.50 D in the study group, and -0.10 +/- 1.50 D in the 5-year study group, all of which were essentially identical. Five years after initial examination, the mean change in refractive error was -1.40 +/- 2.80 D in the control group, -1.52 +/- 1.80 D in the 6-month treatment group, and -1.54 +/- 1.80 D in the 5-year treatment group. These differences in the change in refractive error (myopic shift) were not statistically significant (t test), and the differences are clinically unimportant. CONCLUSION: Overcorrecting minus lens therapy for intermittent exotropia does not appear to cause myopia.+http://www.ncbi.nlm.nih.gov/pubmed/10326961~Kushner, B J Research Support, Non-U.S. Gov't United states Archives of ophthalmology Arch Ophthalmol. 1999 May;117(5):638-42.%0003-9950 (Print) 0003-9950 (Linking)10326961Pediatric Eye and Adult Strabismus Clinic, Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, USA. bkushner@facstaff.wisc.edueng||7 Kushner, J.1999Career modification579-80 Surg Neurol515 1999/05/13T*Career Choice *Commerce Humans Neurosurgery/*manpower *Specialization United StatesMay+http://www.ncbi.nlm.nih.gov/pubmed/10321897VKushner, J Letter United states Surgical neurology Surg Neurol. 1999 May;51(5):579-80.%0090-3019 (Print) 0090-3019 (Linking)10321897eng||7EMel'nichenko, E. M. Kushner, A. N. Zafranskaia, M. M. Miliutin, A. A.1999h[The immunoglobulin content in the saliva of children living under different radioecological conditions]12-4Stomatologiia (Mosk)782 1999/05/04lAdolescent Analysis of Variance Binomial Distribution Child Discriminant Analysis *Ecology Environmental Exposure/adverse effects/*analysis/statistics & numerical data Humans Immunodiffusion/statistics & numerical data Immunoglobulins/*analysis/radiation effects Republic of Belarus Saliva/*chemistry/radiation effects Soil Pollutants, Radioactive/*adverse effectsSalivary specimens of 80 children aged 8-14 years from the Stolin District and of 34 children of the city of Minsk are examined by radial immunodiffusion in gel and by enzyme immunoassay. Residents of a region contaminated with radionuclides (soil contamination with 137Cs 185-555 kBq/m2) develop an imbalance in the production and secretion of specific salivary antibodies: the production of IgM in early periods of immune response is suppressed and the level of IgE is increased.+http://www.ncbi.nlm.nih.gov/pubmed/10224900Mel'nichenko, E M Kushner, A N Zafranskaia, M M Miliutin, A A English Abstract Russia Stomatologiia Stomatologiia (Mosk). 1999;78(2):12-4.%0039-1735 (Print) 0039-1735 (Linking)10224900mSoderzhanie immunoglobulinov v sliune detei, prozhivaiushchikh v razlichnykh radioekologicheskikh usloviiakh.rusU||7Kushner, B. J.19990The 100th monkey phenomenon and medical research65-6J AAPOS32 1999/04/30]Eye Diseases/*history/therapy History, 20th Century History, Ancient Humans Research/*historyApr+http://www.ncbi.nlm.nih.gov/pubmed/10221795 Kushner, B J Editorial Historical Article United states Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus / American Association for Pediatric Ophthalmology and Strabismus J AAPOS. 1999 Apr;3(2):65-6.%1091-8531 (Print) 1091-8531 (Linking)10221795eng||7Kushner, B. J.1999PSurgical treatment of paralysis of the inferior division of the oculomotor nerve485-9Arch Ophthalmol1174 1999/04/17Adult Diplopia/etiology/surgery Female Humans Male Middle Aged Oculomotor Muscles/*transplantation Oculomotor Nerve Diseases/complications/*surgery *Ophthalmologic Surgical Procedures Tendons/*surgery Visual FieldsAprBACKGROUND: Paralysis of the inferior division of the oculomotor nerve is relatively rare. Little has been written about its surgical treatment. METHODS: Five patients with paralysis of the inferior division of the oculomotor nerve were treated with transposition of the superior rectus muscle toward the insertion of the medial rectus muscle, transposition of the lateral rectus muscle toward the insertion of the inferior rectus muscle, and tenotomy of the superior oblique tendon in the affected eye. RESULTS: All 5 patients had a satisfactory outcome. They were free of diplopia in the primary position as of their last examination. Follow-up ranged from 3 to 10 years after surgery. CONCLUSION: Paralysis of the inferior division of the oculomotor nerve can be adequately treated by simultaneous transposition of the superior rectus muscle toward the insertion of the medial rectus muscle, transposition of the lateral rectus muscle toward the insertion of the inferior rectus muscle, and tenotomy of the superior oblique tendon in the affected eye.+http://www.ncbi.nlm.nih.gov/pubmed/10206576Kushner, B J Case Reports Research Support, Non-U.S. Gov't United states Archives of ophthalmology Arch Ophthalmol. 1999 Apr;117(4):485-9.%0003-9950 (Print) 0003-9950 (Linking)10206576rDepartment of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, USA. bkushner@facstaff.wisc.edueng||7 Kushner, L. I. Mackin, A. J.1999AAnesthesia case of the month. Cyanosis in a dog during anesthesia1007-9J Am Vet Med Assoc2147 1999/04/14Anesthesia, General/adverse effects/*veterinary Animals Blood Gas Analysis/veterinary Cyanosis/etiology/*veterinary Dog Diseases/congenital/*etiology Dogs Female Methemoglobinemia/complications/congenital/*veterinary Oximetry/veterinaryApr 1+http://www.ncbi.nlm.nih.gov/pubmed/10200793Kushner, L I Mackin, A J Case Reports United states Journal of the American Veterinary Medical Association J Am Vet Med Assoc. 1999 Apr 1;214(7):1007-9.%0003-1488 (Print) 0003-1488 (Linking)10200793qAnimal Health Center, College of Veterinary Medicine, Mississippi State University, Mississippi State 39762, USA.eng7||7!]Forbes, D. A. King, K. M. Kushner, K. E. Letourneau, N. L. Myrick, A. F. Profetto-McGrath, J.1999'Warrantable evidence in nursing science373-9 J Adv Nurs292 1999/04/10[*Evidence-Based Medicine Female Feminism Humans *Nursing Research Nursing Theory PhilosophyFebConsensus among nurse scholars has not been reached regarding suitable qualities for accepting or rejecting the evidence arising from various world views. The authors' purpose in writing the paper is to describe the qualities or warrants for evaluating scientific findings (the 'evidence') of different research perspectives. The warrantable evidence pertinent to post-positivist, interpretivist, critical social theorist, and feminist perspectives are described and common warrants are suggested. Three warrants common to these scientific perspectives are proposed: (a) scrutiny and critique of methodological rigor and findings by the scientific community; (b) corroboration and intersubjectivity; and (c) scope of the evidence. The identification of common warrantable evidence will assist nurses in developing some core values regarding the constituents of good science or good scholarship even in the face of pluralism in nursing science approaches.+http://www.ncbi.nlm.nih.gov/pubmed/10197937Forbes, D A King, K M Kushner, K E Letourneau, N L Myrick, A F Profetto-McGrath, J Review England Journal of advanced nursing J Adv Nurs. 1999 Feb;29(2):373-9.%0309-2402 (Print) 0309-2402 (Linking)10197937CCentre for Health Promotion Studies, University of Alberta, Canada.eng||7"$Rao, R. Morton, G. V. Kushner, B. J.1999'Ocular torticollis and facial asymmetry27-32Binocul Vis Strabismus Q141 1999/03/23Facial Asymmetry/diagnosis/*etiology Head Humans Nystagmus, Pathologic/complications/diagnosis Ocular Motility Disorders/*complications/diagnosis Ophthalmoplegia/complications/diagnosis Photography Posture Prospective Studies Video RecordingzOBJECTIVE: Ocular torticollis secondary to congenital superior oblique palsy can be associated with facial asymmetry. The purpose of this study was to determine if other ocular causes of head tilting also carry the same association. DESIGN: The study design was clinical evaluation of patients. PARTICIPANTS: Fifteen patients with marked, moderate, or mild head tilts associated with dissociated vertical deviation (DVD), and 3 patients with nystagmus and a torsional null point. A control group was comprised of 3 patients with congenital superior oblique palsy, 3 with traumatic superior oblique palsy, and two normal patients. INTERVENTION: A masked observer analyzed full-face photographs of the subjects. MAIN OUTCOME MEASURE: The presence of facial asymmetry. RESULTS: Facial asymmetry due to bending in/of the sagittal plane of at least two degrees was found in 3 of 4 patients with a marked head tilt from DVD, in 2 of 5 five patients with a moderate head tilt from DVD, in one of 3 patients with a head tilt due to nystagmus, and in one of 3 patients with a head tilt due to congenital superior oblique palsy. None of the patients with a mild head tilt from DVD, traumatic superior oblique palsy, or the normal controls had clinically noticeable facial asymmetry. CONCLUSION: Facial asymmetry can be associated with abnormal head postures, specifically, large head tilts from DVD or nystagmus.+http://www.ncbi.nlm.nih.gov/pubmed/10085531Rao, R Morton, G V Kushner, B J Comparative Study Research Support, Non-U.S. Gov't United states Binocular vision & strabismus quarterly Binocul Vis Strabismus Q. 1999;14(1):27-32.%1088-6281 (Print) 1088-6281 (Linking)10085531Pediatric Eye and Adult Strabismus Clinic, Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, USA.eng||7#FKushner, B. J. Alvares, M. G. Paysse, E. A. Brooks, S. E. Borchert, M.1999Grand rounds #53: A case of small angle strabismus, torsion, aniseikonia and diplopia associated with epiretinal membranes [clincical conference]46-51; discussion 51-2Binocul Vis Strabismus Q141 1999/03/17Aged Aniseikonia/*complications/diagnosis/surgery Diplopia/diagnosis/*etiology/surgery Epiretinal Membrane/*complications/diagnosis Esotropia/*complications/diagnosis/surgery Eye Movements Female Humans Oculomotor Muscles/surgery Refraction, Ocular Torsion Abnormality Visual Acuity+http://www.ncbi.nlm.nih.gov/pubmed/10076106Kushner, B J Alvares, M G Paysse, E A Brooks, S E Borchert, M Case Reports Clinical Conference United states Binocular vision & strabismus quarterly Binocul Vis Strabismus Q. 1999;14(1):46-51; discussion 51-2.%1088-6281 (Print) 1088-6281 (Linking)10076106eng w||7$Kushner, B. J.1999^Diagnosis and treatment of exotropia with a high accommodation convergence-accommodation ratio221-4Arch Ophthalmol1172 1999/02/26*Accommodation, Ocular Child Child, Preschool *Convergence, Ocular Exotropia/*diagnosis/*therapy Eyeglasses Follow-Up Studies Humans Oculomotor Muscles/surgery Sensory Deprivation Vision TestsFebBACKGROUND: Patients with exotropia often have a slow-to-dissipate fusional mechanism at near, which masks the true near deviation. Consequently, determination of the accommodation convergence-accommodation (AC/A) ratio in patients with exotropia must be based on near measurements obtained after prolonged monocular occlusion (typically 1 hour). When determined in that manner, the presence of a high AC/A ratio before surgery in an exotropic patient has been reported to be predictive of an esotropia at near after surgery. OBJECTIVE: To investigate the diagnosis and management of exotropia with a high AC/A ratio. METHODS: Three hundred four consecutive patients with exotropia were studied. In addition to the usual measurements, measurements were obtained at near after 1 hour of monocular occlusion, with and without additional +3.00-diopter lenses. Also, a gradient AC/A ratio was obtained by using additional minus lenses at distance fixation. RESULTS: One hundred fifty-four (50.7%) of 304 patients would have been thought to have a high AC/A ratio if that diagnosis was based on measurements obtained before prolonged monocular occlusion. In fact, only 22 patients (7.2%) actually had a high AC/A ratio; 132 patients (43.4%) had a pseudo-high AC/A ratio. Six of 22 patients with a high AC/A ratio underwent surgery to correct the exotropia. The presence of a high AC/A ratio before surgery had sensitivity, specificity, and positive and negative predictive values of 100% for predicting a postoperative esotropia at near associated with a high AC/A ratio. The remaining 16 patients with high AC/A ratios were treated with overcorrecting minus lens therapy (including a bifocal). Ten of them have been followed up to at least 18 years of age, by which time 9 have shown normalization of the AC/A ratio. CONCLUSIONS: Near measurements used to calculate the AC/A ratio in exotropic patients must be made after prolonged monocular occlusion. Otherwise, many patients with a pseudo-high AC/A ratio will be thought to have a true high AC/A ratio. The presence of a high AC/A ratio is infrequent in patients with esotropia, but it is highly predictive of a postoperative esotropia at near fixation.+http://www.ncbi.nlm.nih.gov/pubmed/10037567}Kushner, B J Research Support, Non-U.S. Gov't United states Archives of ophthalmology Arch Ophthalmol. 1999 Feb;117(2):221-4.%0003-9950 (Print) 0003-9950 (Linking)10037567rDepartment of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, USA. bkushner@facstaff.wisc.edueng||7%WJohnston, S. R. Lu, B. Scott, G. K. Kushner, P. J. Smith, I. E. Dowsett, M. Benz, C. C.1999Increased activator protein-1 DNA binding and c-Jun NH2-terminal kinase activity in human breast tumors with acquired tamoxifen resistance251-6Clin Cancer Res52 1999/02/26Aged Antineoplastic Agents, Hormonal/*therapeutic use Breast Neoplasms/drug therapy/enzymology/*metabolism Calcium-Calmodulin-Dependent Protein Kinases/*metabolism DNA, Neoplasm/metabolism DNA-Binding Proteins/metabolism Drug Resistance, Neoplasm Female Humans JNK Mitogen-Activated Protein Kinases *Mitogen-Activated Protein Kinases Receptors, Estrogen/metabolism Tamoxifen/*therapeutic use Transcription Factor AP-1/*metabolismFeb Human breast tumors that are initially responsive to tamoxifen (TAM) eventually relapse during treatment. Estrogen receptor (ER) expression and function are often preserved in these tumors, and clinical evidence suggests that this relapse may be related to TAM's known agonistic properties. ER can interact with the activator protein-1 (AP-1) transcription factor complex through protein-protein interactions that are independent of ER DNA binding and, in certain ER-positive cells, this may allow TAM to exert an agonist response on AP-1-regulated genes. We, therefore, assessed both AP-1 DNA binding and the known AP-1 activating enzyme, c-Jun NH2-terminal kinase (JNK), in a panel of 30 ER-positive primary human breast tumors with acquired TAM resistance, as compared to a matched panel of 27 untreated control ER-positive breast tumors and a separate control set of 14 primary tumors, which included 7 ER-positive tumors that were growth-arrested by 3 months of preoperative TAM. AP-1 DNA binding activity was measured from cryopreserved tumor extracts using a labeled oligonucleotide probe containing a consensus AP-1 response element by electrophoretic mobility shift assay. JNK was first extracted from the tumor lysates by incubation over a Sepharose-bound c-Jun(1-89) fusion protein, and its activity was then measured by chemiluminescent Western blot by detection of the phosphorylated product using a phospho-Jun(Ser-63)-specific primary antibody. The set of control ER-positive breast tumors growth arrested by TAM showed no significant difference from untreated control tumors in their AP-1 DNA binding and JNK activities. In contrast, there was a significant (P < 0.001) increase in mean AP-1 DNA binding activity for the panel of ER-positive TAM-resistant (TAM-R) tumors as compared to its matched control panel of untreated tumors. Mean JNK activity in the TAM-R tumors was also significantly higher than that found in the untreated tumors (P = 0.038). Overall, there was no significant correlation between JNK activity and AP-1 DNA binding; however, regression analysis showed that, for any given level of JNK activity, the TAM-R tumors possessed a 3.5-fold increase in AP-1 DNA binding activity as compared to the untreated tumors. These findings indicate that, when compared to untreated ER-positive primary breast tumors, TAM-R tumors demonstrate significantly increased levels of AP-1 DNA binding and JNK activity, consistent with experimental models suggesting that TAM-stimulated ER-positive tumor growth may be mediated by enhanced AP-1 transcriptional activity. These observations support the need for further evaluation of these markers in breast tumors as predictors of TAM resistance.+http://www.ncbi.nlm.nih.gov/pubmed/10037172JJohnston, S R Lu, B Scott, G K Kushner, P J Smith, I E Dowsett, M Benz, C C CA-71468/CA/NCI NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states Clinical cancer research : an official journal of the American Association for Cancer Research Clin Cancer Res. 1999 Feb;5(2):251-6.%1078-0432 (Print) 1078-0432 (Linking)10037172sDepartment of Medicine, Royal Marsden Hospital and Institute of Cancer Research, London, England. stephen@icr.ac.ukeng P||7&zAshby, C. R., Jr. Rohatgi, R. Ngosuwan, J. Borda, T. Gerasimov, M. R. Morgan, A. E. Kushner, S. Brodie, J. D. Dewey, S. L.1999Implication of the GABA(B) receptor in gamma vinyl-GABA's inhibition of cocaine-induced increases in nucleus accumbens dopamine151-3Synapse312 1999/02/19nAnimals Cocaine/*pharmacology Dopamine/*metabolism Dopamine Uptake Inhibitors/*pharmacology Enzyme Inhibitors/*pharmacology GABA Antagonists/pharmacology Male Morpholines/pharmacology Nucleus Accumbens/*drug effects/metabolism Rats Rats, Sprague-Dawley Receptors, GABA-B/*drug effects/metabolism Vigabatrin gamma-Aminobutyric Acid/*analogs & derivatives/pharmacologyFeb Previously, we demonstrated that gamma vinyl-GABA (GVG, Vigabatrin) dose-dependently inhibits cocaine-induced increases in dopamine (DA) concentrations in both the rodent and primate brain. Furthermore, it abolishes cocaine self-administration and conditioned place preference, while having no effect on locomotor activity or drug delivery to the brain. In an effort to better understand the mechanisms underlying this inhibition, we examined the effect of the selective GABA(B) receptor antagonist SCH 50911 on the GVG-induced decrease in cocaine's elevation of extracellular DA concentrations in the nucleus accumbens (NACC). Cocaine administration alone (20 mg/kg i.p.) produced a 480% increase in extracellular NACC DA levels. GVG (300 mg/kg i.p.) significantly reduced this increase by 25% (P<0.01). In sharp contrast, extracellular DA levels increased to 550% after the sequential administration of SCH 50911 (3 mg/kg i.p.), GVG, and cocaine. This increase is significantly different than GVG and cocaine (P<0.05) but similar to cocaine alone. These results demonstrate that the GABA(B) antagonist SCH 50911 was able to completely abolish GVG's inhibition of cocaine-induced increases in DA in the NACC and implicates the GABA(B) receptor in the mechanism underlying this inhibition.+http://www.ncbi.nlm.nih.gov/pubmed/10024012CAshby, C R Jr Rohatgi, R Ngosuwan, J Borda, T Gerasimov, M R Morgan, A E Kushner, S Brodie, J D Dewey, S L MH49165/MH/NIMH NIH HHS/United States R2955155/PHS HHS/United States Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. United states Synapse (New York, N.Y.) Synapse. 1999 Feb;31(2):151-3.%0887-4476 (Print) 0887-4476 (Linking)10024012bDepartment of Pharmaceutical Health Sciences, St. John's University, Jamaica, New York 11439, USA.10.1002/(SICI)1098-2396(199902)31:2<151::AID-SYN8>3.0.CO;2-W [pii] 10.1002/(SICI)1098-2396(199902)31:2<151::AID-SYN8>3.0.CO;2-Weng |t7'Kushner, D. B. Ricciardi, R. P.1999Reduced phosphorylation of p50 is responsible for diminished NF-kappaB binding to the major histocompatibility complex class I enhancer in adenovirus type 12-transformed cells2169-79 Mol Cell Biol193 1999/02/18/Adenoviruses, Human/*genetics Animals Cell Line Cell Nucleus/metabolism *Cell Transformation, Viral Deoxycholic Acid/pharmacology *Enhancer Elements, Genetic Histocompatibility Antigens Class I/*genetics Humans NF-kappa B/*metabolism NF-kappa B p50 Subunit Phosphorylation Rats Transcription Factor RelAMarReduced cell surface levels of major histocompatibility complex class I antigens enable adenovirus type 12 (Ad12)-transformed cells to escape immunosurveillance by cytotoxic T lymphocytes (CTL), contributing to their tumorigenic potential. In contrast, nontumorigenic Ad5-transformed cells harbor significant cell surface levels of class I antigens and are susceptible to CTL lysis. Ad12 E1A mediates down-regulation of class I transcription by increasing COUP-TF repressor binding and decreasing NF-kappaB activator binding to the class I enhancer. The mechanism underlying the decreased binding of nuclear NF-kappaB in Ad12-transformed cells was investigated. Electrophoretic mobility shift assay analysis of hybrid NF-kappaB dimers reconstituted from denatured and renatured p50 and p65 subunits from Ad12- and Ad5-transformed cell nuclear extracts demonstrated that p50, and not p65, is responsible for the decreased ability of NF-kappaB to bind to DNA in Ad12-transformed cells. Hypophosphorylation of p50 was found to correlate with restricted binding of NF-kappaB to DNA in Ad12-transformed cells. The importance of phosphorylation of p50 for NF-kappaB binding was further demonstrated by showing that an NF-kappaB dimer composed of p65 and alkaline phosphatase-treated p50 from Ad5-transformed cell nuclear extracts could not bind to DNA. These results suggest that phosphorylation of p50 is a key step in the nuclear regulation of NF-kappaB in adenovirus-transformed cells.+http://www.ncbi.nlm.nih.gov/pubmed/10022903Kushner, D B Ricciardi, R P 5-T32-AI0735/AI/NIAID NIH HHS/United States CA29797/CA/NCI NIH HHS/United States Research Support, U.S. Gov't, P.H.S. United states Molecular and cellular biology Mol Cell Biol. 1999 Mar;19(3):2169-79.%0270-7306 (Print) 0270-7306 (Linking)8400910022903yDepartment of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.eng|||7(3Caruso, M. Boguslaw, B. Kraut, R. A. Kushner, G. M.1999'Large radiolucent lesion of the maxilla179-83J Oral Maxillofac Surg572 1999/02/11Adolescent Ameloblastoma/*pathology Diagnosis, Differential Female Giant Cell Tumor of Bone/pathology Granuloma, Giant Cell/pathology Humans Maxillary Diseases/pathology Maxillary Neoplasms/*pathology Odontogenic Tumors/pathologyFeb*http://www.ncbi.nlm.nih.gov/pubmed/9973127Caruso, M Boguslaw, B Kraut, R A Kushner, G M Case Reports Clinical Conference United states Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg. 1999 Feb;57(2):179-83.%0278-2391 (Print) 0278-2391 (Linking)9973127TMontefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY 10467, USA.S0278-2391(99)90235-5 [pii]eng-||7)Gabay, C. Kushner, I.1999AAcute-phase proteins and other systemic responses to inflammation448-54 N Engl J Med3406 1999/02/11Acute-Phase Proteins/analysis/*physiology Acute-Phase Reaction/*physiopathology C-Reactive Protein/analysis Cytokines/blood/*physiology Humans Inflammation/*diagnosis/physiopathologyFeb 11*http://www.ncbi.nlm.nih.gov/pubmed/9971870Gabay, C Kushner, I AG 02467/AG/NIA NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Review United states The New England journal of medicine N Engl J Med. 1999 Feb 11;340(6):448-54.%0028-4793 (Print) 0028-4793 (Linking)9971870dDepartment of Medicine, University of Colorado Health Sciences Center, Denver, USA. ixk2@po.cwru.edu10.1056/NEJM199902113400607eng ||7*[Cole, P. Ladanyi, M. Gerald, W. L. Cheung, N. K. Kramer, K. LaQuaglia, M. P. Kushner, B. H.1999eSynovial sarcoma mimicking desmoplastic small round-cell tumor: critical role for molecular diagnosis97-101Med Pediatr Oncol322 1999/02/09yAbdominal Neoplasms/chemistry/*diagnosis/genetics Adult Diagnosis, Differential Humans Immunohistochemistry Male RNA, Neoplasm/analysis Reverse Transcriptase Polymerase Chain Reaction Sarcoma, Ewing's/chemistry/diagnosis/genetics Sarcoma, Small Cell/chemistry/*diagnosis/genetics Sarcoma, Synovial/chemistry/*diagnosis/genetics Translocation, Genetic/genetics Vimentin/analysisFeb[BACKGROUND: The identification of recently described nonrandom chromosomal defects specific for various small round-cell and spindle-cell sarcomas can eliminate diagnostic uncertainty arising from the clinical and histopathologic overlap of soft tissue neoplasms. METHODS: A 26-year-old man presented with bulky abdominal-pelvic disease. Immunohistochemical and molecular studies on tumor were performed. Treatment was instituted using cycles of high-dose cyclophosphamide (4,200 mg/m2) with doxorubicin (75 mg/m2). RESULTS: Clinical findings pointed to desmoplastic small round-cell tumor. The tumor was histologically undifferentiated and immunoreactive for vimentin but negative for other markers. Reverse transcriptase-polymerase chain reaction revealed the SYT/SSX2 fusion transcript of the synovial sarcoma t(X;18) chromosomal rearrangement. The high-dose chemotherapy, plus surgery, achieved a complete remission, but recurrent disease emerged 13 months from diagnosis. CONCLUSIONS: This clinically unique case of synovial sarcoma highlights how the use of now readily available molecular techniques will allow more accurate appraisals of the incidence and anatomic distribution of soft tissue neoplasms-information that bears upon pathogenesis and treatment. This case confirms the utility of high-dose alkylator-based therapy for synovial sarcoma. It also demonstrates that with nonlocalized solid tumors, the eradication of minimal residual disease remains an elusive goal. One alternative involves immunologic attack against markers derived from tumor-specific chromosomal defects such as those found in our patient.*http://www.ncbi.nlm.nih.gov/pubmed/9950196Cole, P Ladanyi, M Gerald, W L Cheung, N K Kramer, K LaQuaglia, M P Kushner, B H Case Reports United states Medical and pediatric oncology Med Pediatr Oncol. 1999 Feb;32(2):97-101.%0098-1532 (Print) 0098-1532 (Linking)9950196`Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.A10.1002/(SICI)1096-911X(199902)32:2<97::AID-MPO5>3.0.CO;2-J [pii]eng ^||7+2Cheung, N. K. Heller, G. Kushner, B. H. Kramer, K.1999bDetection of neuroblastoma in bone marrow by immunocytology: is a single marrow aspirate adequate?84-7Med Pediatr Oncol322 1999/02/09Antibodies, Monoclonal/chemistry Biopsy, Needle Bone Marrow/chemistry/*pathology Bone Marrow Neoplasms/*chemistry/*pathology Fluorescent Antibody Technique Gangliosides/immunology Humans Immunohistochemistry Neuroblastoma/*chemistry/*pathologyFebOBACKGROUND: Except at diagnosis and relapse, when gross disease is present, histologic evaluation is less sensitive than immunocytology (IC) of bone marrow for detecting metastatic neuroblastoma. We examined whether the chance of a positive IC from a single marrow site was comparable to an IC of pooled marrow from multiple sites. PROCEDURE: We carried out 47 marrow examinations on 29 patients with high-risk neuroblastoma on therapy. Each examination consisted of histologic evaluation of four aspirates and two biopsies (six sites), IC of a 2.5-5-mL heparinized sample from a single site (the right posterior iliac crest; IC-RPIC), as well as IC of 8-10 mL of heparinized marrow pooled from bilateral anterior and bilateral posterior iliac crests (IC-pooled). IC was performed using a panel of monoclonal antibodies specific for ganglioside GD2. RESULTS: The number of GD2-positive tumor cells detected by IC-pooled had a strong linear correlation with that by IC-RPIC (R = 0.91), although IC-pooled detected an average of 3.3 times more GD2-positive cells. Of 47 examinations, 15 tested positive by histology (6 sites), 20 by IC- pooled, and 17 by IC-RPIC. Among 29 patients, the level of agreement between IC-RPIC and IC-pooled was generally good (kappa statistic > or = 0.72), giving a false negative rate of < or = 30%. CONCLUSIONS: Compared to conventional histologic examinations, immunocytology of a single marrow aspirate generally agrees with that of marrow pooled from six sites. However, the false negative rate may be too high in the setting of examination prior to bone marrow or stem cell harvest.*http://www.ncbi.nlm.nih.gov/pubmed/9950193Cheung, N K Heller, G Kushner, B H Kramer, K CA-61017/CA/NCI NIH HHS/United States FD-R-001041/FD/FDA HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states Medical and pediatric oncology Med Pediatr Oncol. 1999 Feb;32(2):84-7.%0098-1532 (Print) 0098-1532 (Linking)9950193rDepartment of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. cheungn@mskcc.orgA10.1002/(SICI)1096-911X(199902)32:2<84::AID-MPO2>3.0.CO;2-1 [pii]eng ||7,/Kushner, J. Bradley, G. Young, B. Jordan, R. C.1999HAberrant expression of cyclin A and cyclin B1 proteins in oral carcinoma77-81J Oral Pathol Med282 1999/02/09Carcinoma, Squamous Cell/chemistry/*metabolism/pathology Cross-Sectional Studies Cyclin A/analysis/*biosynthesis Cyclin B/analysis/*biosynthesis Cyclin B1 Female G2 Phase Humans Immunoenzyme Techniques Ki-67 Antigen/analysis Male Middle Aged Mitosis Mouth Floor/chemistry/metabolism/*pathology Mouth Neoplasms/chemistry/*metabolism/pathology Retrospective Studies Statistics, NonparametricFebjCyclins play an important role in regulating the passage of dividing cells through critical checkpoints in the cell cycle. Aberrant expression of cyclin proteins has been found in a number of human cancers, including carcinomas of the head and neck, where amplification of the cyclin D1 gene is a common finding. The objective of this study was to examine cell cycle kinetics in oral carcinomas by determining the expression of the S phase protein cyclin A and the M phase protein cyclin B1. Routinely processed tissue sections of 50 oral squamous cell carcinomas from the floor of the mouth were stained by immunohistochemistry for cyclin A, cyclin B1 and Ki-67 proteins. Ten specimens of normal epithelium from the floor of the mouth were used as controls. The number of cells showing nuclear staining for cyclin A, cyclin B1 and Ki-67 proteins was determined by computer image analysis. There were 17 well-differentiated, 25 moderately differentiated and 8 poorly differentiated tumours. Mean counts for cyclin A (29.50+/-4.10, mean+/-95% CI), cyclin B1 (2.05+/-0.30) and Ki-67 (49.46+/-5.91) proteins in the carcinomas were significantly higher than counts for the normal epithelial controls (cyclin A: 9.30+/-1.72; cyclin B1: 1.01+/-0.36; Ki-67: 17.40+/-4.17). For cyclin A, cyclin B1 and Ki-67, mean staining scores for all tumour grades were significantly higher than controls. There was a strong correlation between Ki-67 and cyclin A scores in all tumour groups (r2=0.68); however, the correlations between cyclin B1 and cyclin A scores (r2=0.35) and between cyclin B1 and Ki-67 scores (r2= 0.39) were weak. We conclude that there is overexpression of cyclin A and cyclin B1 proteins in oral carcinoma. Furthermore, the poor correlations for cyclin B1 scores with other cell cycle indices suggest that there may be aberrant cell cycle progression at the G2/M checkpoint in oral carcinomas.*http://www.ncbi.nlm.nih.gov/pubmed/9950254Kushner, J Bradley, G Young, B Jordan, R C Research Support, Non-U.S. Gov't Denmark Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology J Oral Pathol Med. 1999 Feb;28(2):77-81.%0904-2512 (Print) 0904-2512 (Linking)9950254[Department of Oral Pathology, Faculty of Dentistry, University of Toronto, Ontario, Canada.eng&||7-Kushner, S. A. McElgin, W. T. Kung, M. P. Mozley, P. D. Plossl, K. Meegalla, S. K. Mu, M. Dresel, S. Vessotskie, J. M. Lexow, N. Kung, H. F.1999IKinetic modeling of [99mTc]TRODAT-1: a dopamine transporter imaging agent150-8 J Nucl Med401 1999/02/06Animals Brain/*metabolism/radionuclide imaging Carrier Proteins/*metabolism Dopamine/*metabolism Dopamine Plasma Membrane Transport Proteins Female Humans *Membrane Glycoproteins *Membrane Transport Proteins *Nerve Tissue Proteins Organotechnetium Compounds/*diagnostic use/pharmacokinetics Papio Tomography, Emission-Computed, Single-Photon Tropanes/*diagnostic use/pharmacokineticsJan^ [99mTc]Technetium[2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo [3.2.1] oct-2-yl]-methyl] (2-mercaptoethyl) amino] ethyl] amino] ethane-thiolato(3-)-N2,N2',S2,S2']oxo-[1R-(exo-exo)] ([99mTc] TRODAT-1) is a useful imaging agent for central nervous system dopamine transporters. The purpose of this study was to characterize the in vivo binding potential and kinetic rate constants of this agent in nonhuman primates. METHODS: A series of four SPECT scans were performed on each of two female baboons with a bolus injection of [99mTc]TRODAT-1 (717+/-78 MBq; 19.38+/-2.12 mCi). Dynamic images of the brain were acquired over 4 h using a triple-head camera equipped with fan-beam collimators. Arterial and venous blood were sampled frequently using a peristaltic pump throughout the duration of the study. Regions of interest were drawn on the corresponding MRI scan to which each functional image was coregistered. Using analytical solutions to the three-compartment model with the Levenberg-Marquardt minimization technique, each study was individually fitted to a kinetic parameter vector (method I). Additionally, within each subject, three corresponding intrasubject studies were fitted simultaneously to a single parameter vector by constraining the binding potential, distribution volume and dissociation rate constant to improve the identifiability of the parameter estimates (method II). RESULTS: The results clearly indicated that [99mTc] TRODAT-1 localized in the striatum with slower washout rate than other brain regions. A maximal target/nontarget ratio of 3.5 between striatum and cerebellum was obtained. SPECT image analysis of the striatum yielded unconstrained k3/k4 values of 3.4+/-1.4, 2.4+/-0.7, 3.0+/-1.5, and 4.0+/-10.3, with respective constrained (fixed k4) values of 2.9 +/- 0.4, 2.4 +/- 0.4, 1.7+/-0.4 and 1.8+/-0.4 in one baboon using method I. With method II, the corresponding simultaneously fitted values were 2.1+/-0.3 using no constraints and 2.2+/-0.2 using a fixed k4. The second baboon had similar results. CONCLUSION: These findings suggest that the binding potential and corresponding kinetic rate constants can be reliably estimated in nonhuman primates with dynamic SPECT imaging of the dopamine transporter using a technetium-based tropane analogue. Furthermore, method II parameter vectors compare favorably to those produced using method I based on SEEs.*http://www.ncbi.nlm.nih.gov/pubmed/9935071mKushner, S A McElgin, W T Kung, M P Mozley, P D Plossl, K Meegalla, S K Mu, M Dresel, S Vessotskie, J M Lexow, N Kung, H F NS18509/NS/NINDS NIH HHS/United States NS24538/NS/NINDS NIH HHS/United States Research Support, U.S. Gov't, P.H.S. United states Journal of nuclear medicine : official publication, Society of Nuclear Medicine J Nucl Med. 1999 Jan;40(1):150-8.%0161-5505 (Print) 0161-5505 (Linking)9935071MDepartment of Radiology, University of Pennsylvania, Philadelphia 19104, USA.eng ||7.-Falkner, B. Sherif, K. Sumner, A. Kushner, H.1999AHyperinsulinism and sex hormones in young adult African Americans107-12 Metabolism481 1999/01/270Adult African Continental Ancestry Group Body Mass Index Diabetes Mellitus, Type 2/etiology Female Glucose Tolerance Test Gonadal Steroid Hormones/*blood Humans Hyperinsulinism/blood/complications/*ethnology Insulin Resistance Male Regression Analysis Sex Factors Sex Hormone-Binding Globulin/*metabolismJan Hyperinsulinemia is a risk factor for cardiovascular disease, and is linked with non-insulin-dependent diabetes mellitus (NIDDM), hyperlipidemia, obesity, and hypertension. Sex hormones also play a role in the metabolic alterations associated with the risk for cardiovascular disease. A reduction in sex hormone-binding globulin (SHBG) may be predictive of future NIDDM particularly in women. The postmenopausal decline in estrogen is also associated with an increase in risk factor expression in women. Since African Americans experience a greater prevalence of NIDDM, obesity, and hypertension, conditions associated with hyperinsulinemia, the purpose of this study was to determine if alterations in sex hormone levels are associated with the plasma insulin concentration in young adult African Americans, and to determine if there are sex differences in the effect of insulin on lipids and sex hormones. In a sample of 221 nondiabetic African American men (n = 105) and women (n = 116) with a mean age of 31 years, we examined the relationship of the plasma insulin concentration with the body mass index (BMI), blood pressure, plasma lipids, and sex hormones, including free testosterone, estradiol, and SHBG. Plasma insulin increased with the BMI and other measures of adiposity (P<.001) in men and women. Significant correlations of insulin with plasma lipids were also present in both sexes. There was a significant inverse correlation of insulin with SHBG in both men (r = .28, P = .007) and women (r = .27, P = .02). There was a significant direct correlation of insulin with free testosterone in women (r = .032, P<.001). Stepwise multiple regression analyses with insulin as the dependent variable detected the BMI, triglyceride, and apolipoprotein A1 as significant contributors to the plasma insulin concentration in men. In women, the multiple regression model detected percent body fat, low-density lipoprotein (LDL) cholesterol, and free testosterone as significant contributors to plasma insulin. These data on young African Americans demonstrate a significant relationship between hyperinsulinemia and obesity, atherogenic lipid status, and lower SHBG. In the premenopausal women, the lower SHBG is linked with higher free testosterone, favoring a condition of relative androgen excess.*http://www.ncbi.nlm.nih.gov/pubmed/9920153Falkner, B Sherif, K Sumner, A Kushner, H DK46107/DK/NIDDK NIH HHS/United States HL51547/HL/NHLBI NIH HHS/United States Research Support, U.S. Gov't, P.H.S. United states Metabolism: clinical and experimental Metabolism. 1999 Jan;48(1):107-12.%0026-0495 (Print) 0026-0495 (Linking)9920153Institute for Women's Health and the Department of Medicine, Allegheny University for the Health Sciences, Philadelphia, PA 19129, USA.S0026-0495(99)90018-5 [pii]eng||7/Kushner, L. I.1999:ECG of the month. Atrioventricular block in a Muscovy duck33-6J Am Vet Med Assoc2141 1999/01/15Animals Animals, Wild Bird Diseases/diagnosis/*physiopathology *Ducks Electrocardiography/*veterinary Heart Block/diagnosis/physiopathology/*veterinary MaleJan 1*http://www.ncbi.nlm.nih.gov/pubmed/9887936Kushner, L I Case Reports United states Journal of the American Veterinary Medical Association J Am Vet Med Assoc. 1999 Jan 1;214(1):33-6.%0003-1488 (Print) 0003-1488 (Linking)9887936bMississippi State University, College of Veterinary Medicine, Animal Health Center, MS 39762, USA.eng&||70 Kushner, T.1999DLocal heroes: Belgian refugees in Britain during the First World War1-28 Immigr Minor181 1999/01/01!*Acculturation Belgium/ethnology *Cultural Characteristics *Employment/economics/history/legislation & jurisprudence/psychology Ethnic Groups/education/ethnology/history/legislation & jurisprudence/psychology Great Britain/ethnology *Historiography History, 20th Century Humans Minority Groups/education/history/legislation & jurisprudence/psychology Minority Health/economics/ethnology/history/legislation & jurisprudence *Refugees/education/history/legislation & jurisprudence/psychology *Residential Mobility Socioeconomic Factors World War IeThe Belgians during the First World War represented the largest refugee movement in British history. Despite the size of this influx - at its peak some 250,000 were present in Britain - there has been an almost total absence of reference to them. This article suggests that this neglect is unfortunate both with regard to our understanding of the First World War and the history of refugees during the twentieth century. In particular, this article stresses the importance of local responses and reactions to the refugees and the significance of place in the process of rebuilding lives and identities in Britain.+http://www.ncbi.nlm.nih.gov/pubmed/20169682\Kushner, T Historical Article England Immigrants & minorities Immigr Minor. 1999;18(1):1-28.%0261-9288 (Print) 0261-9288 (Linking)20169682The University of Southampton.10.1080/02619288.1999.9974966eng 4||714Ekdawi, N. S. Nusz, K. J. Diehl, N. N. Mohney, B. G.2010DThe development of myopia among children with intermittent exotropia503-7Am J Ophthalmol1493 2010/02/23Adolescent Child Child, Preschool Disease Progression Exotropia/diagnosis/*physiopathology Female Follow-Up Studies Humans Infant Kaplan-Meier Estimate Male Myopia/diagnosis/*physiopathology Refraction, Ocular/physiology Retrospective StudiesMariPURPOSE: To describe the long-term refractive error changes in children diagnosed with intermittent exotropia (IXT) in a defined population. DESIGN: Retrospective, population-based observational study. METHODS: Using the resources of the Rochester Epidemiology Project, the medical records of all children (<19 years) diagnosed with IXT as residents of Olmsted County, Minnesota, from January 1, 1975 through December 31, 1994 were retrospectively reviewed for any change in refractive error over time. RESULTS: One hundred eighty-four children were diagnosed with IXT during the 20-year study period; 135 (73.4%) had 2 or more refractions separated by a mean of 10 years (range, 1-27 years). The Kaplan-Meier rate of developing myopia in this population was 7.4% by 5 years of age, 46.5% by 10 years, and 91.1% by 20 years. There were 106 patients with 2 or more refractions separated by at least 1 year through 21 years of age, of which 43 underwent surgery and 63 were observed. The annual overall progression was -0.26 diopters (SD +/- 0.24) without a statistically significant difference between the observed and surgical groups (P = .59). CONCLUSION: In this population-based study of children with intermittent exotropia, myopia was calculated to occur in more than 90% of patients by 20 years of age. Observation versus surgical correction did not alter the refractive outcome.+http://www.ncbi.nlm.nih.gov/pubmed/20172074Ekdawi, Noha S Nusz, Kevin J Diehl, Nancy N Mohney, Brian G R01-AR30582/AR/NIAMS NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States American journal of ophthalmology Am J Ophthalmol. 2010 Mar;149(3):503-7.*1879-1891 (Electronic) 0002-9394 (Linking)20172074^Department of Ophthalmology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.5S0002-9394(09)00791-0 [pii] 10.1016/j.ajo.2009.10.009eng>O|?2Wilson, M. Edward20089Pediatric ophthalmology : current thought and a practicalNew YorkSpringer1st2008940289 Wilson, M. Edward, Saunders, Richard, Trivedi, Rupal H. ; [edited by] Wilson, M. Edward, Saunders, Richard, Trivedi, Rupal H.%9783540686323 (hard cover alk. paper)15497159 ||73-Hiles, D. A. Davies, G. T. Costenbader, F. D.1968;Long-term observations on unoperated intermittent exotropia436-42Arch Ophthalmol804 1968/10/01Child Child, Preschool Female Follow-Up Studies Humans Infant Infant, Newborn Male *Strabismus/classification/epidemiology Vision TestsOct*http://www.ncbi.nlm.nih.gov/pubmed/5674800wHiles, D A Davies, G T Costenbader, F D United states Archives of ophthalmology Arch Ophthalmol. 1968 Oct;80(4):436-42.%0003-9950 (Print) 0003-9950 (Linking)5674800eng||74Hiles, D. A. Font, R. L.1968zBilateral intraocular cryptococcosis with unilateral spontaneous regression. Report of a case and review of the literature98-108Am J Ophthalmol651 1968/01/01e*Cryptococcosis/pathology *Eye Diseases Fundus Oculi Humans Male Meningitis/complications Middle AgedJan*http://www.ncbi.nlm.nih.gov/pubmed/5635576lHiles, D A Font, R L United states American journal of ophthalmology Am J Ophthalmol. 1968 Jan;65(1):98-108.%0002-9394 (Print) 0002-9394 (Linking)5635576engw||75Solan, H. A. Mozlin, R.1986oThe correlations of perceptual-motor maturation to readiness and reading in kindergarten and the primary grades28-35J Am Optom Assoc571 1986/01/01*Auditory Perception Automatism Child Child Development Child, Preschool Cognition Female Humans *Learning Male *Motor Skills Prognosis *Reading *Visual Perception VocabularyJan This study lends further support to the additive nature of perceptual-motor skills and their correlation with reading. Using multivariate analysis, the investigation quantifies the extent to which success in readiness and reading in kindergarten and grades one and two is related to perceptual-motor organization. In addition to establishing concurrent validity, the results support the hypothesis that perceptual skills in kindergarten predict reading proficiency at the end of grade one. Perceptual skills play a significant role in learning to read in the primary grades. Beyond grade two, however, when cognitive and language skills appear to have a greater influence in normal children, perceptual organization remains a necessary but not a significant condition for learning.*http://www.ncbi.nlm.nih.gov/pubmed/3950309ySolan, H A Mozlin, R United states Journal of the American Optometric Association J Am Optom Assoc. 1986 Jan;57(1):28-35.%0003-0244 (Print) 0003-0244 (Linking)3950309engE||76)von Noorden, G. K. Murray, E. Wong, S. Y.19861Superior oblique paralysis. A review of 270 cases1771-6Arch Ophthalmol10412 1986/12/01Adolescent Adult Aged Animals Child Child, Preschool Female Head Humans Infant Male Middle Aged Ophthalmoplegia/classification/congenital/physiopathology/*surgery PostureDecTIn 270 patients with superior oblique paralyses treated between 1973 and 1984, congenital and traumatic causes were most frequent, and one fourth of all traumatic cases had bilateral involvement. Among the diagnostic features distinguishing bilateral from unilateral paralysis were a right hypertropia in left gaze and left hypertropia in right gaze, and a positive Bielschowsky test on tilting the head toward either shoulder. However, absence of either sign did not exclude bilateral paralysis. Large excyclotropia and a V-pattern esotropia are suggestive of but not diagnostic for bilateral paralysis. Complaints about cyclotropia are limited to acquired paralysis. Cyclotropia in the normal eye, head tilt toward the involved side, or absence of any abnormal head posture limits the diagnostic value of these associated signs. Overshoot of the contralateral superior oblique occurred in 19% of the patients and is thought to be caused by contracture of the ipsilateral superior rectus muscle. Surgical treatment in 112 patients resulted in an 85% cure rate with an average of 1.45 operations per patient.*http://www.ncbi.nlm.nih.gov/pubmed/3789976.von Noorden, G K Murray, E Wong, S Y EY 01120/EY/NEI NIH HHS/United States EY 02520/EY/NEI NIH HHS/United States EY 07001/EY/NEI NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United states Archives of ophthalmology Arch Ophthalmol. 1986 Dec;104(12):1771-6.%0003-9950 (Print) 0003-9950 (Linking)3789976eng||77 Mejias, E.19867Superior oblique muscle paralysis in the CREST syndrome27-9P R Health Sci J51 1986/04/01Cranial Nerve Diseases/complications Diplopia/*complications Female Humans Middle Aged Paralysis/*complications Scleroderma, Systemic/*complications Syndrome Trochlear NerveAprA 54 year old male with the CREST (Calcinosis, Raynauds, Esophageal hypomotility, Sclerodactyly, Telangiectasia) variant of progressive systemic sclerosis (PSS) presented with vertical diplopia diagnosed as a left superior oblique muscle paralysis. Although cranial nerves abnormalities have been reported in PSS, to our knowledge this is the first report of the CREST syndrome in association with a IV nerve palsy in whom no other etiology could be found.*http://www.ncbi.nlm.nih.gov/pubmed/3797624lMejias, E Case Reports Puerto rico Puerto Rico health sciences journal P R Health Sci J. 1986 Apr;5(1):27-9.%0738-0658 (Print) 0738-0658 (Linking)3797624eng||78-Hullo, A. Magnard, P. Bongard, C. Bourron, M.1986B[Surgical indications in paralysis of the superior oblique muscle]415-8Bull Soc Ophtalmol Fr863 1986/03/01Adult Child Craniocerebral Trauma/complications Female Humans Male Microsurgery/methods Ophthalmoplegia/congenital/etiology/*surgeryMar*http://www.ncbi.nlm.nih.gov/pubmed/3802357Hullo, A Magnard, P Bongard, C Bourron, M Case Reports France Bulletin des societes d'ophtalmologie de France Bull Soc Ophtalmol Fr. 1986 Mar;86(3):415-8.%0081-1270 (Print) 0081-1270 (Linking)3802357<Indications operatoires dans le paralysies du grand oblique.fre~|794King, A. J. Stacey, E. Stephenson, G. Trimble, R. B.1995=Spontaneous recovery rates for unilateral sixth nerve palsies476-8 Eye (Lond) 9 ( Pt 4) 1995/01/01*Abducens Nerve Adolescent Adult Aged Aged, 80 and over Child Child, Preschool Cranial Nerve Diseases/*complications Diplopia/etiology Female Humans Male Middle Aged Ophthalmoplegia/*etiology Remission, Spontaneous Time FactorsTwo hundred and thirteen patients with unilateral isolated sixth nerve palsies were assessed to determine what proportion of them underwent spontaneous recovery and over what period of time this recovery occurred. All were primary ophthalmic referrals from which trauma was excluded. In all, 78.4% of patients experienced spontaneous recovery of their palsy, 36.6% recovering by 8 weeks and 73.7% by 24 weeks. Only 16.4% failed to recover. Of this group, however, nearly 40% had serious underlying pathology accounting for their palsy.*http://www.ncbi.nlm.nih.gov/pubmed/7498570nKing, A J Stacey, E Stephenson, G Trimble, R B England Eye (London, England) Eye (Lond). 1995;9 ( Pt 4):476-8.%0950-222X (Print) 0950-222X (Linking)7498570University of Leicester, UK.eng?:Howell, Edwin R1991CThe Differential Diagnosis of Accommodation / Convergence Disorders20-26Behavioural OptometryJanuary/February!||7;von Noorden, G. K. Olivier, P.1982.Superior oblique tenectomy in Brown's syndrome303-9 Ophthalmology894 1982/04/01Adolescent Child Child, Preschool Female Follow-Up Studies Head Humans Infant Infant, Newborn Male Oculomotor Muscles/*surgery Ophthalmoplegia/complications/diagnosis/*surgery Postoperative Complications Posture Syndrome Tendons/surgeryAprSince its description in 1950, numerous surgical techniques have been advocated to treat Brown's superior oblique tendon sheath syndrome. Of these, a tenectomy of the homolateral superior oblique has emerged as the most effective method. However, an iatrogenically produced superior oblique paralysis has been found to be a frequent complication of this procedure. Of 12 patients with Brown's syndrome treated with a superior oblique tenectomy, this problem was encountered in eight patients, and additional surgery became necessary in each instance. The clinical management of such patients presents special problems and their solution will be illustrated by two case reports.*http://www.ncbi.nlm.nih.gov/pubmed/7099550von Noorden, G K Olivier, P Case Reports Research Support, Non-U.S. Gov't United states Ophthalmology Ophthalmology. 1982 Apr;89(4):303-9.%0161-6420 (Print) 0161-6420 (Linking)7099550eng!||7<von Noorden, G. K. Olivier, P.1982.Superior oblique tenectomy in Brown's syndrome303-9 Ophthalmology894 1982/04/01Adolescent Child Child, Preschool Female Follow-Up Studies Head Humans Infant Infant, Newborn Male Oculomotor Muscles/*surgery Ophthalmoplegia/complications/diagnosis/*surgery Postoperative Complications Posture Syndrome Tendons/surgeryAprSince its description in 1950, numerous surgical techniques have been advocated to treat Brown's superior oblique tendon sheath syndrome. Of these, a tenectomy of the homolateral superior oblique has emerged as the most effective method. However, an iatrogenically produced superior oblique paralysis has been found to be a frequent complication of this procedure. Of 12 patients with Brown's syndrome treated with a superior oblique tenectomy, this problem was encountered in eight patients, and additional surgery became necessary in each instance. The clinical management of such patients presents special problems and their solution will be illustrated by two case reports.*http://www.ncbi.nlm.nih.gov/pubmed/7099550von Noorden, G K Olivier, P Case Reports Research Support, Non-U.S. Gov't United states Ophthalmology Ophthalmology. 1982 Apr;89(4):303-9.%0161-6420 (Print) 0161-6420 (Linking)7099550eng||7=Reny, A. Brichet, B.19729[Stilling-Turk-Duane's syndrome. Electromyographic study]1063-83Ann Ocul (Paris)20510 1972/10/01Abducens Nerve/abnormalities *Electromyography Female Humans Male Oculomotor Muscles/*abnormalities/innervation/physiopathology Oculomotor Nerve/abnormalities Ophthalmoplegia/classification/*diagnosis/physiopathologyOct*http://www.ncbi.nlm.nih.gov/pubmed/4659625[Reny, A Brichet, B France Annales d'oculistique Ann Ocul (Paris). 1972 Oct;205(10):1063-83.%0003-4371 (Print) 0003-4371 (Linking)4659625>Le syndrome de Stilling-Turk-Duane. Etude electromyographique.fre>||7>Scott, A. B. Wong, G. Y.1972,Duane's syndrome. An electromyographic study140-7Arch Ophthalmol872 1972/02/01Adolescent Adult Child *Electromyography Eye/innervation *Eye Movements Eyelids/innervation Humans Infant Middle Aged Oculomotor Muscles/innervation/surgery Oculomotor Nerve/physiopathology Ophthalmoplegia/*physiopathologyFeb*http://www.ncbi.nlm.nih.gov/pubmed/5057862cScott, A B Wong, G Y United states Archives of ophthalmology Arch Ophthalmol. 1972 Feb;87(2):140-7.%0003-9950 (Print) 0003-9950 (Linking)5057862eng{~|7?-Blodi, F. C. Vanallen, M. W. Yarbrough, J. C.1964ADuane's Syndrome: A Brain-Stem Lesion. An Electromyographic Study802-9$Trans Am Acad Ophthalmol Otolaryngol68 1964/09/01Q*Adolescent *Brain Diseases *Brain Stem *Child *Electromyography *OphthalmoplegiaSep-Oct+http://www.ncbi.nlm.nih.gov/pubmed/14211237Blodi, f c Vanallen, m w Yarbrough, j c United states Transactions - American Academy of Ophthalmology and Otolaryngology. American Academy of Ophthalmology and Otolaryngology Trans Am Acad Ophthalmol Otolaryngol. 1964 Sep-Oct;68:802-9.%0002-7154 (Print) 0002-7154 (Linking)14211237eng~|7@-Blodi, F. C. Vanallen, M. W. Yarbrough, J. C.1964ADuane's Syndrome: A Brain Stem Lesion. An Electromyographic Study171-7Arch Ophthalmol72 1964/08/01>*Brain Diseases *Brain Stem *Electromyography *OphthalmoplegiaAug+http://www.ncbi.nlm.nih.gov/pubmed/14162939sBlodi, f c Vanallen, m w Yarbrough, j c United states Archives of ophthalmology Arch Ophthalmol. 1964 Aug;72:171-7.%0003-9950 (Print) 0003-9950 (Linking)14162939engN||7A Zhang, F.1999A[Clinical features of 201 cases with Duane's retraction syndrome]280-2Zhonghua Yan Ke Za Zhi354 2002/02/12Adolescent Adult Child Child, Preschool Diagnosis, Differential Duane Retraction Syndrome/*diagnosis Female Humans Infant Male Retrospective StudiesJulOBJECTIVE: To summarize the clinical features of 201 cases with Duane's retraction syndrome (DRS) and discuss its differential diagnosis. METHODS: The 201 cases in 1979 similar 1996 were retrospectively summarized. The clinical features including chief complaints, sex distribution, age at first visit, laterality, type of presentation, ocular deviation in the primary position, refractive errors, amblyopia, globe retraction, change of the palpebral fissure, upshoot and downshoot in adduction, binocular single vision, and its associated ocular and non-ocular anomalies were analyzed. RESULTS: There were 99 males and 102 females with a female-to-male ratio of 1:1.65.88% of DRS cases had left eye involvement with two-to-one predilection for the left eye. The most common form of the syndrome was type 1 (184 patients, 91.54%). Exotropia was the most common deviation in the primary gaze (72 patients, 35.82%). Among 118 patients, most had abduction deficits, globe retraction in adduction, and face-turn for maintaining single binocular vision. Crocodile tears (26 patients, 12.93%) were the most frequently encountered ocular abnormality. CONCLUSIONS: Diagnosis of DRS in a typical case is not difficult, however, children with bilateral abduction deficits which may mimic DRS must be differentiated from the following four motility disorders, namely, abducens nerve palsy, Moebius' syndrome, congenital oculomotor apraxia, and congenital or infantile esotropia.+http://www.ncbi.nlm.nih.gov/pubmed/11835823Zhang, F English Abstract China [Zhonghua yan ke za zhi] Chinese journal of ophthalmology Zhonghua Yan Ke Za Zhi. 1999 Jul;35(4):280-2.%0412-4081 (Print) 0412-4081 (Linking)11835823fDepartment of Ophthalmology, Affiliated Tong Ren Hospital, Capital Medical University, Beijing 100730.chiU||7B Zhang, F.1997?Clinical features of 201 cases with Duane's retraction syndrome789-91Chin Med J (Engl)11010 1998/06/27Abducens Nerve Adolescent Adult Child Child, Preschool Diagnosis, Differential Duane Retraction Syndrome/*diagnosis Facial Paralysis/diagnosis Female Humans Infant Male Ophthalmoplegia/diagnosis Retrospective StudiesOctOBJECTIVE: To summarize the clinical features of 201 cases with Duane's retraction syndrome (DRS) and discuss its differential diagnosis. METHODS: We retrospectively summarized the 201 cases from 1979 to 1996. The clinical features including chief complaints, sexual distribution, age at first visit, laterality, type of presentation, ocular deviation in the primary position, refractive errors, amblyopia, globe retraction, change of the palpebral fissure, upshoot and downshoot in adduction, binocular single vision, and its associated ocular and non-ocular anomalies were analysed. RESULTS: There were 99 males and 102 females with a female-to-male ratio 1:1. The 65.88% of DRS cases had left eye involvement with two-to-one predilection for the left eye. The most common form of the syndrome was type I (184 patients, 91.54%). Exotropia was the most common deviation in the primary gaze (72 patients, 35.8%). Among 118 patients, most had abduction deficits, globe retraction in adduction, and faceturn as to maintaining single binocular vision. Crocodial tears (26 patients, 11.93%) was the most frequently encounted ocular abnormalities. CONCLUSIONS: Diagnosis of DRS in a typical case is not difficult, however, children with bilateral abduction deficits which may mimic DRS must be differentiated from the following four motility disorders, namely, abducens nerve palsy, Moebius syndrome, congenital oculomotor apraxia, and congenital or infantile esotropia.*http://www.ncbi.nlm.nih.gov/pubmed/9642311RZhang, F China Chinese medical journal Chin Med J (Engl). 1997 Oct;110(10):789-91.%0366-6999 (Print) 0366-6999 (Linking)9642311fDepartment of Ophthalmology, Affiliated Tong Ren Hospital, Capital Medical University, Beijing, China.eng||7C!Tredici, T. D. von Noorden, G. K.1985;Are anisometropia and amblyopia common in Duane's syndrome?23-5J Pediatr Ophthalmol Strabismus221 1985/01/01Adolescent Amblyopia/*epidemiology Child Duane Retraction Syndrome/*complications Female Humans Male Ophthalmoplegia/*complications Refractive Errors/*epidemiologyJan-FebBSeventy cases of Duane's syndrome are summarized with particular attention to the prevalence of anisometropia and amblyopia. We found a 17% prevalence of anisometropia and a 3% prevalence of amblyopia among these patients. Amblyopia and anisometropia are not more common in Duane's syndrome than in the general population.*http://www.ncbi.nlm.nih.gov/pubmed/3981378Tredici, T D von Noorden, G K Research Support, Non-U.S. Gov't United states Journal of pediatric ophthalmology and strabismus J Pediatr Ophthalmol Strabismus. 1985 Jan-Feb;22(1):23-5.%0191-3913 (Print) 0191-3913 (Linking)3981378eng||7DKirkham, T. H.1970/Anisometropia and amblyopia in Duane's syndrome774-7Am J Ophthalmol695 1970/05/01Amblyopia/*complications Functional Laterality Humans Myopia/complications Ophthalmoplegia/*complications Refractive Errors/*complications Vision, Ocular Visual AcuityMay*http://www.ncbi.nlm.nih.gov/pubmed/5441354cKirkham, T H United states American journal of ophthalmology Am J Ophthalmol. 1970 May;69(5):774-7.%0002-9394 (Print) 0002-9394 (Linking)5441354engg||7E9Cnotliwy, M. Turowski, R. Sych, Z. Gutowski, P. Sobus, A.2000k[Factors influencing the length of hospital stay of patients qualified for elective carotid endarterectomy]597-602Wiad Lek5311-12 2001/03/15mAdult Aged Carotid Artery Diseases/epidemiology/surgery Comorbidity Diabetes Mellitus, Type 1/epidemiology Diabetic Angiopathies/epidemiology/surgery Endarterectomy, Carotid/*statistics & numerical data Female Humans Length of Stay/*statistics & numerical data Male Middle Aged Poland Preoperative Care/statistics & numerical data Retrospective Studies Risk Factors,The aim of this retrospective study was to identify the factors affecting long hospital stay of patients who underwent carotid endarterectomy. The analysis was based on 233 records of all patients operated on between 1995 and 1998. We have found that the main reasons of lengthened preoperative hospitalization were: insulin dependent diabetes and admission on the day excluding the chance of operation in a short time. Postoperatively, monitoring in intensive care unit and unfounded delay of discharge were the leading reasons of prolonged hospital stay.+http://www.ncbi.nlm.nih.gov/pubmed/11247400Cnotliwy, M Turowski, R Sych, Z Gutowski, P Sobus, A English Abstract Poland Wiadomosci lekarskie (Warsaw, Poland : 1960) Wiad Lek. 2000;53(11-12):597-602.%0043-5147 (Print) 0043-5147 (Linking)11247400uCzynniki wplywajace na dlugosc okresu hospitalizacji chorych kwalifikowanych do operacji udroznienia tetnic szyjnych.]Katedry i Kliniki Chirurgii Ogolnej i Naczyniowej Pomorskiej Akademii Medycznej w Szczecinie.pol '||7F?Carcenac, M. Gutowski, M. Rouanet, P. Larroque, C. Pelegrin, A.20004[Cancer immunophotodetection and immunophototherapy]804-12 Bull Cancer8711 2000/12/23Animals Antibodies, Monoclonal/diagnostic use/therapeutic use Coloring Agents/diagnostic use Humans Immunologic Tests/*methods Immunotherapy/*methods Immunotoxins/diagnostic use/therapeutic use Mice Neoplasms/*diagnosis/*therapy Photochemotherapy/*methodsNovSome dyes can be used for cancer diagnosis and therapy. Following administration, the dye concentrate with some specificity in the tumor and can react to an irradiation with light. Some excited dyes can be fluorescent allowing detection of very small tumors. Some other dye can be phototoxic and lead to the destruction of the tumor. These attractive techniques are however limited because of the too low tumor specificity of the currently used dyes (hematoporphyrin and phthalocyanine). A new strategy has be developed in which the fluorescent or phototoxic dye is coupled to an antibody directed against a tumor associated antigen. This approach allow the selection of the dye only for its optimal photochemical properties, the antibody being used as carrier to concentrate the dye in the tumor. Many experimental immunophototherapy studies have been performed with different phototoxic dyes. Some results are encouraging but the involved mechanisms are complex and they limit the current clinical applications of immunophototherapy. Concerning immunophotodetection, two dyes have been coupled to anti-tumor antibodies: fluorescein and indocyanin. The antibody-dye conjugates have been evaluated in experimental studies and in pilot clinical trials. The most recent results concern the use of this technique in intraoperative situation and to visualize neo-vascularization. Immunophotodetection gives a very precise image of tumors. The detected tumor nodules are in the millimeter range. However, according to the limited light pathway in the tumor, this technique can be applied only to cutaneous areas, endoscopy accessible areas and intraopearative situations. Immunophotodetection is an attractive imaging technique using antibodies.+http://www.ncbi.nlm.nih.gov/pubmed/11125289Carcenac, M Gutowski, M Rouanet, P Larroque, C Pelegrin, A English Abstract Review France Bulletin du cancer Bull Cancer. 2000 Nov;87(11):804-12.%0007-4551 (Print) 0007-4551 (Linking)111252898Immunophotodetection et immunophototherapie des cancers.^JE2176, universite Montpellier I, CRLC Val-d'Aurelle-Paul-Lamarque, 34298 Montpellier Cedex 5.fre||7G Gutowski, K. A. Orenstein, H. H.2000aRestoration of elbow flexion after brachial plexus injury: the role of nerve and muscle transfers#1348-57; quiz 1358; discussion 1359Plast Reconstr Surg1066 2000/11/18Accessory Nerve/transplantation Brachial Plexus/*injuries Elbow Joint/*physiopathology Humans Intercostal Nerves/transplantation Muscle, Skeletal/*transplantation *Nerve Transfer Phrenic Nerve/transplantation *Range of Motion, ArticularNovRBrachial plexus trauma results in a variable loss of upper extremity function. The restoration of this function requires elbow flexion of adequate strength and range of motion. A proper evaluation of brachial plexus lesions is a prerequisite to any reconstructive procedure, and appropriate guidelines are presented. One option for restoring elbow flexion is a nerve transfer. The best results with this procedure are obtained in young patients treated within 6 months of injury. Another option is a free or pedicled muscle transfer, which should be considered in older patients or patients treated more than 6 months after an injury. Muscle transfers may also be used to augment the results of nerve transfer procedures. Choices and clinical results of donor nerves and muscle for transfer are discussed, and an algorithm for treatment is presented.+http://www.ncbi.nlm.nih.gov/pubmed/11083569Gutowski, K A Orenstein, H H United states Plastic and reconstructive surgery Plast Reconstr Surg. 2000 Nov;106(6):1348-57; quiz 1358; discussion 1359.0032-1052 (Print)11083569eInstitute of Reconstructive Plastic Surgery, New York University, NY 10016, USA. kagutowski@yahoo.comeng||7H=Gutowski, K. A. Olivier, W. A. Mehrara, B. J. Friedman, D. W.2000WArteriovenous malformation of a persistent median artery with a bifurcated median nerve1336-9Plast Reconstr Surg1066 2000/11/18uArteriovenous Malformations/*complications/*surgery Child Humans Male Median Nerve/*abnormalities Wrist/*blood supplyNovA patient with arteriovenous malformations of the volar forearm and hand arising from a persistent median artery with an associated bifid median nerve is presented. Surgeons should be aware of high median nerve bifurcations, particularly when a persistent median artery is identified, and should remember that additional structures that can lead to nerve compression may be present in the carpal tunnel. Specifically, more than one median nerve may need to be identified and protected in such cases.+http://www.ncbi.nlm.nih.gov/pubmed/11083565Gutowski, K A Olivier, W A Mehrara, B J Friedman, D W Case Reports United states Plastic and reconstructive surgery Plast Reconstr Surg. 2000 Nov;106(6):1336-9.0032-1052 (Print)11083565PInstitute of Reconstructive Plastic Surgery, New York University, NY 10016, USA.eng ||7I(Liu, M. Y. Gutowski, S. Sternweis, P. C.2001NThe C terminus of mammalian phospholipase D is required for catalytic activity5556-62 J Biol Chem2768 2000/11/18Animals *Catalytic Domain Humans Mutation Peptide Fragments/metabolism/pharmacology Phospholipase D/genetics/*metabolism Recombinant Proteins/metabolismFeb 23rThe activity of phospholipase D (PLD) is regulated by a variety of hormonal stimuli and provides a mechanistic pathway for response of cells to extracellular stimuli. The two identified mammalian PLD enzymes possess highly homologous C termini, which are required for catalytic activity. Mutational analysis of PLD1 and PLD2 reveals that modification of as little as the C-terminal threonine or the addition of a single alanine attenuates activity of the enzyme. Protein folding appears to be intact because mutant enzymes express to similar levels in Sf9 cells and addition of peptides representing the C-terminal amino acids, including the simple hexamer PMEVWT, restores partial activity to several of the mutants. Analysis of several mutants suggests a requirement for the hydrophobic reside at the -2-position but not an absolute requirement for the hydroxyl side chain of threonine at the C terminus. The inability of peptides amidated at their C termini to effect restoration of activity indicates the involvement of the C-terminal alpha carboxyl group in functional activity of these enzymes. The ability of peptides to restore activity to PLD enzymes mutated at the C terminus suggests a flexible interaction of this portion of the molecule with a catalytic core constructed on conserved HKD motifs. Participation of these C termini residues in either stabilization of the catalytic site or the enzymatic reaction itself remains to be determined. This requirement for the C terminus provides an excellent potential site for interaction with regulatory proteins that may either enhance or down-regulate the activity of these enzymes in vitro.+http://www.ncbi.nlm.nih.gov/pubmed/11083860Liu, M Y Gutowski, S Sternweis, P C GM31954/GM/NIGMS NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States The Journal of biological chemistry J Biol Chem. 2001 Feb 23;276(8):5556-62. Epub 2000 Nov 16.%0021-9258 (Print) 0021-9258 (Linking)11083860kDepartment of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9041, USA.'10.1074/jbc.M006404200 M006404200 [pii]eng||7J+Gutowski, M. Skurski, P. Li, X. Wang, L. S.2000W(MgO)(-)(n) (n = 1-5) clusters: multipole-bound anions and photodetachment spectroscopy3145-8 Phys Rev Lett8515 2000/10/06Oct 9Photoelectron spectra of (MgO)(-)(n) (n = 1-5) reveal a surprising trend: The electron binding energy decreases from n = 1 to 4, and then increases from 4 to 5. Ab initio calculations suggest this pattern is related to the electrostatic interaction between the extra electron and the charge distribution of the neutral cluster. This interaction is significant in MgO (-) and (MgO)-5, for which the lowest nonvanishing multipole moment (LNM) is a dipole; it is smaller for (MgO)-2 and (MgO)-3, for which a quadrupole is the LNM; and it is the smallest for (MgO)-4, for which an octopole is the LNM. The cubic (MgO)-4 is the first octopole-bound anion yet observed experimentally and characterized theoretically.+http://www.ncbi.nlm.nih.gov/pubmed/11019287uGutowski, M Skurski, P Li, X Wang, L S United States Physical review letters Phys Rev Lett. 2000 Oct 9;85(15):3145-8.%0031-9007 (Print) 0031-9007 (Linking)11019287tMaterials Resources, Pacific Northwest National Laboratory, Richland, Washington 99352, USA. maciej.gutowski@pnl.goveng.||7K7Evans, J. C. Frayling, T. M. Ellard, S. Gutowski, N. J.2000xConfirmation of linkage of Duane's syndrome and refinement of the disease locus to an 8.8-cM interval on chromosome 2q31636-8 Hum Genet1066 2000/08/15Chromosome Mapping Chromosomes, Human, Pair 2/*genetics Duane Retraction Syndrome/*genetics Female Genes, Dominant/genetics Genetic Linkage/*genetics Haplotypes/genetics Humans Lod Score Male Microsatellite Repeats PedigreeJunDuane's syndrome is a congenital abnormality of eye movement, which may be inherited as an autosomal dominant trait but usually occurs sporadically. Genetic mapping in a Mexican family has recently identified a locus for Duane's syndrome within a 17.8-cM region of chromosome 2q31. The region was flanked by the microsatellite markers D2S2330 and D2S364. We performed linkage and haplotype analysis in a four-generation UK family with autosomal dominant transmission of Duane's syndrome. Linkage to 2q31 was confirmed with a maximum logarithm of differences (lod) score of 3.3 at theta = 0. The genetic interval was reduced to an 8.8-cM region between markers D2S326 and D2S364 that includes the candidate homeobox D gene cluster.+http://www.ncbi.nlm.nih.gov/pubmed/10942112Evans, J C Frayling, T M Ellard, S Gutowski, N J Research Support, Non-U.S. Gov't Germany Human genetics Hum Genet. 2000 Jun;106(6):636-8.%0340-6717 (Print) 0340-6717 (Linking)10942112Molecular Genetics, Division of Clinical Science, School of Postgraduate Medicine and Health Sciences, University of Exeter, UK.eng `||7LgMonneret, G. Seffert, O. Debard, A. L. Gutowski, M. C. Couprie, N. Larbre, J. P. Tebib, J. Bienvenu, J.2000|[Standardization and automation of HLA B27 typing by flow cytometry: validation and comparison with microlymphocytotoxicity]461-6Ann Biol Clin (Paris)584 2000/08/10Automation/methods/standards Cytotoxicity Tests, Immunologic/*methods Female Flow Cytometry/*methods/standards HLA-B27 Antigen/*blood/genetics Histocompatibility Testing/*methods/standards Humans Male Middle Aged Phenotype Quality Control Spondylitis, Ankylosing/diagnosis/immunologyJul-AugOne of the strongest known association between human leukocyte antigen (HLA) phenotype and disease is that of ankylosing spondylitis and HLA-B27. Thus, the determination of HLA-B27 status is an useful tool in the diagnosis of ankylosing spondylitis. To date, the 2 reference methods for HLA typing (microlymphocytotoxicity and molecular biology techniques), are costly in terms of both technician time and materials, and require a great deal of experience. In total, these techniques are not well-suited for routine application in clinical immunology laboratories. Use of flow cytometry has recently been applied for HLA-B27 typing. Nevertheless, it requires an extensive validation protocol. We developed a flow cytometry technique as standardized as possible (whole blood, automated lysing system, automated photomultiplier voltage calibration, definition of thresholds stable with time) and validated our results by comparison with microlymphocytotoxicity. In total, 326 samples were analyzed. We found 99% of concordant results between the 2 techniques, and neither false positive results nor false negative results with flow cytometry could be observed. These results illustrate the reliability of the protocol. It should be remembered that reference technique remains necessary to confirm the few results (< 1%) found in "grey zone" by flow cytometry. Standardization of flow cytometry techniques, as described in this work for HLA B27, seems to be a reasonable goal for the next decade in clinical immunology laboratories.+http://www.ncbi.nlm.nih.gov/pubmed/10932047Monneret, G Seffert, O Debard, A L Gutowski, M C Couprie, N Larbre, J P Tebib, J Bienvenu, J Comparative Study English Abstract France Annales de biologie clinique Ann Biol Clin (Paris). 2000 Jul-Aug;58(4):461-6.%0003-3898 (Print) 0003-3898 (Linking)10932047Standardisation et automatisation du typage HLA B27 par une technique cytofluorimetrique: validation par comparaison a la microlymphocytoxicite.7Laboratoire d'immunologie, Centre hospitalier Lyon-Sud.fre|t7MGutowski, W. D.2000&Access to the morning-after pill in BC1554CMAJ16211 2000/06/22ZBritish Columbia *Contraceptives, Postcoital Drug Prescriptions *Ethics Humans PharmacistsMay 30+http://www.ncbi.nlm.nih.gov/pubmed/10862225Gutowski, W D Comment Letter Canada CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne CMAJ. 2000 May 30;162(11):1554.%0820-3946 (Print) 0820-3946 (Linking)123133010862225eng&||7N+Cunningham, B. L. Lokeh, A. Gutowski, K. A.2000TSaline-filled breast implant safety and efficacy: a multicenter retrospective review2143-9; discussion 2150-1Plast Reconstr Surg1056 2000/06/062Breast Implantation/adverse effects/statistics & numerical data *Breast Implants/adverse effects/statistics & numerical data Female Follow-Up Studies Humans Outcome Assessment (Health Care) Patient Satisfaction Prosthesis Failure Retrospective Studies Risk Factors Safety *Sodium Chloride Survival AnalysisMay Our center undertook an industry-funded, outcomes-based, multicenter, retrospective review to evaluate the safety and efficacy of saline-filled breast implants. Our review was part of a pre-market approval review process mandated by the U.S. Food and Drug Administration. The design of our review was modeled on a Plastic Surgery Educational Foundation outcomes study previously conducted by our center. For this study, several significant changes were made to our previous protocol, including improved patient tracking, stronger biostatistical support, and a mandatory 10-year minimum patient follow-up period. Physician-reported and patient-reported data on 450 patients with 882 saline-filled breast implants placed between January 1, 1980, and June 30, 1986, were obtained. Mean patient follow-up period was 13.0 years. Most implants (93.9 percent) were placed for breast augmentation. Seventy-four percent were placed in a submammary position; 25.6 percent, subpectorally; and 0.2 percent, subcutaneously. The overall complication rate was 20.2 percent. Reoperation for capsular contracture or implant deflation was necessary in 104 of 450 patients (23.1 percent). Deflation occurred in 73 implants (8.3 percent) and was underreported according to the physicians' record review alone. This deflation rate is higher than the 5.5 percent previously reported by our center. However, 26 of these 73 deflations (35.6 percent) occurred in a single cohort of patients at one center using Surgitek saline implants. If this cohort is excluded, the deflation rate drops to 5.8 percent, a figure more consistent with data published in the literature and found in our previous study. Of the 73 deflations, spontaneous deflation was reported for 50 (74.6 percent), and the remainder were iatrogenic. Actuarial survival of the non-Surgitek implants was 98.4 percent to 99.8 percent at 5 years and 96.9 percent to 98.9 percent at 10 years (95 percent confidence interval). Risk factors for implant deflation included the use of Surgitek saline-filled implants (odds ratio = 17.5, p < 0.01), use of Heyer-Schulte and Mentor model 1800 implants (odds ratio = 3.0, p < 0.01), and implant size greater than 450 cc (odds ratio = 1.01, p < 0.02). Risk factors for capsular contracture included submammary implant position (odds ratio = 2.05, p = 0.03) and implant size greater than 450 cc (odds ratio = 1.01, p < 0.01). Overall, satisfaction was high: 93 percent of patients were "satisfied" or "very satisfied" with their implants. As in our earlier study, risk factors for patient dissatisfaction were reconstruction after mastectomy (odds ratio = 7.6, p = 0.011), significant breast firmness (odds ratio = 6.2, p < 0.001), and patient desire for smaller implants (odds ratio = 3.0, p = 0.020). In conclusion, our review provides additional outcomes-based evidence that saline-filled breast implants remain a safe, effective alternative to silicone gel-filled models.+http://www.ncbi.nlm.nih.gov/pubmed/10839417Cunningham, B L Lokeh, A Gutowski, K A Multicenter Study United states Plastic and reconstructive surgery Plast Reconstr Surg. 2000 May;105(6):2143-9; discussion 2150-1.0032-1052 (Print)10839417}Division of Plastic and Reconstructive Surgery, University of Minnesota Medical School, Minneapolis, USA. cunni001@tc.umn.edueng||7OGutowski, N. J.2000Duane's syndrome145-9 Eur J Neurol72 2000/05/16A*Duane Retraction Syndrome/classification/genetics/therapy HumansMarDuane's syndrome is an unusual congenital form of strabismus where there is paradoxical anomalous lateral rectus innervation of the affected eye due to misdirection of axons destined for the medial rectus. Three types of Duane's syndrome are recognized. Most cases of Duane's syndrome are sporadic but up to 10% are familial, usually with autosomal dominant inheritance. Several autosomal dominant syndromes with dysmorphic features are associated with Duane's syndrome. Chromosomal loci for genes contributing to Duane's syndrome have been suggested at 4q, 8q and 22q. Duane's syndrome is heterogeneous at multiple levels with variations in its ocular manifestations, accompanying systemic manifestations and in the chromosomal loci with which it may be associated. The definition clinically and genetically of the various subgroups of Duane's syndrome will provide a valuable insight into brainstem axonal guidance to the extraocular muscles during human development.+http://www.ncbi.nlm.nih.gov/pubmed/10809934Gutowski, N J Review England European journal of neurology : the official journal of the European Federation of Neurological Societies Eur J Neurol. 2000 Mar;7(2):145-9.%1351-5101 (Print) 1351-5101 (Linking)10809934gDepartment of Neurology, Royal Devon and Exeter Hospital, Exeter EX2 5DW, UK. n.j.gutowski@exeter.ac.uk ene029 [pii]engi||7P4Monneret, G. Benoit, Y. Gutowski, M. C. Bienvenu, J.2000dDetection of basophil activation by flow cytometry in patients with allergy to muscle-relaxant drugs275-7Anesthesiology921 2000/01/198Adult Androstanols/*adverse effects Anesthetics, Inhalation/adverse effects Basophils/*metabolism Drug Hypersensitivity/*diagnosis/immunology Female Flow Cytometry Histamine Release Humans Immunoglobulin E/metabolism Middle Aged Neuromuscular Depolarizing Agents/*adverse effects Succinylcholine/*adverse effectsJan+http://www.ncbi.nlm.nih.gov/pubmed/10638929Monneret, G Benoit, Y Gutowski, M C Bienvenu, J Case Reports Research Support, Non-U.S. Gov't United states Anesthesiology Anesthesiology. 2000 Jan;92(1):275-7.%0003-3022 (Print) 0003-3022 (Linking)10638929<Immunology Laboratory, Centre Hospitalier, Lyon-Sud, France.eng ||7QVoog, E. Bienvenu, J. Warzocha, K. Moullet, I. Dumontet, C. Thieblemont, C. Monneret, G. Gutowski, M. C. Coiffier, B. Salles, G.2000Factors that predict chemotherapy-induced myelosuppression in lymphoma patients: role of the tumor necrosis factor ligand-receptor system325-31 J Clin Oncol182 2000/01/19Adult Aged Aged, 80 and over Antineoplastic Agents/*adverse effects/therapeutic use Cyclophosphamide/administration & dosage Doxorubicin/administration & dosage Female Granulocyte Colony-Stimulating Factor/administration & dosage Humans Ligands Lymphoma/*drug therapy Male Middle Aged Neutropenia/*chemically induced/diagnosis Predictive Value of Tests Receptors, Tumor Necrosis Factor/*physiology Risk Assessment Tumor Necrosis Factor-alpha/*pharmacologyJanPURPOSE: To analyze factors that predict the occurrence of chemotherapy-induced myelosuppression and, in particular, the role of the tumor necrosis factor (TNF) ligand-receptor system in lymphoma patients at the beginning of their treatment. PATIENTS AND METHODS: We investigated the predictive factors for myelosuppression after the first course of chemotherapy in a cohort of 101 consecutive, previously untreated lymphoma patients receiving regimens that include doxorubicin and cyclophosphamide. Plasma samples were tested at baseline by enzyme-linked immunosorbent assay for TNF and its soluble receptors. Univariate and multivariate analyses were performed with a forward regression procedure that included all of the parameters that were found to be significant in the univariate analysis. The dose of chemotherapy and the prophylactic treatment with granulocyte colony-stimulating factor were deliberately included in this model. RESULTS: Sixty-seven patients experienced World Health Organization (WHO) grade 4 neutropenia, and 37 patients experienced febrile neutropenia, which was responsible for WHO grade 2 through 4 infections in 23 patients. In multiparametric regression analysis, the occurrence of grade 4 neutropenia was associated with high doses of cyclophosphamide (odds ratio inverted question markOR, 19.8; P =.008) and high levels of soluble p75-R-TNF (OR, 8.52; P =.001). The duration of grade 4 neutropenia for more than 5 days was associated with the lack of hematopoietic growth factor administration (OR, 6.76; P =.004) and high levels of soluble p75-R-TNF (OR, 5.84; P =.0023). The occurrence of febrile neutropenia was associated with high doses of cyclophosphamide (OR, 4.7; P =.007), altered performance status (OR, 18.8; P <.0001) and high levels of soluble p75-R-TNF (OR, 3.49; P =.029). CONCLUSION: This study indicates that in addition to the dose of chemotherapy and the administration of hematopoietic growth factors, poor performance status and high p75-R-TNF levels can predict the occurrence of chemotherapy-induced myelosuppression in lymphoma patients. This model may help in selecting patients for prophylactic growth factor administration.+http://www.ncbi.nlm.nih.gov/pubmed/10637246&Voog, E Bienvenu, J Warzocha, K Moullet, I Dumontet, C Thieblemont, C Monneret, G Gutowski, M C Coiffier, B Salles, G Research Support, Non-U.S. Gov't United states Journal of clinical oncology : official journal of the American Society of Clinical Oncology J Clin Oncol. 2000 Jan;18(2):325-31.%0732-183X (Print) 0732-183X (Linking)10637246hService d'Hematologie and Laboratoire d'Immunologie, Centre Hospitalier Lyon-Sud, Pierre-Benite, France.eng||7RPalmieri, L. Mazza, C.1969*[Congenital and acquired Brown's syndrome]789-806Ann Ottalmol Clin Ocul9510 1969/10/01#Adult Child Child, Preschool HumansOct*http://www.ncbi.nlm.nih.gov/pubmed/5408123wPalmieri, L Mazza, C Italy Annali di ottalmologia e clinica oculistica Ann Ottalmol Clin Ocul. 1969 Oct;95(10):789-806.%0003-4665 (Print) 0003-4665 (Linking)5408123)Sindrome di Brown congenita ed acquisita.ita||7S$Espesson, Y. Hudelo, J. Weiss, J. B.1969%[Brown's syndrome and pseudosyndrome]812-5Bull Soc Ophtalmol Fr699 1969/09/01]Accidents, Traffic Adult Eye Injuries/*classification Female Humans *Ophthalmoplegia *TendonsSep-Oct*http://www.ncbi.nlm.nih.gov/pubmed/5402830Espesson, Y Hudelo, J Weiss, J B France Bulletin des societes d'ophtalmologie de France Bull Soc Ophtalmol Fr. 1969 Sep-Oct;69(9):812-5.%0081-1270 (Print) 0081-1270 (Linking)5402830%Syndrome et pseudo-syndrome de Brown.fre~|7TStein, H. J. Papst, W.1969}[Electromyographic studies on the pathogenesis and therapy of the superior oblique tendon sheath syndrome (Brown's syndrome)]618-24&Ber Zusammenkunft Dtsch Ophthalmol Ges69 1969/01/01rAdolescent Child Diagnosis, Differential *Electromyography Humans Male Ophthalmoplegia/*diagnosis/etiology/surgery*http://www.ncbi.nlm.nih.gov/pubmed/5395109Stein, H J Papst, W Germany, west Bericht uber die Zusammenkunft. Deutsche Ophthalmologische Gesellschaft Ber Zusammenkunft Dtsch Ophthalmol Ges. 1969;69:618-24.%0070-427X (Print) 0070-427X (Linking)5395109Elektromyographische Untersuchungen zur Pathogenese und Therapie des Musculus obliquus superior-Sehnenscheidensyndroms (Brown-Syndrom)ger ||7UsKraft, S. P. Nabi, N. U. Wilson, M. E. Roarty, J. D. Budning, A. S. De Faber, J. T. Ellis, G. S., Jr. Pritchard, C.2000JBilateral idiopathic Brown's syndrome with delayed onset in the second eye158-63J AAPOS43 2000/06/10Child Child, Preschool Eye Movements/physiology Female Humans Infant Male Ocular Motility Disorders/*congenital/diagnosis/*etiology/surgery Oculomotor Muscles/physiopathology/surgery Sensory Deprivation Syndrome Tendon Transfer Vision, Binocular Visual AcuityJunQPURPOSE: We describe 6 cases of a previously unreported variation of bilateral Brown's syndrome that presented in congenital form in one eye and developed later in the fellow eye with no underlying cause. METHODS: We reviewed the clinical records of 6 patients from 6 separate practices to determine whether there were any common clinical features on presentation or in their clinical courses. RESULTS: All 6 patients were diagnosed with unilateral congenital Brown's syndrome at the first ophthalmologic assessment but showed no evidence of the syndrome in the fellow eye. In 5 cases the contralateral syndrome developed in the second eye after surgery was performed on the first eye, and in 1 case it developed before any surgery was done. The ages at onset of the syndrome in the second eye ranged from 2 to 8 years. None of the children had any evidence of systemic illness or local orbital disease to explain an acquired Brown's syndrome. CONCLUSION: To our knowledge, this is the first reported series of cases of bilateral Brown's syndrome that manifested sequentially in the eyes with no known causes for an acquired syndrome in the second eye. This finding supports the premise that congenital and acquired Brown's syndrome are on a continuum with a common pathophysiology of restriction of free movement of the superior oblique tendon in the trochlea.+http://www.ncbi.nlm.nih.gov/pubmed/10849392QKraft, S P Nabi, N U Wilson, M E Roarty, J D Budning, A S De Faber, J T Ellis, G S Jr Pritchard, C Case Reports United states Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus / American Association for Pediatric Ophthalmology and Strabismus J AAPOS. 2000 Jun;4(3):158-63.%1091-8531 (Print) 1091-8531 (Linking)10849392Department of Ophthalmology, the Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada. stephen.kraft@sickkids.on.caS1091853100542396 [pii]eng||7V-Wilson, M. E. Eustis, H. S., Jr. Parks, M. M.1989Brown's syndrome153-72Surv Ophthalmol343 1989/11/01Cranial Nerves/physiopathology *Eye Diseases Female Forecasting Humans Incidence Male *Ocular Motility Disorders Sex Factors Syndrome Tendons/physiopathology Trochlear Nerve/physiopathologyNov-DecMBrown's syndrome is a well-recognized clinical disorder of ocular motility manifesting most notably a restriction of active and passive elevation in adduction. The original name, "superior oblique tendon sheath syndrome," is no longer appropriate, since it has been shown that the tissue surrounding the anterior superior oblique tendon is blameless as a restrictive force. "True" and "simulated" as descriptive modifiers should also be discarded, as they relate to the disproven sheath concept. Brown's syndrome occurs as a congenital or acquired, constant or intermittent condition; the common link is restriction of free movement through the trochlea pulley mechanism. The various etiologic theories are reviewed and the spectrum of medical and surgical treatments are described and evaluated. Evidence suggests that subtypes of Brown's syndrome lie on a single continuum and that spontaneous resolution occurs in each group, probably more often than previously recognized. A simplified classification scheme is encouraged and possible future directions in Brown's syndrome research are introduced.*http://www.ncbi.nlm.nih.gov/pubmed/2694414~Wilson, M E Eustis, H S Jr Parks, M M Review United states Survey of ophthalmology Surv Ophthalmol. 1989 Nov-Dec;34(3):153-72.%0039-6257 (Print) 0039-6257 (Linking)2694414ODepartment of Ophthalmology, National Naval Medical Center, Bethesda, Maryland.0039-6257(89)90100-8 [pii]engU||7WGregersen, E. Rindziunski, E.1993FBrown's syndrome. A longitudinal long-term study of spontaneous course371-6Acta Ophthalmol (Copenh)713 1993/06/01Adolescent Adult Child Child, Preschool Female Follow-Up Studies Humans Longitudinal Studies Male Ocular Motility Disorders/etiology/*physiopathology Prognosis SyndromeJunThe prognosis for spontaneous improvement of Brown's syndrome has not yet been clarified. The present longitudinal long-term study comprised 10 patients with idiopathic Brown's syndrome arising or noticed during the first or second year of life. They were followed for an average of 13 years during which each had a mean of 9 examinations. Spontaneous improvement occurred in 9 of the patients, 3 of whom were cured, obtaining normal motility. All three cases had initially been permanent and monolateral, with initially mild, moderate, and severe restriction, respectively. In the remaining 6 patients who changed for the better, the spontaneous improvement consisted of a reduction of the initial hypotropia and the initial depression of the adducted eye. When the patients were last seen, the sensorial state of binocular vision demonstrated in 4 of the 10 normal binocularity, in 2 binocularity corresponding to microstrabismus, and in 4 alternating suppression.*http://www.ncbi.nlm.nih.gov/pubmed/8362637hGregersen, E Rindziunski, E Denmark Acta ophthalmologica Acta Ophthalmol (Copenh). 1993 Jun;71(3):371-6.%0001-639X (Print) 0001-639X (Linking)8362637TDepartment of Ophthalmology, University Clinic, Rigshospitalet, Copenhagen, Denmark.eng ||7X Keane, J. R.2010BThird nerve palsy: analysis of 1400 personally-examined inpatients662-70Can J Neurol Sci375 2010/11/10 Adolescent Adult Aged Aged, 80 and over Child Child, Preschool Female Humans Inpatients Longitudinal Studies Male Middle Aged Oculomotor Nerve/physiopathology Oculomotor Nerve Diseases/epidemiology/etiology/pathology/*physiopathology Retrospective Studies Young AdultSepBACKGROUND: Most studies of third nerve palsy (TNP) antedate computerized imaging and focus primarily on chart review of referral outpatients. METHODS: To compare a large contrasting population, I reviewed 1400 personally-examined municipal hospital inpatients with TNPs seen over 37 years. RESULTS: TNPs were bilateral in 11%, complete in 33%, without other neurological signs (isolated) in 36%, and associated with recurrent cranial neuropathies in 7%. Third nerve damage occurred in the subarachnoid space in 32%, the cavernous sinus in 23%, the brainstem in 14%, as a nonlocalized peripheral neuropathy in 18% and at an uncertain location in 13%. Causes were trauma (26%), tumor (12%), diabetes (11%), aneurysm (10%), surgery (10%), stroke (8%), infection (5%), Guillain-Barre and Fisher syndromes (5%), idiopathic cavernous sinusitis (3%), benign self-limited (2%), miscellaneous (4%), and unknown (3%). Local causes, besides an abundance of trauma, included six cases involving cysticercosis, four with wound botulism, and one with coccidiomycotic meningitis. Of 234 patients with diabetes, microvascular ischemia was the cause of TNP in only two-thirds (five had aneurysms) and 53% of those with diabetic microvascular ischemia had pupillary involvement-often bilateral, suggesting concomitant autonomic neuropathy. Only 2% of aneurysms spared the pupil. Apainful onset occurred with 94% of aneurysm and 69% of diabetic cases. CONCLUSIONS: Bilateral TNPs, multiple cranial neuropathies, and accompanying neurological signs were common among our inpatients, as were causes rare in outpatient settings such as severe trauma, transtentorial herniation, midbrain strokes, and the Guillain-Barre syndrome. Few cases remained undiagnosed and nondiabetic ischemia was rare.+http://www.ncbi.nlm.nih.gov/pubmed/21059515Keane, James R Canada The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques Can J Neurol Sci. 2010 Sep;37(5):662-70.%0317-1671 (Print) 0317-1671 (Linking)21059515OUniversity of Southern California Medical School, Los Angeles, California, USA.E567204X62382130 [pii]eng||7Y Keane, J. R.1993+Third-nerve palsy due to penetrating trauma1523-7 Neurology438 1993/08/01Adult Female Humans Male Middle Aged Oculomotor Nerve Diseases/*etiology/pathology Wounds, Penetrating/*complications/pathologyAugPenetrating trauma is an unusual etiology of third-nerve palsy. Of 815 hospitalized patients with third-nerve palsies, 20 had such an etiology, with gunshot wounds being the usual cause.*http://www.ncbi.nlm.nih.gov/pubmed/8351005QKeane, J R Case Reports United states Neurology Neurology. 1993 Aug;43(8):1523-7.%0028-3878 (Print) 0028-3878 (Linking)8351005]Department of Neurology, Los Angeles County/University of Southern California Medical Center.eng||7Z Keane, J. R.1993;Intermittent third nerve palsy with cryptococcal meningitis124-6J Clin Neuroophthalmol132 1993/06/01AIDS-Related Opportunistic Infections/*complications Adult Cerebrospinal Fluid/microbiology Cryptococcus neoformans/isolation & purification Humans Intracranial Pressure Male Meningitis, Cryptococcal/*complications Oculomotor Nerve Diseases/*etiologyJunIn the several days before death, two AIDS patients with cryptococcal meningitis and increased intracranial pressure (ICP) experienced episodic unilateral third nerve palsies seemingly related to transient peaks in ICP. While cryptococcal neuritis may have predisposed the nerves to pressure effects, CT scans showed no evidence of tentorial herniation. These cases raise the possibility that severe elevations of ICP can precipitate third nerve paresis on rare occasions.*http://www.ncbi.nlm.nih.gov/pubmed/8340478{Keane, J R Case Reports United states Journal of clinical neuro-ophthalmology J Clin Neuroophthalmol. 1993 Jun;13(2):124-6.%0272-846X (Print) 0272-846X (Linking)8340478^Department of Neurology, Los Angeles County, University of Southern California Medical Center.eng,||7[ Keane, J. R.1989IRhythmic pupillary oscillations accompanying a complete third-nerve palsy169-70; discussion 171J Clin Neuroophthalmol93 1989/09/01Adult Eye Movements Fixation, Ocular Humans Iris Diseases/*complications Male Ophthalmoplegia/*complications Visual Acuity Visual FieldsSepAn automobile accident left a 26-year-old man in stupor with a complete right third-nerve palsy. Although fixed to light, the right pupil (only) exhibited continual concentric oscillations, initially at 1 Hz but slowing to 0.3 Hz during 2 weeks' observation. The pathophysiologic characteristics of this unique movement are uncertain but may involve central parasympathetic nervous system dysfunction.*http://www.ncbi.nlm.nih.gov/pubmed/2529275Keane, J R Case Reports United states Journal of clinical neuro-ophthalmology J Clin Neuroophthalmol. 1989 Sep;9(3):169-70; discussion 171.%0272-846X (Print) 0272-846X (Linking)2529275]Department of Neurology, Los Angeles County/University of Southern California Medical Center.eng||7\ Keane, J. R.1988%Isolated brain-stem third nerve palsy813-4 Arch Neurol457 1988/07/01Adult Cerebral Hemorrhage/complications/radiography Humans Male Ophthalmoplegia/*etiology/physiopathology Tomography, X-Ray ComputedJulMidbrain hemorrhage from a presumed vascular anomaly caused a severe third nerve palsy without other ocular motor or neurologic signs or symptoms.*http://www.ncbi.nlm.nih.gov/pubmed/3390036^Keane, J R Case Reports United states Archives of neurology Arch Neurol. 1988 Jul;45(7):813-4.%0003-9942 (Print) 0003-9942 (Linking)3390036]Department of Neurology, Los Angeles County/University of Southern California Medical Center.eng|?]Elizabeth Jackson2009*Learinng Related Visual Problem Case Study25-28Behavioural Optometry124PK q>I/**refs.frm 0B< !// !HPRIMARYyearIndex 6ByP/) idreference_type text_stylesauthoryear title pages secondary_title volume numbernumber_of_volumessecondary_authorplace_published publishersubsidiary_authoredition keywords type_of_workdate2)  abstractlabelurltertiary_titletertiary_author notes isbn custom_1 custom_2 custom_3 custom_4alternate_titleaccession_number call_number short_title custom_5 custom_6sectionoriginal_publicationH) reprint_editionreviewed_itemauthor_addressimagecaption custom_7 electronic_resource_number link_to_pdf translated_author translated_titlename_of_databasedatabase_providerresearch_notes language access_datelast_modified_date !! H!H!H! (H! 3H! >H! IH! TH!_H!jH!uH! H!H!H! H! H!H! H!H!H!H!H! H! H! H! H! %H! 0H!;H!FH! QH! \H! gH! rH!}H!H!H!H!H!H!H! H! H! H! H! H!H! H!H! "H! -H!8H!idreference_typetext_stylesauthoryeartitlepagessecondary_titlevolumenumbernumber_of_volumessecondary_authorplace_publishedpublishersubsidiary_authoreditionkeywordstype_of_workdateabstractlabelurltertiary_titletertiary_authornotesisbncustom_1custom_2custom_3custom_4alternate_titleaccession_numbercall_numbershort_titlecustom_5custom_6sectionoriginal_publicationreprint_editionreviewed_itemauthor_addressimagecaptioncustom_7electronic_resource_numberlink_to_pdftranslated_authortranslated_titlename_of_databasedatabase_providerresearch_noteslanguageaccess_datelast_modified_datePKE?dPhrefs.MYDPK q>I/**refs.frmPKl