Comparison of immunological parameters in patients with pemphigus vulgaris following rituximab and IVIG therapy.

BACKGROUND: Information on certain immunological parameters in patients with pemphigus vulgaris (PV) treated with rituximab (RTX) and intravenous immunoglobulin (IVIG) therapy is limited. OBJECTIVE: Comparing immunological parameters in patients who achieved long-term clinical remission (LTR) with those who relapsed. METHODS: Retrospective analysis of 19 patients treated at a single centre using the same protocol. Comparisons were made between patients who went into LTR and those who relapsed following completion of the protocol. Treatments prior to IVIG and RTX included prednisone with or without an immunosuppressive agent. The immunological parameters measured included peripheral blood B cells (CD19+), serum quantitative immunoglobulin levels, and levels of antibodies to desmogleins (Dsg) 1 and 3. RESULTS: Eleven patients achieved LTR. Eight patients developed 15 relapses. The mean follow-up time for the LTR group was 29·6±11·2months, and for the relapse group, 40·0±7·0 months. There were no significant differences in times to B-cell depletion, repopulation, or recovery to pretreatment levels between the patients who achieved LTR and those who relapsed. Recurrences usually occurred after B-cell repopulation. Repeated treatments did not influence the time to B-cell repopulation. IgM levels were decreased after therapy and remained decreased. A consistent increase in anti-Dsg1 antibody levels occurred at the time of relapse in patients with mucocutaneous disease. CONCLUSIONS: The majority of patients treated with rituximab and IVIG therapy achieved LTR. Retreatment of relapses can induce LTR. Decreased serum IgM levels persisted following treatment. Increases in anti-Dsg1 antibodies during therapy in patients with mucocutaneous disease suggests a close follow-up for a potential relapse is required.

Very brief visual experience eliminates plasticity in the cat visual cortex.

Rearing cats in the dark extends the critical period for development of visual cortical neurons, which indicates that the experience of visual input is necessary to begin the developmental process. A single brief pulse of visual input (6 hours) during a period of dark-rearing eliminates delayed development in the visual cortex. Light therefore seems to rapidly trigger the developmental process, and once triggered, that process runs to completion in the absence of further input.

Periodontal disease and risk of subsequent cardiovascular disease in U.S. male physicians.

OBJECTIVES: We sought to prospectively assess whether self-reported periodontal disease is associated with subsequent risk of cardiovascular disease in a large population of male physicians. BACKGROUND: Periodontal disease, the result of a complex interplay of bacterial infection and chronic inflammation, has been suggested to be a predictor of cardiovascular disease. METHODS: Physicians' Health Study I was a randomized, double-blind, placebo-controlled trial of aspirin and beta-carotene in 22,071 U.S. male physicians. A total of 22,037 physicians provided self-reports of presence or absence of periodontal disease at study entry and were included in this analysis. RESULTS: A total of 2,653 physicians reported a personal history of periodontal disease at baseline. During an average of 12.3 years of follow-up, there were 797 nonfatal myocardial infarctions, 631 nonfatal strokes and 614 cardiovascular deaths. Thus, for each end point, the study had >90% power to detect a clinically important increased risk of 50%. In Cox proportional hazards regression analysis adjusted for age and treatment assignment, physicians who reported periodontal disease at baseline had slightly elevated, but statistically nonsignificant, relative risks (RR) of nonfatal myocardial infarction, (RR, 1.12; 95% confidence interval [CI], 0.92 to 1.36), nonfatal stroke (RR, 1.10; CI, 0.88 to 1.37) and cardiovascular death (RR, 1.20; CI, 0.97 to 1.49). Relative risk for a combined end point of all important cardiovascular events (first occurrence of nonfatal myocardial infarction, nonfatal stroke or cardiovascular death) was 1.13 (CI, 0.99 to 1.28). After adjustment for other cardiovascular risk factors, RRs were all attenuated and nonsignificant. CONCLUSIONS: These prospective data suggest that self-reported periodontal disease is not an independent predictor of subsequent cardiovascular disease in middle-aged to elderly men.

Blood levels of homocysteine and increased risks of cardiovascular disease: causal or casual?

BACKGROUND: Accumulating data from epidemiological studies suggest that individuals with elevated blood levels of homocysteine have increased risks of cardiovascular disease. We reviewed the currently available evidence of an association between homocysteine and cardiovascular disease and examined whether the strength of the evidence varies according to study design. METHODS: We used a computerized MEDLINE literature search, 1966 through September 1998, to identify all epidemiological studies that examined the relationship of homocysteine level with risks of coronary heart or cerebrovascular disease. Two measures of plasma homocysteine level and its association with risk of cardiovascular disease were extracted: mean homocysteine level in cases and controls, and relative risk of cardiovascular disease for elevated homocysteine level. RESULTS: A total of 43 studies were reviewed. Most crosssectional and case-control studies indicated higher mean homocysteine levels (either fasting or after methionine load) and/or a greater frequency of elevated homocysteine level in persons with cardiovascular disease as compared with persons without cardiovascular disease. Results of most prospective studies, however, indicated smaller or no association. The few prospective studies that reported a positive association between homocysteine level and risks of cardiovascular disease included patients with preexisting vascular disease. CONCLUSIONS: In contrast to cross-sectional and case-control studies, results of prospective studies indicated less or no predictive ability for plasma homocysteine in cardiovascular disease. Instead, elevated homocysteine level may be an acute-phase reactant that is predominantly a marker of atherogenesis, or a consequence of other factors more closely linked to risks of cardiovascular disease. Randomized trials are necessary to test reliably whether lowering homocysteine levels will decrease risks of cardiovascular disease.

Dark rearing prolongs physiological but not anatomical plasticity of the cat visual cortex.

Recent studies (Cynader and Mitchell, '80; Mower et al., '81) have shown that total dark rearing prolongs susceptibility to the physiological effects of monocular deprivation (MD) in visual cortex beyond the normal age limits. The present study addressed whether this delayed physiological plasticity is accompanied by delayed anatomical plasticity in the geniculocortical pathway. Ocular dominance (OD) columns as defined by transsynaptic autoradiography following injection of 3H proline into one eye were studied both qualitatively and quantitatively in 17 cats. Compared to normal rearing (N-3), both binocular eyelid suture (N-2) and total dark rearing (N-3) resulted in incomplete segregation of OD columns in area 17. This apparent immaturity after binocular deprivation, however, did not reflect a delayed capacity for development and plasticity. Visual experience after dark rearing produced no marked changes. In cats who experienced MD after dark rearing, injection of either the nondeprived (N-2) or deprived eye (N-3) resulted in a nearly uniform distribution of label throughout layer IV of area 17. The same result occurred with binocular vision after dark rearing (N-1). MD from birth, however, produced expansion of columns from the nondeprived eye (N-1) and contraction of columns from the deprived eye (N-1). MD imposed after 4 months of normal vision resulted in normal OD columns (N-1). Electrophysiological studies revealed a high proportion of binocular cells within layer IV in cats who experienced monocular or binocular vision after dark rearing. Outside of layer IV there were clear environmental effects on OD of single cells in these cats. Measurements of cell sizes in the clateral geniculate nucleus showed shrinkage of cells innervated by the deprived eye when MD was initiated at birth (N-3). MD after dark rearing (N-4) produced no differences in cell sizes. It is concluded that visual input is necessary for the formation of normal OD columns, the critical period for formation and environmental modification of OD columns is limited to early life, and the physiological effects of visual experience after dark rearing reflect changes occurring beyond the geniculocortical pathway.

Relations of body fat distribution and height with cataract in men.

BACKGROUND: Cataract is the leading cause of blindness worldwide. Body mass index (BMI; in kg/m(2)) is a risk factor for cataract, but other anthropometric measurements may also be important. OBJECTIVE: We tested relations of alternative measures of body size, including height and waist-to-hip ratio (WHR), as well as BMI, with cataract. DESIGN: This was a prospective follow-up study. We analyzed data from 20271 participants in the Physicians' Health Study who did not have cataract at baseline and for whom there was complete information on weight, height, and other risk factors. For analyses concerning WHR, we excluded 3121 additional men for whom we did not have these measurements, assessed at the ninth year of follow-up. The main outcome measures were incident cataract and cataract surgery. RESULTS: Among the 17150 men for whom there were complete data, we confirmed an incident cataract in 1727 during an average of 14 y of follow-up. In proportional hazards regression models that adjusted for many known or suspected risk factors, higher BMI [rate ratio (RR) = 1.25 for >/=27.8 compared with <22, P: for trend = 0. 03], height (RR = 1.23 for >/=184 cm compared with

Antioxidants and eye disease.

Oxidative mechanisms are believed to play an important role in the pathogenesis of age-related eye disease, in particular, cataract and macular degeneration, the two most important causes of visual impairment in older adults. For this reason, there is considerable interest in determining whether vitamins and trace minerals with antioxidant properties can be of benefit in preventing the onset or progression of disabling eye disease. Basic research studies have shown that antioxidants can protect against the cumulative effects of oxidative stress in animal models of cataract and macular degeneration. Data from observational epidemiologic studies in humans, however, are inconclusive. While results from several studies, primarily cross-sectional and case-control, are compatible with a possible protective role for micronutrients in cataract and macular degeneration, data for specific nutrients or specific disease types have often been inconsistent. Further, these observational studies are limited because of the inherent imprecision of dietary exposure data and the likely effects of uncontrolled confounding. Thus, reliable data regarding a potentially important benefit of vitamin supplementation in eye disease will emerge mainly from well-designed, large-scale, randomized trials. Such data are already being collected in the National Eye Institute-sponsored Age Related Eye Disease Study, as well as in the Physicians' Health Study and Women's Health Study.

Determinants of retinopathy progression in type 1 diabetes mellitus.

PURPOSE: To determine the risk factors for retinopathy progression in type 1 (insulin-dependent) diabetes mellitus in a prospective cohort study. SUBJECTS AND METHODS: Subjects were 485 participants in the Sorbinil Retinopathy Trial, a randomized trial of aldose reductase inhibition among patients aged 18 to 56 years with type 1 diabetes mellitus (duration of 1 to 15 years) and no or only mild retinopathy. Retinopathy progression, assessed by seven-field stereoscopic fundus photography, was defined as worsening by two or more levels on a standardized grading scale at the end of follow-up (median, 41 months). RESULTS: The relative risks for retinopathy progression according to successively greater quintiles of total glycosylated hemoglobin level at baseline, after adjusting for age, diabetes duration, sorbinil assignment, and other variables, were 1.0, 2.0, 1.6, 3.7, and 4.4 (P trend <0.0001). Risk increased with greater baseline diastolic blood pressure: 1.0 for <70 mm Hg, 1.2 for 70 to 79 mm Hg, and 1.8 for > or =80 mm Hg (P for trend = 0.04). Diastolic blood pressure was a significant risk factor for progression in participants with mild baseline retinopathy (P for trend <0.02) but not in those without retinopathy at entry. Systolic blood pressure, by comparison, was not associated with progression. Baseline total cholesterol level was a marginally significant predictor of retinopathy progression when examined as a categorical variable (relative risks for increasing quartiles; 1.0, 1.6, 1.8, 1.9; P for trend = 0.03) but not when it was examined as a continuous variable or when hypercholesterolemic patients were compared with those with normal levels. Furthermore, when cholesterol levels were updated in subsequent visits, it was not a significant predictor of progression, and low density lipoprotein (LDL) cholesterol levels did not predict progression no matter how analyzed. Smoking was not associated with progression of retinopathy. CONCLUSIONS: Levels of hyperglycemia and diastolic blood pressure predicted progression of retinopathy in type 1 diabetes mellitus. We found only a suggestion of an association between total cholesterol level (but not of LDL cholesterol level) and progression of retinopathy; resolution of this issue will require additional studies with larger sample sizes and longer follow-up.

Design of Physicians' Health Study II--a randomized trial of beta-carotene, vitamins E and C, and multivitamins, in prevention of cancer, cardiovascular disease, and eye disease, and review of results of completed trials.

PURPOSE: To assess the balance of benefits and risks of supplementation with beta-carotene, vitamin E, vitamin C, and multivitamins on cancer, cardiovascular (CVD), and eye diseases. DESIGN: Physicians' Health Study II (PHS II) is a randomized, double-blind, placebo-controlled trial enrolling 15,000 willing and eligible physicians aged 55 years and older. PHS II will utilize a 2 x 2 x 2 x 2 factorial design to test alternate day beta-carotene, alternate day vitamin E, daily vitamin C, and a daily multivitamin, in the prevention of total and prostate cancer, CVD, and the age-related eye diseases, cataract and macular degeneration. PRIOR RESULTS: The final results of the recently completed Physicians' Health Study I (PHS I), a randomized, double-blind, placebo-controlled trial in 22,071 healthy US male physicians, indicated that beta-carotene supplementation (50 mg on alternate days) had no significant benefit or harm on cancer or CVD during more than 12 years of treatment and follow-up. In regards to cancer, there were possible benefits on total and prostate cancer in those with low baseline levels assigned to beta-carotene, a finding compatible with the Chinese Cancer Prevention Study for combined treatment with beta-carotene, vitamin E, and selenium in a poorly nourished population. Further, with respect to CVD, there were apparent benefits of beta-carotene supplementation on subsequent vascular events among a small subgroup of 333 men with prior angina or revascularization. The currently available data from randomized trials of primary prevention are sparse and inconsistent for vitamin E and non-existent for vitamin C and multivitamins. For eye diseases, namely cataract and age-related macular degeneration, there are no completed large-scale randomized trials of antioxidant vitamins. CONCLUSIONS: PHS II is unique in several respects. PHS II is the only primary prevention trial in apparently healthy men testing the balance of benefits and risks of vitamin E on cancer and CVD. In addition, PHS II is the only primary prevention trial in apparently healthy men to test the balance of benefits and risks of vitamin C, multivitamins, as well as any single antioxidant vitamin, alone and in combination, on cancer, CVD, and eye diseases. Finally, PHS II is the only trial testing a priori the hypotheses that beta-carotene and vitamin E may reduce the risks of prostate cancer. Thus, PHS II will add unique as well as importantly relevant and complementary information to the totality of evidence from other completed and ongoing large-scale randomized trials on the balance of benefits and risks of beta-carotene, vitamin E, vitamin C, and multivitamins alone and in combination on prevention of cancer, CVD and eye diseases.

Antioxidants and age-related eye disease. Current and future perspectives.

Oxidative mechanisms may play an important role in the pathogenesis of age-related eye disease, in particular cataract and macular degeneration, the two most important causes of visual impairment in older adults. For this reason, there is considerable interest in determining whether vitamins and trace minerals with antioxidant properties can be of benefit in preventing the onset or progression of disabling eye disease. Basic research studies have shown that antioxidants can protect against the cumulative effects of oxidative stress in animal models of cataract and macular degeneration. Data from observational epidemiological studies in humans, however, are inconclusive. While results from several studies, primarily cross-sectional and case-control, are compatible with a possible protective role for micronutrients in disease development, data for specific nutrients or specific disease types have often been inconsistent. Further, these observational studies are limited because of the inherent imprecision of dietary exposure data and the likely effects of uncontrolled confounding. Thus, reliable data regarding a potentially important benefit of vitamin supplementation in eye disease will emerge mainly from well-designed, large-scale, randomized trials.

A prospective study of blood pressure and risk of cataract in men.

PURPOSE: Cataract is the leading cause of blindness worldwide. Blood pressure has been identified as a risk factor in some, but not all, previous studies. We aimed to test prospectively the hypothesis that high blood pressure increases risk of age-related cataract. METHODS: Participants in the Physicians' Health Study of 22,071 men aged 40 to 84 years in 1982 completed annual questionnaires that provided medical history including self-reported blood pressure, treatment for hypertension, and cataract. Over 12 years, 1392 cataracts were confirmed by medical record review among 17,762 physicians with complete data and no reported cataract at baseline. We used proportional hazards regression models to examine relations of systolic blood pressure (SBP), diastolic blood pressure (DBP), hypertension, as well as antihypertensive medications with cataract, after control for potential confounding factors. RESULTS: In models adjusting for age and randomized treatment assignment, there was a significant relationship of SBP, but not DBP, hypertension, or antihypertensive medications (each p > or = 0.23) with incident cataract. Estimates were attenuated after adjusting for multiple potential confounders, although the relationship of SBP with incident cataract remained significant. The multivariate adjusted rate ratio (95% confidence interval) of cataract for SBP > or = 150 versus < 120 mm Hg was 1.31 (1.04-1.66), p for trend = 0.04. For DBP > or = 90 versus < 70 mm Hg, the estimate was 1.11 (0.84-1.45), p for trend = 0.33. CONCLUSIONS: Overall, these data suggest that the relationship of blood pressure with cataract is not strong, and is subject to confounding by other risk factors. The modest magnitude of the association with SBP and lack of significant relationships with DBP and hypertension may suggest a non-causal relationship of blood pressure with cataract.

High levels of plasma C-reactive protein and future risk of age-related cataract.

PURPOSE: Chronic intraocular inflammation, with or without systemic inflammation, is associated with increased risk of cataract. Whether systemic inflammation alone is associated with cataract is unknown. This study examined the association between plasma C-reactive protein (CRP), a marker of systemic inflammation, and risk of cataract. METHODS: In the Physicians' Health Study, we recently analyzed plasma CRP levels in baseline blood specimens from 543 men who later developed cardiovascular disease, and 543 who did not. These data provided a cost-efficient means to explore whether baseline plasma CRP is associated with future risk of age-related cataract. After excluding 252 men with prior diagnosis of cataract or missing data, we followed the remaining 834 men defined by baseline CRP level for 11 years for incident cataract. We used proportional hazards regression models, stratified by cardiovascular disease status. RESULTS: Baseline CRP was significantly higher among men who later developed cataract than levels among those who remained free of cataract, P = 0.02 (median 1.53 versus 1.23 mg/L). In a multivariable model adjusted for cardiovascular disease, randomized aspirin and beta carotene assignments, age, diabetes, cigarette smoking, alcohol consumption, body mass index, exercise, and parental history of myocardial infarction, the levels of CRP remained significantly associated with development of cataract (P = 0.001); but the association was less significant in a model using log CRP levels (P = 0.038). In exploratory analyses of a threshold effect, the excess risk was significant only among men with levels at or above the 97.5th centile (6.17 mg/L); compared to those with lower levels, the relative risk in these men was 3.00 (95% confidence interval, 1.53 to 5.91; P = 0.002). Relative risks associated with CRP levels at or above versus below the 85th, 90th, and 95th percentiles were not significant (relative risks 1.29, 1.50, and 1.77, respectively). CONCLUSIONS: Overall, our results suggest that elevated levels of CRP are associated with future risk of cataract in these apparently healthy men. This early report raises the possibility that systemic inflammation may play a role in the pathogenesis of age-related cataract.

A prospective study of alcohol consumption and the risk of age-related macular degeneration.

PURPOSE: Vascular risk factors, including alcohol intake, have been hypothesized to play a role in the development of age-related macular degeneration (AMD). We examined the relationship of alcohol intake with AMD in the Physicians' Health Study (PHS). METHODS: The PHS was a randomized trial of aspirin and beta-carotene among 22,071 U.S. male physicians age 40 to 84 years at entry. A total of 21,041 physicians with complete data on alcohol consumption and no AMD at baseline were included in this analysis. Proportional hazards models were used to estimate relative risks (RR) and 95% confidence interval (CI). RESULTS: During an average follow-up period of 12.5 years, 278 physicians were confirmed by medical record review to have incident AMD resulting in vision loss ( acuity 20/30 or worse). After adjusting for age, randomized treatment assignment, and other potential risk factors, the RR for > or = 1 drink/week versus < 1 drink/week was 0.97 (CI: 0.78-1.21). For categories of alcohol intake, the RRs for those reporting alcohol consumption of < 1 drink/week, 1 drink/week, 2-4 drinks/week, 5-6 drinks/week, and > or = 1 drink/day were 1.00 (referent), 1.00 (0.65-1.55), 0.68 (0.44-1.04), 1.32 (0.89-1.95), and 1.27 (0.93-1.73), respectively. CONCLUSIONS: These prospective data indicate that alcohol intake is not appreciably associated with the risk of incident AMD. However, the width of the confidence intervals are compatible with a possible small effect (reduction or increase) in risk for low to moderate levels of alcohol intake, which warrant further investigation.

Body mass index and the incidence of visually significant age-related maculopathy in men.

BACKGROUND: Reports have suggested relationships of body weight with age-related maculopathy (ARM), particularly its nonneovascular (dry) forms, but results are inconsistent and prospective data are scarce. OBJECTIVE: To examine prospectively relationships of body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) with visually significant dry and neovascular ARM during an average of 14.5 years of follow-up. METHODS: Incident ARM was assessed by medical record confirmation of self-reported ARM among the 21 121 men participating in the Physicians' Health Study who (1) were followed up for at least 7 years, (2) were free of visually significant ARM at baseline, and (3) had information on BMI and cigarette smoking. We used proportional hazards regression models to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for visually significant dry ARM (256 cases) and neovascular ARM (84 cases) within 4 categories of BMI: lean (< 22.0), normal (22.0-24.9), overweight (25.0-29.9), and obese (> or = 30.0). RESULTS: Adjusting for age, randomized aspirin and beta carotene assignments, and cigarette smoking, the incidence for visually significant dry ARM was lowest in men with a normal BMI. Compared with these men, the RRs (95% CIs) were as follows: 1.43 (1.01-2.04) for lean, 1.24 (0.93-1.66) for overweight, and 2.15 (1.35-3.45) for obese men. Although there was no significant relationship of BMI with the diagnosis of neovascular ARM, due to the small number of cases these analyses could not rule out an important relationship. CONCLUSIONS: Obesity is a risk factor for visually significant ARM in men, in particular for dry ARM. However, the relationship of BMI with dry ARM appears to be J-shaped, and the leanest individuals also appear to be at increased risk.

Body mass index. An independent predictor of cataract.

OBJECTIVE: To examine whether body mass index is an independent predictor of cataract. (Body mass index is a standardized measure defined as weight in kilograms divided by the square of the height in meters.) DESIGN: Prospective cohort study, with 5 years of follow-up. PARTICIPANTS: A total of 17,764 US male physicians participating in the Physicians' Health Study, aged 40 to 84 years, who were free of cataract, myocardial infarction, stroke, and cancer at baseline and reported complete information about body mass index and other cataract risk factors. MAIN OUTCOME MEASURE: Incident cataract, defined as a self-report, confirmed by medical record review, first diagnosed after randomization, age-related in origin, and responsible for a decrease in best corrected visual acuity to 20/30 or worse. RESULTS: Incident cataract occurred during follow-up in 370 participants. In proportional hazards models that adjusted for potential confounding variables, body mass index had a strong, graded relationship with risk of cataract. Relative to those with body mass index less than 22, relative risks (95% confidence intervals) associated with body mass index of 22 to less than 25, 25 to less than 27.8, and 27.8 or more were 1.54 (1.04 to 2.27), 1.46 (0.98 to 2.20), and 2.10 (1.35 to 3.25), respectively. Relative to any given level of body mass index, a 2-unit higher level predicted a 12% increase in risk of cataract (95% confidence interval, 5% to 19%). Higher body mass index was especially strongly related to risk of posterior subcapsular and nuclear sclerotic cataracts and was also significantly related to risk of cataract extraction. CONCLUSIONS: In a prospective cohort study of apparently healthy men, higher body mass index, a potentially modifiable risk factor, was a determinant of cataract. The leanest men had the lowest rates, consistent with experimental evidence that restriction of energy intake slows development of cataract. Although precise mechanisms are unclear, the effect of body mass index on cataractogenesis is apparently independent of other risk factors, including age, smoking, and diagnosed diabetes.

Aspirin use and risk of cataract in posttrial follow-up of Physicians' Health Study I.

BACKGROUND: In Physicians' Health Study I, randomized trial results indicated no major beneficial effect of 5 years of low-dose aspirin treatment on total cataract (relative risk [RR], 0.94; 95% confidence interval [CI], 0.79-1.13) or cataract extraction (RR, 0.81; 95% CI, 0.65-1.01) during the period of treatment. OBJECTIVE: To examine the effect of assigned aspirin treatment and posttrial, self-selected aspirin use on the risk of age-related cataract over the 15 years of follow-up of Physicians' Health Study I. METHODS: Participants were 20 968 US male physicians enrolled in Physicians' Health Study I who did not report cataract at baseline. At 7 years, after termination of the randomized aspirin component of the trial, self-selected aspirin use was computed from annual questionnaires. The main outcome measures were age-related cataract and extraction of age-related cataract, defined as an incident, age-related lens opacity responsible for a reduction in best-corrected visual acuity to 20/30 or worse based on self-report confirmed by medical record review. RESULTS: During a median of 14.9 years of follow-up, there were 2081 cataracts and 1198 cataract extractions. Overall, the age- and beta carotene-adjusted RR of cataract in men assigned to aspirin compared with those assigned to placebo was 1.09 (95% CI, 1.00-1.18). For cataract extraction, the RR was 1.09 (95% CI, 0.98-1.22). During a median posttrial follow-up of 7.9 years, a total of 1225 incident cataracts and 635 cataract extractions were documented. The multivariate RR of cataract in men who reported using aspirin frequently (>/=180 days per year) at 7 years compared with nonusers (0-13 days per year) was 1.20 (95% CI, 1.03-1.40). For cataract extraction, the multivariate RR was 1.22 (95% CI, 0.98-1.51). Results for diagnosis and extraction of cataract subtypes were similar. CONCLUSIONS: Analyses based on randomized aspirin assignment indicated no long-term benefit of 5 years of low-dose aspirin treatment on total cataract or cataract extraction. Posttrial, observational data also indicated no decreased risk of cataract in aspirin users and suggested a small increased risk of cataract in aspirin users. Further randomized trial data to investigate the effect of longer term treatment with low-dose aspirin are being collected as part of the ongoing Women's Health Study, a randomized trial of low-dose aspirin and vitamin E among 39 876 apparently healthy, postmenopausal US female health professionals.

Age-related maculopathy in a randomized trial of low-dose aspirin among US physicians.

OBJECTIVE: To examine the development of age-related maculopathy (ARM) in a large-scale trial of low-dose aspirin treatment. METHODS: The Physicians' Health Study I was a randomized, double-masked, placebo-controlled trial of low-dose aspirin (325 mg every other day) and beta carotene (50 mg every other day) in the prevention of cardiovascular disease and cancer conducted among 22 071 US male physicians aged 40 to 84 years in 1982. A total of 21 216 participants did not report ARM at baseline, were followed up for at least 7 years, and are included in this analysis. MAIN OUTCOME MEASURES: Total ARM, defined as a self-report confirmed by medical record evidence of an initial diagnosis subsequent to randomization, and ARM with vision loss, defined as total ARM but with vision loss to 20/30 or worse attributable to ARM. RESULTS: Early termination of the randomized aspirin component of the Physicians' Health Study I, after an average of 60.2 months of treatment and follow-up due to a statistically extreme 44% reduced risk of first myocardial infarction, resulted in a far lower number of incident cases of ARM during the aspirin treatment period than would have accrued without early termination. Thus, during an average of 60.2 months of follow-up, a total of 117 cases of ARM were confirmed, including 57 cases responsible for vision loss to 20/30 or worse. There were 51 cases of ARM in the aspirin group and 66 in the placebo group (relative risk, 0.77; 95% confidence interval, 0.54-1.11). For ARM with vision loss, there were 25 cases in the aspirin group and 32 in the placebo group (relative risk, 0.78; 95% confidence interval, 0.46-1.32). CONCLUSIONS: These randomized trial data tend to exclude any large beneficial effect of 5 years of low-dose aspirin treatment on ARM. However, a smaller, but potentially important, beneficial effect cannot be ruled out and would require testing in randomized trials of adequate size and duration.

Low-dose aspirin and risks of cataract in a randomized trial of US physicians.

Observational studies have raised the question of a possible benefit of aspirin on the development of cataract. The Physicians' Health Study, a randomized double-masked placebo-controlled trial among 22,071 male physicians, aged 40 to 84 years, provided the opportunity to collect information about whether low-dose aspirin therapy (325 mg on alternate days) affects the development or extraction of cataract. There were 173 age-related cataracts among those physicians assigned to aspirin therapy and 180 among those given placebo (relative risk, 0.95; 95% confidence interval, 0.74 to 1.22). Cataract extractions were less frequent in the aspirin than in the placebo group, but this difference was not statistically significant (relative risk, 0.80; 95% confidence interval, 0.56 to 1.15). Among younger men (aged 40 to 59 years), the relative risks were 0.62 (95% confidence interval, 0.40 to 0.94) for cataract development and 0.67 (95% confidence interval, 0.38 to 1.31) for cataract extraction. These randomized trial data tend to exclude any large benefit of aspirin. While the overall findings concerning cataract development seem to be null, the data on extraction of age-related cataract, while not statistically significant, cannot exclude a possible small to moderate benefit of alternate-day aspirin therapy on the extraction of age-related cataract.

Effects of monocular occlusion and diffusion on visual system development in the cat.

The effects of two forms of monocular deprivation (occlusion or diffusion) on visual system development were investigated. One group of cats monocularly deprived of all form stimulation but permitted diffuse light stimulation (diffusion, n = 4) during development showed a pattern of deficits similar to those reported for monocularly sutured cats. Most cells in the visual cortex were driven exclusively by the non-deprived eye and there were eye-specific deficits in X-cell acuity, proportion of Y-cells, and cell body size (binocular and monocular segment) in the lateral geniculate nucleus (LGN). A second group of cats monocularly deprived of all form and light stimulation (occlusion, n = 4) during development showed a less severe pattern of deficits. There was no acuity loss in LGN X-cells driven by the deprived eye, and cell body shrinkage was of smaller magnitude than in diffusion reared cats and was restricted to the binocular segment. Cortical deficits and LGN Y-cell loss were similar in the two groups. The results are consistent with the idea that monocular occlusion produces only deficits due to binocular competition while monocular diffusion reflects the combined effects of binocular competition and abnormal stimulation.

Effects of early monocular deprivation on the acuity of lateral geniculate neurons in the cat.

Acuity assessments on lateral geniculate X-cells in 8 monocularly deprived cats indicated that deprived cells had significantly lower acuities than non-deprived cells. Within deprived laminae, cells having low acuity were intermixed with cells having normal acuity. Deprivation effects were clearly evident in both A and A1 laminae and in both adult and young cats. The results also pointed out several factors which should be considered in analyzing deprivation effects.