Sugar-sweetened beverage consumption and age at menarche in a prospective study of US girls.

STUDY QUESTION: Is sugar-sweetened beverage (SSB) consumption associated with age at menarche? SUMMARY ANSWER: More frequent SSB consumption was associated with earlier menarche in a population of US girls. WHAT IS KNOWN ALREADY: SSB consumption is associated with metabolic changes that could potentially impact menarcheal timing, but direct associations with age at menarche have yet to be investigated. STUDY DESIGN, SIZE, DURATION: The Growing up Today Study, a prospective cohort study of 16 875 children of Nurses' Health Study II participants residing in all 50 US states. This analysis followed 5583 girls, aged 9-14 years and premenarcheal at baseline, between 1996 and 2001. During 10 555 person-years of follow-up, 94% (n = 5227) of girls reported their age at menarche, and 3% (n = 159) remained premenarcheal in 2001; 4% (n = 197) of eligible girls were censored, primarily for missing age at menarche. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cumulative updated SSB consumption (composed of non-carbonated fruit drinks, sugar-sweetened soda and iced tea) was calculated using annual Youth/Adolescent Food Frequency Questionnaires from 1996 to 1998. Age at menarche was self-reported annually. The association between SSB consumption and age at menarche was assessed using Cox proportional hazards regression. MAIN RESULTS AND THE ROLE OF CHANCE: More frequent SSB consumption predicted earlier menarche. At any given age between 9 and 18.5 years, premenarcheal girls who reported consuming >1.5 servings of SSBs per day were, on average, 24% more likely [95% confidence interval (CI): 13, 36%; P-trend: <0.001] to attain menarche in the next month relative to girls consuming ≤2 servings of SSBs weekly, adjusting for potential confounders including height, but not BMI (considered an intermediate). Correspondingly, girls consuming >1.5 SSBs daily had an estimated 2.7-month earlier menarche (95% CI: -4.1, -1.3 months) relative to those consuming ≤2 SSBs weekly. The frequency of non-carbonated fruit drink (P-trend: 0.03) and sugar-sweetened soda (P-trend: 0.001), but not iced tea (P-trend: 0.49), consumption also predicted earlier menarche. The effect of SSB consumption on age at menarche was observed in every tertile of baseline BMI. Diet soda and fruit juice consumption were not associated with age at menarche. LIMITATIONS, REASONS FOR CAUTION: Although we adjusted for a variety of suspected confounders, residual confounding is possible. We did not measure SSB consumption during early childhood, which may be an important window of exposure. WIDER IMPLICATIONS OF THE FINDINGS: More frequent SSB consumption may predict earlier menarche through mechanisms other than increased BMI. Our findings provide further support for public health efforts to reduce SSB consumption. STUDY FUNDING/COMPETING INTERESTS: The Growing up Today Study is supported by grant R03 CA 106238. J.L.C. was supported by the Breast Cancer Research Foundation; Training Grant T32ES007069 in Environmental Epidemiology from the National Institute of Environmental Health Sciences, National Institutes of Health; and Training Grant T32HD060454 in Reproductive, Perinatal and Pediatric Epidemiology from the National Institute of Child Health and Human Development, National Institutes of Health. A.L.F. is supported by the American Cancer Society, Research Scholar Grant in Cancer Control. K.B.M. was supported in part by the National Cancer Institute at the National Institutes of Health (Public Health Service grants R01CA158313 and R03CA170952). There are no conflicts of interest to declare.

Clinical malaria diagnosis in pregnancy in relation to early perinatal mother-to-child transmission of HIV: a prospective cohort study.

OBJECTIVES: We prospectively investigated fever symptoms and maternal diagnosis of malaria in pregnancy (MIP) in relation to child HIV infection among 2368 pregnant HIV-positive women and their infants, followed up from pregnancy until 6 weeks post-delivery in Tanzania. METHODS: Doctors clinically diagnosed and treated MIP and fever symptoms during prenatal health care. Child HIV status was determined via DNA polymerase chain reaction (PCR). Multivariable logistic regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for HIV mother-to-child transmission (MTCT) by the 6th week of life. RESULTS: Mean gestational age at enrolment was 22.2 weeks. During follow-up, 16.6% of mothers had at least one MIP diagnosis, 15.9% reported fever symptoms and 8.7% had both fever and MIP diagnosis. Eleven per cent of HIV-exposed infants were HIV-positive by 6 weeks. The RR of HIV MTCT was statistically similar for infants whose mothers were ever vs. never clinically diagnosed with MIP (RR 1.24; 95% CI 0.94-1.64), were diagnosed with one vs. no clinical MIP episodes (RR 1.07; 95% CI 0.77-1.48) and had ever vs. never reported fever symptoms (RR 1.04; 95% CI 0.78-1.38) in pregnancy. However, the HIV MTCT risk increased by 29% (95% CI 4-58%) per MIP episode. Infants of women with at least two vs. no MIP diagnoses were 2.1 times more likely to be HIV infected by 6 weeks old (95% CI 1.31-3.45). CONCLUSIONS: Clinical MIP diagnosis, but not fevers, in HIV-positive pregnant women was associated with an elevated risk of early HIV MTCT, suggesting that malaria prevention and treatment in pregnant HIV-positive women may enhance the effectiveness of HIV prevention in MTCT programmes in this setting. Future studies using a laboratory-confirmed diagnosis of malaria are needed to confirm this association.

PREDICTORS OF INCIDENT TUBERCULOSIS IN HIV-EXPOSED CHILDREN IN TANZANIA.

OBJECTIVE: To examine the predictors of tuberculosis infection in HIV-exposed children. DESIGN: A longitudinal cohort study nested within a randomised controlled trial. SETTING: Antenatal clinics in Dar-es-Salaam, Tanzania. SUBJECTS: Children born to 875 HIV-infected women in Tanzania. RESULTS: A total of 82 children developed tuberculosis during the follow-up period. In multivariate analyses, HIV infection was associated with a six-fold increase in risk of tuberculosis. Breastfeeding duration, child mid-upper arm circumference, and maternal CD4 T-cell counts were inversely related to risk of tuberculosis. In HIV-infected children, greater number of people eating at the same household meal and child CD8 T-cell counts were associated with increased risk of tuberculosis; higher maternal lymphocyte counts, increased duration of breastfeeding, and lower vitamin E levels were associated with reduced risk of tuberculosis. In HIV-uninfected children, breastfeeding duration and increased child mid-upper arm circumference were associated with reduced risk of tuberculosis. CONCLUSION: Breastfeeding duration, HIV status, maternal and child nutritional and immunological status were important predictors of child tuberculosis. Appropriate infant feeding and nutritional interventions could represent important adjuncts to prevent tuberculosis in children born to HIV-infected women in sub-Saharan Africa.

Validation of the Gail et al. model for predicting individual breast cancer risk.

BACKGROUND: The Gail et al. model is considered the best available means for estimating an individual woman's risk of developing breast cancer. Such estimates are useful in decision making on the part of women, in designing prevention trials, and in targeting screening and prevention efforts. PURPOSE: Our purpose was to evaluate the ability of the model to accurately predict individual breast cancer risk, using a large population independent of the one from which the model was derived. METHODS: We compared the number of cancer cases predicted by the model to the actual number of cases observed in the Nurses' Health Study. The study population was 115,172 women who did not have breast cancer at the beginning of the study. Questionnaires were sent to participants every 2 years, seeking data on risk factors and diagnoses of breast cancer. Follow-up compliance was 95% over the 12-year study period. RESULTS: The model over-predicted absolute breast cancer risk by 33% (95% confidence interval [CI] = 28%-39%), with the overprediction more than twofold among premenopausal women (95% CI = 1.9-2.2), among women with extensive family history of breast cancer (95% CI = 1.1-3.9), and among women with age at first birth younger than 20 years (95% CI = 1.3-4.7). The correlation coefficient between observed and predicted risk was 0.67, indicating that the model is less than satisfactory for ranking individual levels of breast cancer risk. Overprediction occurred at all deciles of predicted risk. CONCLUSIONS: The model's performance is unsatisfactory for estimating breast cancer risk for individual women aged 25-61 years who do not participate in annual screening. Lower mammography screening rates in the Nurses' Health Study may account for some, but not all, of the discrepancy between observed and predicted cases. IMPLICATIONS: A recent modification of the model by the tamoxifen trial investigators is likely to have provided accurate power calculations. This modified form of the model should be useful for planning other large, population-based studies.

Hormone levels during dietary changes in premenopausal African-American women.

BACKGROUND: In the United States, 5-year survival rates of 69% and 84%, respectively, have recently been reported for African-American and Caucasian women diagnosed with breast cancer. Differences in the levels of endogenous sex hormones in these populations could explain some of the variation in survival rates, since estrogen is recognized as a risk factor for this type of cancer. PURPOSE: Dietary factors are known to affect endogenous hormone levels; therefore, our study was designed to determine the serum hormone levels of African-American women consuming a typical North American diet, to determine the effect of a low-fat and high-fiber diet on their serum hormone levels, and to compare the base-line serum hormone levels in the African-American women with hormone data from our study of Caucasian women (n = 68) consuming the same control diet. METHODS: Twenty-one healthy, premenopausal, African-American women who agreed to eat only food prepared in a clinical study unit were recruited into the study. The control diet was similar to their usual diet, being high in fat (40% of calories from fat) and low in fiber (12 g/day), and was consumed on average for 3 weeks. The concentrations of estrone (E1), estrone sulfate (E1SO4), estradiol (E2), free E2, androstenedione, and sex hormone-binding globulin (SHBG) in serum samples obtained from the participants during the last week of the control diet and during the follicular phase of their menstrual cycle were determined. The women were then switched to a diet low in fat (20% of calories as fat) and high in fiber (40 g/day); they consumed this diet for two menstrual cycles before blood samples were collected for determination of serum hormone levels. Repeated-measures regression modeling was used to investigate the relationship between diet and hormone levels in African-American and Caucasian women. All P values resulted from two-sided statistical tests. RESULTS: Analysis of serum hormone levels in the African-American women indicated that the change in diet caused a significant decrease in E2 (-8.5%; 95% confidence interval [CI] = -16.1% to -0.3%; P < or = .03) and E1SO4 (-16.2%; 95% CI = -22.1% to -9.8%; P < .0001) and a significant increase in androstenedione levels (+18.3%; 95% CI = +10.3% to +26.8%; P < .0001). SHBG levels of the African-American women were 5.6% (95% CI = -14.0% to +3.7%) lower for those on the experimental diet compared with those on the control diet, but the difference was not statistically significant. Comparison of control serum hormone values in the African-American women in this study with those in Caucasian women previously studied indicated that the Caucasian women had statistically significant lower levels of E1 (-37%; 95% CI = -61.2% to -16.4%; P < or = .0002), E2 (-54.5%; 95% CI = -90.9% to -25.1%; P < or = .0001), free E2 (-30.2%; 95% CI = -65.7% to -2.3%; P < .03), and androstenedione (-48.3%; 95% CI = -83.7% to -19.7%; P < or = .0004). CONCLUSION: African-American women appear to have higher levels of serum hormones than Caucasian women, and dietary modification can result in a lowering of serum estrogens.

Socio-economic and demographic factors associated with prevalence of HIV infection among pregnant women in Dar es Salaam, Tanzania.

BACKGROUND: HIV/AIDS epidemic has become generalised in low resource settings in sub-Saharan Africa where 90% of all maternal-foetal transmission of HIV infection occurs. Global effort to scale-up pMTCT is underway, however, mechanisms to maximise screening of HIV- 1 positive women for Nevirapine treatment and other interventions, are not clear. OBJECTIVE: To identify socioeconomic and demographic characteristics associated with the prevalence of HIV- 1 infection among Tanzanian women. DESIGN: Cross-sectional study. SETTING: Four antenatal clinics in Dar es Salaam. RESULTS: HIV prevalence rate was 13.1 (95% confidence interval (CI): 12.7% - 13.5%) and it increased with increasing maternal age. Older age than 25, mid-arm circumference less than 25cm, geographic location, working in a public house, and partner's occupation were independently associated with higher prevalence of infection. Women in monogamous marriages were 77% less likely to be HIV infected compared to women with no regular partner. Similarly, women with more than five persons per household, and those who spent less on food had a significantly lower HIV prevalence. CONCLUSION: HIV infection is sufficiently widespread among women in Dar es Salaam suggesting that screening based on socioeconomic and demographic characteristics would miss a large proportion of the positives. There is need to increase facilities for counselling and testing using an opt-out approach for testing in all antenatal clinics in the city.

Factors related to diabetes mellitus in Puerto Rican men.

Urban-rural comparisons of the prevalence of diabetes were made in a cohort of 2567 rural and 6190 urban participants aged 45 to 64, in the Puerto Rico Heart Health Program. The prevalence of diabetes in the urban population was more than double that in the rural. Consistent with this, blood glucose concentrations were significantly higher in urban than in rural populations. The prevalence of diabetes increased with age and relative weight. It was associated with elevations of serum cholesterol, blood pressure, and fasting serum triglycerides. A positive family history was found more commonly in diabetics than in nondiabetics. If there was a history in both a sibling and a parent, there was at least a threefold increased prevalence over those with no family history. The reason for the higher prevalence of diabetes in the urban than in the rural area is elusive. In obese men, the urban and rural prevalence rates are the same, but, among relatively lean men, the prevalence in the urban area is twice that of the rural men.

Vitamin A supplementation and severity of pneumonia in children admitted to the hospital in Dar es Salaam, Tanzania.

Vitamin A deficiency and acute lower respiratory tract infections coexist as important public health problems in many developing countries. We carried out a randomized, double-blind, placebo-controlled trial to examine whether large doses of vitamin A given to Tanzanian children who are admitted to the hospital with nonmeasles pneumonia would reduce the severity of respiratory disease. Six hundred eighty-seven children were randomly assigned to receive either placebo or vitamin A [200 000 IU (60 mg retinol equivalents) for children > 1 y of age and 100000 IU (30 mg retinol equivalents) for infants] on the day of admission and another dose on the following day. Of the 346 children in the vitamin A group, 13 died in the hospital, compared with 8 of 341 children in the placebo group; the relative mortality was 1.63 (95% CI: 0.67, 3.97; P = 0.28). The mean number of days of hospitalization was the same in both groups (4.2 d). There were no differences between the vitamin A and placebo groups in the duration of hospital stay when examined within categories of children stratified by age, sex, breast-feeding status, nutritional status at baseline, or quartile of dietary vitamin A intake in the 4 mo before admission to the hospital. There were also no differences in the mean number of days of fever, rapid respiratory rate, or hypoxia, whether these endpoints were examined in the total number of subjects or in a subset with more severe clinical conditions at baseline. Large doses of vitamin A had no protective effect on the course of pneumonia in hospitalized Tanzanian children.

Determinants of low birth weight among HIV-infected pregnant women in Tanzania.

BACKGROUND: Low birth weight (LBW) increases the risk of infant death, but little is known about its causes among HIV-infected populations in sub-Saharan Africa. OBJECTIVE: We assessed sociodemographic, nutritional, immunologic, parasitic, and infant risk factors for birth weight, LBW, and small-for-gestational-age (SGA) status in a cohort of 822 HIV-positive women enrolled in a clinical trial of vitamin supplementation and pregnancy outcomes in Dar es Salaam, Tanzania. DESIGN: Women were enrolled at prenatal care clinics during their second trimester, at which time blood, stool, urine, and genital specimens were collected, and anthropometric measurements and sociodemographic data were recorded. Birth weight was measured at hospital delivery. RESULTS: The mean (+/-SD) birth weight was 3015 +/- 508 g, 11.1% of newborns weighed <2500 g (LBW), and 11.5% were SGA. In multivariate analyses, maternal weight at enrollment and a low CD8 cell count were inversely associated with LBW. Advanced-stage HIV disease, previous history of preterm birth, Plasmodium falciparum malaria, and any helmintic infection were associated with higher risk of LBW. The intestinal parasites Entamoeba histolytica and Strongyloides stercoralis were predictors of LBW despite their low prevalence in the cohort. In a multivariate-adjusted linear regression model, BMI, midupper arm circumference, a CD4 cell count <200 x 10(6) cells/L (200 cells/mm(3)), primiparity, maternal literacy, and infant HIV infection at birth were significantly associated with birth weight in addition to risk factors included in the LBW model. Determinants of SGA included maternal weight, low serum vitamin E concentration, candidiasis, malaria, and infant HIV infection at birth. CONCLUSION: Prevention of HIV disease progression and vertical transmission, improved nutritional status, and better management of malaria and intestinal parasitic infections are likely to reduce the incidence of LBW in Tanzania.

Morphology and function of the aqueous outflow system in monkey eyes perfused with sulfhydryl reagents.

The aqueous outflow system from anterior chamber to Schlemm's canal was examined by electron microscopy in pairs of enucleated macaque and baboon eyes, perfused via the anterior chamber with mock aqueous humor in one eye and the same fluid with added iodoacetamide (IA) or N-ethyl maleimide (NEM) in the other eye. Many details of the electron micrographs were analyzed in a masked manner using a digitizing bit pad and computer, and also using visual evaluation. Both IA and NEM increased aqueous humor outflow facility, but the morphologic changes induced by IA were quantitatively different from those induced by NEM. Intercellular junctions were not affected by IA, but were disrupted by NEM (P less than 0.01). Vacuoles in the endothelial lining of Schlemm's canal tended to increase in area, but not in number, under the influence of IA, whereas they were not so affected by NEM. No loss of extracellular material was observed in either IA- or NEM-treated eyes. The results indicate that the chemical status of cellular-SH groups may influence aqueous humor outflow facility at multiple sites in the outflow pathway.

The relationship between pore density and outflow facility in human eyes.

The inner wall (IW) endothelial lining of Schlemm's canal was examined in six normal human eyes and four eyes with primary open angle glaucoma (POAG). Outflow facility was measured using constant pressure perfusion at 15 mmHg, eyes were fixed at 15 mmHg, and the IW endothelial lining was isolated and examined by scanning electron microscopy. Pore density, pore diameter, and bulge density were recorded by quadrant, and pore size and density were used to estimate IW endothelial facility, resistance, and hydraulic conductivity (facility per unit area). In POAG eyes, pores were less common (489 +/- 172 vs 1437 +/- 423 pores/mm2; P less than .005) and appeared to be more unevenly distributed than in normal eyes. A regional analysis of pore density (by quadrant) failed to detect a significant difference between quadrants of normal or POAG eyes. Pore density was correlated with measured outflow facility in normal eyes alone (P less than .02) and when normal eyes were pooled with POAG eyes (P less than .001). The percentage of total resistance attributed to the IW endothelium was 5.8% in normals compared to 9.5% in POAG eyes. This indicates there is a greater pressure drop across the IW endothelium in POAG eyes, suggesting that an intrinsic difference in IW endothelial function exists between normal and glaucomatous eyes. However, this difference alone does not account for the decreased outflow facility in POAG eyes. IW endothelial hydraulic conductivity is markedly higher than that of other vascular endothelia. We hypothesize that this may protect the IW endothelial lining of Schlemm's canal from mechanical stress induced by the relatively high rate of transcellular fluid flow.

A randomized trial of vitamin A supplements in relation to mortality among human immunodeficiency virus-infected and uninfected children in Tanzania.

OBJECTIVES: To determine whether vitamin A supplements result in reduced mortality among HIV-infected and uninfected children. DESIGN: Randomized, double blind, placebo-controlled trial. METHODS: Starting in April, 1993, we randomized 687 children age 6 months to 5 years who were admitted to the hospital with pneumonia. Children who were severely malnourished or had clinical signs of vitamin A deficiency were excluded. At baseline children received placebo or 400 000 IU (or half that for infants) of vitamin A, in addition to standard treatment for pneumonia. They received further doses of the same regimen 4 and 8 months after hospital discharge. Sera from children were tested for HIV antibodies by enzyme-linked immunosorbent assay and Western blot tests. For positive children <15 months of age, HIV infection was confirmed by amplified heat-denatured HIV-p24 antigen assays with confirmatory neutralization assays. HIV status was ascertained for 648 of 687 enrolled children. The mean duration of follow-up was 24.4 months (SD = 12.1). RESULTS: Of 648 children 58 (9%) were HIV-infected. Compared with uninfected children, all-cause mortality was higher among HIV-infected children, as was mortality caused by pneumonia or diarrhea (P < 0.001 for each). Overall vitamin A supplements resulted in a 49% reduction in mortality [relative risk (RR), 0.51; 95% confidence interval (CI), 0.29 to 0.90, P = 0.02]. Vitamin A supplements reduced all-cause mortality by 63% among HIV-infected children (RR 0.37; CI 0.14 to 0.95, P = 0.04) and by 42% among uninfected children (RR 0.58, CI 0.28 to 1.19, P = 0.14). Vitamin A supplements were also associated with a 68% reduction in AIDS-related deaths (P = 0.05) and a 92% reduction in diarrhea-related deaths (P = 0.01). CONCLUSION: Vitamin A deficiency, which is common among children in many developing countries, is particularly severe among HIV-infected children. Our findings indicate that vitamin A supplements, a low cost intervention, reduce mortality of HIV-infected children.

Effects of long-acting versus short-acting calcium channel blockers among older survivors of acute myocardial infarction.

OBJECTIVE: Recent studies have highlighted the potentially harmful effects of short-acting calcium channel blockers, especially of the dihydropyridine type, in patients with coronary heart disease. Some have argued that long-acting calcium channel blockers are safer, but few outcome data exist. The objective of the study was to compare the occurrence of adverse outcomes among recipients of long-acting versus short-acting calcium channel blockers, with dihydropyridines and non-dihydropyridines compared separately. SETTING: The New Jersey Medicare population. DESIGN: A retrospective cohort study using linked Medicare and drug claims data. PARTICIPANTS: Older survivors of acute myocardial infarction (MI) occurring in 1989 and 1990. Eligible subjects had survived at least 30 days after the MI, participated in Medicare and a drug benefits program, and were prescribed a single type of either a long-acting or a short-acting calcium channel blocker within 90 days after the MI. MEASUREMENTS: The two outcome measures were rates of all-cause mortality and cardiac rehospitalization. Using separate Cox regression models for dihydropyridines (nifedipine, nicardipine) and non-dihydropyridines (diltiazem, verapamil), we examined these outcomes for recipients of long-acting compared with short-acting calcium channel blockers. RESULTS: Of the 833 patients eligible for the study, 160 were prescribed long-acting and 673 short-acting calcium channel blockers. Clinical characteristics of long-acting and short-acting users were comparable. During 2 years of follow-up, 221 deaths and 300 rehospitalizations occurred. Controlling for age, sex, race, and indicators of disease severity and comorbidity, the relative risk of dying for recipients of long-acting, compared with short-acting, dihydropyridines was .42 (95% confidence interval (CI), 0.21-0.86). For cardiac rehospitalization, the relative risk was 0.57 (95% CI, 0.34-0.94). For the long-acting versus short-acting nondihydropyridines, the adjusted relative risk of dying was 1.43 (95% CI, 0.88-2.32), and for cardiac rehospitalization, .65 (95% CI, 0.40-1.05). CONCLUSION: Use of long-acting dihydropyridine calcium channel blockers after acute MI was associated with substantially lower rates of cardiac rehospitalization and death compared with use of their short-acting counterparts. More data are needed to address the possibility that long-acting, compared with short-acting, non-dihydropyridines could decrease rehospitalization rates but increase mortality.

Carbonic anhydrase inhibitors induce elevations in human whole-blood zinc levels.

The use of carbonic anhydrase inhibitors (CAIs) was associated with mean increases in whole-blood zinc levels of 82 micrograms/dL and 70 micrograms/dL, respectively, in a cross-sectional survey and in a prospective study of patients with glaucoma. The time course of the increase suggests that CAIs induce reticulocyte synthesis of carbonic anhydrase.

A case-control study of risk factors in open angle glaucoma.

In a case-control study using an exploratory health questionnaire, we examined the relationship between primary open angle glaucoma (POAG) and a variety of personal characteristics and potential toxic exposures in patients in a general eye service. There were 83 patients with definite POAG, 121 POAG suspects, and 237 controls. Using multiple logistic regression analysis for simultaneous evaluation of potential risk factors, we found that black race (rate ratio = 6.8; 95% confidence interval [CI] = 2.8 to 16.0) and untreated systolic hypertension (rate ratio = 5.8; 95% CI = 2.2 to 15) were the most important risk factors. Current cigarette smoking was also associated with glaucoma (rate ratio = 2.9; 95% CI = 1.3 to 6.6). Suggestive associations were found with family history of glaucoma, definite or borderline diabetes, and myopia. The effects of many of these personal characteristics and exposures as risk factors were also noted for the glaucoma suspect group, though not as strongly as for the definite glaucoma cases.

Quantification of nerve fiber layer thickness in normal and glaucomatous eyes using optical coherence tomography.

PURPOSE: Quantitative assessment of nerve fiber layer (NFL) thickness in normal and glaucomatous eyes, and correlation with conventional measurements of the optic nerve structure and function. METHODS: We studied 59 eyes of 33 subjects by conventional ophthalmologic physical examination, Humphrey 24-2 visual fields, stereoscopic optic nerve head photography, and optical coherence tomography. RESULTS: Nerve fiber layer thickness as measured by optical coherence tomography demonstrated a high degree of correlation with functional status of the optic nerve, as measured by visual field examination (P = .0001). Neither cupping of the optic nerve nor neuroretinal rim area were as strongly associated with visual field loss as was NFL thickness (P = .17 and P = .21, respectively). Cupping correlated with NFL thickness only when the cup was small (cup-to-diameter ratio, 0.1 to 0.3) or large (cup-to-diameter ratio, 0.8 to 1.0) (P = .006); there was no correlation between cupping and NFL thickness otherwise. Nerve fiber layer, especially in the inferior quadrant, was significantly thinner in glaucomatous eyes than in normal eyes (P = .04). Finally, we found a decrease in NFL thickness with aging, even when controlling for factors associated with the diagnosis of glaucoma (P = .03). CONCLUSIONS: Nerve fiber layer thickness can be measured using optical coherence tomography. These measurements provide good structural and functional correlation with known parameters.

Changes in plasma lipoprotein concentrations and composition in response to a low-fat, high-fiber diet are associated with changes in serum estrogen concentrations in premenopausal women.

We have investigated the effects of a low-fat, high-fiber diet on plasma lipid and lipoprotein levels and serum sex hormone concentrations in 22 normal premenopausal women (mean age, 25.8 +/- 3.8 years). Participants consumed a baseline diet for 4 weeks (40% of calories as fat, 16% as saturated fatty acids, 8% as polyunsaturated fatty acids, 400 mg/d cholesterol, and 12 g/d dietary fiber) and then a low-fat, high-fiber diet for 8 to 10 weeks (16% to 18% of calories as fat, 4% as saturated fatty acids, 4% as polyunsaturated fatty acids, 150 mg/d cholesterol, and 40 g/d fiber). Blood samples for determination of plasma lipids and serum hormones were obtained during the follicular and luteal phases of the menstrual cycle during both diets. Compared with the baseline diet, the low-fat, high-fiber diet resulted in significant decreases in total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol concentrations during both the follicular and luteal phases (TC, -14% and -16%; LDL cholesterol, -14% and -17%; and HDL cholesterol, -15% and -18%, respectively). During the follicular phase but not the luteal phase on the low-fat, high-fiber diet, women exhibited significant increases in plasma triglyceride ([TG] 22%) and very-low-density lipoprotein (VLDL)-TG (36%) concentrations. During the follicular phase, serum estrone sulfate concentrations decreased by 25% (P < .0001) when subjects were fed the low-fat, high-fiber diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Adequacy of the ELISA test for screening corneal transplant donors.

Using a simple mathematical model, we calculated the risk for a patient undergoing penetrating keratoplasty to receive a cornea from a human immunodeficiency virus-infected donor despite negative results on serologic testing of donor serum. This error in serologic testing occurred when false-negative results were obtained from the enzyme-linked immunosorbent assay used to screen donor corneas for human immunodeficiency virus exposure. The average risk of transplanting an infected cornea was low, 0.03%, but increased by a factor of ten when donor tissue from donors at high risk for AIDS was used. Current screening procedures are probably adequate to prevent transmission of human immunodeficiency virus, but increased vigilance for high-risk donor populations may be appropriate.

A double-masked comparison of betaxolol vs timolol in the treatment of open-angle glaucoma.

We conducted a six-month prospective, double-masked randomized trial comparing betaxolol with timolol at 0.25% and 0.5% concentrations in the treatment of primary open-angle glaucoma in 38 patients. To qualify, patients had to demonstrate an average intraocular pressure in at least one eye of greater than or equal to 26 mm Hg without treatment. The median intraocular pressure was consistently lower in the timolol group than in the betaxolol group (after four weeks of therapy, it was 20.2 mm Hg for timolol vs 22.5 mm Hg for betaxolol; P less than .04). Adjunctive therapy was required in eight patients in the betaxolol group compared to one in the timolol group (P less than .05). Betaxolol appears to be a clinically effective and safe agent in the treatment of open-angle glaucoma. However, the magnitude of the decrease in intraocular pressure with it may not be as great as that with timolol and there may be a greater need for adjunctive therapy with it than with timolol.

Topical indomethacin therapy before argon laser trabeculoplasty.

Fifty treatment sessions for 43 eyes (35 patients) receiving argon laser trabeculoplasty to one-half the angle were randomly assigned in a double-masked fashion to pretreatment with either topical indomethacin 1% or placebo. In 25 treatments intraocular pressure increased 3 mm Hg or more within four hours. Topical indomethacin pretreatment had no effect on the incidence, magnitude, or time course of this acute increase. It also did not alter the long-term effectiveness of the laser treatment (-3.8 mm Hg in the indomethacin-treated group vs -4.3 mm Hg in the placebo-treated group). The overall incidence of new peripheral anterior synechiae found on gonioscopy at one month was 32% (16 of 50 treatments). Synechiae formation was much higher in blacks (ten of 11 eyes or 91%) than in whites (five of 38 eyes or 13%). Although there was an association between acute anterior chamber inflammation after laser treatment and ultimate synechia formation (P less than .05), indomethacin pretreatment did not alter its occurrence.