Magnesium and anabolic hormones in older men.

Optimal nutritional and hormonal statuses are determinants of successful ageing. The age associated decline in anabolic hormones such as testosterone and insulin-like growth factor 1 (IGF-1) is a strong predictor of metabolic syndrome, diabetes and mortality in older men. Studies have shown that magnesium intake affects the secretion of total IGF-1 and increase testosterone bioactivity. This observation suggests that magnesium can be a modulator of the anabolic/catabolic equilibrium disrupted in the elderly people. However, the relationship between magnesium and anabolic hormones in men has not been investigated. We evaluated 399 ≥65-year-old men of CHIANTI in a study population representative of two municipalities of Tuscany (Italy) with complete data on testosterone, total IGF-1, sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate (DHEAS) and serum magnesium levels. Linear regression models were used to test the relationship between magnesium and testosterone and IGF-1. Mean age of the population was 74.18 ± 6.43 (years ± SD, age range 65.2-92.4). After adjusting for age, magnesium was positively associated with total testosterone (ß ± SE, 34.9 ± 10.3; p = 0.001) and with total IGF-1 (ß ± SE, 15.9 ± 4.8; p = 0.001). After further adjustment for body mass index (BMI), log (IL-6), log (DHEAS), log (SHBG), log (insulin), total IGF-1, grip strength, Parkinson's disease and chronic heart failure, the relationship between magnesium and total testosterone remained strong and highly significant (ß ± SE, 48.72 ± 12.61; p = 0.001). In the multivariate analysis adjusted for age, BMI, log (IL-6), liver function, energy intake, log (insulin), log (DHEAS), selenium, magnesium levels were also still significantly associated with IGF-1 (ß ± SE, 16.43 ± 4.90; p = 0.001) and remained significant after adjusting for total testosterone (ß ± SE, 14.4 ± 4.9; p = 0.01). In a cohort of older men, magnesium levels are strongly and independently associated with the anabolic hormones testosterone and IGF-1.

Relationship of household food insecurity to anaemia in children aged 6-59 months among families in rural Indonesia.

BACKGROUND: Anaemia is a significant global public health problem in developing countries with adverse health effects on young children. Household food insecurity, which reflects a household's access, availability and utilisation of food, has not been well characterised in relation to anaemia in children. OBJECTIVE: To examine the relationship of household food insecurity with anaemia (Hb <11 g/dl) in children. METHODS: In a cross-sectional study of 4940 rural households participating in the Indonesian Nutrition Surveillance System, household food insecurity was measured using a modified 9-item food security questionnaire and related to anaemia in children aged 6-59 months. RESULTS: The proportion of households with an anaemic child was 56·6%. In households with and without anaemic children, the mean (SD) food insecurity score was 1·82 (1·72) vs 1·55 (1·54) (p<0·0001), respectively. In a multivariate logistic regression model, food insecurity score was related to anaemia in children (odds ratio 0·77, 95% confidence interval 0·63-0·95, p=0·01) when the highest quintile of food insecurity score was compared with the lowest quintile, adjusting for potential confounders. CONCLUSION: A higher household food insecurity score is associated with greater prevalence of anaemia in children in rural families in Indonesia.

Circulating beta-carotene levels and type 2 diabetes-cause or effect?

AIMS/HYPOTHESIS: Circulating beta-carotene levels are inversely associated with risk of type 2 diabetes, but the causal direction of this association is not certain. In this study we used a Mendelian randomisation approach to provide evidence for or against the causal role of the antioxidant vitamin beta-carotene in type 2 diabetes. METHODS: We used a common polymorphism (rs6564851) near the BCMO1 gene, which is strongly associated with circulating beta-carotene levels (p = 2 x 10(-24)), with each G allele associated with a 0.27 standard deviation increase in levels. We used data from the InCHIANTI and Uppsala Longitudinal Study of Adult Men (ULSAM) studies to estimate the association between beta-carotene levels and type 2 diabetes. We next used a triangulation approach to estimate the expected effect of rs6564851 on type 2 diabetes risk and compared this with the observed effect using data from 4549 type 2 diabetes patients and 5579 controls from the Diabetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium. RESULTS: A 0.27 standard deviation increase in beta-carotene levels was associated with an OR of 0.90 (95% CI 0.86-0.95) for type 2 diabetes in the InCHIANTI study. This association was similar to that of the ULSAM study (OR 0.90 [0.84-0.97]). In contrast, there was no association between rs6564851 and type 2 diabetes (OR 0.98 [0.93-1.04], p = 0.58); this effect size was also smaller than that expected, given the known associations between rs6564851 and beta-carotene levels, and the associations between beta-carotene levels and type 2 diabetes. CONCLUSIONS/INTERPRETATION: Our findings in this Mendelian randomisation study are in keeping with randomised controlled trials suggesting that beta-carotene is not causally protective against type 2 diabetes.

Low serum carotenoids are associated with a decline in walking speed in older women.

BACKGROUND AND OBJECTIVES: Walking speed is an important measure of physical performance that is predictive of disability and mortality. The relationship of dietary factors to changes in physical performance has not been well characterized in older adults. The aim was to determine whether total serum carotenoid concentrations, a marker for fruit and vegetable intake, and serum selenium are related to changes in walking speed in older women. SUBJECTS AND METHODS: The relationship between total serum carotenoids and selenium measured at baseline, 12, and 24 months follow-up and walking speed assessed at baseline and every six months for 36 months was examined in 687 moderately to severely disabled women, 65 years or older, living in the community. RESULTS: Mean total serum carotenoids were associated with mean walking speed over three years of follow-up (P = 0.0003) and rate of change of walking speed (P = 0.007) in multivariate linear regression models adjusting for age, body mass index, and chronic diseases. Mean serum selenium was associated with mean walking speed over three years of follow-up (P = 0.0003) but not with the rate of change of walking speed (P = 0.26). CONCLUSIONS: These findings suggest that a higher fruit and vegetable intake, as indicated by higher total serum carotenoid concentrations, may be protective against a decline in walking speed in older women.

Paternal smoking and increased risk of child malnutrition among families in rural Indonesia.

OBJECTIVE: To determine whether paternal smoking is associated with an increased risk of child malnutrition among families in rural Indonesia. METHODS: The relation between paternal smoking and child malnutrition was examined in a population-based sample of 438 336 households in the Indonesia Nutrition and Health Surveillance System, 2000-2003. Main outcome measures were child underweight (weight-for-age Z score <-2) and stunting (height-for-age Z score <-2) and severe underweight and severe stunting, defined by respective Z scores <-3, for children aged 0-59 months of age. RESULTS: The prevalence of paternal smoking was 73.7%. The prevalence of underweight and stunting was 29.4% and 31.4%, and of severe underweight and severe stunting was 5.2%, and 9.1%, respectively. After adjusting for child gender, child age, maternal age, maternal education, weekly per capita household expenditure and province, paternal smoking was associated with an increased risk of underweight (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01 to 1.05, p = 0.001) and stunting (OR 1.11, 95% CI 1.09 to 1.13, p<0.001) and severe underweight (OR 1.06, 95% CI 1.01 to 1.10) p = 0.020) and severe stunting (OR 1.12, 95% CI 1.08 to 1.16, p<0.001). CONCLUSIONS: Paternal smoking is associated with an increased risk of child malnutrition in families living in rural Indonesia.

Markers of B-vitamin deficiency and frailty in older women.

OBJECTIVE: To evaluate the association between markers of vitamins B12, B6 and folate deficiency and the geriatric syndrome of frailty. DESIGN: Cross-sectional study of baseline measures from the combined Women's Health and Aging Studies. SETTING: Baltimore, Maryland. PARTICIPANTS: Seven hundred three community-dwelling women, aged 70-79. MEASUREMENTS: Frailty was defined by five-component screening criteria that include weight, grip strength, endurance, physical activity and walking speed measurements and modeled as binary and 3-level polytomous outcomes. Independent variables serum vitamin B6, vitamin B12, methylmalonic acid, total homocysteine, cystathionine and folate were modeled continuously and as abnormal versus normal. RESULTS: Serum biomarker levels varied significantly by race. All analyses were race-stratified and results are reported only for Caucasian women due to small African American sample size. In polytomous logistic regression models of 3-level frailty, Caucasian women with increasing MMA, defined either continuously or using a predefined threshold, had 40-60% greater odds of being prefrail (p-values < 0.07) and 1.66-2.33 times greater odds of being frail (p-values < 0.02) compared to nonfrails after adjustment for age, education, low serum carotenoids, alcohol intake, cardiovascular disease and renal impairment. Both binary and polytomous frailty models evaluating vitamin B12 as the main exposure estimated odds ratios that were similar in trend yet slightly less significant than the MMA results. CONCLUSIONS: These results suggest that vitamin B12 deficiency may contribute to the frailty syndrome in community-dwelling older women. Future studies are needed to explore these relationships longitudinally.

Micronutrient supplements and mortality of HIV-infected adults with pulmonary TB: a controlled clinical trial.

SETTING: Zomba and Blantyre, Malawi, Africa. OBJECTIVES: To determine whether daily micronutrient supplementation reduces the mortality of human immunodeficiency virus (HIV) infected adults with pulmonary tuberculosis (TB). DESIGN: A randomised, controlled clinical trial of micronutrient supplementation for HIV-positive and HIV-negative adults with pulmonary TB. Participants were enrolled at the commencement of chemotherapy for sputum smear-positive pulmonary TB and followed up for 24 months. RESULTS: A total of 829 HIV-positive and 573 HIV-negative adults were enrolled. During follow-up, 328 HIV-positive and 17 HIV-negative participants died. The proportion of HIV-positive participants who died in the micronutrient and placebo groups was 38.7% and 40.4%, respectively (P = 0.49). Micronutrient supplementation did not reduce mortality (hazard ratio [HR] 0.93, 95%CI 0.75-1.15) among HIV-positive adults. CONCLUSIONS: Micronutrient supplementation at the doses used in this study does not reduce mortality in HIV-positive adults with pulmonary TB in Malawi.

Denture use, malnutrition, frailty, and mortality among older women living in the community.

BACKGROUND: The relationships between denture use, malnutrition, frailty, and mortality in older women have not been well characterized. OBJECTIVE: To determine whether women who use dentures and have difficulty chewing or swallowing are at higher risk of malnutrition, frailty, and mortality. DESIGN: Cross-sectional and longitudinal study of 826 women, aged 70-79, from the Women's Health and Aging Studies, two population-based longitudinal studies of community-dwelling women in Baltimore, Maryland. At enrollment, data on frailty and self-reported denture use and difficulty chewing or swallowing that limited the ability to eat was collected, and plasma vitamins A, D, E, B6, and B12, carotenoids, folate, and albumin were measured. RESULTS: 63.5% of women reported using dentures, of whom 11.6% reported difficulty chewing or swallowing food. Denture users with and without difficulty chewing or swallowing and those not using dentures had, respectively, geometric mean (95% Confidence Interval [C.I.]) total plasma carotenoid concentrations of 1.481 (1.302, 1.684), 1.616 (1.535, 1.700), and 1.840 (1.728, 1.958) micromol/L, respectively (P < 0.0001), and 25- hydroxyvitamin D of 50.90 (44.25, 58.55), 47.46 (45.15, 50.40), and 54.0 (50.9, 56.8) nmol/L (P < 0.0001). The proportion using dentures among non-frail, pre-frail, and frail women was 58%, 66%, and 73%, respectively (P = 0.018). Women who used dentures and reported difficulty chewing or swallowing had lower five-year survival (H.R. 1.43, 95% C.I. 1.05-1.97), after adjusting for potential confounders. CONCLUSIONS: Older women living in the community who use dentures and have difficulty chewing or swallowing have a higher risk of malnutrition, frailty, and mortality.

Low plasma selenium concentrations, high plasma human immunodeficiency virus load and high interleukin-6 concentrations are risk factors associated with anemia in adults presenting with pulmonary tuberculosis in Zomba district, Malawi.

BACKGROUND: Although anemia is common among adults with pulmonary tuberculosis and human immunodeficiency virus (HIV) infection in sub-Saharan Africa, the factors contributing to its pathogenesis have not been well characterized. OBJECTIVE: To characterize the antioxidant micronutrient status, interleukin-6 (IL-6) concentrations, and HIV load in relationship with anemia in adults with pulmonary tuberculosis. SETTING: Zomba district, Malawi. METHODS: Erythropoietin, IL-6, plasma HIV load, and markers of micronutrient status (hemoglobin (Hb), plasma concentrations of retinol, alpha-tocopherol, carotenoids, ferritin, zinc, and selenium) were measured in 500 adults who presented with pulmonary tuberculosis in Zomba Central Hospital, Malawi. RESULTS: Among 370 HIV-positive and 130 HIV-negative adults, the prevalence of anemia was 88 and 77%, respectively (P = 0.002), and moderate to severe anemia (Hb < 80 g/l) occurred in 30 and 15%, respectively (P = 0.001). Geometric mean IL-6 concentration was 21.1 pg/ml, with no difference between HIV-positive and -negative adults. The erythropoietin response to anemia was not different between adults with elevated IL-6 and those with lower IL-6 concentrations. In a multivariate logistic regression model, HIV load, and lower plasma selenium concentrations were associated with moderate to severe anemia. In a final multivariate linear regression model, IL-6, plasma HIV load, and plasma selenium concentrations were associated with Hb concentrations. CONCLUSION: This study suggests that low selenium concentrations, high HIV load, and high IL-6 concentrations are associated with anemia in adults with pulmonary tuberculosis in sub-Saharan Africa.

Epidemiology and microbiology of subclinical mastitis among HIV-infected women in Malawi.

The epidemiology and microbiology of subclinical mastitis, a risk factor for perinatal HIV transmission, have not been well characterized. In all, 250 HIV-infected women were followed from two weeks to 12 months postpartum in Blantyre, Malawi, and subclinical mastitis was assessed by breast milk leukocyte counts. The point prevalence of subclinical mastitis at 2, 4, 6, 10, and 14 weeks, and 6, 9, and 12 months was 12.2%, 7.8%, 6.8%, 3.7%, 10.6%, 5.1%, 4.9%, and 1.9%, respectively (P = 0.002), and 27.2% of women had at least one episode of subclinical mastitis. There was no significant relationship between maternal plasma HIV load or parity and subclinical mastitis. Staphylococcus aureus was isolated in 30% of women with subclinical mastitis, and the proportion of women with positive cultures decreased during follow-up (P = 0.02). Subclinical mastitis is prevalent among breastfeeding mothers and further studies are needed to characterize the differences between infectious and non-infectious subclinical mastitis.

Increased mortality associated with vitamin A deficiency during human immunodeficiency virus type 1 infection.

OBJECTIVE: To determine whether plasma vitamin A levels are associated with immunologic status and clinical outcome during human immunodeficiency virus type 1 (HIV-1) infection. PATIENTS AND METHODS: Analysis of vitamin A levels, CD4 T cells, complete blood cell count, and serologic markers for liver disease in a random subsample of 179 subjects from a cohort of more than 2000 intravenous drug users with longitudinal follow-up to determine survival. RESULTS: Mean (+/- SE) follow-up time was 22.8 +/- 1.1 months, and 15 subjects died during follow-up. More than 15% of the HIV-1-seropositive individuals had plasma vitamin A levels less than 1.05 mumol/L, a level consistent with vitamin A deficiency. The HIV-1-seropositive individuals had lower mean plasma vitamin A levels than HIV-1-seronegative individuals (P < .001). Vitamin A deficiency was associated with lower CD4 levels among both seronegative individuals (P < .05) and seropositive individuals (P < .05). In the HIV-seropositive participants, vitamin A deficiency was associated with increased mortality (relative risk = 6.3; 95% confidence interval, 2.1 to 18.6). CONCLUSION: Vitamin A deficiency may be common during HIV-1 infection, and vitamin A deficiency is associated with decreased circulating CD4 T cells and increased mortality. Vitamin A is an essential micronutrient for normal immune function, and vitamin A deficiency seems to be an important risk factor for disease progression during HIV-1 infection.

Catheter complications in AIDS patients treated for cytomegalovirus retinitis.

PURPOSE: To describe the complications of central venous catheter use for intravenous therapy of cytomegalovirus (CMV) retinitis in patients with AIDS. METHODS: Retrospective review of 388 patients with AIDS and CMV retinitis treated with intravenous medications through an indwelling catheter. RESULTS: The catheter complication rate was 1.2 complications per person-year (0.33 complications per 100 catheter-days). Current injecting drug use increased the risk of infectious complications [hazard ratio (HR), 1.73; P=0.04] whereas former use did not (HR, 0.96; P=0.88). Subdermal port catheters increased the risk of bacteremia (HR, 1.78; P=0.05). Mortality for the first complication was 5.8%. Forty percent of patients required catheter removal, and 86.8% of these patients required reinsertion of another catheter. CONCLUSIONS: Catheter complications are a substantial problem in patients with CMV retinitis treated with daily intravenous therapy.

Association between serum vitamin A and E levels and HIV-1 disease progression.

OBJECTIVE: To examine the associations between serum vitamin A and E levels and risk of progression to three key outcomes in HIV-1 infection: first AIDS diagnosis, CD4+ cell decline to < 200 cells x 10(6)/l, and mortality. DESIGN: Non-concurrent prospective study. METHODS: Serum levels of vitamins A and E were measured at the enrollment visit of 311 HIV-seroprevalent homo-/bisexual men participating in the Baltimore/ Washington DC site of the Multicenter AIDS Cohort Study. Cox proportional hazards models were used to estimate the relative hazard of progression to each outcome over the subsequent 9 years, adjusting for several independent covariates. RESULTS: Men in the highest quartile of serum vitamin E levels (> or = 23.5 mumol/l) showed a 34% decrease in risk of progression to AIDS compared with those in the lowest quartile [relative hazard (RH), 0.66; 95% confidence interval (CI), 0.41-1.06)]. This effect was statistically significant when comparing the highest quartile of serum vitamin E to the remainder of the cohort (RH, 0.67; 95% CI, 0.45-0.98). Associations between serum vitamin A levels and risk of progression to AIDS were less clear, but vitamin A levels were uniformly in the normal to high range (median = 2.44 mumol/l). Similar trends were observed for each vitamin with mortality as the outcome, but neither vitamin was associated with CD4+ cell decline to < 200 cells x 10(6)/l. Men who reported current use of multivitamin or single vitamin E supplements had significantly higher serum tocopherol levels than those who were not taking supplements (P = 0.0001). Serum retinol levels were unrelated to intake of multivitamin or single vitamin A supplements. CONCLUSIONS: These data suggest that high serum levels of vitamin E may be associated with slower HIV-1 disease progression, but no relationship was observed between retinol levels and disease progression in this vitamin A-replete population.

Vitamin A deficiency and maternal-infant transmissions of HIV in two metropolitan areas in the United States.

OBJECTIVE: To determine whether vitamin A deficiency is associated with maternal-infant HIV transmission among HIV-infected pregnant women in two United States cities. METHODS: Third trimester serum vitamin A levels were evaluated using high-performance liquid chromatography in 133 HIV-infected women who delivered livebirths during May 1986 to May 1994 and whose infants had known HIV infection status. RESULTS: Sixteen per cent (seven out of 44) of the transmitting mothers and 6% (five out of 89) of the non-transmitting mothers had severe vitamin A deficiency (< 0.70 mumol/l; P = 0.05). Maternal-infant transmission was also associated with prematurity < 37 weeks gestation (P = 0.02), and Cesarean section delivery (P = 0.04), CD4 percentage (P = 0.03) and marginally associated with duration of membrane rupture of > or = 4 h (P = 0.06) by univariate analysis. In a multivariate logistic regression model, severe vitamin A deficiency [adjusted odds ratio (AOR), 5.05; 95% confidence interval (CI), 1.20-21.24], Cesarean section delivery (AOR, 3.75; 95% CI, 1.10-12.87), and prematurity (AOR, 2.25; 95% CI, 1.22-4.13) were associated with transmission after adjusting for CD4+ percentage, and duration of membrane rupture. CONCLUSION: Increased risk of maternal-infant transmission was associated with severe vitamin A deficiency among non-breastfeeding women in these cohorts from the United States.

Hyporetinolemia and acute phase proteins in children with and without xerophthalmia.

BACKGROUND: The relations among hyporetinolemia, acute phase proteins, and vitamin A status in children are unclear. OBJECTIVE: The objective was to examine the relations between acute phase proteins and plasma retinol concentrations in children with and without clinical vitamin A deficiency (Bitot spots and night blindness). DESIGN: The study was a nonconcurrent analysis of acute phase protein concentrations and other data from a previous clinical trial. Preschool children, 3-6 y of age, with (n = 118) and without (n = 118) xerophthalmia were assigned to receive oral vitamin A (60 mg retinol equivalent) or placebo and were seen at 5 wk. All children received oral vitamin A (60 mg retinol equivalent) at 5 wk. RESULTS: At baseline, alpha(1)-acid glycoprotein (AGP) was elevated in 42.9% and 23.5% (P < 0.003) and C-reactive protein (CRP) was elevated in 17.7% and 13.7% (NS) of children with and without xerophthalmia, respectively. Hyporetinolemia (retinol < 0.7 micromol/L) occurred in 61.0% and 47.4% (P < 0.04) of children with and without xerophthalmia, respectively. A history of fever, a history of cough, and nasal discharge noted on examination were each associated with elevated acute phase proteins. Vitamin A supplementation increased plasma retinol at 5 wk but had no significant effect on concentrations of acute phase proteins. CONCLUSIONS: Elevated acute phase protein concentrations and infectious disease morbidity are closely associated during vitamin A deficiency.

Vitamin D deficiency among older women with and without disability.

BACKGROUND: Vitamin D deficiency is associated with bone loss and bone fractures, and the identification of vulnerable populations is important to clinical practice and public health. OBJECTIVE: The objectives of this study were to determine the prevalence of vitamin D deficiency and to examine associated risk factors for vitamin D deficiency in older women. DESIGN: We measured serum concentrations of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1, 25(OH)(2)D], intact parathyroid hormone (PTH), osteocalcin, and ionized calcium in women aged >/=65 y who were participating in the Women's Health and Aging Study I, an observational study of women representing the approximately one-third most disabled women living in the community, and women aged 70-80 y who were participating in the Women's Health and Aging Study II, an observational study of women among the two-thirds least disabled women living in the community in Baltimore. RESULTS: The women were classified into 4 domains of physical disability. Among 371 women with 0 or 1 domain of disability and 682 women with >/=2 domains of disability, 6.2% and 12.6%, respectively, had vitamin D deficiency [serum concentrations of 25(OH)D < 25 nmol/L]. In univariate analyses, risk factors for vitamin D deficiency included increasing age, black race, low educational level, high body mass index, high triceps skinfold thickness, increasing level of disability, winter season, and elevated creatinine concentration. In multivariate models, black race had a strong association with vitamin D deficiency when other risk factors were adjusted for. CONCLUSIONS: Vitamin D deficiency, a preventable disorder, is a common and important public health problem for older disabled women living in the community; black women are at higher risk than are white women.

Experimental ocular onchocerciasis in cynomolgus monkeys. IV. Chorioretinitis elicited by Onchocerca volvulus microfilariae.

Onchocerciasis is a major cause of blindness worldwide, and much of the blindness is caused by onchocercal chorioretinitis. In an experimental animal model for ocular onchocerciasis, intravitreal injections of 10,000 live Onchocerca volvulus microfilariae isolated from infected humans into the eyes of cynomolgus monkeys (Macaca fascicularis) resulted in patchy, progressive loss of retinal pigment with pigment clumping. Areas of pigment loss were less extensive in animals that had been sensitized with microfilariae. Intravitreal injections of dead O. volvulus microfilariae resulted in mild vitritis with relatively less clinical change noted in the retina and choroid. Histopathologic examination revealed thinning and loss of outer retinal layers with pigment migration into the retina, and inflammation was more pronounced in eyes that received live microfilariae. Clinical changes appeared in eyes receiving live microfilariae before the development of significant antibody or cell-mediated immune responses. O. volvulus microfilariae appear to be more suitable than O. lienalis microfilariae in producing lesions which resemble human onchocerciasis in the primate model.

Experimental ocular onchocerciasis in cynomolgus monkeys. II. Chorioretinitis elicited by intravitreal Onchocerca lienalis microfilariae.

Chorioretinitis due to onchocerciasis is a major cause of blindness, and the pathogenesis is poorly understood. We have developed an experimental model for onchocercal chorioretinitis using cynomolgus monkeys (Macaca fascicularis). Two normal monkeys and two monkeys which had received prior sensitization with subcutaneous injections of live Onchocerca lienalis microfilariae were given intravitreal injections of either 0, 10, 50 or 500 live microfilariae. Posterior segment changes included disc edema, venous engorgement, retinal vasculitis, intraretinal hemorrhage, and progressive retinal pigment epithelial (RPE) disturbances. Histopathological findings included perivascular infiltrates with eosinophils, eosinophilic choroiditis, and RPE hypertrophy, hyperplasia and loss of pigment. Microfilariae in the retina had no surrounding inflammation but were found adjacent to areas of RPE alterations. Overall the inflammatory reaction in the two unsensitized monkeys was more severe than that seen in the sensitized monkeys. The retinal appearance of the monkeys resembled that found in human onchocerciasis, and this model appears to be a promising one for future investigations.

Conjunctival nodules associated with onchocerciasis.

A 14-year-old native of Ethiopia with previously treated onchocerciasis moved to California where he was examined for evidence of persisting nematode infestation. Skin and conjunctival biopsy specimens initially disclosed no abnormalities. Subsequently, conjunctival nodules developed, and a biopsy specimen of one of these revealed microfilariae of Onchocerca volvulus lying adjacent to a necrotic eosinophilic granulomatous inflammatory nodule. To our knowledge, nodules of this type have not heretofore been reported to be a notable feature of ocular onchocerciasis. This type of inflammation has a relationship to degenerating microfilaria in onchocerciasis and in other nematode infestation.

Association between measures of vitamin A and the ocular fundus findings in cerebral malaria.

OBJECTIVE: To investigate the relationship between serum vitamin A levels and conjunctival impression cytology and retinal whitening present in Malawian children with cerebral malaria. METHODS: Standard retinal examination and conjunctival impression cytology were performed at hospital admission on 101 consecutively admitted children with cerebral malaria. Blood samples were drawn from 56 children at 24 hours, frozen at -20 degrees C, and transported for assessment of vitamin A levels by high-performance liquid chromatography. Associations among fundus findings and vitamin A measurements were sought. RESULTS: The whitening of the retina that we have previously described in children with cerebral malaria was found to be associated with a mean+/-SD serum vitamin A level of 0.29+/-0.1 micromol/L, compared with a mean vitamin A level of 0.41+/-0.2 micromol/L in children without retinal whitening. Children with retinal whitening were 2.77 (95% CI, 1.06-7.3) times more likely to have abnormal conjunctival impression cytology results than those without whitening. No child had any clinical or ophthalmologic evidence of chronic vitamin A deficiency. CONCLUSIONS: The retinal whitening described in children with cerebral malaria is associated with low serum vitamin A levels and with abnormal conjunctival impression cytology results and may be due to acute vitamin A deficiency at the tissue level.