Interferon-associated retinopathy in a diabetic patient.
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Biomedical subjects
Publications and source records attributed to R H Gray.
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A random sample of 960 women aged 15-59 years enrolled in a population-based study in rural Uganda were asked to provide self-collected vaginal swabs for human papillomavirus (HPV) testing by hybrid capture assay. The intensity of HPV infection was assessed by the relative light unit (RLU) ratio in the specimen-to-positive control (PC) ratio. In total, 898 women (93%) provided a swab and 737 provided serum for human immunodeficiency virus type 1 (HIV-1) determination. HPV prevalence was 16.7% and was highest in younger women. HIV-1 prevalence was 17.8%. HPV prevalence was 44.3% in HIV-positive and 10.2% in HIV-negative women (rate ratio, 5.36; 95% confidence interval, 3.81-7.54). The intensity of HPV infection was significantly greater among HIV-positive than HIV-negative women (54. 4 vs. 11.1 RLU/PC; P=.026); intensity of infection was highest in women aged <30 years. The higher prevalence and intensity of HPV infection in HIV-positive women could facilitate HPV transmission in this population. Self-collected vaginal swabs could be used in population-based screening to identify women at high risk of cervical neoplasia.
BACKGROUND AND OBJECTIVES: To evaluate a urine HIV-1 test. STUDY DESIGN: Paired urine and blood samples from a sample of 222 subjects were assayed for HIV-1 using Calypte HIV-1 Urine enzyme immunoassay (EIA) with Western blot (WB) confirmation, and sera were tested by EIA and WB. Masked assays were done on stored, refrigerated urine at Johns Hopkins University (JH), and on fresh specimens at the Rakai Project, Entebbe (RP). We assessed the sensitivity and specificity of the urine relative to serum assays. RESULTS: Compliance with provision of urine samples (95.0%) was higher than provision of serum (90.5%). Ninety-six sera were HIV-positive; 92 were HIV-positive on stored urine at JH (sensitivity 95.8%, CI 91.8-99.8%); and 94 (100%) were positive on fresh samples at the RP laboratory (sensitivity = 100.0%). Among serum HIV-negative subjects, all frozen urine were negative at JH and 97.7% of fresh samples were negative at RP. CONCLUSIONS: The Calypte urine HIV-1 EIA with WB is sensitive and specific. In this population, provision of urine was more acceptable than provision of blood samples.
We examined the association between education and prevalent HIV-1 infection in the Rakai district, rural Uganda based on a cross-sectional analysis of a population-based cohort. In 1990, 1397 men and 1705 women aged 13 years and older, were enrolled in 31 randomly selected communities. Strata were comprised of main road trading centres, secondary road trading villages and rural villages. Sociodemographic and behavioural data were obtained by interview and serum for HIV serostatus were obtained in the home. The analysis examines the association between sex-specific prevalent HIV infection and educational attainment, categorized as secondary, primary or none. The odds ratios (ORs) and 95% confidence intervals (95% CIs) of HIV infection were estimated, using no education as the referent group. Higher levels of education were associated with a higher HIV seroprevalence in bivariate analyses (OR 2.7 for primary and 4.1 for secondary education, relative to no education). The strength of the association was diminished but remained statistically significant after multivariate adjustment for sociodemographic and behavioural variables (adjusted OR of HIV infection 1.6 (95% CI: 1.2-2.1)) for primary education and 1.5 (95% CI: 1.0-2.2) for secondary education. Stratified multivariate analyses by place of residence indicated that the association between education and HIV prevalence was statistically significant in the rural villages, but not in the main road trading centres and intermediate trading villages. Educational attainment is a significant predictor of HIV risk in rural Uganda, in part because of risk behaviours and other characteristics among better educated individuals. Preventive interventions need to focus on better educated adults and on school-aged populations.
Childhood mortality and morbidity patterns in the English-speaking Caribbean have changed significantly over the past 40 years. Acute respiratory illness, physical injury and conditions originating in the perinatal period have replaced malnutrition, gastroenteritis and other infectious diseases as major causes of illness and death in Caribbean children. Although population growth has slowed down, about one-third of the population of the English-speaking Caribbean remains under the age of 15 years. Infant mortality rates have also fallen but the major contributor to this decline has been a reduction in post-neonatal deaths. The decrease in mortality and morbidity from infectious diseases has led to a prominence of disorders originating in the perinatal period, psychosocial problems and chronic childhood disorders. Adverse economic conditions are held culpable for the re-emergence of protein energy malnutrition (PEM) and pulmonary tuberculosis in some territories. There is an urgent need to focus attention on the areas of perinatal and adolescent health, childhood disability, accidental and non-accidental injury, sexual abuse and human immunodeficiency virus (HIV) infection. Immunization programmes also require continuing support and expansion. These tasks cannot be accomplished without meaningful long term investment of financial and human resources in the health and educational services of the region.
OBJECTIVE: To describe the design and first-round survey results of a trial of intensive sexually transmitted disease (STD) control to reduce HIV-1 incidence. STUDY DESIGN: Randomized, controlled, community-based trial in Rakai District, Uganda. METHODS: In this ongoing study, 56 communities were grouped into 10 clusters designed to encompass social/sexual networks; clusters within blocks were randomly assigned to the intervention or control arm. Every 10 months, all consenting resident adults aged 15-59 years are visited in the home for interview and sample collection (serological sample, urine, and, in the case of women, self-administered vaginal swabs). Sera are tested for HIV-1, syphilis, gonorrhea, chlamydia, trichomonas and bacterial vaginosis. Following interview, all consenting adults are offered directly observed, single oral dose treatment (STD treatment in the intervention arm, anthelminthic and iron-folate in the control arm). Treatment is administered irrespective of symptoms or laboratory testing (mass treatment strategy). Both arms receive identical health education, condom and serological counseling services. RESULTS: In the first home visit round, the study enrolled 5834 intervention and 5784 control arm subjects. Compliance with interview, sample collection and treatment was high in both arms (over 90%). Study arm populations were comparable with respect to sociodemographic and behavioral characteristics, and baseline HIV and STD rates. The latter were high: 16.9% of all subjects were HIV-positive, 10.0% had syphilis, and 23.8% of women had trichomonas and 50.9% had bacterial vaginosis. CONCLUSIONS: Testing the effects of STD control on AIDS prevention is feasible in this Ugandan setting.
BACKGROUND: To assess the effects of HIV-1 and other sexually transmitted infections on pregnancy, we undertook cross-sectional and prospective studies of a rural population in Rakai district, Uganda. METHODS: 4813 sexually active women aged 15-49 years were surveyed to find out the prevalence of pregnancy by interview and selective urinary human chorionic gonadotropin tests. The incidence of recognised conception and frequency of pregnancy loss were assessed by follow-up. Samples were taken to test for HIV-1 infection, syphilis, and other sexually transmitted diseases. FINDINGS: At time of survey 757 (21.4%) of 3544 women without HIV-1 infection or syphilis were pregnant, compared with 46 (14.6%) of 316 HIV-1-negative women with active syphilis, 117 (14.2%) of 823 HIV-1-positive women with no concurrent syphilis, and 11 (8.5%) of 130 women with both syphilis and HIV-1 infection. The multivariate adjusted odds ratio of pregnancy in HIV-1-infected women was 0.45 (95% CI 0.35-0.57); the odds of pregnancy were low both in HIV-1-infected women without symptoms (0.49 [0.39-0.62]) and in women with symptoms of HIV-1-associated disease (0.23 [0.11-0.48]). In women with concurrent HIV-1 infection and syphilis the odds ratio was 0.28 (0.14-0.55). The incidence rate of recognised pregnancy during the prospective follow-up study was lower in HIV-1-positive than in HIV-1-negative women (23.5 vs 30.1 per 100 woman-years; adjusted risk ratio 0.73 [0.57-0.93]). Rates of pregnancy loss were higher among HIV-1-infected than uninfected women (18.5 vs 12.2%; odds ratio 1.50 [1.01-2.27]). The prevalence of HIV-1 infection was significantly lower in pregnant than in non-pregnant women (13.9 vs 21.3%). INTERPRETATION: Pregnancy prevalence is greatly reduced in HIV-1-infected women, owing to lower rates of conception and increased rates of pregnancy loss. HIV-1 surveillance confined to pregnant women underestimates the magnitude of the HIV-1 epidemic in the general population.
OBJECTIVE: To examine the effects of alcohol and caffeine on conception. DESIGN: Prospective observational study. SETTING: Healthy volunteers in two manufacturing facilities. PATIENT(S): One hundred twenty-four women who provided daily urine samples for measurement of steroid hormones and hCG, and prospective information about alcohol and caffeine consumption. MAIN OUTCOME MEASURE(S): Probability of conception per 100 menstrual cycles. RESULT(S): There was >50% reduction in the probability of conception during a menstrual cycle during which participants consumed alcohol. Caffeine consumption did not independently affect the probability of conception but may enhance alcohol's negative effect. Women who abstained from alcohol and consumed less than one cup of coffee or its equivalent per day conceived 26.9 pregnancies per 100 menstrual cycles compared with 10.5 per 100 menstrual cycles among those who consumed any alcohol and more than one cup of coffee per day. CONCLUSIONS: This study revealed an independent dose-related negative effect of alcohol consumption on the ability to conceive. Our results suggest that women who are attempting to conceive should abstain from consuming alcohol.
PURPOSE: This study aimed to determine the incidence of idiopathic full-thickness macular hole (FTMH) in normal fellow eyes and to evaluate the role of electrodiagnostic and psychophysical tests in identifying eyes at risk. PATIENTS AND METHODS: A prospective longitudinal natural history study of a cohort of patients with unilateral holes and normal, asymptomatic fellow eyes without posterior vitreous detachment was conducted. Subjects underwent baseline examination, pattern reversal electroretinography, electro-oculography (EOG), and color contrast sensitivity (CCS) testing for protan, deutan, and tritan thresholds and were recalled for clinical examination at 18 months and 5 years. RESULTS: At baseline, 114 patients were examined. Eighty were available for review at 18 months, of whom 6 had full-thickness macular holes develop in the fellow eye. At 5 years, 67 of the remaining 74 patients who had not developed holes at 18 months were re-examined and a further 5 were found to have holes develop in the fellow eye. A posterior vitreous detachment without hole formation had developed in 20 fellow eyes at 5 years. Although mean pattern reversal electroretinography and EOG responses were within normal limits in affected and fellow eyes at baseline, mean CCS protan, deutan, and tritan thresholds were elevated significantly in affected eyes at baseline (P = 0.0001). Unaffected fellow eyes showed normal mean protan and deutan thresholds, but significantly elevated mean tritan thresholds (P = 0.01) at baseline. Mean tritan CCS loss was, however, similar in fellow eyes in which holes later developed and in fellow eyes in which holes did not. CONCLUSIONS: The Kaplan-Meier estimated risk of fellow eye involvement is 15.6% (range, 8.4%-22.3%; P = 0.05) at 5 years. Although electrodiagnostic and psychophysical testing was not predictive of fellow eye involvement, tritan CCS loss at baseline, in apparently normal fellow eyes, may indicate subclinical foveal dysfunction, the nature of which is unclear.
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This was a multicentred, prospective study of pregnancies among women using natural family planning. The women maintained natural family planning charts of the conception cycle, recording acts of intercourse and signs of ovulation (cervical mucus changes, including peak day and basal body temperature). Charts were used to assess the most probable day of insemination relative to the day of ovulation and length of the follicular phase of the cycle. The sex ratio (males per 100 females) for 947 singleton births was 101.5, not significantly different from the expected value of 105. The sex ratio did not vary consistently or significantly with the estimated timing of insemination relative to the day of ovulation, with the estimated length of the follicular phase or with the planned or unplanned status of the pregnancy. Although these findings may be affected by imprecision of the data, the study suggests that manipulation of the timing of insemination during the cycle cannot be used to affect the sex of offspring.
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BACKGROUND: In-vitro research has suggested that bacterial vaginosis may increase the survival of HIV-1 in the genital tract. Therefore, we investigated the association of HIV-1 infection with vaginal flora abnormalities, including bacterial vaginosis and depletion of lactobacilli, after adjustment for sexual activity and the presence of other sexually transmitted diseases (STDs). METHODS: During the initial survey round of our community-based trial of STD control for HIV-1 prevention in rural Rakai District, southwestern Uganda, we selected 4718 women aged 15-59 years. They provided interview information, blood for HIV-1 and syphilis serology, urine for detection of Chlamydia trachomatis and Neisseria gonorrhoeae, and two self-administered vaginal swabs for culture of Trichomonas vaginalis and gram-stain detection of vaginal flora, classified by standardised, quantitative, morphological scoring. Scores 0-3 were normal vaginal flora (predominant lactobacilli). Higher scores suggested replacement of lactobacilli by gram-negative, anaerobic microorganisms (4-6 intermediate; 7-8 and 9-10 moderate and severe bacterial vaginosis). FINDINGS: HIV-1 frequency was 14.2% among women with normal vaginal flora and 26.7% among those with severe bacterial vaginosis (p < 0.0001). We found an association between bacterial vaginosis and increased HIV-1 infection among younger women, but not among women older than 40 years; the association could not be explained by differences in sexual activity or concurrent infection with other STDs. The frequency of bacterial vaginosis was similar among HIV-1-infected women with symptoms (55.0%) and without symptoms (55.7%). The adjusted odds ratio of HIV-1 infection associated with any vaginal flora abnormality (scores 4-10) was 1.52 (95% CI 1.22-1.90), for moderate bacterial vaginosis (scores 7-8) it was 1.50 (1.18-1.89), and for severe bacterial vaginosis (scores 9-10) it was 2.08 (1.48-2.94). INTERPRETATION: This cross-sectional study cannot show whether disturbed vaginal flora increases susceptibility to HIV-1 infection. Nevertheless, the increased frequency of HIV-1 associated with abnormal flora among younger women, for whom HIV-1 acquisition is likely to be recent, but not among older women, in whom HIV-1 is likely to have been acquired earlier, suggests that loss of lactobacilli or presence of bacterial vaginosis may increase susceptibility to HIV-1 acquisition. If this inference is correct, control of bacterial vaginosis could reduce HIV-1 transmission.
OBJECTIVES: To describe the epidemiology of HIV-1 infection among adolescents aged 13-19 years, in rural Rakai district, Uganda. STUDY DESIGN: Baseline survey and 2-year follow-up (1990-1992) of adolescents in a population-based, open rural cohort. METHODS: Annual enumeration and behavioral/serological survey of all consenting adolescents aged 13-19 years at recruitment, residing in 31 randomly selected community clusters. RESULTS: At baseline, of 909 adolescents present in study clusters, 824 (90.6%) provided interview data and serological samples. No adolescents aged 13-14 years were HIV-infected. Among those aged 15-19 years, 1.8% of men and 19.0% of women were HIV-positive. Among young women aged 15-19 years in marital/consensual union, 21.3% were HIV-positive; this rate did not differ significantly from the 29.1% prevalence in those reporting non-permanent relationships; prevalence was significantly lower in women reporting no current relationship (4.3%). After multivariate adjustment, female sex, age 17-19 years, residence in trading centers/trading villages and a history of sexually transmitted disease symptoms remained significantly associated with HIV infection. Seventy-nine per cent of adolescents provided a follow-up serological sample. No young men aged 13-14 years seroconverted during the study; in young women aged 13-14 years, HIV seroincidence was 0.6 per 100 person-years (PY) of observation. Among young men aged 15-19 years, there were 1.1 +/- 0.6 seroconversions per 100 PY of observation prior to age 21 years; among women 15-19 years, the incidence rate was 3.9 +/- 1.0 per 100 PY of observation prior to age 21 years. The mortality rate among HIV-positive adolescents aged 15-19 years, at 3.9 per 100 PY of observation, was 13-fold higher than that among the HIV-uninfected. By 1992, knowledge of sexual transmission was almost universal, the proportions reporting multiple partners had decreased and condom use had increased over baseline. CONCLUSIONS: Adolescents, and young women in particular, are vulnerable to HIV infection. Despite reported behavioral changes, HIV incidence rates remain substantial, and there is a need for innovative HIV preventive measures.
OBJECTIVES: To assess whether trends in serial HIV-1 prevalence reflect trend in HIV incidence, and to decompose the effects of HIV-1 incidence, mortality, mobility and compliance on HIV-1 prevalence in a population-based cohort. DESIGN: Two-year follow up (1990-1992) of an open cohort of all adults aged 15-59 years, resident in a sample of 31 representative community clusters in rural Rakai District, Uganda. METHODS: A detailed household enumeration was concluded at baseline and in each subsequent year. All household residents were listed, and all deaths and in- and out-migrations that occurred in the intersurvey year wee recorded. In each year, all consenting adults were interviewed and provided a serological sample; 2591 adults aged 15-59 years were enrolled at baseline. RESULTS: HIV prevalence among adults declined significantly 1990 and 1992 (23.4% at baseline, 21.8% in 1991, 20.9% in 1992; P < 0.05). Declining prevalence was also observed in subgroups, including young adults aged 15-24 years (from 20.6 to 16.2% over 3 years; P < 0.02), women of reproductive age (from 27.1 to 23.5%; P < 0.05), and pregnant women (from 25.4 to 20.0%; not significant), However, HIV incidence did not change significantly among all adults aged 15-59 years (2.1 +/- 0.4 per 100 person-years of observation (PYO) in 1990-1991 and 2.0 +/- 0.3 per 100 PYO in 1991-1992], nor in population subgroups. HIV-related mortality was high (13.5 per 100 PYO among the HIV-positive), removing more infected persons that were added by seroconversion. Net out-migration also removed substantial numbers of HIV-positive individuals. CONCLUSIONS: In this mature HIV epidemic, HIV prevalence declined in the presence of stable and incidence. HIV-related mortality contributed most to the prevalence decline. Prevalence was not an adequate surrogate measure of incidence, limiting the utility or serial prevalence measures in assessing the dynamics of the HIV epidemic and in evaluating the impact of current preventive strategies.