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Biomedical subjects

Z Stein

Publications and source records attributed to Z Stein.

At least 37 records · Page 2Linked to original sources

CCR5del32 in perinatal HIV-1 infection.

CCR5, a chemokine receptor, serves as a coreceptor for macrophage-tropic HIV-1 (1-3). A 32-bp deletion within the gene encoding CCR5, CCR5del32, has been shown to prevent HIV-1 infection of T cells in the absence of a wild-type allele. This alteration is present in low frequency in Caucasian populations (4-6). To investigate the effect of CCR5del32 in perinatal HIV-1 transmission and disease progression, two cohorts of perinatally exposed infected and uninfected children were analyzed for the presence of the allele. Polymerase chain reaction (PCR) was used to identify CCR5del32 in prevalent and prospective cases among 144 African American children from New York City and 73 Caucasian children from Barcelona, Spain. HIV-1 transmission; clinical manifestations of disease, including encephalopathy, opportunistic infections, and death before 2 years of age; survival; Centers for Disease Control and Prevention (CDC) classification; and degree of immunosuppression were compared in children with and without CCR5del32. The allele frequency in HIV-1-infected African Americans (0.016) was lower than in Catalan children (0.041). No evidence for a dominant protective effect of CCR5del32 for HIV-1 transmission or disease progression was found in these cohorts.

Black People↗

Major depressive disorder in the 6 months after miscarriage.

OBJECTIVE: To test a priori hypotheses that miscarrying women are at increased risk for a first or recurrent episode of major depressive disorder in the 6 months following loss and that this increased risk is greater for childless women, women with prior reproductive loss, and women aged 35 years or older; and to evaluate whether risk varies by time of gestation or by attitude toward the pregnancy. DESIGN: Cohort study. SETTING: The miscarriage cohort consisted of women attending a medical center for a spontaneous abortion (n=229); the comparison group was a population-based cohort of women drawn from the community (n=230). PARTICIPANTS: Miscarriage was defined as the involuntary termination of a nonviable intrauterine pregnancy before 28 completed weeks of gestation. Half of all participants were between 25 and 34 years of age; 40% were white and 35% Hispanic; 55% had more than a high school education. Participants constituted 60% of miscarrying women and 72% of community women who completed the first phase of this cohort study. MAIN OUTCOME MEASURE: Major depressive disorder was measured using the Diagnostic Interview Schedule. RESULTS: Risk for an episode of major depressive disorder among miscarrying women in the 6 months following loss was compared with the 6-month risk among community women who had not been pregnant in the preceding year. Among miscarrying women, 10.9% experienced an episode of major depressive disorder, compared with 4.3% of community women. The overall relative risk (RR) for an episode of major depressive disorder for miscarrying women was 2.5 (95% confidence interval [CI], 1.2-5.1) and was substantially higher for childless women (RR, 5.0; 95% CI, 1.7-14.4) than for women with children (RR, 1.3; 95% CI, 0.5-3.5) (P<.06). Among miscarrying women, 72% of cases of major depressive disorder began within the first month after loss; only 20% of community cases started during the comparable period. Among miscarrying women with a history of major depressive disorder, 54% experienced a recurrence. However, RR did not vary significantly by history of prior reproductive loss or by maternal age, nor did risk vary by time of gestation or attitude toward the pregnancy. CONCLUSIONS: Physicians should monitor miscarrying women in the first weeks after reproductive loss, particularly women who are childless or who have a history of major depressive disorder. Where appropriate, supportive counseling or psychopharmacologic treatment should be considered.

Abortion, Spontaneous↗

Infant survival, HIV infection, and feeding alternatives in less-developed countries.

OBJECTIVES: This study examines, in the context of the human immunodeficiency virus (HIV) epidemic, the effects of optimal breast-feeding, complete avoidance of breast-feeding, and early cessation of breast-feeding. METHODS: The three categories of breast-feeding were weighed in terms of HIV transmission and infant mortality. Estimates of the frequency of adverse outcomes were obtained by simulation. RESULTS: Avoidance of all breast-feeding by the whole population always produces the worst outcome. The lowest frequency of adverse outcomes occurs if no HIV-seropositive women breast-feed and all seronegative women breast-feed optimally, given infant mortality rates below 100 per 1000 and relative risks of dying set at 2.5 for non-breast-fed compared with optimally breast-fed infants. For known HIV-seropositive mothers, fewer adverse outcomes result from early cessation than from prolonged breast-feeding if the hazard of HIV transmission through breast-feeding after 3 months is 7% or more, even at high mortality rates, given relative risks of dying set at 1.5 for early cessation compared with optimal duration of breast-feeding. CONCLUSIONS: The risk of HIV transmission through breast-feeding at various ages needs to be more precisely quantified. The grave issues that may accompany a possible decline in breast-feeding in the less developed world demand evaluation.

Adult↗

Association of stressful life events with chromosomally normal spontaneous abortion.

Spontaneous abortion is the most common adverse reproductive outcome. Despite evidence that negative life events increase risk for a number of medical disorders, their role in pregnancy disruption has not been investigated. The present study tested an a priori hypothesis that recent negative life events increase the odds of spontaneous abortion of a chromosomally normal conceptus. Between 1984 and 1986, 192 women aged 18-42 years who visited a medical center after spontaneous abortion were interviewed about positive and negative events that had occurred in the 4-5 months preceding the loss. Subsequently, women with chromosomally normal (n = 111) and chromosomally abnormal (n = 81) losses were identified on the basis of tissue culture after interview. The women with chromosomally abnormal loss provided an estimate of the expected frequency of life events against which to compare the event frequencies of women with chromosomally normal loss. Analyses were adjusted for duration of the recall period, payment status, maternal age, education, and ethnicity. Seventy percent of the women with chromosomally normal losses reported having had one or more negative life events in the months preceding loss, compared with 52% of the women with chromosomally abnormal losses (adjusted odds ratio = 2.6, 95% confidence interval (CI) 1.3-5.2). For private patients (n = 69), the adjusted odds ratio was 4.2 (95% CI 1.3-13.4); for public patients (n = 123), it was 1.9 (95% CI 0.8-4.8). The associations held for postconception events alone and were absent for positive events. Results were unaltered by adjustment for smoking, caffeine intake, and alcohol consumption. With recall bias precluded by the study design, the strength, timing, and specificity of these associations suggest that recent negative life events play a role in chromosomally normal spontaneous abortion. Efforts to replicate these results and to elucidate underlying biologic mechanisms are required.

Abortion, Spontaneous↗

Gender Differences in HIV-Related Neurological Progression in a Cohort of Injecting Drug Users Followed for 3.5 Years.

We evaluated potential gender differences in the development of HIV related neurologic impairment, by matching 38 pairs of HIV positive male and female injecting drug users on their baseline age, education, disease stage and CD4 counts, and following them for 3.5 years. Adjusting for age, education, drug use, history of head injury and baseline CD4 count, more women had sensory abnormalities and symptoms than men at baseline, but the odds of having neurological impairment, particularly extrapyramidal signs and sensory abnormalities were increased over time in men but not in women. Men with ARC or AIDS had more neurological impairment than women in similar stages of illness. This study suggests further investigations of gender differences in HIV disease progression.

CD4 Lymphocyte Count↗

Cigarette smoking and spontaneous abortion of known karyotype. Precise data but uncertain inferences.

Data from the first phase (1974-1979) of this New York City case-control study showed that 1) cigarette smoking during pregnancy was associated positively with chromosomally normal spontaneous abortion and 2) both past and current smoking were associated inversely with trisomic loss in women under age 30 years and positively in older women. The authors used data from two subsequent study phases (1979-1982 and 1982-1986) to test the stability of these associations over time and the homogeneity between payment groups (private vs. public). Spontaneous abortions (cases) were classified as chromosomally normal (n = 1,388), trisomic (n = 557), or other chromosomally aberrant (n = 409). Controls (n = 4,165) were women who had registered for prenatal care before 22 weeks' gestation and delivered at 28 weeks or later. For chromosomally normal loss, later data gave modest support to prior observations. In the total sample, current smoking (defined as smoking during the month of the last menstrual period) of 14 or more cigarettes per day was increased among chromosomally normal cases in comparison with controls (adjusted odds ratio (OR) = 1.3, 95% confidence interval (CI) 1.1-1.7) and in comparison with other aberrant cases (adjusted OR = 1.2, 95% CI 0.8-1.8). Stronger associations in public patients than in private patients (adjusted odds ratios of 1.4-1.5 versus 0.8-0.9, respectively) might indicate either a mediating effect of social disadvantage or a chance fluctuation. For trisomic loss, later data did not support prior observations. Associations between trisomy and past or current smoking did not vary significantly with age in either payment group; assuming no effect modification of age, adjusted odds ratios for smoking in relation to trisomy were 0.9-1.0.

Abortion, Spontaneous↗

Influence of host genotype on progression to acquired immunodeficiency syndrome among children infected with human immunodeficiency virus type 1.

OBJECTIVE: To study the role of host genotype in pediatric infection with human immunodeficiency virus type 1 (HIV-1) and progression to acquired immunodeficiency syndrome (AIDS). METHODS: Human leukocyte antigen (HLA) class II and complement C4 genotypes were determined by means of molecular genetic techniques for 243 black children born to HIV-1-infected mothers in New York City and San Francisco. Survival, cumulative incidences of opportunistic infections and encephalopathy, and rates of CD4+ T cell decline were compared in children of different genotypes. RESULTS: Among HIV-1-infected children, the HLA-DR3 haplotype (DRB1*0301-DQA1*0501-DQB1*0201) was associated with increased incidence of encephalopathy, faster rate of CD4+ cell decline, and death before 2 years of age. Deletion of the C4A gene was independently associated with increased incidences of encephalopathy and early death. DPB1*0101 was associated with survival to at least 2 years of age. The presence of DQB1*0604 was associated with increased risk of HIV infection. CONCLUSIONS: These results are consistent with previously reported associations between HLA genotypes and faster progression to AIDS among HIV-infected adults. The DR3 haplotype and C4A deletion may reflect the same underlying mechanism of susceptibility in that the DR3 haplotype is in linkage disequilibrium with other C4A null alleles. In addition, the class II locus DPB1 may have an independent effect on survival.

Acquired Immunodeficiency Syndrome↗

Sodwanones G, H, and I, new cytotoxic triterpenes from a marine sponge.

Three cytotoxic triterpenes, sodwanones G [5], H [6], and I [7], have been isolated from a marine sponge. The three structures were determined by interpretation of nmr spectra, and in the case of 5, also on the basis of the X-ray diffraction analysis. The X-ray diffraction analysis of two other earlier reported sodwanones, E [3] and F [4] is also discussed. The cytotoxic activity against several cancer cell lines, has been tested. IC50 values between 20 and 0.02 microM were obtained. Compounds 5 and 6 were 10- and 500-fold, respectively, more cytotoxic to A-549 cells than to any of the other cell lines tested (HT-29, MEL-28, P-388).

Animals↗

Timing in prenatal nutrition: a reprise of the Dutch Famine Study.

The array of results discussed in this paper is assembled by stage of gestation in the following table (Table 1). We must allow some uncertainty for some outcomes as to the precise stages of gestation in which they originate. For instance, with obesity, the effects of famine exposure may extend beyond the first trimester into the second. Yet, the table is perhaps sufficient in itself to support the point with which the paper opened, namely, that stage of development is crucial to the appreciation of the effects of prenatal nutrition.

Animals↗

Cigarette smoking and trisomy 21 at amniocentesis.

Several studies raise the possibility that smoking during pregnancy is associated with a slightly decreased odds of trisomy 21 at birth. If it is, associations may reflect decreased incidence at conception, increased intrauterine loss (at one or several times in gestation), or both. Women (n = 13,729) undergoing prenatal diagnosis completed a questionnaire before learning karyotype results. For each women with a trisomy, up to 4 controls with chromosomally normal pregnancies, matched for age and hospital, were selected. Analyses drew on the 89 trisomy 21-control matched m-tuples in which diagnosis was by amniocentesis at 14-26 weeks. We compared the odds of smoking at last menstrual period and in the past in cases and controls. The odds of current smoking versus never smoking were decreased [adjusted odds ratio = 0.8, 95% confidence interval (CI) 0.4-1.6] and the odds of exsmoking increased (adjusted odds ratio = 1.4, 95% CI 0.9-2.4) in trisomy 21 cases. The association with current smoking was essentially unchanged when the unexposed reference group was defined as exsmokers and women who never smoked (adjusted odds ratio = 0.7, 95% CI 0.4-1.4). These results for current smoking agree well with a summary estimate based on combined studies of births. One interpretation is that at amniocentesis, as has been reported for births, current smoking is associated with a slightly decreased odds of trisomy 21. If associations at amniocentesis and birth are of equal magnitude, the explanation that observations at birth reflect increased loss in the second half of pregnancy with current smoking is unlikely to be correct.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Mortality risks in gay men with human immunodeficiency virus infection and cognitive impairment.

We obtained data from 111 gay men who entered a longitudinal study of the natural history of human immunodeficiency virus (HIV) without clinical evidence of acquired immunodeficiency syndrome (AIDS), and examined them regularly over a 36-month period. Using a Cox proportional-hazard regression model to compare cumulative risk of mortality in subjects with and without cognitive impairment and several putative risk factors present at baseline, we found that the mortality risk ratio (RR) associated with poor neuropsychologic test performance was significantly increased (RR = 2.9; 95% confidence interval [CI], 1.1 to 7.8), and increased further (RR = 4.1; 95% CI, 1.3 to 12.5) when adjusted for other factors associated with mortality (a history of a disturbance in movement or gait, CD4-lymphocyte and red blood-cell counts, and age). A significant increase in symptoms related to cognitive impairment and gait, a decline in neuropsychologic test performance, and declines in CD4-lymphocyte and red-cell counts occurred over the study period. A second model was constructed to adjust for changes in CD4-lymphocyte and red-cell counts, age, medical stage, and motor symptoms over the study period, but the mortality RR for poor neuropsychologic test performance at baseline changed very little (RR = 4.7; 95% CI, 1.5 to 14.9). We conclude that the presence of cognitive impairment, manifest by poor neuropsychologic test performance in both asymptomatic and symptomatic gay men with HIV infection, is associated with a significantly increased risk of death. This effect progresses in parallel with the immunologic and systemic effects of HIV.

Adult↗

Increased risk of proteinuria among a cohort of lead-exposed pregnant women.

Long-term exposure to high concentrations of lead results in renal dysfunction. During a prospective study of environmental lead and pregnancy outcomes in 1502 women residing in two towns in Yugoslavia, we explored whether moderate exposure to lead results in increased rates of proteinuria. The geometric mean blood lead concentrations (BPb) were 17.1 and 5.1 micrograms/dl in the smelter and nonexposed towns, respectively. Increases in BPb were associated with increased odds ratios for both trace and > or = 1+ proteinuria, measured using a urinary dipstick. Comparing the women in the upper 10th percentile of exposure to those in the lowest 10th percentile, the adjusted odds ratio for > or = 1+ proteinuria was 4.5 (95% CI 1.5, 13.6). Similarly, the adjusted odds ratio for trace proteinuria was 2.3 (95% CI 1.3, 4.1). Similar to other studies showing associations between chronic exposure to lead and renal dysfunction, our data suggest that long-term exposure to environmental lead may be associated with proteinuria.

Adult↗