Stem cells: prospects for functional repair of brain damage.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to H Watts.
Explore the source record for details and available documents.
To obtain information on the prevalence of anovulation and early menopause and on pituitary-gonadal function among human immunodeficiency virus type 1-infected women, a study was undertaken that used stored serum samples from women aged 20-42 years who participated in selected Adult AIDS Clinical Trials Group protocols. Defined progesterone and follicle-stimulating hormone (FSH) levels were considered presumptive evidence of ovulation and of menopause, respectively. Anovulation occurred in 16 (48%) of 33 women for whom progesterone levels were tested; early menopause occurred in 2 (8%) of 24 women for whom FSH levels were tested. No statistically significant differences were seen in the demographic and clinical characteristics of anovulatory and ovulatory women, although women who ovulated had higher CD4 T cell counts and were less likely to have reported a recent change in menstrual periods. These data support the findings of prior studies of increased frequency of amenorrhea and/or irregular menstrual cycles, particularly among women with lower CD4 T cell counts.
Explore the source record for details and available documents.
OBJECTIVES: To evaluate the effect of the menstrual cycle in HIV-positive women on plasma and genital cytokine levels, interrelationships between vaginal and plasma cytokines, CD4 and CD8 T cell fluctuations, and genital and plasma viral loads. METHODS: Plasma and cervicovaginal lavage specimens were collected from 55 HIV-positive women with CD4 cell counts < 350 cells/microl during phases of the menstrual cycle. Samples were assayed for IL-1beta, IL-6, IL-4, IL-8, IL-10, TGFbeta, TNFalpha, INFgamma, MIP1alpha, MIP1beta, RANTES, and TNFR-II using enzyme-linked immunosorbent assays. CD4 and CD8 T cell expression was evaluated by flow cytometry. Repeated measures regression models were used to assess the effect of the menstrual cycle on cytokines and viral load. Multivariate repeated regression models were used to assess the correlation among selected cytokines and between selected cytokines and HIV viral load. RESULTS: Vaginal IL-1beta, IL-4, IL-6, IL-8, IL-10, MIP1beta, RANTES, TGFbeta, and TNFR-II were significantly elevated during menses but were not altered during other phases. Plasma cytokine levels were not altered during the menstrual cycle. A positive Candida culture increased vaginal IL-8 during menses, whereas vaginal discharge was associated with a reduction in vaginal IL-4, IL-10, and RANTES. CD4 and CD8 cell numbers did not vary with the menstrual cycle. Vaginal cytokine levels correlated only with vaginal viral load, in a sampling method-dependent manner. CONCLUSION: We provide evidence of elevated vaginal cytokine levels during menses, which appear to regulate vaginal and not plasma HIV shedding, suggesting that a menstrual cycle pattern exists for cytokine production in HIV-positive women impacting vaginal shedding of HIV.
OBJECTIVE: To determine incidence, progression, and regression rates for abnormal cervical cytology and their correlates among women with HIV. METHODS: In a multicenter prospective cohort study conducted October 1, 1994, through September 30, 1999 at university, public, and private medical centers and clinics, 1639 HIV-seropositive and 452 seronegative women were evaluated every 6 months for up to 5 years using history, cervical cytology, T-cell subsets, and quantitative plasma HIV RNA. Human papillomavirus (HPV) typing at baseline was determined by polymerase chain reaction. Cytology was read using the Bethesda system, with any smear showing at least atypia considered abnormal. Poisson regression identified factors associated with incident cytologic abnormalities whereas logistic regression identified those associated with progression and regression after an abnormality. RESULTS: At least one abnormal smear was found during all of follow-up among 73.0% of HIV-seropositive patients and 42.3% of seronegatives (p <.001). Only 5.9% of seropositives ever developed high-grade lesions, and the proportion with high-grade findings did not rise over time. Incidence of atypical squamous cells of uncertain significance (ASCUS) or more severe lesions among HIV-seropositive patients and seronegative patients was 26.4 and 11.0/100 woman-years (rate ratio [RR], 2.4; 95% confidence interval [CI], 1.9-3.0), whereas that of at least low-grade squamous intraepithelial lesions (SIL) was 8.9 and 2.2/100 (RR, 4.0; CI, 2.6-6.1). HIV status, detection of the presence of human papillomavirus (HPV), CD4 lymphocyte count, and HIV RNA level predicted incidence of abnormal cytology (p <.05); HPV detection and HIV RNA level predicted progression (p <.01); and HPV detection, CD4 lymphocyte count, and HIV RNA level predicted regression (p <.001). Rates of incidence, progression, and regression of abnormal cytology did not differ between HIV seronegative women and seropositive women with CD4 lymphocyte counts >200/mm(3) and HIV RNA levels <4000/ml of similar HPV status. CONCLUSIONS: Although HIV infected women were at high risk for abnormal cytology, high-grade changes were uncommon. HIV status, HPV detection, CD4 lymphocyte count, and HIV RNA level predicted the incidence of cervical cytologic abnormalities. Progression was significantly increased only among the most immunosuppressed women, while regression was significantly reduced in all HIV seropositive women except those with the best controlled HIV disease.
Anemia is a common manifestation of HIV infection, occurring in approximately 30% of patients with asymptomatic infection and in as many as 75% to 80% of those with AIDS. Anemia has been associated with decreased quality of life and decreased survival. We performed a cross-sectional study nested within a multicenter prospective cohort study to describe the prevalence of anemia in 2056 HIV-infected and 569 HIV-negative women as well as to define the demographic, clinical, immunologic, and virologic correlates of anemia among HIV-infected women. A total of 37% of HIV-positive women and 17% of HIV-negative women had hemoglobin levels < 12 g/dl (p < .001). Factors associated with anemia in HIV-positive and HIV-negative women included mean corpuscular volume (MCV) < 80 fl (p < .001) and black race (p < .001). Among HIV-infected women, multivariate logistic analyses revealed that African American race (p < .0001), MCV < 80 fl (p < .0001), CD4 count < 200 per microliter (p <.0001), higher HIV RNA in plasma (p = .02), current use of ZDV (p = .01), and history of clinical AIDS (p = .004) were all independent predictors of anemia. These data indicate that worsening parameters of HIV disease are associated with anemia among HIV-infected women. Black women and women with low MCV values are at increased risk for anemia independent of HIV status.
OBJECTIVE: Public health agencies have recommended that the criteria for the use of highly active antiretroviral therapy should not be modified because of pregnancy. However, little information has been published with regard to the degree to which these recommendations are being followed. We report here the frequency of highly active antiretroviral therapy use among pregnant women in the Women's Interagency HIV Study and compare the frequencies of its use by pregnant women meeting published criteria for implementing highly active antiretroviral therapy and its use by nonpregnant women meeting the same criteria. STUDY DESIGN: From October 1994 through November 1995, a total of 2059 human immunodeficiency virus type 1-seropositive women were enrolled in a cohort study. Participants were evaluated at baseline and at 6-month intervals with standardized interview instruments. In addition to a general physical examination at each visit, patients had a urine pregnancy test performed and were asked about current pregnancies, pregnancies since the last visit, and which antiretroviral medications they had used since the last visit. Highly active antiretroviral therapy was defined according to 1997 National Institutes of Health guidelines. RESULT: At each calendar interval after October 1996, a greater proportion of nonpregnant women than pregnant women reported the use of highly active antiretroviral therapy. The use of monotherapy declined for both groups during the course of multiple calendar periods (P <.01), although the use of monotherapy remained higher among the pregnant women. In any given calendar period, pregnant women meeting published criteria for highly active antiretroviral therapy use were slightly less likely than similar nonpregnant women to receive highly active antiretroviral therapy (odds ratio, 0.28-0.98). Because of the sample size these differences reached significance in only one calendar period (P =.02). With time pregnant women did demonstrate an increase in the percentage receiving highly active antiretroviral therapy. In nearly all calendar periods a larger percentage of pregnant than nonpregnant women were receiving a regimen that included zidovudine. CONCLUSIONS: Highly active antiretroviral therapy is being received by an increasing percentage of women who meet published criteria for its use, and pregnancy is a relatively small impediment to its use. Further efforts are needed to bolster the use of highly active antiretroviral therapy by all appropriate candidates and to ensure equal access to this therapy for pregnant women. Because of the increasingly frequent use of highly active antiretroviral therapy during pregnancy, ongoing efforts are needed to monitor any long-term effects of in utero exposure to multiple antiretroviral agents.
OBJECTIVE: To determine associations among cervical cytology, colposcopy, and biopsy in HIV-seropositive women. MATERIALS AND METHODS: HIV-seropositive women and uninfected comparison women in a multicenter prospective cohort study underwent colposcopy for protocol indications. Women were eligible if they had a cervix, satisfactory cytology, and colposcopy between October 1994 and September 1999. Cytology, colposcopic impression, and biopsy were compared using equivalent categorizations. Kappa statistics with bootstrap sampling assessed strength of associations. RESULTS: Colposcopy was performed in 978/1370 HIV-seropositive women and in 154/224 seronegative women. Biopsies were performed on 603 (44%) seropositive women at least once during 1015 colposcopy visits and on 82 (37%) seronegative women at 116 visits. The positive predictive value of cytology was 72% for seropositive women and 60% for seronegative women. The positive predictive value of colposcopy was 71% for seropositive women and 55% for seronegative women. CONCLUSION: The correlation between either cervical cytology or colposcopic impression and colposcopic biopsy was poor.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
In 1991 the roof blew off a Swindon Primary School. One child was killed. Two years later 19 of her classmates were interviewed. The parent who collected the child from school that day was also interviewed. Recalled levels of post-traumatic stress syndrome (PTSD) symptoms were assessed in both parent and child in the month following the incident. The children's symptom levels at 2 years were also assessed. Parents and children recalled significant post-traumatic stress reactions at 1 month. The level of symptoms in parents did not correlate with that of their own children.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Weekly high-dose methotrexate with leucovorin rescue and vincristine (HDMTX) and doxorubicin was administered as adjuvant postoperative therapy to 46 patients with a diagnosis of conventional high-grade nonmetastatic osteosarcoma of an extremity between July 1976 and December 1981. The primary lesions were managed by wide or radical amputation (26 patients) or by limb-sparing resection in 20 selected patients. The margins of the resections were retrospectively classified as marginal in three, wide in 16, and radical in one. The 5-year relapse-free survival (RFS) for all patients is 59% (95% confidence interval [CI], 43%, 74%) and overall survival is 78% (95% CI, 65%, 91%). The RFS for patients initially having a limb resection procedure is 55% (95% CI, 32%, 77%) compared with 62% (95% CI, 43%, 81%) for those initially having amputations (P = .52). Using multivariate analysis, the only significant prognostic variables that predicted RFS of greater than or equal to 3 years, were the presence of moderate to marked lymphocytic infiltration of the primary tumor (P less than .002), primary site outside of the proximal humerus (P less than .005), and the absence of a predominance of osteoblastic pattern in the primary tumor (P less than .03).
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Indirect immunofluorescence and cell-type-specific markers were used to determine whether antibodies directed against specific neural cell types were present in patients with Alzheimer's disease (AD), other neurological diseases (OND) and normal controls. Sera and cerebrospinal fluid (CSF) were tested on either frozen sections of rat and human cortex and/or dissociated cell cultures of neonatal rat cerebellum, and human fetal dorsal root ganglia (DRG). All groups of patients and normal subjects were indistinguishable in their pattern of immunoglobulin (Ig) staining. Staining of neurones on frozen sections was predominantly nuclear. In cultures all sera showed weak staining of oligodendrocytes, fibroblasts and Schwann cells. Varying degrees of surface staining of neurones were seen with both sera and CSF within all groups.