Attribution of menopause symptoms in human immunodeficiency virus-infected or at-risk drug-using women

OBJECTIVE: To examine the relationship of human immunodeficiency virus (HIV) and attribution of menopausal symptoms. DESIGN: Peri- and postmenopausal women participating in a prospective study of HIV-infected and at-risk midlife women (the Ms. Study) were interviewed to determine whether they experienced hot flashes and/or vaginal dryness and to what they attributed these symptoms. RESULTS: Of 278 women, 70% were perimenopausal; 54% were HIV-infected; and 52% had used crack, cocaine, heroin, and/or methadone within the past 5 years. Hot flashes were reported by 189 women and vaginal dryness was reported by 101 women. Overall, 69.8% attributed hot flashes to menopause and 28.7% attributed vaginal dryness to menopause. In bivariate analyses, age 45 years and older was associated with attributing hot flashes and vaginal dryness to menopause, and postmenopausal status and at least 12 years of education were associated with attributing vaginal dryness to menopause, but HIV status was not associated with attribution to menopause. In multivariate analysis, significant interactions between age and menopause status were found for both attribution of hot flashes (P=0.019) and vaginal dryness (P=0.029). Among perimenopausal women, older age was independently associated with attribution to menopause for hot flashes (adjusted odds ratio=1.2, 95% CI: 1.1-1.4, P=0.001) and vaginal dryness (adjusted odds ratio=1.3, 95% CI: 1.1-1.6, P=0.011). None of the tested factors were independently associated with attribution to menopause among postmenopausal women. CONCLUSION: Tailored health education programs may be beneficial in increasing the knowledge about menopause among HIV-infected and drug-using women, particularly those who are perimenopausal.     

Protein biochip array technology for cytokine profiling predicts etanercept responsiveness in rheumatoid arthritis

In rheumatoid arthritis (RA) there are currently no useful indicators to predict a clinical response to tumour necrosis factor-alpha (TNF-alpha) blockade. The purpose of this study was to determine the role of peripheral blood cytokine profiling in differentiating between a good versus poor response to etanercept in RA. Peripheral blood samples were collected at baseline and at 3 months from 33 patients with active disease who were treated twice weekly by etanercept therapy. Responders are defined by the presence of three of four American College of Rheumatology criteria: > or =20% decrease in C-reactive protein (CRP), visual analogue score of disease activity, erythrocyte sedimentation rate and improvement of the disease activity score (28; four values) by > or =1.2 obtained at 3 months. Twelve cytokines were measured from serum collected on days 0 and 90 by proteomic array (protein biochip array, Investigator Evidence, Randox France), including interleukin (IL)-6, TNF-alpha, IL-1a, IL-1b, IL-2, IL-8, interferon-gamma, IL-4, IL-10, monocyte chemoattractant protein (MCP)-1, epidermal growth factor (EGF) and vascular endothelium growth factor. Our results showed that high serum levels of MCP-1 and EGF were associated with a response to etanercept. In addition, the increase of two combined parameters CRP and EGF was predictive of a response to etanercept treatment at 3 months (sensitivity: 87.5% and specificity: 75%, accuracy: 84.4%). These findings suggest that cytokine profiling by proteomic analysis before treatment initiation may help to identify a responder patient to TNF-alpha blocking agents in RA.     

Comparison of uroplakin expression during urothelial carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine in rats and mice

The expression of uroplakins, the tissue-specific and differentiation-dependent membrane proteins of the urothelium, was analyzed immunohistochemically in N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-treated rats and mice during bladder carcinogenesis. Male Fischer 344 rats were treated with 0.05% BBN in the drinking water for 10 wk and were euthanatized at week 20 of the experiment. BBN was administered to male B6D2F, mice; it was either provided at a rate of 0.05% in the drinking water (for 26 wk) or 5 mg BBN was administered by intragastric gavage twice weekly for 10 wk, followed by 20 wk without treatment. In rats, BBN-induced, noninvasive, low-grade, papillary, transitional cell carcinoma (TCC) showed decreased uroplakin-staining of cells lining the lumen but showed increased expression in some nonluminal cells. In mice, nonpapillary, high-grade dysplasia, carcinoma in situ, and invasive carcinoma were induced. There was a marked decrease in the number of uroplakin-positive cells lining the lumen and in nonluminal cells. This occurred in normal-appearing urothelium in BBN-treated mice and in dysplasic urothelium, in carcinoma in situ, and in invasive TCC. The percentage of uroplakin-positive nonluminal cells was higher in control mice than in rats, but it was lower in the mouse than in the rat after BBN treatment. Uroplakin expression was disorderly and focal in BBN-treated urothelium in both species. These results indicate that BBN treatment changed the expression of uroplakins during bladder carcinogenesis, with differences in rats and mice being related to degree of tumor differentiation.     

Fine-needle aspiration cytology of Rosai-Dorfman disease of the breast: A case report.

We report the cytologic findings of a case of Rosai-Dorfman disease of the breast in a 52-year-old diabetic woman, initially sampled by fine-needle aspiration biopsy (FNA). The patient presented with a 2-week history of a 3 x 2 cm nodule in the mid-upper area of the left breast. A mammogram taken 6 months prior was negative. FNA smears demonstrated lymphocytes, plasma cells, and large pale cells, with enlarged irregular nuclei, admixed with fragments of fibrous tissue and calcific debris. Lymphophagocytosis (emperipolesis) was scarce. Our diagnosis was atypical lymphohistiocytic proliferation. Flow cytometry was negative, but in the face of a strong clinical suspicion of a lymphoid malignancy, excision was performed. The final diagnosis was Rosai-Dorfman disease (RDD). The differential diagnosis of FNA of breast inflammatory lesions with atypical cytology is discussed, with a review of the literature. The early recognition on FNA of the hallmarks of this rare disease should prevent unnecessary radical surgery. Diagn. Cytopathol. 1999;21:287-291.     

Novel aspects of the insulin-like growth factor binding proteins.

The insulin-like growth factors (IGFs), IGF binding proteins (IGFBPs), and IGFBP proteases regulate somatic growth and cellular proliferation both in vivo and in vitro. IGFs are potent mitogens whose actions are determined by the availability of free IGFs to interact with IGF receptors. IGFBPs comprise a family of six proteins that bind IGFs with high affinity and specificity and thereby regulate IGF-dependent actions. IGFBPs have also recently emerged as IGF-independent regulators of cell growth. Several IGFBP association proteins have been discovered recently which can affect IGFBP action. Cleavage of IGFBPs by specific proteases modulates levels of free IGFs and IGFBPs and thereby their actions. IGFBP-related proteins (IGFBP-rPs) are an emerging group of proteins which bind IGFs with low affinity and also play important roles in cell growth and differentiation. The IGFBPs appear to have emerging roles in the mechanisms underlying human cancer. The GH-IGF-IGFBP axis is complex and powerful. Future research on its physiology promises exciting insights into cell biology as well as advancements in the treatment of a wide range of disease states including cancer, diabetes, vascular disease, asthma, and growth disorders.     

Effects of mood and age on quality of life in depressed inpatients

BACKGROUND: Prior investigations have demonstrated a link between quality of life (QOL) deficits and depression. This report elaborates on prior investigations findings by implementation of formal assignment of the diagnosis of depression and a hierarchical approach to assessment of QOL. METHODS: A masters or doctoral level mental health clinician used the SCID to confirm a diagnosis of major depression in ninety psychiatric inpatients. Function was assessed with the PSMS (a measure of ADL), the IADL scale, and the "daily living and role functioning" and the "relation to self and others" subscales of the Basis-32. RESULTS: Patient age and severity of depression were the most consistent predictors of QOL deficits, although the direction of the age-effect on QOL depended on the specific measure of QOL. Increasing severity of depression was consistently associated with worse QOL, and remained significant after adjusting for age. LIMITATIONS: The cross-sectional method of this study limits the inference of causality between depression severity and poor QOL. CONCLUSIONS: QOL deficits in acutely depressed hospitalized patients occur at multiple strata in the hierarchy of behavior and are most consistently influenced by age and severity of depression. The effect of age on QOL in depressed inpatients is complex, and age is not uniformly associated with poor QOL.     

Rates of receiving HIV test results: data from the U.S. National Health Interview Survey for 1994 and 1995

OBJECTIVE: To determine the frequency and predictors of receipt of HIV test results. METHODS: Analysis of responses from 19,127 adults in 1994 and 16,848 in 1995 surveyed for the U.S. National Health Interview Survey, using logit models to determine factors independently associated with decreased likelihood of receiving HIV test results. RESULTS: Overall, 12.5% (+/-1.0%) of persons tested in 1994 and 13.3% (+/-0.9%) in 1995 had not received their test results. Those whose test was not self-initiated were significantly less likely (p<.05) to receive their test results. The proportion who did not receive results was lowest among persons who had sought testing (6.1% in 1994 and 4.3% in 1995) and highest among persons whose tests were required for hospitalization or surgery (24.2% in 1994 and 22.9% in 1995). CONCLUSIONS: An estimated 2.3 million of the 17.5 million people tested annually for HIV infection did not receive their test results. Alternative measures to increase the number of persons who receive their results need to be evaluated. These may include enhancing prevention counseling about the importance of receiving test results, telephone notification, or using rapid HIV-screening tests that provide results at the time of testing.     

Randomized, double-blind, placebo-controlled, multicentered trial of the efficacy of a single dose of live oral cholera vaccine CVD 103-HgR in preventing cholera following challenge with Vibrio cholerae O1 El tor inaba three months after vaccination

CVD 103-HgR is a live oral cholera vaccine strain constructed by deleting 94% of the gene for the enzymatically active A subunit of cholera toxin from classical Inaba Vibrio cholerae O1 569B; the strain also contains a mercury resistance gene as an identifying marker. This vaccine was well tolerated and immunogenic in double-blind, controlled studies and was protective in open-label studies of volunteers challenged with V. cholerae O1. A randomized, double-blind, placebo-controlled, multicenter study of vaccine efficacy was designed to test longer-term protection of CVD 103-HgR against moderate and severe El Tor cholera in U.S. volunteers. A total of 85 volunteers (50 at the University of Maryland and 35 at Children's Hospital Medical Center/University of Cincinnati) were recruited for vaccination and challenge with wild-type V. cholerae El Tor Inaba. Volunteers were randomized in a double-blind manner to receive, with buffer, a single oral dose of either CVD 103-HgR (2 x 10(8) to 8 x 10(8) CFU) or placebo (killed E. coli K-12). About 3 months after immunization, 51 of these volunteers were orally challenged with 10(5) CFU of virulent V. cholerae O1 El Tor Inaba strain N16961, prepared from a standardized frozen inoculum. Ninety-one percent of the vaccinees had a >/=4-fold rise in serum vibriocidal antibodies after vaccination. After challenge, 9 (39%) of the 23 placebo recipients and 1 (4%) of the 28 vaccinees had moderate or severe diarrhea (>/=3-liter diarrheal stool) (P < 0.01; protective efficacy, 91%). A total of 21 (91%) of 23 placebo recipients and 5 (18%) of 28 vaccinees had any diarrhea (P < 0.001; protective efficacy, 80%). Peak stool V. cholerae excretion among placebo recipients was 1.1 x 10(7) CFU/g and among vaccinees was 4.9 x 10(2) CFU/g (P < 0.001). This vaccine could therefore be a safe and effective tool to prevent cholera in travelers.     

Human neonatal thymectomy induces altered B‐cell responses and autoreactivity

An association between T‐cell lymphopenia and autoimmunity has long been proposed, but it remains to be elucidated whether T‐cell lymphopenia affects B‐cell responses to autoantigens. Human neonatal thymectomy (Tx) results in a decrease in T‐cell numbers and we used this model to study the development of autoreactivity. Two cohorts of neonatally thymectomized individuals were examined, a cohort of young (1–5 years post‐Tx, n = 10–27) and older children (>10 years, n = 26), and compared to healthy age‐matched controls. T‐cell and B‐cell subsets were assessed and autoantibody profiling performed. Early post‐Tx, a decrease in T‐cell numbers (2.75 × 10⁹/L vs. 0.71 × 10⁹/L) and an increased proportion of memory T cells (19.72 vs. 57.43%) were observed. The presence of autoantibodies was correlated with an increased proportion of memory T cells in thymectomized children. No differences were seen in percentages of different B‐cell subsets between the groups. The autoantigen microarray showed a skewed autoantibody response after Tx. In the cohort of older individuals, autoantibodies were present in 62% of the thymectomized children, while they were found in only 33% of the healthy controls. Overall, our data suggest that neonatal Tx skews the autoantibody profile. Preferential expansion and preservation of Treg (regulatory T) cell stability and function, may contribute to preventing autoimmune disease development after Tx.     

2p15-p16.1 microdeletion syndrome: molecular characterization and association of the OTX1 and XPO1 genes with autism spectrum disorders

Reports of unrelated individuals with autism spectrum disorder (ASD) and similar clinical features having overlapping de novo interstitial deletions at 2p15-p16.1 suggest that this region harbors a gene(s) important to the development of autism. We molecularly characterized two such deletions, selecting two genes in this region, exportin 1 (XPO1) and orthodenticle homolog 1 (OTX1) for association studies in three North American cohorts (Autism Spectrum Disorder - Canadian American Research Consortium (ASD-CARC), New York, and Autism Genetic Resource Exchange (AGRE)) and one Italian cohort (Società Italiana per la Ricerca e la Formazione sull'Autismo (SIRFA)) of families with ASD. In XPO1, rs6735330 was associated with autism in all four cohorts (P<0.05), being significant in ASD-CARC cohorts (P-value following false discovery rate correction for multiple testing (P(FDR))=1.29 × 10(-5)), the AGRE cohort (P(FDR)=0.0011) and the combined families (P(FDR)=2.34 × 10(-9)). Similarly, in OTX1, rs2018650 and rs13000344 were associated with autism in ASD-CARC cohorts (P(FDR)=8.65 × 10(-7) and 6.07 × 10(5), respectively), AGRE cohort (P(FDR)=0.0034 and 0.015, respectively) and the combined families (P(FDR)=2.34 × 10(-9) and 0.00017, respectively); associations were marginal or insignificant in the New York and SIRFA cohorts. A significant association (P(FDR)=2.63 × 10(-11)) was found for the rs2018650G-rs13000344C haplotype. The above three SNPs were associated with severity of social interaction and verbal communication deficits and repetitive behaviors (P-values <0.01). No additional deletions were identified following screening of 798 ASD individuals. Our results indicate that deletion 2p15-p16.1 is not commonly associated with idiopathic ASD, but represents a novel contiguous gene syndrome associated with a constellation of phenotypic features (autism, intellectual disability, craniofacial/CNS dysmorphology), and that XPO1 and OXT1 may contribute to ASD in 2p15-p16.1 deletion cases and non-deletion cases of ASD mapping to this chromosome region.