Depression in midlife women attending a menopause clinic is associated with a history of childhood maltreatment.

A growing body of literature has suggested that the perimenopause and the early postmenopausal years are associated with an increased risk of experiencing symptoms of depression and the development of first-onset and recurrent episodes of major depressive disorder. Multiple risk factors have been identified, including stressful life events and lower socioeconomic status, as well as early life adversity. The objective of the current study was to characterize the influence of early life childhood maltreatment and incident depression among women experiencing bothersome menopausal symptoms. Participants were recruited from two university-affiliated specialty clinics caring for women with bothersome menopausal symptoms. Assessments included the Childhood Trauma Questionnaire (CTQ), the Center for Epidemiological Studies - Depression (CES-D) scale and the Greene Climacteric Scale. Findings from this cross-sectional study indicate that adverse childhood experiences, as measured using the CTQ, were highly prevalent among women seeking care for bothersome menopausal symptoms (66%). Further, a greater score on the CTQ was significantly associated with higher CES-D scores, as well as with a greater burden of menopausal symptoms, after adjusting for confounding. Our findings lend support to the growing body of literature suggesting that early life stress affects mental health well into adulthood.

The effect of serotonin reuptake inhibitors on the vaginal epithelium in postmenopausal women.

Purpose: Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are used as alternative treatments for the vasomotor symptoms of menopause in women who are unwilling or unable to receive hormone therapy. These agents have been associated with sexual dysfunction and xerostomia (dry mouth), but the effect on the vagina has not been studied. The objective of this study was to determine the effect of SSRIs and SNRIs on the vaginal epithelium and sexual function in postmenopausal women, using both subjective and objective measures. Materials and methods: A cross-sectional study of postmenopausal women not using any local or systemic estrogen therapy was conducted. The main outcomes included the Female Sexual Function Index (FSFI), vaginal epithelial maturation index (MI), and pH. Results: Sixty-six women were recruited, 30 using SSRIs/SNRIs and 36 who were not (control). Both the proportion of superficial vaginal epithelial cells and the total MI were higher in the SSRI/SNRI group (p = 0.006 and p = 0.047, respectively). There were no significant differences in FSFI scores, vaginal pH, or total MI values. Conclusion: The use of serotonin reuptake inhibiting drugs does not appear to have a negative influence on the vaginal epithelium and associated vaginal atrophy.

The effectiveness of implementing a reminder system into routine clinical practice: does it increase postpartum screening in women with gestational diabetes?

INTRODUCTION: During regular care, women with previous gestational diabetes mellitus (GDM) rarely receive the recommended screening test for type 2 diabetes, a 2-hour oral glucose tolerance test (OGTT), in the postpartum period. The current study examined whether the implementation of a reminder system improved screening rates. METHODS: Based on our previous randomized control trial, we implemented a postpartum reminder (letter or phone call) protocol into routine care at two of three clinical sites. We verified postpartum testing by searching hospital laboratory databases and by linking to the provincial physician service claims database. The primary outcome was the proportion of patients who underwent an OGTT within 6 months of delivery. RESULTS: Women who received care in a setting using a reminder system were more likely to receive an OGTT within 6 months postpartum (28%) compared with usual care (14%). The OGTT rates for both reminder groups were lower than that found in our randomized control trial (28% vs. 60%). CONCLUSION: Although the screening rates remain low, postpartum reminders doubled screening rates using the recommended test, the OGTT.

Relative dominance of epitope-specific cytotoxic T-lymphocyte responses in human immunodeficiency virus type 1-infected persons with shared HLA alleles.

Cytotoxic T lymphocytes (CTL) target multiple epitopes in human immunodeficiency virus (HIV)-infected persons, and are thought to influence the viral set point. The extent to which HLA class I allele expression predicts the epitopes targeted has not been determined, nor have the relative contributions of responses restricted by different class I alleles within a given individual. In this study, we performed a detailed analysis of the CTL response to optimally defined CTL epitopes restricted by HLA class I A and B alleles in individuals who coexpressed HLA A2, A3, and B7. The eight HIV-1-infected subjects studied included two subjects with acute HIV infection, five subjects with chronic HIV infection, and one long-term nonprogressor. Responses were heterogeneous with respect to breadth and magnitude of CTL responses in individuals of the same HLA type. Of the 27 tested epitopes that are presented by A2, A3, and B7, 25 were targeted by at least one person. However, there was wide variation in the number of epitopes targeted, ranging from 2 to 17. The A2-restricted CTL response, which has been most extensively studied in infected persons, was found to be narrowly directed in most individuals, and in no cases was it the dominant contributor to the total HIV-1-specific CTL response. These results indicate that HLA type alone does not predict CTL responses and that numerous potential epitopes may not be targeted by CTL in a given individual. These data also provide a rationale for boosting both the breadth and the magnitude of HIV-1-specific CTL responses by immunotherapy in persons with chronic HIV-1 infection.

Persistence of human immunodeficiency virus type 1-specific cytotoxic T-lymphocyte clones in a subject with rapid disease progression.

We longitudinally measured T-cell receptor transcript frequencies of human immunodeficiency virus type 1 (HIV-1) specific cytotoxic T lymphocytes (CTL) in an individual with rapidly progressive disease and high levels of viremia. CTL clones elicited during acute HIV-1 infection were present at the time of death, despite absent functional CTL responses, arguing against clonal deletion as a mechanism for the decline of CTL responses observed during HIV-1 infection.

Association between virus-specific cytotoxic T-lymphocyte and helper responses in human immunodeficiency virus type 1 infection.

Cellular immune responses are thought to be an important antiviral host defense, but the relationship between virus-specific T-helper and cytotoxic-T-lymphocyte (CTL) responses has not been defined. To investigate a potential link between these responses, we examined functional human immunodeficiency virus type 1 (HIV-1)-specific memory CTL precursor frequencies and p24-specific proliferative responses in a cohort of infected untreated persons with a wide range of viral loads and CD4 cell counts. Levels of p24-specific proliferative responses positively correlated with levels of Gag-specific CTL precursors and negatively correlated with levels of plasma HIV-1 RNA. These data linking the levels of HIV-specific CTL with virus-specific helper cell function during chronic viral infection provide cellular immunologic parameters to guide therapeutic and prophylactic vaccine development.

Levels of human immunodeficiency virus type 1-specific cytotoxic T-lymphocyte effector and memory responses decline after suppression of viremia with highly active antiretroviral therapy.

Therapeutic suppression of human immunodeficiency virus type 1 (HIV-1) replication may help elucidate interactions between the host cellular immune responses and HIV-1 infection. We performed a detailed longitudinal evaluation of two subjects before and after the start of highly active antiretroviral therapy (HAART). Both subjects had evidence of in vivo-activated and memory cytotoxic T-lymphocyte precursor (CTLp) activity against multiple HIV-1 gene products. After the start of therapy, both subjects had declines in the levels of in vivo-activated HIV-1-specific CTLs and had immediate increases in circulating HIV-1-specific CTL memory cells. With continued therapy, and continued suppression of viral load, levels of memory CTLps declined. HLA A*0201 peptide tetramer staining demonstrated that declining levels of in vivo-activated CTL activity were associated with a decrease in the expression of the CD38(+) activation marker. Transient increases in viral load during continued therapy were associated with increases in the levels of virus-specific CTLps in both individuals. The results were confirmed by measuring CTL responses to discrete optimal epitopes. These studies illustrate the dynamic equilibrium between the host immune response and levels of viral antigen burden and suggest that efforts to augment HIV-1-specific immune responses in subjects on HAART may decrease the incidence of virologic relapse.