Methylxanthines and benign proliferative epithelial disorders of the breast in women

The relationship between methylxanthine intake (caffeine, theobromine and theophylline) and risk of benign proliferative epithelial disorders (BPED) of the breast was examined in a case-control study conducted in Adelaide, South Australia. The study involved 383 cases with biopsy-confirmed BPED, 192 controls whose biopsy did not show epithelial proliferation, and 383 unbiopsied community controls individually matched to cases on age and area of residence. Overall, there was relatively little variation in risk of BPED with total methylxanthine intake, or with intake of caffeine or theophylline, while there was a positive association between theobromine intake and risk of BPED, but only when cases were compared with biopsy controls. Total methylxanthine intake was positively associated with risk of BPED showing severe atypia, but the trend in risk was statistically significant only when community controls formed the comparison group. These data do not provide strong support for an association between methylxanthine intake and risk of BPED.     

Thymic function in HIV infection

Current models hold that CD4+ depletion occurs as a result of direct and indirect effects of HIV, which both kill peripheral CD4+ cells and prevent adequate regeneration. Although age-associated involution diminishes thymic reserve and HIV is clearly thymotoxic, clinical trials have nonetheless shown that large proportions of patients who sustain adequate control of viral replication with highly active antiretroviral therapy (HAART) will demonstrate some evidence for thymic-dependent immune reconstitution, which is associated with improved immune competence. Furthermore, patients with insufficient or absent immune reconstitution following HAART generally lack evidence for thymopoiesis. Current studies are focused on improving our understanding of the causes for thymic failure in HIV infection. Recent work has demonstrated that some HIV strains, especially those that are CXCR4 trophic, are more thymotoxic and may contribute to irreversible thymic damage in this population.     

Thymic function in HIV infection

Current models hold that CD4+ depletion occurs as a result of direct and indirect effects of HIV, which both kill peripheral CD4+ cells and prevent adequate regeneration. Although age-associated involution diminishes thymic reserve and HIV is clearly thymotoxic, clinical trials have nonetheless shown that large proportions of patients who sustain adequate control of viral replication with highly active antiretroviral therapy (HAART) will demonstrate some evidence for thymic-dependent immune reconstitution, which is associated with improved immune competence. Furthermore, patients with insufficient or absent immune reconstitution following HAART generally lack evidence for thymopoiesis. Current studies are focused on improving our understanding of the causes for thymic failure in HIV infection. Recent work has demonstrated that some HIV strains, especially those that are CXCR4 trophic, are more thymotoxic and may contribute to irreversible thymic damage in this population.     

A tctex1-Ca2+ channel complex for selective surface expression of Ca2+ channels in neurons

Voltage-gated Ca(2+) channels (VGCCs) are important in regulating a variety of cellular functions in neurons. It remains poorly understood how VGCCs with different functions are sorted within neurons. Here we show that the t-complex testis-expressed 1 (tctex1) protein, a light-chain subunit of the dynein motor complex, interacts directly and selectively with N- and P/Q-type Ca(2+) channels, but not L-type Ca(2+) channels. The interaction is insensitive to Ca(2+). Overexpression in hippocampal neurons of a channel fragment containing the binding domain for tctex1 significantly decreases the surface expression of endogenous N- and P/Q-type Ca(2+) channels but not L-type Ca(2+) channels, as determined by immunostaining. Furthermore, disruption of the tctex1-Ca(2+) channel interaction significantly reduces the Ca(2+) current density in hippocampal neurons. These results underscore the importance of the specific tctex1-channel interaction in determining sorting and trafficking of neuronal Ca(2+) channels with different functionalities.     

Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia.

CONTEXT: Human papillomavirus (HPV) infection is believed to be the central cause of cervical cancer, although most of the epidemiological evidence has come from retrospective, case-control studies, which do not provide information on the dynamics of cumulative or persistent exposure to HPV infection. OBJECTIVE: To assess the risks of cervical neoplasia related to prior persistent HPV infections. DESIGN AND SETTING: Longitudinal study of the natural history of HPV infection and cervical neoplasia in women residing in the city of S?o Paulo, Brazil, which was conducted between November 1993 and March 1997 and involved repeated measurements of HPV and lesions with follow-up until June 2000. PARTICIPANTS: A total of 1611 women with no cytological lesions at enrollment and HPV test results available from the first 2 visits. MAIN OUTCOME MEASURE: Cervical specimens taken for Papanicolaou cytology and HPV testing every 4 months in the first year and twice yearly thereafter. Incident cervical cancer precursor lesions ascertained by expert review of all cytology smears. RESULTS: The incidence rate of squamous intraepithelial lesions (SILs) was 0.73 per 1000 women-months (95% confidence interval [CI], 0.5-0.9) among women free of HPV at the 2 initial visits and 8.68 (95% CI, 2.3-15.1) among women with HPV type 16 or 18 infections persisting over both visits. Relative to those negative for HPV oncogenic types at both initial visits, the relative risk (RR) of incident SIL was 10.19 (95% CI, 5.9-17.6) for persistent infections with any known oncogenic HPV types. The equivalent RR of incident high-grade SIL was 11.67 (95% CI, 4.1-33.3). The RRs of lesions were considerably higher for persistent infections with HPV type 16 or 18. CONCLUSION: A strong relationship exists between persistent HPV infections and SIL incidence, particularly for HPV types 16 and 18.     

Design and methods of the Ludwig-McGill longitudinal study of the natural history of human papillomavirus infection and cervical neoplasia in Brazil. Ludwig-McGill Study Group.

This article reports on a large longitudinal study, begun in 1993, of the natural history of human papillomavirus (HPV) infection and cervical neoplasia in a population of low-income women in S?o Paulo, Brazil, a city with one of the highest risks worldwide for cervical cancer. Known as the Ludwig-McGill cohort study, the epidemiological investigation focuses on persistent infection with oncogenic HPV types as the precursor event leading to cervical neoplasia. The objectives of this study are to: 1) study the epidemiology of persistent cervical HPV infection in asymptomatic women, 2) investigate whether persistent HPV infection increases risk of low-grade and high-grade cervical lesions, 3) search for determinants of persistent HPV infection, 4) search for molecular variants of HPV that may be associated with an increased risk of lesions, 5) investigate whether viral burden is correlated with persistent infections and with lesion risk, 6) study the antibody response to HPV as a predictor of persistence and lesion progression, and 7) examine the role of HLA typing and codon 72 p53 gene polymorphism in mediating HPV persistence and lesion severity. The study accrued 2,528 female subjects through March 1997. Subjects were followed up every 4 months in the first year, with twice-yearly return visits to take place in subsequent years. Participants undergo a questionnaire-based interview, have a cervical specimen taken for Pap cytology and HPV testing, and have a blood sample drawn for HPV antibody testing. A cervicography is performed once in the first year and every two years thereafter. In this article we describe the design and methods of the study, provide baseline cohort characteristics, and present a preliminary assessment of the prognostic value of baseline HPV status.     

Comparison of four habitual physical activity questionnaires in girls aged 7-15 yr

PURPOSE: Questionnaires provide a practical approach to measuring physical activity in children and adolescents, particularly for large-scale epidemiological studies. The purpose of the present study was to compare four habitual physical activity questionnaires and to assess their long-term reliabilities. METHODS: Subjects were female, aged 7-15 yr (and their parents), who participated in a cohort study in which predictors of the onset of menarche were being investigated. Questionnaires consisted of three single-item and one multi-item habitual physical activity questions and were sent to the 640 participants. Test-retest reliability of the questionnaires was assessed on 100 randomly selected participants 11 months later. RESULTS: The Spearman's correlation coefficient was highest (r = 0.40) between the Godin-Shephard Score and the Perspiration Score and was lowest (r = 0.10) between the Stairs Score and the Specific Activity Score. The correlation coefficients were higher when the questionnaires were reported to have been completed by the parents alone, rather than by parents with the assistance of their daughters. The test-retest reliabilities were r = 0.44 for the Perspiration Score, r = 0.59 for the Stairs Score, r = 0.48 for the Godin-Shephard Score, and r = 0.53 for the Specific Activity Score. The reliabilities were higher when the retest was reported to have been completed by the parents alone. CONCLUSIONS: This study suggests that the Perspiration Score, the Godin-Shephard Score, and the Specific Activity Score may provide simple and practical measures of habitual physical activity for children and adolescents.     

Pregnant women and car restraints: beliefs and practices

OBJECTIVE: Motor vehicle collisions are a leading cause of death and disability in pregnant women. The purpose of this study was to examine current restraint practices by pregnant women. Additionally, the beliefs and knowledge of pregnant women about restraint laws and effectiveness were studied. METHODS: From May of 1997 to January of 1998, women were surveyed at initial prenatal visit at four obstetrical clinics. Data collected included age, gravida, ethnicity, educational level attained, payor source, restraint use, and knowledge of effectiveness of restraint use. RESULTS: A total of 807 women completed surveys. Most always wore restraints before pregnancy, but increased restraint use during pregnancy (79% vs. 86%, chi2, p = 0.02). Only 52% used restraints properly. Significantly fewer women believed restraints were beneficial to mother and fetus in late pregnancy compared with early pregnancy. Only 21% of women were educated on proper restraint use during pregnancy. Comparison by payor mix showed no difference in use or education received. CONCLUSIONS: Most women use restraints and continue to do so during pregnancy, but they use them improperly. Pregnant women are familiar with mandatory restraint laws but are less informed about restraint use in pregnancy. Few women receive education from health care providers about proper restraint use. This study highlights the need for aggressive educational efforts to improve car restraint use in pregnant women, thereby reduce maternal and fetal injury and death.