Innervation of the sheep adrenal cortex: an immunohistochemical study with rat corticotrophin-releasing factor antiserum

Using indirect immunohistochemistry and an antiserum raised against rat corticotrophin-releasing factor (CRF) we have outlined an asymmetric network of cells and varicose fibers in sheep adrenal cortex. This network was not associated with the larger splanchnic nerves, but was occasionally found in small bundles or with blood vessels; in most instances fibers were found weaving independently through cortical parenchyma. A plexus of fibers was found in the zona reticularis, with a few fibers ramifying into adjacent medulla. Uni or bipolar cells were found throughout the cortex, with the greatest frequency at the corticomedullary junction; a multipolar-type cell was also found in this area. Staining of varicose structures and most cells was abolished by incubation with excess rat CRF 1-41, but not by ovine CRF or a range of other peptides. Though the immunoreactive species has not as yet been identified, it may thus share homology with sequences present in rat but not ovine CRF.     

Human immunodeficiency virus infection in urban Rwanda. Demographic and behavioral correlates in a representative sample of childbearing women

OBJECTIVE.--To determine behavioral and demographic risk factors for human immunodeficiency virus (HIV) infection in central Africa. DESIGN.--Cross-sectional survey. SETTING.--Kigali, Rwanda. PARTICIPANTS.--A representative sample of 1458 childbearing women aged 19 to 37 years who were recruited from outpatient prenatal and pediatric clinics at the only community hospital in the city. MAIN OUTCOME MEASURE.--Antibodies to HIV assessed by enzyme immunoassay and confirmed by Western blot or indirect immunofluorescence. RESULTS.--The HIV seroprevalence was 32% overall. Infection rates were higher in women who were single, in those in steady relationships that began after 1981, and in the 33% of women reporting more than one lifetime sexual partner. Women in legal marriages or monogamous partnerships had lower rates of infection, but even low-risk women had prevalences on the order of 20%. History of venereal disease in the past 5 years, although the strongest risk factor in a multiple logistic analysis (odds ratio, 2.7; 95% confidence interval, 2.0 to 3.7), was reported by only 30% of those infected. Having a male sexual partner who drank alcohol or who had higher income were significant risk factors for HIV infection in the multivariate analysis, but use of oral contraceptives and having an uncircumcised partner were not. CONCLUSIONS.--The epidemic of the acquired immunodeficiency syndrome in Rwanda has spread beyond high-risk groups to the general population of women without known risk factors. For most of these women, a steady male partner is the source of their HIV risk and therefore a vital target for intervention efforts.     

Molecular epidemiologic studies of polycyclic aromatic hydrocarbon-DNA adducts and breast cancer

We review our studies on the role of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in breast cancer. Additionally we report on analyses of the reliability of the scoring procedures used with immunohistochemical assay for PAH-DNA adducts and of potential bias arising from the use of benign breast disease (BBD) controls. We conducted a case-control study utilizing two control groups: BBD controls who donated tissue and blood samples, and healthy controls who donated blood samples. In comparisons of tumor tissue from cases and benign tissue from BBD controls, increasing adduct levels were significantly associated with case-control status [odds ratio (OR) = 2.40, 95% confidence interval (CI) 1.18-4.92], whereas in comparisons of nontumor tissue from cases and benign tissue from BBD controls the association was nonsignificant (OR = 1.97, 95% CI 0.94-4.17). We also show among cases, but not among BBD controls, that the GSTM1 null genotype is associated with increased adduct levels in breast tissue. Our reliability study found the scoring procedures used with the immunohistochemical assay to have high reliability, 0.93 in nontumor, 0.82 in tumor, and 0.74 in benign tissues. However, we found that the technician significantly contributed to the total variability of a series of data. Finally, we did not find a consistent bias to the null associated with the use of BBD controls; however, BBD controls may overestimate the prevalence of family history of breast cancer compared to that of healthy controls (18% vs.14%). We hypothesize that the higher prevalence results from a referral bias and discuss how this may influence our results.     

Associations between both genetic and environmental biomarkers and lung cancer: evidence of a greater risk of lung cancer in women smokers

This molecular epidemiologic case-control study of lung cancer incorporated three complementary biomarkers: the glutathione S- transferase M1 (GSTM1) null genotype, a potential marker of susceptibility, and polycyclic aromatic hydrocarbon-DNA adducts (PAH- DNA) and sister chromatid exchanges (SCE), both indicators of environmentally induced genetic damage. Associations between biomarkers and lung cancer were investigated, as were possible gene-environment interactions between the GSTM1 null genotype and tobacco smoke exposure. Subjects included 136 primary non-small cell lung cancer surgical patients and 115 controls at the Columbia Presbyterian Medical Center. Questionnaire and Tumor Registry data, pre-treatment blood samples and biomarker measurements on blood were obtained. Overall, GSTM1 null genotype was significantly associated with lung cancer [odds ratio (OR) = 2.04, 95% confidence interval (CI) = 1.13-3.68]. ORs for GSTM1 and lung cancer were significant in females (2.50, 1.09-5.72) and smokers (2.25, 1.11-4.54) and not significant in males (1.4, 0.58-3.38) and non-smokers (0.88, 0.18-4.33). However, ORs for males versus females and smokers versus non-smokers did not differ significantly. The OR for GSTM1 and lung cancer in female smokers was 3.03 (1.09- 8.40), compared with 1.42 (0.53-4.06) in male smokers. In contrast to PAH-DNA adducts in leukocytes, SCE did not differ between cases and controls. Neither biomarker differed significantly between the two GSTM1 genotypes. The combined effect of elevated PAH-DNA adducts and GSTM1 genotype on case-control status (16.19, 1.2-115) appeared multiplicative. Results suggest that the effect of the GSTM1 null genotype is greatest in female smokers, which is consistent with other evidence that indicates that women are at higher risk of lung cancer than males, given equal smoking. Persons with both the GSTM1 deletion and elevated PAH-DNA adducts may represent a sensitive subpopulation with respect to carcinogens in tobacco smoke and other environmental media.      

Design options for molecular epidemiology research within cohort studies.

Past discussions of the relative strengths of nested case-control and case-cohort designs have not fully considered cohorts with stored biological samples in which biomarker analyses are planned. Issues related to biomarker analyses can affect an investigator's choice of design and the conduct of these two designs. The key issues identified are effects of analytic batch, long-term storage, and freeze-thaw cycles on biomarkers. In comparison with the nested case-control design, the case-cohort design is less able to handle these challenges. Problems arise because most implementations of the case-cohort design do not allow for simultaneous evaluation of biomarkers in cases and reference group members, and there is no matching. By design, the nested case-control study controls for storage duration and the batching of biological samples from cases and controls is logistically simple. The allowance for matching also means that subjects can be matched on the number of freeze-thaw cycles experienced by the biological sample. However, the matching generates complex data sets that can be more difficult to analyze, and the costly biomarker data generated from the controls has few uses outside of testing the specific hypotheses of the study. In addition, because the same subject can serve as a control and a case, or multiple times as a control, biomarker analyses and sample batching can be more complex than initially anticipated. However, in total, of the two designs, the nested case-control study is better suited for studying biomarkers that can be influenced by analytic batch, long-term storage, and freeze-thaw cycles.     

A Randomized Controlled Trial Comparing the Effects of Yoga With an Active Control on Ambulatory Blood Pressure in Individuals With Prehypertension and Stage 1 Hypertension

The purpose of this study was to compare the effects of yoga with an active control (nonaerobic exercise) in individuals with prehypertension and stage 1 hypertension. A randomized clinical trial was performed using two arms: (1) yoga and (2) active control. Primary outcomes were 24‐hour day and night ambulatory systolic and diastolic blood pressures. Within‐group and between‐group analyses were performed using paired t tests and repeated‐measures analysis of variance (time × group), respectively. Eighty‐four participants enrolled, with 68 participants completing the trial. Within‐group analyses found 24‐hour diastolic, night diastolic, and mean arterial pressure all significantly reduced in the yoga group (?3.93, ?4.7, ?4.23 mm Hg, respectively) but no significant within‐group changes in the active control group. Direct comparisons of the yoga intervention with the control group found a single blood pressure variable (diastolic night) to be significantly different (P=.038). This study has demonstrated that a yoga intervention can lower blood pressure in patients with mild hypertension. Although this study was not adequately powered to show between‐group differences, the size of the yoga‐induced blood pressure reduction appears to justify performing a definitive trial of this intervention to test whether it can provide meaningful therapeutic value for the management of hypertension.     

Outcomes of treatment with stereotactic radiosurgery or proton beam therapy for choroidal melanoma

Aim

To present our experience of the use of stereotactic radiosurgery and proton beam therapy to treat posterior uveal melanoma over a 10 year period.

Methods and materials

Case notes of patients treated with stereotactic radiosurgery (SRS), or Proton beam therapy (PBT) for posterior uveal melanoma were reviewed. Data collected included visual acuity at presentation and final review, local control rates, globe retention and complications. We analysed post-operative visual outcomes and if visual outcomes varied with proximity to the optic nerve or fovea.

Results

191 patients were included in the study; 85 and 106 patients received Stereotactic radiosurgery and Proton beam therapy, respectively. Mean follow up period was 39 months in the SRS group and 34 months in the PBT group. Both treatments achieved excellent local control rates with eye retention in 98% of the SRS group and 95% in the PBT group. The stereotactic radiosurgery group showed a poorer visual prognosis with 65% losing more than 3 lines of Snellen acuity compared to 45% in the PBT group. 33% of the SRS group and 54% of proton beam patients had a visual acuity of 6/60 or better.

Conclusions

Stereotactic radiosurgery and proton beam therapy are effective treatments for larger choroidal melanomas or tumours unsuitable for plaque radiotherapy. Our results suggest that patients treated with proton beam therapy retain better vision post-operatively; however, possible confounding factors include age, tumour location and systemic co-morbidities. These factors as well as the patient''s preference should be considered when deciding between these two therapies.     

Regional differences in cardiovascular risk factor prevalence in Tasmania: are they consistent with the increased cardiovascular mortality?

Background: The death rate from cardiovascular disease in Tasmania has been among the highest in Australian States for a number of years. The North-West (NW) and Northern regions of Tasmania account for most of the increased mortality.
Aims: To determine the prevalence of cardiovascular risk factors in the North and NW regions of Tasmania and to ascertain whether any differences are consistent with the regional patterns of mortality for ischaemic heart disease (IHD) within the State.
Methods: The design of the study was almost identical to the previous National Heart Foundation (NHF) Risk Factor Prevalence Survey conducted in 1989. The subjects, aged 20–69 years, were randomly selected from the Electoral Roll with 1146 subjects participating in the North and 1219 in the NW. Subjects answered a detailed questionnaire and then underwent a brief physical examination with venipuncture for blood lipids. Hobart data from the NHF Risk Factor Prevalence Survey in 1989 were used as an estimate of risk factor prevalence in the Southern region.
Results: In both males and females, mean systolic blood pressure was significantly higher in the NW than the South which was in turn higher than the North. Mean serum cholesterol levels in males were higher in the NW than the North. Smoking behaviour was similar in males and females in all regions. Males and females in the NW and North were more inactive than those in the South. Similar proportions in all regions were on either 'no specific' or 'fat modified' diets. Body mass index in males and females was higher in the NW and North but waist to hip ratios failed to show a consistent trend.
Conclusions: While the NW has an unfavourable risk factor profile compared with the South, the North does not. The risk factor data are broadly consistent with, but unlikely to be sufficient to explain fully, the regional differences in mortality from IHD. (Aust NZ J Med 1995; 25: 290–296.)