The Ohio Midlife Women's Study

The Ohio Midlife Women's Study was longitudinal with measurements occurring at three, 9-month intervals. Our purpose in doing this research was to examine predictors, moderators, and outcome variables associated with the transition to midlife in Caucasian and African American women. Predictor variables included loss and gain of resources. Moderators included menopause symptoms, menopausal status, attitude toward menopause, coping, and demographic characteristics. Outcome variables included anxiety, depression, and health promoting activities. To obtain the proposed final sample of 160 midlife women, an initial sample of 103 African American and 105 Caucasian "healthy" women were recruited in the community. Consistent predictors of anxiety were loss of resources, coping effectiveness, and education. Consistent predictors of depression were loss of resources and education. Health promoting activities were consistently predicted by attitude toward menopause and coping effectiveness. Stress is a better predictor of negative health outcomes than menopausal status.     

Winter planning. Seasonal cycles

It is possible to forecast emergency admissions and bed requirements with considerable accuracy up to a year in advance. A model is being developed which would analyse the effects of weather, flu epidemics and different surges in demand. The discharge pattern of many hospitals indicates a rush to discharge by the weekend that could raise concerns about appropriate care.     

Human papillomavirus 16 load in normal and abnormal cervical scrapes: an indicator of CIN II/III and viral clearance

The relation between human papillomavirus type 16 (HPV 16) viral load in cervical scrapes and development of high-grade cervical intraepithelial neoplasia (CIN II or III) was studied in a nested case-control study of women with normal cytology (group A) and in a cohort of women with abnormal cytology (group B). HPV 16 DNA load was determined using a quantitative real-time PCR assay. In group A, case women (women with CIN II/III, n = 12) had a significantly higher viral load than control women (women with CIN < or = I, n = 47). This resulted in an increased relative risk of women with the 50% highest viral load for development of CIN II/III (OR 7.7; CI 1.6-33). In group B, women with CIN II/III (n = 38) had a significantly higher viral load than women with CIN < or = I (n = 25). Women with the 50% highest viral load had an increased relative risk of CIN II/III (OR 3.2; CI 1.1-9.3) and a decreased chance of both viral clearance and cytologic regression. Our data suggest that in women with normal cytology an increased HPV 16 load confers an increased risk of developing a CIN lesion. A sustained high viral load is subsequently informative for progression to a high-grade CIN lesion.     

Gemcitabine and Radiotherapy in the Treatment of Brain Metastases from Transitional Cell Carcinoma of the Bladder: A Case Report

Hematogenous metastases occur in over 50% of muscle-invasive transitional cell carcinomas (TCC) of the bladder. Despite treatment (mostly surgery and radiotherapy), patients with brain metastases have an especially poor prognosis (median survival 2–5 months), making palliative treatment an important consideration. We followed a 60-year-old man with multiple brain metastases who was ultimately treated with gemcitabine chemotherapy. He underwent a cystectomy in 1997 because of a T3a N0 M0 G3 TCC of the bladder. Two years later, he developed one brain metastasis and one lung metastasis. Both metastases were resected and adjuvant chemotherapy was planned. Before chemotherapy, the patient suffered from headaches and symptoms of hemiparesis. A magnetic resonance imaging (MRI) showed multiple brain metastases of up to 2cm, particularly in the brain stem. The patient underwent whole-brain radiotherapy with 30Gy, followed by four cycles of a 3-week gemcitabine (800mg/m² on days 1 and 8) schedule. Another MRI showed a nearly complete response after four cycles of chemotherapy, with only small residual tumors remaining in the brain stem. This impressive activity was accomplished without adverse side effects, suggesting that radiotherapy combined with gemcitabine monotherapy may be an excellent choice for palliative treatment of TCC of the bladder.     

Chalkley estimates of angiogenesis in early breast cancer--relevance to prognosis

The aim of this study was to investigate whether Chalkley estimates of angiogenesis add new knowledge regarding prediction of prognosis in 455 consecutive early breast carcinomas, both node-positive (52%) and node-negative (48%). Median follow-up was 101 months. Intense vascularization indicated poor disease-specific (p = 0.003) and overall (p = 0.004) survival. In node-negative patients, Chalkley counts were not associated with prognosis, whereas in node-positive patients, high Chalkley scores indicated poor disease-specific (p = 0.0006) and overall (p = 0.0008) survival. A multivariate analysis showed that positive lymph nodes, high histopathological grades, and negative oestrogen receptors were independent markers of cancer-related death. A high histopathological grade was associated with cancer-related death in node-negative patients, whereas in node-positive patients, many lymph nodes, high malignancy grade, negative oestrogen receptor, and increasing Chalkley counts (both tertiles and continuous) were independent markers of disease-specific death. Thus, in a univariate analysis it was found that high Chalkley estimates of angiogenesis indicated a poor prognosis, but high Chalkley estimates were independent prognostic markers only in node-positive patients.     

Farm exposures,parental occupation,and risk of Ewing's sarcoma in Australia: a national case-control study

Objective: It has been suggested that parental occupation, particularly farming, increased the risk of Ewing's sarcoma in the offspring. In a national case–control study we examined the relationship between farm and other parental occupational exposures and the risk of cancer in the offspring. Methods: Cases were 106 persons with confirmed Ewing's sarcoma or peripheral primitive neuroectodermal tumor. Population-based controls (344) were selected randomly via telephone. Information was collected by interview (84% face-to-face). Results: We found an excess of case mothers who worked on farms at conception and/or pregnancy (odds ratio (OR) = 2.3, 95% confidence interval (CI) 0.5–12.0) and a slightly smaller excess of farming fathers; more case mothers usually worked as laborers, machine operators, or drivers (OR = 1.8, 95% CI 0.9–3.9). Risk doubled for those whose mothers handled pesticides and insecticides, or fathers who handled solvents and glues, and oils and greases. Further, more cases lived on farms (OR = 1.6, 95% CI 0.9–2.8). In the 0–20 years group, the risk doubled for those who ever lived on a farm (OR = 2.0, 95% CI 1.0–3.9), and more than tripled for those with farming fathers at conception and/or pregnancy (OR = 3.5, 95% CI 1.0–11.9). Conclusions: Our data support the general hypothesis of an association of Ewing's sarcoma family of tumors with farming, particularly at younger ages, who represent the bulk of cases, and are more likely to share etiologic factors.     

Effect of renal impairment on the pharmacokinetics and tolerability of capecitabine (Xeloda) in cancer patients

PURPOSE: The primary objective of this study was to investigate the influence of renal impairment on the pharmacokinetics of capecitabine and its metabolites in cancer patients. Capecitabine (Xeloda) is an orally administered precursor of 5'-deoxy-5-fluorouridine (5'-DFUR), which is preferentially activated to 5-fluorouracil (5-FU) in tumors. METHODS: A total of 27 patients were enrolled, of whom 24 were evaluable for pharmacokinetics (6 with normal renal function, 8 with mild, 6 with moderate, and 4 with severe renal impairment at baseline). Patients received capecitabine orally at the standard dosing regimen (1250 mg/m(2) capecitabine twice daily for 2 weeks followed by a 1-week rest period). On study days 1 and 14, blood samples were collected to evaluate the pharmacokinetics of capecitabine and its metabolites. The relationship between the area under the plasma concentration-time curve (AUC) and creatinine clearance (CL(CR)) was assessed by log-linear regression analysis. RESULTS: The primary pharmacokinetic parameter with respect to the effect of renal dysfunction was systemic exposure to 5'-DFUR, 5-FU and FBAL determined on study day 14. Renal impairment led to an increase in the systemic exposure to 5'-DFUR and FBAL (23% and 109% increase in AUC, respectively) for a 50% reduction in CL(CR). By contrast, renal impairment may lead to decreased exposure to 5'-DFCR. There was no evidence for an effect of renal impairment on systemic exposure to 5-FU or capecitabine. Renal impairment did not have a major effect on peak concentration (C(max)) or elimination half-life (t(1/2)) of capecitabine, 5'-DFCR, 5'-DFUR, and 5-FU. However, in the case of FBAL, moderate or severe renal impairment caused up to a twofold increase in C(max) and prolongation of t(1/2). All patients with severe renal impairment (four patients) had drug-related grade 3 or 4 adverse-events (AEs) and serious AEs. Patients with moderate renal impairment experienced a similar number of grade 3 or 4 AEs (six of nine patients) but had a higher incidence of serious AEs (three of nine patients) when compared with those with normal renal function (four of six patients and one of six patients, respectively). A similar effect was seen in patients with mild renal dysfunction (grade 3 or 4 AEs in four of eight patients; serious AEs in three of eight patients). The relationship between systemic exposure to capecitabine or its metabolites and safety was investigated using logistic regression. This exploratory analysis showed a strong positive relationship between AUC of 5'-DFUR and treatment-related grade 3 or 4 AEs, whereas there was no relationship with exposure to capecitabine, 5'-DFCR, 5-FU or FBAL. CONCLUSIONS: Renal impairment has no effect on the pharmacokinetics of capecitabine or 5-FU, but leads to an increase in the systemic exposure to 5'-DFUR and FBAL. However, only the AUC of 5'-DFUR is correlated with safety. Based on the safety results in patients with severe renal impairment, a dose modification cannot be recommended for these patients and they should not be treated with capecitabine. Additional data from the clinical safety database and pharmacokinetic results from the present study support the recommendation that patients with moderate renal impairment should be treated with 75% of the recommended standard starting dose to achieve systemic exposure comparable to that in patients with normal renal function.