Effect of maternal and infant covariates on sibship correlation in birth weight

Birth weight on 12,644 singleton infants from 6,196 sibships born in Maryland between 1980 and 1984 were used to estimate the effects of nine maternal and infant covariates on the sibship correlation in birth weight. Assuming a homogeneous correlation across all families, the estimated intraclass correlation was 0.4664 (+/- 0.0099). This high sibship correlation makes it possible to predict, with reasonable accuracy, the birth weight of a child given information on previous sibs, as well as covariates on the mother and/or infant pertinent to a given pregnancy. The reduction in variance associated with incorporating information on the nine covariates used here was approximately equal to that obtained by conditioning on a single previous sib. Testing for heterogeneity in correlation among different groups of families showed that a crude measure of parity (first live birth vs. other), time between births, mother's marital status, and maternal age at the birth of the last child significantly influenced the sibship correlation in birth weight.     

Retrospective review of pemetrexed with or without platinum in malignant mesothelioma: The Australian 'Special Access Scheme' experience

Background: Pemetrexed and cisplatin have recently been shown to significantly improve survival compared with cisplatin alone. However, there are only limited data reflecting teaching hospital experience outside a clinical trial. Pemetrexed has only been available in Australia on a restricted basis since 2002. We reviewed our experience of patients treated on the Australian ‘Special Access Scheme’ at three major thoracic oncology units. Methods: Charts were reviewed for all patients enrolled on the scheme. Data was extracted on age, World Health Organization (WHO) performance status, histology, prior therapy, time from diagnosis to starting pemetrexed, chemotherapy (pemetrexed alone or with a platinum), cycle number, response rate, actuarial progression‐free and overall survival. Doses were cisplatin 75 mg/m² or carboplatin AUC = 5 and pemetrexed 500 mg/m² every 21 days. Results: 52 patients (32 male and 20 female) were reviewed. Median age was 58 years and 88% were WHO 0–1. Histology included 54% epithelial, 17% biphasic (epithelial and sarcomatoid) and 21% undefined. The median time from diagnosis to administration of pemetrexed was 145 days. Sixty‐five percent had minimal surgical intervention with video assisted thoracoscopy, pleurodesis and biopsy, while 19% had received prior palliative radiation. Seventy‐one percent were chemotherapy naïve, the remaining 29% having received previous platinum and/or gemcitabine regimens. Twenty‐three percent had pemetrexed alone, 35% in combination with carboplatin and 42% with cisplatin. The median number of cycles was 4 (range 1–13). The response rate was 33%. No toxicity was observed in 20% grade 3–4 toxicity in 10% (majority nausea/vomiting). The median progression‐free and overall survival times from starting pemetrexed were 184 days and 298 days, respectively. Conclusions: Pemetrexed‐based regimens are safe and effective in a community setting in malignant mesothelioma.     

FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.     

Family Stress and Functioning in Children: the Moderating Effects of Children''s Beliefs About Their Control Over Parental Conflict

While factors such as gender and SES have been studied as moderators of stress for children, their perceptions of control have received little attention. In the current study, children's domain-specific perceptions of their control during marital conflict were investigated as potential moderators of the impact of family stress on children's behavior problems, and perceptions of competence. Ninety-four children aged 6-12 years and mothers from families ranging in level of parental conflict from nondiscordant to discordant to physically violent were interviewed. Multiple regression analyses revealed that higher levels of conflict control beliefs acted as compensatory moderators of stress, being associated with lower levels of problem behaviors across stress levels. However, higher conflict control beliefs acted as vulnerability moderators with regard to children's perceptions of competence.     

The fate of N1'-methanesulphonyl-N4'-(9-acridinyl)-3'-methoxy-2',5'-cyclohexadiene- 1',4'-diimine (m-AQDI), the primary oxidative metabolite of amsacrine, in transformed Chinese hamster fibroblasts

The cytotoxicity of the anti-leukaemia drug amsacrine (m-AMSA) has been suggested to result from its oxidative metabolism to the corresponding quinonediimine, N1'-methanesulphonyl-N4'-(9-acridinyl)-3'-methoxy-2',5'-cyclohexad iene-1',4'- diimine (mAQDI). The metabolic fate of mAQDI was examined in cultured CHO cells (subline AA8) to identify the end products to be expected following oxidative metabolism of m-AMSA. [Acridinyl-G-3H]-m-AQDI was rapidly accumulated by AA8 cells in phosphate buffered saline with complete conversion in less than one minute to m-AMSA, macromolecular adducts and polar low molecular weight species, each of these three classes being formed in approximately equal amounts. Two of the polar products were chromatographically identical to those formed on reaction of m-AQDI with reduced glutathione. These were identified by 1H NMR spectroscopy as the 1,4-addition product 5'-(S-glutathionyl)-m-AMSA and the previously unreported isomeric 6'-(S-glutathionyl)-m-AMSA. These thiol adducts were also formed rapidly from m-AQDI in deproteinized cell lysates indicating a non-enzymatic process, although the possibility of enzymatic catalysis in intact cells has not been eliminated. The absence of such products in AA8 cells after treatment with m-AMSA places an upper limit of 1% per hour on the rate of its oxidative metabolism in these cells and suggests that generation of m-AQDI is unlikely to be responsible for the cytotoxicity of m-AMSA in cultured tumour cells.