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.     

Cholinergic septal grafts into the hippocampal formation improve spatial learning and memory in aged rats by an atropine-sensitive mechanism

Behaviorally impaired old rats were selected from a population of 75 21- to 23-month-old rats on the basis of the place-investigated abilities in the Morris' water-maze task. After the pretransplant test, half of the old impaired rats received bilateral intrahippocampal cell suspension grafts prepared from the fetal septal-diagonal band region, which is rich in developing cholinergic neurons; the other half were left as sham-operated controls. Twelve weeks after grafting, the rats were retested in the water-maze using alternating cue-navigation and place-navigation trials (i.e., with visible or nonvisible escape platform). While the old impaired controls had deteriorated further between the 2 tests and showed poor retention of the pretransplant performance level, the grafted rats were significantly improved in comparison with both their pretransplant performance and the performance of the old impaired controls in the posttransplant test. The graft-induced effect was due both to an improved retention of the performance level acquired in the test performed prior to transplantation surgery, and to an improved acquisition of spatial memory of the escape platform site during the posttransplant test week (measured as an improved focusing of search over the platform site after platform removal). The acetylcholine esterase inhibitor physostigmine had no or only marginal effects on the performance of any of the young or aged rat groups. By contrast, the recovered navigational abilities and spatial memory in the grafted animals were completely abolished after administration of the muscarinic receptor antagonist atropine. A similar atropine-sensitivity was seen in behaviorally nonimpaired aged rats but not in the well-trained young control rats. The results show that cholinergic septal grafts, implanted into the hippocampal formation, improved spatial learning in the impaired aged rats primarily, or perhaps exclusively, by a recovery of the rats' ability to use spatial cues for place-navigation in the water-maze, while other aspects of the performance deficits in the water-maze task in the aged rats were left unaffected by the septal grafts. On the basis of parallel morphological studies, it is proposed that the effects of the septal grafts on the spatial learning impairments in the aged rats are critically dependent on the direct action of cholinergic neurons in the grafts via synapses formed onto neuronal elements in the host by their ingrowing axons.     

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.     

Examining the dynamics of spouse abuse: an alternative view

Spouse abuse continues to be a great problem in our society. Much of the literature about the problem, however, assumes that the roles of perpetrator and victim are always fixed, with the man as perpetrator and the woman as victim. This perception is understandable if the injuries received are the focus of attention, and the sole informant about the violence is the person who has most often been the recipient of injuries. On occasions when both partners are interviewed, a different perception of violent relationships is likely to emerge. Violence can be viewed as occurring along a continuum. One extreme is represented as mutual combat, in which both partners play a role in the escalation of conflict. The other extreme follows the traditional concept of battering where the woman is victimized by the man. Primary care practitioners are in a position to assist clients who are in violent relationships and to help them learn more functional problem-solving skills. This article focuses on methods of identifying violent couples and teaching them how to interrupt the cycle of violence.     

Urinary medium-chain acylcarnitines in medium-chain acyl-CoA dehydrogenase deficiency, medium-chain triglyceride feeding and valproic acid therapy: sensitivity and specificity of the radioisotopic exchange/high performance liquid chromatography method.

To determine the sensitivity and specificity of detecting urinary medium-chain acylcarnitines for the diagnosis of MCAD deficiency, 114 urine specimens from 75 children with metabolic diseases and controls were analyzed in a blinded fashion using a radioisotopic exchange/HPLC method. All 47 patients with MCAD deficiency were correctly diagnosed using the criterion hexanoylcarnitine or octanoylcarnitine peak areas larger than those of other medium-chain acylcarnitines. The majority of them were tested during the asymptomatic state without L-carnitine loading. Four patients with other defects of fatty acid oxidation and three patients receiving valproic acid had a similar acylcarnitine excretion pattern. To further examine the specificity of the method, eight infants receiving a diet enriched with medium-chain triglycerides and 13 additional patients receiving valproic acid were studied. Most of these also tested positive for MCAD deficiency by the above criterion. Analysis by a new gas chromatographic-mass spectrometric procedure revealed that octanoylcarnitine, not valproylcarnitine, was the most abundant medium-chain carnitine ester excreted by a patient treated with valproic acid. Quantitation of urinary hexanoylcarnitine and octanoylcarnitine showed considerable overlap among patients with MCAD deficiency and those receiving valproic acid or a medium-chain triglyceride-enriched diet. MCAD deficiency can be reliably detected in urine specimens by this method without the need for prior carnitine loading. However, other defects in fatty acid oxidation must be differentiated from MCAD deficiency, and a history of medium-chain triglyceride or valproic acid administration must be considered if the diagnosis of MCAD deficiency is sought through analysis of urinary acylcarnitines.     

Effects of butanedione monoxime on neuromuscular transmission.

1. The amplitude of endplate potentials was increased by concentrations of butanedione monoxime (BDM, 5-20 mM) that typically caused muscle paralysis. 2. Although BDM slowed the decay of spontaneous miniature endplate currents, the effect was insufficient to explain most of the large increase in amplitude of endplate potentials. 3. The quantal content of endplate potentials was increased by BDM in a reversible, concentration-dependent manner. 4. The frequency of miniature endplate potentials was not changed by 10 mM BDM in the presence of normal or raised potassium concentrations, indicating that BDM does not change quantal content by a direct effect on calcium channels or on steady-state intracellular calcium concentration. 5. A change in the time course of the extracellularly recorded nerve terminal action potential caused by BDM was similar to the change produced by 4-aminopyridine (4-AP). 6. The increase in quantal content produced by BDM was only slightly reduced in the presence of 1 mM tetraethylammonium (TEA) but was significantly reduced in the presence of 0.5 to 1 mM 4-AP. 7. It was concluded that BDM blocks a 4-AP-sensitive potassium conductance in motor nerve terminals and, by increasing the duration of the action potential in this way, increases evoked transmitter release.