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.     

Functional innervation of the striatum by ventral mesencephalic grafts in mice with inherited nigrostriatal dopamine deficiency

Weaver mutant mice are characterized by a decrease in striatal dopamine (DA), which is associated with a progressive loss of DA neurones in the substantia nigra. This mutant thus provides the opportunity to examine the functional effects of DA neurones grafted to the striatum in a genetic model of parkinsonism. Ventral mesencephalic tissue from normal foetuses was placed on the surface of the right dorsal striatum of adult weaver mutants. After grafting, animals were tested for methamphetamine-induced circling behaviour. Mutants with DA containing grafts displayed a significant circling bias toward the left, non-grafted side. Mutants without grafts did not display any rotational bias to either side. These results demonstrate that grafted DA containing neurones establish a functional innervation of the weaver striatum and suggest that grafting of neural tissue is a viable approach in restoring function in genetic degenerative disorders of the nigrostriatal system.     

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.     

A comparative study on the immunological effects of bovine and porcine thymic extracts: induction of lymphoproliferative response and enhancement of interleukin-2, gamma-interferon and tumor necrotic factor production in vitro on cord blood lymphocytes

Forty samples of cord blood lymphocytes were isolated from 40 normal healthy full-term newborns. The initial 20 samples were used to determine the dose-response curve of three different thymic extracts (TP-1, bovine thymic extract; TG-15-I and TG-15-II, both porcine thymic extracts) and one of renal origin (KG-1) as a control of non-lymphoid organ extract, by measuring the E-rosette T cells. Results showed that E-rosette T cells increased significantly when the thymic extract concentration was increased to 12.5 micrograms/ml. However, there was no statistical difference between TP-1, TG-15-I and TG-15-II in the increase of E-rosette-forming cells. The remaining 20 samples were preincubated with 0, 12.5, 25 or 50 micrograms/ml of thymic extracts. It was observed that the lymphoproliferation, interleukin-2 (IL-2), gamma-interferon (IFN-gamma) and tumor necrotic factor (TNF) production were all significantly increased after thymic extract treatment. No statistical difference between these three thymic preparations in the stimulation of lymphoproliferative response was found. However, among the three thymic extracts, TP-1 appears to induce the highest amounts of IL-2, IFN-gamma and TNF. Of the TG-15-I and TG-15-II, the former stimulates higher IL-2 production whereas the latter enhances IFN-gamma and TNF production. The different immunostimulating effects and potencies that these three thymic extracts showed may reflect not only the species difference but also the difference in preparation procedures. Different components in these thymic extracts may be responsible for different biological activities. Results from these comparative studies may provide useful information in future clinical trials for the treatment of the primary immunodeficiency diseases according to their pathogenesis and may also indicate a possible beneficial effect of the combination of chemotherapy and thymic extracts.     

Improvement of endoneurial lipid abnormalities in experimental diabetic neuropathy by oxygen modification

Endoneurial hypoxia and a high frequency of closed capillaries have been found in chronic experimental diabetes and human diabetic sural nerve, respectively. These findings have led to the hypothesis that the pathogenesis of diabetic neuropathy is due to endoneurial hypoxia. To evaluate the role of endoneurial hypoxia in experimental diabetic neuropathy, the effects of supplementation and deprivation of oxygen on peripheral nerve lipid biosynthesis were studied in normal control and streptozotocin-induced diabetic rats. Defective lipid biosynthesis in diabetic nerve was partially prevented by oxygen supplementation. When normal rats were placed in a hypoxic chamber, lipid abnormalities similar to those observed in diabetic nerves were demonstrated in the absence of changes in nerve free sugars. These findings suggest that endoneurial hypoxia may underlie some key biochemical abnormalities encountered in experimental diabetic neuropathy.     

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.     

Highly resolved in vivo 1H NMR spectroscopy of the mouse brain at 9.4 T.

An efficient shim system and an optimized localization sequence were used to measure in vivo 1H NMR spectra from cerebral cortex, hippocampus, striatum, and cerebellum of C57BL/6 mice at 9.4 T. The combination of automatic first- and second-order shimming (FASTMAP) with strong custom-designed second-order shim coils (shim strength up to 0.04 mT/cm2) was crucial to achieve high spectral resolution (water line width of 11-14 Hz). Requirements for second-order shim strengths to compensate field inhomogeneities in the mouse brain at 9.4 T were assessed. The achieved spectral quality (resolution, S/N, water suppression, localization performance) allowed reliable quantification of 16 brain metabolites (LCModel analysis) from 5-10-microL brain volumes. Significant regional differences (up to 2-fold, P < 0.05) were found for all quantified metabolites but Asp, Glc, and Gln. In contrast, 1H NMR spectra measured from the striatum of C57BL/6, CBA, and CBA/BL6 mice revealed only small (<13%, P < 0.05) interstrain differences in Gln, Glu, Ins, Lac, NAAG, and PE. It is concluded that 1H NMR spectroscopy at 9.4 T can provide precise biochemical information from distinct regions of the mouse brain noninvasively that can be used for monitoring of disease progression and treatment as well as phenotyping in transgenic mice models.     

Changes in activity level in women aged 40-80 years.

OBJECTIVES: The purpose of this study was to report habitual physical activity levels in women and document the change in level of activity and factors affecting this change over a 5-year period. METHODS: A 5-year prospective cohort design was used. Women aged 40-80 years, living independently in the community, were recruited via the electoral role. The effects were investigated, first, of age, activity level, history of falls, number of co-morbidities and medications, body mass index and stability at baseline on change in activity level and, second, change in these demographics on activity level over the study period. RESULTS: Data from 459 women who completed our study are reported. Only activity level and body mass index at baseline significantly affected change in activity level (p<0.000). Change in activity level was not influenced by change in demographics over the study period. The forties and fifties cohorts accounted for the baseline body mass index effect on activity change (p<0.04). In the forties cohort, number of medical conditions at base line (p<0.03) and, in the sixties cohort, increase in number of medical conditions (p=0.011) affected activity level change. CONCLUSIONS: Activity level at baseline and body mass index in younger women were most likely to affect change over time. Being unsteady or having already fallen did not stimulate change.