Urinary excretion of 3-methylhistidine and creatine in carriers of Duchenne muscular dystrophy.

The mean molar ratio (0.0171) of 3-methylhistidine to creatinine in 24-h urine samples from carriers of Duchenne muscular dystrophy did not differ significantly from that of controls. The creatine/creatinine ratio was also normal.     

Mapping the quality of life and unmet needs of urban women with metastatic breast cancer

Enhancing quality of life and reducing the unmet needs of women are central to the successful management of advanced breast cancer. The objective of this study was to investigate the quality of life and support and information needs of urban women with advanced breast cancer. This study was conducted at four large urban hospitals in Melbourne, Australia. A consecutive sample of 105 women with advanced breast cancer completed a questionnaire that contained the European Organization of Research and Treatment of Cancer Quality of Life Q-C30 and the Supportive Care Needs Survey. Between one quarter and a third of the women reported difficulties with their physical, role and social functioning, and a little over a quarter of the women reported poor global health status. Fatigue was a problem for most women. The highest unmet needs were in the psychological and health information domains. Almost no differences in unmet needs were detected when comparing different demographic and disease characteristics of women. Health care providers should routinely monitor the quality of life and needs of women with advanced breast cancer to ensure that appropriate treatment, information or supportive services are made available.     

Flattening of the interventricular septum (D-shaped left ventricle) in addition to high right ventricular tracer uptake and increased right ventricular volume found on gated SPECT studies strongly correlates with right ventricular overload

BACKGROUND: Flattening of the interventricular septum (D-shaped left ventricle) detected during echocardiographic examination is correlated with significant right ventricular (RV) overload. There are no reports of this finding with cardiac gated single photon emission computed tomography (SPECT) imaging. We report an observational study correlating this finding with the presence of RV overload. METHODS AND RESULTS: Retrospectively, we compared 8 cases with flattening of the interventricular septum on cardiac gated SPECT imaging for which echocardiographic correlations and clinical data were available regarding the presence of RV overload. All patients but 1 had pulmonary hypertension ranging from 42 to 52 mm Hg measured by echocardiographic Doppler studies. All patients but 1 had reasons for RV overload (chronic obstructive pulmonary disease in 3, history of atrial septal defect in 3, pulmonary embolism in 1, and obstructive sleep apnea in 1). Septal flattening present on gated SPECT images was seen in 50% of the cases by echocardiography. Other signs of RV overload (RV enlargement, RV hypertrophy) were observed by echocardiography in 5 patients and by the gated SPECT in 7 patients. CONCLUSION: The presence of interventricular septal flattening on gated SPECT studies correlates with RV overload and should be routinely assessed during interpretation of gated SPECT studies.     

What value health?

The objective of this article was to review the methods used to obtain quality-of-life (utility) weights reported in assessments carried out for the National Institute for Health and Clinical Excellence (NICE).The design of the review was a cross-sectional survey. Health technology assessment (HTA) reports published on the NICE website up to May 2003 were reviewed. Data were extracted on the following: the approach to utility estimation (direct or indirect), how health states were described for indirect estimation, valuation techniques used (standard gamble [SG], time trade-off [TTO], visual analogue scale [VAS], etc.), whether uncertainty in utility estimates was explored in cost-utility analyses, and whether utility values were identified as a priority for further research by assessment authors.Fifty-six assessments were reviewed, of which 28 reported 45 cost-utility analyses. There was striking variation in the values used to describe different health states. Data from patients were used in 15 (33%) analyses, from the general public in 10 (22%) and from clinicians in 4 (9%). In 16 (36%) cases, the source for utility estimates was unclear. Health states were described using a range of generic and disease-specific measures, although the EQ-5D was used most frequently. In 25 analyses (56%), the valuation technique used was not reported. TTO was used in 11 (24%), SG in 3 (7%), magnitude estimation in 5 (11%) and VAS in 1 (2%). Sensitivity analyses based on utility values were reported in 25 cases (56%), more commonly in reports of analyses carried out by independent teams than technology sponsors although this may be subject to reporting bias. Further research into quality of life was recommended in 17 (61%) of the 28 assessment reports that contained at least one cost-utility analysis. Greater transparency and consistency are required in reporting the methods used to obtain quality-of-life weights in cost-utility analyses, and better sources of data are required. Methodological variation results in important differences in values. Therefore, caution must be exercised when comparing the results of different cost-utility analyses.     

The effect of overnourishing singleton-bearing adult ewes on nutrient partitioning to the gravid uterus

Overnourishing the singleton-bearing adolescent sheep throughout pregnancy promotes maternal tissue synthesis at the expense of the nutrient requirements of the gravid uterus. Consequently, the growth of the placenta is impaired and results in the premature delivery of low-birth-weight lambs relative to moderately fed adolescents of equivalent age. To establish if this phenomenon is unique to the growing animal, singleton pregnancies to a single sire were established by embryo transfer into primiparous adult ewes who had attained the normal mature body size for their genotype. Thereafter ewes were offered a maintenance or a high level of a complete diet throughout gestation. High maternal intakes resulted in elevated maternal insulin, no significant change in growth hormone or glucose, and attenuated progesterone and NEFA concentrations. Live weight gain during the first 93 d of gestation was 48 and 244 g/d, and adiposity score at term was 2.4 and 3.7 in the maintenance and high groups, respectively (P<0.001). In spite of achieving levels of adiposity similar to overnourished adolescents, placental (477 (sem 30) v. 518 (sem 41) g) and fetal (5190 (sem 320) v. 5420 (sem 250) g) weights were equivalent in maintenance and high groups. Gestation length was shorter (P<0.01) and colostrum yield at parturition lower (P<0.05) in high v. maintenance dams. Thus, adult sheep appear to be relatively insensitive to the oversupply of nutrients during pregnancy and have the ability to meet the nutrient requirements for normal conceptus growth in spite of their increased adiposity.     

DNA stability and lipid peroxidation in vitamin E–deficient rats in vivo and colon cells in vitro

Summary Background Fruit and vegetable consumption protects against cancer. This is attributed in part to antioxidants such as vitamin E combating oxidative DNA damage. Anthocyanins are found in significant concentrations in the human diet. However, it remains to be established whether they are bioactive in vivo. Aim To investigate the consequence both of vitamin E deficiency on oxidative damage to DNA and lipids and the cytoprotective effect of nutritionally relevant levels of cyanidin–3–glycoside both in vivo in rats and in vitro in human colonocytes. Methods Male Rowett Hooded Lister rats were fed a diet containing less than 0.5 mg/kg vitamin E or a vitamin E supplemented control diet containing 100 mg d–tocopherol acetate/kg. Half of the controls and vitamin E–deficient rats received cyanidin–3–glycoside (100 mg/kg). After 12 weeks endogenous DNA stability in rat lymphocytes (strand breaks and oxidised bases) and response to oxidative stress ex vivo (H₂O₂; 200 µM) was measured by single cell gel electrophoresis (SCGE). Tissue levels of 8–oxo–7,8–dihydro–2–deoxyguanosine (8–Oxo–dG) were measured by HPLC with EC detection. D–tocopherol and lipid peroxidation products (thiobarbituric acid reactive substances; TBARS) were measured by HPLC. Rat plasma pyruvate kinase and the production of reactive oxygen by phagocytes were detected spectrophotometrically and by flow cytometry respectively. Immortalised human colon epithelial cells (HCEC) were preincubated in vitro with the anthocyanins cyanidin and cyanidin–3–glycoside and the flavonol quercetin (all 50 µM) before exposure to H₂O₂ (200 µM). DNA damage was measured by SCGE as above. Results Plasma and liver d–tocopherol declined progressively over 12 weeks in rats made vitamin E deficient. Lipid peroxidation was increased significantly in plasma, liver and red cells. Reactive oxygen levels in phagocytes and plasma pyruvate kinase were increased. Vitamin E deficiency did not affect DNA stability in rat lymphocytes, liver or colon. Cyanidin–3–glycoside did not alter lipid peroxidation or DNA damage in rats. However, it was chemoprotective against DNA damage in human colonocytes.DNA strand breakage was decreased 38.8 ± 2.2 % after pretreatment with anthocyanin. Conclusion while it is accepted that vitamin E alters lipid oxidation in vivo, its role in maintaining DNA stability remains unclear. Moreover, whereas cyanidin–3–glycoside protects against oxidative DNA damage in vitro, at nutritionally relevant concentrations it is ineffective against oxidative stress in vivo.