The relation between birth weight and intima-media thickness in middle-aged adults

BACKGROUND: Birth weight has been found to be inversely associated with the risk of coronary heart disease and stroke, although the mechanisms for this association remain unclear. Here, we investigate the relation between reported birth weight and atherosclerosis in middle age. METHODS: We included the 9817 participants (age 44-65) in the Atherosclerosis Risk in Communities (ARIC) study who were neither a twin nor born prematurely. Carotid atherosclerosis was assessed as intima-media thickness measured by B-mode ultrasound. We studied the association with recalled exact birth weight, and for those unable to recall exact birth weight, with recalled birth weight category. RESULTS: Mean intima-media thickness (+/- standard deviation) was 0.73 +/- 0.17 mm. Mean birth weight for the 4635 participants recalling exact birth weight was 3.49 +/- 0.71 kg. A further 4946 participants recalled birth weight category, with 4730 (96%) reporting "medium" birth weight. In univariate analysis, birth weight and intima-media thickness were positively related. However, adjustment for confounding factors reduced the association to only a 0.004 mm higher intima-media thickness (95% CI = - 0.003 to 0.011) mm per 1 kg of birth weight. The same pattern of univariate positive relationship and attenuation with adjustment was seen for birth weight category and intima-media thickness. There was no evidence of interaction between adult body mass index (BMI) and birth weight, or of interaction between category of adult BMI and birth weight category. An inverse relation between birth weight category and intima-media thickness was seen only for those in the lowest category of adult BMI (BMI <25 kg/m). CONCLUSIONS: We found no evidence of a clinically significant relation between birth weight and carotid atherosclerosis.     

Association of antigens to ISCOMATRIX adjuvant using metal chelation leads to improved CTL responses

The association of antigen with ISCOMATRIX trade mark adjuvant has been shown to be important for the optimal induction of cytotoxic T lymphocyte (CTL) responses. Here, we describe a simple broadly applicable method for associating recombinant proteins with hexa-histidine tags to ISCOMATRIX trade mark adjuvant utilising metal-affinity chelating interactions. The metal chelation binding step can be performed in a wide range of buffers, including commonly used denaturants such as urea, which makes it an ideal strategy for formulating proteins which are otherwise insoluble. Following association of protein with the chelating ISCOMATRIX trade mark adjuvant, the denaturant can be removed. Further, we show enhanced CTL responses with a protein-associated chelating ISCOMATRIX trade mark vaccine compared to a non-associated ISCOMATRIX trade mark vaccine.     

The State Children's Health Insurance Program: successes, shortcomings, and challenges

This paper examines successes and shortcomings of the State Children's Health Insurance Program (SCHIP). SCHIP is a source of coverage for millions of children, improving their access to health care and sparking innovation in program design and improvements in Medicaid. However, SCHIP adds to the complexity of the insurance system and introduces new inequities in access to insurance; it is imperfectly targeting eligible children who are uninsured; and its financing is problematic because of the block-grant funding structure and use of SCHIP funds to cover adults. These issues need to be addressed during the SCHIP reauthorization process.     

Exercise interventions for cancer patients: systematic review of controlled trials

Objective: To systematically review controlled trials investigating the effects of exercise interventions in cancer patients. Methods: Studies were located through searching seven electronic databases (Medline, Embase, Cochrane Library, CancerLit, PsycInfo, Cinahl, SportDiscus), scanning reference lists of relevant articles, contacting experts (n = 20), and checking the contents lists of journals available through ZETOC (Electronic Table of Contents). To be included, trials had to be prospective, controlled, involve participants diagnosed with cancer and test an exercise intervention. Types of outcome were not restricted. Two reviewers independently applied the selection criteria. ResultsThirty-three controlled trials (including 25 randomized trials) were included in the review. There was some evidence that physical function was increased among those who exercised. Furthermore, symptoms of fatigue did not appear to be increased and there were few adverse effects reported. There was insufficient evidence to determine effects on other outcomes, such as quality of life, with results hampered by the heterogeneity between studies as well as poor methodological quality. Data were also lacking on the long term effects of exercise relating to cancer recurrence or survival. Conclusions There is preliminary evidence that exercise interventions for cancer patients can lead to moderate increases in physical function and are not associated with increased symptoms of fatigue. However, it is impossible from current evidence to determine whether exercise has long term beneficial effects on survival or quality of life.     

Hyperinsulinaemia and Increased Risk of Breast Cancer: Findings From the British Women's Heart and Health Study

OBJECTIVE: To assess the association between fasting insulin levels and breast cancer. DESIGN: Cross sectional study. PARTICIPANTS: 3868 women aged 60-79 years. MAIN OUTCOME MEASURE: Prevalent breast cancer (151 cases). RESULTS: Insulin levels were positively associated with breast cancer. The age adjusted odds ratio (95% confidence interval) for a one unit increase in log(e) insulin levels among women without diabetes was 1.34 (1.02, 1.77). This association was not substantively altered by adjustment for potential confounding factors (age of menopause, hysterectomy/oophorectomy, hormone replacement use, oral contraceptive use, parity, adult social class and smoking) or potential mediating factors (body mass index, waist to hip ratio, leg length, age at menarche and childhood social class). Women with both long legs and higher insulin levels were at particularly increased risk, with breast cancer prevalence being 5.7% among women in the highest thirds of both insulin levels and leg-length compared to 1.8% among those in the lowest thirds of both. Positive associations between insulin levels and breast cancer were found for both pre- and post-menopausal breast cancers. Fasting glucose levels, HOMA score, diabetes and a history of gestational glycosuria or diabetes were also positively associated with breast cancer CONCLUSIONS: Hyperinsulinaemia is positively associated with breast cancer in this cohort of older women. This effect may be mediated via a number of hormonal pathways acting at different stages of the life course.     

Establishing the compliance in elderly women for use of a low level mechanical stress device in a clinical osteoporosis study

Non-pharmacologic approaches to prevent bone loss are well suited for elderly patients to avoid polypharmacy and medication side effects. One potential treatment is a vibrating platform that delivers low-level mechanical loading stimulating bone remodeling. However, compliance is a major concern with any daily treatment, and is unknown for an elderly group using this device. Thus we assessed compliance with standing 10 min/day on a vibrating platform device in elderly women, the target population for osteoporosis therapy. We also assessed satisfaction with daily use of the device. We conducted a randomized, placebo-controlled, double-blinded 6-month study for daily use of a 10-min vibrating platform treatment in elderly women who were residents of a Continuing Care Retirement community. Compliance for each subject was calculated as the number of days attended divided by the 182 days in the 6-month trial. The 24 elderly women (mean age 86, range 79–92 years) had 83% compliance (95% CI: 70.5, 94.5) for daily treatment over 6 months. Excluding three study drop-outs, the 21 women had 93% compliance (95% CI: 89.8, 95.6), with no difference in compliance between active and placebo treatment. Main reasons for missing treatment days over the 6 months were vacation (54% of missed days) and illness (29%). Three adverse events occurred; one (syncope) was possibly related to device use, whereas the other two were not related to device use. Among participants, 95% reported overall satisfaction with daily use of the vibrating platform, and 57% preferred the platform versus daily oral medications for prevention of bone loss. Elderly women showed high compliance, high satisfaction and few adverse experiences with a daily non-pharmacological treatment designed to inhibit bone loss. Larger randomized controlled trials should evaluate the long-term efficacy of vibrating platform devices for treatment of low bone mass and osteoporosis in elderly individuals.     

Rescue of in vivo FAS-induced apoptosis of hepatocytes by corticosteroids either associated with alcohol consumption by mice or provided exogenously

The pathogenic effects of many hepatic viral infections are mediated, at least in part, by the immune response to the infected hepatocyte. The immune response in the infected liver involves the interaction of cytotoxic T cells (CTL) with the hepatocytes through the interaction of FAS-ligand on the CTL and FAS on the hepatocyte. The initial hypothesis for this study was that alcohol consumption by mice would sensitize the liver to apoptosis induced by ligation of FAS. C57Bl/6 mice fed ethanol in a liquid diet did show an increased percentage of apoptotic cells 2 h after injection with anti-FAS as compared with the percentage in the control mice. However, 4 and 6 h after anti-FAS injection, control mice showed high percentages of apoptotic cells (20% to 41%) compared with 5% and 4% apoptotic cells in the ethanol-fed mice. The decreased apoptosis of ethanol-fed mice correlated closely with corticosterone levels in the sera. This was confirmed by the finding that adrenalectomized (ADX) mice provided a high level of corticosterone in drinking water were protected against FAS-induced hepatocyte apoptosis. Ethanol-fed mice showed a significant elevation of serum alanine aminotransferase (ALT) levels indicating the development of hepatitis in spite of the relatively low proportion of apoptotic cells in the liver. In conclusion, high levels of corticosterone protect hepatocytes from FAS-mediated apoptosis, but do not prevent the ultimate development of liver damage. In experiments where mice were provided ethanol chronically in drinking water, where stress is minimal, higher levels of ALT were noted in animals in the ethanol group as compared with animals in the control group. These data support the suggestion that ethanol increases hepatocyte sensitivity to FAS-mediated damage.     

Atypical composition and ultrastructure of proteoglycans in the mouse corneal stroma

PURPOSE: Recently, gene-targeted strains of mice with null mutations for specific proteoglycans (PGs) have been used for investigations of the functional role of these molecules. In the present study, the corneal stroma of the mouse was examined to provide some baseline PG morphologies in this species. METHODS: Monoclonal antibodies to specific glycosaminoglycan (GAG) chain sulfation patterns were used to characterize PG composition in corneal extracts by SDS-PAGE and Western blot analysis and to identify their tissue distribution by immunofluorescence microscopy. PGs were also visualized by transmission electron microscopy after contrast enhancement with cationic dye fixation. RESULTS: Western blot analysis of pooled corneal extracts and immunofluorescence of tissue sections identified 4-sulfated, but not 6-sulfated, chondroitin sulfate/dermatan sulfate (CS/DS). Keratan sulfate (KS) was present only as a low-sulfated moiety. Electron microscopic histochemistry disclosed a complex array of corneal PGs present as (1) fine filaments radiating from collagen fibrils, and (2) elongate, straplike structures, running either along the fibril axis or weaving across the primary fibril orientation. These large structures were digested by chondroitinase ABC, but not by keratanase. CONCLUSIONS: KS in the mouse is predominantly undersulfated and generates an immunostaining pattern that differs from that observed in corneas of other mammalian species thus far investigated. The mouse cornea resembles other mammalian corneas in the presence of filamentous arrays of small, collagen-associated stromal PGs visualized by cationic dye staining. However, large dye-positive structures with a CS/DS component are also present and appear to be unique to the cornea of this species.