Effects of alcohol intake on endothelial function in men: a randomized controlled trial

BACKGROUND: Regular light consumption of alcohol appears to reduce the risk of cardiovascular disease, whereas in heavier drinkers the opposite effect is seen. This biphasic relationship could partly be due to contrasting actions of low and high alcohol intake on endothelial function. OBJECTIVE: To determine whether reducing alcohol intake in moderate-to-heavy drinkers (40-110 g/day) would improve conduit artery endothelial function as assessed by post-ischaemic brachial artery flow-mediated dilatation (FMD). METHODS: In a two-way cross-over study, 16 healthy men either substituted their usual alcohol intake with a 0.9% alcohol beer or maintained their usual alcohol intake during sequential 4-week periods. At the end of each period of FMD and glyceryl trinitrate-induced brachial artery dilatation, blood pressure, plasma lipids, homocysteine and biomarkers of alcohol consumption (gamma-glutamyl transpeptidase) and endothelial function (E-selectin, von Willebrand factor, endothelin-1) were assessed. RESULTS: The participants reduced their alcohol intake from 72.4 to 7.9 g/day. This self-reported reduction in alcohol intake was corroborated by significant decreases in gamma-glutamyl transpeptidase (24%). The decrease in alcohol intake resulted in reductions in total cholesterol (5%), high-density lipoprotein cholesterol (17%), homocysteine (9%) and systolic and diastolic blood pressure [5 mmHg (P = 0.01) and 4 mmHg (P = 0.003), respectively]. There was no effect of alcohol on FMD (6.23 +/- 0.75% compared with 6.24 +/- 0.71%, P = NS), glyceryl trinitrate-induced vasodilatation, E-selectin, endothelin-1 and von Willebrand factor. CONCLUSION: Substantial reduction in alcohol intake in healthy moderate-to-heavy drinkers does not improve endothelial function as measured by post-ischaemic flow-mediated dilatation of the brachial artery or biomarkers of endothelial function.     

The Impact of Expressions of Treatment Efficacy and Out-of-pocket Expenses on Patient and Physician Interest in Osteoporosis Treatment: Implications for Pay-for-performance Programs

BACKGROUND Clinical practice guidelines (CPGs) are increasingly used as the basis for pay-for-performance (P4P) programs. It is unclear how support for guidelines varies when treatment efficacy is expressed in varying mathematically equivalent ways. OBJECTIVES To assess: (1) how patient and provider compliance with osteoporosis CPGs varies when pharmacotherapy efficacy is presented as relative risk reduction (RRR) versus absolute risk reduction (ARR) and (2) the impact of increasing out-of-pocket drug expenditures on acceptance of guideline concordant therapy. DESIGN Cross-sectional survey of patients and physicians. SUBJECTS AND SETTING Female patients age >50 years and providers drawn from academic and community outpatient clinics. MEASUREMENTS Patient and provider acceptance of pharmacotherapy when treatment efficacy (reduction in hip fractures) was expressed alternatively in relative terms (35% RRR) versus absolute terms (1% ARR); acceptance of pharmacotherapy as patient drug copayment increased from 0% to 100% of the total drug costs. RESULTS Compliance with CPGs fell significantly when the expression of treatment benefit was switched from RRR to ARR for both patients (86% vs 57% compliance; P < .001) and physicians (97% vs 56% compliance; P < .001). Increasing drug copayment from 0% to 10% of total drug cost decreased patient compliance with CPGs from 80% to 57% (P < .001) but did not impact physician compliance. With increasing levels of copay, both patient and provider interest in treatment decreased. LIMITATIONS Respondents may not have fully understood the risks and benefits associated with osteoporosis and its treatment. CONCLUSION Patient and provider interest in CPG-recommended treatment for osteoporosis is reduced when treatment benefit is expressed as ARR rather than RRR. In addition, minimal increases in drug copayment significantly decreased patient, but not provider, interest in osteoporosis treatment. Designers of P4P programs should consider details including expressions of treatment benefit and patients’ out-of-pocket costs when developing measures to assess quality-of-care. Dr. Sinsky presented this work at the 2006 national SGIM meeting in Los Angeles.     

Association Between 6-<Emphasis Type="Italic">n</Emphasis>-Propylthiouracil (PROP) Bitterness and Colonic Neoplasms

Inadequate vegetable intake appears to increase colon cancer risk. Since genetic variation in taste influences vegetable preference, we tested associations between bitterness of 6-n-propylthiouracil (PROP), a measure of taste genetics, and number of colonic polyps, a measure of colon cancer risk, in 251 men who underwent screening lower endoscopy. Patients used the general Labeled Magnitude Scale to rate bitterness of 1.6 mg PROP delivered via filter paper. A subset of 86 patients reported weekly vegetable intakes, excluding salad or potatoes. PROP bitterness correlated significantly with polyp number, an effect separate from age-associated increases in polyp number. The PROP–polyp relationship was strongest in men over 66 years, and older men with polyps were most likely to be overweight or obese. In the subset reporting vegetable intake, men who tasted PROP as more bitter consumed fewer vegetables. These preliminary findings suggest that taste genetics may influence colon cancer risk, possibly through intake of vegetables.This work was supported by a MAVERIC grant from the Veterans Administration (M.D.B.) and by NIDCD Grant DC00283 (L.M.B. and V.B.D.).     

Ensemble versus single-molecule protein unfolding

Molecular dynamics (MD) simulations are the classic single-molecule "experiments," providing atomic-resolution structural and dynamic information. However, the single-molecule nature of the technique has also been its shortcoming, with frequent criticisms of sampling inadequacies and questions regarding the ensemble behavior of large numbers of molecules. Given the increase in computer power, we now address this issue by performing a large number of simulations and comparing individual and ensemble properties. One hundred independent MD simulations of the protein chymotrypsin inhibitor 2 were carried out for 20 ns each at 498 K in water to more fully describe the potentially diverse routes of protein unfolding and investigate how representative a single trajectory can be. Rapid unfolding was observed in all cases with the trajectories distributed about an average "ensemble" path in which secondary and tertiary structure was lost concomitantly, with tertiary structure loss occurring slightly faster. Individual trajectories did, however, sample conformations far from the average path with very heterogeneous time-dependent properties. Nevertheless, all of the simulations but one followed the average ensemble pathway, such that a small number of simulations (5-10) are sufficient to capture the average properties of these states and the unfolding pathway.     

Sequential development of hematopoietic and cardiac mesoderm during embryonic stem cell differentiation

The ability to generate a wide spectrum of differentiated cell types from ES cells in culture offers a powerful approach for studying lineage induction and specification and a promising source of progenitors for cell replacement therapy. Although significant efforts are being made to optimize culture conditions for the generation of different cell populations from ES cells, the identification and efficient isolation of specific progenitors for many lineages within these cultures remains a major challenge. By specifically tracking hematopoietic and cardiac development, we demonstrate here that these two lineages arise from distinct mesoderm subpopulations that develop in sequential waves from pre-mesoderm cells. Access to these populations provides a unique approach to isolate and characterize the earliest progenitors of these lineages.     

Very recent onset arthritis--clinical,laboratory, and radiological findings during the first year of disease

OBJECTIVE: To describe clinical and radiological findings in patients with very early arthritis (< 3 months of symptoms) during one year of observation. METHODS: In an Austrian multicenter setting, patients were eligible if they had nontraumatic swelling or pain in at least one joint and laboratory signs of inflammation [elevated erythrocyte sedimentation rate, C-reactive protein, leukocytosis, or rheumatoid factor (RF)] within the last 3 months. Clinical and laboratory assessments were performed every 3 months. Radiographs of hands and feet were taken at entry and after one year. Treatment decisions were left to the discretion of the participating center. RESULTS: In total, 108 patients included between 1996 and 2000 had followup investigations during at least one year; 61.1% of these patients had rheumatoid arthritis (RA). Over 65% of RA diagnoses were made at the first visit. Lag time to referral was significantly longer in patients with RA than in patients with other inflammatory joint diseases (median 8 vs 4 weeks). Disease modifying antirheumatic drugs were started 19 +/- 10 (mean +/- SD) weeks after symptom onset in patients with RA. Patients with RA improved significantly (by American College of Rheumatology response criteria and the Disease Activity Score 28) during the first year. Erosions were present in 12.8% of RA patients' initial radiographs, compared to 27.6% after one year. Odds ratio to develop new erosions during the first year of RA was 9.7 (95% CI 1.05-89.93) in RF+ patients compared to RF- individuals (p < 0.05). CONCLUSION: When early referral of patients with arthritis is encouraged, RA can be diagnosed and treatment initiated early, with significant clinical response. Moreover, patients with RA tend to be referred later than patients with other inflammatory joint diseases; RA patients at this very early stage have low frequency of joint damage; and RF predicts erosions in the first year.     

Relation of physician specialty and HIV/AIDS experience to choice of guideline-recommended antiretroviral therapy

BACKGROUND: Controversy exists regarding who should provide care for those with HIV/AIDS. While previous studies have found an association between physician HIV experience and patient outcomes, less is known about the relationship of physician specialty to HIV/AIDS outcomes or quality of care. OBJECTIVE: To examine the relationship between choice of appropriate antiretroviral therapy (ART) to physician specialty and HIV/AIDS experience. DESIGN: Self-administered physician survey. PARTICIPANTS: Random sample of 2,478 internal medicine (IM) and infectious disease (ID) physicians. MEASUREMENTS: Choice of guideline-recommended ART. RESULTS: Two patients with HIV disease, differing only by CD4+ count and HIV RNA load, were presented. Respondents were asked whether ART was indicated, and if so, what ART regimen they would choose. Respondents' ART choices were categorized as "recommended" or not by Department of Health and Human Services guidelines. Respondents' HIV/AIDS experience was categorized as moderate to high (MOD/HI) or none to low (NO/LO). For Case 1, 72.9% of responding physicians chose recommended ART. Recommended ART was more likely (P <.01) to be chosen by ID physicians (88.2%) than by IM physicians (57.1%). Physicians with MOD/HI experience were also more likely (P <.01) to choose recommended ART than those with NO/LO experience. Finally, choice of ART was examined using logistic regression: specialty and HIV experience were found to be independent predictors of choosing recommended ART (for ID physicians, odds ratio [OR], 4.66; 95% confidence interval [95% CI], 3.15 to 6.90; and for MOD/HI experience, OR, 2.05; 95% CI, 1.33 to 3.16). Results for Case 2 were similar. When the analysis was repeated excluding physicians who indicated they would refer the HIV "patient," specialty and HIV experience were not significant predictors of choosing recommended ART. CONCLUSIONS: Guideline-recommended ART appears to be less likely to be chosen by generalists and physicians with less HIV/AIDS experience, although many of these physicians report they would refer these patients in clinical practice. These results lend support to current recommendations for routine expert consultant input in the management of those with HIV/AIDS.     

Research as a tool for empowerment in South Africa

With democracy making inroads in South Africa, oppressed groups have an opportunity to be part of a new research agenda.