A randomized trial comparing low-fat and low-carbohydrate diets matched for energy and protein

Several recent studies have found greater weight loss at 6 months among participants on a very-low-carbohydrate (VLC) weight-loss diet compared with a low-fat (LF) weight-loss diet. Because most of these studies were not matched for calories, it is not clear whether these results are caused by decreased energy intake or increased energy expenditure. It is hypothesized that several energy-consuming metabolic pathways are up-regulated during a VLC diet, leading to increased energy expenditure. The focus of this study was to investigate whether, when protein and energy are held constant, there is a significant difference in fat and weight loss when fat and carbohydrate are dramatically varied in the diet. The preliminary results presented in this paper are for the first four of six postmenopausal overweight or obese participants who followed, in random order, both a VLC and an LF diet for 6 weeks. Other outcome measures were serum lipids, glucose, and insulin, as well as dietary compliance and side effects. Our results showed no significant weight loss, lipid, serum insulin, or glucose differences between the two diets. Lipids were dramatically reduced on both diets, with a trend for greater triglyceride reduction on the VLC diet. Glucose levels were also reduced on both diets, with a trend for insulin reduction on the VLC diet. Compliance was excellent with both diets, and side effects were mild, although participants reported more food cravings and bad breath on the VLC diet and more burping and flatulence on the LF diet.     

Sulfa use, dihydropteroate synthase mutations, and Pneumocystis jirovecii pneumonia

A systematic review was conducted to examine the associations in Pneumocystis jirovecii pneumonia (PCP) patients between dihydropteroate synthase (DHPS) mutations and sulfa or sulfone (sulfa) prophylaxis and between DHPS mutations and sulfa treatment outcome. Selection criteria included study populations composed entirely of PCP patients and mutation or treatment outcome results for all patients, regardless of exposure status. Based on 13 studies, the risk of developing DHPS mutations is higher for PCP patients receiving sulfa prophylaxis than for PCP patients not receiving sulfa prophylaxis (p < 0.001). Results are too heterogeneous (p < 0.001) to warrant a single summary effect estimate. Estimated effects are weaker after 1996 and stronger in studies that included multiple isolates per patient. Five studies examined treatment outcome. The effect of DHPS mutations on treatment outcome has not been well studied, and the few studies that have been conducted are inconsistent even as to the presence or absence of an association.     

Phenotypic expression of the methylenetetrahydrofolate reductase 677C-->T polymorphism and flavin cofactor availability in thyroid dysfunction

BACKGROUND: The 5,10-methylenetetrahydrofolate reductase gene (MTHFR) 677C-->T polymorphism modifies the risk of coronary artery disease and colon cancer and is related to plasma concentrations of total homocysteine (tHcy). Riboflavin status modifies the metabolic effect of the polymorphism, and thyroid hormones increase the synthesis of flavin cofactors. OBJECTIVE: The aim of the study was to investigate the phenotypic expression of the MTHFR 677C-->T polymorphism in terms of plasma tHcy concentrations in patients with thyroid dysfunction. DESIGN: The study population consisted of 182 patients with hyperthyroidism. We studied plasma tHcy in relation to MTHFR genotype, riboflavin, and folate before and during 6 mo of treatment with antithyroid drugs. RESULTS: Before treatment, tHcy was higher in patients with the mutant enzyme than in those with the wild-type enzyme. A genotype effect was observed only at low riboflavin or folate concentrations (P T polymorphism, possibly by modifying the availability of flavin cofactors.     

Changes in knowledge and attitudes of folate, and use of dietary supplements among women of reproductive age in Norway 1998-2000

AIMS: From March 1998, Norwegian nutrition authorities have recommended that women consume a folic acid supplement before and early in pregnancy to prevent neural tube defects. The authors wished to establish Norwegian data on knowledge of, use of, and attitudes to folic acid supplement and dietary supplements before and after implementing national information campaigns on folate and pregnancy. METHODS: Telephone surveys were carried out in late 1998 and in late 2000 among, respectively, 1,146 and 1,218 Norwegian women of reproductive age. RESULTS: Overall, 50% of the women in 1998 and 60% of the women in 2000 had heard about folate, 33% and 46% knew about its role in pregnancy, and 9.5% and 21% knew that it may prevent a congenital malformation. Only 4.0% and 8.5% of the women, respectively, knew that the critical period for folic acid supplement to reduce the risk of neural tube defect is before and early in pregnancy. Knowledge and increase in knowledge between the two surveys were highest among women close to pregnancy (woman planning pregnancy, pregnant women, or women who had given birth within the last 12 months), and among women with high education. Among the 54 women in 1998 and the 55 women in 2000 whose last birth was within the previous year, use of a folic acid supplement before or early in the last pregnancy was reported by 10% (95% confidence interval (CI) 5-21%) and by 47% (95% CI 35-60%), respectively. Among women close to pregnancy, 76% in 1998 and 87% in 2000 stated that they would use a folic acid supplement in a future pregnancy. CONCLUSIONS: Knowledge and use of folate among Norwegian women increased from 1998 to 2000. Future information strategies on folate and pregnancy should in particular aim at increasing women's knowledge on the critical period for folic acid supplementation, as well as reducing socio-demographic differences in use and knowledge of folate.     

Perception of risk: a study of A&E nurses and NHS managers

This exploratory study investigates perceptions of two groups of NHS staff, of a range of risks, topical and relevant to accident and emergency (A&E). Literature suggests that the effectiveness of a risk management strategy is lessened if staff exposed to risk, and managers, have different perceptions of the nature and severity of the risk. A self-administered questionnaire was distributed to registered A&E nurses and to Trust managers at directorate level and above, working in five large inner-city NHS Trusts. Managers and nurses were asked to quantify their perceptions of nine defined adverse events. They were also asked to identify the jobholder with day-to-day responsibility for managing four specific risks. Completed forms were obtained from 38 per cent of managers and nurses. Results showed broadly that managers tended to quantify risks of violence and stress to A&E nurses less highly than did nurses. By contrast, they tended to quantify risks to patients more highly than did nurses. Overall, a coherent pattern of difference in risk perception between the two groups was identified. It is argued that identification of differences of perception is an essential part of the risk management process. Illustrations are given of ways in which these differences can undermine the effectiveness of a risk management strategy.     

Participation in annual skin cancer screening among women seeking routine mammography

BACKGROUND: Early detection of skin cancer is associated with improved prognosis. The American Cancer Society's current skin cancer screening (SCS) recommendation states that adults over the age of 40 should receive an annual skin examination conducted by a health professional. However, little is known about the psychosocial factors related to participation in annual SCS, which remains relatively low among the general public. METHODS: Data were collected from women, aged 50 and older, seeking routine mammography at a large, urban, breast diagnostic facility. RESULTS: A total of 253 eligible women completed the survey. Overall, 20.2% of women reported receiving annual clinical SCS. Physician recommendation, self-efficacy, perceived susceptibility, and age were significantly associated with participation in annual skin screening. CONCLUSIONS: Similar to previously reported findings in the literature, our rates of participation in annual clinical skin screening were lower than reported rates for other types of cancer screening. Among older women, multiple covariates for participation in annual skin cancer screening were determined and may serve to guide future health education interventions to promote screening. Our findings suggest that participation could improve through increasing physician recommendation, screening self-efficacy, and individuals' sense of perceived susceptibility to skin cancer.     

Disparities between ophthalmologists and their patients in estimating quality of life

PURPOSE OF REVIEW: Numerous types of instruments can measure quality of life in a given state of health. This article reviews studies that have measured quality of life of patients and physicians for various types of disease states by using a generic preference-based method known as the time tradeoff method of utility analysis. Of particular interest are comparisons of quality of life estimates between patients and physicians for common ophthalmologic conditions. RECENT FINDINGS: In nearly all of the studies identified, the quality of life estimates of patients differed significantly from those of physicians. In studies involving macular disease, cataracts, and numerous other types of medical conditions, physicians generally underestimated the impact of the condition on patients' quality of life. Less of a disparity between patients and physicians has been reported for estimates of quality of life with glaucoma. Differences in quality of life estimates may be related to poor physician-patient communication. SUMMARY: It is important to appreciate the differences in preferences of patients and physicians. Because only patients themselves know their values and needs regarding treatments and outcomes, physicians should routinely elicit patients' preferences and allow them to participate in decision making about treatment. At the societal levels, patients' preferences should help guide decisions including how to allocate finite health care resources. An important tool for this purpose is cost-utility analysis, which incorporates data on patient preferences, along with survival and cost data, to compare the values of competing health care interventions.     

Selectins and integrins but not platelet-endothelial cell adhesion molecule-1 regulate opioid inhibition of inflammatory pain

1.Control of inflammatory pain can result from activation of opioid receptors on peripheral sensory nerves by opioid peptides secreted from leukocytes in response to stress (e.g. experimental swim stress or surgery). The extravasation of immunocytes to injured tissues involves rolling, adhesion and transmigration through the vessel wall, orchestrated by various adhesion molecules. 2. Here we evaluate the relative contribution of selectins, integrins alpha(4) and beta(2), and platelet-endothelial cell adhesion molecule-1 (PECAM-1) to the opioid-mediated inhibition of inflammatory pain. 3. We use flow cytometry, double immunofluorescence and nociceptive (paw pressure) testing in rats with unilateral hind paw inflammation induced by complete Freund's adjuvant. 4. In inflamed tissue, 43-58% of hematopoietic cells (CD45(+)) expressed opioid peptides. L-selectin and beta(2) were coexpressed by 7 and 98% of opioid-containing leukocytes, respectively. Alpha(4) integrin was expressed in low levels by the majority of leukocytes. Opioid-containing cells, vascular P- and E-selectin and PECAM-1 were simultaneously upregulated. 5. Swim stress produced potent opioid-mediated antinociception in inflamed tissue, unaffected by blockade of PECAM-1. However, blockade of L- and P-selectins by fucoidin, or of alpha(4) and beta(2) by monoclonal antibodies completely abolished peripheral stress-induced antinociception. This coincided with a 40% decrease in the migration of opioid-containing leukocytes to inflamed tissue. 6. These findings establish selectins and integrins alpha(4) and beta(2), but not PECAM-1, as important molecules involved in stress-induced opioid-mediated antinociception in inflammation. They point to a cautious use of anti-inflammatory treatments applying anti-selectin, anti-alpha(4) and anti-beta(2) strategies because they may impair intrinsic pain inhibition.     

Quantitative assessment of the cell penetrating properties of RI-Tat-9: evidence for a cell type-specific barrier at the plasma membrane of epithelial cells

Penetration of epithelial cells represents the rate-determining step for the absorption of many drugs and pharmaceutical macromolecules such as proteins and nucleic acid therapeutics. While the potential of using cell-penetrating peptides (CPPs) to facilitate absorption has been increasingly recognized, the mechanism of cell penetration and the uptake into certain cells have recently been called into question due to methodological artifacts. Therefore, the objective of this study was to quantitatively assess the ability of RI-Tat-9, a proteolytically stable CPP, to penetrate epithelial cell monolayers. The permeability of RI-Tat-9 with two epithelial cell lines, Madin-Darby canine kidney (MDCK) and Caco-2 cells, was comparable to the leakiness of the respective intact monolayers. Microscopic imaging showed that fluorescence-tagged RI-Tat-9 did not enter these cells, further supporting a paracellular transport mechanism. Although insufficient data were generated in these studies to generalize the observed phenomenon, the entry of RI-Tat-9 into nonepithelial T lymphocytic MT2 cells, possibly by endocytosis, suggested that a cell type-specific barrier might exist that controlled uptake of RI-Tat-9 by cells. Compared to that in MT2 and HeLa cells, the active uptake of the peptide into MDCK monolayers was much slower and showed no dependence of cell energy. Furthermore, the equilibrium binding of RI-Tat-9 to MDCK cells at 0 degrees C was indicative of an interaction with a nonspecific receptor. A correlation between binding density and concentration difference across a leaky separation barrier suggested that repulsion of free peptide molecules by bound peptide molecules at the MDCK monolayer surface may be significant at micromolar concentrations. The results of this study quantitatively show that Tat CPP uptake into two commonly used epithelial cell types is minimal and possibly cell type-specific. Implications for Tat CPP-assisted drug delivery are discussed.