Randomized clinical trial of folate supplementation in patients with peripheral arterial disease.

BACKGROUND: The aim was to determine whether folate supplementation improved arterial function in patients with peripheral arterial disease (PAD). METHODS: Individuals with PAD were randomly assigned to receive 400 microg folic acid (45 patients) or 5-methyltetrahydrofolate (5-MTHF) (48) daily, or placebo (40) for 16 weeks. Primary endpoints were changes in plasma total homocysteine (tHcy), ankle : brachial pressure index (ABPI) and pulse wave velocity (PWV). Secondary outcomes were changes in plasma inflammatory markers. RESULTS: Plasma tHcy was significantly reduced in folic acid and 5-MTHF groups compared with controls: median difference: - 2.12 (95 per cent confidence interval - 3.70 to - 0.75) micromol/l (P = 0.002) and - 2.07 (-3.48 to - 0.54) micromol/l (P = 0.007) respectively. ABPI improved significantly: median difference 0.07 (0.04 to 0.11) (P < 0.001) and 0.05 (0.01 to 0.10) (P = 0.009) respectively. Brachial-knee PWV (bk-PWV) decreased significantly in individuals receiving 5-MTHF and tended to be reduced in those taking folic acid compared with controls: median difference: - 1.10 (-2.20 to - 0.20) m/s (P = 0.011) and - 0.90 (-2.10 to 0.00) m/s (P = 0.051) respectively. Plasma levels of inflammatory markers were not affected. CONCLUSION: Folate administration reduced plasma homocysteine, and slightly improved ABPI and bk-PWV.

Homocysteine and peripheral arterial disease: systematic review and meta-analysis.

OBJECTIVE: To evaluate homocysteine (Hcy) levels in patients with peripheral arterial disease (PAD) as compared to unaffected controls, and to review the clinical effects of therapy aimed at lowering homocysteine in PAD patients. METHODS: MEDLINE, EMBASE and Cochrane databases were searched from 1950 to December 2007. We selected observational studies and trials that evaluated Hcy levels in patients with PAD compared to unaffected controls. We also included trials on the effect of Hcy-lowering therapy (folate supplementation) in PAD patients. Continuous outcomes were pooled in a random effects meta-analysis of the weighted mean difference between comparator groups. RESULTS: We retrieved 33 potentially suitable articles from our search. Meta-analysis of 14 relevant studies showed that Hcy was significantly elevated (pooled mean difference +4.31micromoll; 95% C.I. 1.71, 6.31, p<0.0001 with significant heterogeneity) in patients with PAD compared to controls. As all 14 studies consistently demonstrated raised plasma Hcy levels in PAD patients, the significant heterogeneity in this meta-analysis probably arises from differences in the degree of Hcy elevation. The effect of folate supplementation on PAD was tested in eight clinical trials but clinically important end points were inconsistently reported. CONCLUSION: Patients with PAD have significantly higher Hcy levels than unaffected controls. However, we did not find any robust evidence on clinically beneficial effects of folate supplementation in PAD.

Lipase-catalyzed modification of rice bran oil to incorporate capric acid.

Capric acid (C10:0) was incorporated into rice bran oil with an immobilized lipase from Rhizomucor miehei as the biocatalyst. Effects of incubation time, substrate mole ratio, enzyme load, and water addition on mole percent incorporation of C10:0 were studied. Transesterification was performed in an organic solvent, hexane, and under solvent-free condition. Pancreatic lipase-catalyzed sn-2 positional analysis and tocopherol analysis were performed before and after enzymatic modification. Products were analyzed by gas-liquid chromatography (GLC) for fatty acid composition. After 24 h of incubation in hexane, there was an average of 26.5 +/- 1.8 mol % incorporation of C10:0 into rice bran oil. The solvent-free reaction produced an average of 24.5 +/- 3.7 mol % capric acid. In general, as the enzyme load, substrate mole ratio, and incubation time increased, the mole percent of capric acid incorporation also increased. Time course reaction indicated C10:0 incorporation increased up to 27.0 mol % at 72 h, for the reaction in hexane, and up to 29.6 mol % at 12 h, for the solvent-free reaction. The highest C10:0 incorporations (53.1 and 43.2 mol %) for the mole ratio experiment occurred at a mole ratio of 1:8 for solvent and solvent-free reactions, respectively. The highest C10:0 incorporation (27.9 mol %) for the reaction in hexane occurred at 10% enzyme load, and the highest incorporation (34.4 mol %) for the solvent-free reaction occurred at 20% enzyme load. Incorporation of C10:0 into rice bran oil declined with the addition of increasing amounts of water after reaching 30.3 mol % at 2% water addition in hexane, and in the solvent-free reaction after reaching 35.9 mol %.

A classification scheme for outcome indicators.

PURPOSE: To provide a framework for classifying outcome indicators for a more comprehensive view of outcomes and quality. METHODS: Review of outcomes literature published since 1974 from medicine, nursing, and health services research to identify indicators. Outcome indicators were clustered inductively. FINDINGS: Three groups of outcome indicators were identified: patient-focused, provider-focused, and organization-focused. Although investigators tend to focus on a select few outcome indicators, such as patient satisfaction, quality of life, and mortality, many indicators exist to measure outcomes. CONCLUSIONS: Selecting and integrating a wide array of outcome indicators from the various categories will provide a more balanced view of health care delivery as compared with focusing on a few common indicators or only one category.

Bone mineral density and the risk of fracture in patients receiving long-term inhaled steroid therapy for asthma.

To determine whether high-dose or prolonged inhaled steroid therapy for asthma increases a patient's risk of osteoporosis and fracture, we measured bone density in 26 men and 43 women (41 postmenopausal, all of whom had received supplemental estrogen therapy) after treatment with an inhaled steroid for 10.1 +/- 5.5 years and oral prednisone for 10.7 +/- 9.7 years (mean +/- SD). Most had stopped receiving prednisone since commencing the inhaled steroid therapy. We found that bone densities (adjusted for age and sex to yield a z score) were lower in association with higher daily doses of inhaled steroid (p = 0.013 ANCOVA) and with the duration of past prednisone therapy (p = 0.032). Larger cumulative inhaled steroid doses were associated with higher bone densities (p = 0.002) and a reduction in the numbers of patients at risk of fracture. Bone density also increased with the amount of supplemental estrogen therapy (p = 0.058) and, at equivalent levels of inhaled and oral steroid use, women showed higher bone density z scores than did men. Women with a lifetime dose of inhaled steroid greater than 3 gm had normal bone density regardless of the amount of past or current prednisone use or the current dose of inhaled steroid. These data indicate that the daily dose, but not the duration, of inhaled steroid therapy may adversely affect bone density, and that estrogen therapy may offset this bone-depleting effect in postmenopausal women.

Differential effects of inhaled budesonide and oral prednisolone on serum osteocalcin.

Inhaled glucocorticosteroids have been developed for the treatment of asthma in an attempt to minimize the suppression of endogenous adrenal function that complicates oral or injected steroid usage, but it is unclear whether this strategy leads to reduced systemic complications in other areas, such as the skeleton. In this study we evaluated serum osteocalcin levels as a marker of skeletal metabolism in healthy volunteers treated with oral and inhaled steroids alone and in response to an oral calcitriol stimulation test. Forty subjects, aged 33 +/- 9 (mean +/- SD) yr were randomized to receive either high or low dose oral prednisolone (40 vs. 10 mg/day) or inhaled budesonide (3.2 vs. 0.8 mg/day). Each dose of budesonide is known to have a greater antiasthmatic potency than the dose of prednisolone with which it was compared. In addition 10 control subjects received placebos containing no active steroid drugs. During the second week of treatment, half of the subjects in each of the 4 steroid-treated groups and all subjects in the control group received oral calcitriol (2.0 micrograms/day). There was a marked dose-dependent reduction in serum cortisol levels, but this reduction was significantly less pronounced during budesonide treatment, such that low dose budesonide was without effect. During the first week of steroid therapy there were significant dose-dependent reductions in serum osteocalcin (P = 0.003), but this reduction was not significantly different between budesonide and prednisolone treatments. In response to calcitriol, serum osteocalcin increased by 35% in the control group (P = 0.06). Osteocalcin levels increased by 56% and 50% in the low dose budesonide and prednisolone groups and by 106% in the high dose budesonide group, but did not change in the high dose prednisolone group. The osteocalcin response to calcitriol was significantly higher in the budesonide groups (P = 0.03, by analysis of variance). High dose prednisolone caused increases in serum 1,25-dihydroxyvitamin D3 (P less than 0.02), urinary calcium excretion (P = 0.07), and urinary hydroxyproline (P less than 0.01). None of these changes was seen during budesonide therapy. There are as yet no data for these variables after long term use of inhaled budesonide in asthmatic patients, but our acute studies suggest that this potent topical glucocorticoid may have considerably less impact on the skeleton than oral prednisolone, even if used at doses high enough to suppress endogenous adrenal function.

T-cell rosette test in squamous cell carcinoma of the head and neck.

The percentage of total T-lymphocytes was measured in 38 patients with histologically diagnosed squamous cell carcinoma of the head and neck. This measure of cellular immunity, which appears to be important in tumor-cell destruction, is demonstrably lowered in advanced stages of this disease. With the use of this test, the effect of a combined chemoimmunotherapeutic regimen consisting of methotrexate sodium, isoniazid, and BCG vaccine was sutdied. In this small series, no decrease of the T-cell count following treatment by methotrexate was demonstrated, except when a high dosage followed by leucovorin calcium was used. The BCG vaccine appeared to enhance T-cell counts, and one patient who was treated with cryosurgery had a dramatic increase in circulating T-lymphocytes. The T-cell test may be of clinical importance in the development of treatment sequences that provide maximum reduction of tumor cell mass while preserving host T cells.