Therapeutic applications of melatonin and related compounds

Increasing knowledge of the pharmacological effects of melatonin has suggested various possible therapeutic applications for the hormone. Because, as a natural substance, melatonin cannot be patented, melatonin-related compounds have been synthesized by industrial groups. The scope of such compounds is also to specifically target the recently discovered melatonin receptor subtypes. The sleep-inducing properties of melatonin are disputed, but are distinct from those of benzodiazepines. The observed effects on sleep latency or sleep efficiency, which remain to be confirmed, could be accounted for by the effects of melatonin on core body temperature and on circadian rhythms. There is also an urgent need for safety data, both in animals and in humans, particularly when long-term use is envisaged.     

Abnormal carnitine distribution in the muscles of patients with idiopathic inflammatory myopathy

OBJECTIVE: To analyze the levels of free carnitine and carnitine esters in the muscles of patients with inflammatory myopathies. METHODS: Six men and 7 women with inflammatory myopathy and 25 age-matched healthy controls were studied. Free carnitine and carnitine esters in muscle homogenates were measured by a radiochemical procedure. Muscle histochemical staining and measurement of respiratory chain enzyme activity were also performed. RESULTS: Eleven patients had muscle carnitine insufficiency. Five of them had subsarcolemmal oxidative accumulations, 5 had lipid droplets, and 4 had defects of the respiratory chain enzyme complexes. CONCLUSION: Abnormal distribution of muscle carnitine is present in patients with inflammatory myopathies and could impair muscle function. Coexistent mitochondrial dysfunction may contribute to carnitine insufficiency.     

Medicaid reform: an opportunity for the osteopathic medical profession

The autoantigen in adjuvant arthritis in Lewis rats is still unknown despite the knowledge that the 65 kDa mycobacterial heat-shock protein (hsp) is involved in the disease process. T cells and antibodies obtained from rats with adjuvant arthritis respond to chondrocyte membrane antigen(s). In Western blots a 65 kDa chondrocyte membrane protein (CH65) is stained by sera from arthritic rats. In addition, spleen cells from rats with adjuvant arthritis proliferate in vitro to chondrocyte membranes and CH65 as antigens. Furthermore, pretreatment of rats with CH65 or mycobacterial hsp65 but not human hsp60, induces a significant retardation of the onset of adjuvant arthritis in Lewis rats. The data suggest that CH65 is a potential autoantigen involved in the pathogenesis of adjuvant arthritis in Lewis rats.     

Health economic benefits and quality of life during improved glycemic control in patients with type 2 diabetes mellitus: a randomized, controlled, double-blind trial

CONTEXT: Although the long-term health benefits of good glycemic control in patients with diabetes are well documented, shorter-term quality of life (QOL) and economic savings generally have been reported to be minimal or absent. OBJECTIVE: To examine short-term outcomes of glycemic control in type 2 diabetes mellitus (DM). DESIGN: Double-blind, randomized, placebo-controlled, parallel trial. SETTING: Sixty-two sites in the United States. PARTICIPANTS: A total of 569 male and female volunteers with type 2 DM. INTERVENTION: After a 3-week, single-blind placebo-washout period, participants were randomized to diet and titration with either 5 to 20 mg of glipizide gastrointestinal therapeutic system (GITS) (n = 377) or placebo (n = 192) for 12 weeks. MAIN OUTCOME MEASURES: Change from baseline in glucose and hemoglobin A1c (HbA1c) levels and symptom distress, QOL, and health economic indicators by questionnaires and diaries. RESULTS: After 12 weeks, mean (+/-SE) HbA1c and fasting blood glucose levels decreased with active therapy (glipizide GITS) vs placebo (7.5% 0.1% vs 9.3%+/-0.1% and 7.0+/-0.1 mmol/L [126+/-2 mg/dL] vs 9.3+/-0.2 mmol/L [168+/-4 mg/ dL], respectively; P<.001). Quality-of-life treatment differences (SD units) for symptom distress (+0.59; P<.001), general perceived health (+0.36; P= .004), cognitive functioning (+0.34; P=.005), and the overall visual analog scale (VAS) (+0.24; P=.04) were significantly more favorable for active therapy. Subscales of acuity (+0.38; P=.002), VAS emotional health (+0.35; P=.003), general health (+0.27; P=.01), sleep (+0.26; P=.04), depression (+0.25; P=.05), disorientation and detachment (+0.23; P= .05), and vitality (+0.22; P=.04) were most affected. Favorable health economic outcomes for glipizide GITS included higher retained employment (97% vs 85%; P<.001), greater productive capacity (99% vs 87%; P<.001), less absenteeism (losses = $24 vs $115 per worker per month; P<.001), fewer bed-days (losses = $1539 vs $1843 per 1000 person-days; P=.05), and fewer restricted-activity days (losses = $2660 vs $4275 per 1000 person-days; P=.01). CONCLUSIONS: Improved glycemic control of type 2 DM is associated with substantial short-term symptomatic, QOL, and health economic benefits.     

Renal duplex scanning: correlation with angiography and isotopic renography

The purpose of this study was to assess the accuracy of Duplex scanning in detecting renovascular disease and to compare it with angiography, renal scintigraphy and captopril test for plasma renin activity and isotopic renography. A Duplex scan was performed in 92 renal arteries (46 patients) and compared to angiography. Three degrees of stenoses were established: 0-60%, 61-99% and occlusion. The peak systolic velocity (PSV) in the renal artery and its ratio to the peak velocity in the aorta (RAR) were used to discriminate stenoses > 60%. PSV in the interlobar arteries was used to assess the relative perfusion of both parenchyma. Angiography demonstrated a stenoses > 60% in 23 hypertensive patients. In all of the patients, plasma renin activity was measured and isotopic renograms (pre- and post-captopril) obtained in order to discriminate hypertension of vascular origin. A PSV in the renal artery > 210 cm/s and a RAR > 3.5 were found to be the diagnostic criteria with the best sensitivity and specificity in detecting stenoses > 60%. Based on these data, Duplex correctly identified 49/54 stenoses > 60%; 28/33 stenoses < 60%; and 5/5 occlusions (kappa 0.79). Sensitivity and specificity in detecting stenoses > 60% were 89.5 and 90.7%, respectively. The ratio between PSV in the interlobar arteries of both parenchyma accurately predicted the relative perfusion (ratio between DTPA uptake in both kidneys) in the isotopic test (n = 23, r = 0.91, p = 0.001). The captopril test (for plasma renin activity and isotopic renography) was positive in only five patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Estimating confidence intervals for cost-effectiveness ratios: an example from a randomized trial

Cost-effectiveness ratios usually appear as point estimates without confidence intervals, since the numerator and denominator are both stochastic and one cannot estimate the variance of the estimator exactly. The recent literature, however, stresses the importance of presenting confidence intervals for cost-effectiveness ratios in the analysis of health care programmes. This paper compares the use of several methods to obtain confidence intervals for the cost-effectiveness of a randomized intervention to increase the use of Medicaid's Early and Periodic Screening, Diagnosis and Treatment (EPSDT) programme. Comparisons of the intervals show that methods that account for skewness in the distribution of the ratio estimator may be substantially preferable in practice to methods that assume the cost-effectiveness ratio estimator is normally distributed. We show that non-parametric bootstrap methods that are mathematically less complex but computationally more rigorous result in confidence intervals that are similar to the intervals from a parametric method that adjusts for skewness in the distribution of the ratio. The analyses also show that the modest sample sizes needed to detect statistically significant effects in a randomized trial may result in confidence intervals for estimates of cost-effectiveness that are much wider than the boundaries obtained from deterministic sensitivity analyses.     

介绍一种生产冲挤用铝合金坯料的新工艺

哈兹列特铝板带连铸连轧工艺已被成功地用于铝和铝合金冲击挤压用坯料的生产。在对哈氏四个有关用户扫描的基础上，列举了其产品及其用途，并介绍了相关工艺及其优点。     

利用数学模型分析复吹转炉吹炼工艺

在冶金热力学和动力学及反应工程学原理的基础上，建立了模拟复吹转炉冶炼过程的数学模型．在用梅钢150t复吹转炉工业试验的结果对模型加以验证之后，利用模型对具有中高磷铁水特点的梅钢转炉吹炼工艺进行了分析讨论．     

砂浆立方体抗压强度与底模的关系

建筑砂浆试件的制作目前均执行《建筑砂浆基本性能试验方法》(JGJ70-1990)有关规定，所用底模系含水量不大于2％的普通粘土砖。