Long‐term high‐physiological‐dose growth hormone reduces intra‐abdominal fat in HIV‐infected patients with a neutral effect on glucose metabolism

Objectives

The aim of the study was to investigate the effect of long‐term high‐physiological‐dose recombinant human growth hormone (rhGH) therapy on fat distribution and glucose metabolism in HIV‐infected patients.

Methods

Forty‐six HIV‐infected Caucasian men on highly active antiretroviral therapy (HAART), with an age range of 21–60 years and no significant comorbidity, were included in this randomized, placebo‐controlled, double‐blind, single‐centre trial. Twenty‐eight subjects were randomized to 0.7 mg/day rhGH, and 18 subjects to placebo, administered as daily subcutaneous injections between 1 and 3 pm for 40 weeks. Endpoints included changes in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), limb fat mass, percentage of limb fat, plasma lipids, insulin resistance and glucose tolerance.

Results

VAT and trunk fat mass decreased significantly in the GH group compared with the placebo group [−19 cm² (−11%) vs. 12 cm² (6%), P=0.03, and −548 g (−9%) vs. 353 g (6%), P<0.01, respectively]. The beneficial fat redistribution in the GH group occurred without concomitant changes in subcutaneous fat at the abdomen or extremities. rhGH therapy was well tolerated. Insulin resistance, glucose tolerance, and total plasma cholesterol and triglycerides did not significantly change during intervention.

Conclusions

Daily 0.7 mg rhGH treatment for 40 weeks reduced abdominal visceral fat and trunk fat mass in HIV‐infected patients. This treatment appeared to be safe with respect to glucose tolerance and insulin sensitivity.

     

Gute Compliance mit Buccaltablette

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Thromboserezidiv-prophylaxe mit Dalteparin     

Induction of a rat liver benzo[a]pyrene-trans-7,8-dihydrodiol glucuronidating activity by oltipraz and beta-naphthoflavone

We report here that rats possess a hitherto unrecognized xenobiotic- inducible hepatic 7,8-dihydro-7,8-diol-benzo[a]pyrene (BPD) UDP- glucuronosyltransferase (UGT) activity. BPD UGT activity is induced in female F344 rat liver by treatment with the selective Phase 2 conjugation enzyme inducer oltipraz [4-methyl-5-(2-pyrazinyl)-1,2- dithiole-3-thione at 75-450 mg/kg per day for 3 days] and also by a polycyclic aromatic hydrocarbon-type inducer, beta-naphthoflavone (80 mg/kg per day for 3 days). Incubations of oltipraz-treated rat liver microsomes with racemic trans BPD (100 microM) resulted in formation of two fluorescent glucuronides that were resolved by silica thin layer chromatography (Rf 0.5 and 0.6). Incubations with either the (-) or (+) trans BPD isomers resulted in selective formation of the Rf 0.5 [designated -DS, for (-) diol specific] or Rf 0.6 [designated +DS, for (+) diol specific] glucuronide, respectively. The -DS and +DS BPD glucuronides were fluorescent under long wave ultraviolet irradiation, dependent on the presence of UDP-glucuronic acid in the incubation, and were beta-glucuronidase-sensitive. The inducing effect of oltipraz on BPD UGT activity was dose-dependent. The mean BPD UGT activity of the vehicle-treated control group was 0.05 +/- 0.02 nmol/mg per min compared with 0.53 +/- 0.07 nmol/mg per min in the group treated with oltipraz (450 mg/kg per day for 3 days) (P < 0.001). The apparent Km of the induced BPD UGT for BPD was 20 microM, suggesting that the enzyme has the capacity to bind and turnover BPD under physiological conditions. Pretreatment with beta-naphthoflavone, but not phenobarbital, induced BPD UGT activity to approximately the same extent as oltipraz. Neither oltipraz nor beta-naphthoflavone exhibited induction of BPD UGT in livers of homozygous Gunn rats, which lack functional UGT1-encoded isozymes. We conclude that the oltipraz- and polycyclic hydrocarbonresponsive BPD UGT is a member of the UGT1 family. The role of this isoform as a modifier of susceptibility to carcinogenesis elicited by B[a]P remains to be determined.      

Analysis of VH genes used by neoplastic B cells in endemic Burkitt's lymphoma shows somatic hypermutation and intraclonal heterogeneity

Tumor cell lines from six typical cases of endemic Epstein-Barr virus (EBV) genome-positive Burkitt's lymphoma (BL) have been investigated for usage and mutational pattern of Ig VH genes. The neoplastic cells all had a t(8;14) (q24;q32) translocation involving the c-myc protooncogene. The VH genes were derived from VH1, VH3 and VH4, and both the IgM-positive (four cases) and IgG-positive (two cases) were extensively mutated from germline sequence. In two cases, early and late passage tumor cells were available, and the VH nucleotide sequences were identical, indicating that mutations had not accumulated in vitro. In a further case, there was evidence of sequence heterogeneity, which appeared to have been generated in vivo, indicating that the tumor cell VH gene was able to undergo posttranslocation somatic hypermutation. Analysis of the relatively nonpolymorphic VH4 genes for the pattern of replacement or silent mutations did not show a role for antigen selection in the expressed sequences.     

rhBMP-2 cDNA转染的NIH-3T3细胞和rhBMP-2m对小鼠急性放射损伤的治疗作用

0 引言我们曾报道[1,2]重组人骨形成蛋白-2成熟肽(rhBMP-2m)和rhBMP-2 cDNA转染的NIH-3T3细胞对小鼠急性放射损伤有治疗作用,其机制与它促进放射损伤后骨髓细胞造血功能的恢复有关.     

GM-CSF和rhBMP-2m对小鼠急性放射损伤的治疗作用

0 引言 我们曾报道[1]重组人骨形成蛋白-2成熟肽(rhBMP-2m)对小鼠急性放射损伤有治疗作用,其机理与它促进放射损伤后骨髓细胞造血功能的恢复有关. GM-CSF是公认的造血生长因子,它对放射损伤有较好的治疗作用[2]. 我们旨在比较GM-CSF和rhBMP-2m对小鼠急性放射损伤的治疗效果.     

Simple nutritional indicators as independent predictors of mortality in hemodialysis patients

A strong association exists between nutritional status and morbidity and mortality in patients with end-stage renal disease who are treated with hemodialysis. Described here is the predictive value for mortality over 5 years of follow-up of a number of risk factors, recorded at baseline, in a national sample of 3,607 hemodialysis patients. Among the variables studied were case-mix covariates, caregiver classifications of nutritional status, serum albumin concentration, and body mass index (BMI). The Case Mix Adequacy special study of the United States Renal Data System (USRDS) provided these measurements as of December 31, 1990. The USRDS patient standard analysis file provided follow-up data on mortality for all patients through December 31, 1995, by which time 64.7% of the patients had died. BMI is a simple anthropometric measurement that has received little attention in dialysis practice. Caregiver classification refers to documentation in a patient's dialysis facility medical records that stated an individual to be "undernourished/cachectic," "obese/overweight," or "well-nourished." The mean serum albumin was 3.7 +/- 0.45 (SD) g/dL, and the mean BMI was 24.4 +/- 5.3 (SD) kg/m2. By caregiver classification, 20.1% of patients were undernourished, and 24.9% obese. In hazard regression models, including but not limited to the Cox proportional hazards model, low BMI, low serum albumin, and the caregiver classification "undernourished" were independently and significantly predictive of increased mortality. In analyses allowing for time-varying relative mortality risks (ie, nonproportional hazards), the greatest predictive value of all three variables occurred early during follow-up, but the independent predictive value of baseline serum albumin and BMI measurements on mortality risk persisted even 5 years later. No evidence of increasing mortality risk was found for higher values of BMI. Serum albumin was confirmed to be a useful predictor of mortality risk in hemodialysis patients; BMI was established as an independently important predictor of mortality; both serum albumin and BMI, measured at baseline, continue to possess predictive value 5 years later; the subjective caregiver classification of nutritional status "undernourished" has independent value in predicting mortality risk beyond the information gained from two other markers of nutritional status--BMI and serum albumin.     

Median nerve entrapment. pronator teres syndrome

Summary The surgical anatomy of interest in the pronator teres syndrome was studied to shed light on the ramifying pattern of the median nerve, the number of its muscular branches and their branching levels and to pinpoint the location of the fibrous bands which may cause median nerve entrapment. The fibrous arch of the pronator teres muscle (pronator arch) was found to lie 3 cm to 7.5 cm below Hueter's line, that of the flexor digitorum superficialis muscle (superficialis arch), which is distal to the pronator arch, was found to lie 6.5 cm below Hueter's line in its most proximal position. Symptom patterns in terms of muscle weakness caused by median nerve entrapment at different levels were also evaluated.

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Compression du nerf médian. Syndrome du rond pronateur. Anatomie chirurgicale et corrélation aux tableaux cliniques

Résumé L'anatomie chirurgicale relative au syndrome du rond pronateur a été étudiée pour éclairer les modalités de ramification du n. médian, le nombre de ses branches musculaires et leur niveau d'origine, et pour préciser la situation des arcades fibreuses qui peuvent comprimer le n. médian. L'arcade fibreuse du m. rond pronateur a été trouvé'e à 3 à 7,5 cm au-dessous de la ligne de Hueter, celle du m. fléchisseur superficiel des doigts, qui est distale par rapport à celle du m. rond pronateur, a été retrouvée à 6,5 cm au-dessous de la ligne de Hueter dans sa position la plus proximale. Les tableaux cliniques de déficit musculaire causés par la compression du n. médian à divers niveaux sont également analysés.

     

对中医学"心主神明"和"脑主神明"的再认识

在回顾《黄帝内经》及历代医家关于心、脑功能的论述的基础上,提出变革“心主神明”说,确立“脑主神明”论的观点。指出：传统中医学虽以“心主神明”立论,但对脑与精神、感觉、知觉及生命健康的关系也有描述,与“脑主神明”的认识相按近;并从系统修正、审慎扬弃、理论建设、方法研究等四个方面分析,强调确立“脑主神明”论符合中医药学自身发展规律。