塞来昔布对体外培养软骨细胞活性及细胞外基质合成影响的实验研究

目的:通过细胞学实验来研究塞来昔布对体外培养软骨细胞活性及细胞外基质合成的影响.方法:用酶消化法分离兔关节软骨细胞,利用相差显微镜和H.E.染色软骨细胞形态学观察,Ⅱ型胶原免疫细胞化学染色,Western blot检测金属蛋白酶(MMP-1)、MMP-3蛋白,阿利新蓝法检测糖氨多糖(GAG)的合成.结果:随传代次数增加,细胞逐渐变大,72 h后见细胞大部分贴壁并延伸呈成纤维细胞形态.5 W时A组、B组、C组的阳性免疫染色的灰度值A、C组灰度弱于B组(P＜0.05),A、C组间差异无统计学意义(P＞0.05).在3、5 w时C组软骨细胞较B组软骨细胞的MMP-1、3蛋白表达量下降,P＜0.01,A组在各周无明显变化.3 W与5 W时A、C组糖氨多糖含量高于B组(P＜0.01).结论:塞来昔布可以抑制IL-1所产生的不良效应;可通过减少MMPs的合成,保护软骨基质的降解来维持细胞活性与细胞外基质的合成.     

CHRONIC NEPHROTOXICITY OF ANTI-INFLAMMATORY DRUGS USED IN THE TREATMENT OF ARTHRITIS

We determined the consumption of non-steroidal anti-inflammatorydrugs (NSAIDs) and the prevalence of chronic renal impairmentand renal papillary necrosis (RPN) in patients with varioustypes of arthritis. Ninety-four patients with chronic arthritiswho had consumed more than 1000 capsules and/or tablets of NSAIDswere studied. Renal profiles and radiological investigationssuch as intravenous urogram (IVU), ultrasonography (US) andcomputed tomography (CT) were performed to look for evidenceof RPN. Twelve patients did not complete the study. Ten of the82 patients who had completed the study (12.2%) had radiologicevidence of RPN. Five out of 53 patients (9.4%) with rheumatoidarthritis, three out of 11 patients (27.3%) with gouty arthritisand two out of seven patients (28.6%) with osteoarthritis hadRPN. Renal impairment (serum creatinine levels of 125—451µmol/I) was found in 20 patients (24.4%). The patientshad consumed 1000–26 300 capsules and/or tablets overa period ranging from 1 yr to more than 30 yr. Patients withchronic arthritis who consume excessive amount of NSAIDs areat risk of developing RPN and chronic renal impairment. KEY WORDS: Arthritis, Non-steroidal anti-inflammatory drugs, Renal papillary necrosis, Chronic renal impairment     

Thyroid function in pre-eclampsia

Summary. Thyroid function was studied in 24 proteinuric pre-eclamptic patients and 24 gestation-matched controls. The pre-eclamptic patients had significantly lower mean total (TT4) and free thyroxine (FT4), and thyroxine-binding globulin (TBG) concentrations, and the concentration of thyroid-stimulating hormone was significantly higher. The mean total triiodothyronine (TT3) concentration, however, was similar to the controls. This is at variance with the classical low T3 syndrome reported previously for pre-eclamptic patients. Compared to the controls, 33·3% and 29·2% of the pre-eclamptic patients had low TT4 and TT3 concentrations respectively. Pre-eclamptic patients with low TT4/ TT3 had significantly higher plasma urate concentrations. Thyroid hormone concentrations may reflect the severity of pre-eclampsia.     

Treatment of aplastic anemia with antithymocyte globulin,cyclosporin A,methylprednisolone, danazole and recombinant human granulocyte-colony stimulating factor

The main purpose of the present study was to determine the response rate to immunosuppressive therapy combined with recombinant human granulocyte-colony stimulating factor (rhG-CSF) and its efficacy for preventing infections in patients with severe aplastic anemia. The treatments included one course of antithymocyte globulin, cyclosporin A, methylprednisolone, danazole and rhG-CSF. Three patients had very severe aplastic anemia and two had moderate aplastic anemia. One patient relapsed 13 months following the first course of therapy and received a second course. Five patients received six courses of treatment and the response rate at 6 months was 83.3%. All patients achieved an absolute neutrophil count of greater than 1.0 × 10⁹/L within 40 days. All patients with a complete response are transfusion-free and doing well. All five patients are currently alive and have not had any episode of infection for 17–53 months. The results of the study indicate that this therapy may improve the poor prognosis of young patients with severe aplastic anemia. It has a good response rate and induces a rather rapid increase in the neutrophil count, which protects against life-threatening bacterial and fungal infections.     

RANDOMIZED COMPARATIVE STUDY OF 3 VERSUS 8-MONTH NEOADJUVANT HORMONAL THERAPY BEFORE RADICAL PROSTATECTOMY: BIOCHEMICAL AND PATHOLOGICAL EFFECTS

PURPOSE: A prospective phase 3 trial was initiated to determine whether 8 compared with 3-month neoadjuvant hormonal therapy reduces prostate specific antigen (PSA) recurrence rates after radical prostatectomy. Our interim analysis includes secondary end points of differences in biochemistry, pathology and adverse events between the 2 groups. MATERIALS AND METHODS: Men with clinically confined prostate cancer were randomized to receive 7.5 mg. leuprolide intramuscularly monthly and 250 mg. flutamide orally 3 times daily for 3 or 8 months before radical prostatectomy. Our study was powered to detect a 35% decrease in PSA recurrence, assuming a 30% recurrence rate in the 3-month arm after 3 years. RESULTS: A total of 547 men were randomized between August 1995 and April 1998. Men in the 8 and 3-month groups were equally stratified for T stage (29% T1c, 70% T2), Gleason grade (68% less than 4, 32% 4 or greater) and pretreatment PSA (63% less than 10, 27% 10 to 20 and 10% greater than 20 microg./l.). Mean pretreatment PSA was slightly higher in the 8-month compared with the 3-month group (11.64 versus 9.95 microg./l., respectively, p = 0.0539). A total of 44 men withdrew from study before surgery and, therefore, were nonevaluable. Preoperative PSA nadir was less than 0.1 microg./l. in 43.3% versus 75.1% (p <0.0001), and 0.3 microg./l. or greater in 21% versus 9.2% after 3 versus 8 months, respectively (p <0.0006). Mean serum PSA decreased 98% to 0.12 microg./l. after 3 months, with a further 57% to 0.052 microg./l. from 3 to 8 months. Transrectal ultrasound determined that prostatic volume decreased 37% from a mean of 40.6 to 25.4 cc after 3-month neoadjuvant hormonal therapy (p = 0.0001) and a further 13% to 22.2 cc after 8 months (p = 0.03). Mean hemoglobin decreased 15% (148.2 to 125.4 gm./dl.) after 3-month neoadjuvant hormonal therapy but stabilized thereafter. Radical prostatectomy was completed in 500 men, while surgery was aborted intraoperatively in 3. Positive margin rates were significantly lower in the 8 than 3-month group (12% versus 23%, respectively, p = 0.0106). There were no fatal adverse events and no differences between the 2 groups in the severity or causality (p = 0.287, 0.0564) of adverse events, or incidence of increased liver enzymes or diarrhea (p = 0.691, 0.288, respectively). However, men in the 8-month group noticed a higher number of newly reported adverse events (4.5 versus 2.9, p <0.0001) and higher incidence of hot flushes than the 3-month group (87% versus 72%, respectively, p <0.0001). CONCLUSIONS: Ongoing biochemical and pathological regression of prostate tumors occurs between 3 and 8 months of neoadjuvant hormonal therapy, suggesting that the optimal duration of neoadjuvant hormonal therapy is longer than 3 months. Longer followup is needed to determine whether longer therapy alters PSA recurrence rates.     

High Vegetable and Fruit Diet Intervention in Premenopausal Women with Cervical Intraepithelial Neoplasia

OBJECTIVE: To examine whether diet intervention can promote increased vegetable and fruit intake, as reflected in increased plasma carotenoid and decreased plasma total homocysteine concentrations, in premenopausal women with cervical intraepithelial neoplasia, a precancerous condition. DESIGN: Randomized controlled diet intervention study. SUBJECTS: Fifty-three free-living premenopausal women who had been diagnosed with cervical intraepithelial neoplasia, were randomly assigned to an intervention (n = 27) or a control (n = 26) group. INTERVENTION: Individualized dietary counseling to increase vegetable and fruit intake. MAIN OUTCOME MEASURES: Diet was assessed by food frequency questionnaire. Plasma carotenoids and total homocysteine were measured at enrollment and at 6 months follow up. ANALYSIS: Associations between baseline plasma concentrations of carotenoids and homocysteine and influencing factors were examined with multiple regression analysis. Repeated measures analysis of variance was used to test for group by time effects in these plasma concentrations. Plasma carotenoids at baseline and 6 months in the study groups, and differences in homocysteine concentrations from baseline to 6 months, were compared with independent sample t tests. RESULTS: Repeated measures analysis of variance showed significant group by time effects (P<.01) in plasma carotenoid and homocysteine concentrations. In the intervention group, total plasma carotenoids increased by an average of 91%, from 2.04+/-0.13 (mean+/-standard error of the mean) to 3.90+/-0.56 micromol/L and plasma total homocysteine was reduced by 11%, from 9.01+/-0.40 to 8.10+/-0.44 micromol/L (P<.003). Neither changed significantly in the control group. APPLICATIONS: Individualized dietary counseling can effectively promote increased vegetable and fruit intake in premenopausal women. This dietary pattern may reduce risk for cancer and other chronic diseases and also promote an improvement in folate status.     

CHARACTERIZATION OF HIV INCUBATION DISTRIBUTIONS AND SOME COMPARATIVE STUDIES

In this paper we use a general stochastic model to characterize the HIV incubation distributions. We generate some Monte Carlo data under different conditions and compare the fitting of HIV incubation distributions by some well known parametric models and some non-parametric methods. The parametric models include most of those that have appeared in the literature. The non-parametric methods include the Kaplan–Meier method, the EMS method, the spline approximation and the Bacchetti method. The comparison criteria are the chi-square statistic, the residual sum of squares, the AIC and the BIC. We show that the non-parametric methods, especially the EMS method, provide excellent fits in almost all cases; for the parametric models, the generalized log-logistic distributions with three and with four parameters fit better than other parametric models.