Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. Alzheimer's Disease Cooperative Study

CONTEXT: Several reports from small clinical trials have suggested that estrogen replacement therapy may be useful for the treatment of Alzheimer disease (AD) in women. OBJECTIVE: To determine whether estrogen replacement therapy affects global, cognitive, or functional decline in women with mild to moderate AD. DESIGN: The Alzheimer's Disease Cooperative Study, a randomized, double-blind, placebo-controlled clinical trial conducted between October 1995 and January 1999. SETTING: Thirty-two study sites in the United States. PARTICIPANTS: A total of 120 women with mild to moderate AD and a Mini-Mental State Examination score between 12 and 28 who had had a hysterectomy. INTERVENTIONS: Participants were randomized to estrogen, 0.625 mg/d (n = 42), or 1.25 mg/d (n = 39), or to identically appearing placebo (n = 39). One subject withdrew after randomization but before receiving medication; 97 subjects completed the trial. MAIN OUTCOME MEASURES: The primary outcome measure was change on the Clinical Global Impression of Change (CGIC) 7-point scale, analyzed by intent to treat; secondary outcome measures included other global measures as well as measures of mood, specific cognitive domains (memory, attention, and language), motor function, and activities of daily living; compared by the combined estrogen groups vs the placebo group at 2, 6, 12, and 15 months of follow-up. RESULTS: The CGIC score for estrogen vs placebo was 5.1 vs 5.0 (P = .43); 80% of participants taking estrogen vs 74% of participants taking placebo worsened (P = .48). Secondary outcome measures also showed no significant differences, with the exception of the Clinical Dementia Rating Scale, which suggested worsening among patients taking estrogen (mean posttreatment change in score for estrogen, 0.5 vs 0.2 for placebo; P = .01). CONCLUSIONS: Estrogen replacement therapy for 1 year did not slow disease progression nor did it improve global, cognitive, or functional outcomes in women with mild to moderate AD. The study does not support the role of estrogen for the treatment of this disease. The potential role of estrogen in the prevention of AD, however, requires further research.     

Safety and efficacy of T-614 in the treatment of patients with active rheumatoid arthritis: a double blind, randomized, placebo-controlled and multicenter trial

Background A novel anti-rheumatic drug, T-614, has been shown to have an anti-inflammatory effect and to improve abnormal immunological findings in rheumatoid arthritis （RA）. To assess the safety and efficacy of T-614 versus placebo in patients with active RA we conducted a 24-week clinical study in 280 Chinese patients. Methods In a multicenter, randomized, double blind, placebo controlled study, 280 patients were randomly assigned to receive placebo （n=95） or T-614 at 50 mg （n=93） or 25 mg （n=92） daily. Active disease was defined by 4 of the following 5 criteria： 〉5 tender joints, 〉3 swollen joints, morning stiffness lasting for 〉60 minutes, and Westergren erythrocyte sedimentation rate （ESR） 〉28 mm/h, the assessment of pain at the rest by patient as moderate or severe. Clinical and laboratory parameters were analyzed at baseline, 2, 4, 6, 12, 18 and 24 weeks. The primary efficacy variable at week 24 was the American College of Rheumatology （ACR） response rate using the intent-to-treat population. Results The ACR response rate was significantly higher in the T-614 treatment group compared with the placebo group within 8 weeks after the initiation of treatment. After 24 weeks, the 25 mg/d and 50 mg/d dosage groups and the placebo group showed 39.13%, 61.29% and 24.21% in ACR20 and 23.91%, 31.18% and 7.37% in ACR50, respectively. A time-response in ACR response was observed, with clear superiority for the 25 mg/d and 50 mg/d dosage groups compared to placebo （P〈0.0001）, and the 50 mg/d dose compared to the 25 mg/d dose （P〈0.05） when using the ACR response analyses after 24 weeks. ESR and c-reactive protein （CRP） were significantly different in the treatment groups after 24 weeks. The incidence of adverse events （AEs） was not significantly higher with T-614 than with placebo, but upper abdominal discomfort, leucopenia, elevated serum alanine aminotransferase （sALT）, skin rash and/or pruritus were more common in the 50 mg and 25 mg dosage groups. Conclusion     

Cimetidine in the treatment of duodenal ulcer.

In a double-blind trial performed in two centres, 67 outpatients with endoscopically confirmed duodenal (55) or pyloric canal (12) ulcers received cimetidine (34 patients) or placebo (33 patients) for six weeks. At 6 weeks complete healing of ulcers was significantly increased in patients receiving cimetidine (82%) compared with those receiving placebo (39%) (chi2=11-27; P less than 0-0008). Patients receiving cimetidine had significantly less daytime pain and required less antacid than those receiving placebo. Gastric acid secretion measured one week after cessation of treatment demonstrated that there was no rebound hypersecretion of acid in patients who had received cimetidine. The pretrial basal acid output of those patients whose ulcers failed to heal during cimetidine therapy was significantly greater than that of those whose ulcers healed during treatment with the drug (P less than 0-001). No side effects were encountered.     

盐酸西布曲明治疗单纯性肥胖的疗效与安全性

目的 :评价盐酸西布曲明治疗单纯性肥胖患者的疗效与安全性。方法 :采用随机、双盲、安慰剂平行对照研究方法 ,选择 80例年龄 18～ 6 0岁 ,体重指数≥ 2 5kg/m2 的单纯性肥胖患者 ,随机分为两组 :口服盐酸西布曲明片 (治疗组 ) 10mg/d ;口服安慰剂片 (对照组 )每天 1片共 12周。结果 :有效病例数为 6 6例 ,其中治疗组 31例 ,对照组 35例 ;经 12周治疗 ,治疗组体重平均降低值为 (2 .7± 2 .5 )kg ,显著大于对照组 (- 0 .1± 1.8)kg(P <0 .0 1) ;治疗组不良反应发生率为 5 8.0 %,高于对照组 2 5 .7%(P <0 .0 5 ) ,但症状轻 ,多在 1～ 2周内消失 ,不影响继续治疗。结论 :盐酸西布曲明 10mg/d能有效降低体重 ,治疗的安全性及耐受性较好 ,适用于单纯性肥胖患者的治疗。     

Long-term weight loss with sibutramine: a randomized controlled trial

CONTEXT: Treatment of obesity requires long-term therapy, which can be hampered by difficulties in achieving patient compliance. The effectiveness of sibutramine hydrochloride in treating obesity has been shown in randomized controlled trials. OBJECTIVE: To compare the effectiveness of 2 distinct sibutramine regimens with each other and with placebo for weight reduction among obese persons. DESIGN: Randomized, double-blind, parallel-group placebo-controlled trial from April 1997 to September 1998. SETTING: One hundred eight private practices and 3 outpatient departments of university hospitals in Germany. PATIENTS: A total of 1102 obese adults (body mass index, 30-40 kg/m(2)) entered the 4-week open-label run-in period with 15 mg/d of sibutramine, 1001 of whom had weight loss of at least 2% or 2 kg were randomized into the 44-week randomized treatment period. INTERVENTIONS: Patients were randomly assigned to receive 15 mg/d of sibutramine continuously throughout weeks 1-48 (n = 405); 15 mg/d of sibutramine intermittently during weeks 1-12, 19-30, and 37-48, with placebo during all other weeks (n = 395); or placebo for weeks 5-48 (n = 201). MAIN OUTCOME MEASURE: Weight loss during the randomized treatment period, compared among all 3 groups. RESULTS: Mean weight loss in the intention-to-treat population during the 44-week randomized treatment period was 3.8 kg (4.0%) in patients receiving continuous therapy (95% confidence interval [CI], - 4.42 to - 3.20 kg) and was 3.3 kg (3.5%) in patients receiving intermittent therapy (95% CI, - 3.96 to - 2.66 kg), vs a mean weight gain of 0.2 kg (0.2%) (95% CI, - 0.60 to 0.94 kg) in patients receiving placebo. Therapeutic equivalence of the 2 active treatments could be shown. Although there was a greater weight loss in the continuous than in the intermittent group, this difference was nonsignificant (P =.28) and the 95% CIs were within the predefined range of therapeutic equivalence-0 +/-1.5 kg (-1.37 to 0.28 for the intent-to-treat population). Overall weight loss during the 48-week period was 7.9 kg and 7.8 kg in the continuous and intermittent groups, respectively, but was 3.8 kg in the sibutramine run-in placebo group. Waist circumference reduction, triglyceride levels, and high-density lipoprotein cholesterol concentrations were also positively influenced by sibutramine treatment. Systolic and diastolic blood pressures were stable across all 3 groups. Overall, adverse events occurred at similar frequencies across all treatment groups, but the proportion was lowest in the group receiving intermittent therapy. CONCLUSIONS: Sibutramine, administered for 48 weeks to a typically obese population, results in clinically relevant weight loss compared with placebo. Regarding effectiveness, continuous and intermittent sibutramine therapies are equivalent and the safety profiles for both treatments are comparable.     

Cholinesterase Inhibition for Alzheimer Disease: A Meta-analysis of the Tacrine Trials

Objectives.— To determine the effects of cholinesterase inhibition with tacrine hydrochloride for the symptoms of Alzheimer disease in terms of cognitive performance, clinical global impression, behavior, and functional autonomy. Data Sources.— The Cochrane Dementia Group registry of trials. Study Selection.— Unconfounded, randomized, double-blind, placebo-controlled trials in which tacrine had been given for more than 1 day and that were completed before January 1, 1996. Data Extraction.— Two reviewers independently selected trials for inclusion and individual patient data were sought. Data Synthesis.— Data were analyzed from 12 trials that included 1984 patients with Alzheimer disease. At 12 weeks, cognitive performance, as measured by the Mini-Mental State Examination (score range, 0-30), was better in patients receiving tacrine than in patients receiving placebo by 0.62 points (95% confidence interval [CI], 0.23-1.00; P=.002). Compared with similar untreated patients who would be expected to deteriorate by 0.50 to 1.00 points on the Mini-Mental State Examination during 12 weeks, the progress of patients receiving tacrine would be expected to range between an improvement of 0.12 and a deterioration of 0.38 points. The odds ratio for improvement on the Clinical Global Impression of Change scale (range, 1-7) for patients receiving tacrine compared with those receiving placebo was 1.58 (95% CI, 1.18-2.11; P=.002). The behavioral noncognitive subscale of the Alzheimer's Disease Assessment Scale (range, 0-50) showed a difference in favor of tacrine of 0.58 points (95% CI, 0.17-1.00; P=.006). Improvement on the Progressive Deterioration Scale, largely an index of functional activities, was not significant (0.75; 95% CI, -0.43 to 1.93; P=.21). Age, severity of dementia, and exposure to tacrine prior to randomization had no clear influence on the treatment effect. There was a nonsignificant trend toward increasing effect with increasing dose for cognitive function and the Clinical Global Impression of Change. For patients without prior exposure to tacrine, the odds of patients' withdrawing during the study while they were receiving tacrine compared with placebo was 3.63 (95% CI, 2.80-4.71; P<.001). Eleven (95% CI, 7-31) patients would need to be treated to achieve any improvement on the Clinical Global Impression scale, and 42 (95% CI, 23-125) to achieve a moderate or marked improvement. One patient would be expected to withdraw for every 4 (95% CI, 3-5) patients treated. Conclusions.— Cholinesterase inhibition with tacrine appears to reduce deterioration in cognitive performance during the first 3 months and increase the odds of global clinical improvement. Effects observed on measures of behavioral disturbance were of questionable clinical significance, and functional autonomy was not significantly affected. The clinical relevance of the benefits of cholinesterase inhibition remains controversial, and long-term trials with clinically relevant end points are required.      

Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: the ADMIT study: A randomized trial. Arterial Disease Multiple Intervention Trial

CONTEXT: Although niacin increases low levels of high-density lipoprotein cholesterol (HDL-C), which frequently accompany diabetes, current guidelines do not recommend use of niacin in patients with diabetes because of concerns about adverse effects on glycemic control; however, this is based on limited clinical data. OBJECTIVE: To determine the efficacy and safety of lipid-modifying dosages of niacin in patients with diabetes. DESIGN AND SETTING: Prospective, randomized placebo-controlled clinical trial conducted in 6 clinical centers from August 1993 to December 1995. PARTICIPANTS: A total of 468 participants, including 125 with diabetes, who had diagnosed peripheral arterial disease. INTERVENTIONS: After an active run-in period, participants were randomly assigned to receive niacin (crystalline nicotinic acid), 3000 mg/d or maximum tolerated dosage (n = 64 with diabetes; n = 173 without diabetes), or placebo (n = 61 with diabetes; n = 170 without diabetes) for up to 60 weeks (12-week active run-in and 48-week double-blind). MAIN OUTCOME MEASURES: Plasma lipoprotein, glucose, hemoglobin A(1c) (HbA(1c)), alanine aminotransferase, and uric acid levels; hypoglycemic drug use; compliance; and adverse events, in patients with diabetes vs without who were receiving niacin vs placebo. RESULTS: Niacin use significantly increased HDL-C by 29% and 29% and decreased triglycerides by 23% and 28% and low-density lipoprotein cholesterol (LDL-C) by 8% and 9%, respectively, in participants with and without diabetes (P<.001 for niacin vs placebo for all). Corresponding changes in participants receiving placebo were increases of 0% and 2% in HDL-C and increases of 7% and 0% in triglycerides, and increases of 1% and 1% in LDL-C. Glucose levels were modestly increased by niacin (8.7 and 6.3 mg/dL [0.4 and 0.3 mmol/L]; P =.04 and P<.001) in participants with and without diabetes, respectively. Levels of HbA(1c) were unchanged from baseline to follow-up in participants with diabetes treated with niacin. In participants with diabetes treated with placebo, HbA(1c) decreased by 0.3% (P =.04 for difference). There were no significant differences in niacin discontinuation, niacin dosage, or hypoglycemic therapy in participants with diabetes assigned to niacin vs placebo. CONCLUSIONS: Our study suggests that lipid-modifying dosages of niacin can be safely used in patients with diabetes and that niacin therapy may be considered as an alternative to statin drugs or fibrates for patients with diabetes in whom these agents are not tolerated or fail to sufficiently correct hypertriglyceridemia or low HDL-C levels. JAMA. 2000;284:1263-1270     

美金刚改善帕金森病认知功能和运动障碍的疗效分析

目的 本研究旨在探讨美金刚对帕金森病认知功能障碍和运动功能改善的临床疗效.方法 选取河南省人民医院门诊2007年3月至2010年3月间确诊的55例帕金森病痴呆患者,随机分为治疗组28例和对照组27例.治疗组采用帕金森病基本药物治疗加美金刚20 mg/d治疗;对照组仅采用帕金森病基本药物基本治疗.在治疗前和治疗后12、24周后分别对两组患者进行疗效评估.主要评估指标包括简易精神状态量表(MMSE)、阿尔茨海默病评价量表-认知分量表(ADAS-cog)、统一帕金森病评分量表第三部分运动评分(UPDRS-Ⅲ)及帕金森病的分期Hoehn & Yahr(H&Y,修正)分级量表.结果 在24周后治疗组患者量表评分MMSE(22.8±1.8),ADAS-cog(18.6±2.3)和UPDRS-Ⅲ(34.6±4.2)较对照组MMSE(18.5±1.7),ADAS-cog(21.9±2.4)和UPDRS-Ⅲ(41.2±4.0)均有明显改善(P＜0.05),且治疗组上述评分显著优于对照组(P＜0.05).结论 美金刚能有效地改善帕金森患者的认知功能障碍和运动障碍,且用药安全,耐受性好.

Abstract：

Objective To study the effects of memantine on cognitive and motor impairment in patients with Parkinson's disease (PD). Methods A total of 55 PD patients omplicated by varying degrees of cognitive impairment were randomly divided into two groups. The patients of experimental group ( n = 28 )received memantine (20 mg/d) while those in the control group (n = 27 ) conventional antiparkinsonian drug therapy alone. The cognitive and motor evaluations were assessed at pre-treatment and 12, 24 weeks posttreatment by clinical assessment, rating scales and neuropsychological tests. Results At week 24 the patients m the memantine group had better MMSE (22.8 ±1.8), ADAS-cog (18.6 ±2.3), and UPDRS-Ⅲ (34.6 ±4.2) scales scores than those taking placebo MMSE (18.5 ±1.7), ADAS-cog (21.9 ±2.4), and UPDRS-Ⅲ (41.2 ±4.0). Patients treated with memantine had better improvement on the MMSE (P ＜ 0.05), ADAScog (P＜ 0.05), and UPDRS-Ⅲ (P＜ 0.05) scales compared with the control group by the end of study week 24. Conclusion Memantine may improve the cognitive and motor impairments of PD. And it is both safe and well-tolerated.     

小剂量激素合甲氨蝶呤治疗早期类风湿性关节炎疗效观察

目的观察小剂量激素泼尼松(PDN)联合甲氨蝶呤(MTX)治疗早期类风湿性关节炎(RA)的疗效及安全性。方法未接受过治疗的早期RA患者60例,随机分为观察组30例,予PDN联合MTX治疗(PDN 10~15mg/d,MTX7.5~20mg/w),对照组30例,予MTX(7.5~20mg/w)加安慰剂治疗,疗程均12周。治疗0、4、8、12周评估两组疗效及安全性。以美国风湿病学会(ACR)疗效评价指标ACR20、DAS28-ESR指标、疼痛目视模拟测试表(VAS)评分、患者对病情活动的总体VAS评分、医生对病情活动的总体VAS评分、压痛关节数、肿胀关节数、健康评估问卷(HAQ-DI)评分、晨僵持续时间、CRP和ESR作为疗效指标。结果治疗第4周和第8周,观察组达到ACR20改善者分别为43.3%、66.7%,对照组分别为16.7%、30.0%,两组比较差异均有统计学意义(P均0.05)。治疗第12周,观察组83.3%(25例)达到ACR20的改善,对照组为43.3%(13例)(P=0.001)。第4周起,观察组DAS28-ESR评分均持续低于对照组(P均0.05,P0.01)。治疗12周,除关节压痛数、晨僵时间和CRP,观察组其它各项临床和实验室炎症指标改善均优于对照组(P0.05,P0.01)。观察组RA病程与12周DAS28-ESR评分存在显著正相关(r=0.643,P=0.000)。结论小剂量GC联合MTX治疗能显著改善ERA症状、体征和实验室炎性指标,疗效优于单用MTX。两者联合治疗安全耐受性良好。     

缓释烟酸及其与阿托伐他汀合用的调脂疗效与安全性

目的 观察烟酸缓释片单用和与阿托伐他汀合用对冠心病及其等危症患者的调脂疗效及安全性。方法 110例血清总胆固醇（TC）≥3．5mmoL／L的冠心病及其等危症患者分为3组：（1）烟酸缓释片组（n=38）,给予烟酸缓释片500mg／d,4周后加量至1000mg／d;（2）阿托伐他汀组（n=38）,给予阿托伐他汀10mg／d;（3）联合治疗组（n=34）,给予阿托伐他汀10mg／d和烟酸缓释片500mg／d,4周后烟酸缓释片加量至1000mg／d。3组患者均干预8周,分别在干预前、干预4周和8周后测定血脂水平并评估不良反应。结果 （1）烟酸缓释片组干预8周后,甘油三酯（TG）降低30％,高密度脂蛋白-胆固醇（HDL-C）升高16％（均P〈0．05）;阿托伐他汀组干预8周后TC、低密度脂蛋白．胆固醇（LDL-C）、TG分别降低19％、26％和17％（均P〈0．05）;联合治疗组干预8周后TC、LDL-C和TG分别降低28％、38％和39％,HDL-C升高23％（均P〈0．05）,其TC和LDL-C的降低明显优于单药治疗组（均P〈0．05）。（2）联合治疗组的LDL-C达标率为73．5％,明显高于单药治疗组（均P〈0．05）。（3）烟酸缓释片组的不良反应以潮红（15．8％）和消化道症状（23．7％）较常见,联合治疗组不良反应未见增加,各组均未见严重的不良反应。结论 烟酸缓释片有良好的调脂作用,尤以降低TG和升高HDL-C效果明显。烟酸缓释片与他汀类药物联合使用有助于血脂谱的全面改善,并具有良好的安全性和耐受性。     

Comparison of nifedipine (retard formulation) and mefruside in the treatment of mild to moderate hypertension--a prospective randomized double-blind crossover study in general practice

Twenty-two patients under general practice care, suffering mild to moderate hypertension and receiving no active treatment had three baseline blood pressure measurements taken during a single blind 4-week placebo run-in period. One patient was secondarily excluded at this stage because of a placebo response and one patient dropped out for personal reasons. The remaining 20 patients were randomized to receive either nifedipine 20 mg twice a day or mefruside 25 mg once a day in a classical two-period crossover design with 8-week treatment periods separated by a 4-week single-blind placebo washout. During 8 weeks nifedipine therapy the mean supine blood pressure was reduced from 173 (s.d. = 15.4)/107(s.d. = 6.4) mmHg to 150(s.d. = 16.7)/93(s.d. = 10.8) mmHg whereas the corresponding reduction for mefruside was from 174(s.d. = 15.9)/107(s.d. = 9.4) mmHg to 153(s.d. = 19.1)/94(s.d. = 9.7) mmHg. Neither drug affected postural changes in blood pressure. Standing blood pressure measurements under 8 weeks nifedipine therapy fell from 172(s.d. = 12.3)/103(s.d. = 5.6) mmHg to 150(s.d. = 17.9)/94(s.d. = 10.0) mmHg with corresponding changes for mefruside being 174(s.d. = 14.7)/106(s.d. = 9.0) mmHg to 150(s.d. = 20.2)/95(s.d. = 9.4) mmHg. Since blood pressures returned to within 4% of baseline values by the end of the placebo washout period it can be inferred that each therapy was a significant (P less than 0.05 for all blood pressure variables) antihypertensive treatment in its own right.     

Effect of omalizumab on symptoms of seasonal allergic rhinitis: a randomized controlled trial.

CONTEXT: Seasonal allergic rhinitis is a common IgE-mediated disorder that produces troublesome symptoms. A recombinant humanized monoclonal anti-IgE antibody (omalizumab) forms complexes with free IgE, blocking its interaction with mast cells and basophils and lowering free IgE levels in the circulation. OBJECTIVE: To assess the efficacy and safety of omalizumab for prophylaxis of symptoms in patients with seasonal allergic rhinitis. DESIGN: Randomized, double-blind, dose-ranging, placebo-controlled trial conducted from July 25 through November 21, 1997. SETTING: Twenty-five outpatient centers throughout the United States. PATIENTS: Five hundred thirty-six patients aged 12 to 75 years with at least a 2-year history of moderate to severe ragweed-induced seasonal allergic rhinitis and a baseline IgE level between 30 and 700 IU/mL. INTERVENTIONS: Patients were randomly assigned to receive omalizumab, 50 mg (n = 137), 150 mg (n = 134), or 300 mg (n = 129), or placebo (n = 136) subcutaneously just prior to ragweed season and repeated during the pollen season every 3 weeks in patients with baseline IgE levels of 151 to 700 IU/mL (4 total treatments) and every 4 weeks in patients with baseline IgE levels of 30 to 150 IU/mL (3 total treatments). MAIN OUTCOME MEASURES: Self-assessed daily nasal symptom severity scores (range, 0-3), rescue antihistamine use, and rhinitis-specific quality of life during the 12 weeks from the start of treatment. RESULTS: Nasal symptom severity scores were significantly lower in patients who received 300 mg of omalizumab than in those who received placebo (least squares means, 0.75 vs 0.98, respectively; P =.002). A significant association was observed between IgE reduction and nasal symptoms and rescue antihistamine use. Rhinitis-specific quality of life scores were consistently better in patients who received 300 mg of omalizumab than in those who received lower dosages or placebo and did not decline during peak season. The frequency of adverse events was not significantly different among the omalizumab and placebo groups. CONCLUSION: Omalizumab decreased serum free IgE levels and provided clinical benefit in a dose-dependent fashion in patients with seasonal allergic rhinitis.     

Purified poloxamer 188 for treatment of acute vaso-occlusive crisis of sickle cell disease: A randomized controlled trial.

CONTEXT: Sickle cell disease (SCD) can cause severe painful episodes that are often thought to be caused by vaso-occlusion. The current therapy for these uncomplicated painful episodes includes hydration, oxygen, and analgesics. Purified poloxamer 188 may increase tissue oxygenation and thereby reduce inflammation, pain, and the overall duration of such painful episodes in patients with SCD. OBJECTIVE: To compare the duration of painful episodes in patients with SCD treated with purified poloxamer 188 to that of similar episodes experienced by patients who receive a placebo. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled, intention-to-treat trial conducted between March 1998 and October 1999 in 40 medical centers in the United States. PARTICIPANTS: Two hundred fifty-five patients with SCD (aged 9-53 years) who had a painful episode sufficiently severe to require hospitalization and narcotic analgesics. INTERVENTION: Patients were randomly assigned to receive an intravenous infusion of purified poloxamer 188, 100 mg/kg for 1 hour followed by 30 mg/kg per hour for 47 hours (n = 127), or a matching volume of saline placebo (n = 128). MAIN OUTCOME MEASURE: Duration of the painful episode, from randomization to crisis resolution. RESULTS: Mean (SD) duration of the painful episodes was 141 (42) hours in the placebo group compared with 133 (41) hours in those treated with purified poloxamer 188, a 9-hour reduction (P =.04). Subset analyses indicated an even more pronounced purified poloxamer 188 effect in children aged 15 years or younger (21 hours; P =.01) and in patients who were receiving hydroxyurea (16 hours; P =.02). Finally, the proportion of patients achieving crisis resolution was increased by purified poloxamer 188 (65/126 [52%] vs 45/123 [37%]; P =.02). Similar results were observed in children aged 15 years or younger (22/37 [60%] vs 10/36 [28%]; P =.009) and in patients who were also receiving hydroxyurea (12/26 [46%] vs 4/28 [14%]; P =.02). CONCLUSIONS: A decrease in the duration of painful episodes and an increase in the proportion of patients who achieved resolution of the symptoms were observed when the purified poloxamer 188-treated patients were compared with the patients receiving placebo. However, the difference between these groups was significant but relatively small. In subgroup analysis, a more significant effect on both parameters was observed in children and in patients who were receiving concomitant hydroxyurea. It is important to confirm both of these observations in further prospective trials.     

急性冠脉综合征应用小剂量辛伐他汀联合阿昔莫司降脂治疗的疗效观察

目的观察小剂量辛伐他汀联合阿昔莫司降脂治疗急性冠脉综合征（ACS）的疗效及安全性。方法选择156例ACS合并高脂血症患者,将患者随机分为4组：A组：辛伐他汀10mg/d,38例;B组：辛伐他丁联合阿昔莫司（辛伐他汀10mg/d、阿昔莫司750mg/d）,40例;C组：辛伐他汀20mg/d,38例;D组：辛伐他丁联合阿昔莫司（辛伐他汀20mg/d、阿昔莫司750mg/d）,40例。4组患者经上述药物及常规治疗,在治疗后12周观察调脂药物的疗效、肝肾功能损害等。结果4组患者治疗后,B、D组降低总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、三酰甘油（TG）以及升高高密度脂蛋白胆固醇（HDL-C）水平均优于C、A组,差异亦均有统计学意义（P〈0.05）,而D组与B组比较,差异有统计学意义（P〈0.05）,但不良反应明显增加。结论小剂量辛伐他汀联合阿昔莫司能有效地使LDL-C、TC达标,同时对降低TG、升高HDL-C也具有较好的效果,不良反应无明显增加。     

EFFECTS OF SIMVASTAIN COMBINED WITH OMEGA-3 FATTY ACIDS ON HIGH SENSITIVE C-REACTIVE PROTEIN,LIPIDEMIA,AND FIBRINOLYSIS IN PATIENTS WITH MIXED DYSLIPIDEMIA

Objective To evaluate the effects of simvastatin combined with omega-3 fatty acids on high sensitive C-reactive protein (HsCRP), lipidemia, and fibrinolysis in coronary heart disease (CHD) and CHD risk equivalent patients with mixed dyslipidemia.Methods A randomized, double-blind placebo controlled and parallel group trial was conducted. Patients with CHD and CHD risk equivalents with mixed dyslipidemia were treated with 10 or 20 mg simvastatin for 6-12 weeks. Following with the treatment of patients whose low-density lipoprotein cholesterol (LDL-ch) reaching goal level (＜ 100 mg/dL) or close to the goal (＜ 130 mg/dL), while triglyceride (TG) ≥ 200 mg/dL and ＜ 500 mg/dL, was combined with omega-3fatty acids (3 g/d) or a placebo for 2 months. The effects of the treatment on HsCRP, total cholesterol (TC), LDL-ch, highdensity lipoprotein cholesterol (HDL-ch), TG, lipoprotein (a) [LP (a)], apolipoprotein Al (apoAl), apolipoprotein B (apoB),plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (tPA) were investigated. Forty patients finished the study with each group consisting of twenty patients.Results (1) There were significant reductions of HsCRP, TG, TC, and TC/HDL-ch, which decreased by 2.16 ± 2.77mg/L (38.5%), 94.0± 65.4 mg/dL (31.1%), 13.3 ± 22.3 mg/dL (6.3%), 0.78 ± 1.60 respectively in the omega-3 fatty acids group (P ＜ 0.01, ＜ 0.001, ＜ 0.05, ＜ 0.05) compared to the baseline. HsCRP and triglyceride reduction were more significant in omega-3 fatty acids group compared to the placebo group (P= 0.021 and 0.011 respectively). (2) In the omega-3 fatty acids group, the values and percentage of TG reduction had a significantly positive relation with HsCRP reduction (r = 0.51and 0.45, P=0.021 and 0.047 respectively).Conclusion In CHD and CHD risk equivalent patients with mixed dyslipidemia, dyslipidemia's therapeutic effect using simvastatin and omega-3 fatty acids may result from not only the combination of lipid adjustment, but also enhancement of their own nonlipid influences.     

阿托伐他汀在治疗扩张型心肌病心力衰竭中的应用

目的探讨他汀类药物在非缺血性心力衰竭的治疗中的应用。方法将30例特发性扩张型心肌病患者随机分为阿托伐他汀组（n=15）和安慰剂组（n=15）。阿托伐他汀组在常规治疗的基础上，加用阿托伐他汀20need。结果治疗16周后，阿托伐他汀组较安慰剂组血浆总胆固醇和低密度脂蛋白水平降低，心功能改善，左室射血分数提高，为（39．11±3．45）％对（34．23±3．14）％，P〈0．01。血浆肿瘤坏死因子-α（TNF—α）和C-反应蛋白（CRP）水平在阿托伐他汀组显著降低（P〈0．01）。结论阿托伐他汀可以显著改善扩张型心肌病心袁患者的心功能和血管内皮功能，提示他汀类药物可用于治疗非缺血性心力衰竭。     

Testosterone replacement and resistance exercise in HIV-infected men with weight loss and low testosterone levels

CONTEXT: Previous studies of testosterone supplementation in HIV-infected men failed to demonstrate improvement in muscle strength. The effects of resistance exercise combined with testosterone supplementation in HIV-infected men are unknown. OBJECTIVE: To determine the effects of testosterone replacement with and without resistance exercise on muscle strength and body composition in HIV-infected men with low testosterone levels and weight loss. DESIGN AND SETTING: Placebo-controlled, double-blind, randomized clinical trial conducted from September 1995 to July 1998 at a general clinical research center. PARTICIPANTS: Sixty-one HIV-infected men aged 18 to 50 years with serum testosterone levels of less than 12.1 nmol/L (349 ng/dL) and weight loss of 5% or more in the previous 6 months, 49 of whom completed the study. INTERVENTIONS: Participants were randomly assigned to 1 of 4 groups: placebo, no exercise (n = 14); testosterone enanthate (100 mg/wk intramuscularly), no exercise (n = 17); placebo and exercise (n = 15); or testosterone and exercise (n = 15). Treatment duration was 16 weeks. MAIN OUTCOME MEASURES: Changes in muscle strength, body weight, thigh muscle volume, and lean body mass compared among the 4 treatment groups. RESULTS: Body weight increased significantly by 2.6 kg (P<.001) in men receiving testosterone alone and by 2.2 kg (P = .02) in men who exercised alone but did not change in men receiving placebo alone (-0.5 kg; P = .55) or testosterone and exercise (0.7 kg; P = .08). Men treated with testosterone alone, exercise alone, or both experienced significant increases in maximum voluntary muscle strength in leg press (range, 22%-30%), leg curls (range, 18%-36%), bench press (range, 19%-33%), and latissimus pulls (range, 17%-33%). Gains in strength in all exercise categories were greater in men assigned to the testosterone-exercise group or to the exercise-alone group than in those assigned to the placebo-alone group. There was a greater increase in thigh muscle volume in men receiving testosterone alone (mean change, 40 cm3; P<.001 vs zero change) or exercise alone (62 cm3; P = .003) than in men receiving placebo alone (5 cm3; P = .70). Average lean body mass increased by 2.3 kg (P = .004) and 2.6 kg (P<.001), respectively, in men who received testosterone alone or testosterone and exercise but did not change in men receiving placebo alone (0.9 kg; P = .21).Hemoglobin levels increased in men receiving testosterone but not in those receiving placebo. CONCLUSION: Our data suggest that testosterone and resistance exercise promote gains in body weight, muscle mass, muscle strength, and lean body mass in HIV-infected men with weight loss and low testosterone levels. Testosterone and exercise together did not produce greater gains than either intervention alone.     

功能性电刺激改善急性脑卒中患者肢体功能的随机对照研究

目的研究功能性电刺激(FES)对急性脑卒中偏瘫患者下肢运动和步行能力的影响。方法 46例初发脑卒中患者,年龄71岁±8岁,发病后9d±4 d,随机分为 FES 组(13例)、安慰电刺激组(15例),对照组(13例)。3组常规治疗相同,FES 组给予功能性电刺激治疗,每天1次,每次30 min,共3周(15次);安慰组给予没有电流输出的电刺激,对照组不给电刺激。用综合痉挛量表(CSS)评定踝跖屈肌群肌张力,用表面肌电图评定踝背伸和跖屈肌群最大等长收缩(MIVC)时的力矩、积分肌电图和肌肉的协同收缩率,以及患者在住院期间独自行走的能力。结果 3组患者一般资料及治疗前各项评定结果的差异无统计学意义。治疗3周后,FES 组踝跖屈肌群痉挛增加程度最低,CSS 增加率3组分别为30%±35%、50%±88%、65%±65%。踝背伸时胫前肌 MIVC 明显增加(9 Nm±5 Nm、5 Nm±3 Nm、4 Nm±5 Nm),踝背伸时的协同收缩率明显降低(8%±5%、27%±26%、28%±19%)。治疗3周内,FES 组恢复行走能力的时间较其他2组平均早2～3 d(18 d±8 d,20 d±7 d,21d±8 d)。结论 FES 能明显改善初发脑卒中急性期偏瘫患者下肢的运动功能和步行能力。     

石杉碱甲治疗阿尔茨海默病的有效性和安全性的多中心双盲随机对照试验

目的：与安慰剂双盲对照评估石杉碱甲治疗轻、中度阿尔茨海默病（AD）患者的临床疗效和安全性。方法：来自全国15个中心202例可能或可能的AD患者随机接受石杉碱甲或安慰剂治疗12周。石杉碱甲组100例,400μg/,安慰剂组102例,每6周评估1次。结果：202例患者进入意向性治疗分析,其中197例患者通过末次观察前推法（LOCF）完成统计。比较石杉碱甲组和安慰剂组各种疗效评估量表的评分自基线水平至治疗6周和12周时评分变化的均值,以及治疗12周时评分和基线相比有改善的患者的比例：治疗12周和基线相比,简易精神状态检查（MMSE）平均改善2．7分;AD评估量表的认知分量表（ADAS－Cog)得分平均改善4．6分,改善至少4分者56．1％;ADAS非认知副表（ADAS－non-Cog)得分平均改善1．5分,临床好转的患者为59．2％;日常生活活动量表（ADL）得分平均改善2．4分,改善至少10％的患者32．7％;印象变化量表（CIBIC plus)获1－3分的患者为70％,1－2分者27．8％。这些指标和安慰剂组比较,两组间的差异有显著意义。总的不良反应率石杉碱甲组为3％,均为轻度、一过性反应。结论：石杉碱甲可显著改善AD患者认知功能、行为和心境障碍、日常生活活动能力和总体功能,具有良好的安全性。     

Effect of tetrahydroaminoacridine on cognition, function and behaviour in Alzheimer's disease.

OBJECTIVE: To determine the efficacy of tetrahydroaminoacridine (THA) in Alzheimer's disease. DESIGN: Randomized, double-blind, multiple crossover trial with three treatment periods, each consisting of 3 weeks of active drug therapy and 3 weeks of placebo administration. SETTING: Referral-based geriatric practice in a community hospital. PATIENTS: Thirty-four patients with moderate to severe Alzheimer's disease. Subjects were included if they had stage 3 to 6 disease (as determined by the Reisberg scale) and had not been taking psychotropic drugs for at least 1 month and if informed consent had been obtained from the patients and their next of kin. INTERVENTIONS: Fifty to 100 mg of THA daily and matched placebo. RESULTS: Of the initial 34 patients 14 experienced liver toxicity and 3 gastrointestinal side effects during the study; however, all 22 who completed the study were able to tolerate at least the minimum dose. For the 22 patients there was no clinically or statistically significant effect of THA on cognition, functional status or behaviour. The results for individual patients showed no subgroup of THA-responsive patients. CONCLUSION: THA has no clinically important benefits in Alzheimer's disease and is associated with appreciable toxic effects.