Controlled Trial of Azathioprine and Prednisone in Chronic Renal Disease

Patients with various forms of glomerulonephritis, but excluding those with minimal glomerular changes, were admitted to a controlled trial of a regimen which combined azathioprine in a dosage of 2·5 mg/kg/day with prednisone in a dosage of 20 mg/day (adults) or 0·5 mg/kg/day (children). Of 149 patients included, 32 of them under the age of 15, 72 were randomly allocated to the “treatment” group and 77 to the “control” group. There was no evidence of benefit from the treatment group as a whole; and the mortality was in fact higher in the treated group.     

Long-term Study of Disodium Cromoglycate in Treatment of Severe Extrinsic or Intrinsic Bronchial Asthma in Adults

The results are reported here of a long-term double-blind controlled clinical trial of disodium cromoglycate (D.S.C.G.) and isoprenaline, D.S.C.G. alone, isoprenaline alone, and a placebo given as a powder for inhalation in the treatment of severe bronchial asthma.At the end of one year 16 out of 20 patients on D.S.C.G.-isoprenaline remained on the allocated capsules, compared with 10 out of 15 on D.S.C.G., 5 out of 20 on isoprenaline, and 3 out of 19 taking the placebo. The differences between each of the D.S.C.G.-isoprenaline and D.S.C.G. regimens compared with the isoprenaline and placebo regimens were statistically significant. After eight weeks on four capsules a day the patients in each group were allocated at random so that half continued on full dosage and half on a reducing regimen. At the end of the year there was no significant difference in the failure rate between patients allocated the full dosage and the patients on the reducing dosage. The capsules were well tolerated and toxicity to D.S.C.G. was not observed.     

Randomised trial of prophylactic daily aspirin in British male doctors

A six year randomised trial was conducted among 5139 apparently healthy male doctors to see whether 500 mg aspirin daily would reduce the incidence of and mortality from stroke, myocardial infarction, or other vascular conditions. Though total mortality was 10% lower in the treated than control group, this difference was not statistically significant and chiefly involved diseases other than stroke or myocardial infarction. Likewise, there was no significant difference in the incidence of non-fatal myocardial infarction or stroke—indeed, disabling strokes were somewhat commoner among those allocated aspirin. The lower confidence limit for the effect of aspirin on non-fatal stroke or myocardial infarction, however, was a substantial 25% reduction. Migraine and certain types of musculoskeletal pain were reported significantly less often in the treated than control group, but as the control group was not given a placebo the relevance of these findings was difficult to assess. There was no apparent reduction in the incidence of cataract in the treated group.The lack of any apparent reduction in disabling stroke or vascular death contrasts with the established value of antiplatelet treatment after occlusive vascular disease.     

吉西他滨联合化疗方案治疗复发转移性乳腺癌的临床疗效观察

目的:观察吉西他滨与顺铂联合以及吉西他滨与紫杉醇联合治疗复发转移性乳腺癌的疗效和不良反应。方法:本研究收集65例女性乳腺癌术后复发转移的患者作为研究对象。随机分成两组,分别应用吉西他滨与顺铂(GP方案组)、吉西他滨与紫杉醇(GT方案组)联合进行治疗。GP方案组患者有30例,第1天、第8天用吉西他滨800mg~1000mg/m2溶于0.9%的100mL生理盐水中静脉滴注;第1天~第3天,21天重复用顺铂30mg/m2溶于0.9%的250mL生理盐水中静脉滴注;GT方案组患者有35例,吉西他滨的使用方法与GP方案组相同,第2天,21重复用紫杉醇135mg/m2溶于0.9%的500mL生理盐水中静脉滴注。对化疗时产生的不良反应进行对症处理。结果 :GP方案组化疗有效率为46.67%,疾病控制率为70.00%;GT方案组化疗有效率为42.86%,疾病控制率为68.57%,两组比较差异均无统计学意义(P0.05)。GT组脱发的发生率为62.86%,明显高于GP组的10.00%(P0.001),其他不良反应在两组之间差异无统计学意义(P0.05)。结论:GP方案和GT方案在治疗复发转移性乳腺癌有较好的疗效,不良反应较轻,可作为复方转移性乳腺的一种化疗方案。     

阿斯匹林治疗急性缺血性脑卒中临床疗效随机双盲对照研究

目的 探讨阿斯匹林抗血小板治疗急性缺血性脑卒中,对降低死亡率,改善致残率的临床疗效。方法 采取随机、双盲、安慰剂对照,对发病48h内的急性缺血性脑卒中患者,均经头颅CT检查排除出血性脑卒中。入选患者在常规治疗的基础上,口服阿斯匹林,每天160mg或安慰剂4周。结果 服阿斯匹林的患者（阿斯匹林组）和服安慰剂的患者（安慰剂组）相比较,两组对降低死亡率,减轻致残率的结果差异无统计学意义（P＞0．05）。结论 在常规治疗急性缺血性脑卒中的基础上,加服阿斯匹林160mg对降低病死率和出院时的致残率效果不明显。     

Perspectives from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial--Lipid Lowering Trial and the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm

PURPOSE OF REVIEW: The design, process and outcomes are compared between two large clinical trials of LDL cholesterol reduction with statin treatment in patients with known high blood pressure. This new information is placed in the context of previous clinical trials of cholesterol reduction, which have provided analyses of sub-groups with high blood pressure. RECENT FINDINGS: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial failed to find a significant reduction of total mortality (primary endpoint), cardiovascular mortality or major cardiovascular events. This differed sharply from the Anglo-Scandinavian Cardiac Outcomes Trial, Lipid Lowering Arm, which was stopped before the planned termination due to a marked reduction (36%) in coronary death or myocardial infarction (primary endpoint). This trial also found significant reductions in stroke (27%) and separately, all major vascular events (21%). The two studies were similar in that they each contained over 10 000 participants with documented high blood pressure requiring drug therapy and they both used a fixed dose of a single statin. Pravastatin (40 mg/day) was used in the former and atorvastatin 10 mg/day in the latter. The major difference was that the control group in the Anglo-Scandinavian trial was treated with placebo with a double blind design whereas antihypertensive and lipid-lowering trial was open label with controls receiving usual care. SUMMARY: The benefit of achieving and maintaining significant LDL cholesterol reduction in patients with high blood pressure was convincingly demonstrated in the Anglo-Scandinavian trial. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial failed to achieve similar success due to use of a less effective drug and loss of the differential effect with increasing statin treatment in the usual care control group.     

重度有机磷农药中毒致多器官功能障碍综合症死亡因素的探讨

目的:探讨重度有机磷农药中毒发生多脏器功能障碍综合症的死亡因素。方法:分析78例急性有机磷农药中毒发生多脏器功能障碍综合症的临床资料,分为治愈组和死亡组,分别对两组的一般资料、治疗过程、并发症等情况进行比较。结果:治愈组64.5%的中毒物为中低毒性,而死亡组50%的患者中毒物为高毒类,两组中毒物毒性程度的构成比比较差异有统计学意义(P0.05)。死亡组患者中毒后至洗胃的时间间隔较治愈组明显延长(6.8±4.1 vs 4.2±3.5h,p=0.038),入院24小时内氯磷定用量明显低于治愈组(6.2±3.8 vs 8.6±2.6,P=0.045)。两组阿托品总用量及24小时总用量比较未见显著性差异(669.4±393.1 vs 427.9±290.7,P=0.956),但死亡组阿托品日均用量明显高于治愈组(120.2±96.31 vs 39.5±62.0,P=0.042)。入院第1天,死亡组Pa O2/Fi O2、MAP明显低于治愈组,Scr、HR及CK-MB明显高于治愈组;治疗3天后,死亡组MAP仍明显低于治愈组,Scr、HR较高,且Ach E明显低于治愈组,差异均有统计学意义(P0.05)。结论:中毒物的毒性程度、未能早期足量的应用肟类复能剂、过量使用阿托品或阿托品中毒、发病初期缺少足够的多器官功能支持治疗可能是AOPP合并MODS的患者死亡的重要因素。     

Ischaemic Heart Disease: A Secondary Prevention Trial Using Clofibrate

A trial is reported of the effects of giving clofibrate to prevent progression of pre-existing ischaemic heart disease. There were two groups randomly distributed between clofibrate (350 patients) and placebo (367 patients) regimens. The trial lasted about six years and was conducted in 19 hospitals in Scotland. The criteria of acceptance into the trial were precise and were monitored by one observer. The standards of diagnosis of events were defined and all protocols and electrocardiograms were read blind by one observer.Three categories of patients were admissible to the trial: (1) patients with one myocardial infarction (W.H.O. E.C.G. criteria) between 8 and 16 weeks before the start of the trial; (2) patients with angina of a duration of 3 to 24 months, provided their E.C.G. showed signs of myocardial ischaemia at rest or after exercise; and (3) patients with one recent myocardial infarction and pre-existing angina as defined above.There were fewer deaths in patients with angina (categories 2 and 3 above) treated with clofibrate than in those on placebo. The mortality in the former group was reduced by 62%, and this is a statistically significant difference. Clofibrate did not have any statistically significant effect in reducing the rate of non-fatal infarction in patients with angina or in those with myocardial infarction and pre-existing angina, though a beneficial trend was evident when both subgroups were combined (a 44% reduction compared with the placebo group). There was a significant reduction in all events (fatal and non-fatal) in patients with angina (“all anginas”) in the clofibrate-treated group; the rate was reduced by 53%.Clofibrate did not alter the overall mortality or morbidity rates in patients admitted to the trial with recent myocardial infarction without preceding angina of more than three months'' duration. In one subgroup there was a statistically significant adverse effect in the clofibrate-treated group. The lack of any overall effect in patients with myocardial infarction might be related to the unexpectedly low mortality rate (2·97%) in the placebo group; it is usually in the region of 4-9% per annum after first myocardial infarction.In patients categorized as “all anginas” there was significant reduction in events whether the initial serum cholesterol level was high (greater than 260 mg/100 ml) or normal. Clofibrate seemed to have a small but not significant beneficial effect in patients with myocardial infarction with initially high serum cholesterol levels, but was of no value in those with initially normal serum cholesterol levels. There was no significant relationship between the response or lack of response of serum cholesterol to clofibrate and the incidence of events either in patients with angina or in those with infarction.The main conclusion of this trial is that clofibrate had a beneficial effect in reducing mortality and, to a lesser extent, morbidity in patients who presented with angina (“all anginas”). This effect was independent of initial serum cholesterol levels or the extent to which serum cholesterol was lowered. The drug had no significant overall effect on prognosis in patients with myocardial infarction alone.     

The effect on winter illness of large doses of vitamin C

Between December 1972 and February 1973, 2349 volunteers participated in a double-blind trial to assess the effect of large doses of vitamin C on the incidence and severity of winter illness. In addition, records were kept but no tablets taken during March. Subjects were randomly allocated to eight treatment regimens: three prophylactic-only (daily dose 0.25, 1 or 2 g), two therapeutic-only (4 or 8 g on the first day of illness), one combination (1 g daily and 4 g on the first day of illness), and two all-placebo. None of the groups receiving vitamin C showed a difference in sickness experience that was statistically significant from that of the placebo groups, but the results obtained were compatible with an effect of small magnitude from both the prophylactic and therapeutic regimens, and an effect of somewhat greater magnitude from the combination regimen. The combination regimen was associated more with a reduction in severity than frequency of illness, although the extra dosage was limited to the first day of illness. In spite of the eightfold range in daily dose, the three prophylactic-only regimens showed no evidence of a dose-related effect, but the 8 g therapeutic dose was associated with less illness than the 4 g therapeutic dose. There was no evidence of side effects from the 1 and 2 g prophylactic doses of vitamin C, and no evidence of a rebound increase in illness during the month following withdrawal of the daily vitamin supplements. On the basis of this and other studies it is suggested that the optimum daily dose of vitamin C is less than 250 mg, except possibly at the time of acute illness, when a larger daily intake may be beneficial.     

Comparison of day 2 and overnight day 3 frozen embryo transfers: A prospective randomized controlled trial

In certain patients cleavage stage embryos may be preferred. The relationship between an additional day in culture and pregnancy outcomes is not well established. We aimed to compare outcomes of day 2 versus overnight day 3 frozen embryo transfer (FET). In this randomized controlled trial, patients with day 2 cryopreserved embryos were allocated to two groups. In group A embryos were transferred on day 2, the same day of thawing. In group B embryos were transferred one day after thawing, on day 3 after overnight incubation. Out of 410 patients eligible, 92 were recruited. Finally, 72 patients participated, 39 in group A and 33 in group B. No significant difference in implantation (11 % in group A and 14 % in group B, p = 0.81), clinical pregnancy (18 % in group A and 21 % in group B, p = 0.73) or live birth rates (13 % in group A and 18 % in group B, p = 0.53) was found. To conclude, no significant difference in reproductive outcomes was found when comparing patients with day 2 or overnight day 3 FET. Considering published data on blastocyst transfer, cleavage stage ET may still be a relevant option and the decision between day 2 or overnight day 3 ET depends on patients’ and physicians’ preference and recommendation.     

A life support-based comprehensive treatment regimen dramatically lowers the in-hospital mortality of patients with fulminant myocarditis: a multiple center study

Fulminant myocarditis(FM) has unacceptable high mortality. This study aimed to evaluate the therapeutic efficacy of a life support-based comprehensive treatment regimen(LSBCTR), a completely novel treatment regimen, for FM. A total of 169 FM patients recruited from January 2008 to December 2018 were divided into two groups: patients receiving LSBCTR(81 cases),which includes(i) mechanical life support(positive pressure respiration, intra-aortic balloon pump with or without extracorporeal membrane oxygenation),(ii) immunomodulation therapy using sufficient doses of glucocorticoids and immunoglobulins, and(iii) application of neuraminidase inhibitors, and those receiving conventional treatment(88 cases). The endpoints were in-hospital death and heart-transplantation. Of all the population, 44 patients(26.0%) died in hospitals. Inhospital mortality was 3.7%(3/81) for LSBCTR group and 46.6%(41/88) for traditional treatment(P0.001). Early application of LSBCTR, mechanical life support, neuraminidase inhibitors, and immunomodulation therapy significantly contributed to reduction in in-hospital mortality. This study describes a novel treatment regimen for FM patients that dramatically reduces inhospital mortality. Its generalization and clinical application will efficiently save lives although further optimization is needed.This study offers an insight that virus infection induced inflammatory waterfall results in cardiac injury and cardiogenic shock and is the therapeutic target.     

Control of severe pain with sustained-release morphine tablets v. oral morphine solution.

Recently a sustained-release morphine sulfate tablet (MS Contin [MSC]) was introduced in Canada. In a randomized double-blind crossover trial we compared MSC given every 12 hours with a morphine sulfate solution (MSS) given every 4 hours to 17 patients suffering from chronic severe pain. After titration of the morphine dosage to optimize the analgesic effect, each patient received 10 days of therapy with either MSC or MSS, then 10 days of therapy with an equal daily dose of the other formulation. Both preparations provided effective pain control, with minimal side effects. There was no significant difference between MSC and MSS in pain scores on a visual analogue scale (VAS), severity scores for tiredness and nausea, amount of supplemental morphine needed for break-through pain or patient preference. The plasma morphine concentrations tended to be greater during treatment with MSC. The study had an 89% probability of detecting a clinically significant difference in VAS pain scores. We conclude that an individualized, twice-daily regimen of MSC is as effective as MSS given every 4 hours for control of severe pain. The twice-daily regimen has several advantages: it provides for an uninterrupted night''s sleep, it is substantially more convenient than the six doses per day required with MSS, and it should help reduce both medication errors and noncompliance.     

Controlled Comparison of Oral Twice-weekly and Oral Daily Isoniazid plus PAS in Newly Diagnosed Pulmonary Tuberculosis

A controlled clinical trial was undertaken in 247 patients with newly diagnosed pulmonary tuberculosis to assess the relative efficacies of a fully supervised twice-weekly oral regimen of isoniazid plus PAS (para-aminosalicylic acid) and a standard self-administered daily regimen of the same drugs following an initial intensive phase of two weeks of daily streptomycin, PAS, and isoniazid. Among patients who had isoniazid-sensitive cultures initially and who attended the clinic regularly the numbers with a favourable bacteriological response at the end of the year of chemotherapy were 79 (88%) out of 90 for the twice-weekly regimen and 72 (87%) out of 83 for the daily regimen; the numbers of patients with considerable radiographic improvement were 54 (60%) and 53 (64%) respectively. Complaints of vomiting or diarrhoea that did not require a reduction of the PAS dosage were made on one or two occasions by 23(21%) out of 109 twice-weekly and 25 (23%) out of 108 daily patients, and on at least three occasions by 4 (4%) and 12 (11%) respectively. Finally, all five patients who had chemotherapy changed on account of hypersensitivity to PAS had been receiving the daily regimen, as also had one patient who died of agranulocytosis.     

Incidences of fatal postoperative pulmonary embolism after prophylaxis with dextran 70 and low-dose heparin: an international multicentre study.

A total of 4352 patients were admitted to a prospective'' randomised multicentre trial comparing the prophylactic efficacy of dextran 70 and low-dose heparin against fatal pulmonary embolism after elective operations for general, orthopaedic, urological, and gynaecological conditions. Out of 3984 patients correctly admitted, 1993 were allocated to receive dextran 70 and 1991 to receive low-dose heparin. Withdrawal of prophylaxis because of bleeding or technical difficulties occurred more often in the heparin group, but allergic reactions were more common in the dextran group. Of the 75 patients who died within 30 days after operation, 38 had been given dextran and 37 low-dose heparin. Necropsy was performed in 33 and 32 of these cases respectively. In six patients in each group pulmonary embolism was the sole or a contributory cause of death. Of these, five patients in the dextran group and two in the heparin group had received a full course of prophylaxis. There was no statistically significant difference between the two treatment groups in the incidence of fatal pulmonary embolism after a full course of prophylaxis.     

Optimal timing of operation for bleeding peptic ulcer: prospective randomised trial.

From October 1980 to September 1983 all patients with upper gastrointestinal bleeding were admitted to a centralised unit and investigated by early endoscopy. A total of 142 patients with a proved duodenal or gastric ulcer were randomised after stratification for age and site of ulcer to early (aggressive) surgical management or a delayed (conservative) policy. Significantly more operations (n = 42; 60%) were performed in the early than in the delayed (n = 9; 20%) groups (p less than 0.01). There were no deaths among the 42 patients under 60. The overall mortality in the 100 patients aged over 60 was 10% and when analysed on an "intention to treat" basis there was no difference between early and delayed surgery. When, however, an unrelated death from a bleeding colonic polyp was excluded and the data analysed on "treatment received" the mortality was only 2% in the early group compared with 13% in the delayed group (p less than 0.05). When analysis was confined to gastric ulcer the difference between early (0%) and delayed (24%) treatment was even greater. The results of this trial indicate that for patients over 60 an aggressive surgical policy is associated with a significant reduction in mortality.     

Some observations on the effect of Daflon (micronized purified flavonoid fraction of Rutaceae aurantiae) in bancroftian filarial lymphoedema

BACKGROUND: Morbidity management is a core component of the global programme for the elimination of lymphatic filariasis. In a double-blind clinical trial, the tolerability and efficacy of Daflon (500 mg) + DEC (25 mg) or DEC (25 mg) alone, twice daily for 90 days, was studied in 26 patients with bancroftian filarial lymphoedema. RESULTS: None of the patients in either drug group reported any adverse reaction throughout the treatment period (90 days). Haematological and biochemical parameters were within normal limits and there was no significant difference between the pre-treatment (day 0) and post-treatment (day 90) values. The group receiving Daflon showed significant reduction in oedema volume from day 90 (140.6 PlusMinus; 18.8 ml) to day 360 (71.8 PlusMinus; 20.7 ml) compared to the pre-treatment (day 0, 198.4 PlusMinus; 16.5 ml) value. This accounted for a 63.8% reduction in oedema volume by day 360 (considering the pre-treatment (day 0) as 100%). In the DEC group, the changes in oedema volume (between day 1 and day 360) were not significant when compared to the pre-treatment (day 0) value. The percentage reduction at day 360 was only 9%, which was not significant (P > 0.05). CONCLUSION: This study has shown that Daflon (500 mg, twice a day for 90 days) is both safe and efficacious in reducing oedema volume in bancroftian filarial lymphoedema. Further clinical trials are essential for strengthening the evidence base on the role of this drug in the morbidity management of lymphatic filariasis.     

Heparin Prophylaxis against Fatal Postoperative Pulmonary Embolism

Low-dose heparin prophylaxis against fatal pulmonary embolism has been studied in a random and prospective trial in 300 patients over the age of 50 who underwent major surgery. A dose of 5,000 IU mucous heparin sodium given two hours preoperatively and for five days post operatively prevented fatal pulmonary embolism in all 156 patients so treated, whereas out of 144 patients in the unheparinized group 6 (4·2%) died of pulmonary embolism. This difference is statistically significant. There was no increase in operative or post-operative bleeding or in the formation of wound haematomas in the heparinized group.     

重组人E1A激活基因阻遏子/myc-His融合糖蛋白的纯化及功能鉴定

目的:纯化重组人E1A激活基因阻遏子(hCREG)糖蛋白,验证重组hCREG糖蛋白具有抑制体外培养的人胸廓内动脉平滑肌细胞(HITASY)增殖的生物学功能。方法:根据6×His亲和层析原理,应用Ni-NTA柱纯化重组hCREG蛋白,纯化后蛋白通过HiTrap脱盐柱脱盐。用流式细胞周期分析研究添加0.5μg/ml、1μg/ml及2μg/ml重组hCREG/myc-His融合糖蛋白对体外培养HITASY细胞增殖的影响。用BrdU掺入方法研究重组蛋白对体外培养HITASY细胞增殖的影响。结果:根据6×His亲和层析原理用Ni-NTA纯化重组hCREG蛋白,浓缩并脱盐后的重组hCREG蛋白浓度为1.6mg/ml,纯度为92%,此蛋白仍保留了糖基化形式。流式细胞仪细胞周期分析结果提示重组hCREG蛋白可抑制体外培养的HITASY细胞增殖,且低浓度组的抑制效应要高于高浓度组。BrdU掺入实验结果提示,添加2μg/ml重组hCREG蛋白组与对照组相比可显著抑制体外培养的HITASY细胞增殖,组间比较有统计学差异(P0.05)。结论:具有生物学功能的重组hCREG/myc-His糖蛋白的成功纯化,为hCREG蛋白的功能研究及生物工程制备提供了实验平台。     

Long-term Anticoagulant Therapy after Myocardial Infarction in Women

A multicentre trial from five medical departments in Oslo has been carried out to determine the value in women patients of one year''s long-term anticoagulant therapy. Follow-up long-term laboratory control and anticoagulant dosage were performed at one centre (the Rikshospitalet). One hundred and fifty-nine patients were assigned randomly into two similar well-matched groups (control and treatment). Dosage was controlled by Thrombotest, aiming at 10–20% levels, and 50% of the tests were less than 14%. Compared with the control group, the treatment group showed a significant reduction in mortality and in reinfarction rate. No serious bleeding complications occurred. It is concluded that women benefit as much as men from long-term anticoagulant therapy.     

Reduction in mortality after myocardial infarction with long-term beta-adrenoceptor blockade. Multicentre international study: supplementary report.

In a controlled multicentre trial carried out to assess the value of long-term practolol treatment after myocardial infarction the provisional results showed a significant reduction in mortality, though some of the data were lacking. These have now been included and the results updated. The final figures for all deaths were 78 in the placebo group of 1533 patients and 48 in the practolol group of 1520 patients. The reduction in mortality (38%) was significant at the 1% level. The figures for non-fatal reinfarction (97 in the placebo group, and 75 in the practolol group) were not significantly different. Patients with pre-entry anterior infarction, and especially those with a diastolic blood pressure equal to or below the mean (78 mm Hg) at entry to the trial, were at high risk but benefited particularly well from beta-adrenoceptor blockade. After pre-entry inferior infarction the percentage reduction in deaths occurring within two hours after symptoms of a new event was similar to that after anterior infarction, but the incidence of death more than two hours after the event was greater in the practolol-treated group. Thus the difference between groups in total deaths after pretrial inferior infarction was marginal. Until the results of further trials are reported long-term beta-adrenoceptor blockade (possibly up to two years) is recommended after uncomplicated anterior myocardial infarction.