大黄苷元联合溶栓对血栓栓塞性脑缺血大鼠肺胃损伤的保护作用

目的:观察大黄苷元联合溶栓治疗对大鼠脑缺血损伤肺胃组织的保护作用。方法:实验于2005-08/2006-07在河南中医学院老年医学研究所实验室完成。①260只SD大鼠采用随机数字法分为假手术组20只、模型组60只、尿激酶组60只、大黄苷元组60只、大黄苷元 尿激酶组60只;除假手术组外,其余各组根据缺血后动脉用药时间又各分为3,6,9h3个时间点,每个时间点20只。②自体血栓结合线栓阻塞大鼠大脑中动脉制备局灶性脑缺血动物模型。③各组大鼠均于术前4d灌胃用药,大黄苷元组、大黄苷元 尿激酶组用大黄苷元灌胃(灌胃体积为每100g大鼠1mL),假手术组、模型组和尿激酶组用等体积的生理盐水灌胃;动脉用药除假手术组外,其余各组分别于造模后3,6,9h经导管由区域动脉给药,尿激酶组与大黄苷元 尿激酶组用尿激酶(用药体积为20μL),模型组和大黄苷元组区域动脉用同等体积的生理盐水。④动脉给药后24h,观察大鼠脑组织病理损伤、颅内和胃出血率、脑和肺组织含水量、肺和胃病理损伤变化。结果:实验过程中因麻醉、操作等原因死亡及剔除大鼠156只,进入结果分析104只。①颅内和胃出血率:尿激酶组9h大鼠颅内出血率较模型组高(66.67%,28.57%,P<0.05);尿激酶组9h脑和胃出血率较3h高(脑:66.67%,18.75%;胃:41.18%,17.65,P<0.05);大黄苷元 尿激酶组9h颅内出血率较尿激酶组9h低(P<0.05)。②脑和肺及胃组织病理改变:各模型组大鼠脑、胃和肺组织病理损伤均较假手术组明显;各用药组脑和肺组织分别较相应时间模型组减轻;各组脑、胃和肺组织损伤9h均较其3h明显;大黄苷元 尿激酶组9h较相应时间点尿激酶组和大黄苷元组损伤减轻(P<0.05)。③脑和肺组织含水量:各模型组脑和肺组织含水量均较假手术组增高(P<0.01);尿激酶组和大黄苷元 尿激酶组各时间点均较模型组降低(P<0.01);各组9h分别较其3h脑和肺含水量增加(P<0.01,P<0.05);大黄苷元 尿激酶组6h脑组织和9h肺含水量分别较尿激酶组降低(P<0.05)。结论:脑缺血后延迟溶栓治疗可引起大鼠脑和胃出血率增高、脑组织和肺组织水肿加重,脑和肺及胃组织病理损伤明显;大黄苷元联合溶栓可降低脑出血率,改善神经细胞超微结构,降低脑和肺组织含水量,对脑缺血肺和胃组织损伤具有保护作用。     

Bronchoscopy and Tuberculostearic Acid Assay in the Diagnosis of Sputum Smear-negative Pulmonary Tuberculosis: A Prospective Study with the Addition of Transbronchial Biopsy

A prospective study of the efficacy of bronchoscopy and tuberculostearicacid assay in the diagnosis of sputum smear-negative pulmonarytuberculosis (TB) was carried out in 39 patients with symptomsand radiographic changes suggestive of active pulmonary TB.The diagnosis of TB was confirmed in 15 patients, probable TBwas diagnosed in eight and 16 patients did not have TB. An earlydiagnosis of TB was made by bronchoscopy in six patients (40per cent). Culture of sputum obtained before bronchoscopy waspositive in nine patients (60 per cent) while combined withbronchoscopy specimens, a positive mycobacterial culture wasobtained in 12 patients (80 per cent). Mycobacteria were culturedfrom transbronchial biopsy specimens from five patients (33per cent) but none of these was exclusively positive. Histologicalexamination of transbronchial biopsy tissue was diagnostic ofTB in four patients and it was the exclusive means of earlydiagnosis in two. Transbronchial biopsy also provided an alternativediagnosis in four other patients. Tuberculostearic acid assayhad a sensitivity of 0.40 in bronchial aspirate, 0.80 in bronchoalveolarlavage fluid, and 0.27 in transbronchial biopsy specimens: thecombined result was 0.87. In nine patients with pulmonary TBin whom an early diagnosis could not be made, the tuberculostearicacid assay was positive in seven (78 per cent). We concludethat bronchoscopy with bronchoalveolar lavage and transbronchialbiopsy is helpful in providing early diagnosis and positiveculture results. Assay of tuberculostearic acid in bronchoalveolarlavage fluid is a useful adjunct to early diagnosis. However,mycobacterial culture and assay of tuberculostearic acid intransbronchial biopsy specimens have little diagnostic value.     

心肌梗死大鼠心肌细胞凋亡及磷酸肌酸的干预

目的:缺血引起的心肌能量供应不足是心肌细胞凋亡主要的因素之一,观察补充外源性能量磷酸肌酸对缺血心肌细胞凋亡和心功能的影响。方法:实验于2003-04/06在解放军总医院老年心血管病研究所实验室完成。选用SD大鼠50只,按随机数字表法分为3组:①磷酸肌酸组19只,结扎左冠状动脉制作心肌梗死模型,结扎前30min按200mg/kg的剂量腹腔注射磷酸肌酸1次。②缺血对照组21只,心肌缺血方法同磷酸肌酸组,结扎前30min腹腔注射相同体积的50g/L葡萄糖注射液1次。③正常对照组10只,仅在冠状动脉下穿线,不结扎冠状动脉,其余同缺血对照组。结扎冠状动脉6h后,取各组大鼠心脏标本做石蜡切片,缺口末端标记法染色,高倍镜下计数心肌细胞凋亡指数,凋亡指数=凋亡心肌细胞数/心肌细胞总数;取心脏标本前,测左心室收缩压、舒张末压和压力变化速度,并进行组间比较。结果:磷酸肌酸组大鼠造模时死亡9只;缺血对照组造模时死亡10只,造模成功后6h内死亡1只,进入结果分析共30只大鼠,每组10只。①缺血对照组大鼠的左心室舒张末压显著高于正常对照组[(13.9±5.3vs.2.8±3.2)mmHg(P<0.01)],左心室压力变化速度显著低于正常对照组[(705.8±111.7vs.1141.7±94.5)mmHg/s(P<0.01)];磷酸肌酸组大鼠的左心室舒张末压显著低于缺血对照组[(8.9±3.5)mmHg(P<0.05)];左心室压力变化速度显著高于缺血对照组[(841.5±76.1)mmHg/s(P<0.01)];左心室收缩压与缺血对照组差异无显著性意义(P>0.05)。②磷酸肌酸组大鼠的心肌细胞凋亡指数显著低于缺血对照组(0.203±0.054vs.0.278±0.052,P=0.006)。结论:补充外源性能量磷酸肌酸可以减少缺血后心肌细胞凋亡,并改善心功能,磷酸肌酸抑制缺血心肌细胞凋亡可能是改善心肌梗死后心功能的主要作用途径之一。     

“You’ve got to breathe,you know” – asthma patients and carers’ perceptions around purchase and use of asthma preventer medicines

Objective : To explore influences on patients’ purchase and use of asthma preventer medicines and the perceived acceptability of financial incentives via reduced patient co‐payments. Methods : Semi‐structured telephone or face‐to‐face interviews were conducted with adults and carers of children with asthma. Interviews were recorded, transcribed verbatim and coded. Data were analysed using thematic analysis via grounded theory. Results : Twenty‐four adults and 20 carers for children aged 3–17 years with asthma were interviewed. For medicines choice, most participants did not consider themselves the primary decision‐maker; cost of medicines was an issue for some, but effectiveness was described as more important. For adherence, cost, side‐effects, perceived benefit and patient behaviours were important. Conclusions : Patient barriers to adherence with asthma preventer medicines including cost are ongoing. Healthcare professionals need to encourage empathic discussion with patients about cost issues. Implications for public health : Asthma patients and carers could benefit from greater involvement and respect within shared decision‐making. Healthcare professionals should be aware that cost may be a barrier for patient adherence, and provided with information about the relative costs of guideline‐recommended asthma medicines. Patients and healthcare professionals need education around the efficacy of ICS‐alone treatment and the rationale behind co‐payments, for initiatives around quality use of medicines to succeed.     

Brivudin compared with famciclovir in the treatment of herpes zoster: effects in acute disease and chronic pain in immunocompetent patients. A randomized, double-blind, multinational study

OBJECTIVE: This was a double-blind, randomized multicentre trial comparing efficacy and safety of brivudin (125 mg, once a day) and famciclovir (250 mg, three times a day), both given orally for 7 days, in the treatment of herpes zoster. METHODS: A total of 2027 immunocompetent zoster patients>or=50 years with zoster-related pain at presentation were included. Outcome measures embraced prevalence of postherpetic neuralgia (PHN), defined as at least moderate pain 3 months after treatment initiation, duration of PHN, prevalence and duration of zoster-associated pain (ZAP), duration of vesicle formation and rash healing. RESULTS: The prevalence of PHN at month 3 was 11.3% with brivudin and 9.6% with famciclovir [per-protocol (PP) population]. Equivalence of the two drugs could be demonstrated (P=0.01, PP and intention-to-treat analysis). The median duration of PHN was 46.5 days with brivudin and 58 days with famciclovir (P=0.54, PP analysis). Prevalence and duration of ZAP did not differ significantly between treatment groups. The prevalence of PHN was higher in patients>or=65 years (brivudin: 16.4%, famciclovir: 16.4%), and in patients with severe rash (brivudin: 13.4%, famciclovir: 15.7%), without significant differences between treatment groups. In patients>or=65 years, median duration of PHN was shorter with brivudin than with famciclovir (39.5 vs. 57.5 days), although the difference was not statistically significant. The two drugs had equivalent efficacy in being able to accelerate the stop of vesicle formation, and lesion healing. Adverse events were similar in nature and prevalence among groups. CONCLUSIONS: The study demonstrated equivalent efficacy of brivudin and famciclovir in the treatment of herpes zoster regarding the prevention of chronic pain and the resolution of signs and symptoms of acute herpes zoster. Compared with famciclovir, brivudin provides equivalent efficacy and safety at a more convenient once-daily dose schedule.     

Association between human recombinant EPO and peripheral vascular disease in diabetic patients receiving peritoneal dialysis

Peripheral vascular disease is a serious and frequent problem in diabetic patients. Since the beginning of the widespread use of erythropoietin (EPO), we have noted an increase in peripheral vascular disease in diabetic patients receiving peritoneal dialysis and erythropoietin. This prompted us to study the effects of erythropoietin on peripheral vascular disease in patients receiving peritoneal dialysis. We retrospectively reviewed medical records of all diabetic patients in our program who received peritoneal dialysis from 1990 to 1996. Demographic and laboratory data as well as EPO use data were collected. Hospital days and occurrence of vascular events (defined as peripheral vascular surgery, amputation, or recommendation of vascular surgery or amputation by a vascular surgeon) were determined for diabetic patients receiving peritoneal dialysis. Comparisons were made between those who received EPO and those who did not received EPO, as well as comparing vascular events in 28 patients who received peritoneal dialysis before and after beginning EPO. Patients who received erythropoietin were found to have a significantly shorter time to a first vascular event, a greater number of vascular events, and more hospital days associated with vascular disease than diabetic patients who did not receive erythropoietin. With multivariate analysis, significant risk factors for the development of peripheral vascular disease in these patients were erythropoietin use, erythropoietin dose, and smoking. Twenty-eight patients who initially performed peritoneal dialysis without receiving EPO, and later received EPO, had a significant increase in vascular events, including amputations only while receiving EPO. We found the use of erythropoietin to be associated with peripheral vascular events in diabetic patients who receive peritoneal dialysis. Further investigation is warranted.     

A randomized prospective comparison of oral versus intraperitoneal ofloxacin as the primary treatment of CAPD peritonitis

Summary: Oral ofloxacin has been successfully used in our centres for the primary treatment of peritonitis complicating continous ambulatory peritoneal dialysis (CAPD). In view of the progressive rise in the resistance rate to ofloxacin among peritoneal bacterial isolates, a study was conducted to determine if oral ofloxacin remains a viable first line treatment for CAPD peritonitis in our centres and if the result can be improved by changing from an oral to an intraperitoneal (i.p.) route. In patients on three 2 L daily CAPD exchanges, ofloxacin given at the i.p. dosage of 200 mg loading followed by 25 mg/L of peritoneal dialysate achieved overnight trough peritoneal levels which are at least four times the minimal 90% inhibitory concentration (MIC90) of most bacterial pathogens without significant accumulation in the systemic circulation. This i.p. dosage was therefore chosen for the clinical study and the result was compared to that using ofloxacin given in the oral dosage of 400 mg loading followed by 300 mg once daily as maintenance. of all the recruited episodes, 35 were eligible for analysis. the overall primary cure rate including primary failures and relapses was 55.6% (10/18) in the oral treatment group and 70.6% (12/17) in the i.p. treatment group. the corresponding figures for gram positive bacterial (g +) infections were 36.4% and 50%, for gram negative bacterial (g -) infections were 66.7 and 80% and for culture negative infections were 75 and 80%. In culture positive cases, all treatment failures were due to resistant infections which were observed in 42.3% of all bacterial isolates, 47.1% of g + isolates and 33.3% of g - isolates. Due to the high background level of bacterial resistance among our CAPD population, ofloxacin monotherapy given either by the oral or the i.p. route can no longer be recommended for the primary treatment of CAPD peritonitis.     

Patient preferences for managing asthma: results from a discrete choice experiment

Effective control of asthma requires regular preventive medication. Poor medication adherence suggests that patient preferences for medications may differ from the concerns of the prescribing clinicians. This study investigated patient preferences for preventive medications across symptom control, daily activities, medication side-effects, convenience and costs, using a discrete choice experiment embedded in a randomized clinical trial involving patients with mild-moderate persistent asthma. The present data were collected after patients had received 6 weeks' treatment with one of two drugs. Three choice options were presented, to continue with the current drug, to change to an alternative, hypothetical drug, or to take no preventive medication. Analysis used random parameter multinomial logit. Most respondents chose to continue with their current drug in most choice situations but this tendency differed depending on which medication they had been allocated. Respondents valued their ability to participate in usual daily activities and sport, preferred minimal symptoms, and were less likely to choose drugs with side-effects. Cost was also significant, but other convenience attributes were not. Demographic characteristics did not improve the model fit. This study illustrates how discrete choice experiments may be embedded in a clinical trial to provide insights into patient preferences.     

General practitioner-delivered adherence counseling in asthma: feasibility and usefulness of skills,training and support tools

Objective: Poor medication adherence contributes to uncontrolled asthma in primary care. Good doctor-patient communication around adherence increases patients’ medication taking but general practitioners (GPs) often feel poorly equipped to provide effective adherence counseling. This study aimed to assess the feasibility and usefulness of adherence counseling training, skills and support tools for GPs. Methods: Twenty-five GPs enrolled in a 6-month cluster randomized-controlled trial of adherence interventions for asthma were randomized to an intervention delivering personalized adherence discussions. They received 2 hours training in delivering brief, motivational-interviewing-based adherence counseling and were provided with asthma-specific counseling support tools. At baseline, post-training and study end, GPs rated the training, reported confidence/frequency of using counseling skills and satisfaction with their consultations, and commented on support tools. Patients reported their barriers to adherence and rated their GPs empathy at baseline and at 6-months. Results: 96% of GPs rated adherence counseling training as very/extremely useful. At the end of the study (17?±?4 months) GPs’ confidence in using counseling skills increased, as did the frequency they applied the skills and their satisfaction with consultations. GPs were positive about counseling support tools, stating that they were easy to use and facilitated covering more ground within single consultations. Half the GPs expressed some difficulty implementing counseling due to time constraints. Patients reported good GP empathy and no significant change in adherence barriers. Conclusions: GPs valued counseling training and support tools. Although implementation was sometimes challenging, GPs reported increased frequency of use and confidence in applying adherence counseling skills, which persisted for 17 months.