右旋佐匹克隆Ⅰ期耐受性试验

目的 评价健康受试者单次口服右旋佐匹克隆的安全性和耐受性。方法 选择18～45岁的健康受试者26例，随机分为1．8，3、75，7．5，11．25和15．0mg共5个剂量组。观察指标有临床症状、生命体征、血尿常规、肝。肾功能、电解质和心电图。结果 在1．8～11．25mg，各项观察指标在服药前后没有明显变化，主要药物不良反应为口苦和头晕，高剂量(15mg)出现恶心呕吐、走路不稳等。结论 剂量在1．8～11．25mg，右旋佐匹克隆的安全性和耐受性较好。     

倍哚普利和非洛地平治疗高血压的比较

比较30例倍哚普利与30例非洛地平治疗的降压效果。两组剂量分别为4mg／日和5mg／日2次。4周后未达目标血压（≤140／90mmHg）者，加倍剂量。8周后倍哚普利组未达目标血压者，加用小剂量氯噻嗪。结果：8周后非洛地平组血压下降23／20mmHg，80％达到目标血压；倍哚普利组分别为11／10mmHg及36．3％（P值均＜0．01）。倍哚普利加氯噻嗪（12．5mg／日）后，血压进一步下降14／gmmHg，70．0％达到目标血压。非洛地平、倍哚普利及加用氯噻嗪三组的显效率和总有效率分别为93．3％，100．0％；43，3％，63．3％；86．7％，96．7％。非洛地平和倍哚普利均具有降压效果，非洛地平优于信哚普利。倍哚普利和小剂量氯噻嗪联合应用可达到满意的血压下降。     

健康志愿者单次皮下注射重组人胰高血糖素类多肽-1(7-36)[rhGLP-1(7-36)]耐受性研究

目的：在中国健康成年志愿者中评价单次皮下注射重组人胰高血糖素类多肽-1（7-36）[rhGLP-1（7-36）]的安全性、耐受性。方法：根据GCP设计试验方案，并获得伦理委员会批准。受试者须自愿签署知情同意书。选择42名18～50岁健康成人，将受试者随机分至0．10～0．45mg7个剂量组，每组6名，男女各半，分别接受单次皮下注射rhGLP-1（7-36），进行临床和实验室检查，考察药物耐受性。结果：单次皮下注射rhGLP-1（7-36）耐受性试验中，各组受试者各项指标测定值均在正常范围内，条件均衡，具较好可比性。因剂量至0．30mg时，不良事件（恶心、呕吐）在该组发生率超过50％，故于该剂量组试验完成后终止了下一剂量组试验，仅有4个剂量组共24名健康受试者完成了本试验。24例受试者完成的4个剂量组耐受性试验中，给药后实验室检查未见有临床意义的改变。试验中出现10例（共15例次）可能与药物有关的不良反应，如头晕、恶心、呕吐等，但均可耐受，且为一过性反应，于给药后1h内自行消失。其中，不良反应主要发生在0.25、0．30mg组（共7例12例次），而低剂量组（0．10、0．20mg）仅有3例发生轻度不良反应。15例次不良反应中，头晕、恶心有10例次，呕吐有5例次；整个试验过程未见严重不良事件。结论：24名中国健康成年受试者分别单次皮下注射rhGLP-1（7-36），最大剂量至0．20mg，比较安全、耐受性较好，为最大耐受剂量。而单次给药剂量至0．25mg或0．30mg则不良反应发生率较高，最大耐受剂量为0．20mg。建议单次用药剂量不宜超过0．20mg。在Ⅱ期临床试验中需严密观察恶心、呕吐这些与药物可能有关的不良反应及其发生机制。     

右旋与消旋佐匹克隆治疗睡眠障碍的随机双盲双模拟临床试验

目的以消旋佐匹克隆为阳性对照药评价右旋佐匹克隆治疗睡眠障碍的疗效及安全性。方法用双盲双模拟随机对照临床试验方法，每晚睡前，分别口服（试验与对照药）右旋和消旋佐匹克隆口服3，7．5mg，疗程为14天。结果右旋佐匹克隆（试验组）为68例，痊愈率为20．59％；消旋佐匹克隆（对照组）为57例，痊愈率为14．04％。药物不良反应发生率分别为36．76％，49．12％。2组临床疗效及药物不良反应发生率比较具有统计学差异。结论右旋佐匹克隆治疗睡眠障碍，安全、有效。     

甲氯噻嗪片治疗轻中度原发性高血压的疗效和安全性

目的：观察甲氯噻嗪片治疗轻、中度原发性高血压的降压效果和安全性。方法：门诊轻、中度原发性高血压病人，随机分为甲氯噻嗪组和氢氯噻嗪组，每组各24例，分别服甲氯噻嗪2．5mg或氢氯噻嗪25mg，qd，治疗4周后舒张压≥90mmHg者剂量加倍，疗程8周。服药后每2周随访1次，测定血压和心率。治疗前后测定血、尿常规，血生化指标及心电图，并监测血钾，必要时口服补钾。结果：服药第2、4、6、8周末两组血压均较治疗前降低（P〈0．01）；治疗8周后与治疗前比较，甲氯噻嗪组和氢氯噻嗪组收缩压／舒张压（SBP／DBP）分别下降（16．0±7．9）／（15．7±5．2）mmHg和（17．2±6．4）／（16．2±5．0）mmHg；组间下降值无统计学差异；降压总有效率分别为87．5％和83．3％（P〉0．05）。两组治疗前后心率均无明显变化，不良反应轻微，出现较多的是头痛、头晕。甲氯噻嗪组和氢氯噻嗪组分别于用药4周后出现低血钾2例和1例，补钾后恢复正常。其余实验室指标无明显改变。结论：甲氯噻嗪片治疗轻、中度原发性高血压安全、有效。     

易瑞沙联合放化疗治疗肺癌脑转移的疗效观察

目的探讨易瑞沙联合放化疗治疗肺癌脑转移的疗效。方法将54例肺癌脑转移患者分为观察组30例与对照组24例，对照组采用放疗联合化疗治疗，观察组在对照组治疗基础上口服易瑞沙治疗，剂量为每天250mg，服用时间为从入组至开始至病情出现进展，比较两组患者的疗效及随访生存期。结果对照组治疗后完全缓解4例（16．7％），部分缓解10例（41．7％），无变化6例（25．0％），肿瘤进展4例（16．7％）；观察组治疗后完全缓解9例（30．0％），部分缓解16例（53．3％），无变化3例（10．0％），肿瘤进展2例（6．7％）；观察组治疗有效率显著高于对照组（P〈0．05）。随访28～40个月后观察组生存率为23．3％，对照组为12．5％，差异无统计学意义（P〉0．05）。不良反应：两组均出现不同程度的脱发、恶心、呕吐、白细胞及血小板减少状况，观察组患者服药3周内出现皮疹11例，其中Ⅰ度皮疹7例、Ⅱ度皮疹4例，服药2周内出现轻度腹泻9例。结论易瑞沙联合同步放化疗可增加对肺癌脑转移患者局部病灶的控制率，但不能显著提升生存率。     

小剂量阿司匹林不同时间给药对2型糖尿病患者CD62P表达的影响

目的：探讨小剂量阿司匹林不同时间给药对2型糖尿病患者血小板膜糖蛋白CD62p,表达水平的影响。方法：56例2型糖尿病不伴微血管病变患者,按就诊时间随机分为阿司匹林晨服组36例（100mg·d^-1,8：00服药）和晚服组20例（100mg·d^-1,20：00服药）,采用流式细胞术测定阿司匹林治疗前后血小板CD62p的表达,采用高效液相色谱法测定水杨酸血药浓度。结果：两组患者服药后CD62p阳性表达率均显著降低,服药前CD62p分别为（7．43±3．25）％,（7．28±2．94）％,服药后分别降为（5．69±2．81）％,（5．83±2．53）％,但两组差值无明显差异（P〉0．05）。水杨酸血药浓度分别为（2．39±0．92）和（0．85～4．11）mg·L^-1,与cD62P差值不相关（r=-0．175;P〉0．05）。结论：口服小剂量阿司匹林能够显著降低2型糖尿病不伴微血管病变患者血小板CD62P的表达水平,时辰给药对CD62P表达水平的影响不显著。     

左布匹卡因与罗比卡因用于手术后患者硬膜外自控镇痛的观察

目的：观察左布匹卡因与罗比卡因用于腹部手术后自控硬膜外镇痛（PCEA）的效果及不良反应。方法：60例ASAⅠ～Ⅱ级腹部手术患者，随机分为0．15％左布匹卡因加2mg／L芬太尼组（A组）30例与0．2％罗比卡因加2mg／L芬太尼组（B组）30例，以5mL／h行术后硬膜外泵注镇痛。记录术后4、8、24、48h的疼痛视觉模拟评分（VAS0～10分）、满意度评分、运动阻滞测试（改良Bromage评分）及术后活动能力4级评分；48h内按压PCA次数（PCAd）、PCA有效次数（PCAe）、D／D比值（PCAd／PCAe）及不良反应。结果：2组镇痛效果满意，2组各观察指标差别均无统计学意义（P〉0．05）。在术后第1天。A组有14例（46．7％）可以短时间行走，而B组有25例（83．3％）。第2天，A组有15例（50．0％）可以自由行走，而B组有26例（86．7％），2组差别有统计学意义（P〈0．05）。不良反应：恶心发生率A组13．3％（4／30），B组10．0％（3／30）。皮肤瘙痒发生率2组均为6．7％（2／30），差异无统计学意义（P〉0．05）。结论：0．15％左布匹卡因与0．2％罗比卡因用于患者术后硬膜外镇痛均可获得满意的效果，而0．2％罗比卡因较0．15％左布匹卡因术后活动能力恢复早。     

那格列奈治疗70岁以上2型糖尿病患者的疗效观察

目的：观察那格列奈治疗70岁以上2型糖尿病人的疗效及安全性。方法：70岁以上2型糖尿病患者95例，治疗前未用过任何降糖药物，在适当控制饮食的基础上，随机分为两组。观察组46例予那格列奈片60～180mg/次，起始剂量120mg，三餐前1～15min口服；对照组49人，予瑞格列奈片0．5—2mg／次，起始剂量1mg，三餐前1—15min口服。共治疗12周。观察空腹、餐后2h血糖，HbAlc，TG，TC，体重，低血糖发生率。结果：治疗后，两组患者FBG、PBG、HbAlc，TG、TC均较治疗前明显下降（P〈0．01）。而治疗后两比较，差异无统计学意义（P〉0．05）。观察组发生低血糖1例（2．2％）；对照组发生7例（14．3％），两组差异有统计学意义（P〈0．05）。结论：那格列奈对70岁以上2型糖尿病患者降糖效果确切．安全。     

放化疗联合治疗晚期非小细胞肺癌50例临床分析

目的比较同步放化疗和序贯放化疗的临床效果和毒性反应，探讨非小细胞肺癌化疗和放疗的顺序和时机。方法50例Ⅲ期非小细胞肺癌患者分为两组，序贯组（A组24例）先化疗后放疗；同步组（B组26例）放疗和化疗同时进行。序贯组为诱导化疗3个周期后开始放疗，放疗结束后再化疗1个周期，同步组为化疗同时开始放疗。两组患者放疗技术和剂量相同．总剂量为60GY／6周。化疔方案TP方案：紫杉醇135mg／m^2＋顺铂（DDP）80mg／m^2第1天。结果结束治疗．序贯组和同步组缓解率分别为70．8％、80．7％，两组比较差异无统计学意义（P〉0．05）。1、2、3年生存率A组分别为65％、25％、15％，B组为67％、43％、32％，差异无统计学意义（P〉0．05）。Ⅲ～Ⅳ度放射性食管炎的发生率分别为8．3％和23．1％（P〈0．05）；Ⅲ～Ⅳ度白细胞下降发生率分别为25．0％和61．5％（P〈0．05）。结论同步放化疗是治疗晚期非小细胞肺癌的一种较好的治疗方法。     

不同时间给药对非杓型高血压的影响

目的 探讨不同时间服用氨氯地平对非杓型高血压患者血压昼夜节律的影响.方法 经动态血压监测,选取非杓型高血压患者84例,随机分为两组:晨起服药组(n=42)和睡前服药组(n=42),分别于7:00～9:00和20:00～22:00服用氨氯地平5 mg,连续治疗12周.给药前后分别进行动态血压监测,观察晨起服药组和睡前服药对非杓型高血压患者昼夜血压节律的影响.结果 晨起服药组与睡前服药组在治疗后24 h平均收缩压及舒张压均明显降低(P<0.05),与晨起服药组相比睡前服药组夜间收缩压和舒张压明显下降(P<0.05),睡前服药组对非杓型高血压的血压模式明显改善,两组有效率分别为16.7%和47.6%(P<0.01).结论 对非杓型高血压患者采取睡前服用氨氯地平不但可以有效降低血压,还可以改善异常的血压昼夜节律,从而更好地保护靶器官.     

国产艾司佐匹克隆治疗失眠症的对照研究

目的:评价国产艾司佐匹克隆治疗失眠症的有效性和安全性。方法:采用多中心随机双盲双模拟、阳性药物平行对照的研究方法。入选228例,其中试验组113例,对照组115例。分别口服艾司佐匹克隆3～6 mg·d-1和佐匹克隆7．5～15 mg·d-1,疗程均为14 d。结果:睡眠障碍量表(SDRS)评分在治疗结束时两组较基线均显著降低(P<0．05);试验组和对照组的有效率分别为60．2％和62．6％,两组比较无显著性差异(P>0．05)。不良反应发生率分别为32．7％和33．9％,较常见的不良反应为口苦及头晕。结论:艾司佐匹克隆能改善睡眠,不良反应较少,是一种治疗睡眠障碍安全而有效的新药。     

Comparison of once daily atenolol, nitrendipine and their combination in mild to moderate essential hypertension.

1. The aim of the study was to compare the efficacy and the tolerability of treatment with atenolol (50-100 mg once daily), nitrendipine (20-40 mg once daily) and their combination (atenolol 50 mg + nitrendipine 20 mg) once daily in patients with mild to moderate essential hypertension. 2. The study was a randomised, double-blind, placebo controlled parallel groups design: blood pressures were measured at 'trough' effect (i.e. 24 h after dosing) to assess the adequacy of once-daily treatment. 3. Mean blood pressures (mm Hg) recorded on four occasions over 12 weeks of treatment were significantly lower both with atenolol (155/97 sitting: 155/104 standing) and with the combination of atenolol plus nitrendipine (153/96 sitting: 152/104 standing) than with placebo (169/108 sitting: 169/114 standing). Nitrendipine alone had no significant effect on blood pressure 24 h after dosing (165/104 sitting: 165/110 standing). 4. Withdrawals due to adverse effects were more common during treatment with nitrendipine: 7/32 of the patients experienced adverse effects attributable to intense systemic vasodilatation (e.g., flushing, erythema, headache). 2/37 patients taking atenolol were withdrawn: one because he developed a psoriatic rash and the other because of impaired peripheral circulation. Of the 35 patients taking combination treatment, two were withdrawn: one developed headaches and dyspnoea, and the other asthma. 5. The results suggest that once daily dosing with nitrendipine does not control blood pressure throughout the 24 h period in the majority of patients, and is associated with a considerable burden of adverse effects. Combination treatment was better tolerated but appeared to offer no advantages over atenolol alone in terms either of blood pressure control or adverse effects.     

Reduction in the elevated blood pressure of Dahl salt-sensitive rats treated chronically with L-5-hydroxytryptophan

Rats of the Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) strains were placed on a 4% NaCl diet and blood pressures were monitored. Chronic subcutaneous infusion L-5-hydroxytryptophan (L-5-HTP, 12.6 mg/day) by osmotic minipumps significantly decreased the elevated systolic blood pressure of DS rats on a 4% NaCl diet. Blood pressures of DR rats were unaffected by treatment with L-5-HTP. Cardiac hypertrophy was associated with Dahl salt-induced hypertension. However, treatment with L-5-HTP failed to reduce the weight of the heart significantly. These results suggest that chronic administration of L-5-HTP was effective in reducing the elevated blood pressure in the DS model. The specific mechanisms by which L-5-HTP reduces the elevated blood pressure in DS rats is not clear and remains for further study.     

The Effects of Urine pH Modification on the Pharmacokinetics and Pharmacodynamics of Phenylpropanolamine

To determine whether uninary alkalinization had an effect on the plasma pharmacokinetics and pharmacodynamics of phenylpropanolamine, a double-blind crossover study was conducted in four healthy, normotensive male volunteers. The subjects received 25 mg immediate-release phenylpropanolamine and either placebo or sodium bicarbonate in a balanced randomized order. The bicarbonate treatment consisted of 6 g sodium bicarbonate 30 min prior to the phenylpropanolamine and then 3 g sodium bicarbonate every 4 hr for the next 16 hr. During the control treatment, phenylpropanolamine and a placebo for bicarbonate (lactose) were given on the same schedule. Blood and urine samples were collected over 24 hr and analyzed by HPLC. A supine blood pressure and pulse were obtained before each blood sample. The bicarbonate treatment significantly increased the urine pH throughout the study period and decreased phenylpropanolamine renal clearance by 33.5%. The apparent total-body clearance was also decreased by 31.5% and resulted in higher postabsorptive plasma phenylpropanolamine concentrations in each subject as compared to the control treatment. Both systolic and diastolic blood pressures changed significantly from baseline in both treatments. The bicarbonate treatment was accompanied by significantly higher diastolic blood pressures than in the control treatment, but there was no effect on systolic blood pressures. Generally, when the blood pressure–concentration pairs were plotted chronologically, clockwise hysteresis curves resulted. Heart rates did not change significantly from baseline values for either treatment. In this small group of normotensive healthy male volunteers, urinary alkalinization significantly depressed the renal clearance of phenylpropanolamine, producing higher postabsorptive phenylpropanolamine plasma concentrations and a small but significant increase in the diastolic blood pressure.     

Penbutolol or hydrochlorothiazide once a day in hypertension. A controlled study with home measurements.

1 The hypotensive effect of single daily dosing with 80 mg penbutolol was compared to 100 mg hydrochlorothiazide and placebo in a double-blind cross-over controlled trial with daily home measurements in ten hypertensive patients. 2 Penbutolol, 80 mg once a day, reduced significantly the supine and standing blood pressure. 3 This hypotensive effect was more potent than hydrochlorothiazide 100 mg particularly in the evening. 4 The hypotensive effect remained for 24 h as shown by the evening (14 h after dose) and morning (24 h after dose) blood pressure readings. 5 No relevant subjective or physical side effects were recorded. There was no significant change nor individual noticeable variation in biochemical data during penbutolol treatment. However, during hydrochlorothiazide treatment, the expected electrolyte changes were observed (symptom-free hypokalemia and hyperuricemia). 6 Penbutolol serum concentration showed no cumulation after one month of treatment. 7 Sudden withdrawal of penbutolol after 1 month of therapy resulted in a slow return to baseline blood pressures over a 2-week period without rebound.     

轻、中度高血压病病人口服多沙唑嗪控释片与贝那普利比较

目的 :评价多沙唑嗪控释片对轻、中度高血压病病人降压有效性及安全性。方法 :采用双盲、双模拟、随机化、平行对照研究方法。 5 8例服多沙唑嗪控释片 4mg ,poqd× 8wk ,5 6例服贝那普利 10mg ,poqd× 8wk。此外 ,对 3 3例开放服多沙唑嗪控释片 4mg ,qd× 8wk。服药前后行 2 4h动态血压监测 (2 4hABPM)。结果 :2组均能有效地降压 ,有效率分别为 81%及 77% (P >0 .0 5 )。多沙唑嗪组不良反应明显少于贝那普利组 (3 %及 2 0 % ) ,P <0 .0 1,无体位性低血压及反射性心动过速。 2 4hABPM示等幅度降日间血压及夜间血压。谷 /峰比值 :SBP为 0 .69,DBP为 0 .5 9。结论 :多沙唑嗪控释片是一种有效安全的长效肾上腺素α1受体阻滞剂。     

ISOLATED SYSTOLIC HYPERTENSION: DOES IT REALLY EXIST ON AMBULATORY BLOOD PRESSURE MONITORING?

1. The diagnosis of isolated systolic hypertension, diastolic hypertension and normotension in elderly subjects, as defined by casual office blood pressure measurement, was compared with 24 h ambulatory blood pressure monitoring using an Accutracker II. 2. Mean day-time ambulatory blood pressure monitoring underestimated the casual systolic blood pressure in all three clinical groups. Diastolic pressure was not underestimated to the same extent. 3. Ambulatory blood pressure monitoring best reflected casual blood pressure determination for normotensive subjects. In subjects with isolated systolic hypertension ambulatory blood pressures were only consistent with that diagnosis for 8% of the day time period. For 34% of the day time, their ambulatory blood pressures were consistent with diastolic/mixed hypertension. 4. It is concluded that isolated systolic hypertension may not be a sustained condition, but rather an isolated response to office measurement of blood pressure.     

Influence of captopril on symptomatic and hormonal responses to hypoglycaemia in humans

AIMS: Hypoglycaemic symptoms and hormonal counter-regulation are of high importance to avoid the risk of severe hypoglycaemia in patients with diabetes mellitus. Various antihypertensive drugs, such as angiotensin-converting enzyme (ACE) inhibitors, have been suspected for a long time to reduce this response to hypoglycaemia in diabetic subjects. Although ACE inhibitors are approved for controlling diabetic complications, previous investigations regarding this putative side-effect are controversial. METHODS: We performed clamp experiments in 16 healthy men lasting for 6 h each. The subjects were pretreated for 7 days with captopril 3 x 25 mg day-1 vs placebo in a randomized, double-blind, crossover study. Plasma glucose was decreased in a stepwise manner during a hypoglycaemic clamp session and counter-regulatory hormones [epinephrine (adrenaline), norepinephrine (adrenaline), ACTH, cortisol, glucagon], symptoms, and haemodynamic parameters (blood pressure, heart rate] were measured. RESULTS: Counter-regulatory hormone concentrations significantly increased in both sessions (ACE inhibitor vs placebo) during hypoglycaemia. The rise of counter-regulatory hormones as well as symptom scores were equal under both ACE inhibitor and placebo treatment. Systolic blood pressure and heart rate increased (from 110 +/- 3 vs 115 +/- 3 mmHg to 132 +/- 4 vs 133 +/- 4 mmHg) whereas diastolic blood pressure slightly decreased (from 63 +/- 2 vs 70 +/- 3 mmHg to 61 +/- 2 vs 64 +/- 2 mmHg) independent of pretreatment. Systolic and diastolic blood pressure were significantly lower in the captopril session vs placebo (P < 0.05). CONCLUSIONS: Our results demonstrate that subchronic treatment with captopril does not attenuate symptomatic and hormonal response to hypoglycaemia. Thus, to patients at risk of hypoglycaemia who require antihypertensive or nephroprotective treatment, we would continue giving an ACE inhibitor.