衰老人胚肺成纤维细胞核转录活性的研究

目的研究人胚肺成纤维细胞（简称２ＢＳ）核体外转录活性与代龄的关系。方法用３ＨＵＴＰ掺入法研究不同代龄２ＢＳ细胞核体外转录活性。结果衰老２ＢＳ细胞核转录活性较年轻组下降３３％（Ｐ＜００１），其催化ｒＲＮＡ和ｔＲＮＡ合成的ＲＮＡ聚合酶（ＲＮＰ）Ⅰ和Ⅲ的转录活性下降２４％（Ｐ＜００５），催化合成ｍＲＮＡ的ＲＮＰⅡ转录活性下降３８％（Ｐ＜００１）；衰老２ＢＳ细胞核内ＲＮＡ被转运至核外的量为总合成量的２９％，明显低于年轻细胞组的４５％（Ｐ＜００１）。结论衰老２ＢＳ细胞核转录活性的下降可能与其ＲＮＰ的活性与ＲＮＡ的转运水平下降有关。     

慢性HCV感染者IFN治疗前后血清HCV RNA水平

目的评价ＩＦＮ对丙肝患者病毒血症水平的作用．方法竞争性逆转录聚合酶链反应（ＣＲＴＰＣＲ）法定量检测１２例慢性ＨＣＶ感染者（男８例，女４例，ＨＣＶＲＮＡ阳性，ＡＬＴ异常持续６个月以上）ＩＦＮ治疗（ＩＦＮａ２ｂ３ＭＵ，肌注，３次／周，疗程３个月）前后（随访６个月）血清ＨＣＶＲＮＡ水平．结果慢性ＨＣＶ感染者１２例，３例呈完全反应，６例呈部分反应，另外３例无反应．９例有反应者中４例复发，有反应者治疗结束时血清ＨＣＶＲＮＡ水平明显下降（５１７±０４０８ｖｓ２０６±１５５，１０ｃｏｐｉｅｓ／５０μｌｓｅｒｕｍ，ｘ±ｓ，Ｐ＜００５），无反应者血清ＨＣＶＲＮＡ水平未见明显下降（５６７±０５８ｖｓ４５±０８７，ｘ±ｓ，Ｐ＞００５）．３例完全反应者仅１例血清ＨＣＶＲＮＡ持续阴性，３例无反应者２例血清ＨＣＶＲＮＡ水平略有下降．结论ＩＦＮ治疗丙肝有效，但ＩＦＮ不能有效清除病毒，仅抑制病毒复制，未见治疗前血清ＨＣＶＲＮＡ水平与复发与否有关．     

钙拮抗剂与血管紧张素转换酶抑制剂对高血压靶器官的影响

目的探讨用钙拮抗剂（ＣａＡ）和血管紧张素转换酶抑制剂（ＡＣＥＩ）长期治疗对高血压病靶器官的影响。方法对３８６例高血压病Ｉ期或Ｉ期患者服用ＣａＡ或ＡＣＥＩ平均５．１±０．６年，按服药情况分为ＣａＡ组、ＡＣＥＩ组、对照组（间断服药）。结果长期服用ＣａＡ或ＡＣＥＩ不仅能使血压持续稳定在较低水平，而且随着血压的下降，左室肥厚逆转、心脏舒张功能改善、尿蛋白排泄量下降（Ｐ＜０．００１）、眼底病变好转（Ｐ＜０．０１），且无脑卒中发生（Ｐ＜０．０５～０．０１）；而对照组上述各项指标均较ＣａＡ组和ＡＣＥＩ组有加重趋势，其加重程度和观察时间呈正相关（Ｐ＜０．０１）。结论长期ＣａＡ或Ａ－ＣＥＩ治疗对高血压病患者的预后有益。     

培哚普利、卡托普利和硝苯地平对老年轻中度高血压患者肾功能的影响

目的：观察培哚普利、卡托普利和硝苯地平对老年轻中度高血压患者肾功能的影响。方法：９４例老年轻中度高血压心室肥厚患者随机分为培哚普利、卡托普利和硝苯地平３组，服用２周安慰剂后用药３个月，剂量逐月递增。用药前后测定血压、尿微白蛋白分泌率（ＭＡＥＲ）、尿素氮、肌酐、肌酐清除率和血钾、血钠。结果：３组用药后血压均明显下降达正常范围；尿ＭＡＥＲ在培哚普利组显著下降（Ｐ＜０．０１），另两组下降不显著；尿素氮、肌酐、肌酐清除率３组治疗前后无明显变化；血钾在卡托普利组和培哚普利组均有上升（Ｐ＜０．００５和Ｐ＜０．０５），血钠水平３组间均无变化。结论：培哚普利、卡托普利和硝苯地平均可有效控制血压，培哚普利同时可降低尿ＭＡＥＲ，改善肾功能，但培哚普利与卡托普利均可引起血钾升高，应引起注意。     

载脂蛋白E基因多态性与冠心病关系的研究

目的：探讨载脂蛋白（Ａｐｏ）Ｅ基因多态性与冠心病的相关性，以及ＡｐｏＥ基因多态性对冠心病患者血脂水平的影响。方法：１００例冠心病患者和４３例正常对照者。按常规方法测定血浆脂质和Ａｐｏ水平。ＡｐｏＥ基因型的确定采用聚合酶链反应和ＨｈａＩ酶切的方法。结果：本研究只发现３种常见的ＡｐｏＥ基因型，即Ｅ３／３，Ｅ３／４，Ｅ３／２。在病例组和正常对照组之间，ＡｐｏＥ等位基因频率以及基因型频率分布没有统计学差异（Ｐ＞０．０５）。在冠心病患者不同基因型之间，总胆固醇和ＡｐｏＢ的水平有差异（Ｐ＜０．０５）；其它血脂指标无差异（Ｐ＞０．０５）。结论：本研究证实ＡｐｏＥ基因多态性影响冠心病患者总胆固醇和ＡｐｏＢ的水平；但ＡｐｏＥ基因多态性并不是冠心病发病的直接危险因子。     

组织型纤溶酶原激活剂基因导入犬血管壁预防血管成形术后再狭窄

目的：组织型纤溶酶原激活剂（ｔ－ＰＡ）基因治疗，为防治血栓性疾病提供了一个可能全新的方法与前景。探索ｔ－ＰＡ基因转移至犬血管壁后基因表达持续的时限以及预防血管成行术后再狭窄的价值。方法：１８条家犬，其中对照组６条，另１２条在形成再狭窄模型时随机分为３０天、６０天和９０天３个观察亚组，每组４条犬，并用多孔球囊输注导管将携带ｔ－ＰＡ基因的逆转录病毒载体直接高压注入冠状动脉及股动脉壁。结果：经过３０天、６０天和９０天不同时间的观察，发现在脱氧核糖核酸（ＤＮＡ）水平（原位杂交、ＤＮＡ印迹）、转录水平［（信使核糖核酸（ｍＲＮＡ）点杂交］及产物水平（免疫组化）等方面均证实ｔ－ＰＡ基因的存在和活性产物表达，而且发现再狭窄组３个月时基因治疗组比对照组的百分狭窄面积小２２．２％。结论：ｔ－ＰＡ基因治疗有一定的预防血管成形术后再狭窄的作用     

培哚普利,卡托普利和硝苯地平对高血压左心室肥厚及心功能影响

目的观察培哚普利、卡托普利和硝苯地平对老年高血压心室肥厚（ＬＶＨ）及心功能的影响。方法将９４例老年轻、中度高血压ＬＶＨ病人随机分为培哚普利、卡托普利和硝苯地平３组。服用安慰剂２周后分别用药３个月，剂量递增，于实验前、用药前、用药后每月分别测定动脉血压，超声心动图左室舒张末内径、舒张期室间隔厚度、左室后壁厚度，并由此计算左室质量指数（ＬＶＭＩ），同时测定左室缩短分数，Ｅ／Ａ比值和射血分数。结果３组病人用药前一般情况无明显差别，用药后血压均有显著下降（Ｐ＜０．００１），组间无差异。ＬＶＭＩ培哚普利组（Ｐ＜０．０１）和卡托普利组（Ｐ＜０．００１）用药后有显著减低，Ｅ／Ａ比值明显升高（均Ｐ＜０．００１）。而硝苯地平组仅有Ｅ／Ａ比值升高（Ｐ＜０．０５）。左室缩短分数和射血分数３组均未见明显变化。结论对老年轻中度高血压ＬＶＨ病人，三药均可有效降低血压，卡托普利和培哚普利明显减轻ＬＶＨ，并改善左室舒张功能，硝苯地平亦可改善左室舒张功能     

静脉输注丙种球蛋白治疗川崎病的疗效观察

１２８例川崎病住院患者，分为静脉输注丙种球蛋白＋阿司匹林组（ＧＧ＋ＡＳＡ组）和单纯阿司匹林组（ＡＳＡ组）；结果：前组较后组退热迅速（Ｐ＜０．０１）；冠状动脉病变（ＣＡＬ）的比率显著动态下降（６个月Ｐ＜０．００５，１２个月Ｐ＜０．０５）；ＧＧ＋ＡＳＡ组内病程≤１０天应用ＧＧ组比＞１０天应用ＧＧ组ＣＡＬ恢复正常比率明显上升（６个月Ｐ＜０．０５）。应用ＧＧ过程中有１４．５％的患者出现暂时的类似输液反应的情况。提示川崎病患者静脉输注ＧＧ可取得满意疗效。     

缓释维拉帕米与比索洛尔治疗高血压效果的比较

按照随机双盲法将５０例原发性高血压病人分为２组（Ａ组缓释维拉帕米和Ｂ组比索洛尔），服安慰药２周后服治疗药。用药前后进行血压、心率、ＲＡＡ系统检查，结果显示：（１）两组血压、心率在治疗后均有明显下降（Ｐ＜０．０１）；（２）Ａ组平均收缩压及心率的下降弱于Ｂ组（Ｐ＜０．０１）；（３）Ｂ组治疗后肾素水平明显降低（Ｐ＜０．０５），Ａ组稍有升高（Ｐ＞０．０５），两组血管紧张素Ⅱ及醛固酮无明显变化，提示两种缓释长效降压药均有明显降压作用，降压效果明显。     

依那普利对高血压病患者胰岛素抵抗影响的临床观察

测定５１例高血压病患者与２２例正常人空腹血糖（ＳＧ）、血胰岛素水平（ＩＳ）、Ｃ肽（ＣＰ），显示ＩＳ、ＩＳ／ＳＧ、胰岛素敏感指数（ＩＡＩ）、两组间有显著性差异（Ｐ＜０．０１），而ＣＰ／ＩＳ比值无统计学差异。高血压病患者用依那普利５～１０ｍｇ／ｄ，疗程４～１５个月（平均１１．２９±３．７１个月），后复查上述指标并与用药前进行对比分析。结果除血压明显下降外（Ｐ＜０．００１），空腹ＩＳ、ＩＳ／ＳＧ、ＩＡＩ亦均显著下降（Ｐ＜０．０１），而ＣＰ／ＩＳ比值治疗前后差异无显著性（Ｐ＞０．０５）。提示，原发性高血压病患者存在胰岛素抵抗现象，依那普利治疗除可有效降低血压外，尚有改善胰岛素抵抗的作用。     

Adrenergic activity and left ventricular function during treatment of essential hypertension with calcium antagonists

The effects of 2 calcium antagonist drugs, verapamil and nifedipine, on blood pressure, heart rate (HR), plasma catecholamines, plasma renin activity and some echocardiographic indexes of left ventricular anatomy and function were studied in 67 patients with essential hypertension. The short- and long-term antihypertensive effect of verapamil was not associated with significant changes in HR, plasma catecholamines or plasma renin activity; the decrease in blood pressure after nifedipine was associated with a significant increase in HR and plasma catecholamines (mainly noradrenaline) (p less than or equal to 0.05). These findings were confirmed in a crossover comparison in 12 hospitalized patients treated with verapamil and nifedipine for 8 days each. The dose of isoproterenol that increased HR by 25 beats/min was significantly increased during verapamil treatment (p less than 0.05) and decreased during nifedipine treatment (p less than 0.01). Stroke volume and shortening fraction increased slightly but significantly (p less than 0.05) with 3 months of nifedipine treatment, while no change was detected with verapamil treatment. Left ventricular mass was significantly decreased after effective antihypertensive treatment for 3 months with verapamil or nifedipine (p less than or equal to 0.05).     

Pharmacologically induced pulmonary vasodilatation in children and young adults with primary pulmonary hypertension

To evaluate pulmonary vasoreactivity in children and young adults with primary pulmonary hypertension, we performed cardiac catheterizations on nine patients with primary pulmonary hypertension (nine months to 23 years old) and made hemodynamic measurements: before and after infusing prostacyclin, and before and after administering sublingual nifedipine. Based upon the response to prostacyclin, patients were divided into responders and nonresponders using the following criteria: 20 percent or greater decrease in mean pulmonary arterial pressure; an increase in cardiac index; and no change, or a decrease in the pulmonary vascular resistance to systemic vascular resistance ratio. By these criteria, five of the nine patients had a reactive pulmonary vascular bed and responded to prostacyclin administration. In addition, they all responded to nifedipine. The remaining four did not respond to either drug. There was a close correlation (r = 0.85, p less than 0.01) between the magnitude of the pulmonary vasodilator response to treatment with prostacyclin and nifedipine. There was also a significant inverse correlation between the age of the patient at the time of the study and the pulmonary vasodilator response to administration of prostacyclin (r = 0.91, p less than 0.01) and nifedipine (r = 0.82, p less than 0.01); ie, both drugs produced a greater fall in pulmonary arterial pressure in younger patients with primary pulmonary hypertension than in older ones.     

Differential therapy with calcium antagonists in pulmonary hypertension secondary to COPD. Hemodynamic effects of nifedipine, diltiazem, and verapamil

In 53 patients with COPD and precapillary pulmonary hypertension, we investigated the effect of three typical calcium antagonists on hemodynamics at rest and during bicycle ergometer exercise. In the responders, the decrease in pulmonary vascular resistance following nifedipine was 23 percent at rest (p less than 0.0005) and 35 percent during exercise (p less than 0.0005); following diltiazem, it was 10 percent at rest (p less than 0.05) and 23 percent during exercise (p less than 0.025); following verapamil, it was 22 percent at rest (p less than 0.005) and 11 percent during exercise (p less than 0.025). The cardiac index rose significantly at rest and under exercise only after the administration of nifedipine (+16 percent and +8 percent, resp). Nifedipine caused the most distinctive peripheral vasodilation. The heart rate increased slightly following nifedipine and decreased slightly following diltiazem and verapamil. After long-term therapy with nifedipine (13 +/- 5 months), the decrease in pulmonary artery pressure and pulmonary vascular resistance was no longer significant. In our opinion, the different hemodynamic action profiles will have consequences for the differential therapy in patients with COPD and pulmonary hypertension.     

Felodipine compared to nifedipine as "third-line drug" in resistant hypertension

Felodipine is a new dihydropyridine calcium antagonist, and in hypertension it is a much more effective "third-line" drug than hydralazine. Nifedipine, on the other hand, is the established dihydropyridine calcium antagonist that has been increasingly used to treat hypertension. Information is now needed on the relative merits and demerits of these two drugs. This study appraised, therefore, the therapeutic utility of twelve months' treatment with nifedipine 20-60 mg twice daily in 55 patients with previous drug-resistant hypertension who had been successfully treated for the previous year with felodipine 5-20 mg twice daily, each calcium antagonist being used in combination with atenolol 100 mg daily with or without chlorthalidone 25 mg daily. Initially, nifedipine maintained comparable blood pressure control to that which had been achieved by felodipine, although in the longer term (over eight months) nifedipine proved less effective than felodipine had (p less than 0.02) and more patients became uncontrolled (supine diastolic blood pressure, Phase V, greater than or equal to 90 mmHg) on the maximum tolerated dose of the calcium antagonist (chi 2 = 4.13, p less than 0.05 greater than 0.025). The former degree of blood pressure control was, however, reestablished by increasing the dose of nifedipine or reintroducing the diuretic as necessary, and this control was maintained over the next four months. Minor side effects were less common on nifedipine than they had been during the preceding felodipine treatment phase. Felodipine thus has more pronounced and sustained antihypertensive effects than nifedipine, though its side effect burden may appear to be greater.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impaired venoarteriolar reflex as a possible cause for nifedipine-induced ankle oedema

Ankle oedema is not an uncommon side effect of treatment with nifedipine. To evaluate the possible effect of nifedipine on the microcirculation of the skin, 18 patients with systemic hypertension who were known to develop ankle oedema after nifedipine and 19 patients with systemic hypertension who did not develop ankle oedema after nifedipine were studied. Following four weeks of nifedipine therapy (10 mg, three times daily), the microcirculation on the dorsum of the foot was measured using laser-Doppler flowmetry. Estimation of the microcapillary flow was made both after supine resting and on standing upright. The venoarteriolar reflex was expressed as the standing flow in percentage of the resting flow. There was no significant difference between the two groups of patients in the resting flow, supine flow, or the venoarteriolar reflex before nifedipine therapy (P > 0.4). Before nifedipine, the blood blow in the skin of both groups of patients was reduced from the supine level upon standing, thus indicating a normal response to dependency. After nifedipine administration, no significant difference was observed between the two groups of patients in the resting flow (P > 0.5). The flow on standing, however, was 96.2% of that measured during resting supine in patients who developed ankle oedema and 79.8% of the resting flow in the patients who did not develop ankle oedema, suggesting a weaker venoarteriolar reflex in patients who developed ankle oedema following administration of nifedipine (P < 0.0001). Thus, the microcapillary flow did not decrease upon standing in patients who developed ankle oedema following nifedipine therapy, indicating an abnormal venoarteriolar reflex. This may explain why ankle oedema develops in such patients following nifedipine.     

Comparison of the effects of adenosine and nifedipine in pulmonary hypertension.

The hemodynamic effects of intravenously administered adenosine, a potent vasodilator, were examined in 15 patients with pulmonary hypertension. All patients were given adenosine, 50 micrograms/kg per min, increased by 50 micrograms/kg per min at 2 min intervals to a maximum of 500 micrograms/kg per min or until the development of untoward side effects. The patients were then given oral nifedipine, 20 mg every hour, until a greater than or equal to 20% decrease in pulmonary vascular resistance or systemic hypotension occurred. The administration of maximal doses of adenosine, 256 +/- 46 micrograms/kg per min, produced a 2.4% reduction in pulmonary artery pressure (p = NS), a 37% decrease in pulmonary vascular resistance (p less than 0.001) and a 57% increase in cardiac index (p less than 0.001). The administration of maximally effective doses of nifedipine (91 +/- 36 mg) produced a 15% reduction in the mean pulmonary artery pressure (p less than 0.05), a 24% decrease in pulmonary vascular resistance (p less than 0.01) and an 8% increase in cardiac index (p = NS). There was a significant correlation (r = 0.714, p = 0.01) between the reduction in pulmonary vascular resistance that resulted from adenosine administration and that achieved with the administration of nifedipine. Six patients had substantial reductions in pulmonary vascular resistance with adenosine but not with nifedipine. Thus, adenosine is an effective vasodilator in patients with pulmonary hypertension and can be used for safe and rapid assessment of vasodilator reserve in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute effect of nifedipine on blood pressure and left ventricular ejection fraction in severely hypertensive outpatients: predictive effects of acute therapy and prolonged efficacy when added to existing therapy

Nifedipine is known to reduce blood pressure both acutely and chronically. However, the following questions remain to be answered: can nifedipine be given acutely and safety to patients with severe hypertension in an outpatient setting, would its efficacy be retained with long-term therapy, and is nifedipine safe in the presence of cardiomegaly? Nifedipine (10 mg capsule sublingually) was given to 46 outpatients with severe or apparently refractory hypertension; 19 were followed-up for 18 months and 18 for 24 months. Nifedipine reduced blood pressure acutely and safely in 43 of 46 outpatients (mean control diastolic pressure 137 mm Hg), irrespective of prior treatment regimen. Blood pressure levels after 2 to 24 months of twice daily oral nifedipine (10 mg) were similar to 20-minutes levels, showing that tolerance did not occur. In a separate series of 37 patients, who had radiologic cardiomegaly in addition to hypertension, the control ejection fraction was 62%. Nifedipine, when used acutely, slightly increased the ejection fraction to 65% (p less than 0.005). Our studies show that in outpatients with severe hypertension, sublingual nifedipine is an antihypertensive agent which acts swiftly and safely, without causing a decrease in the ejection fraction when it is used for acute blood pressure reduction, and that subsequent therapy with oral nifedipine results in a predictive long-term hypotensive effect.     

A randomized comparison of nifedipine and sodium nitroprusside in severe hypertension

We randomized patients with severe hypertension in the Medical Intensive Care Unit to a treatment regimen of oral nifedipine or intravenous nitroprusside. Patients treated with nifedipine achieved a sustained reduction in diastolic blood pressure to less than or equal to 120 mm Hg in an average of less than five hours. Patients treated with nitroprusside achieved a similar reduction in 14 hours (p less than 0.05). Treatment with nifedipine was less expensive and required less time in the ICU than treatment with nitroprusside and was accompanied by no associated increase in morbidity or mortality. Oral nifedipine can be used as an alternative to intravenous nitroprusside in severe uncomplicated hypertension.     

三种国产降压药治疗轻中度高血压病临床研究

目的 :观察国产降压药比索洛尔、依那普利、缓释硝苯地平对轻、中度高血压病的降压效果和耐受性。方法 :采用随机、双盲对照法 ,将部队检出的轻、中度高血压病患者 14 2例 ,分别用比索洛尔(n =4 7)、依那普利 (n =4 9)和缓释硝苯地平 (n =4 6 )治疗 4周。比较 3种药物的降压疗效和对血糖、血脂、肝肾功能的影响及不良反应 ,并对治疗中的 6 0例随访 6个月。结果 :比索洛尔、依那普利和缓释硝苯地平治疗轻、中度高血压病患者至 4周末 ,收缩压和舒张压较治疗前明显下降 (P均 <0 0 1) ;3种药物的总有效率分别为 83 0 %、77 6 %和 76 1% (P >0 0 5 ) ,均无严重不良反应 (P >0 0 5 ) ;6 0例随访 6个月者血压仍得到有效控制。结论 :国产比索洛尔、依那普利和缓释硝苯地平治疗轻、中度高血压病降压效果好 ,不良反应轻 ,耐受性好     

Effects of nifedipine on carbohydrate metabolism in the non-insulin dependent diabetic

The aim of this prospective, randomized, double-blind, placebo controlled study was to investigate the effect of nifedipine on carbohydrate metabolism in diabetic patients after a 3-day and a 3-month course of treatment. Sixteen non obese, well controlled non-insulin dependent diabetics, (HbA1 less than 10%), with moderate untreated hypertension were divided in two groups: nifedipine (group N, 8 patients) and placebo (group P, 8 patients). An oral glucose tolerance test (OGTT, 75 g glucose) and an arginine infusion were performed before, after a 3-day, and a 3-month course, either of nifedipine 30 mg/D or placebo. Blood samples obtained during OGTT were assayed for glucose and insulin, and during arginine infusion for insulin, glucagon and growth hormone. The differences between basal and peak values during tests were compared between both groups before and after treatment using Wilcoxon's rank sum test. Neither acute nor chronic administration of nifedipine or placebo modified the glucose tolerance. However, basal insulin levels were reduced by 3 month-administration of nifedipine (from 19 +/- 2 micromicrons/ml to 10 +/- 1 micromicrons/ml, p = 0,01). Otherwise the basal and peak hormonal values during tests were not significantly affected by nifedipine either at the start of after 3 months of treatment. These results suggest that nifedipine, when given in standard dosage for 3 months, has minor effects on carbohydrate metabolism in non-insulin dependent diabetic patients.