Mortality Amongst Patients of the Glasgow Blood Pressure Clinic was High in the 1970s and 80s but has Fallen Since,Why?

Established in 1968 the Glasgow Blood Pressure Clinic has over 11,000 patients on its computer record. Up to 1980, mortality from all-causes and from cardiovascular causes was high: relative risks compared with two local control populations were greater than 2.0. Since 1980, all-cause mortality has decreased to 1.31 (859 deaths, CI 1.23–1.39). Lower mortality from cardiovascular causes, particularly coronary heart disease, contributes to the decrease. Reasons for the decrease are under investigation currently. Referral of patients with slightly lower blood pressure contributes, as may better blood pressure control with newer antihypertensive drugs. ACE inhibitors and calcium channel blockers were introduced in 1980 and during the 16-year period to 1995, all-cause mortality has decreased most in patients taking ACE inhibitor. A decrease also occurred in patients taking antihypertensive drugs other than ACE inhibitor.     

Nitrosamine Contamination in Pharmaceuticals: Threat,Impact, and Control

Nitrosamine-contaminated medicinal products have raised safety concerns towards the use of various drugs, not only valsartan and all tetrazole-containing angiotensin II receptor blockers, but also ranitidine, metformin, and other medicines, many of which have been recalled and prone to shortage. At any stages, from drug substance synthesis throughout each product's lifetime, these impurities may evolve if an amine reacts with a nitrosating agent coexisting under appropriate conditions. Consequently, drug regulatory authorities worldwide have established stringent guidelines on nitrosamine contamination for all drug products in the market. This review encompasses various critical elements contributing to successful control measures against current and upcoming nitrosamine issues, ranging from accumulated knowledge of their toxicity concerns and potential root causes, precise risk evaluation, as well as suitable analytical techniques with sufficient sensitivity for impurity determination. With all these tools equipped, the impact of nitrosamine contamination in pharmaceuticals should be mitigated. An evaluation aid to tackle challenges in risk identification, as well as suitable industry-friendly analytical techniques to determine nitrosamines and other mutagenic impurities, are among unmet needs that will significantly simplify the risk assessment process.     

The Secondary Prevention of myocardial infarction by drug treatment; excluding lipid lowering agents

About 10% of survivors of an acute myocardial infarction will die in the following year. Thereafter the risk declines but reinfarction is still an important cause of mortality and morbidity.

The post infarction trials have clearly shown that the best proven agents to mitigate this toll are aspirin, beta adrenoceptor blockers, and verapamil (but not other calcium blockers, except diltiazem for non Q wave infarction). In the context of hypertension treatment these post infarction trials may have important lessons for drug selection and ancillary treatment since the majority of subjects will ultimately die of ischaemic heart disease

Although the newer agents such as ACE and renin inhibitors, newer calcium channel blockers and alpha blockers have many promising properties in terms of risk factor reduction, no convincing mortality data exists; it is needed.

This review will deal with the known effects (both good and bad) of antihypertensive agents and will also review other drug strategies relevant to the hypertensive patient. It will also point out large areas of ignorance.     

Angiotensin receptor blockers in acute myocardial infarction

It has been established from multiple randomised, placebo-controlled trials that angiotensin-converting enzyme inhibitors reduce the risk of death and major non-fatal cardiovascular events after acute myocardial infarction, especially when these agents are used for long-term treatment in high-risk patients. Angiotensin receptor blockers represent a theoretically appealing class of drugs for use in combination with or as alternatives to angiotensin-converting enzyme inhibitors in such patients. The Valsartan in Acute Myocardial Infarction (VALIANT) trial compared the effects of valsartan, captopril and the combination of both in a population of high-risk patients with evidence of left ventricular dysfunction after acute myocardial infarction. This article discusses this important study and its implications for the clinical management of these high-risk patients.     

Treatment of Rheumatoid Arthritis

This section is reserved for commentaries and brief essays dealing with matters of interest to physicians. Material for consideration should not exceed Ave double-spaced typewritten pages. An honorarium of $75 is offered at the time of publication. Submissions should be addressed to: Editor, POSTGRADUATE MEDICINE, 4530 W 77th St, Minneapolis, MN 55435.     

牛磺酸对大鼠胸主动脉的舒张作用及其机制的研究

目的研究牛磺酸舒血管作用的可能机制。方法记录苯肾上腺素(PE)和KCl预收缩的离体大鼠主动脉环张力变化,观察牛磺酸的舒血管作用及不同工具药对其作用的影响。结果牛磺酸(20~80mmol.L-1)对PE(1μmol.L-1)或KCl(60mmol.L-1)预收缩的大鼠主动脉环均有非内皮依赖的、浓度依赖性的舒张作用。在内皮完整的血管环,左旋硝基精氨酸甲酯(0.1mmol.L-1)对牛磺酸的舒血管作用无明显影响;β-丙氨酸(60mmol.L-1)在PE预收缩的血管环增强牛磺酸的舒血管作用,而在KCl预收缩的血管环则降低牛磺酸的舒血管作用;在KCl预收缩基础上,钾通道阻断剂格列本脲(10μmol.L-1)和四乙胺(10mmol.L-1)明显抑制牛磺酸的舒血管作用,而4-氨基吡啶(1mmol.L-1)和BaCl2(1mmol.L-1)无影响。结论牛磺酸有浓度依赖性的血管舒张作用,此作用不依赖血管内皮,可能与其跨细胞膜转运有关,可能有钙依赖性钾通道和ATP敏感性钾通道的参与。     

缬沙坦联合辛伐他汀治疗早期糖尿病肾病临床观察

目的 探讨缬沙坦联合辛伐他汀治疗早期糖尿病肾病的临床疗效及作用机制.方法 将80例早期糖尿病肾病患者随机分为对照组40例(缬沙坦80 mg,1次/d)、治疗组40例(在对照组治疗基础上加辛伐他汀20 mg,每晚一次).疗程均为12周,比较治疗前后血脂、尿白蛋白排泄率(UAER)、C-反应蛋白(CRP)的变化.结果 两组治疗后UAER较治疗前明显减少(均P<0.01),治疗组减少程度较对照组更明显(P<0.05);治疗组治疗后血脂、CRP水平明显下降(P<0.05).结论 早期糖尿病肾病患者应用缬沙坦联合辛伐他汀治疗能明显降低UAER、CRP,改善血脂,有效延缓肾损害进展.