健康寿命年——一个新的测量疾病负担的指标

介绍一种新的测量疾病负担的指标——健康寿命率（ＨｅａＬＹ）。我们用此指标对１９９０～１９９３年北京ＭＯＮＩＣＡ资料进行了重新估算和分析,并将其与几年前ＷＨＯ和世界银行提出的另一个测量疾病负担的指标ＤＡＬＹ进行了比较。     

创建爱婴市 强化爱婴行动

深圳市从１９９３年开展创建爱婴医院、争创爱婴市活动。主要做法：提高认识,加强领导,全面推进爱婴行动;部门协作,齐抓共管,形成社会系统工程;儿童优先,母亲安全,促进医院产科改革;建章立制,规范管理,巩固和发展－创建成果;进入社区,进入家庭,促进妇幼保健工作。到１９９６年底,全市有１０张以上产科床位的医疗保健机构３５间已全部通过市、省和国家爱婴医院三级评审;住院期间和４个月的母乳喂养率分别提高到９６．２％和５２．６％;孕产妇和婴儿死亡率分别降至１２．９／１０万和１３．４‰。     

Atrial peptides, ANP(1-98) and ANP(99-126) in health and disease in an elderly population

Circulating immunoreactive atrial natriuretic peptide, Ir ANP(99-126)and the N-terminal fragment of the prohormone, Ir ANP(1–98)were measured in two population samples from the general populationof Gothenburg, Sweden. A group of 85-year olds (974 subjects)and a group of 40-year olds (191 subjects) were investigatedin respect of cardiovascular, renal and metabolic disease. Ir ANP(99-126) and Ir ANP(1-98) were significantly higher inthe 85-year olds compared to tile 40-year olds, and were significantlyincreased in subjects with congestive heart failure, ischaemicheart disease, atrial fibrillation and renal dysfunction butnot in subjects with hypertension. Eighty-five-year-old subjectswho were on treatment with digitalis, ß-adrenergic-blockers,nitrates and diuretics had significantly increased Ir ANP(99-126)and Ir ANP(1-98). In multivariate analysis Ir ANP(99-126) concentrationswere predictive for congestive heart failure, ischaemic heartdisease, atrial fibrillation and treatment with ß-blockersand anti-depressant drugs. Ir ANP(1–98) was predictivefor congestive heart failure, ischaemic heart disease, atrialfibrillation, diabetes mellitus, renal failure and drug treatmentwith ß-blockers and neuroleptics. We conclude that measurements of circulating concentrationsof Ir ANP(99-126) and/or Ir ANP(1-98) may add valuable informationin the diagnosis of congestive heart failure and ischaemic heartdisease in an elderly population. It remains to be determinedwhether routine measurements of circulating Ir ANP(99–126)and Ir ANP(1–98) may be of value in predicting currentcardiovascular disease for the individual patient.     

Steady-state kinetics of bezafibrate and clofibrate in healthy female volunteers

Summary The steady-state kinetics of chlorophenoxyisobutyric acid (CPIB) and of bezafibrate were investigated in a strictly controlled, randomised cross-over study in 10 female volunteers, after the conventional oral doses of clofibrate 0.5 g and bezafibrate 0.2 g at 8-h intervals. The mean steady-state concentration of CPIB in serum was 34 times higher than that of bezafibrate, which was due to the considerable cumulation of CPIB, whereas no cumulation of bezafibrate was observed. This is supported by comparison of the AUCs, and of the maximum and mean concentrations of bezafibrate after the first and last doses. (0.44 and 0.49 h^–1) and the half-lives (1.6 and 1.4 h) were almost identical after the first and last doses of bezafibrate. The median total clearances of CPIB and bezafibrate amounted to 10.5 and 142.5 ml/min, respectively, if complete absorption of both drugs is assumed. Since the apparent volumes of distribution were in the same range for both drugs, the amount of drug present in the organism in steady-state also differed by a factor of approximately 30 under the usual dosage regimen.     

Unaltered insulin sensitivity during calcium channel blockade with amlodipine

Summary The sensitivity of peripheral tissues to insulin is of pathophysiological, therapeutic and possibly also of prognostic relevance. Calcium channel blockers are widely used in the treatment of cardiovascular disorders that are commonly associated with decreased insulin sensitivity (S_I). To evaluate the effects of calcium channel blokkade on S_I, glucose homoeostasis and lipid profiles, studies were made of S_I (determined by the Minimal Model Method of Bergman), basal glucose and insulin levels, serum total triglyceride (Tg) and lipoprotein cholesterol (C) fractions and certain other variables in 38 healthy young men (24 y) during placebo and after 3 weeks of calcium channel blockade with amlodipine 5 mg once daily. Measurements were made after 3 days on a standard diet (2200 kcal · day^–1, 45% carbohydrates, 40% fat and 15% proteins) and after an overnight fast. Compared to placebo, amlodipine decreased supine systolic blood pressure (P<0.01). Heart rate, body weight and 24 h urinary sodium excretion were unaltered, and so were fasting plasma glucose (placebo vs amlodipine: 4.86 vs 4.83 mmol·1^–1, respectively) and insulin levels (7.7 vs 7.9 U·ml^–1), S_I (10.5 vs 9.6·10^–4 × min^–1 pro U·ml^–1), serum total Tg, C and lipoprotein C fractions.The findings demonstrate unchanged insulin sensitivity and secretion, as well as lipoprotein regulation, during maintenance administration of 5 mg amlodipine daily to healthy young men.This work was supported in part by the Swiss National Science Foundation     

Time course of the anti-oedematous effect of O-(β-hydroxyethyl)-rutosides in healthy volunteers

Summary O-(-hydroxyethyl)-rutosides (HR) is used for the treatment of disorders of the venous and microcirculatory systems. In order to evaluate the time course of its activity, the effect of HR on a provocation model of orthostatic oedema in healthy volunteers was used. After a 2 week placebo run-in period, 16 healthy volunteers were randomized to HR (2 tablets of 500 mg/day) of placebo for a further 3 weeks, in a double-blind parallel design. Oedema was provoked by standing motionless for 1 h, with measurement of leg volume before and afterwards. The procedure was undertaken at entry to the study and then weekly during the entire 5 week period.There were no significant differences in the extent of oedema produced by the orthostatic challenge during the 2 week run-in period or in the subjects who continued on placebo (90 arbitrary units i.e. 48 ml). During the 3 week treatment with HR, however, there was a progressive reduction (–1.1, –5.9, and –7.6 arbitrary units after 1, 2, and 3 weeks, respectively) in the volume of induced oedema, which was significant after 2 and 3 weeks of treatment compared to the placebo group.     

Noninvasive assessment of the inodilator action of amrinone in healthy man

Summary The effects of a single dose of 2 mg/kg amrinone (60 min constant rate IV infusion) have been assessed in a double-blind, placebo-controlled, within-subject cross-over study in six healthy volunteers. Combined impedance cardiography, phonocardiography and electrocardiography revealed a protracted drop in mean ventricular ejection time and electromechanical systole together, with a protracted rise in the contractility indices dZ/dt_max and the Heather index HI. The profile is compatible with combined venous vasodilation and positive inotropic action. In spite of the methodological constraints, endpoints were reached that were both detectable and relevant. The profiling permitted a better distinction to be made between the possible levels of action than systolic time intervals alone could have done. Therefore, these methods may be of value in the early development of inodilator drugs.     

The pharmacokinetics and pharmacodynamics of lisuride in healthy volunteers after intravenous,intramuscular, and subcutaneous injection

Summary The plasma concentration of lisuride and prolactin have been measured in twelve healthy male volunteers after IV, IM or SC injection of 25 g lisuride hydrogen maleate as an aqueous solution.After IV administration the plasma lisuride fell in two phases with half-lives of 14 min and 1.5 h. Total clearance was 13 ml·min^–1·kg^–1. After IM and SC injection the plasma concentrations peaked at 12 to 15 min and the profiles were similar to that found after IV administration. The systemic availabilities were 90% and 94%, respectively. Prolactin concentrations were reduced by a maximum of 60% relative to the normal circadian rhythm after all three routes of administration.The treatments were well tolerated, the only adverse reactions reported by some of the volunteers being mild, transient dizziness, tiredness, and nausea.     

Yohimbine pharmacokinetics and interaction with the sympathetic nervous system in normal volunteers

Summary The pharmacokinetics of yohimbine and its effects on sympathoadrenal function were studied in 13 young, healthy, male volunteers after an IV bolus dose of 0.25 or 0.5 mg · kg^–1.Pharmacokinetic analysis showed that distribution was rapid, with a half life between 0.4 and IS min, and the elimination half life ranged between 0.25 and 2.5 h. The volume of distribution (V_ss) was 741, (range 26 to 1271). Only 0.5 to 1 % of unchanged yohimbine was found in the urine, indicating that the major part of the drug was eliminated by hepatic clearance. Total plasma clearance was 1171. h^–1, which exceeds the hepatic plasma flow. This means that yohimbine is a high extraction drug with considerable extra-hepatic metabolism. Fractional urine sampling revealed that 0.5-1 % of unchanged yohimbine was excreted in urine in a biphasic manner. The data also suggested the existence of a slower elimination phase, with a half life of 13 h. The venous plasma concentration of noradrenaline (NA) increased 3-fold within 15 min after the yohimbine injection while plasma adrenaline (A) and neuropeptide Y-like immunoreactivity (NPY LI) remained unchanged. The plasma concentration-effect relationship of the changes in circulating NA followed counter-clockwise hysteresis. The results show that the hyperadrenergic state elicited by therapeutic doses of the ₂-adrenergic autoreceptor antagonist, yohimbine, is due to an interaction with NA but not to release of A or NPY in man.     

The effect of saturable binding to plasma proteins on the pharmacokinetic properties of disopyramide

Disopyramide exhibits saturable binding to plasma proteins in the therapeutic plasma concentration range. Because of this property, controversy exists in the literature regarding the pharmacokinetic properties of the drug. The purposes of this study were to reassess the pharmacokinetic properties of disopyramide in humans, taking into consideration both total and unbound concentrations and to use disopyramide as a model compound to study the effect of drug binding on the renal clearance of both total and unbound drug. A single intravenous dose of disopyramide (1.5 mg/kg) was administered to eight normal volunteers. Blood and urine samples were collected for 36h. Total concentrations of disopyramide in plasma and urine were determined by high pressure liquid chromatography. Binding of disopyramide to plasma proteins was determined by equilibrium dialysis. In all subjects, the binding of disopyramide to plasma proteins was saturable, but there were considerable differences in binding between subjects. The volume of distribution, total body clearance, and renal clearances of both total and unbound drug were calculated. Because only the total body clearance and renal clearance of unbound compound are not dependent upon unbound fraction (), these are the only parameters which can be reported without qualification as to the concentration. The mean ± SD total body clearance of unbound drug in the eight subjects was 5.40± 2.80 ml/min/kg. About 50% of this was due to renal elimination. A statistically significant negative correlation of the renal clearance of total disopyramide with time was observed in seven of eight subjects, whereas a significant correlation between the renal clearance of unbound disopyramide and time was observed in only one subject. This suggests that the renal clearance of unbound disopyramide is independent of , while the renal clearance of total disopyramide is dependent upon .