明天的医学向何处去——平衡医学方法论略谈

《明天的医学向何处去》一文是王佑三同志应中国中医研究院、中西医结合研究会1990～2010年中医药研究的重大进展与突破预测研究课题组和中国人体科学学会之约所撰。本报征得作者同意稍加删节后发表,期望引起对“明天的医学”的关注。     

地尔硫静脉滴注治疗冠心病心绞痛

目的：观察地尔硫Ｚｈｕｏ注射液静脉滴注治疗冠心病心绞痛的疗效。方法：８６例心绞痛患者分为两组，其中治疗组４６例，用地尔硫Ｚｈｕｏ５０ｍｇ加入５％葡萄糖液２５０ｍｌ中静滴，１次／ｄ，连续１０ｄ；对照组４０例用丹参液１６ｍｌ加入５％葡萄糖液２５０ｍｌ中静滴，１次／ｄ，连续１０ｄ。结果：治疗组症状控制总有效率９８％，患者心电图改善率６１％，明显高于对照组的３７％和２８％，地尔硫Ｚｈｕｏ改善心功能效果明显     

心绞痛患者血小板功能改变及丹参对其影响

本实验观察了心绞痛患者血小板环核苷酸水平,血浆TXB_2、6酮PGF_(10)深度、血小板内外5—HT含量及血小板聚集性的变化以及丹参治疗前后各指标的改变。结果表明,心绞痛患者血小板聚集性血浆5—HT和血浆TXB_2水平明显增高,而血小板内5—HT、血浆6—酮—PGF_(10)水平则明显低于对照组。丹参能增加血小板内cAMP水平,降低血浆5—HT水平,对血小板聚集性有抑制作用。     

Additional molsidomine in refractory unstable angina pectoris

Summary In a prospective single-blind study we examined the effects of additional molsidomine in 20 patients (63±10 years; 15 males, 5 females) with unstable resting angina (3 attacks/24 hours) refractory to triple therapy (nitrates, calcium antagonists, and beta blockers) combined with heparin or aspirin. All but one patient had coronary artery disease documented by coronarography (n=17) or by recent myocardial infarction (n=3). Two patients had angiographically documented severe coronary spasms. Patients entered the study if coronary bypass surgery or PTCA could not be performed within 3 days after angiography (n=9) or was not feasible due to anatomical or technical reasons (n=6), concomitant malignant disease (n=2), or age greater than 75 years (n=3). All patients received molsidomine orally 12 to 24 mg/day. In 15 of the 20 patients molsidomine was given i.v. initially, starting with 20 mg i.v., followed by infusion of 1 to 4 mg/hour. Heart rate and blood pressure did not change significantly, and eight patients had a slight decrease of systolic and diastolic blood pressure. Severe adverse effects did not occur, and moderate headaches were reported by five patients. In 13 patients, unstable angina could be stabilized, and they remained free of resting angina; five had a marked reduction of the frequency of anginal attacks. In two patients, molsidomine was without demonstrable beneficial effects. After a follow-up of 4 weeks, nine patients were free of symptoms after bypass surgery or PTCA, 10 continued to have angina NYHA class II or III, and one patient died due to acute myocardial infarction and cardiogenic shock 4 days after starting additional molsidomine. We conclude that molsidomine is well tolerated and has a marked beneficial effect in patients with refractory unstable angina. Molsidomine should therefore be considered for routine therapy of unstable angina, especially in those patients who are suspected of tolerance to nitrate therapy.     

Perceiving a stable world during active rotational and translational head movements

When a person moves through the world, the associated visual displacement of the environment in the opposite direction is not usually seen as external movement but rather as a changing view of a stable world. We measured the amount of visual motion that can be tolerated as compatible with the perception of moving within a stable world during active, sinusoidal, translational and rotational head movement. Head movements were monitored by means of a low-latency, mechanical head tracker and the information was used to update a helmet-mounted visual display. A variable gain was introduced between the head tracker and the display. Ten subjects adjusted this gain until the visual display appeared stable during sinusoidal yaw, pitch and roll head rotations and naso-occipital, inter-aural and dorso-ventral translations at 0.5 Hz. Each head movement was tested with movement either orthogonal to or parallel with gravity. A wide spread of gains was accepted as stable (0.8 to 1.4 for rotation and 1.1 to 1.8 for translation). The gain most likely to be perceived as stable was greater than that required by the geometry (1.2 for rotation; 1.4 for translation). For rotational motion, the mean gains were the same for all axes. For translation there was no effect of whether the movement was inter-aural (mean gain 1.6) or dorso-ventral (mean gain 1.5) and no effect of the relative orientation of the translation direction relative to gravity. However translation in the naso-occipital direction was associated with more closely veridical settings (mean gain 1.1) and narrower standard deviations than in other directions. These findings are discussed in terms of visual and non-visual contributions to the perception of an earth-stable environment during active head movement.     

Soluble Antiapoptotic Molecules and Immune Activation in Chronic Heart Failure and Unstable Angina Pectoris

Programmed myocyte cell death and activation of the immune system have been shown to occur in patients with congestive heart failure. Besides, unstable angina episodes are likely to be associated with immune activation. Our aim was to evaluate the role of changes in circulating levels of soluble Fas (sFas), suggestive of an enhanced inhibitory response to ongoing apoptosis, and soluble IL2 receptor (sIL2-R), indicative of T-lymphocyte activation, in chronic heart failure and unstable angina pectoris. Thirty patients affected by chronic heart failure (20 idiopathic and 10 ischemic cardiomyopathy) and 13 patients with unstable angina were evaluated. Twenty healthy individuals matched for age and gender were used as controls. A complete biochemical determination of indexes of myocardial damage including cardiac troponin I (cTnI) and creatine kinase (MB/CK) was performed. The results demonstrated that mean levels of sFas and sIL2-R were significantly increased in patients affected by chronic heart failure and unstable angina and were not associated with changes in renal function or with serum levels of cTnI. Highest values of sFas were found in NYHA class IV patients (IV NYHA class = 7.39 ± 0.52 vs. controls = 1.34 ± 0.12 ng/ml; P < 0.01) and more elevated in idiopathic than in ischemic cardiomyopathy (3.64 ± 0.40 vs. 1.82 ± 0.37 ng/ml; P < 0.01). Moreover, in chronic heart failure patients sFas and ejection fraction were negatively correlated (P = 0.01), whereas sFas and sIL2-R were positively correlated (P < 0.01). In unstable angina patients too, sFas and sIL2-R appeared to be correlated (P = 0.03); whereas sFas (angina group = 3.18 ± 0.39 vs. controls = 1.34 ± 0.12 ng/ml; P < 0.01) and sIL2-R (angina group = 0.46 ± 0.11 vs. controls = 0.00 UI/ml; P < 0.01) were higher in angina group than in controls. In most of the cases, the increase of sFas was associated with comparable changes in sIL2-R serum levels, indicating that the activation of Fas system is strictly associated with autoimmune–inflammatory reactions. This phenomenon, both in chronic heart failure and in unstable angina, occurs in the absence of biochemical evidences of myocardial damage and seems to parallel the activation of T cell. Soluble Fas could have a role in sustaining inflammatory response and in prolonging the detrimental effects correlated with it in chronic heart failure and angina pectoris.     

Availability of glucose ingested during muscle exercise performed under acipimox-induced lipolysis blockade

This study investigated the percentage of carbohydrate utilization than can be accounted for by glucose ingested during exercise performed after the ingestion of the potent lipolysis inhibitor Acipimox. Six healthy male volunteers exercised for 3 h on a treadmill at about 45% of their maximal oxygen uptake, 75 min after having ingested 250 mg of Acipimox. After 15-min adaptation to exercise, they ingested either glucose dissolved in water, 50 g at time 0 min and 25 g at time 60 and 120 min (glucose, G) or sweetened water (control, C). Naturally labelled [¹³C]glucose was used to follow the conversion of the ingested glucose to expired-air CO₂. Acipimox inhibited lipolysis in a similar manner in both experimental conditions. This was reflected by an almost complete suppression of the exercise-induced increase in plasma free fatty acid and glycerol and by an almost constant rate of lipid oxidation. Total carbohydrate oxidation evaluated by indirect calorimetry, was similar in both experimental conditions [C, 182, (SEM 21); G, 194 (SEM 16) g · 3 h^–1], as was lipid oxidation [C, 57 (SEM 6); G, 61 (SEM 3) g · 3 h^–1]. Exogenous glucose oxidation during exercise G, calculated by the changes in¹³C:¹²C ratio of expired air CO₂, averaged 66 (SEM 5) g · 3 h^–1 (19% of the total energy requirement). Consequently, endogenous carbohydrate utilization was significantly smaller after glucose than after placebo ingestion: 128 (SEM 18) versus 182 (SEM 21) g · 3 h^–1, respectively (P < 0.05). Symptoms of intense fatigue and leg cramps observed with intake of sweet placebo were absent with glucose ingestion.In conclusion, we found glucose ingestion during 3-h exercise with lipolysis blockade could provide metabolic substrate permitting a significant sparing of endogenous carbohydrate and consequently an improvement in performance.     

孕血清中早孕因子（EPF）的活性及其对T淋巴细胞亚群影响的研究

本文分别用抗人E受体、抗T_H、Ts细胞单抗的Ea花结抑制试验检测孕血清中EPF活性并对其进行了动态观察,同时检测了EPF活性与HCG-β、AFP、孕酮的关系以及对T淋巴细胞亚群的影响。结果说明:孕血清中EPF活性明显高于对照组(P<0.001)。孕血清中EPF活性主要通过对T_H细胞的作用实现。在孕早期EPF活性较高,随孕期延长活性逐渐下降,至孕6个月活性渐趋消失,分娩前10周基本消失。EPF活性与血中HCG-β、AFP浓度无关,与孕酮呈负相关。EPF不能直接抑制淋巴细胞的花结形成,但能显著地增强ATS、anti-CCT_3、anti-CD_4的花结抑制效应。     

The effect of isosorbide-5-mononitrate (5-ISMN) Durules(R) on exercise tolerance in patients with exertional angina pectoris. A placebo controlled study

Twenty-four patients with stable exercise-induced angina pectorisentered a double-blind cross-over study. Isosorbide-5-mononitrate(5-ISMN) 60 mg in a controlled release formulation (Durules^®)given once daily was compared with identical placebo. The exercisetolerance was determined by bicycle ergometry before and 3 hafter a single dose of 5-ISMN and following one week's treatmentwith 5-ISMN and placebo. Nineteen patients completed the study.Exercise tolerance until the onset of chest pain and until 1mm ST segment depression increased significantly 3 h after dose.The same increase was seen both after a single dose and thesame dose under steady-state conditions. No increase was seenwith placebo. The heart rate and systolic blood pressure reactionsin the standing position were less pronounced 3 h after dosein steady-state than after a single dose of 5-ISMN. Headachewas the only bothersome side-effect reported. The study demonstratesthat 60 mg 5-ISMN in a Durules^® formulation given once dailyhas a significant anti-anginal effect and that tolerance doesnot develop.     

Effects of single oral doses of bisoprolol and atenolol on airway function in nonasthmatic chronic obstructive lung disease and angina pectoris

Summary A randomized, placebo-controlled, double-blind crossover investigation in 12 patients with non-asthmatic chronic obstructive lung disease and co-existing stable angina pectoris was done to compare two ₁-selective adrenoceptor blocking agents, atenolol 100 mg and bisoprolol 20 mg. Systolic and diastolic blood pressures (SBP, DBP), heart rate (HR) as well as airway resistance (AWR, and less frequently forced expiratory volume in 1 s (FEV₁) and intrathoracic gas volume (ITGV) were measured in the sitting position before and at various times up to 24 h after drug intake.During the first 4 h both beta-blockers produced a significant reduction in HR in comparison to placebo (p<0.01). Atenolol 100 mg significantly increased AWR relative to placebo and bisoprolol (p<0.05). After 24 h, a significant reduction in HR (p<0.01) could only be demonstrated after bisoprolol, whereas atenolol alone led to a significant elevation in AWR relative to placebo and bisoprolol (p<0.05) at that time.It is concluded that bisoprolol appears to have a high degree of beta₁-selectivity, thus providing a wide split between beta₁- and beta₂-adrenoceptor blockade. Bisoprolol in its therapeutic dose range is expected to be relatively safe as regards bronchoconstriction in patients suffering both from hypertension and/or angina pectoris and chronic obstructive lung disease.