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Background: In 1989, the European Working Party on High Blood Pressure in the Elderly started the double-blind, placebo-controlled, Systolic Hypertension in Europe Trial to test the hypothesis that antihypertensive drug treatment would reduce the incidence of fatal and nonfatal stroke in older patients with isolated systolic hypertension. This report addresses whether the benefit of antihypertensive treatment varied according to sex, previous cardiovascular complications, age, initial blood pressure (BP), and smoking or drinking habits in an intention-to-treat analysis and explores whether the morbidity and mortality results were consistent in a per-protocol analysis., Methods: After stratification for center, sex, and cardiovascular complications, 4695 patients 60 years of age or older with a systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg were randomized. Active treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d) and/or hydrochlorothiazide (12.5-25 mg/d), titrated or combined to reduce the sitting systolic BP by at least 20 mm Hg, to below 150 mm Hg. In the control group, matching placebo tablets were employed similarly., Results: In the intention-to-treat analysis, male sex, previous cardiovascular complications, older age, higher systolic BP, and smoking at randomization were positively and independently correlated with cardiovascular risk. Furthermore, for total (P = .009) and cardiovascular (P = .09) mortality, the benefit of antihypertensive drug treatment weakened with advancing age; for total mortality (P = .05), the benefit increased with higher systolic BP at entry, while for fatal and nonfatal stroke (P = .01), it was most evident in nonsmokers (92.5% of all patients). In the perprotocol analysis, active treatment reduced total mortality by 24% (P = .05), reduced all fatal and nonfatal cardiovascular end points by 32% (P<.001), reduced all strokes by 44% (P = .004), reduced nonfatal strokes by 48% (P = .005), and reduced all cardiac end points, including sudden death, by 26% (P = .05)., Conclusions: In elderly patients with isolated systolic hypertension, stepwise antihypertensive drug treatment, starting with the dihydropyridine calcium channel blocker nitrendipine, improves prognosis. The per-protocol analysis suggested that treating 1000 patients for 5 years would prevent 24 deaths, 54 major cardiovascular end points, 29 strokes, or 25 cardiac end points. The effects of antihypertensive drug treatment on total and cardiovascular mortality may be attenuated in very old patients.

Objective: To assess cognitive functions and their correlates for a dementia-free cohort of old patients with isolated systolic hypertension., Design: Cross-sectional data from the randomization period of the European Trial in Elderly with Systolic Hypertension (Syst-Eur Vascular Dementia Project)., Setting: Sixteen European countries and Israel., Participants: We studied 2252 patients aged 60-100 years (mean 70)., Main Outcome Measures: Mini Mental State Examination (MMSE) and Spearman correlation of MMSE scores to demographic data or blood pressure., Results: The MMSE was successfully completed for 1474 women and 751 men. The baseline blood pressure averaged 173 +/- 10/86 +/- 6 mmHg (means +/- SD). Median age at which education of patients at school had stopped was 15 years. Men and women who consumed alcohol (28%) had median intakes of 8 and 3 g/day, respectively. The median MMSE score was 29 (range 15-30). The maximum score of 30 was attained by 609 (30%) subjects. Fifty-nine (3%) patients had a MMSE score of 23 or less. The MMSE score decreased with advancing age (r = -0.21, P < 0.001). Both for men and for women, it was positively correlated to the level of education (r = 0.30 and r = 0.32, P < 0.001). For women after adjustment for age and the level of education, the score was correlated negatively to systolic blood pressure (r = -0.07, P < 0.05) but positively to intake of alcohol (r = 0.06, P < 0.05)., Conclusion: In a cohort of elderly patients with isolated systolic hypertension, baseline cognitive function measured in terms of the MMSE score was high, probably due to selective recruitment of patients who were not clinically demented. Blood pressure was a weak contributor to cognitive status compared with age and level of education. Baseline cognitive function of women was negatively and independently correlated to systolic blood pressure.

The dynamics of binding of exogenous alpha-tocopherol (alpha-T) added to native or oxidatively modified LDLs (LDLs or oxLDLs) were investigated. Venous blood from 31 clinically healthy blood donors (15 males and 16 females) was used. LDLs were isolated by density gradient ultracentrifugation. LDLs were oxidized in vitro by CuSO4. LDLs or oxLDLs were enriched with exogenous alpha-T (initial concentrations: 0; 10; 20; 50; or 100 nmol per mg protein). The contents of alpha-T in LDLs or in oxLDLs were measured by HPLC. Lag-phase of LDL oxidation before or after saturation with alpha-T was recorded. Correlation analysis of the lag-phase of LDL oxidation and alpha-T content in LDLs was carried out by the method of Esterbauer et al. The experimental results demonstrated that: (i) alpha-T was incorporated into native LDLs to a higher extent as compared to oxLDLs. (ii) A saturation of LDLs and oxLDLs with alpha-T was observed. (iii) A positive correlation was observed between the duration of the lag-phase of LDL oxidation in vitro and the content of alpha-T in LDLs. (iv) Based on LDL saturation with alpha-T, the persons could be classified in two groups: LDLs from group I of 26 persons were found to incorporate exogenous alpha-T to the extent of 1.8 to 3 times its initial concentration; LDLs from group II of 5 persons incorporated little or no exogenous alpha-T. In the first group, oxidation of LDLs lead to a considerable decrease in alpha-T dependent variable k and to a moderate reduction of alpha-T-independent variable alpha in the equation of Esterbauer et al.: lag-phase = k.[alpha-tocopherol]+alpha. In the second group, oxidation of LDLs lead to insignificant changes in k, as well as in a. (v) According to the levels of k and a the native LDLs from the second group of 5 persons were very close to oxLDLs from the first group of 26 persons. Presumably, native LDLs from the second group of persons were initially oxidatively modified, and probably this will be a risk group in relation to atherogenic disorders.

A precise diagnosis of initial reticular forms of pneumoconioses is very difficult. The present study focuses on 30 patients with initial reticular forms of silicosis, asbestos induced interstitial lung fibrosis, mixed dust pneumoconioses and pneumoconioses of electrowelders. The anterior-posterior chest radiography (according to the ILO International Radiological Classification of Pneumoconioses, 1980), high-resolution computed tomography (HRCT), perfusion scintigraphy with 99mTc and the changes in the diffusion capacity were compared. The diagnostic value of these methods was assessed. The study continues by expanding the groups of patients examined and by including the membrane component of diffusion.

Oxidative modifications of blood serum in humans with and without coronary artery disease were investigated. Four parameters were analyzed: the intensity of serum fluorescence, which is indicative of the content of lipofuscine-like lipid peroxidation products; the content of thiobarbituric acid-reactive substances; the lag-phase of serum oxidation by azo-compounds; and the content of lipophilic natural antioxidants--alpha-tocopherol, beta-carotene and ubiquinol-9(10). It was found that coronary artery disease resulted in a significant increase of serum fluorescence and the content of TBARS. The atherogenic disorders in humans with coronary artery disease drastically decreased the lag-phase of serum oxidation in the presence of 2,2'-azo-bis-(2-amidinopropane) dihydrochloride. The oxidative modifications of serum were in close correlation with the balance of natural lipophilic antioxidants in blood serum, i.e. alpha-tocopherol, ubiquinols and beta-carotene. The contents of all antioxidants tested in serum were significantly decreased in patients with coronary artery disease.

The identification of apometallothionein (AMT) in rat liver by reversed-phase high-performance liquid chromatography (RP-HPLC) after gel permeation was realized in experiments performed both in vivo and in vitro. The reliable assignment of the corresponding AMT peak permitted the detection and determination of AMT in different groups of experimental and control rats. In all animals studied (more than 100 rats), AMT was always present in amounts higher than that of metallothionein (MT) or compatible with it. Induction of MT synthesis by CdCl2 subcutaneous injections decreased the AMT level and increased the MT level, but nevertheless the amount of AMT still remained relatively high.

The influence of Zn-complexes with biologically active ligands like aminoacids: picolinic acid as Zn(pic)2 and asparaginic acid as Zn(asp)2 on HSV-1 infection in vitro was investigated. Studies on kinetics of Zn-ions using labeled 65Zn(pic)2 as a marker, show that at the 45th min Zn-ions are exposed onto or into cells. When cells were infected 60min after the treatment with 65Zn(pic)2, 1h later the activity of Zn-ions in the cell fraction decreased while in the medium increased. This result shows that soon after the infection cells expelled part of their Zn. If Zn(pic)2 or Zn(asp)2 are added at the end of the adsorption period, ICP4 and ICP8 are localized in the cytoplasm but not in the nucleus of infected cells, while the synthesis of gH is decreased. A sharply increased number of nucleocapsids with low electron density cores was also found.

The metallothionein (MT) synthesis was induced in the liver of spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats through sc injections of CdCl2 for 3 and 6 days. The MT contents of the liver of these animals and of untreated rats from both groups were determined by gel filtration, HPLC, SDS/PAGE and amino acid analysis. The isoforms MT1 and MT2 were identified and their Cd, Zn and SH-group contents were determined. The SHR showed significantly higher values of MT than WKY rats in the untreated animals and on the 3rd day of the induction. On the 6th day, the MT levels in both groups were equal. The Cd and Zn contents followed the MT concentration in the homogenates. The possible relation between the arterial hypertension and the zinc and copper homeostasis is discussed.

1. The alpha- and beta-adrenoceptor blocking action of AH 5158A was investigated in man using the veins of the hand, the arterial bed of the forearm, and certain responses of the circulation as a whole.2. In the veins, locally infused AH 5158A resulted in specific and competitive antagonism of the constrictor response to locally infused noradrenaline and of the dilator response to isoprenaline.3. Brachial artery infusions of AH 5158A resulted in competitive antagonism of the arterial blood flow changes produced by local infusions of noradrenaline and isoprenaline.4. Systemic infusion of AH 5158A (0.5-0.9 mg/kg) produced clear blockade of the heart rate response to systemic infusion of isoprenaline. It also attenuated the response to exercise at 80 watts for 4 min; mean arterial pressure during exercise was reduced by 16% and heart rate by 18%. Blockade lasted at least 1 hour.5. AH 5158A caused small changes in arterial pressure and heart rate at rest supine, but had no effect on the response of pressure and rate to tilting.

1. The antagonism at alpha-adrenoceptors by thymoxamine and phentolamine of the response to noradrenaline was investigated in the limb veins and arteries of man.2. Brachial artery infusions of thymoxamine (40 mug/min) produced rises in resting arterial flow of up to 100%. When infused mixed with noradrenaline, thymoxamine (40 mug/min) attenuated the blood flow response to noradrenaline. Blockade was of a similar degree to that which occurred following a 10 min infusion of phentolamine (40 mug/min).3. Local intravenous infusion of thymoxamine (400-2,000 ng/min) mixed with noradrenaline attenuated the venoconstrictor response to noradrenaline. The degree of attenuation was similar to that seen after a 10 min infusion of phentolamine (500 ng/min). Blockade after thymoxamine did not last longer than 16 minutes. Neither thymoxamine nor phentolamine altered resting venous compliance.4. Local intravenous infusions of thymoxamine (500 ng/min) and phentolamine (500 ng/min) abolished the sympathetically mediated venoconstriction produced by overbreathing.5. Systemic injection of thymoxamine (0.1 mg/kg) did not block the reduction in forearm arterial flow produced by locally infused noradrenaline. In two out of three experiments, however, it produced some antagonism of noradrenaline induced venoconstriction. Systemic phentolamine (5 mg) blocked the effect of noradrenaline in the arterial bed, but antagonized its actions in the veins in only one out of three experiments.