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Objective: To assess the efficacy of non pharmacological primary prevention of hypertension., Methods: Analysis of all the available trials with a minimal one-year follow-up and one recently study with 8 weeks follow-up. The outcomes consisted in blood pressure changes and incidence of hypertension at the end of the study., Results: Five reviewed randomized controlled trials with a minimal one year follow-up and one recently study with eight weeks follow-up assessed the following intervention: advice about sodium restriction, weight reduction, physical exercise and relaxation, a diet rich in fruits vegetables and low fat dairy foods. All the results were available according to the "intention to treat principle". The feasibility appeared to be initially good, but decreased with time, confirming the difficulty of long term prevention. The prevention effect was mild with a decrease in hypertension incidence of a few percent (2%) and blood pressure decrease of only a few mmHg reduction (mean of 3 mmHg). Three community studies were reviewed. The prevention interventions were carried out on entire populations. The feasibility was bad (great number of lost-follow-up). The results on the blood pressure incidence were available in only one study and the blood pressure decrease estimates were heterogeneous, so the results cannot be generalized., Conclusion: The primary prevention of hypertension shows disappointing results when the intervention duration is above one year. It leaves little hope for a significant effect on blood pressure dependent cardiovascular events.

The neoantigens of the C5b-9 complement complex, IgG, C3, C4, S-protein/vitronectin, fibronectin, and macrophages were localized on 17 samples of breast cancer and on 6 samples of benign breast tumors using polyclonal or monoclonal antibodies and the streptavidin-biotin-peroxidase technique. All the tissue samples with carcinoma in each the TNM stages presented C5b-9 deposits on the membranes of tumor cells, thin granules on cell remnants, and diffuse deposits in the necrotic areas. When chemotherapy and radiation therapy preceded surgery, C5b-9 deposits were more intense and extended. The C5b-9 deposits were absent in all the samples with benign lesions. S-protein/vitronectin was present as fibrillar deposits in the connective tissue matrix and as diffuse deposits around the tumor cells, less intense and extended than fibronectin. IgG, C3, and C4 deposits were present only in carcinoma samples. The presence of C5b-9 deposits is indicative of complement activation and its subsequent pathogenetic effects in breast cancer.

Tumor necrosis factor-alpha (TNF-alpha) was demonstrated in human normal and atherosclerotic aorta, iliac and femoral arteries by immunohistochemistry using monoclonal and polyclonal antibodies. TNF was present in the cells of the arterial wall and as granular and diffuse extracellular deposits in the connective tissue matrix. Quantitative determinations of TNF by ELISA showed mean values of 21.7 +/- 0.7 ng/100 mg total extracted protein in normal intima, 38.2 +/- 0.5 in intimal thickenings, 25.5 +/- 1.1 in fibrous plaques and 16.8 +/- 0.2 ng/100 mg total extracted protein in media. Intimal thickenings presented the highest amounts of TNF with a statistically significant difference when compared to normal intima (P less than 0.05) and media (P less than 0.01). TNF-alpha concentrations in arterial eluates were about 200 times higher than in the corresponding serum samples. Western blotting analysis confirmed TNF-alpha eluted from the arterial wall to be about 17 kDa similar to human recombinant TNF-alpha. TNF-alpha in human atherosclerotic wall could be actively involved in the inflammatory events associated with atherosclerosis.

The study included 62 patients with atherosclerosis obliterans of the lower extremities, of whom 47 in stage II, 5 in stage III and 10 in stage IV of the disease. In 22 patients were present single arterial obliteration, in 30 patients multiple, layered arterial obliterations, in 8 distal arterial obliterations and 2 a diffuse atherosclerosis of the lower extremities. Patients were examined in admission to the clinic, after the treatment performed at the clinic and at various intervals, during 2-4 years. The segmental arterial pressure, the pressure index and the ultrasonogram recorded with the Cardior electrocardiograph were followed-up. The arterial pressure and the pressure indices returned to normal values only after invasive procedures. The medical treatment can bring about the clinical regression and stabilization of the disease, as well as the improvement of the ultrasonogram. For the choice of therapeutic means, the pressure index is the best criterion, since it correlates with the severity of the disease. In the case of a pressure index 0.75, the medical treatment or the transluminal dilatation is preferred, whereas at an index of 0.7 the surgical revascularisation is considered necessary. Other ultrasonic parameters were also taken into account, such as the systolic passage time and the maximum velocity, which are less important in the attainment of the mentioned aims.(ABSTRACT TRUNCATED AT 250 WORDS)

Decay-accelerating factor (DAF) is an intrinsic membrane inhibitor that regulates the activity of C3 and C5 convertases of the classical and alternative complement pathways. Using two monoclonal antibodies, IC6 and IA10, DAF was localized by immunohistochemistry using streptavidin-biotin-peroxidase complex or silver-intensified immunogold techniques in aortic, iliac and femoral samples obtained at surgery and autopsy from 32 patients. DAF was localized on the cells and in the connective tissue matrix of the arterial wall. Fibrous plaques and intimal thickenings presented larger amounts than fatty streaks, intimae and normal areas. By Western blotting analysis, DAF extracted from the arterial wall had a molecular weight of about 67 kDa. Using a double-labeling technique, DAF and C5b-9 complexes were co-localized on nucleated cells and on cell debris. The cells isolated after enzyme digestion of the arterial wall were tested for the protective role of DAF to complement-mediated damage. When DAF of the sensitized cells was blocked by monoclonal antibodies, complement-mediated cell lysis was enhanced from 10-15% to 60-70%. The effect of anti-DAF antibodies was dose-dependent. DAF blocking in the absence of antibodies used for sensitization led to a lysis under 10%. These data suggest a protective role of DAF against autologous complement activation, however insufficient to prevent complement activation in the human atherosclerotic wall.

Concentration and preferential retention of immunoglobulins and complement components were studied in comparison with other plasma proteins in 42 human aortae with atherosclerosis. Saline and acid extracted IgG, IgA, IgM, C1q, C3c, C4, C9, C3A, C-reactive protein, alpha 1-antitrypsin, alpha 2-macroglobulin, albumin, transferrin and fibrinogen were quantitatively determined using the radial immunodiffusion. The fibrous plaques and their adjacent areas contained higher levels of each protein than intima with only fatty streaks. No significant differences were found between the fibrous plaques and their adjacent areas presenting intimal thickenings. Saline eluted IgG and IgA were significantly higher in the fibrous plaque intima than in intimal samples with fatty streaks and were the only proteins detected in the acid eluates. The complement components were present in all saline eluates, while C-reactive protein was found in 23 samples. Crossed immunoelectrophoretic studies showed the activation of saline C3 and C4. In 8 cases serum levels of the studied proteins were compared with their concentration in saline eluates obtained from intima and media. The immunoglobulins and complement components presented higher intima/serum and lower media/intima retention ratios than the other studied proteins suggesting their preferential retention in the intima. The presence of immune related proteins in the atherosclerotic intima and their preferential retention might be explained not only by an altered permeability but also in relation to their function.

The co-localization of terminal C5b-9 complement complexes and macrophages was investigated in human arteries with atherosclerosis using a double-labeling immunohistochemical technique. Macrophages were found in all the atherosclerotic arteries, with the accumulation correlating positively with the degree of atherosclerosis. This accumulation was associated with an increase of C5b-9 deposits, as well as with an increase in the number of deposits containing both complement components and macrophages ('co-localization'). This co-localization was found to pertain both to intact macrophages and to macrophage remnants. These data suggest that C5b-9 complement complex might be formed on macrophages with subsequent promotion of inflammatory events and progression of the atherosclerotic lesions.

S-protein/vitronectin is a multifunctional glycoprotein interacting with both complement activation and coagulation pathways. Its presence was investigated in 5 femoral and 5 iliac atherosclerotic human arteries, obtained at surgery, by immunoelectron microscopy using an affinity purified rabbit IgG specific for human S-protein/vitronectin. The immunoelectron dense specific deposits were found in both intimal thickenings and fibrous plaques in association with elastic fibers, collagen bundles and cell debris in the vicinity of elastin. Cell debris embedded in the collagen matrix were S-protein/vitronectin negative. S-protein/vitronectin was also absent on intact cells, lipid droplets and cholesterol clefts. All cell debris, however, was positive for C5b-9 deposits suggesting that complement activation had occurred at these sites with or without S-protein/vitronectin interaction. S-protein/vitronectin may play a role in the arterial wall defence by restricting the extent of complement activation.

The absolute and relative bioavailability of nifedipine (1) from different formulations administered as single oral doses in healthy volunteers was determined. Serum concentrations of 1 were measured by GC. The absolute bioavailability of 1 was 53% because of presystemic metabolism. The bioavailability of Adalat (Bayer) tablets, Nifedipina (Terapia) and Corinfar (VEB Arzneimittelwerk Dresden) sugar-coated tablets was 93%, 92% and 86% (respectively) as compared with Adalat capsules. The AUC were not significantly different. The Cmax and tmax values were different, indicating that the absorption of 1 showed differences in first-order rate constants of dissolution in the above mentioned order. Despite the differences among the formulations studied, each preparation may have its merits. In a multiple dose regimen of 20 mg 1 (Nifedipina, Terapia) t.i.d., minimal therapeutic drug levels were achieved and maintained during steady state, from the 1st d of treatment.

Gamma-glutamyltransferase (gamma-GT) was found to exceed the upper normal limit in 31 of the 32 patients with liver metastases verified during surgery or at autopsy, while the level of this enzyme was normal in 25 of the 28 patients with proven neoplasma but without evidence of metastatic involvement of the liver. Particularly high values of gamma-GT activity were noted in 9 patients in whom liver metastases were accompanied by clinical jaundice. A similar behaviour was noted for alkaline phosphatase but changes affecting this enzyme were less obvious. Thus, for a mean increase of gamma-GT to levels up to seven times the upper normal limit, the level of alkaline phosphatase increased only three times. A decrease of serum pseudocholinesterase occurred in most patients with neoplasma, the process being more evident when liver metastases were present. It is concluded that an increase of gamma-GT in a patient with neoplasma could be considered as a marker of hepatic metastases, if chronic alcoholism or hepatobiliary disease can be excluded.

Decreased levels of serum cholesterol and beta-lipoproteins occurring in hyperthyroidism were found to be accompanied by an enchanced activity of pseudocholinesterase, while in patients with myxedema, the pathologically increased levels of serum cholesterol and beta-lipoproteins were associated with diminished serum pseudocholinesterase activity. The percentage of the pre-beta fraction was found to be increased in both hypo- and hyperthyroid patients, but mechanisms leading to this change are probably different in the two pathological conditions. The behaviour of cholesterol and pseudocholinesterase activity and especially the ratio between these paramameters might be used for the diagnosis of thyroid disease and for the control of therapeutic efficiency.

Serum concentration of ionic calcium and the effect of dietary salt restriction on serum total calcium was studied in patients with essential arterial hypertension. The concentration of serum ionic calcium was significantly lower than in controls in all the evolutive stages of the disease (p less than 0.005; p less than 0.005; p less than 0.001). During salt restriction serum total calcium rises significantly (p less than 0.005) as compared with the values found under a salt containing diet. It was suggested that increased chronic ingestion of sodium or restriction of dietary salt produces alterations in Na-Ca exchanges across semipermeable membrane of the smooth muscle.

Electrocardiographic signal recorded in right unipolar leads (2V1, 3V1, V1) was amplified (up to 500,000 times) averaged (256 or 512 cardiac cycles) and finally digitally filtered, in order to record His-Purkinje (HP) activity. A group of 41 patients with sinus rhythm and PR intervals ranging between 100 and 250 ms was repeatedly investigated. Distinct and highly reproducible waveforms located in the PR segment, attributable to HP activity, were recorded on the averaged unfiltered traces in 14 patients (34%). Waveforms, with an amplitude ranging between 4 and 80 microV, were positive in 13 patients and negative in one. In one patient, with atrial tachycardia with 2:1 atrioventricular block, two positive successive deflections suggested the possibility of recording the proximal and distal His activity. Externally recorded averaged unfiltered traces could be useful for the investigation of HP activity in a relatively large proportion of patients.