The ability of the SCORE high-risk model to predict 10-year cardiovascular disease mortality in Norway.

AIMS: To evaluate the predictive accuracy of the Systematic Coronary Risk Evaluation (SCORE) project high-risk function in Norway. METHODS AND RESULTS: We included 57 229 individuals screened in 1985-1992 from two population-based surveys in Norway (age groups 40-49, 50-59, and 60-69 years). The data have been linked to the Norwegian Cause of Death Registry. The SCORE high-risk algorithm for the prediction of 10-year cardiovascular disease (CVD) mortality was applied, and the risk factors entered into the model were age, sex, total cholesterol, systolic blood pressure, and smoking (yes/no). The number of expected events estimated by the SCORE model (E) was compared with the observed numbers (O). The SCORE low-risk algorithm was studied for comparison. In men, the observed number of CVD deaths was 718, compared with 1464 estimated by the SCORE high-risk function (O/E ratios 0.53, 0.53 and 0.45, for age groups 40-49, 50-59 and 60-69, respectively). In women, the observed and expected numbers were 226 and 547. The O/E ratios decreased with age (ratios 0.60, 0.45 and 0.37, respectively), i.e. the overestimation increased with age. The low-risk function predicted reasonably well for men (ratios 0.85, 0.92 and 0.79, respectively), whereas an overestimation was found for women aged 50-59 and 60-69 years (ratios 0.69 and 0.56, respectively). CONCLUSION: The SCORE high-risk model overestimated the number of CVD deaths in Norway. Before implementation in clinical practice, proper adjustments to national levels are required.     

Effects of the angiotensin II type 1 receptor antagonist telmisartan on monocyte adhesion and activation in patients with essential hypertension.

Circulating monocytes from hypertensive patients show elevated secretion patterns of pro-inflammatory cytokines, an increased expression of adhesion molecules, and an increased adhesion to vascular endothelial cells. We tested the hypothesis that telmisartan, an angiotensin II type 1 (AT(1)) receptor antagonist, reduces the activation of circulating monocytes from hypertensive patients and diminishes the monocyte-endothelial cell adhesion. Monocytes of 20 hypertensive patients and 20 normotensive controls were isolated by density gradient centrifugation and Dynabeads, and the monocyte adhesion to human aortic endothelial cell monolayers was measured by adhesion assays. To characterize monocyte activation we assessed the expression of activity-related cell surface markers that are also involved in monocyte adhesion to endothelial cells, such as CD11a/b and CD54, as well as the chemokine receptors CCR1, CCR2 and CCR5 before and after telmisartan therapy using flow cytometry. Spontaneous adhesion of monocytes from hypertensive patients and the adhesion after stimulation with angiotensin II were significantly increased compared with those in normotensive controls (p<0.05). Treatment of hypertensive patients with the AT(1) receptor antagonist telmisartan significantly diminished the adhesion of circulating monocytes to human endothelial cells (p=0.02) despite the increase in the expressions of CD11b, CD54 and CCR5 after telmisartan therapy. Reducing monocyte adhesion may be a novel beneficial effect of the AT(1) receptor antagonist telmisartan helping to prevent vascular alterations in hypertension. The mechanism of action remains to be elucidated, since reduction in monocyte adhesion was not attributable to changes in adhesion molecule expression.     

Schock

Shock is defined as a disproportion between oxygen supply and consumption based on a deficient perfusion of vital organs. Reduction of circulating blood volume (hypovolemic shock), cardiac failure with low output (cardiac shock) or the failure of peripheral vascular resistance (distributive shock) can result in shock. Preclinically the diagnosis of shock is determined by exploration, physical examination and – some – monitoring only. Therapy is directed towards the underlying cause whilst recovery and maintenance of adequate perfusion of vitals and tissue are of primary importance. This strategy includes the application of oxygen, fluids and catecholamines. Moreover, the choice of the hospital for further therapy is crucial in case of emergency.     

Structure-activity relations of antineoplastic platinum II and platinum IV coordination compounds

Five diammine-Pt(II) or Pt(IV) coordination compounds, namely cis-diammine-dichloro-platinum (II) "cis-DDP", transdihydroxy-cis-diammine-dichloro-platinum (IV) "trans-ODDP", and derived substitution products of lactic acid (racemates or L-forms) with diminished toxicity in comparison to cis-DDP have been tested against mouse leukemia P388, and partly on melanoma B16 for antineoplastic activity. The results have been compared with those obtained with the clinical approved cis-DDP. They were not in every way equal to the antitumor efficiency of cis-DDP. Improved physicochemical properties as well as favorable differences of side effects in contrast to cis-DDP, could be decisive for the potential value of these substances.     

Effect of ω-conotoxin GVIA on release of 3H-γ-aminobutyric acid from slices of rat neostriatum

Summary -Conotoxin GVIA (-CT) diminished the potassium-induced in vitro release of ³H--aminobutyric acid (³H-GABA) from slices of rat neostriatum in a manner which depended on the concentration of potassium. -CT (0.1 nmol/l) decreased the release of ³H-GABA induced by 25 mmol/l K⁺ from 11.6% to 6.1% of tissue content, ie. by 48%, while it did not affect the release of ³H-GABA caused by 20 mmol/l K⁺, which was 4.8% of tissue content. However, in the presence of a polyclonal antiserum or cysteamine (600 mol/l), both of which diminish the effects of endogenous somatostatin, 0.1–10 nmol/l -CT decreased the release of ³H-GABA induced by 20 mmoles/l K⁺ by 40%. It is concluded that -CT did not only inhibit GABA-neurones, but had an additional inhibitory effect on somatostatin neurones which are known to depress the release of ³H-GABA. It is further concluded that neuronal interactions, which are possible in brain slice preparations, may impede the interpretation of effects of drugs, especially if agents are used which affect basic mechanisms of transmitter release and thus the release of various transmitters from neurones. Send offprint requests to D. K. Meyer at the above address     

PCR analysis of pulsed-field gel electrophoresis-purified plastid DNA,a sensitive tool to judge the hetero-/homoplastomic status of plastid transformants

The genetic transformation of plastids of higher plants has developed into a powerful approach for both basic research and biotechnology. Due to the high copy number of the plastid genome per plastid and per cell, repeated cycles of shoot regeneration under conditions selective for the modified plastid chromosome are required to obtain transformants entirely lacking wild-type plastid genomes. The presence of promiscuous plastid DNA in nuclear and/or mitochondrial genomes that generally contaminate even gradient-purified plastid fractions reduces the applicability of the highly sensitive PCR approach to monitor the absence of residual wild-type plastid chromosomes in transformed lines. It is therefore difficult, or even impossible, to assess reliably the hetero- or homoplastomic state of plastid transformants in this manner. By analysing wild-type and transplastomic mutants of tobacco, we demonstrate that separation of plastid chromosomes isolated from gradient-purified plastid fractions by pulsed-field gel electrophoresis can overcome the problem of (co)amplification of interfering promiscuous plastid DNA. PCR analyses with primers specific for plastid, mitochondrial and nuclear genes reveal an impressive purity of such plastid DNA fractions at a detection limit of less than one wild-type plastid chromosome copy per ten transplastomic cells.