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.     

Situational and psychophysiological factors in psychologically induced pain

To investigate pain that occurs in the absence of painful stimulation, normal subjects were connected to a sham stimulator and were told that a headache could occur as a result of the electrical current they would receive. Half of the subjects who received this suggestion reported pain. The frequency and intensity of pain reports in a group which was given prior pain experience as a reference point in reporting pain and in a group which was exposed to a manipulation designed to reduce intentional deception were not significantly different from the pain reports of a group not exposed to these manipulations. The frequency of pain reports in subjects not connected to the sham stimulator but still asked to report pain was 25% which was significantly less than the frequency for subjects who were told there would be stimulation to the head. Pain ratings increased as the settings of the sham stimulator were increased. Subjects who reported pain had significantly fewer electrodermal responses to tones signaling them to prepare for a reaction time task. The results suggest that pain can be produced in the absence of peripheral stimulation. The pain does not appear to be due to intentional deception or the lack of a standard for comparison, but is strongly influenced by environmental cues. Psychophysiologically, pain responders were less attentive to signal stimuli.     

Role of cytokines and chemokines in prion infections of the central nervous system

Prion infections of the central nervous system (CNS) are characterised by a reactive gliosis and the subsequent degeneration of neuronal tissue. The activation of glial cells, which precedes neuronal death, is likely to be initially caused by the deposition of misfolded, proteinase K-resistant, isoforms (termed PrP(res)) of the prion protein (PrP) in the brain. Cytokines and chemokines released by PrP(res)-activated glia cells may contribute directly or indirectly to the disease development by enhancement and generalisation of the gliosis and via cytotoxicity for neurons. However, the actual role of prion-induced glia activation and subsequent cytokine/chemokine secretion in disease development is still far from clear. In the present work, we review our present knowledge concerning the functional biology of cytokines and chemokines in prion infections of the CNS.     

The apex cardiac beat: not a reliable clinical sign in elderly patients.

To assess its reliability as a marker of cardiomegaly in elderly patients, we compared a clinical assessment of heart size with that calculated from chest radiography. In 100 hospitalized subjects of median age 78 years, the apex beat was palpable in only 35% and its palpability declined with increasing age. Even when palpable, the apex beat had low specificity (74%) and sensitivity (69%) as a marker of cardiomegaly and its positive predictive value (69%) and negative predictive value (74%) were poor. The clinical assessment of heart size in elderly hospitalized patients should be interpreted with caution.     

Comparative investigation of hair with the genRES® MPX-SP1, genRES MPX-SP2, and genRES MPX-2 kits

In recent years there has been considerable improvement in short-tandem repeat (STR) investigations of hair, which were previously marred by small amounts of nuclear DNA and its degradation. This study examined the suitability of two STR kits with shortened amplicons for the investigation of hairs from routine casework. The overall sucess rate was more than 20%. Furthermore, the usefulness of quantification with real-time ploymerase chain reaction as a screening method was demonstrated.