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Vascular smooth muscle cells (VSMCs) exhibit an extraordinary capacity to undergo phenotypic change during development, in vitro and in association with disease. Unlike other muscle cells they do not terminally differentiate. Development and maintenance of the mature contractile phenotype is regulated by a number of interacting transcription factors. In response to injury contractile VSMCs can be induced to change phenotype, proliferate and migrate to effect repair. On completion of the repair process VSMCs return to a nonproliferating contractile phenotype. In this way, in the context of atherosclerosis, a protective fibrous cap is formed and maintained at sites of injury. However in disease, when modulatory signals are perturbed, this phenotypic transition is dysregulated and VSMCs are induced to undergo inappropriate differentiation into cells with features of other mesenchymal lineages such as osteoblasts, chondrocytes and adipocytes. Moreover, evidence is accumulating that these aberrant phenotypic transitions contribute to the pathogenesis of vascular diseases such as atherosclerosis and Monckeberg's Sclerosis. Indeed, the osteo/chondrocytic conversion of VSMCs and the association of this phenotype with vascular calcification is a paradigm for how inappropriate differentiation can influence disease processes. Understanding of the mechanisms and signalling pathways involved in this particular phenotype change is well advanced offering the possibility for the design of successful therapeutic interventions in the future. [ABSTRACT FROM AUTHOR]

The article offers information on vascular and valvar calcification. It says that the increasing clinical burden of valvar calcification in elderly has emphasized the vitality of understanding the calcification within vascular tissues. It states that vascular calcification occurs in intima and the media arteries, while medial calcification occurs in artherosclerosis and intimal calcification. Moreover, medial calcification is a strong predictor of cardiovascular mortality in diabetics.

The influence of beta blockade on the ability of ST depression, during pre-discharge exercise testing, to predict coronary anatomy and subsequent complications was studied in 300 consecutive post-infarct patients, 125 of whom underwent cardiac catheterisation. At the time of exercise 62 patients were taking a beta blocker. The exercise test had a higher sensitivity in predicting multivessel disease in patients who were not taking beta blockers than in patients who were (95% v 76%). beta Blockade did not, however, influence the ability of the test to identify patients at risk of subsequent cardiac events (sensitivity 84% and 85% respectively). These results suggest that it is not necessary to stop treatment with beta blockers before predischarge exercise testing of patients who have had an acute myocardial infarction. [ABSTRACT FROM PUBLISHER]

A protocol for programmed ventricular stimulation is described in which the effect of increasing stimulation current on ventricular refractoriness and arrhythmia induction was specifically examined. The protocol was evaluated prospectively in 70 patients undergoing electrophysiological study for documented or suspected ventricular arrhythmias. Programmed electrical stimulation was performed at the right ventricular apex and outflow tract using single and double extrastimuli and burst pacing. Stimulation currents of 2, 5, 10, and 20 mA were used in ascending order. The initial (lowest) current was never less than twice diastolic threshold and was maintained during each stimulation run until refractoriness was reached. The current was then increased to the next level to facilitate premature capture until refractoriness was encountered at 20 mA or a sustained arrhythmia occurred. Ventricular arrhythmias were induced in 34 patients, 31 of whom had presented with a sustained ventricular arrhythmia. The incidence of induced arrhythmias was low in those patients who had presented with symptoms alone, a non-sustained arrhythmia, or a sustained arrhythmia in association with a predisposing clinical event. Only one patient with a negative result had further ventricular arrhythmias during the mean follow up period of 15 months. Although each increase in stimulation current caused a decrease in measured ventricular refractoriness, this resulted in only four arrhythmias. Only one arrhythmia was induced above 5 mA. These results suggest that this simple protocol using two extrastimuli and a single stimulation current of 5 mA will reliably identify most patients who have symptomatic ventricular arrhythmias. [ABSTRACT FROM PUBLISHER]

Comments on several issues related to medicine in Great Britain. Problems associated to perinatal pathology; Ventricular fibrillation induced by xipamide; Effectiveness of child health clinics.

Replication-deficient adenoviral vectors have been widely used for gene transfer with the aim of delivering genes of interest to investigate their function and potentially to treat human disease. The ability to critically evaluate the biological role of a gene of interest, using adenovirus-based vectors, has been hampered by the development of local inflammation at the site of delivery. We have demonstrated that high multiplicity infection of human VSMCs with a replication-deficient adenoviral vector expressing no transgene leads to activation of the transcription factor NFκB. Activation of NFκB by this mechanism was able to augment gene expression from the human cytomegalovirus immediate–early promoter (CMV-IEP) and induce expression of the adhesion molecule ICAM-1 in human VSMCs. These effects were inhibited by pretreatment with Nα-p-tosyl-L-lysine chloromethyl ketone (TLCK), a serine protease inhibitor known to inhibit the activation of NFκB. This important effect of the vector itself may have profound implications when replication-deficient adenoviral vectors are used for experimental gene transfer at a high multiplicity of infection. [ABSTRACT FROM AUTHOR]

It has been reported previously in white patients with essential hypertension that red cell sodium pump activity as measured by ouabain-sensitive uptake of the potassium analogue Rb from a potassium-free medium, is very significantly greater than in white controls. In a further study of black (West Indian) subjects reported here no similar abnormality was present in black hypertensives when compared with black normotensive individuals. Red cell rubidium uptake was significantly lower in normotensive blacks than in normotensive whites although sodium pump activity was the same. These results may be relevant to observed racial differences in sodium handling and in the pathophysiology of essential hypertension. [ABSTRACT FROM PUBLISHER]

A 76 year old man developed a left pneumothorax after implantation of a permanent endocardial pacemaker via the left subclavian vein. The resulting surgical emphysema caused temporary failure of the pacing system. [ABSTRACT FROM PUBLISHER]

A letter to the editor is presented in response to the article about aortic plaque inflammation as a potential cause of stroke that was published in the previous issue of the periodical.

The article focuses on a study that relates plaque inflammation measured by 1 8FDG PET to high resolution Maganetic resonance imaging (MRI) which, by imaging the vessel wall, can identify non-stenotic atherosclerosis, in patients with recent transient ischaemic attacks. 11 patients scheduled for carotid endarterectomy following TIA on the basis of angiographic appearance were studied. High-resolution (MRI) was carried out using a dedicated phased array neck MR coil, on a GE 1.5 Tesla machine. PET scans were acquired using a 3D dynamic protocol with injection of 1 85MBq of 1 8FDG.