Platelet alpha 2 adrenoceptor characteristics during the morning increase in platelet aggregability.

The incidence of myocardial infarction and sudden cardiac death increases in the morning, as do platelet aggregability and sympathetic activity. We considered the possibility that increased platelet aggregability in the morning was due to an increase in platelet alpha 2 adrenergic receptor number or agonist binding affinity, or to a temporal disparity between the increase in sympathetic activity that accompanies arising and the anticipated decrease in platelet high affinity alpha 2 adrenoceptors. To evaluate these possibilities, we studied eight healthy male volunteers (20-35 years) before and 1-1.5 and 3-4 h after they arose at 08.00 h and performed routine morning activities. Platelet aggregability was determined in platelet-rich plasma; alpha 2 adrenoceptor density and agonist binding affinity were determined in intact platelets and in membrane preparations using the alpha 2 selective ligand [3H]-yohimbine. The threshold concentration of epinephrine required to produce biphasic aggregation decreased (i.e. platelet aggregability increased) from 3.6 +/- 1.2 to 0.9 +/- 0.3 microM (P less than 0.05) after arising. However, alpha 2 adrenoceptor density (380 +/- 71 to 365 +/- 51 sites per platelet) and agonist binding affinity assessed simultaneously did not change after arising, suggesting that the increase in platelet aggregability is due to factors extrinsic to the platelets or to an intra-platelet mechanism distal to the receptor level.     

Variation in the gene for human peroxisome proliferator activated receptor gamma (PPARgamma) does not play a major role in the development of morbid obesity

OBJECTIVE: To determine the extent of variation in the gene for peroxisome proliferator activated receptor gamma (PPARgamma) in patients with morbid obesity. SUBJECTS: Two hundred morbidly obese patients who underwent gastric banding surgery and 192 healthy blood donors. Diabetics were excluded. EXPERIMENTAL: The frequency of the P115Q and P12A variants in the PPARgamma gene was determined. Single strand conformational polymorphism (SSCP) analysis was performed on all exons, exon/intron boundaries and part of the promoter of the PPARgamma gene on a sub-group of 67 morbid obese patients. RESULTS: None of the morbid patients or the blood donors were carriers of the P115Q mutation. The frequency of the P12A polymorphism did not differ significantly between morbid obese patients and controls and there was no statistically significant association between P12A and BMI. Male blood donors who were A12A homozygotes had statistically significant higher serum leptin concentrations (P = 0.001). Mutation screening revealed that one patient had a T -->G transversion at -208 in the promoter of PPARgamma-2, two had silent mutations, one a T-->C transition in the third base of codon 144 and the other a C-->T transition in codon 297. The fourth patient had a CGC-->TGC transition in codon 316 resulting in the replacement of an arginine with a cysteine. This mutation was not found in any other morbidly obese patient. CONCLUSION: Variation in the PPARgamma gene is unlikely to play a major role in the development of morbid obesity.     

Non-hodgkin's lymphoma of the heart in patients infected with human immunodeficiency virus

A case of HIV-associated cardiac non-Hodgkin's lymphoma (NHL) is described, and the epidemiologic and clinicopathologic features of 21 cases previously reported in the literature are analyzed. All patients were homosexual males, and the cardiac NHL was the first acquired immune deficiency syndrome-defining condition in the majority. Patients were referred with nonspecific clinical findings including dyspnea and tachycardia, but rapid progression of cardiac dysfunction was frequent after symptoms appeared. Echocardiography constitutes the most useful noninvasive procedure in the diagnosis of cardiac NHL. Most of the patients had disseminated disease at initial presentation; pathologically, the lymphomas were of B lymphocyte origin and of high-grade subtypes. Prognosis of HIV-associated cardiac NHL is generally poor, although clinical remission has been observed with combination chemotherapy. Cardiac lymphomas in HIV-associated patients are typically high-grade and often disseminate early. Although the prognosis is poor, patients in whom dissemination has not occurred could have longer survival under systemic chemotherapy.     

Different relation between 24-h blood pressure and distensibility at different peripheral arteries. Data from the European Lacidipine Study on Atherosclerosis (ELSA)

INTRODUCTION: The European Lacidipine Study on Atherosclerosis (ELSA) has been planned to investigate the effect of reduction in office and ambulatory blood pressure by lacidipine versus atenolol on carotid artery wall thickness in mild to moderate essential hypertensive patients with no metabolic abnormalities. One prespecified sub-study of ELSA focused on measurements of arterial distensibility in the carotid as well as in the radial artery to determine the relationship of functional arterial properties with office versus ambulatory blood pressure (BP) values as well as the correspondence between functional and structural arterial alterations. METHODS: The sub-study was conducted on 124 patients recruited in four centres (Monza-Milan, Paris, Grenoble and Glasgow). BP was measured both by a mercury sphygmomanometer and by 24-h ambulatory monitoring. Common carotid artery wall thickness was measured by certified sonographers as described in the main study. Common carotid and radial artery distensibility were obtained by echotracking techniques, which allowed to relate changes in arterial diameter with systo-diastolic BP changes. RESULTS: Carotid artery wall distensibility showed (1) a negative correlation with office and more so 24-h average systolic BP (r = -0.45 and -0.58, P < 0.008 and 0.001) but not with office or 24-h diastolic BP) and (2) a negative correlation with the corresponding wall thickness (r = -0.47, P < 0.005). In contrast, at the radial artery level distensibility and thickness showed no correlation with each other and with BP. Carotid (but not radial) artery distensibility also correlated with ambulatory systolic BP variability but the correlation was lost after adjustment for age and mean BP values. CONCLUSION: These data suggest that stiffening of large elastic artery is reflected more by ambulatory than office BP elevations, systolic BP being much more important than diastolic. Alterations of large elastic arteries function is related to structural wall changes. Functional and structural properties of middle-size muscle arteries are independent of BP.     

Mutation screening in dilated cardiomyopathy: prominent role of the beta myosin heavy chain gene.

AIMS: Familial dilated cardiomyopathy (FDCM) is associated with mutations in more than 10 genes, but genes mutation frequencies and associated clinical features remain largely unknown. Here, we performed a mutation analysis of four genes involved in FDCM in a population of idiopathic DCM. METHODS AND RESULTS: A SSCP and sequencing mutation screening of all the exons coding for beta myosin heavy chain (MYH7 gene), cardiac T troponin (TNNT2 gene), phospholamban (PLN gene), and the cardio-specific exon of metavinculin (VCL gene) were performed in 96 independent patients (54 familial and 42 sporadic). It led to the identification of eight heterozygous mutations, seven new ones in MYH7, and the already described R141W mutation in TNNT2. MYH7 mutations (in five familial and two sporadic cases) substitute residues located either in the head (I201T, T412N, A550V) or tail domains (T1019N, R1193S, E1426K, R1634S) of the protein. DCM was not associated with skeletal myopathy or conduction defects in any patients. Contrasting clinical features were observed between MYH7 and TNNT2 mutations carriers. In MYH7 vs. TNNT2, mean age at diagnosis was late (P<0.03), penetrance was incomplete in adults (56 vs. 100%), and mean age at major cardiac event was higher (P<0.04). CONCLUSION: We have identified seven mutations in MYH7, one in TNNT2, and none in PLN or in the VCL cardio-specific exon. MYH7 appears as the most frequently mutated gene in our FDCM population (approximately 10%), and mutation carriers present with delayed onset, in contrast to TNNT2.     

Neurohormones in patients with ischemic left ventricular dysfunction

Measurements of plasma neurohormones in patients with left ventricular dysfunction are generally performed for research purpose rather than for diagnostic purpose or to guide therapy. These studies have shown that in patients with left ventricular dysfunction, several neurohormonal systems were activated, even in the absence of symptoms of congestive heart failure. This suggested that the cardiovascular system was not in a steady state and pointed out potential culprits for the progression of the disease. It has also been shown that the levels of several of these markers, particularly plasma norepinephrine, had an important prognostic value. Another value of neurohormonal studies obviously is the design of new therapeutic approaches aimed at improving symptoms and prognosis. In this respect, important therapeutic successes have been obtained with agents that interfere with the actions of some of these neurohormonal systems, such as with the use of the angiotensin-converting enzyme (ACE) inhibitors, particularly captopril and enalapril, and to a lesser extent, with beta-blockers. It can therefore be expected that, in the future, most patients with severe ischemic dysfunction will be treated with an ACE inhibitor. Nonetheless, neurohormonal control is not complete with these drugs; powerful vasoconstrictor forces, such as endothelin-1, remain activated, and an escape of angiotensin II from the control of ACE inhibition may exist. Thus, morbidity (e.g., progression towards congestive heart failure and angina pectoris) and mortality remain high despite treatment with ACE inhibitors. In the search for further improvements, the new generation of long-acting dihydropyridines is worth considering. Their afterload reducing action, coupled with powerful coronary vasodilation, might hypothetically delay the progression of ischemic LV dysfunction. In addition, the improved pharmacokinetic profile of these drugs avoiding wide peak and trough variations in plasma levels may avoid triggering some neurohormonal reflexes.     

Self-Expandable nitinol stent for cardiovascular applications: canine and human experience

The initial experimental and clinical experience with the cardiovascular self-expandable Nitinol stent (vascular and coronary versions) is described. The stent is designed as a helical coil with two terminal balls that are used for restraining it on the delivery catheter. Upon release, the stent self-expands immediately. A temporary stent version continues with a long wire that can be removed by pulling it as a straight wire through a small profile catheter. The stent uncoils in its own groove upon removal, a relatively atraumatic procedure. The stents have been studied in dogs and in peripheral arteries in patients. The results show a transient nonocclusive proliferative response to the stent that is maximal at 3–6 mo. The removability of the permanent stent has been proven in dogs. The preliminary results in patients are encouraging and demonstrate its feasibility for permanent and potentially temporary arterial support. © 1994 Wiley-Liss,Inc..     

Detection of ploidy in colorectal tumors

Parallel investigations of ploidy by flow cytometry and cytogenetics were performed in 20 colorectal tumors. Flow cytometry detected an aneuploidy in 13 tumors with DNA indices ranging from 1.13 to 2.21. The other samples exhibited an apparent diploid DNA content. Cytogenetic analyses revealed an abnormal chromosome count in 14 cases and a frequent implication of numerical or structural changes in chromosomes 1, 7, 12, 17, 18, and 20. DNA content evaluated by both techniques was generally concordant with minor discrepancies not exceeding 10%. In six cases, cytogenetics failed to find the cell populations detected by flow cytometry. These results indicate that flow cytometry and cytogenetics are reliable and complementary techniques, particularly in near-diploid tumors, where flow cytometry has some difficulties in detecting variations from diploidy below to 8%.     

Coronary arteriography in acute transmural myocardial infarction

Coronary arteriography was performed 16 ± 3 days (range 7 to 21 days) in 106 patients with acute transmural myocardial infarction (61 posterior infarct, 45 anterior infarct). Coronary arteriography was performed without serious complications. Only 44 per cent of patients with anterior infarct had total occlusion of the left anterior descending artery while a significant stenosis of the vessel was observed in the others ?27 per cent had a single vessel disease, 49 per cent had two lesions and 22 per cent had three lesions; one patient had angiographically normal coronary arteries. Among the patients with posterior infarction, 21 per cent had one vessel disease and double or triple lesions accounted for 39 per cent of each.Sixty per cent of patients with anterior infarction and 45 per cent with posterior infarction had no collateral vessels. In the others patients collateral circulation had a protective effect only in anterior infarction. Age has no effect on the distribution and number of lesions nor on the development of a collateral circulation. The location and severity of the lesions were not different in patients who presented with arrythmias and those who did not.