Molecular cloning of the mouse homologue of Rab3c

Small GTP-binding proteins of the Rab subfamily are key regulators of intracellular vesicle transport. Here we report the isolation of a cDNA clone encoding the complete Rab3c isoform from mouse embryo using a degenerative PCR-based approach. Multiple sequence alignment revealed that the predicted amino acid sequence was identical to the previously identified rat Rab3c isoform and 98% identical to the published bovine Rab3c GTPase from brain. Furthermore by in situ hybridisation, Rab3c mRNA was detectable within various regions of the brain, cartilage and highly enriched within intestinal villi of foetal tissues. Chondrocytes in the hypertrophic zone, but not reserve or proliferative zones, expressed high levels of Rab3c. This pattern of expression corresponds with the genesis of matrix vesicles during endochondral ossification.In all, our results suggest that in addition to its functional role during regulated secretion in brain, Rab3c may play a part in matrix vesicle trafficking during skeletal development.     

Forty-years (1961-2001) of all-cause and coronary heart disease mortality and its determinants: the Corfu cohort from the Seven Countries Study

AIMS: This study examined risk factors in relation to 40-year all-cause and coronary heart disease mortality in the Corfu cohort of the Seven Countries Study. METHODS: The population studied in this analysis consisted of 529 rural middle-aged men enrolled in 1961. Multivariate analysis was performed using the proportional hazards Cox model with all-cause as well as coronary heart disease death as end points and age, blood pressure, serum total cholesterol, smoking, physical activity, body mass index, skinfold thickness, vital capacity and forced expiratory volume as predictors. RESULTS: The 40-year all-cause mortality rate was 87.1% (461 deaths/529 individuals at entry), while the CHD mortality rate was 22.7% (120 deaths/529 individuals at entry). The proportion of CHD deaths varied from 16 to 28.5% of all deaths during the period investigated. Age (hazard ratio (HR)=1.08, P<0.001), smoking (HR=1.40, P<0.01), diastolic blood pressure (HR=1.01, P<0.05), and forced expiratory volume (HR=0.97, P<0.05) were independently associated with 40-year all-cause mortality. Moreover, age (HR=1.093, P<0.001), smoking (HR=1.596, P<0.05), and body mass index (HR=1.05, P<0.05) were independently associated with 40-year CHD mortality. CONCLUSION: Among the investigated cardiovascular risk factors, age, smoking, physical activity, skinfold thickness, diastolic blood pressure, and forced expiratory volume seem to be associated with all-cause mortality, while age, smoking, and body mass index were consistently associated with 40-year CHD mortality.     

An integrated assessment of family history on the risk of developing acute coronary syndromes (CARDIO2000 study)

OBJECTIVE: In this work we assessed a risk score for developing a first event of acute coronary syndrome (ACS) based on the family history of the cardiovascular risk factors. METHODS AND RESULTS: The studied population consisted of 848 randomly selected middle-aged patients with first event of ACS and 1078 sex-age-region matched controls admitted to the same hospitals for minor operations and without any clinical suspicion of cardiovascular disease in their life. A Family History Score (FHS) was developed based on the presence of coronary heart disease, hypertension, hypercholesterolaemia and diabetes mellitus, among first-degree relatives of the participants after adjusting for the family size. The evaluation of FHS was based on conditional logistic regression analysis, after controlling for demographic variables as well as for the mutual confounding effects of other risk factors. Family history of CHD, hypercholesterolaemia and diabetes was highly associated with the development of the disease. The introduced FHS was also highly associated with the development of ACS among participants who had no family history of CHD (odds ratio = 10.9, p < 0.001), whereas it was not associated with the development of the disease among participants who had a family history of CHD (odds ratio = 1.41, p = 0.543). CONCLUSIONS: The suggested FHS could be a useful tool in the primary prevention of ACS, as well as in detecting and understanding associations between genetic vulnerability and cardiovascular risk factors.     

Clinical features of hypertrophic cardiomyopathy caused by an Arg278Cys missense mutation in the cardiac troponin T gene

To further examine the genetic and clinical features of hypertrophic cardiomyopathy caused by mutations in the cardiac troponin T (cTnT) gene, we screened 143 probands from our hypertrophic cardiomyopathy population for mutations in this gene. We report that the Arg278Cys missense mutation in the cTnT gene had a different clinical presentation in 2 different families and was associated with a clinical profile that deviates from what is currently expected for cTnT gene mutations.     

Climatological variations in daily hospital admissions for acute coronary syndromes

OBJECTIVE: We examined the association between climatologic parameters and daily admissions for non-fatal acute coronary syndromes (ACS) to emergency units of hospitals in the greater Athens area, from January 2001 to August 2002. METHODS: Daily mean, maximum and minimum temperatures, relative humidity, wind speed, barometric pressure and a thermo-hydrological index (T.H.I.) were measured at the meteorological station of the Laboratory of Climatology of the Geology Department of the University of Athens. In addition, the daily number of admissions for acute myocardial infarction or unstable angina in the five major general hospitals in the greater Athens area was recorded. Generalized additive models (GAM) were applied to regress-time-series of daily numbers of outpatients with acute cardiac events against climatological variations, after controlling for possible confounders and adjustment for over dispersion and serial correlation. RESULTS: Five thousand four hundred fifty-eight Athenians with non-fatal acute cardiac events were admitted to the selected hospitals during the period of the study, 4093 (75%) males and 1365 (25%) females. There was a negative correlation between hospital admissions and mean daily temperature (MDT) with a 1 degrees C decrease in mean air temperature yielding a 5% increase in hospital admissions (P<0.05). This association was stronger in females and the elderly (P<0.01). Relative humidity was positively correlated with hospital admissions (P<0.05). CONCLUSION: Despite the relatively short study period (<2 years), these findings suggest a significant association between cold weather and increased coronary heart disease incidence, especially in the elderly and females.     

QRS dispersion: an electrocardiographic index of systolic left ventricular dysfunction in patients with left bundle branch block

The presence of complete left bundle branch block (LBBB) in patients with congestive heart failure has been proposed to be a factor that negatively affects left ventricular (LV) systolic function. The aim of this study was to evaluate the relative predictive value of QRS dispersion (QRSD) and QRS duration (QRSd) in relation to systolic performance of the left ventricle. The ejection fraction of 130 consecutive patients with LBBB was evaluated by standard echocardiographic methods, whereas QRSd and QRSD were measured. It was demonstrated that QRSD in patients with complete LBBB is strongly related to LV contractility. We, therefore, suggest that this simple electrocardiographic index may serve as a useful screening test for detection of patients with LV systolic dysfunction.     

Efficacy of antithrombotic therapy in chronic heart failure: the HELAS study

BACKGROUND: It is not clear if long-term antithrombotic treatment has a beneficial effect on the incidence of thromboembolism in chronic heart failure (CHF). The HELAS study (Heart failure Long-term Antithrombotic Study) is a multicentre, randomised, double-blind, placebo-controlled trial to evaluate antithrombotic treatment in patients with CHF. METHODS: 197HF patients (EF <35%) were enrolled. Patients with Ischaemic Heart Disease were randomised to receive either aspirin 325mg or warfarin. Patients with Dilated Cardiomyopathy (DCM) were randomised to receive either warfarin or placebo. RESULTS: Analysis of the data from 312 patient years showed an incidence of 2.2 embolic events per 100 patient years, with no significant difference between groups. The incidence of myocardial infarction, hospitalisation, exacerbation of heart failure, death and haemorrhage were not different between the groups. No peripheral or pulmonary emboli were reported. Echocardiographic follow-up for 2years showed an overall increase in left ventricular ejection fraction from 28.2+/-6 to 30.3+/-7 p<0.05, which was most obvious in patients with DCM taking warfarin (EF 26.8+/-5.3 at baseline, 30.7+/-10 at 2 years, p<0.05). CONCLUSIONS: (1) Overall embolic events are rare in heart failure regardless of treatment. (2) Treatment does not seem to affect outcome.     

Communication between left main stem trunk and proximal segment of left anterior descending coronary artery rescues left ventricular ejection fraction of a patient with three-vessel disease

The well-known congenital anomalies of the left main stem refer mainly to its anomalous origin from the pulmonary artery or the right aortic sinus. We present a patient with a large communication between the left main stem trunk and the proximal segment of the left anterior descending coronary artery which preserves the left ventricular systolic performance in the setting of significant three-vessel disease.     

Isolated native tricuspid valve Candida endocarditis in a non-drug-addicted patient: case report and review of the literature

A case is reported of isolated native tricuspid calve Candida parapsilosis endocarditis (INTVCE) in a male patient with no history of drug abuse or heart disease. The patient had received hyperalimentation and antibiotics for four months via a central venous catheter after abdominal surgery. He underwent successful treatment with tricuspid valve debridement, liposomal amphotericin (AmBisome) and fluconazole, and remained without relapse during an eight-year follow up. A literature review of 12 similar cases (including the present patient) without history of drug abuse or heart disease, dating from 1970, is included.