G20210A mutation in prothrombin gene and risk of myocardial infarction, stroke, and venous thrombosis in a large cohort of US men.
(57/106621)
BACKGROUND: A single base pair mutation in the prothrombin gene has recently been identified that is associated with increased prothrombin levels. Whether this mutation increases the risks of arterial and venous thrombosis among healthy individuals is controversial. METHODS AND RESULTS: In a prospective cohort of 14 916 men, we determined the prevalence of the G20210A prothrombin gene variant in 833 men who subsequently developed myocardial infarction, stroke, or venous thrombosis (cases) and in 1774 age- and smoking status-matched men who remained free of thrombosis during a 10-year follow-up (control subjects). Gene sequencing was used to confirm mutation status in a subgroup of participants. Overall, carrier rates for the G20210A mutation were similar among case and control subjects; the relative risk of developing any thrombotic event in association with the 20210A allele was 1.05 (95% CI, 0.7 to 1.6; P=0.8). We observed no evidence of association between mutation and myocardial infarction (RR=0.8, P=0.4) or stroke (RR=1.1, P=0.8). For venous thrombosis, a modest nonsignificant increase in risk was observed (RR=1.7, P=0.08) that was smaller in magnitude than that associated with factor V Leiden (RR=3.0, P<0. 001). Nine individuals carried both the prothrombin mutation and factor V Leiden (5 controls and 4 cases). One individual, a control subject, was homozygous for the prothrombin mutation. CONCLUSIONS: In a large cohort of US men, the G20210A prothrombin gene variant was not associated with increased risk of myocardial infarction or stroke. For venous thrombosis, risk estimates associated with the G20210A mutation were smaller in magnitude than risk estimates associated with factor V Leiden. (+info)
Regulation of fatty acid homeostasis in cells: novel role of leptin.
(58/106621)
It is proposed that an important function of leptin is to confine the storage of triglycerides (TG) to the adipocytes, while limiting TG storage in nonadipocytes, thus protecting them from lipotoxicity. The fact that TG content in nonadipocytes normally remains within a narrow range, while that of adipocytes varies enormously with food intake, is consistent with a system of TG homeostasis in normal nonadipocytes. The facts that when leptin receptors are dysfunctional, TG content in nonadipocytes such as islets can increase 100-fold, and that constitutively expressed ectopic hyperleptinemia depletes TG, suggest that leptin controls the homeostatic system for intracellular TG. The fact that the function and viability of nonadipocytes is compromised when their TG content rises above or falls below the normal range suggests that normal homeostasis of their intracellular TG is critical for optimal function and to prevent lipoapoptosis. Thus far, lipotoxic diabetes of fa/fa Zucker diabetic fatty rats is the only proven lipodegenerative disease, but the possibility of lipotoxic disease of skeletal and/or cardiac muscle may require investigation, as does the possible influence of the intracellular TG content on autoimmune and neoplastic processes. (+info)
An epidemiological study on the association between the total leukocyte and neutrophil counts, and risk factors of ischemic heart disease by smoking status in Japanese factory workers.
(59/106621)
Several epidemiologic studies have shown the association between total leukocyte count and the risk of developing myocardial infarction. The purpose of this study was to assess the association between the total leukocyte and neutrophil counts and risk factors of ischemic heart disease in 1,384 Japanese factory workers. Total leukocyte and neutrophil counts were significantly higher in current smokers than in non-smokers. Among current smokers, the total leukocyte and neutrophil counts were positively associated with the number of cigarettes smoked daily and the duration of cigarette smoking and alcohol consumption. Being independent of smoking habit, the total leukocyte and neutrophil counts were also related to several characteristics recorded at the physical examinations. The total leukocyte and neutrophil counts were positively associated with serum total cholesterol, serum triglyceride and hematocrit levels, and inversely associated with the serum HDL-cholesterol level. No significant associations of the total leukocyte or neutrophil counts were found with the red blood cell count and hemoglobin level. These results suggest that the total leukocyte and neutrophil counts may represent the metabolic condition with a high coronary risk among apparently healthy people. (+info)
Hepatitis virus infection in haemodialysis patients from Moldavia.
(60/106621)
BACKGROUND: Although the epidemiology of hepatitis B (HBV) and C (HCV) now seems well established for Western European countries, in Central and Eastern Europe < 50% of all dialysis centres routinely test for hepatitis C antibodies since testing is not available or is not applied to all patients. This study describes the prevalence, risk factors and clinical significance of HBV and HCV infection for the haemodialysis population of the North Eastern region of Romania, Moldavia. METHODS: The presence of HBV antigens was determined with an ELISA kit (Wellcome, Abbot) and HCV antibodies with the ELISA-3 Ortho-HCV, third generation test. The following individual data were collected: gender, age, duration of dialysis, rural/urban domicile, actual and previous HBV status, actual HCV status, known acute, clinically evident hepatitis episodes in the last 3 years, monthly alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) levels, complete biochemical hepatic assessment at the time of the study, transfusions for the past 3 years and family history. RESULTS: HBV and HCV prevalences were 17% (stable over the last 3 years) and 75%, respectively; co-infection was seen in 10% of the subjects. Hospitalization (nosocomial infection) for HBV, blood transfusions and duration on dialysis for HCV, emerged as the main risk factors for hepatitis infection. Socio-economic conditions appear to be equally important for HCV infection, since the prevalence was significantly higher among patients from rural, underdeveloped areas than urban areas (80.8 vs 60.3%), and infection was already present in a large proportion of patients (47%) before starting dialysis, without being related to previous disease duration or blood transfusions. HBV and/or HCV was not associated with a worse clinical or biochemical profile at the time of the study. However, infected patients had significantly more previous cytolytic episodes, with higher, transient increases in ALAT and ASAT levels. CONCLUSIONS: HCV infection is endemic among dialysis centres in Moldavia. Apart from previously well-known risk factors for hepatitis infection, our study demonstrates the negative impact of socio-economic underdevelopment. Simple measures such as enforced general asepsia rules, careful disinfection and equipment sterilization, routine testing of patients from economically disadvantaged areas and monthly, serial determination of hepatic enzymes should be the common practice in dialysis centres in Romania. (+info)
Hypertension in the haemodialysis population: any relationship to 2-years survival?
(61/106621)
BACKGROUND: Few studies have quantified the effect of hypertension on survival in the haemodialysis (HD) population. We have previously reported lack of adverse effect of hypertension on 1-year mortality in a cohort of 649 haemodialysis patients (Am J Kidney Dis 1996; 28: 737-744). We report here the effect of hypertension on 2-year survival in the same cohort of patients. METHODS: We reviewed the complete computerized files on 649 HD patients enrolled in 10 haemodialysis centres in the state of Mississippi, USA. One-month dialysis records for each patient from mid-October 1994 to mid-November 1994 were reviewed. Predialysis mean arterial pressure was calculated as immediate predialysis diastolic pressure plus one-third the difference between systolic and diastolic pressure. Patients were classified as hypertensive if their average pre-MAP was more than 114 mmHg or they were receiving antihypertensive drugs during the study period. Normotensives had a pre-MAP < 114 and were not receiving any antihypertensives. We followed these patients for 2 years to determine their survival and the effect of their BP status, as determined in October 1994, on 2-year mortality. RESULTS: In univariate analysis, hypertension was associated with improved 2-years survival (relative risk 0.64, P=0.08 compared to normotensives). Furthermore, among the hypertensives, good blood pressure control (less than 140/90) was associated with increased relative risk of death at 2 years (RR 1.86, P=0.004). In multivariate analysis, taking age, race, serum albumin, and diabetic status into consideration, there was a 27% reduction in mortality among hypertensives compared to normtensives (RR 0.73, P=0.06). Other factors of significance in multivariate analysis were age (RR 1.03/year, P=0.02), serum albumin (RR 0.36/g, P<0.0001), diabetes mellitus (RR 1.35, P=0.07), and race (RR 0.64, P=0.05). CONCLUSIONS: Our study suggests that hypertension has no adverse effect on survival at 2 years in the haemodialysis population. (+info)
Gender-specific differences in dialysis quality (Kt/V): 'big men' are at risk of inadequate haemodialysis treatment.
(62/106621)
BACKGROUND: Inadequate dialysis dose is closely related to mortality and morbidity of maintenance haemodialysis (MHD) patients. According to the DOQI guidelines a minimum prescribed dialysis dose of single-pool Kt/V (Kt/Vsp)=1.3, equivalent to equilibrated double pool Kt/V (e-Kt/Vdp)=1.1, is recommended. Knowledge of patient-related risk factors for inadequate delivery of hacmodialysis would be helpful to select patient subgroups for intensive control ofdialysis adequacy. METHODS: A retrospective survey was conducted to assess the prevalence of inadequate dialysis dose according to DOQI criteria during a 7-month period. A total of 320 e-Kt/Vdp measurements in 62 MHD patients were evaluated (mean effective dialysis time 222+/-32 min). Residual renal function (RRF) was expressed as renal weekly Kt/V (r-Kt/Vweek) and included into assessment of total weekly renal and dialytic Kt/V (t-Kt/Vweek). RESULTS: Inadequacy (e-Kt/Vdp<1.10) was prevalent in 37.2% of all measurements and in 22/62 patients (35.5%). In 54% of underdialysed patients r-Kt/Vweek compensated for insufficient dialytic urea removal. Mean weekly Kt/V was inadequate (t-Kt/Vweek<3.30) in 12/62 patients (19.4%) of whom 91.7% (11/12) were male. Body-weight, urea distribution volume (UDV). and body-surface area (BSA) were significantly higher in inadequately is adequately dialysed males. UDV>42.0 litres or BSA>2.0 m2 and a lack of RRF (r-Kt/Vweek<0.3) put 'big men' at increased risk to receive an inadequate dose of dialysis. CONCLUSION: Our data identify patients at risk for inadequate haemodialysis treatment. Special attention should be focused on 'big men' with UDV>42.0 litres or BSA>2.0 m2. In this subset of patients frequent measurements of t-Kt/Vweek and assessment of RRF should be mandatory. (+info)
Relationship between glycosylated hemoglobin and the prevalence of proteinuria in Japanese men.
(63/106621)
A total of 5,174 Japanese men were included in a cross-sectional study to examine the relationship between the glycated hemoglobin (HbA1C) level and the prevalence of proteinuria as determined using a reagent strip. The prevalence of proteinuria rose significantly at HbA1C levels above 5.9%, whereas no relationship was observed at HbA1C levels below 5.9%. Multiple logistic regression analysis showed that blood pressure and a family history of diabetes were independent factors associated with proteinuria in subjects with a HbA1C below 5.9% who were not under medication for diabetes. In contrast, HbA1C, obesity and smoking were associated with proteinuria in subjects who were under medication for diabetes and/or have a HbA1C above 5.9%. These findings suggest that maintaining a HbA1C level below 5.9%, non-smoking and a standard body weight may reduce the prevalence of proteinuria in Japanese men. Healthy life-style and standard body weight are especially important for subjects with a family history of diabetes. (+info)
Identifying families with likely genetic protective factors against Alzheimer disease.
(64/106621)
Elderly individuals who lived beyond the age of 90 years without dementia were hypothesized to have increased concentrations of genetic protective factors against Alzheimer disease (AD), conferring a reduced liability for this disease relative to less-aged nondemented elderly. However, testing this hypothesis is complicated by having to distinguish such a group from those who may lack genetic risk factors for AD, have had protective environmental exposures, or have escaped dementia for other reasons. Probands carrying genetic protective factors, however, should have relatives with lower illness rates not only for earlier-onset disease, when genetic risk factors are a strong contributing factor to the incidence of AD, but also for later-onset disease, when the role of these factors appears to be markedly diminished. AD dementia was assessed through family informants in 6,660 first-degree relatives of 1,049 nondemented probands aged 60-102 years. The probands were grouped by age (60-74, 75-89, and 90-102 years), and the cumulative survival from AD and 10-year-age-interval hazard rates of AD were calculated in their first-degree relatives. Cumulative survival from AD was significantly greater in the relatives of the oldest proband group (aged 90-102 years) than it was in the two younger groups. In addition, the reduction in the rate of illness for this group was relatively constant across the entire late life span. The results suggest that genetic factors conferring a lifelong reduced liability of AD may be more highly concentrated among nondemented probands aged >/=90 years and their relatives. Efforts to identify protective allele-bearing genes that are associated with very late-onset AD should target the families of nonagenarians and centenarians. (+info)