Effect of MTHFR 677C>T on plasma total homocysteine levels in renal graft recipients. (33/106621)

BACKGROUND: Hyperhomocysteinemia is an established, independent risk factor for vascular disease morbidity and mortality. The 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism C677T has been shown to result in increased total homocysteine concentrations on the basis of low folate levels caused by a decreased enzyme activity. The effect of this polymorphism on total homocysteine and folate plasma levels in renal transplant patients is unknown. METHODS: We screened 636 kidney graft recipients for the presence of the MTHFR C677T gene polymorphism. The major determinants of total homocysteine and folate plasma concentrations of 63 patients, who were identified to be homozygous for this gene polymorphism compared with heterozygotes (N = 63), and patients with wild-type alleles (N = 63), who were matched for sex, age, glomerular filtration rate (GFR), and body mass index, were identified by analysis of covariance. The variables included sex, age, GFR, body mass index, time since transplantation, folate and vitamin B12 levels, the use of azathioprine, and the MTHFR genotype. To investigate the impact of the kidney donor MTHFR genotype on total homocysteine and folate plasma concentrations, a similar model was applied in 111 kidney graft recipients with stable graft function, in whom the kidney donor C677T MTHFR gene polymorphism was determined. RESULTS: The allele frequency of the C677T polymorphism in the MTHFR gene was 0.313 in the whole study population [wild-type (CC), 301; heterozygous (CT), 272; and homozygous mutant (TT), 63 patients, respectively] and showed no difference in the patient subgroups with various renal diseases. The MTHFR C677T gene polymorphism significantly influenced total homocysteine and folate plasma concentrations in renal transplant recipients (P = 0.0009 and P = 0.0002, respectively). Furthermore, a significant influence of the GFR (P = 0.0001), folate levels (P = 0.0001), age (P = 0.0001), body mass index (P = 0.0001), gender (P = 0.0005), and vitamin B12 levels (P = 0.004) on total homocysteine concentrations was observed. The donor MTHFR gene polymorphism had no influence on total homocysteine and folate levels. Geometric mean total homocysteine levels in patients homozygous for the mutant MTHFR allele were 18.6 micromol/liter compared with 14.6 micromol/liter and 14.9 micromol/liter in patients heterozygous for the MTHFR gene polymorphism and those with wild-type alleles (P < 0.05 for TT vs. CT and CC). Geometric mean folate levels were lower in CT and TT patients (11.2 and 10.2 nmol/liter) compared with CC patients (13.6 nmol/liter, P < 0.05 vs. CT and TT). CONCLUSIONS: This study demonstrates that homozygosity for the C677T polymorphism in the MTHFR gene significantly increases total homocysteine concentrations and lowers folate levels in kidney graft recipients, even in patients with excellent renal function (GFR more than median). These findings have important implications for risk evaluation and vitamin intervention therapy in these patients who carry an increased risk for the development of cardiovascular disease.  (+info)

Septicemia in dialysis patients: incidence, risk factors, and prognosis. (34/106621)

BACKGROUND: Infection is second to cardiovascular disease as a cause of death in patients with end-stage renal disease (ESRD), and septicemia causes a majority of these infectious deaths. To identify patients at high risk and to characterize modifiable risk factors for septicemia, we examined the incidence, risk factors, and prognosis for septicemia in a large, representative group of U.S. dialysis patients. METHODS: We conducted a longitudinal cohort study of incident ESRD patients in the case-mix study of the U.S. Renal Data System with seven years of follow-up from hospitalization and death records. Poisson regression was used to examine independent risk factors for hospital-managed septicemia. Cox proportional hazards analysis was used to assess the independent effect of septicemia on all-cause mortality and on death from septicemia. Separate analyses were performed for patients on peritoneal dialysis (PD) and hemodialysis (HD). RESULTS: Over seven years of follow-up, 11.7% of 4005 HD patients and 9.4% of 913 PD patients had at least one episode of septicemia. Older age and diabetes were independent risk factors for septicemia in all patients. Among HD patients, low serum albumin, temporary vascular access, and dialyzer reuse were also associated with increased risk. Among PD patients, white race and having no health insurance at dialysis initiation were also risk factors. Patients with septicemia had twice the risk of death from any cause and a fivefold to ninefold increased risk of death from septicemia. CONCLUSIONS: Septicemia, which carries a marked increased risk of death, occurs frequently in patients on PD as well as HD. Early referral to a nephrologist, improving nutrition, and avoiding temporary vascular access may decrease the incidence of septicemia. Further study of how race, insurance status, and dialyzer reuse can contribute to the risk of septicemia among ESRD patients is indicated.  (+info)

A train passenger with pulmonary tuberculosis: evidence of limited transmission during travel. (35/106621)

In January 1996, smear- and culture-positive tuberculosis (TB) was diagnosed for a 22-year-old black man after he had traveled on two U.S. passenger trains (29.1 hours) and a bus (5.5 hours) over 2 days. To determine if transmission had occurred, passengers and crew were notified of the potential exposure and instructed to undergo a tuberculin skin test (TST). Of the 240 persons who completed screening, 4 (2%) had a documented TST conversion (increase in induration of > or = 10 mm between successive TSTs), 11 (5%) had a single positive TST (> or = 10 mm), and 225 (94%) had a negative TST (< 10 mm). For two persons who underwent conversion, no other risk factors for a conversion were identified other than exposure to the ill passenger during train and/or bus travel. These findings support limited transmission of Mycobacterium tuberculosis from a potentially highly infectious passenger to other persons during extended train and bus travel.  (+info)

Risk factors for nosocomial bloodstream infections due to Acinetobacter baumannii: a case-control study of adult burn patients. (36/106621)

Risk factors for Acinetobacter baumannii bloodstream infection (BSI) were studied in patients with severe thermal injury in a burn intensive care unit where A. baumannii was endemic. Of 367 patients hospitalized for severe thermal injury during the study period, 29 patients with nosocomial A. baumannii BSI were identified (attack rate, 7.9%). Cases were compared with 58 matched controls without A. baumannii BSI. The overall mortality rate was 31% among cases and 14% among controls; only two deaths (7%) were considered directly related to A. baumannii BSI. Molecular typing of A. baumannii blood isolates by means of randomly amplified polymorphic DNA analysis and pulsed-field gel electrophoresis revealed the presence of three different strain types. Multivariate analysis showed that female gender (P = .027), total body surface area burn of > 50% (P = .016), prior nosocomial colonization with A. baumannii at a distant site (P = .0002), and use of hydrotherapy (P = .037) were independently associated with the acquisition of A. baumannii BSI in burn patients. These data underscore the need for effective infection control measures for this emerging nosocomial problem.  (+info)

Alternate child care, history of hospitalization, and preschool child behavior. (37/106621)

BACKGROUND: With more single mothers entering the workforce due to welfare reform efforts, more hospitalized children from single-parent families will have experienced alternate child care arrangements where routine care is provided by adults other than the child's mother. OBJECTIVES: To investigate with secondary analysis of data whether experience with alternate child care has a moderating effect on the relationship between hospitalization and behavior of preschool children living in female-headed single-parent families. METHOD: A sample of 60 preterm and 61 full-term children who were 3, 4, or 5 years old was recruited for the larger longitudinal study. Behavior problems were measured with the Child Behavior Checklist. History of hospitalization and alternate child care arrangements were measured with the Life History Calendar. RESULTS: Preschool children who experienced hospitalization without alternate child care experience had more somatic complaints, but those with both hospital and alternate child care experience had fewer aggressive behaviors than other children. For children with a history of hospitalization, aggressive behaviors decreased as the proportion of the child's life in alternate child care increased. CONCLUSIONS: Experience with alternate child care may ameliorate some of the negative effects of hospitalization, and potentially other novel and negative experiences, for preschool children. This could be due to child care providing positive experiences with separation from the mother, a peer group with which to talk about the novel experience, or actual instruction about the novel experience.  (+info)

Prospective evaluation of the thrombotic risk in children with acute lymphoblastic leukemia carrying the MTHFR TT 677 genotype, the prothrombin G20210A variant, and further prothrombotic risk factors. (38/106621)

The reported incidence of thromboembolism in children with acute lymphoblastic leukemia (ALL) treated with L-asparaginase, vincristine, and prednisone varies from 2.4% to 11.5%. The present study was designed to prospectively evaluate the role of the TT677 methylenetetrahydrofolate reductase (MTHFR) genotype, the prothrombin G20210A mutation, the factor V G1691A mutation, deficiencies of protein C, protein S, antithrombin, and increased lipoprotein (a) concentrations in leukemic children treated according to the ALL-Berlin-Frankfurt-Muenster (BFM) 90/95 study protocols with respect to the onset of vascular events. Three hundred and one consecutive leukemic children were enrolled in this study. Fifty-five of these 301 subjects investigated had one established single prothrombotic risk factor: 20 children showed the TT677 MTHFR genotype; 5 showed the heterozygous prothrombin G20210A variant; 11 were carriers of the factor V G1691A mutation (heterozygous, n = 10; homozygous, n = 1); 4 showed familial protein C, 4 protein S, and 2 antithrombin type I deficiency; 9 patients were suffering from familially increased lipoprotein (a) [Lp(a)] concentrations (>30 mg/dL). In addition, combined prothrombotic defects were found in a further 10 patients: the FV mutation was combined with the prothrombin G20210A variant (n = 1), increased Lp(a) (n = 3), protein C deficiency (n = 1), and homozygosity for the C677T MTHFR gene mutation (n = 1). Lp(a) was combined with protein C deficiency (n = 2) and the MTHFR TT 677 genotype (n = 2). Two hundred eighty-nine of the 301 patients were available for thrombosis-free survival analysis. In 32 (11%) of these 289 patients venous thromboembolism occurred. The overall thrombosis-free survival in patients with at least one prothrombotic defect was significantly reduced compared with patients without a prothrombotic defect within the hemostatic system (P <.0001). In addition, a clear-cut positive correlation (P <.0001) was found between thrombosis and the use of central lines. However, because the prothrombotic defects diagnosed in the total childhood population studied were all found within the prevalences reported for healthy Caucasian individuals, the interaction between prothrombotic risk factors, ALL treatment, and further environmental factors is likely to cause thrombotic manifestations.  (+info)

Effect of the interval between pregnancies on perinatal outcomes. (39/106621)

BACKGROUND: A short interval between pregnancies has been associated with adverse perinatal outcomes. Whether that association is due to confounding by other risk factors, such as maternal age, socioeconomic status, and reproductive history, is unknown. METHODS: We evaluated the interpregnancy interval in relation to low birth weight, preterm birth, and small size for gestational age by analyzing data from the birth certificates of 173,205 singleton infants born alive to multiparous mothers in Utah from 1989 to 1996. RESULTS: Infants conceived 18 to 23 months after a previous live birth had the lowest risks of adverse perinatal outcomes; shorter and longer interpregnancy intervals were associated with higher risks. These associations persisted when the data were stratified according to and controlled for 16 biologic, sociodemographic, and behavioral risk factors. As compared with infants conceived 18 to 23 months after a live birth, infants conceived less than 6 months after a live birth had odds ratios of 1.4 (95 percent confidence interval, 1.3 to 1.6) for low birth weight, 1.4 (95 percent confidence interval, 1.3 to 1.5) for preterm birth, and 1.3 (95 percent confidence interval, 1.2 to 1.4) for small size for gestational age; infants conceived 120 months or more after a live birth had odds ratios of 2.0 (95 percent confidence interval, 1.7 to 2.4);1.5 (95 percent confidence interval, 1.3 to 1.7), and 1.8 (95 percent confidence interval, 1.6 to 2.0) for these three adverse outcomes, respectively, when we controlled for all 16 risk factors with logistic regression. CONCLUSIONS: The optimal interpregnancy interval for preventing adverse perinatal outcomes is 18 to 23 months.  (+info)

Effects of family history and place and season of birth on the risk of schizophrenia. (40/106621)

BACKGROUND: Although a family history of schizophrenia is the best-established risk factor for schizophrenia, environmental factors such as the place and season of birth may also be important. METHODS: Using data from the Civil Registration System in Denmark, we established a population-based cohort of 1.75 million persons whose mothers were Danish women born between 1935 and 1978. We linked this cohort to the Danish Psychiatric Central Register and identified 2669 cases of schizophrenia among cohort members and additional cases among their parents. RESULTS: The respective relative risks of schizophrenia for persons with a mother, father, or sibling who had schizophrenia were 9.31 (95 percent confidence interval, 7.24 to 11.96), 7.20 (95 percent confidence interval, 5.10 to 10.16), and 6.99 (95 percent confidence interval, 5.38 to 9.09), as compared with persons with no affected parents or siblings. The risk of schizophrenia was associated with the degree of urbanization of the place of birth (relative risk for the capital vs. rural areas, 2.40; 95 percent confidence interval, 2.13 to 2.70). The risk was also significantly associated with the season of birth; it was highest for births in February and March and lowest for births in August and September. The population attributable risk was 5.5 percent for a history of schizophrenia in a parent or sibling, 34.6 percent for urban place of birth, and 10.5 percent for the season of birth. CONCLUSIONS: Although a history of schizophrenia in a parent or sibling is associated with the highest relative risk of having the disease, the place and season of birth account for many more cases on a population basis.  (+info)