Short-term variability in the measurement of plasma homocysteine, fasting and post-methionine loading

OBJECTIVES: Hyperhomocysteinemia is associated with premature cerebral, peripheral and coronary vascular disease. Evaluation of the significance of changes in plasma total homocysteine (tHcy) results obtained by analysis of serial specimens may be accomplished only by taking into account biologic (between-person and within-person) as well as analytical variation. Since the repeatability of a measurement significantly determines our ability to associate tHcy level with the presence of disease, this study was performed to evaluate various components of variation in tHcy values. DESIGN AND METHODS: We report the within-person, between-person, and methodological variability of tHcy, both fasting and postmethionine load (PML) values, in 20 healthy volunteers from whom samples were drawn weekly for 4 weeks. RESULTS: The short-term reliability coefficient (R) was 0.72 for fasting tHcy and 0.83 for PML tHcy. CONCLUSIONS: The current study demonstrates for the first time that the short-term reliability coefficient for PML tHcy is relatively high (0.83), suggesting that an individual's PML tHcy, like fasting tHcy, is relatively constant over at least one month, and that a single measurement should provide a reasonable characterization of an individual's PML tHcy concentration.     

A prospective study of coronary heart disease and the hemochromatosis gene (HFE) C282Y mutation: the Atherosclerosis Risk in Communities (ARIC) study

Increased iron stores may play a role in the development of coronary heart disease (CHD) by increasing lipoprotein oxidation. Recently, mutations have been discovered in the gene (HFE) for hereditary hemochromatosis, an autosomal recessive condition of disordered iron metabolism, absorption, and storage. It is possible that people who carry HFE mutations have increased risk of CHD. We used a prospective case-cohort design (243 CHD cases and 535 non-cases) to determine whether the HFE C282Y mutation was associated with incident CHD in a population-based sample of middle-aged men and women. The frequencies of homozygosity and heterozygosity for the C282Y mutation in the ARIC study population were 0.2% (one homozygous person) and 6%, respectively. The C282Y mutation was associated with nonsignificantly increased risk of CHD (relative risk=1.60, 95% CI 0.9-2.9). After adjusting for other confounding risk factors (age, race, gender, ARIC community, smoking status, diabetes status, hypertension status, LDL cholesterol, HDL cholesterol, and triglycerides), the association became stronger (relative risk=2.70, 95% CI 1.2-6.1). However, a sensitivity analysis showed that this estimate of relative risk was somewhat unstable due to few subjects in some strata. Our prospective findings suggest that individuals carrying the HFE C282Y mutation may be at increased risk of CHD.     

Off-pump technique in coronary artery bypass grafting in elderly patients

Background: The use of cardiopulmonary bypass (CPB) during coronary artery bypass grafting (CABG) is associated with substantial morbidity and mortality, especially in the elderly. The purpose of this study was to evaluate the feasibility of beating heart coronary artery revascularization in patients aged at least 80 years. Methods: A retrospective chart review was carried out for 17 patients aged over 80 years who underwent isolated off‐pump CABG at the Tri‐Service General Hospital, Taiwan, during the period July 1999 to December 2000. The demographic characteristics, operative data, postoperative results and short‐term outcomes of patients were compared with those of 12 patients who underwent conventional CABG using CPB during the same time period. Results: The off‐pump group consisted of 13 men and four women with a mean age of 82.2 ± 0.9 years and an ejection fraction of 53.4 ± 4.1%. The on‐pump group consisted of eight men and four women with a mean age of 83.5 ± 0.5 and an ejection fraction of 42.0 ± 4.8%. The mean number of anastomoses performed per patient was 3.1 ± 0.3 in the off‐pump group and 3.0 ± 0.14 in the on‐pump group. There was no occurrence of stroke, myocardial infarction, re‐entry for bleeding or renal failure among patients in the off‐pump group. Intubation time (10.6 vs 48.4 h), intensive care unit stay (2.9 vs 4.2 days) and postoperative stay (12.7 vs 18.1 days) were significantly shorter in the off‐pump group than in the on‐pump group. No patient died in the off‐pump group, whereas one patient died in the on‐pump group. Conclusions: The results of this study suggest that the off‐pump technique is a safe and efficacious method for myocardial revascularization in elderly patients and that the short‐term outcome obtained with this technique are promising. Our data suggest that the off‐pump technique is preferable in these patients.     

Allelic variants of the tryptophan hydroxylase (A218C) and serotonin 1B receptor (A-161T) and personality traits

Human personality traits have a considerable hereditary component, and central serotonergic activity is implicated in the personality factors of the Tridimensional Personality Questionnaire (TPQ). Our population-based association study tested the hypothesis that the tryptophan hydroxylase (TPH) A218C and serotonin 1B receptor (HTR1B) A-161T polymorphisms were associated with TPQ personality trait scores in a sample population of 209 young healthy Chinese. No significant differences were demonstrated comparing scores of subjects bearing different TPH or HTR1B genotypes; however, a trend for difference in the novelty seeking score comparing TPH genotype groups was determined for the male population. Our negative findings suggest that the TPH A218C and HTR1B polymorphisms do not play major roles in the determination of TPQ personality traits.     

Early embryonic death of glutamate carboxypeptidase II (NAALADase) homozygous mutants

Glutamate carboxypeptidase II (EC 3.4.17.21) catalyzes the hydrolysis (Km = 0.2 microM) of the neuropeptide N-acetylaspartylglutamate to yield N-acetylaspartate and glutamate and also serves as a high-affinity folate hydrolase in the gut, cleaving the polyglutamate chain to permit the absorption of folate. N-acetylaspartylglutamate is an agonist at the mGluR3 metabotropic receptor and a source of extracellular glutamate through hydrolysis by glutamate carboxypeptidase II. Given the important role of glutamate in brain development and function, we were interested in the effects of a null mutation of glutamate carboxypeptidase II that would potentiate the effects of N-acetylaspartylglutamate. The PGK-Neomycin cassette was inserted to delete exons 9 and 10, which we previously demonstrated encode for the zinc ligand domain essential for enzyme activity. Successful germline transmission was obtained from chimeras derived from embryonic stem cells with the targeted mutation of glutamate carboxypeptidase II. Homozygous null mutants did not survive beyond embryonic day 8. Folate supplementation of the heterozygous mothers did not rescue the homozygous embryos. Mice heterozygous for the null mutation appeared grossly normal and expressed both mutated and wild-type mRNA but the activity of glutamate carboxypeptidase II is comparable to the wild-type mice. The results indicate that the expression of glutamate carboxypeptidase II is upregulated when one allele is inactivated and that its activity is essential for early embryogenesis.     

Diabetes and idiopathic cardiomyopathy: a nationwide case-control study

OBJECTIVE: Controversy exists regarding the relation between diabetes and nonischemic idiopathic cardiomyopathy (ICM), and only limited data on the incidence of ICM in adults with diabetes are available. Therefore, we used the 1995 Nationwide Inpatient Sample (NIS) to determine discharge rates and test the hypothesis that diabetes is independently associated with ICM. RESEARCH DESIGN AND METHODS: The 1995 NIS includes demographic and diagnostic data on all discharges from >900 representative hospitals in 19 states. ICD-9 codes were used to identify ICM, defined as discharges with a diagnosis of primary cardiomyopathy but without established risk factors for cardiomyopathy. Control subjects were selected by stratified random sampling by age to yield 10 per ICM case. The analyzed covariates included age, race, median income, diabetes, and hypertension. Multivariate logistic regression was used to conduct case-control analyses. RESULTS: Using sampling weights, we estimated that in 1995, the rate of hospital discharge for ICM among individuals diagnosed with diabetes was 7.6 per 1000. The prevalence of diabetes was substantially higher in the 44837 ICM vs. 450254 control subjects (26.6 vs. 17.2%), corresponding to a relative odds (RO) of 1.75 (95% CI 1.71-1.79). After adjusting for age, sex, race, hypertension, and median income using multiple logistic regression, diabetes remained significantly associated with ICM (RO 1.58, 95% CI 1.55-1.62). CONCLUSIONS: We concluded that diabetes is independently associated with ICM in the general U.S. population.     

Choanal atresia: an unusual serious complication of complementary and alternative medical treatment

The use of complementary and alternative medicine (CAM) is common among patients with chronic, long-standing nasal disease. Complications resulting from inappropriate CAM practices are sometimes reported, but serious complications such as choanal atresia and stenosis are rare. We report a case of choanal atresia and stenosis due to herbal drug (ie, chemical) cauterization of the nasal cavity in a 39-year-old man. We reviewed the literature on why patients previously given conventional treatment seek alternative therapies. The patient underwent surgical intervention to relieve choanal atresia and stenosis. The postoperative course was unremarkable, and follow-up for 1 year revealed no evidence of restenosis. Choanal atresia and stenosis resulting from CAM treatment are rare. Otolaryngologists should be aware of possible complications occurring in patients receiving such treatments.