[The association of biological markers with echocardiographic indices in patients with myocardial infarction with ST segment elevation and preserved left ventricular ejection fraction].

AIM: To compare dynamics of biological marker concentrations with echocardiographic data in patients with ST elevation myocardial infarction (STEMI) and preserved LV function during the hospitalization period. MATERIALS AND METHODS: The study successively included 100 patients with diagnosis of STEMI and LV ejection fraction.

A protocadherin gene cluster regulatory variant is associated with nicotine withdrawal and the urge to smoke.

Nicotine withdrawal symptoms contribute to relapse in smokers, thereby prolonging the harm caused by smoking. To investigate the molecular basis for this phenomenon, we conducted a genome-wide association study of DSM-IV nicotine withdrawal in a sample of African American (AA) and European American (EA) smokers. A combined AA and EA meta-analysis (n=8021) identified three highly correlated single nucleotide polymorphisms (SNPs) in the protocadherin (PCDH)-α, -ß and -γ gene cluster on chromosome 5 that were associated with nicotine withdrawal (P<5 × 10-8). We then studied one of the SNPs, rs31746, in an independent sample of smokers who participated in an intravenous nicotine infusion study that followed overnight smoking abstinence. After nicotine infusion, abstinent smokers with the withdrawal risk allele experienced greater alleviation of their urges to smoke, as assessed by the Brief Questionnaire on Smoking Urges (BQSU). Prior work has shown that the PCDH-α, -ß and -γ genes are expressed in neurons in a highly organized manner. We found that rs31746 mapped to a long-range neuron-specific enhancer element shown previously to regulate PCDH-α, -ß and -γ gene expression. Using Braincloud mRNA expression data, we identified a robust and specific association between rs31746 and PCDH-ß8 mRNA expression in frontal cortex tissue (P<1 × 10-5). We conclude that PCDH-α, -ß and -γ gene cluster regulatory variation influences the severity of nicotine withdrawal. Further studies on the PCDH-α, -ß and -γ genes and their role in nicotine withdrawal may inform the development of novel smoking cessation treatments and reduce the harm caused by tobacco smoking.

FKBP5 variation is associated with the acute and chronic effects of nicotine.

Stress and hormones released in response to stress influence the effects of nicotine and the severity of nicotine withdrawal. Here, we systematically examine the contribution of a stress response gene, FKBP5, to the acute and chronic behavioral effects of nicotine in smokers. Subjects were European- and African-American (EA and AA) heavy smokers who participated in an intravenous (IV) nicotine administration study (total n=169). FKBP5 rs3800373 genotype was analyzed for association to several outcomes, including nicotine withdrawal and the acute subjective, heart rate (HR), blood pressure and plasma cortisol responses to IV nicotine. Nicotine withdrawal was also examined in relation to rs3800373 allele frequencies in an independent cohort of EA and AA current smokers (n=3821). For a subset of laboratory subjects FKBP5 mRNA (n=48) expression was explored for an association to the same outcomes. The rs3800373 minor allele was associated with less severe nicotine withdrawal in laboratory subjects and the independent cohort of smokers. The rs3800373 minor allele was also associated with lower subjective ratings of negative drug effects in response to IV nicotine. Low FKBP5 mRNA expression was associated lower cortisol levels, lower subjective ratings of negative drug effects and a blunted HR response to nicotine. Stress hormone regulation via FKBP5 warrants further investigation as a potential contributor to the effects of nicotine withdrawal, which occurs commonly, and has an important role in the maintenance of smoking behavior and relapse following a quit attempt.

COMT Val158Met modulates subjective responses to intravenous nicotine and cognitive performance in abstinent smokers.

The catechol-O-methyltransferase (COMT) Val158Met polymorphism may be a risk factor for nicotine addiction. This study examined the influence of the COMT Val158Met polymorphism on subjective, physiological and cognitive effects of intravenous (IV) nicotine use in African Americans (AAs; n=56) and European Americans (EAs; n=68) smokers. Overnight abstinent smokers received saline followed by 0.5 and 1.0 mg per 70 kg doses of nicotine, administered 30 min apart. Smokers with valine (Val)/Val genotype, compared with methionine (Met) carriers, had greater negative subjective effects from IV nicotine and had more severe withdrawal severity following overnight abstinence from smoking. Women with Val/Val genotype reported greater difficulty concentrating and irritability than men with Val/Val or Met carrier genotypes. The Val/Val genotype was associated with better performance on the math task and in AA smokers it was associated with greater systolic blood pressure. These results support the rationale of pharmacologically inhibiting COMT to aid with smoking cessation among Val/Val genotype smokers.

Anemia severity and missed dialysis treatments in erythropoietin-treated hemodialysis patients.

Neither the sociodemographic correlates nor the biochemical/clinical consequences of missed dialysis treatments have been well defined. During a 10 week period, the authors enumerated missed dialysis treatments among 430 patients randomly selected from a pool of 1,395 hemodialysis patients. A forward logistic regression model was used to determine whether a relationship existed between missed dialysis treatments and the following independent variables: age, gender, race, renal diagnosis, length of time on maintenance hemodialysis, co-morbidity index, modified Karnofsky score, employment status, household residents, and laboratory indices. Forty-three (10%) of 430 patients missed a total of 96 treatments. Despite equivalent treatment with erythropoietin, patients who missed dialysis treatment(s) had a lower mean hematocrit (27 +/- 4.3%) at the end of the study than those patients who underwent all treatments (29 +/- 4.5%) (p = 0.0287). Mean serum albumin and creatinine levels were equivalent in compliant and noncompliant patients. Recent starts (p = 0.0048), and younger patients (p = 0.0424) were most likely to miss dialysis treatment(s). One of the major consequences of missed dialysis treatment(s) is exacerbation of anemia, and younger patients and freshly started patients are more likely to miss scheduled dialysis treatments than their respective counterparts.

Correlates of vascular access and nonvascular access-related hospitalizations in hemodialysis patients.

Four hundred and thirty randomly selected hemodialysis patients, aged 20 years and over, were studied to identify risk factors for vascular access and nonvascular access-related hospitalizations in the immediately preceding 1 year. Risk estimates for hospitalization were assessed using a multinominal logistic analysis model. We measured functional status, utilizing a 14-point Karnofsky scale, and in a separate analysis of covariance, in which Karnofsky score was the outcome, we examined the relationships of age, gender, ethnicity, renal diagnosis, and hospitalization. Individual comparisons were adjusted for multiple comparison bias by Tukey's Honest Difference method. There were a total of 508 hospitalizations of which 322 (63%) lasted > or = 1 week. Two hundred and sixty (60%) patients were hospitalized at least once; 105 (24.4%) for access problems only, 115 (27%) for a nonaccess problem only, and 40 for access and nonaccess-related problems. Access-related problems, accounted for 48% of all hospitalizations. The risk of hemodialysis vascular access morbidity was increased in women (p < 0.028) and white (p < 0.048) hemodialysis patients. Neither diabetic nor elderly hemodialysis patients were at greater risk for access hospitalization than their respective counterparts, though a greater proportion of the access hospitalizations in the elderly (> or = 64 years) lasted > or = 1 week (p < 0.0006). More access-related hospitalizations in blacks (64.5%), lasted for > or = 1 week than in whites (40.6%) (p < 0.001). Hispanics (p < 0.043), whites (p < 0.002), and the older patients (p < 0.054) were at greater risk for nonaccess hospitalization than blacks and younger patients, respectively. Even after adjusting for age, race, and diabetes, each decrease of one unit in the modified Karnofsky score was associated with a 3-4% increased risk for all types of hospitalization (p < 0.001)--poor functional status is associated with increased risk for all hospitalizations. We conclude that the risk for hemodialysis vascular access morbidity is increased in women and white hemodialysis patients. Poor functional status is associated with increased risk for all hospitalizations.

Pervasive failed rehabilitation in center-based maintenance hemodialysis patients.

At its inception in 1972, the end-stage renal disease (ESRD) program was conceived with a set of assumptions about cost, rate of growth, and treatment outcomes in its client population. Despite the potential to correct anemia with recombinant erythropoietin (EPO) introduced in 1987 and improved survival, the level of physical activity among some segments of the hemodialysis population remains suboptimal. This study was undertaken, among other reasons, to identify correlates of poor functional status as measured by a modified Karnofsky scale. Using a modified Karnofsky scale, we measured the functional status of 430 patients who had been treated by hemodialysis for at least 1 year and some of whom were also receiving concomitant treatment with EPO. Patients studied were randomly selected from eight dialysis units in urban New York and suburban New Jersey. A Karnofsky score of less than 70 indicated frank disability--the subject was unable to perform routine living chores without assistance. In addition, current vocational activity was ascertained, and comorbid conditions were quantified. The necessity for wheelchair dependence was noted for each patient. The mean age (+/- SD) of the study population was 56 +/- 14 years (range, 21 to 92 years). Subjects had been on maintenance hemodialysis for 4.09 +/- 3.8 years (range, 1 to 23 years). The study group included 215 men and 215 women, of whom 65% were black, 27% white, 6% Hispanic, and 2% Asian; 36.5% had diabetes mellitus. Although 376 members (87%) of the study group were under treatment with EPO, the mean hematocrit of the study population was only 29% +/- 4.5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Hydrolysis of wheat straw hemicellulose with trifluoroacetic acid. Fermentation of xylose with Pachysolen tannophilus.

Treatment of wheat straw with 1N trifluoroacetic acid (TFA) for 7 h at reflux temperature yielded 23% xylose based upon initial straw weight. This corresponds to about an 80% xylose yield based on the xylan content of the hemicellulose. The cellulose component of wheat straw was largely unaffected, as evidenced by low glucose yields. Decomposition of xylose by prolonged refluxing (23 h) was minimal in 1N TFA compared to 1N HCl. Treatment of wheat straw with refluxing 1N TFA converts about 10% of the lignin initially present in straw into water-soluble lignin fragments. Fermentation of the xylose-rich wheat straw hydrolyzate to ethanol with Pachysolen tannophilus was comparable to the fermentation of reagent grade xylose, indicating that furfural and toxic lignin by-products were not produced by 1N TFA in sufficient amounts to impair cell growth and ethanol production. Cellulase treatment of the wheat straw residue after TFA hydrolysis resulted in a 70-75% conversion of the cellulose into glucose.

Mating responses in Candida lipolytica.

Culture medium that restricted cell multiplication increased fertility in selected heterothallic stocks of Candida lipolytica and triggered sporulation in newly formed diploids; a medium that supported vigorous cell growth prevented sporulation and permitted the newly formed diploids to bud.

Sexual reproduction in Candida lipolytica.

Candida lipolytica is a rather common yeast isolated more frequently from substrates containing lipids or proteins, such as dairy products, than from substrates rich in sugars. This species assimilates hydrocarbons and is currently being studied for its potential to convert petroleum into yeast cells for use in feeds and foods. We have found C. lipolytica to exist in nature primarily in the heterothallic haploid state. When appropriate strains of opposite sex are mixed on a suitable sporulation medium, conjugation occurs followed by the production of ascospores. Since heterothallism permits laboratory control of hybridization, this characteristic of C. lipolytica enhances the possibility of im proving its strains for technological uses.

Respiratory-deficient mutants in Saccharomyces lactis.

Six independent ultraviolet-induced respiratory-deficient mutants (petites) of Saccharomyces lactis were isolated and characterized. Two possessed a normal cytochrome spectrum, another displayed an increased level of all the cytochromes, and three suffered from a partial or complete loss of one or more of the cytochromes a, b, c, and c(1). All of the mutants were segregational petites; none was vegetative. Determination of linkage relationships between mutants was restricted because matings between mutants, homozygous or heterozygous, for loci affecting cytochrome content were blocked at various stages in the mating-sporulating sequence. At least three of the petites were genetically nonidentical. Three of the mutations appeared to occupy loci within the same linkage group; two of the three mutations that mapped within this region were cytochrome-deficient. Growth at high or low temperatures, under increased osmotic pressure or in media supplemented with various fatty acids or sterols, did not relieve the physiological defects in these mutants. Reasons for the differences in survival of segregational and vegetative petites within this species are examined.

Viability in fertile stocks of Pseudomonas aeruginosa.

Diluent composition, time consumed in experimental manipulations, and the presence of pyocine-like lethal agents affected the viability of sexual fertility factor-positive and fertility factor-negative auxotrophic stocks of Pseudomonas aeruginosa. In the same cultures, recovery of prototrophic revertants increased as the number of viable cells dispensed per plate was reduced. As a result, the number of revertants recovered was indirectly determined by the combined activities of the three conditions affecting viability. Possible modifications by these conditions affecting viability on the expression and interpretation of the fertility factor-positive sex factor-mediated system of genetic recombination are presented.