Preliminary evidence for a role of apolipoprotein E alleles in identifying haemodialysis patients at high vascular risk

Conventional risk factors have very low predictive power in identifying haemodialysis patients at high risk of vascular accidents. A role for apolipoprotein E isotypes was looked for in a small, but rigorously defined, cohort of longterm haemodialysis patients. In individuals with high vascular risk, as identified by higher common carotid intima/media thickness, we found an excess of apolipoprotein E4 alleles. This preliminary result requires confirmation in large patient cohorts.      

Can Electrocardiographic Criteria Predict Adverse Cardiac Events and Positive Cardiac Markers?

OBJECTIVES: To determine electrocardiogram (ECG) predictors of positive cardiac markers and short-term adverse cardiac events in an undifferentiated chest pain population presenting to emergency departments (EDs). The authors hypothesized that specific ECG findings, other than those previously identified in higher-risk populations, would be predictive of cardiac outcomes and positive cardiac markers. METHODS: This study used data from a prospectively collected, retrospectively analyzed Internet-based data registry of undifferentiated chest pain patients (i*trACS). Logistic regression modeling was performed to determine the ECG findings that were predictive of 1) positive cardiac markers and 2) short-term adverse cardiac events. RESULTS: ST-segment elevation (STE), ST-segment depression (STD), pathological Q-waves (PQW), and T-wave inversion were associated with increased odds of percutaneous coronary intervention or catheterization, myocardial infarction, or coronary artery bypass grafting. The odds of creatine kinase-MB (CK-MB) measuring positive were increased if STE, STD, or PQW were present [odds ratio (OR) 2.495, 2.582, and 1.295, respectively]. A right bundle branch block tended to decrease the odds of CK-MB measuring positive (OR 0.658). A similar pattern of results was observed for troponin I (OR 3.608 for STE, 3.72 for STD, 1.538 for PQW). Troponin T showed an increased odds of measuring positive if any of STE, STD, left bundle branch block, or T-wave inversion were evident (OR 2.313, 2.816, 1.80, and 1.449, respectively). CONCLUSIONS: Initial ECG criteria can be used to predict short-term cardiac outcomes and positive cardiac markers. These findings can be important aids in the risk-stratification and aggressive treatment regimens of chest pain patients presenting to EDs.     

Effect of aging and caloric restriction on intestinal permeability.

Intestinal permeability is increased in several disorders such as Crohn's disease or rheumatoid arthritis. Since aging leads to alteration of many biological functions, the effect of aging on intestinal permeability was studied by measuring the intestinal permeability in aging rats gavaged with different size permeability probes--mannitol, polyethylene glycol (PEG) 400, and inulin. In rats fed with control diet, there was a significant increase in intestinal permeability to medium size probes PEG 400 (14.8 +/- 0.4 and 21.0 +/- 1.1% at 3 and 28 months respectively, p less than .01) and mannitol (3.41 +/- 0.4 and 5.3 +/- 0.5% at 3 and 28 months, respectively, p less than .01). Intestinal permeability of the large macromolecule inulin did not change (0.42 +/- 0.03 and 0.38 +/- 0.02% at 3 and 28 months, respectively) with aging. There was no correlation between weight of the rats and their intestinal permeability. Because dietary caloric restriction has been found to prolong the life span, retard deterioration of several biological functions, and affect intestinal absorptive functions, we examined the effect of lifelong calorie restriction on intestinal permeability changes. Lifelong calorie-restricted diet did not affect age-related change in intestinal permeability. We conclude that intestinal permeability of medium size probes increases with aging and that lifelong caloric restriction does not prevent this change. We speculate that age-associated deterioration in intestinal barrier functions could permit increased systemic absorption of lumenal antigens and could perhaps contribute to the genesis of antigen-related age-associated diseases.     

Effects of chronic fluoxetine treatment on behavioral and neuroendocrine responses to meta-chlorophenylpiperazine in obsessive-compulsive disorder

To investigate the effect of fluoxetine on serotonergic sensitivity in obsessive-compulsive disorder (OCD), the partial serotonin agonist metachlorophenylpiperazine (mCPP) was compared to placebo under double-blind conditions in six patients with OCD before and during treatment with fluoxetine. Readministration of oral mCPP (0.5 mg/kg) after at least 12 weeks of fluoxetine treatment did not increase obsessive-compulsive (OC) symptoms, in contrast to exacerbation of OC symptoms produced by mCPP before treatment. Chronic fluoxetine treatment resulted in a significant increase in prolactin and cortisol response to mCPP. This may be accounted for, however, by substantially increased plasma mCPP levels during fluoxetine treatment. Chronic fluoxetine treatment diminished the behavioral sensitivity to mCPP and did not diminish, but may have partially normalized, the neuroendocrine response to mCPP in patients with OCD. These adaptive homeostatic effects may reflect fluoxetine's antiobsessional mechanism.