Coronary revascularization: a procedure in transition from on-pump to off-pump? The role of glucose-insulin-potassium revisited in a randomized,placebo-controlled study

OBJECTIVE: To investigate an optimized glucose-insulin-potassium (GIK) solution regimen as an alternate myocardial protective strategy in off-pump coronary artery bypass graft (OP-CAB) surgery and as a supplement to conventional coronary artery bypass graft (CABG) surgery using cardiopulmonary bypass (CPB). DESIGN: Prospective, randomized, placebo-controlled. SETTING: Single institution, cardiothoracic specialty hospital. PARTICIPANTS: Forty-four patients scheduled for elective multivessel coronary artery surgery using either conventional CPB (n = 22) or OP-CAB techniques (n = 22). INTERVENTIONS: Preischemic, ischemic, and postischemic administration of GIK solution was carried out, optimally dosed to ensure nonesterified fatty acid (NEFA) suppression, and supplemented with magnesium, a glycolytic enzymatic cofactor. MEASUREMENTS AND MAIN RESULTS: GIK solution therapy reduced plasma NEFA levels (p < 0.001) in OP-CAB surgery and CPB groups but failed to affect the incidence of non-Q wave perioperative myocardial infarction, incidence of postoperative atrial fibrillation, incidence of postoperative infection, reduction in creatinine clearance, or duration of postoperative intensive care unit or hospital length of stay. After adjusting for GIK solution therapy, OP-CAB surgery resulted in significantly less ischemic injury (troponin I >15 microg/L, 19.0% v 91.3%; p = 0.0001) and reduced postoperative infections (14.3% v 43.5%; p = 0.049). CONCLUSION: GIK solution therapy achieved NEFA suppression and an insignificant trend toward reduced biochemical parameters of ischemic injury in OP-CAB surgery and CPB groups, but no major clinical benefit (perioperative myocardial infarction, intensive care unit length of stay, or hospital length of stay) was shown after elective CABG surgery in low-risk patients. Compared with CPB, OP-CAB surgery significantly reduced ischemic injury and postoperative infections.     

Association between the GCG polymorphism of the selenium dependent GPX1 gene and the risk of young onset prostate cancer

Epidemiological studies have suggested an association between low selenium levels and the development of prostate cancer. Human cellular glutathione peroxidase I (hGPX1) is a selenium-dependent enzyme that protects against oxidative damage and its peroxidase activity is a plausible mechanism for cancer prevention by selenium. The GPX1 gene has a GCG repeat polymorphism in exon 1, coding for a polyalanine tract of five to seven alanine residues. To test if the GPX1 GCG repeat polymorphism associates with the risk of young-onset prostate cancer we conducted a case-control study. The GPX1Ala genotypes were determined for 267 prostate cancer cases and 260 control individuals using polymerase chain reaction (PCR) amplification with fluorescently labelled primers and an ABI 377 automated genotyper. Associations between specific genotypes and the risk of prostate cancer were examined by logistic regression. We found no significant association between the GPX1 genotypes and prostate cancer. There was however an increased frequency of the GPX1Ala6/Ala6 genotype in the prostate cancer cases compared to controls (OR: 1.67; 95% CI: 0.97-2.87). The result of this study suggests that the GPX1 genotype is unlikely to be associated with the risk of developing prostate cancer.     

Five years later: poor women's health care coverage after welfare reform

The 1996 welfare reform law aims to increase poor women's participation in the work force and encourage their financial independence. Because women's ability to obtain and retain employment is affected by their health status, welfare reform's success is fundamentally tied to poor women's access to health care and to health insurance. Despite this, the rate of uninsurance among poor women with children has grown by half in recent years, leaving 37% of poor mothers uninsured in 2000. Coverage through employer-sponsored insurance has increased only slightly, and Medicaid participation has dropped. Although many factors contributed to this, welfare policies and procedures and low Medicaid eligibility levels had unintended yet significant negative effects on women's health care coverage. The sharp decline in poor women's health care coverage is likely to be one of several health-related issues that Congress will consider as it debates the reauthorization of the welfare law in 2002. Both public and private efforts will be necessary to improve coverage for poor women with children. Much progress has been made during the past 5 years in covering poor and near-poor children, but their parents have been left behind. The same efforts that proved successful for children, including broadening eligibility for coverage and simplifying the application process, can be used to improve the health and well-being of parents and to strengthen their ability to care for and support their families.     

Neuropsychological profile of acute alcohol intoxication during ascending and descending blood alcohol concentrations.

Numerous studies have investigated the effects of alcohol on motor processes during rising and declining blood alcohol concentrations (BAC), however, relatively little research has examined the alcohol-induced impairment of cognitive performance on the two limbs of the BAC curve. This experiment administered a neuropsychological test battery to assess the degree to which rising and declining BACs during an acute dose of alcohol impair nine cognitive processes within an individual. In all, 20 healthy male social drinkers (university students) were assigned to one of two groups (n = 10) who received a beverage containing either 0.0 g/kg (placebo) or 0.65 g/kg alcohol and performed the test battery when BAC was increasing and was decreasing. Comparisons of alcohol and placebo groups revealed impairment (slower response and/or increased errors) in seven of the cognitive processes: long-term verbal memory; information processing; declarative memory; inhibitory control; short-term visual memory; long-term visual memory, and visual-spatial working memory. However, some processes were impaired only during rising BACs whereas the impairment of others during declining BACs was evident only by an increase in errors. These results show cognitive tasks performed by an individual are not similarly affected by rising and declining BACs, and call attention to the importance of assessing both speed and accuracy on both limbs of the BAC curve. The particular cognitive processes differentially affected by rising vs declining BACs raised the possibility that acute alcohol intoxication may impair one cerebral hemisphere to a greater degree than the other, and this could be explored by neuroimaging techniques.     

An updated physiologically based pharmacokinetic model for hexachlorobenzene: incorporation of pathophysiological states following partial hepatectomy and hexachlorobenzene treatment.

Physiologically based pharmacokinetic (PBPK) modeling is generally used for describing xenobiotic disposition in animals and humans with normal physiological conditions. We describe here an updated PBPK model for hexachlorobenzene (HCB) in male F344 rats with the incorporation of pathophysiological conditions. Two more features contribute to the distinctness of this model from the earlier published versions. This model took erythrocyte binding into account, and a particular elimination process of HCB, the plasma-to-gastrointestinal (GI) lumen passive diffusion (i.e., exsorption), was incorporated. Our PBPK model was developed using data mined from multiple pharmacokinetic studies in the literature, and then modified to simulate HCB disposition under the conditions of our integrated pharmacokinetics/liver foci bioassay. This model included plasma, erythrocytes, liver, fat, rapidly and slowly perfused compartments, and GI lumen. To account for the distinct characteristics of HCB absorption, the GI lumen was split into an upper and a lower part. HCB was eliminated through liver metabolism and the exsorption process. The pathophysiological changes after partial hepatectomy, such as alterations in the liver and body weights and fat volume, were incorporated in our model. With adjustment of the transluminal diffusion-related parameters, the model adequately described the data from the literature and our bioassay. Our PBPK model simulation suggests that HCB absorption and exsorption processes depend on exposure conditions; different exposure conditions dictate different absorption and exsorption rates. This model forms a foundation for our further exploration of the quantitative relationship between HCB exposure and development of preneoplastic liver foci.     

Fostering coping skills and resilience in Home Enteral Nutrition (HEN) consumers.

BACKGROUND: Home enteral nutrition (HEN) is a lifesaving therapy that provides benefits along with countless challenges. This qualitative study examined how HEN consumers learned to cope successfully with HEN-related challenges and uncovered how healthcare providers could help foster the process of coping in other HEN consumers. METHODS: Twelve adult HEN consumers who perceived that they were coping successfully and overcoming the adversity associated with HEN, and met the criteria for resilience using the Resilience Scale, self-selected for the study. Participants engaged in a series of 2 in-depth interviews. Data were coded and analyzed using grounded theory methodology. RESULTS: One overarching theme and 5 main categories emerged from the data, revealing that these individuals coped successfully with HEN by developing an attitude of personal responsibility to accept new life conditions, take charge of their own well-being, seek and accept support, maximize independence and normality, and focus on the positive. In addition, these participants used a variety of problem- and emotion-focused coping strategies and shared resilient characteristics such as self-efficacy and perseverance. CONCLUSIONS: Implications for clinical practice and HEN education, along with suggestions for healthcare providers to foster coping with HEN are provided. An educational manual with self-help suggestions for adult HEN consumers is also available at http://www.copingwell.com.