Increased mortality after coronary artery bypass graft surgery is associated with increased levels of postoperative creatine kinase-myocardial band isoenzyme release: results from the GUARDIAN trial

OBJECTIVES: We sought to determine if elevated cardiac serum biomarkers after coronary artery bypass graft surgery (CABG) are associated with increased medium-term mortality and to identify patients that may benefit from better postoperative myocardial protection. BACKGROUND: The relationship between the magnitude of cardiac serum protein elevation and subsequent mortality after CABG is not well defined, partly because of the lack of large, prospectively studied patient cohorts in whom postoperative elevations of cardiac serum markers have been correlated to medium- and long-term mortality. METHODS: The GUARD during Ischemia Against Necrosis (GUARDIAN) study enrolled 2,918 patients assigned to the entry category of CABG and considered as high risk for myocardial necrosis. Creatine kinase-myocardial band (CK-MB) isoenzyme measurements were obtained at baseline and at 8, 12, 16 and 24 h after CABG. RESULTS: The unadjusted six-month mortality rates were 3.4%, 5.8%, 7.8% and 20.2% for patients with a postoperative peak CK-MB ratio (peak CK-MB value/upper limits of normal [ULN] for laboratory test) of < 5, > or = 5 to <10, > or =10 to < 20 and > or =20 ULN, respectively (p < 0.0001). The relationship remained statistically significant after adjustment for ejection fraction, congestive heart failure, cerebrovascular disease, peripheral vascular disease, cardiac arrhythmias and the method of cardioplegia delivery. Receiver operating characteristic curve analysis revealed an area under the curve of 0.648 (p < 0.001); the optimal cut-point to predict six-month mortality ranged from 5 to 10 ULN. CONCLUSIONS: Progressive elevation of the CK-MB ratio in clinically high-risk patients is associated with significant elevations of medium-term mortality after CABG. Strategies to afford myocardial protection both during CABG and in the postoperative phase may serve to improve the clinical outcome.     

A randomized controlled trial of cognitive behavior therapy, relaxation training, and routine clinical care for the irritable bowel syndrome

OBJECTIVES: Psychological treatments are considered to be useful in the irritable bowel syndrome (IBS), although the evidence is based on small, often flawed trials. Although cognitive behavior therapy (CBT) and relaxation therapy have both been promising, we hypothesized that CBT would be superior to relaxation and standard care alone in IBS patients. The objective of this study was to test this assumption by comparing the effects of cognitive behavior therapy with relaxation therapy and routine clinical care alone in individuals with IBS. METHODS: Patients (n = 105) with Rome I criteria for IBS were recruited from advertisement (n = 51) and outpatient clinics (n = 54); those patients with resistant IBS were not included. A randomized controlled trial with three arms (standard care for all groups plus either CBT or relaxation) for 8 wk was conducted, which applied blinded outcome assessments using validated measures with 1 yr of follow-up. The primary outcome for this study was bowel symptom severity. RESULTS: Of 105 patients at the commencement of treatment, the mean bowel symptom frequency score for the whole sample was 21.1 and at the end of treatment had fallen to 18.1; this persisted at the 52-wk follow-up, with a significant linear trend for scores to change over time (F = 39.57 p < 0.001). However, there were no significant differences among the three treatment conditions. Significant changes over time were found for physical functioning (F = 4.37, p < 0.001), pain (F = 3.12, p < 0.05), general health (F = 2.71, p < 0.05), vitality (F = 2.94, p < 0.05), and the social functioning scales on the Medical Outcomes Study Short Form 36 (F = 4.08, p < 0.05); however, all three arms showed similar improvement. There were significant reductions in anxiety, depression, and locus of control scales, but no significant differences among the treatment groups were detected. CONCLUSION: Cognitive behavior and relaxation therapy seem not to be superior to standard care alone in IBS.     

Feline leukemia virus-induced erythroid aplasia: in vitro hemopoietic culture studies

Colony forming unit (CFU) assays were developed for feline granulocyte-macrophage (CFUGM), early erythroid (day 2 CFUE), and late erythroid (day 7 CFUE) colonies in methylcellulose medium. Feline CFUGM and both day 2 and day 7 CFUE were enhanced by feline macrophage conditioned medium and late CFUE often were intimately associated with macrophages. Kittens were inoculated with the Kawakami-Theilen (KT) strain of feline leukemia virus (FeLV) and sequential changes in marrow CFU determined. Erythroid aplasia, characterized by progressive non-regenerative anemia, lymphopenia, and a profound decrease in early and late CFUE but not CFUGM was induced by 3 to 5 weeks after FeLV-KT inoculation. The susceptibility of kittens to FeVL-induced erythroid aplasia was strongly age-related; neonatal kittens were most sensitive and substantial natural resistance developed by 4 weeks of age. The results demonstrate that FeLV-KT infection induced a rapid and selective suppression of erythroid progenitor cells and represents a suitable model of experimentally-induced acquired erythroid aplasia.     

Clopidogrel administration prior to coronary artery bypass grafting surgery: the cardiologist's panacea or the surgeon's headache?

AIMS: Thrombotic complications after percutaneous coronary intervention procedures have decreased in past years mainly due to the use of clopidogrel antiplatelet therapy. However, the risk of bleeding due to enhanced and irreversible platelet inhibition in patients who will require surgical coronary revascularization instead has not been adequately addressed in the literature. The purpose of this study was to evaluate the effect of pre-operative clopidrogel exposure in haemorrhage-related re-exploration rates, peri-operative transfusion requirements, morbidity, and mortality in patients undergoing coronary artery bypass grafting (CABG) surgery. METHODS AND RESULTS: A study population of 2359 patients undergoing isolated CABG between January 2000 and June 2002 was reviewed. Of these, 415 (17.6%) received clopidogrel prior to CABG surgery, and 1944 (82.4%) did not. A risk-adjusted logistic regression analysis was used to assess the association between clopidogrel pre-medication (vs. no) and haemostatic re-operation, intraoperative and post-operative blood transfusion rates, and multiple transfusions received. Haemorrhage-related pre-operative risk factors identified from the literature and those found significant in a univariate model were used. Furthermore, a sub-cohort, matched-pair by propensity scores analysis, was also conducted. The clopidogrel group had a higher likelihood of haemostatic re-operation [OR = 4.9, (95% CI, 2.63-8.97), P < 0.01], an increase in total packed red blood cell transfusions [OR = 2.2, (95% CI, 1.70-2.84), P < 0.01], multiple unit blood transfusions [OR = 1.9, (95% CI, 1.33-2.75), P < 0.01] and platelet transfusions [OR = 2.6, (95% CI, 1.95-3.56), P < 0.01]. Surgical outcomes and operative mortality [OR = 1.5, (95% CI, 0.36-6.51), P = 0.56] were not significantly different. CONCLUSION: Pre-operative clopidogrel exposure increases the risk of haemostatic re-operation and the requirements for blood and blood product transfusion during, and after, CABG surgery.     

Insulin-sensitive tyrosine kinase activity changes in parallel with plasma insulin and glucose concentrations in humans

Insulin receptor tyrosine kinase is an important step in insulin action. We examined the relationship between diet-induced changes in glucose metabolism and changes in skeletal muscle insulin-sensitive tyrosine kinase activity in 12 nondiabetic subjects. Subjects were fed a traditional, high carbohydrate Pima Indian diet and a modern, high fat western diet for 2 weeks in a randomized cross-over design. At the end of each dietary period, glucose tolerance was assessed, insulin sensitivity (SI) was estimated by Bergman's minimal model method, and insulin receptor concentration and tyrosine kinase activity were determined on lectin-purified extracts from quadriceps femoris muscle. Compared to the traditional diet, the modern diet was associated with a deterioration of glucose tolerance and an increase in glucose-induced plasma insulin levels. As expected, SI changes were associated with opposite changes in plasma insulin levels. However, the changes in maximal tyrosine kinase activity were negatively correlated with changes in SI (r = -0.69; P less than 0.01) and positively correlated with changes in plasma glucose (r = 0.70; P less than 0.01) and insulin response to glucose (r = 0.57; P less than 0.025). These results suggest that the site of diet-induced changes in insulin action is beyond the insulin-sensitive tyrosine kinase. The results further suggest that the kinase activity is modulated by prevailing plasma insulin levels.     

Is Health Care Seeking for Irritable Bowel Syndrome and Functional Dyspepsia a Socially Learned Response to Illness?

In a population-based study of 207 subjects with irritable bowel syndrome (IBS) or functional dyspepsia (FD) and controls (n = 100), we aimed to determine whether dimensions of abnormal illness behavior from the Abnormal Illness Behaviour Questionnaire and aspects of social learning of illness behavior from the Social Learning of Illness Behaviour scale were independent predictors of health care seeking for IBS and FD. Results showed that dimensions of abnormal illness behavior and aspects of social learning of illness behavior (encouragement, reinforcement, and modeling) did not significantly differentiate between consulters and nonconsulters with IBS and/or FD. The Disease Conviction scale (OR = 1.55; 95% CI, 1.15–2.09) of the Abnormal Illness Behaviour Questionnaire was an independent predictor of having a diagnosis of IBS and/or FD, independent of age and gender, psychiatric diagnoses, and symptom severity. We conclude that a belief in the presence of serious pathology characterizes community subjects with IBS and FD, but not health care seeking.     

Evaluation of a live, cold-passaged, temperature-sensitive, respiratory syncytial virus vaccine candidate in infancy

A live-attenuated, intranasal respiratory syncytial virus (RSV) candidate vaccine, cpts-248/404, was tested in phase 1 trials in 114 children, including 37 1-2-month-old infants-a target age for RSV vaccines. The cpts-248/404 vaccine was infectious at 104 and 105 plaque-forming units in RSV-naive children and was broadly immunogenic in children >6 months old. Serum and nasal antibody responses in 1-2 month olds were restricted to IgA, had a dominant response to RSV G protein, and had no increase in neutralizing activity. Nevertheless, there was restricted virus shedding on challenge with a second vaccine dose and preliminary evidence for protection from symptomatic disease on natural reexposure. The cpts-248/404 vaccine candidate did not cause fever or lower respiratory tract illness. In the youngest infants, however, cpts-248/404 was unacceptable because of upper respiratory tract congestion associated with peak virus recovery. A live attenuated RSV vaccine for the youngest infant will use cpts-248/404 modified by additional attenuating mutations.     

Scoring technique for diagnosis of ventricular hypertrophy from three orthogonal lead electrocardiogram.

A prospective study for the development of scoring techniques for the diagnosis of ventricular hypertrophy from the three orthogonal lead electrocardiogram was undertaken. A total of 51 hearts was examined at necropsy in a training group on which the scoring techniques were developed and a test group of a further 82 hearts was studied to assess the sensitivity and specificity of the method. The hearts were classified as being normal or having left ventricular hypertrophy, right ventricular hypertrophy, biventricular hypertrophy, or were placed in a borderline category. These classifications were based on the measurement of the weight of the left ventricular free wall, the interventricular septum, and the right ventricular free wall. Classical electrocardiographic variables were selected and assigned a point score on the basis of their diagnostic value. The electrocardiographic diagnosis of left ventricular hypertrophy, right ventricular hypertrophy, and biventricular hypertrophy was then made when the relevant score exceeded four points. After excluding 25 cases which showed conduction defects or were regarded as borderline at necropsy, 57 cases remained in the test group for assessing the technique. The sensitivity and specificity for left ventricular hypertrophy were 65 per cent and 91 per cent, respectively. For right ventricular hypertrophy corresponding results were 53 and 90 per cent. For biventricular hypertrophy the sensitivity was lower at 42 per cent, with a corresponding specificity of 93 per cent. These results represent a considerable improvement over older techniques, with up to a tenfold increase in sensitivity being obtained. The technique can be applied with or without computer assistance.