Reduced force production during low blood flow to the heart correlates with altered troponin I phosphorylation

A rat model of low myocardial blood flow was established to test the hypothesis that post-translational changes to proteins of the thin and thick muscle filaments correlate with decreased cardiac contractility. Following 3 days of low blood flow by constriction of the left anterior descending artery, rat hearts demonstrated a reduction in fractional shortening at rest and a relative decline in fractional shortening when challenged with high dose versus low dose dobutamine, reflecting reduced energy reserves. Permeabilized fibers from low blood flow hearts demonstrated a decline in maximum force per cross-section and Ca²⁺ sensitivity as compared to their sham operated counterparts. An examination of sarcomeric proteins by twodimensional gel electrophoresis, mass spectrometry, and phospho-specific antibodies provided evidence for Ser23/24 and Ser43/45 phosphorylation of troponin I (TnI). Total TnI phosphorylation was not different between the groups, but Ser23/24 phosphorylation declined with low blood flow, implying an accompanying increase in phosphorylation at other sites of TnI. Affinity chromatography demonstrated that TnI from low blood flow myocardium had reduced relative affinity to Ca²⁺ bound troponin C compared to TnI from sham operated hearts, providing a mechanism for reduced Ca²⁺ sensitivity of force production in low blood flow fibers. These findings suggest that altered TnI function, due to changes in the distribution of phosphorylated sites, is an early contributor to reduced contractility of the heart.     

Integrated malaria vector control with microbial larvicides and insecticide-treated nets in western Kenya: a controlled trial

Objective

To assess the contributions of both microbial larvicides and insecticide-treated nets (ITNs) in terms of reducing malaria incidence in an integrated vector management programme in an area moderately endemic for malaria in the western Kenyan highlands.

Methods

A pre-post, control group design was used. Larval and adult vector populations were surveyed weekly in six separate valley communities. The incidence of Plasmodium infections in children 6 months to 13 years of age was measured during the long and short rainy seasons each year. Baseline data were collected for 17 months, after which Bacillus-based larvicides were applied weekly to aquatic habitats in three of the valleys for another 19 months. At around the same time the larviciding was initiated, ITNs were introduced gradually into all study communities by the National Malaria Control Programme. The effect of larviciding, ITNs and other determinants of malaria risk was assessed by means of generalized estimating equations.

Findings

The risk of acquiring new parasite infections in children was substantially and independently reduced by ITN use (odds ratio, OR: 0.69; 95% confidence interval, CI: 0.48–0.99) and larvicide application (OR: 0.44; 95% CI: 0.23–0.82), after adjusting for confounders.

Conclusion

Vector control with microbial larvicides enhanced the malaria control achieved with ITNs alone. Anti-larval measures are a promising complement to ITN distribution in the economically important highland areas and similar transmission settings in Africa.     

Addiction and substance abuse in anesthesiology

Despite substantial advances in our understanding of addiction and the technology and therapeutic approaches used to fight this disease, addiction still remains a major issue in the anesthesia workplace, and outcomes have not appreciably changed. Although alcoholism and other forms of impairment, such as addiction to other substances and mental illness, impact anesthesiologists at rates similar to those in other professions, as recently as 2005, the drug of choice for anesthesiologists entering treatment was still an opioid. There exists a considerable association between chemical dependence and other psychopathology, and successful treatment for addiction is less likely when comorbid psychopathology is not treated. Individuals under evaluation or treatment for substance abuse should have an evaluation with subsequent management of comorbid psychiatric conditions. Participation in self-help groups is still considered a vital component in the therapy of the impaired physician, along with regular monitoring if the anesthesiologist wishes to attempt reentry into clinical practice.     

Insight in schizophrenia: associations with executive function and coping style

It has been suggested that lack of awareness of illness in schizophrenia may result from deficits in executive function and/or an avoidant style of coping. To examine this question, 132 persons with schizophrenia spectrum disorders were rated as either "aware," "partially unaware" or "unaware" of: (a) their illness, (b) need for treatment and (c) consequences of disorder on the abbreviated Scale to Assess Unawareness of Mental Disorder. We next compared the performance of the aware, partially unaware and unaware groups on the "escape-avoidance" and "positive reappraisal" subtests of the Ways of Coping Questionnaire and on two tests of executive function: the Letter Number Sequencing Subtest of the WAIS III and Wisconsin Card Sorting Test. MANCOVA followed by ANCOVA and planned comparisons, controlling for age indicated that the participants who were unaware of symptoms, treatment need and consequences generally performed more poorly than the aware groups on tests of executive function. Participants unaware of symptoms also had a greater preference for positive reappraisal than aware or partially unaware participants. The participants unaware of the consequences of disorder endorsed a greater preference for escape-avoidance than the partially unaware participants. Implications for understanding the etiology of lack of awareness in schizophrenia are discussed.     

Brivudin compared with famciclovir in the treatment of herpes zoster: effects in acute disease and chronic pain in immunocompetent patients. A randomized, double-blind, multinational study

OBJECTIVE: This was a double-blind, randomized multicentre trial comparing efficacy and safety of brivudin (125 mg, once a day) and famciclovir (250 mg, three times a day), both given orally for 7 days, in the treatment of herpes zoster. METHODS: A total of 2027 immunocompetent zoster patients>or=50 years with zoster-related pain at presentation were included. Outcome measures embraced prevalence of postherpetic neuralgia (PHN), defined as at least moderate pain 3 months after treatment initiation, duration of PHN, prevalence and duration of zoster-associated pain (ZAP), duration of vesicle formation and rash healing. RESULTS: The prevalence of PHN at month 3 was 11.3% with brivudin and 9.6% with famciclovir [per-protocol (PP) population]. Equivalence of the two drugs could be demonstrated (P=0.01, PP and intention-to-treat analysis). The median duration of PHN was 46.5 days with brivudin and 58 days with famciclovir (P=0.54, PP analysis). Prevalence and duration of ZAP did not differ significantly between treatment groups. The prevalence of PHN was higher in patients>or=65 years (brivudin: 16.4%, famciclovir: 16.4%), and in patients with severe rash (brivudin: 13.4%, famciclovir: 15.7%), without significant differences between treatment groups. In patients>or=65 years, median duration of PHN was shorter with brivudin than with famciclovir (39.5 vs. 57.5 days), although the difference was not statistically significant. The two drugs had equivalent efficacy in being able to accelerate the stop of vesicle formation, and lesion healing. Adverse events were similar in nature and prevalence among groups. CONCLUSIONS: The study demonstrated equivalent efficacy of brivudin and famciclovir in the treatment of herpes zoster regarding the prevention of chronic pain and the resolution of signs and symptoms of acute herpes zoster. Compared with famciclovir, brivudin provides equivalent efficacy and safety at a more convenient once-daily dose schedule.     

Management of the patient at high risk for postoperative nausea and vomiting

Postoperative nausea and vomiting continue to be problematic areas in anesthesia as evidenced by frequent reports of therapies in the literature. No single therapy has been proven curative for all cases, in part because of the several emetic centers, all of which may be blocked by different classes of drugs and the diverse risk factors which act alone or in combination to cause vomiting. Identification of the patient most at risk allows for cost effective prophylactic management. An appropriate anesthetic technique can be planned that, relying on evidence based medicine, will decrease if not prevent the incidence of this most troubling complication.     

Impact of intellectual status on response to cognitive task training in patients with schizophrenia

Cognitive remediation is a promising rehabilitation procedure for people with schizophrenia, but very little is known about who can benefit. In the current analyses, we examined the role of pre-morbid and morbid intellectual function in predicting response to cognitive remediation in a sample of 152 patients diagnosed with schizophrenia or schizoaffective disorder. They were participants in a trial of work therapy and cognitive remediation and had been randomized to receive either Neurocognitive Enhancement Therapy with Work Therapy (NET+WT) or Work Therapy only (WT only). For the current analyses, patients were divided into three intellectual subgroups based on their pattern of premorbid and morbid deficits (preserved intelligence, compromised intelligence, and deteriorated intelligence), and their cognitive remediation outcomes were examined. Cognitive remediation response was measured in two ways: normalization of performance on a computerized training task, and pre-post neuropsychological test performance. Subjects in NET+WT showed greater improvement in cognition than those in WT only, but response differed by intellectual group. For patients in the compromised group, those in NET+WT showed a significantly higher proportion of task normalization than those in the WT only condition, but no such differences were found with the preserved and deteriorated intellectual groups. For patients in the preserved and deteriorated intellectual groups, those in the NET+WT condition showed significantly greater improvement in the analysis of pre-post neuropsychological test performance, but this difference was not found in the compromised intellectual group. These findings suggest that the compromised intellectual group, which had the lowest frequency of normal performers at intake, benefited from NET by achieving dramatic increases in normalization, but that they had difficulty in generalizing these gains to untrained tasks. Those in the preserved and deteriorated intellectual groups were more successful in generalizing their training.