A Canadian multicenter trial assessing memory and executive functions in patients with schizophrenia spectrum disorders treated with olanzapine

Serial verbal learning task (explicit long-term memory) and verbal fluency (generation of a response) are tests that are usually severely impaired in schizophrenia. Despite the growing literature supporting the clinical efficacy of olanzapine, psychiatrists still question its cognitive consequences. This study assessed the efficacy of olanzapine on neurocognitive functioning. Patients (N = 134) meeting diagnostic criteria for schizophrenia, schizophreniform, or schizoaffective disorders began an 8-week, open-label olanzapine treatment at a dose of 5 mg/d, which was increased to 10 mg/d after 1 week. Daily dosage was subsequently adjusted between 5 and 20 mg/d based on individual clinical status. All previous antipsychotics were tapered and discontinued during the first 2 weeks of the study. Neuropsychologic assessments were carried out at baseline and at 4 and 8 weeks. Explicit long-term memory was assessed with the Rey Auditory-Verbal Learning Test: the average immediate recall score significantly improved (P < 0.001), as did the delayed recall score (P < 0.001). The average total score on category fluency improved from 34.6 words at baseline to 37.6 words at end point (P < 0.0001). Time on both Trail A and B making tasks significantly decreased (P < 0.0001). Lack of a control arm makes it impossible to exclude a practice effect as an explanation for the enhanced cognitive performance, although the Word List Recall test represents one of the better resources to avoid a practice effect. After switching to olanzapine, there was a statistically significant improvement of cognitive function in the 3 main domains tested and no significant worsening of any memory or executive function measure.     

Hypertonic resuscitation of hemorrhagic shock upregulates the anti-inflammatory response by alveolar macrophages

BACKGROUND: Resuscitated hemorrhagic shock predisposes patients to the development of acute respiratory distress syndrome (ARDS). Hypertonic saline (HTS) has been shown to inhibit immune cell activation in response to lipopolysaccharide (LPS) in vitro and to reduce lung damage when used for resuscitation of hemorrhagic shock in vivo. We hypothesize that HTS resuscitation of hemorrhagic shock may exert this anti-inflammatory effect by modulating alveolar macrophage function leading to an altered balance between the proinflammatory and the counter-inflammatory response. METHODS: A 2-hit rat model of shock resuscitation was used. Alveolar macrophages were harvested by bronchoalveolar lavage (BAL), and tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 were quantified in the cell culture supernatants by enzyme-linked immunosorbent assay (ELISA). Alternatively, 1 hour after resuscitation, animals received endotracheal LPS followed by endotracheal anti-IL-10 neutralizing antibody. Lung injury was determined by measuring BAL neutrophil counts 4 hours after LPS in vivo administration. RESULTS: Systemic administration of HTS significantly modulates the responsiveness of alveolar macrophages. Specifically, HTS resuscitation inhibited LPS-induced TNF-alpha production while enhancing IL-10 release in response to LPS administered ex vivo and in vivo. Anti-IL-10 antibody in vivo partially reversed the lung protective effect of HTS resuscitation. CONCLUSIONS: HTS resuscitation exerts an immunomodulatory effect on alveolar macrophages by shifting the balance of pro- and counter-inflammatory cytokine production in favor of an anti-inflammatory response. The in vivo data suggest a causal role for HTS-induced augmented IL-10 as protective. These findings suggest a novel mechanism for the in vivo salutary effect of HTS resuscitation on lung injury after resuscitated hemorrhagic shock.     

Radical causes of cancer

Free radicals are ubiquitous in our body and are generated by normal physiological processes, including aerobic metabolism and inflammatory responses, to eliminate invading pathogenic microorganisms. Because free radicals can also inflict cellular damage, several defences have evolved both to protect our cells from radicals--such as antioxidant scavengers and enzymes--and to repair DNA damage. Understanding the association between chronic inflammation and cancer provides insights into the molecular mechanisms involved. In particular, we highlight the interaction between nitric oxide and p53 as a crucial pathway in inflammatory-mediated carcinogenesis.     

Effect of sodium hypochlorite and EDTA on mercury released from amalgam

OBJECTIVES: The effect of sodium hypochlorite (NaOCl) and EDTA on mercury released from dental amalgam was assessed in vitro. STUDY DESIGN: Fifty-six samples of dental amalgam of similar size were prepared and exposed to a 10-mL solution of either 1% NaOCl, 3% NaOCl, 10% EDTA in 1% NaOCl, or 10% EDTA in 3% NaOCl for periods of 20, 40, and 60 minutes. Mercury concentrations in the solutions were measured by using a cold-vapor atomic absorption Mercury Analyzer System, and the differences between the groups were statistically analyzed. RESULTS: All amalgam samples exposed to 1% NaOCl and 3% NaOCl-either alone or in combination with EDTA-released mercury into the solutions. Mercury release was significantly higher in the test groups than in the EDTA, distilled water, or phosphate buffer controls (P <.001). Increase in the mean concentration levels of mercury in solution was time-dependent and directly related to NaOCl concentration. The addition of EDTA caused a reduction in mercury levels detected in solution, which was more significant in amalgam samples exposed to 1% NaOCl combined with EDTA (P <.001). CONCLUSIONS: NaOCl solutions commonly used for root canal cleaning and shaping cause mercury release from dental amalgam and may alter its chemo-physical properties as a sealant for root perforations.     

Clinical relapses of multiple sclerosis are associated with 'novel' valleys in natural killer cell functional activity

Natural killer (NK) cells are implicated in the pathogenesis of multiple sclerosis (MS). Nine relapsing-remitting MS (RRMS) patients along with age, sex, and NK responder status matched controls were studied serially. Although the average NK cell functional activity (FA) was not significantly different between both groups, four clinical relapses in RRMS patients were associated with the development of 'novel' valleys in FA. These valleys are of greater depth and duration than cyclical valleys observed in both RRMS and controls, precede the onset of clinical attacks, and are observed in RRMS but not controls. In both RRMS and controls, cyclical peaks and valleys in FA are determined by the number of CD33+, CD3-CD56+, and to a lesser extent CD3+CD56+ cells capable of binding targets and inducing cell-mediated cytotoxicity (CMC). In contrast, 'novel' valleys in FA result from a reduction in the ability of CD3-CD56+ bound to targets to induce CMC. The results suggest that RRMS patients are at greater risk for clinical relapses during 'novel' valleys in FA. Furthermore, these valleys are the result of cells with a NK cell phenotype being unable to deliver a 'lethal' hit to targets.     

Intratympanic gentamicin for intractable Meniere's disease: 5-year follow-up

OBJECTIVE: To determine the efficacy and morbidity of intratympanic gentamicin titration therapy on patients with incapacitating unilateral Meniere's disease. METHOD: The study consisted of a retrospective chart review and patient interviews. Sixty-eight patients had been followed for a minimum of 24 months and were reported on in an earlier study. Forty-six of these individuals were available for detailed follow-up at 5 years post-gentamicin therapy. MAIN OUTCOME MEASURES: Vertigo frequency, hearing status, personal disability ratings, and tinnitus level before and after gentamicin therapy were measured. RESULTS: Seventy-four percent of patients showed complete vertigo control and an additional 7% showed substantial vertigo control. There was also significant improvement in personal ratings of social and economic functioning. Overall, the group showed no combined statistically significant changes in any of the hearing parameters. CONCLUSION: Intratympanic gentamicin titration therapy provides excellent vertigo control, with a similarly significant improvement in both personal and occupational functioning.     

Physiological responses to incremental exercise in patients with chronic fatigue syndrome

PURPOSE: The purpose of this investigation was to characterize the physiological response profiles of patients with chronic fatigue syndrome (CFS), to an incremental exercise test, performed to the limit of tolerance. METHODS: Fifteen patients (12 women and three men) who fulfilled the case definition for chronic fatigue syndrome, and 15 healthy, sedentary, age- and sex-matched controls, performed an incremental progressive all-out treadmill test (cardiopulmonary exercise test). RESULTS: As a group, the CFS patients demonstrated significantly lower cardiovascular as well as ventilatory values at peak exercise, compared with the control group. At similar relative submaximal exercise levels (% peak VO(2)), the CFS patients portrayed response patterns (trending phenomenon) characterized, in most parameters, by similar intercepts, but either lower (VCO(2), HR, O(2pulse), V(E), V(T), PETCO(2)) or higher (B(f), V(E)/VCO(2)) trending kinetics in the CFS compared with the control group. It was found that the primary exercise-related physiological difference between the CFS and the control group was their significantly lower heart rate at any equal relative and at maximal work level. Assuming maximal effort by all (indicated by RER, PETCO(2), and subjective exhaustion), these results could indicate either cardiac or peripheral insufficiency embedded in the pathology of CFS patients. CONCLUSION: We conclude that indexes from cardiopulmonary exercise testing may be used as objective discriminatory indicators for evaluation of patients complaining of chronic fatigue syndrome.