Search

Venlafaxine, a dual serotonin and noradrenaline re-uptake inhibitor, has been found to be effective at doses below 375 mg daily, but for patients with major depression higher doses can be required. In this retrospective naturalistic study, we investigated the effectiveness and resource implications of prescribing higher than standard doses of venlafaxine (tablet preparation). Ninety-six outpatients fulfilling DSM-IV criteria for major depressive disorder were assigned to two demographically matched cohorts: cohort A, receiving high doses (n = 38; doses ≥375 mg/day) and cohort B, receiving standard doses (n = 58; doses <375 mg/day). Data on hospital resources, drugs and medical profiles were extracted from patients' records. Information on cohort A was also obtained before their high-dose regime, while taking standard doses. A within-group analysis of cohort A showed that patients spent fewer days in hospital (P = 0.03) and had fewer outpatients visits (P < 0.01) when on high doses than when on standard doses. A between-group analysis found that cohort A, while on higher doses, had fewer outpatient visits compared with cohort B (P < 0.01). Patients in both groups had satisfactory drug tolerability and efficacy profiles. There were no differences between cohorts with regard to baseline characteristics, a part from the more intensive use of additional medications made by cohort A. Our preliminary investigation suggests that higher doses of venlafaxine may be cost-saving in relation to selected hospital resources. However, one cannot firmly conclude that the change in service use is due to the higher-dose regime, and we recommend further research to ascertain the cost-effectiveness of adequate dose prescribing in patients with poor symptom resolution at lower doses of venlafaxine. [ABSTRACT FROM AUTHOR]

Background: Functional imaging studies indicate that delusions and hallucinations in schizophrenia are associated with overactivity of the left hippocampus and ventral striatum. Hippocampal neuronal firing modulates feedback to cortex via cortico-striato-thalamic loops.Aims: To test the hypothesis that recovery from psychosis is associated with decrease in activity in cortico-striato-thalamic circuits, and, furthermore, that reduction in hippocampal activity predicts the degree of alleviation of delusions and hallucinations.Method: Positron emission tomography (PET) was used to measure the effects of the atypical antipsychotic, risperidone, on glucose metabolism in eight first-episode schizophrenia patients.Results: A single dose of risperidone produced decreases in metabolism in ventral striatum, thalamus and frontal cortex. The magnitude of decreases in left hippocampus predicted subsequent reduction in delusions and hallucinations. After six weeks' treatment with risperidone, the decreases in frontal metabolism were more extensive.Conclusions: The mechanism of antipsychotic action of risperidone entails reduction of hippocampal activity together with reduced feedback via cortico-striato-thalamic loops. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate the independent effects of leptin and adiponectin on insulin sensitivity as well as insulin secretion and beta-cell function in overweight Hispanic adolescents. Despite pubertal changes in hormone secretion, studies investigating the independent effect of both hormones on insulin sensitivity and beta-cell function in adolescents are lacking. In a cross-sectional study, 175 overweight Hispanic adolescent boys (n=101) and girls (n=74) with a family history of diabetes were recruited and insulin sensitivity (SI), acute insulin response to glucose (AIR), disposition index (DI), body composition, total serum adiponectin, and leptin were assessed. Over age, leptin significantly increased in girls but not in boys (p for age x gender interaction=0.005) while adiponectin was similar in boys and girls. Leptin was not correlated to adiponectin. Leptin (partial r=-0.180; p=0.019) and adiponectin (partial r=0.230; p=0.003) predicted SI independent of age, gender, body fat, lean body mass, and Tanner stage but together, they explained 5% of the unique variation in SI (p for R (2)-change<0.001). Leptin or adiponectin were not related to AIR or DI. With regard to SI, AIR, and DI, no significant gender, age, or Tanner stage interactions were observed suggesting similar effects of adiponectin and leptin among gender, age, and Tanner stages. Leptin and adiponectin were independently associated with SI, but not with insulin secretion or beta-cell function.

Objectives: To evaluate the hypotheses that subjective memory ratings are more accurate in the oldest old than in the young old and more accurate in a representative sample than in a convenience sample., Methods: Outcomes of hierarchical regressions of subjective ratings and participant characteristics on recall were compared between a nationally representative sample of 6,446 adults ages 70 to 103 and a convenience sample of 326 adults ages 70 to 97., Results: Education interacted with memory ratings in the prediction of performance in the representative sample, with better prediction for more highly educated participants than for participants with lower levels of education., Discussion: The general pattern of findings was consistent across both samples and neither hypothesis was supported. Possible explanations for the similarity of results across samples are considered.

Objective: The goal was assessment of a revolutionary approach to laryngeal stenting. A radically designed, atraumatic, inflatable, low-pressure, high-volume, endoscopically inserted laryngeal stent for effective intralaryngeal support or long-term prevention of aspiration was prospectively evaluated in a canine model to reveal any significant short- and long-term anatomic and functional changes in the larynx., Methods: A self-sustaining, tube-free, long-term flap tracheostomy was performed in 14 dogs, followed by endoscopic laryngeal stent insertion. The stents were inflated, and their intraluminal pressures were monitored daily. The stenting period ranged between 3 and 46 days (mean 27.4 days). The animals were then euthanized, and total laryngectomy was performed. The larynges underwent gross and microscopic examinations, and a grading scale of reactive changes caused by the stent placement was created on the basis of the findings., Results: Dye studies for aspiration were negative in all animals. Gross findings consisted of varying degrees of small ulceration, localized polypoid lesions, and granulomas. Grossly, 9 dogs exhibited small superficial ulceration of the true vocal cords and posterior commissure. Six dogs developed minor polyps or polypoid changes and/or granulomas, respectively. No gross changes were seen in 2 of the dogs. Histopathologically, 10 dogs demonstrated grade I or II histopathologic changes. Only 4 of the dogs exhibited inflammation extending into the underlying cartilages, grade III. One dog did not complete the observation period., Conclusion: This new stent demonstrated safety and biocompatibility with minimal local tissue reaction to its extended long-term placement. Good tolerance to the stent was documented, with minimal side effects similar to those that would be observed in human subjects after endotracheal intubation. When followed up in human patients, such minimal lesions have not resulted in significant long-lasting functional impairments. These initial results would indicate that this stent is well tolerated for long-term application and qualify as the preferred device for both management of aspiration and postoperative endolaryngeal bolstering support.

Background: The neuroreceptor changes involved in therapeutic efficacy of various antidepressants remain unclear. Preclinical studies have shown that long-term administration of various antidepressants causes down-regulation of brain serotonin 2 (5-HT2) receptors in rodents, but it is unknown if similar changes occur following antidepressant treatment in depressed patients. Our purpose, therefore, was to assess the effects of treatment with desipramine hydrochloride on brain 5-HT2 receptors in depressed patients using positron emission tomography (PET) and fluorine-18 (18F)-labeled setoperone., Methods: Eleven patients who met DSM-IV criteria for major depression as determined by a structured clinical interview for DSM-III-R diagnosis and suitable for treatment with desipramine were recruited. Ten patients underwent a PET scan before and another after 3 to 4 weeks of treatment with desipramine., Results: Eight of the 10 patients responded to desipramine treatment as indicated by more than 50% decrease in Hamilton Depression Rating Scale scores. Depressed patients showed a significant decrease in 5-HT2 receptor binding as measured by setoperone binding in frontal, temporal, parietal, and occipital cortical regions following desipramine treatment. The decrease in 5-HT2 receptor binding was observed bilaterally and was particularly prominent in frontal cortex., Conclusions: Depressed patients showed a significant reduction in available 5-HT2 receptors in the brain following desipramine treatment, but it is unknown if this change in 5-HT2 receptors is due to clinical improvement or an effect of desipramine that is unrelated to clinical status.

Objective: To compare the interval to delivery of the first shock by first responders in mannequin-based cardiac arrest scenarios using two automated external defibrillator (AED) algorithms., Methods: Thirty-six (18 pairs) of Toronto firefighters (FFs) trained in two AED algorithms, algorithm I (A-I) and algorithm II (A-II), were studied. A-II mandates the immediate application of the AED once pulselessness is established. In contrast to A-I, A-II dictates that no CPR be initiated until it is required by the AED voice prompts. Each FF pair alternated roles while performing "shock-indicated," mannequin-based scenarios according to A-I and A-II. The interval from mannequin contact to delivery of the first shock was recorded. Five pairs were videotaped. The intervals to complete predetermined steps were compared between algorithms to determine in which step(s) time saving occurred., Results: The mean (+/-SD) interval to the first shock in A-I was 80.7 seconds (+/-10.5 sec) (95% CI = 77.2 to 84.2 sec) vs 61.1 seconds (+/-8.75 sec) (95% CI = 58.2 to 64.0 sec) in A-II (p < 0.001). A-II shortened the interval to the first shock by 19.6 sec (+/-11.5) (95% CI = 15.8 to 23.4 sec). The time saving was a direct result of delaying CPR in A-II., Conclusion: A-II reduced the interval from mannequin contact to the first shock in standard training scenarios.

Eight rats with lesions of the dorsomedial thalamus and 10 rats with sham operations were compared on acquisition and subsequent reversals of a spatial discrimination. The rats with thalamic damage showed greater perseveration to the incorrect choices (p less than 0.002) and made fewer reversals (p less than 0.05) and more errors (p less than 0.02) during the 100 reversal trials following initial acquisition than did the sham-operated animals. The two groups did not differ on the original acquisition.