Association between impaired insulin sensitivity and stroke

BACKGROUND: Prior research has indicated an association between insulin resistance and stroke; we sought to determine if this association persists after adjusting for stroke risk factors, including glycemic control. METHODS: We used data from the Third National Health and Nutrition Survey (1988-1994), including participants aged > or =40 years. We assessed insulin sensitivity using the homeostasis model assessment (HOMA): HOMA = (FPGSI x FPI)/22.5, where FPGSI refers to fasting plasma glucose (mmol/l) and FPI refers to fasting plasma insulin (microU/l). Increasing HOMA indicates decreasing insulin sensitivity. We used glycosylated hemoglobin (HbA1c) to measure glycemic control. Multivariable logistic regression analysis was used to identify factors that were independently associated with stroke. RESULTS: Among 3,844 participants, 168 (4%) reported a stroke history. Participants with stroke had lower insulin sensitivity than participants without stroke: HOMA mean +/- standard deviation, 4.0 +/- 4.0 vs. 3.3 +/- 3.0; p = 0.022. HOMA was independently associated with stroke (odds ratio 1.06, 95% CI: 1.01-1.12; adjusted for age, hypertension, myocardial infarction, claudication, activity, and HbA1c). The strength of the association between HOMA and stroke was similar to the association between claudication and stroke (index R(2): 0.0032 vs. 0.0036). CONCLUSIONS: Impaired insulin sensitivity is independently associated with stroke, even after adjustment for glycemic control.     

Effects of sleep disruption on rat dentate granule cell LTP in vivo

Sleep frequently fragmented or disrupted for prolonged periods can result in mood changes and impaired mental ability and performance. Sleep deprivation is defined as depriving a person or organism of sleep for various periods of fixed durations. Sleep disruption (SD) occurs when a person is awakened at any time when they would normally be sleeping; sometimes on a schedule but usually unexpectedly. It seems as if any disruption of an entrained sleep pattern can induce learning and memory impairment; and mood changes including irritability and aggression. Because memory is impaired under these conditions several studies have been conducted recently to examine changes in long term potentiation (LTP) in hippocampal brain slices following various periods of sleep deprivation in rats. Results of the present study show clearly that LTP is also decreased following SD but to a greater extent than that observed following sleep deprivation. The purpose of the present study was to measure dentate granule cell LTP in anesthetized rats following 1-, 2-, or 3-day schedules of SD using a modified flower pot procedure. Results showed that a single disruption of 3 h reduced LTP from a normal 38.7-7.6%; that endured for at least 14 h; and 9 h reduced it completely. Easy to handle animals become irritable, hyperactive, and aggressive following SD. Results are discussed in terms of stress related effects of SD and changes in synaptic plasticity.     

An introduction to economic evaluation: what's in a name?

OBJECTIVE: This paper describes the main types of economic evaluation techniques. METHOD: To examine the strengths and limitations of different types of economic evaluations, we used a hypothetical example to review the reasoning underlying each method and to illustrate when it is appropriate to use each method. RESULTS: The choice of economic evaluation method reflects a decision about what should represent "success" and how success should be valued. Measures of benefit and cost must be considered systematically and simultaneously. Claiming that a new treatment is cost-effective requires making a value judgment based on the personal beliefs of the claimant. Even when cost and effect data are objective, a verdict of cost-effective is subjective. The conclusions of an economic study can change significantly, depending on which patient outcome is used to measure success. CONCLUSIONS: Clinicians must be sure that important patient outcomes are not excluded from economic evaluations. Economic evaluation is a process designed to produce an estimate rather than a decision. New treatment can be more costly and still be cost-effective (if the extra benefit is valued more than the extra cost to produce it). However, since economic evaluation does not explicitly consider a decision maker's available budget, a new treatment can be deemed cost-effective but too expensive to approve.     

Alterations in regional cerebral glucose metabolism across waking and non-rapid eye movement sleep in depression

BACKGROUND: Depression is associated with sleep disturbances, including alterations in non-rapid eye movement (NREM) sleep. Non-rapid eye movement sleep is associated with decreases in frontal, parietal, and temporal cortex metabolic activity compared with wakefulness. OBJECTIVE: To show that depressed patients would have less of a decrease than controls in frontal metabolism between waking and NREM sleep and to show that during NREM sleep, they would have increased activity in structures that promote arousal. DESIGN: Subjects completed electroencephalographic sleep and regional cerebral glucose metabolism assessments during both waking and NREM sleep using [(18)F]fluoro-2-deoxy-D-glucose positron emission tomography. SETTING: General clinical research center. PATIENTS: The study included 29 unmedicated patients who met the Structured Clinical Interview for DSM-IV criteria for current major depression and who had a score of 15 or greater on a 17-item Hamilton Rating Scale for Depression and 28 medically healthy subjects of comparable age and sex who were free of mental disorders. MAIN OUTCOME MEASURES: Electroencephalographic sleep and regional cerebral metabolism during waking and NREM sleep. RESULTS: Depressed patients showed smaller decreases than healthy subjects in relative metabolism in broad regions of the frontal, parietal, and temporal cortex from waking to NREM sleep. Depressed patients showed larger decreases than healthy subjects in relative metabolism in the left amygdala, anterior cingulate cortex, cerebellum, parahippocampal cortex, fusiform gyrus, and occipital cortex. However, in post hoc analyses, depressed patients showed hypermetabolism in these areas during both waking and NREM sleep. CONCLUSIONS: The smaller decrease in frontal metabolism from waking to NREM sleep in depressed patients is further evidence for a dynamic sleep-wake alteration in prefrontal cortex function in depression. Hypermetabolism in a ventral emotional neural system during waking in depressed patients persists into NREM sleep.     

Sarcosine or D-serine add-on treatment for acute exacerbation of schizophrenia: a randomized, double-blind, placebo-controlled study

CONTEXT: Agents that enhance N-methyl-D-aspartate (NMDA) function through the glycine modulatory site (D-serine, glycine, or D-cycloserine) or through glycine transporter 1 (sarcosine) improve the symptoms of patients with stable chronic schizophrenia. OBJECTIVE: To determine whether NMDA-glycine site agonists or glycine transporter-1 inhibitors have better efficacy and whether NMDA receptor-enhancing agents have beneficial effects for acute exacerbation of schizophrenia. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Inpatient units of 2 major medical centers in Taiwan.Patients Sixty-five schizophrenic inpatients with acute exacerbation. INTERVENTIONS: Six weeks of treatment with sarcosine (2 g/d), D-serine (2 g/d), or placebo and concomitant optimal risperidone therapy. MAIN OUTCOME MEASURES: Positive and Negative Syndrome Scale (PANSS) and Scale for the Assessment of Negative Symptoms (SANS) (20 and 17 items) total scores. RESULTS: The sarcosine group revealed more reductions in PANSS total scores than the placebo (P = .04) and D-serine (P<.001) groups. Sarcosine adjunctive treatment was also superior to placebo in reducing SANS-20 (P = .007) and SANS-17 (P = .003) scores and to D-serine in decreasing SANS-20 (P = .006) and SANS-17 (P = .002) scores. The PANSS-general, PANSS-cognitive, and PANSS-depressive symptoms scores and SANS-alogia and SANS-blunted affect scores improved significantly more in sarcosine-cotreated patients than in risperidone monotherapy patients (P< or =.02 for all). Sarcosine adjunctive therapy also surpassed D-serine in terms of PANSS-general, PANSS-positive, PANSS-negative, and PANSS-depressive symptoms scores (P< or =.04 for all). D-serine and risperidone cotreatment did not differ significantly from risperidone monotherapy in all efficacy domains. CONCLUSIONS: This first short-term treatment study on NMDA receptor-enhancing agents suggests that sarcosine, superior to D-serine, can benefit not only patients with long-term stable disease but also acutely ill persons with schizophrenia. This finding indicates that a glycine transporter 1 inhibitor may be more efficacious than NMDA-glycine site agonists for adjuvant treatment of schizophrenia, at least during the acute phase. Further studies are needed.     

Antinociceptive tolerance to morphine from repeated nociceptive testing in the rat

Repeated morphine administration has been shown to produce tolerance to the antinociceptive effects of morphine. However, the degree to which repeated morphine administration decreases antinociception is exaggerated by repeated behavioral testing, a phenomenon known as behavioral tolerance. An important question is whether behavioral tolerance can be overcome by direct administration of morphine into the ventrolateral periaqueductal gray (vPAG), a key structure contributing to morphine antinociception. Rats were injected with morphine or saline into the vPAG (Experiment 1) or subcutaneously (Experiment 2) followed 20 min later with hot-plate testing. The control groups received the same drug administration, but no nociceptive testing. Repeated nociceptive testing or repeated morphine administration produced antinociceptive tolerance regardless of whether morphine was injected into the vPAG or systemically. Administration of a high dose of morphine (20 mg/kg, s.c.) was able to overcome the development of behavioral tolerance, but not pharmacological tolerance revealing separate mechanisms for these two types of tolerance. These data indicate that behavioral tolerance is independent of the route of morphine administration.     

Is craniofacial dysmorpholgy correlated with structural brain anomalies in schizophrenia?

This study aimed to examine the relationship between craniofacial dysmorphology and anomalies of brain morphology in schizophrenia. Assessments of craniofacial dysmorphology and magnetic resonance imaging of brain were performed independently of each other and blind to each other in 24 males with schizophrenia and 16 male controls. Ventricular cerebrospinal fluid volume was negatively correlated with total dysmorphology score in males with schizophrenia (i.e., the larger the ventricular cerebrospinal fluid volume, the lower the total dysmorphology score) but not in male controls. These findings suggest that craniofacial dysmorphology and anomalies of brain morphology may be associated with independent processes in the etiology of schizophrenia.