Periosteal gouty tophi of the anterior mid tibia.
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Biomedical subjects
Publications and source records attributed to L Friedman.
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BACKGROUND: In this study, we tested the hypothesis that low smooth pursuit gain in schizophrenia is related to an abnormality in motion perception. METHODS: The subjects were 19 schizophrenics treated with clozapine and 19 controls. In addition to smooth pursuit and motion perception paradigms, sustained attention was also assessed using a continuous performance task (CPT). RESULTS: In the patient group, there was a statistically significant negative correlation between smooth pursuit gain and motion perception threshold (r = -0.60, P < 0.01). This relationship was not secondary to attention deficits as assessed by the CPT. CONCLUSIONS: Our results are consistent with the notion that the smooth pursuit gain deficit is related to a deficit in motion perception rather than in attention. Brain area V5 (also referred to as "MT' in macaque), located in the parieto-occipital region, is known to be critically important both for motion perception and gain. Thus, our results point to an abnormality in this area in schizophrenia.
Approximately one quarter of patients with AD-type dementia reportedly exhibit disruptive, restless, and/or confused behavior that tends to be more apparent in late afternoon or early evening. Research has yet to document the phenomenon in a definitive manner to facilitate standardized assessment and clinical trials. Recent work attempting to define precisely the prevalence of abnormal behaviors during different periods of time of day in AD patients is reviewed. Caregiver reports of confusion and aggressive, disruptive behavior have been associated with going to bed early, increased use of sedative-hypnotics, and more severe cognitive impairment. Because there is evidence that the sleep of many AD patients is of poor quality, one might try to treat such patients with behavioral approaches useful in insomnia in other populations. Futhermore, as psychotropic medications can adversely affect sleep and/or have "hangover" effects on daytime cognition, one should carefully manage these medications to optimize care. Advances in assessment of sundowning, combined with longitudinal studies of sleep and circadian rhythm changes associated with dementia progression, should enhance efforts to treat behavioral and sleep disturbances.
BACKGROUND: It has been reported that a substantial proportion of cases of hypercalciuria and nephrolithiasis are idiopathic. Several studies suggested that stressful life events increase lithogenic urinary constituents (calcium, oxalate and uric acid). OBJECTIVE: To test the hypothesis that there is an association between stressful life events and symptomatic kidney stone. METHODS: A case-control study of 200 symptomatic kidney stone cases and 200 matched controls was designed to test the hypothesis. In this study, the stressors include those life events that the subjects perceived as highly stressful and inflicted upon them an intense emotional impact with apprehension and distress for at least one week in duration. RESULTS: Ten of eleven (91%) categories and 41 of 60 (68%) subcategories of stressful events occurred more frequently among cases than controls. Eighteen stressful events had odds ratios of 1.5 or greater. Of the seven significant (P < 0.05) variables that were entered into a multivariate logistic regression model, the following three remained statistically significant between cases and controls: annual family income (lower for cases); stressful morgage problems; and emotional life events. CONCLUSION: The overall prevalence rate of stressful life events was significantly (P < 0.00001) higher among cases than controls. The data support the hypothesis that there is an association between stressful life event(s) and symptomatic kidney stones.
BACKGROUND AND PURPOSE: Drug treatment of high blood pressure has been shown to reduce the associated cardiovascular risk. Stroke represents the type of event more strongly linked with high blood pressure, responsible for a high rate of death or invalidity, and with the highest proportion of events that can be avoided by treatment. Hypertensive patients with a history of cerebrovascular accident are at particularly high risk of recurrence. Specific trials of blood pressure lowering drugs in stroke survivors showed inconclusive results in the past. METHODS: We performed a meta-analysis using all available randomized controlled clinical trials assessing the effect of blood pressure lowering drugs on clinical outcomes (recurrence of stroke, coronary events, cause-specific, and overall mortality) in patients with prior stroke or transient ischemic attack. RESULTS: We identified 9 trials, including a total of 6752 patients: 2 trials included 551 hypertensive stroke survivors; 6 trials of hypertensive patients included a small proportion of stroke survivors (536 patients); 1 trial included stroke survivors, whether hypertensive or not (5665 patients). The recurrence of stroke, fatal and nonfatal, was significantly reduced in active groups compared with control groups consistently across the different sources of data (relative risk of 0.72, 95% confidence interval: 0.61 to 0.85). There was no evidence that this intervention induced serious adverse effect. CONCLUSIONS: Blood pressure lowering drug interventions reduced the risk of stroke recurrence in stroke survivors. Available data did not allow to verify whether such benefit depends on initial blood pressure level. More data are needed before considering antihypertensive therapy in normotensive patients at high cerebrovascular risk.
OBJECTIVE: The purpose of this study was to determine whether adolescent schizophrenia is characterized by neuropsychological deficits. METHOD: The performance on a battery of neuropsychological tests of 17 adolescents with schizophrenia (mean age = 15.71 years) was compared with that of 17 normal adolescents (mean age = 15.12 years). RESULTS: Compared with the normal subjects, the patients were impaired on 10 of the 13 measures; larger effect sizes were shown for measures involving working memory and attention than for those involving secondary memory, generative naming, and executive functions. CONCLUSIONS: Adolescents with schizophrenia have generalized cognitive dysfunction, which is most apparent on tests of attention and working memory.
The purpose of this preliminary report was to explore overall level and diurnal patterning of caregiver reports of abnormal behavior and to explore relationships with actigraphic measures of sleep/wake activity in Alzheimer's disease (AD) patients. Our primary behavioral measure was the Time-based Behavioral Disturbance Questionnaire (TBDQ). The overall score on this measure was shown to have adequate test-retest reliability and convergent validity with another behavioral measure. Significant correlations were obtained between the TBDQ overall score and actigraphically scored sleep efficiency (r = -.35, P < .05) and wake after sleep onset (r = .43, P < .01) in 41 subjects. The data suggest a moderate relationship between actigraphic measures of sleep/wake and disturbed behavior in home-dwelling AD patients.
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We describe the obstetric anesthetic management of a patient with complex congenital heart anomaly consisting of transposed great arteries, double inlet left ventricle and subpulmonic stenosis. Successful management of a patient with Fontan physiology mandates a thorough understanding of the hemodynamic consequences of this procedure and the alterations during pregnancy. The major considerations are related to the fact that the systemic venous return reaches the pulmonary vasculature without the augmentation of a functioning ventricle.
Several meta-analyses are presented that address the issue of brain and/or cranial size reductions in schizophrenia. Separate meta-analyses were conducted for brain size (n = 27 studies), intracranial size (n = 18) or extracranial size (n = 8). For each meta-analysis, the weighted composite effect size (d) was tested for statistical significance (the direction of the effect size was negative if patients with schizophrenia had smaller structure size than controls). The influence of several potential modifiers of effect size (age, methods, region, gender) was individually evaluated. The composite effect sizes for studies of brain, intracranial and extracranial measures were d = -0.26, (p < 0.0001), d = -0.18, (p = 0.0012), and d = +0.14, (p = 0.16), respectively. Thus, the review found evidence for a small, but statistically significant reduction in brain and intracranial size in schizophrenia, but no evidence for a reduction in extracranial size. Studies based on axial image slices had significantly larger effects (d = -0.60) than the studies based on sagittal images (d = -0.09) (chi(2) = 14.0, p = 0.0002). In summary, the findings clearly support a small yet highly significant reduction of brain and intracranial size in schizophrenia.
Neuropeptide Y (NPY) plays important roles in the central control of appetite and energy balance, but the receptor subtype responsible for this function has not been cloned. Here we report the cloning by expression of a novel NPY receptor subtype from a rat hypothalamus cDNA library. The novel receptor, referred to as the NPY Y5 receptor, has a transcript of approximately 2.6 kilobases with an open reading frame of 1335 base pairs that encodes a 445-amino acid protein. The amino acid sequence deduced from the rat Y5 cDNA clone shows only 30-33% identity to other NPY receptors, including Y1, Y2, and Y4/PP1. Using the rat Y5 receptor cDNA probe, the human homologue was obtained by low stringency hybridization. The human Y5 amino acid sequence has 88% identity to the rat Y5 receptor. Importantly, pharmacological analysis shows that the rat and human Y5 receptors have high affinity for the peptides that elicit feeding (e.g. NPY, PYY, (2-36)NPY, and (LP)NPY) and low affinity for nonstimulating peptides (e.g. (13-36)NPY and rat PP), suggesting that it is the NPY feeding receptor subtype.
Although several studies have reported ventricular enlargement and sulcal prominence in mixed samples of patients with affective disorders (unipolar and bipolar subtypes), it is not established if these findings extend to a homogeneous sample of relatively young patients with unipolar major depression ventricular:brain ratio (VBR) and prefrontal sulcal prominence (PSP). In the present study, measures of ventricle-brain ratio (VBR) and prefrontal sulcal prominence (PSP) were compared in patients with affective disorders (n = 24, mean age = 39), medical control subjects (n = 40), patients with schizophrenia (n = 101) on ventricular : brain ratio (VBR) and prefrontal sulcal prominence (PSP). No statistically significant differences were noted in VBR in the three groups. Both patient groups had significantly greater PSP than the medical control subjects but did not differ significantly from each other. The results of the present study extend the finding of prefrontal sulcal prominence, but not ventricular enlargement, to relatively young patients with unipolar depression. Furthermore, the results of the present study suggest that patients with schizophrenia and patients with affective disorders differ only slightly or not at all in brain morphology, at the level of resolution studied.
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Transport of glutamic acid by the choroid plexus, the blood-cerebrospinal fluid (CSF) barrier, was investigated by using the isolated choroid plexi from the fourth (FVCP) and lateral ventricles (LVCP) of the young adult miniswine in vitro. Glutamic acid uptake was very pronounced, with concentrations 7-fold (LVCP) and 2.4-fold (FVCP) higher in tissue than in medium after only 5 min of incubation with 1 microM glutamic acid. Tissue/medium ratios reached steady state by 15 min at 30-fold (LVCP) and 11-fold (FVCP). Uptake was energy-dependent and inhibited by ouabain and hypothermia. L-Aspartic acid was shown to be inhibitory in a concentration-dependent manner, suggesting that it shares a common transport system, whereas neither octanoic acid nor okadaic acid (transported by a separate fatty acid system) inhibited glutamic acid transport. At the same temperature, the labeled metabolite of glutamate (glutamine) in the tissue was 64.7%, 73.2%, and 72.5% of total radioactivity at 5, 30, and 60 min, respectively. The estimated Km values for glutamate uptake by the choroid plexus are 264 microM (FVCP) and 196 microM (LVCP); Vmax values are 87 (FVCP) and 147 (LVCP) nmol/g/min, respectively. These results indicate that, in addition to the metabolism of glutamate to glutamine, an active uptake mechanism is present in the choroid plexus of miniswine which may serve to regulate glutamic acid concentration in the CSF.
K252 family of alkaloid toxins-kinase inhibitors are the most widely used compounds in biological research on the role of protein kinases in cellular transduction systems, biological functions and pathophysiology of neurological disorders. The wide research interest in these toxins is due to their potency in inhibiting cellular protein kinases. However, lack of kinase specificity is one of their major drawbacks. Synthesis of new K252 derivatives can be expected to open up a new generation of kinase inhibitors. Staurosporine might be considered as a prototype neurotropic drug in view of its ability to induce neurite outgrowth and to increase tau protein levels. Because it mimics some of the neuroprotective effects of NGF and might blocks certain signals required to enhance cellular levels and/or beta amyloid processing, staurosporine might play a beneficial role in the treatment of Alzheimer's disease. The ability of staurosporine to promote neuronal regeneration and brain cholinergic neurons survival has been also demonstrated in animal studies (Nabeshima et al., 1991). The beneficial effects of K252a on the experimental autoimmune encephalomyelitis (EAE) disease mice model and it's ability to supress macrophage activation suggest an important role of protein kinases inhibitors as immunosupressive agents. These results may also point to the potential clinical relevance of K252 microbial toxins as prototypes for the development of new drugs for the management of neuronal diseases.