Role of the serotonergic system in the postmortem analysis of suicide.
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Biomedical subjects
Publications and source records attributed to M Stanley.
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Lithium (Li) has been previously reported to increase acetylcholine turnover and release in rat brain and to potentiate the neurotoxicity of cholinergic agents. We studied the effect of chronic Li administration, alone and in combination with the muscarinic antagonist, scopolamine, on two cholinergically-mediated responses and on muscarinic cholinergic receptor (MCR) binding in rat brain. Administered separately, Li and scopolamine enhanced the cataleptic and hypothermic responses to pilocarpine; combined administration resulted in an additive effect on both these measures. [3H]Quinuclidinyl benzilate ([3H]QNB) binding was increased by Li in the corpus striatum but not in the cortex, hippocampus and hypothalamus. Scopolamine increased [3H]QNB binding in the striatum, cortex and hippocampus; Li and scopolamine effects on striatal MCR were not additive. Contrary to a previous report, antagonist-induced MCR supersensitivity was not prevented by concurrent Li administration in any of the brain areas studied. The additive effect of Li and scopolamine on pilocarpine-induced catalepsy and a trend in this direction for pilocarpine-induced hypothermia suggest that the actions of the two agents to enhance cholinergically mediated responses may be achieved by different mechanisms. Supersensitive responses following scopolamine may be attributed to antagonist-induced up-regulation of postsynaptic muscarinic receptors as demonstrated in the binding studies. The effects of Li to enhance cholinergically-mediated catalepsy and hypothermia are interpreted as extending previous reports that Li stimulates brain cholinergic function by a presynaptic increase in acetylcholine turnover and release.
Brain and cerebrospinal fluid (CSF) levels of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were simultaneously measured in 48 individuals at autopsy. Concentrations of 5-HIAA and HVA in the cerebral cortex were positively correlated with their levels in the CSF for the same individual. Additionally a positive correlation was observed between postmortem CSF levels of 5-HIAA and HVA and a significant concentration gradient for both metabolites was observed in serial fractions of CSF. These findings suggest that determinations of 5-HIAA and HVA in CSF from living individuals may reflect brain metabolite levels as well as the functional activity of these specific neuronal systems.
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The effects of chronic administration of quinacrine, a phospholipase A2 inhibitor, on striatal homovanillic acid (HVA) levels and behavioral sensitivity to challenge with a dopamine agonist were examined in rats. Moreover, the ability of chronic phospholipase A2 inhibition to modulate the behavioral supersensitivity and striatal HVA reduction induced by chronic haloperidol administration was also examined. Daily intraperitoneal injection of quinacrine resulted in a significant reduction of striatal HVA levels. Coadministration of haloperidol with quinacrine in this paradigm caused a more profound reduction of striatal HVA levels than either drug administered alone. That this effect of combined administration is not simply due to postsynaptic effects of quinacrine on dopamine receptor sensitivity is suggested by the fact that behavioral supersensitivity was not induced by quinacrine alone nor was the behavioral supersensitivity induced by the quinacrine-haloperidol combination greater than that induced by chronic haloperidol administration alone. There were no effects of any treatment condition on striatal levels of serotonin (5-HT) or 5-hydroxyindoleacetic acid (5-HIAA). These data implicate phospholipase A2 activity in the regulation of dopaminergic transmission.
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A double-blind placebo-controlled study was conducted in 10 individuals with probable Alzheimer's disease to assess the effects of varying doses of Naltrexone (0, 25, 50 and 100 mg) on cognitive functioning and on plasma cortisol. Each individual participated in four separate sessions at least three days apart. Naltrexone was found to improve performance in only one of the six psychometric tasks employed (Token Test). However, enhancement of Token Test performance was limited to the 25 mg Naltrexone dose and was mainly the result of an improvement on the part of the two most severely impaired patients. In contrast to the previous reports of elevations of plasma cortisol following administration of opiate antagonists to younger, non-demented subjects, Naltrexone administration failed to produce any significant increase in plasma cortisol in Alzheimer's patients.
A patient with extensive thromboses of portal and mesenteric veins and sarcoid of the liver developed recurrent pulmonary emboli, which necessitated the insertion of an umbrella into the inferior vena cava. Chylous ascites appeared shortly thereafter; the ascitic fluid fat content was strikingly reduced after reduction of dietary long chain triglycerides, but the ascitic fluid volume was reduced only after insertion of a peritoneovenous shunt (LeVeen). The shunt was found to be nonfunctioning 4 months later, but ascites did not recur. Seven years later, while eating a normal diet and still having a nonfunctioning shunt, he remains free of ascites. We postulate that iatrogenic obstruction of the inferior vena cava in the presence of mesenteric and portal vein thromboses, as well as obstruction of mesenteric lymphatics by sarcoid lymphadenopathy, led to the formation of chylous ascites and that establishment of adequate mesenteric and portal venous and/or lymphatic collateral circulation was responsible for his sustained improvement.
A case is reported of a patient who died as a result of lithium toxicity. Brain lithium levels and changes in brain glycine levels are discussed.
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The effects of diazepam on memory and psychomotor performance in healthy elderly (N = 12) and young (N = 12) individuals were examined. Diazepam was administered acutely in a single, oral 2.5 mg dose. Diazepam impaired memory, both immediate and delayed recall, and psychomotor performance in the elderly subjects. In addition, the drug caused an increase in self-reported sedation in elderly subjects but not in young subjects. These findings suggest an age-related increase in the sensitivity of elderly individuals to the central depressant effects of diazepam.
Rats were administered one electroconvulsive shock daily for 7 days (ECS X 7) and were killed 24 hours after the last treatment. Muscarinic cholinergic receptor number, as determined by [3H] quinuclidinyl benzilate [( 3H]QNB) binding, was significantly reduced in the cerebral cortex. A parallel group of rats was trained on a passive avoidance task 24 hours following the last ECS and tested for retention of the original avoidance response 24 hours later; these animals exhibited a profound amnesia. Animals tested 1 hour following training were not amnestic, indicating that learning was unimpaired. Animals trained 7 days following ECS X 7 were not amnestic and [3H] QNB binding changes were not demonstrable at this time. A single ECS which does not significantly affect cortical [3H] QNB binding, did not induce amnesia in rats trained 24 hours after the treatment and tested 24 hours later. The parallel, cumulative nature of ECS-induced muscarinic receptor down-regulation and ECS-induced anterograde amnesia suggests a possible causative relationship.
Informed consent with the elderly patient and the competency of this patient population have been neglected issues in medicine and law. Particularly, the competency of the elderly patient has received little empirical investigation. The present study examines the capacity of geriatric patients to consent to research participation. Competency is investigated through the use of hypothetical consent information on three dimensions: comprehension of consent material, quality of reasoning about the decision to participate or not participate in research, and reasonable choice regarding participation. The results indicate that elderly patients' choices about those projects in which participation is "reasonable" do not differ, by and large, from younger patients. However, the elderly show significantly poorer comprehension of consent information. Thus, screening for competency and providing special instructions may become an important part of the research process when the elderly are participants.
The effect of serotonin (5-HT) deficiency on hypothalamic-pituitary-adrenal (HPA) activity was investigated by using 5,7-dihydroxytryptamine (5,7-DHT) for the selective destruction of central 5-HT neurons, and corticosterone response to suppression by dexamethasone as the index of HPA activity. Dexamethasone was shown to significantly suppress serum corticosterone levels in sham-treated rats, but did not suppress corticosterone in the 5,7-DHT-lesioned animals. This finding supports the conclusion that 5-HT is involved in the negative feedback mechanism of HPA regulation.
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During a ten-year period, 92 patients underwent an umbilical herniorrhaphy. Patients were divided into three groups: group 1, cirrhotic patients with ascites with functioning peritoneovenous shunts (n = 15); group 2, cirrhotic patients with ascites with nonfunctioning or no peritoneovenous shunts (n = 24); and group 3, noncirrhotic patients (n = 53). The charts were analyzed for postoperative mortality and morbidity and recurrence of the umbilical hernia. Umbilical hernia in cirrhotic patients with uncontrolled ascites was associated with significant mortality (8.3%) and morbidity (16.6%) and a significantly greater incidence of recurrence (16.6%). Umbilical herniorrhaphy in patients with functioning peritoneovenous shunts was associated with minimal morbidity (7%). These data suggest that cirrhotic patients with ascites who require an umbilical herniorrhaphy preferably should undergo peritoneovenous shunting before repair of the hernia.