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Biomedical subjects

R M Post

Publications and source records attributed to R M Post.

At least 217 records · Page 12Linked to original sources
PubMed1989

Chronic carbamazepine inhibits the development of local anesthetic seizures kindled by cocaine and lidocaine.

The effects of carbamazepine (CBZ) treatment on local anesthetic-kindled seizures and lethality were evaluated in different stages of the kindling process and under different methods of CBZ administration. Chronic oral CBZ inhibited the development of both lidocaine- and cocaine-induced seizures, but had little effect on the fully developed local anesthetic seizures. Chronic CBZ also decreased the incidence of seizure-related mortality in the cocaine-injected rats. Acute CBZ over a range of doses (15-50 mg/kg) had no effect on completed lidocaine-kindled or acute cocaine-induced seizures. Repeated i.p. injection of CBZ (15 mg/kg) also was without effect on the development of lidocaine- or cocaine-kindled seizures. The differential effects of CBZ depending upon stage of seizure development suggest that distinct mechanisms underlie the development versus maintenance of local anesthetic-kindled seizures. The effectiveness of chronic but not repeated, intermittent injections of CBZ suggests that different biochemical consequences result from the different treatment regimens. The possible utility of chronic CBZ in preventing the development of toxic side effects in human cocaine users is suggested by these data, but remains to be directly evaluated.

Anesthetics↗
PubMed1989

Evidence for a common site of action of lidocaine and carbamazepine in voltage-dependent sodium channels.

The finding that the development of lidocaine-kindled seizures is blocked by carbamazepine suggests an interaction of carbamazepine with local anesthetic mechanisms. To study the site of interaction, the effects of lidocaine, carbamazepine and another anticonvulsant drug, phenytoin on scorpion venom-enhanced specific binding of [3H]batrachotoxinin A 20-alpha-benzoate to the sodium channel gating complex were examined in vitro in a rat brain hippocampus preparation. Lidocaine shifted the concentration inhibition curve of carbamazepine to the right and vice versa. Carbamazepine shifted the concentration inhibition curve of phenytoin to the right and vice versa. The experimentally determined apparent dissociation constants were in a good agreement with the dissociation constants calculated for a one-site model, suggesting that the interaction occurs because lidocaine shares a common binding site with carbamazepine and phenytoin in the voltage-dependent sodium channels.

Animals↗
PubMed1989

Benzodiazepine withdrawal delirium with catatonic features. Occurrence in patients with partial seizure disorders.

We report the cases of 3 patients with medically intractable seizures in whom withdrawal of treatment with a long-acting benzodiazepine (clorazepate dipotassium, 2 patients; clonazepam, 1 patient) was followed by delirium with catatoniclike features. While an increase in seizure frequency occurred during withdrawal and prior to the onset of behavioral changes, electroencephalograms did not show epileptiform activity during the delirium. We compared these 3 patients with 10 others with intractable seizures in whom antiepileptic therapy was withdrawn without subsequent behavior changes. High-dose benzodiazepine therapy and a history of viral encephalitis may be risk factors for withdrawal delirium.

Adult↗
PubMed1989

Dysphoric mania. Clinical and biological correlates.

Patients studied at peak severity of a manic episode showed substantial degrees of depression (dysphoria) and anxiety. Compared with nondysphoric manics (n = 26), the dysphoric manics (n = 22) had a significantly greater number of previous hospitalizations, and they displayed less rapid cycling both in the year before and during the index hospitalization admission. The severity of manic dysphoria tended to correlate with the number of previous hospitalizations, a finding that was highly significant in women (n = 27). Medication-free manic patients (n = 22) had significant elevations in cerebrospinal fluid norepinephrine concentrations compared with depressed and euthymic patients and normal volunteers, and the degree of elevation correlated significantly with the degree of manic dysphoria, anger, and anxiety rated at the time of the lumbar puncture. Patients with dysphoric mania, recognized by Kraepelin to have poor prognoses, have been reported to respond poorly to lithium carbonate but may be among those who respond to carbamazepine. Clinical, biologic, and pharmacologic response characteristics of manic subgroups, particularly those with extreme dysphoric components to their illness, appear to be clinically meaningful and deserving of further investigation.

Affect↗
PubMed1989

The addition of lithium to carbamazepine. Antidepressant efficacy in treatment-resistant depression.

The addition of lithium carbonate to various antidepressant agents, including heterocyclics and monoamine oxidase inhibitors, has been reported to rapidly effect an antidepressant response in otherwise treatment-unresponsive depressed patients. Fifteen depressed patients diagnosed by DSM-III criteria who had not responded to double-blind treatment with carbamazepine were treated with the blind addition of lithium to carbamazepine. Eight patients (53%) responded with a moderate to marked improvement. The time to onset of substantial clinical improvement was rapid; ie, the mean (+/- SD) was 4.1 +/- 2.4 days for lithium potentiation compared with 9.7 +/- 4.1 days in a separate group of depressed patients responding to lithium alone. Side effects during carbamazepine-lithium combination therapy were minimal. The mechanisms by which lithium appears to rapidly potentiate the effects of carbamazepine in treatment-resistant depression are discussed.

Adult↗
PubMed1989

Corpus callosum dimensions measured by magnetic resonance imaging in bipolar affective disorder and schizophrenia.

Magnetic resonance imaging (MRI) brain scans were performed on 24 schizophrenic patients, 22 bipolar affective patients, and 25 normal control subjects without medical or psychiatric illness using a Picker Vista 0.5 tesla scanner. Specific callosal regions and the cerebral area on the midsagittal slice were measured utilizing the technique described by Nasrallah et al. (1986). No significant differences were found among diagnostic groups in anterior, mid, or posterior callosal width, callosal area, cerebral area, callosal to cerebral area ratio, or the genu (first quartile) to splenium (fourth quartile) ratio. However, male subjects had a significantly greater callosal and cerebral area than female subjects. Gender differences were shown in the genu to splenium ratio in the control groups, but not the affective or schizophrenic groups. The implications of these gender differences are discussed in relation to other studies.

Adult↗
PubMed1989

Evidence for common alterations in cerebral glucose metabolism in major affective disorders and schizophrenia.

Regional glucose metabolic rates were measured in affectively disordered patients during the performance of auditory discrimination. Those regions previously observed as abnormal in schizophrenia were examined to see if similar alterations might be associated with affective disorder. The abnormalities observed in the mid-prefrontal cortex, an area that appears to be an important biologic determinant of the sustained attention required of subjects in this task, are similar to those previously observed in schizophrenia. Moreover, the abnormalities do not appear to relate directly to symptomatology or the subject's performance. The authors discuss the possibility that this abnormality may reflect dysfunction in the integrating component of the attention network critical for the maintenance of goal-directed behavior and thus represent a psychosis vulnerability factor in some patients.

Acoustic Stimulation↗
PubMed1989

Mouse brain c-fos mRNA distribution following a single electroconvulsive shock.

The regional distribution of c-fos mRNA in the mouse brain has been investigated by in situ hybridization autoradiography after seizures induced by an acute electroconvulsive shock (ECS). ECS led to a widespread induction of the proto-oncogene c-fos in the brain, with highest concentrations in discrete areas within the limbic system and also in the hypothalamus and cerebellum. The mild stress of sham treatment in earclipped animals induced a weaker and qualitatively different pattern of c-fos mRNA expression involving the cortex, hippocampus, and cerebellum. These data suggest the usefulness of c-fos in situ hybridization as a marker of neuronal stimulation and in mapping a range of effects from a mild stress to the robust changes of an electroconvulsive seizure.

Animals↗
PubMed1989

Pyruvate dehydrogenase interactions with peripheral-type benzodiazepine receptors.

Although peripheral-type benzodiazepine recognition sites have been demonstrated in the brain of various species, the precise identity and function of the peripheral benzodiazepine receptor have not been established yet. In light of the recent demonstration of the mitochondrial localization of this receptor and its potential role in intermediary metabolism, we investigated the relationship between the benzodiazepines and the enzyme pyruvate dehydrogenase (PDH), a component of the mitochondrial membrane. The results obtained in the present study demonstrate a specific interaction between PDH and the ligands for the peripheral-type type benzodiazepine receptor, which might account for their effects on cell growth and differentiation.

Animals↗
PubMed1989

Adding lithium carbonate to carbamazepine: antimanic efficacy in treatment-resistant mania.

Although lithium and carbamazepine used alone are effective in treating acute mania, some patients do not respond adequately to either of these medications used alone. We assessed, under double-blind conditions, a potential synergism between carbamazepine and lithium in the acute treatment of mania. Six of 7 manic patients who had previously been largely refractory to lithium alone, and who still showed substantial mania after several weeks of double-blind treatment with carbamazepine, improved following the blind addition of lithium. The clinical and theoretical implications of the response to this combination treatment are discussed.

Adult↗
PubMed1989

Temporal lobe measurement in primary affective disorder by magnetic resonance imaging.

Magnetic resonance imaging brain scans were performed on 17 patients with primary affective disorder and 21 normal subjects. A coronal slice through the temporal lobes at the level of the pons and interpeduncular cistern was selected in each subject, and specific temporal lobe structures and the cerebral area were measured. Ratios between structures of the same hemisphere were calculated. The ratio of the temporal lobe to cerebral area was smaller in patients than controls both on the left (p less than .02) and on the right (p less than .03). The data suggest that patients with primary affective disorder may have a relative decrease in the size of the temporal lobe compared with normal controls.

Adult↗
PubMed1989

Emerging perspectives on valproate in affective disorders.

The anticonvulsants, especially carbamazepine and valproate, offer new clinical and theoretical perspectives in the treatment of lithium-refractory bipolar disorders. They appear effective in a group of patients who often respond poorly to lithium, that is, those with rapid cycling illness. Given that these drugs have different profiles of clinical antiepileptic activity and different biochemical mechanisms of action, it is not unexpected that preliminary evidence indicates that some affectively ill patients may selectively respond to one, but not the other, agent. It remains to be determined whether common mechanisms underlie the anticonvulsant and psychotropic effects and whether "limbic" actions are important to their properties in affective illness. The potential role of valproate in acute and long-term treatment of bipolar illness deserves further controlled evaluation given the preliminary data summarized in the series of papers in this volume.

Adult↗
PubMed1989

Context-dependent cocaine sensitization: differential effect of haloperidol on development versus expression.

Repeated, intermittent administration of psychomotor stimulants has been shown to produce increasing effects (behavioral sensitization) in many species of animals. In a novel two-day sensitization paradigm, rats that received a single high dose of cocaine (40 mg/kg) compared with saline on day 1 showed an increased locomotor response to a challenge dose (10 mg/kg) on day 2. This effect is conditioned or context-dependent; i.e., it is only observed if the rats received cocaine in an environment similar to the test environment. If the cocaine-induced hyperactivity on day 1 is prevented with pharmacological agents such as haloperidol and diazepam, sensitization on day 2 does not occur. Furthermore, although moderate (0.2 mg/kg) and high doses (0.5 mg/kg) of haloperidol (day 1) prevented the development of sensitization to cocaine, they were ineffective when given prior to the day 2 challenge dose in preventing the expression of sensitization. Thus, this type of cocaine sensitization appears to involve conditioning, show stimulus generalization, and offer a possible model for clinical neuroleptic nonresponsiveness once stimulant-induced pathological behavior has been induced.

Animals↗
PubMed1989

Sensitization, kindling, and anticonvulsants in mania.

Cocaine can induce manic syndromes ranging from mild hypomania to severe dysphoric and psychotic mania, in part depending on the number and duration of drug administrations. Repeated cocaine administration in animals results in increased motor (behavioral sensitization) and convulsive (pharmacologic kindling) responses. Study of these progressive syndromes in animals may provide insights into principles underlying the longitudinal evolution of manic syndromes in man, including the increased vulnerability to recurrence following successive episodes. Different phases in the evolution of behavioral sensitization are differentially responsive to neuroleptics while the same principle is evident for different anticonvulsants in kindling. The authors examine whether pharmaco-responsivity may also differ as a function of stage of progression of mania. Antimanic effects of lithium, neuroleptics, and the newer anticonvulsants, such as carbamazepine, valproic acid, and clonazepam, are discussed in this context.

Animals↗
PubMed1988

Normal urinary free cortisol and plasma MHPG in panic disorder: clinical and theoretical implications.

Abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis and noradrenergic function have been reported in patients with panic disorder. Mean urinary free cortisol and plasma MHPG were measured in 12 medication-free panic disorder patients and 12 normal controls. No significant difference in urinary free cortisol and plasma MHPG was observed between the patients and controls. There was no relationship between plasma MHPG and urinary free cortisol in the panic patients or normal controls. These findings are described within the context of current concepts of stress and noradrenergic dysfunction in panic disorder.

Adult↗
PubMed1988

Salivary cortisol: a practical method for evaluation of adrenal function.

Salivary cortisol represents a simple, noninvasive, stress-free measure that can greatly facilitate the longitudinal study of hypothalamic-pituitary-adrenal axis activity in patients with psychiatric disorders. By means of a slight modification of a commercially available radioimmunoassay kit, we studied the stability of salivary cortisol under different conditions, as well as the relationship between plasma and salivary cortisol under basal circadian conditions and following stimulation (CRH) and suppression (dexamethasone). We observed that salivary cortisol was quite stable at room temperature without centrifugation and that salivary and plasma cortisol values were highly correlated. Additionally, we observed a close correspondence in circadian and ultradian fluctuations in salivary and plasma cortisol. The salivary cortisol response to ovine and human CRH was similar to that observed with plasma cortisol, but was greater in magnitude. Finally, employing a plasma criterion as the standard, salivary measures identified 48% of the nonsuppressed Dexamethasone Suppression Tests (DSTs) and 97% of the suppressed DSTs.

Adult↗