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Biomedical subjects

B M Cohen

Publications and source records attributed to B M Cohen.

At least 109 records · Page 6Linked to original sources
PubMed1988

Neuroleptic drugs in the treatment of acute psychosis: how much do we really know?

The efficacy of neuroleptic antipsychotic drugs has been well demonstrated and neuroleptics are the standard treatment of acute psychosis. However, important aspects of neuroleptic treatment, including course of response, optimal doses, and mechanism of action, remain poorly studied or controversial. Placebo-controlled studies of the onset of the response of acute psychosis to neuroleptics are few and yield conflicting results. Studies of the relationship of doses and blood levels to the therapeutic effects of neuroleptics suggest that the optimal range of doses and levels is narrow and that commonly used doses are too high. Finally, studies of the mechanism of action of neuroleptics suggest that the dopamine hypothesis is based on unsupported assumptions concerning drug effects, drug distribution, and effective doses of drug. Alternative hypotheses, that the antipsychotic effects of the neuroleptics are mediated, at least in part, through alpha 1-adrenergic or serotonin 5-HT2 receptor antagonism, are reviewed. The evidence regarding these issues and controversies is discussed, and specific approaches to increase our understanding and enhance our use of the neuroleptics are suggested.

Acute Disease↗
PubMed1988

Receptor affinity, neurochemistry and behavioral characteristics of the enantiomers of thioridazine: evidence for different stereoselectivities at D1 and D2 receptors in rat brain.

The binding characteristics of the enantiomers of thioridazine were assessed in the brain of the rat using competitive radioreceptor assays with tritiated ligands selective for dopamine D1 (SCH-23390), D2 (spiperone), norepinephrine alpha-1 (prazosin) and muscarinic (quinuclinidinyl benzilate) receptors. (+)-Thioridazine was shown to have 2.7 and 4.5 times higher affinity than (-)-thioridazine for D2 and alpha-1 receptors, respectively. In contrast, (-)-thioridazine had 10 times higher affinity for the D1 receptor. Both enantiomers showed similar affinities for the muscarinic receptor. In a second experiment, thioridazine, dopamine, norepinephrine, serotonin and their metabolites were assayed in the brain of the rat after acute administration of the enantiomers of thioridazine and the assessment of catalepsy. (+)-Thioridazine was 4.1 times as potent as (-)-thioridazine in elevating the turnover of dopamine in the striatum, but neither enantiomer affected the other monoamines. The concentration of thioridazine and its metabolites in the brain, for a given dose, was similar for both enantiomers. (-)-Thioridazine induced slightly more catalepsy than (+)-thioridazine and appeared to be more toxic at large doses. While racemic thioridazine had an intermediate effect between that of its two enantiomers in the binding and neurochemical assays, it appeared to induce more catalepsy than either enantiomer, suggesting a synergistic effect in this behavioral assay. It was concluded that (+)- and (-)-thioridazine act as partially selective D2 and D1 antagonists, respectively. Therefore, clinical administration of only one enantiomer of thioridazine, rather than the currently prescribed racemate, may result in an improved therapeutic profile and so be worthy of further investigation.

Animals↗
PubMed1988

Severe daytime somnolence in patients treated with an MAOI.

Eight patients with hypersomnolent, anergic major depression benefited markedly from treatment with relatively high doses of phenelzine or tranylcypromine but experienced intense afternoon somnolence and disrupted sleep. Reducing the dose of monoamine oxidase inhibitor (MAOI) or substituting isocarboxazid sometimes provided relief, but altering the schedule of drugs or meals did not. Bedtime sedation alleviated the disrupted sleep but had little effect on daytime somnolence. The mechanism underlying this side effect is unknown; sleep deprivation, narcolepsy, or hypotension does not account for it. Patients given an MAOI should be assessed for this disturbance and cautioned to avoid risk of injury when it occurs.

Adult↗
PubMed1988

Comparison of MRI and CT scans in a group of psychiatric patients.

The authors compared the results of computerized tomography (CT) and magnetic resonance imaging (MRI) scans of 16 psychotic patients with various diagnoses whose neurologic examinations suggested structural brain abnormalities. Blind readings showed a high concordance of findings, including ventricle-to-brain ratios, although MRI appeared superior in visualizing midline structures and identifying atrophic changes. Because it requires no ionizing radiation, MRI allows multiple studies of the same patient, study of family members, and recruitment of unbiased samples of control subjects. Use of MRI may help address questions regarding the specificity and prevalence of brain abnormalities observed with CT in psychotic patients.

Adolescent↗
PubMed1988

Metabolism of thioridazine in the elderly.

Metabolism of drugs may change with age. Yet, there are few studies that provide data to help define appropriate doses of neuroleptic drugs in the treatment of the elderly. To address this issue, we determined serum concentrations of thioridazine and its active metabolites, mesoridazine and sulforidazine, by high performance liquid chromatography in young adult (mean age, 28 +/- 7.6 years) and elderly (mean age, 76 +/- 7.7 years) patients after single 25-mg oral doses of thioridazine. At both times measured, 4 and 8 hours after dosing, the concentrations of parent compound and metabolites in serum were 1.5- to twofold higher, and side effects (especially postural hypotension and dry mouth) were more frequent and severe in the elderly patients. These results, along with those reported in a small number of studies of serum drug levels during extended treatment of the elderly, support the practice of using smaller doses of phenothiazine neuroleptics in older patients.

Adult↗
PubMed1988

S-adenosyl-L-methionine in the treatment of Alzheimer's disease.

Patients with Alzheimer's disease (AD) have an apparent abnormality possibly representing an increase in the average fluidity of their cell membranes. Changes in membrane fluidity of similar magnitude to those observed in AD have been noted to lead to marked alterations in cell function. Therefore, the changes in fluidity observed in AD may be related to the symptoms of that disorder, representing either an underlying cause of dysfunction or cellular attempts to compensate for dysfunction in AD. To test these possibilities, we administered S-adenosyl-L-methionine (SAMe), an agent shown to increase membrane fluidity in animals, to patients with AD. Treatment with SAMe led to marked increases in membrane fluidity. However, it produced neither improvement nor worsening of symptoms. The results imply that while SAMe may be useful for other conditions associated with altered membrane fluidity (such as normal aging), changing membrane fluidity per se is not likely to lead to marked changes in symptoms in AD.

Aged↗
PubMed1988

Long-term response to carbamazepine: a retrospective study.

Carbamazepine is now used by many clinicians in the treatment of bipolar disorder (BD) refractory to standard treatments, including lithium and neuroleptics. Little information is yet available about the utility and efficacy of this novel treatment during long-term use. We carried out a retrospective study of 50 patients (34 with BD) who had received carbamazepine for the treatment of a psychotic disorder. Two-thirds (22) of the BD patients and two of the 16 patients with other diagnoses appeared to respond to carbamazepine acutely. However, follow-up 3 to 4 years later revealed that only eight patients (seven with BD) were still receiving the drug. In only two cases was the treating psychiatrist convinced that carbamazepine was clearly beneficial. Side effects, particularly hematological abnormalities, during both short- and long-term treatment were troublesome. Carbamazepine may only infrequently be useful in the long-term care of patients who fail to respond to standard treatment.

Adult↗
PubMed1987

Family study of platelet membrane fluidity in Alzheimer's disease.

The fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene in labeled platelet membranes, an index of membrane fluidity, identifies a prominent subgroup of patients with Alzheimer's disease who manifest distinct clinical features. In a family study, the prevalence of this platelet membrane abnormality was 3.2 to 11.5 times higher in asymptomatic, first-degree relatives of probands with Alzheimer's disease than in neurologically healthy control subjects chosen without regard to family history of dementia. The pattern of the platelet membrane abnormality within families was consistent with that of a fully penetrant autosomal dominant trait. Thus, this abnormality of platelet membranes may be an inherited factor that is related to the development of Alzheimer's disease.

Aged↗
PubMed1987

Abnormal platelet membrane composition in Alzheimer's-type dementia.

An abnormality of membranes, possibly representing an increase in internal membranes, has been reported in fluorescence spectroscopic and electron microscopic studies of platelets of patients with Alzheimer's-type dementia (AD). To further define this abnormality, the cholesterol and phospholipid content of platelet and erythrocyte membranes was determined and compared for patients with AD and matched control subjects. No significant differences in either cholesterol or phospholipid, per se, were observed in comparing platelets from subjects in the two study groups. However, the ratio of cholesterol to phospholipid was significantly lower (p less than 0.01) in the platelets of patients with AD (9.37 +/- 1.11) than in the platelets of control subjects (10.20 +/- 1.04). Furthermore, the cholesterol to phospholipid ratio correlated significantly (rs = 0.53, p less than 0.01) with a separately determined measure of platelet membrane characteristics, the steady-state anisotropy of DPH (diphenylhexatriene). No differences were observed between the study groups for any of the same parameters measured in erythrocytes, which lack internal membranes. The findings suggest that there is no general abnormality of membrane lipids in Alzheimer's-type dementia. Rather, because normal internal membranes are reported to be low in their cholesterol to phospholipid ratio and in anisotropy of DPH, the results of these studies, together with the results of studies employing electron microscopy, suggest that platelets of patients with AD have an increase in internal membranes. Such membranes, while present in excess, may be normal in composition.

Aged↗
PubMed1987

Adrenoceptors and the pharmacology of affective illness: a unifying theory.

Based on recent clinical and preclinical research, it is theorized that antimanic and antidepressant effects of clinically available drugs can be produced through their actions on alpha-1 adrenoreceptor-mediated neurotransmission in the central nervous system. The theory suggests that final effects on alpha-1 mediated neurotransmission may be produced not only by drugs which have direct effects on the alpha-1 receptor or its second messenger, but also by drugs having effects on neurotransmitter systems such as acetylcholine, GABA, and serotonin, among others, which modulate the activity of central norepinephrine neurons or, via feedback mechanisms, by drugs having effects on adrenergic receptors other than the alpha-1 receptor itself.

Adrenergic alpha-Agonists↗
PubMed1987

Platelet membrane abnormality in Alzheimer's disease.

Fluorescence studies of membrane fluidity were conducted double-blind using platelet and red cell membranes prepared from 24 demented patients with probable Alzheimer's disease and 36 neurologically healthy subjects. The fluidity of the hydrocarbon and lipid-aqueous interface regions of cell membranes was determined at 37 degrees C by fluorescence spectroscopy using the lipid probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH), respectively. The rotation rate of TMA-DPH in labeled platelet membranes did not differ between the groups. In contrast, the rotation rate of DPH in labeled platelet membranes from the demented patients (2.15 +/- 0.24 X 10(8)/sec, SD) was greater than that for the normal controls (1.93 +/- 0.13 X 10(8)/sec, SD, p = 3.8 X 10(-5)). This difference was reflected by a reduction in the steady-state anisotropy of DPH in labeled platelets from the demented group (0.1887 +/- 0.0085, SD) when compared to the respective mean for the controls (0.2000 +/- 0.0060, SD; p = 1.3 X 10(-7)). Abnormal membrane fluidity was significantly correlated with severity of dementia, but not with duration of illness or apparent age of onset. The findings do not support the hypothesis that Alzheimer's disease results from a pathological acceleration of the normal aging process, since normal aging is associated with decreased fluidity of cell membranes from platelets, as well as from lymphocytes, hepatocytes, and neurons.

Aged↗
PubMed1987

Microsurgical reconstruction of congenital tubal anomalies.

Significant numbers of infertile women have congenital anomalies or anatomical distortion of the fimbrial-gonadal mechanism in their otherwise healthy oviducts. The diagnosis and surgical treatment of multiple congenital accessory tubal ostia, the elongated fimbria-ovarica syndrome, and management of paratubal cysts is described. Microsurgical correction of these defects was followed by term pregnancies in 46%, 57% and 28% of the three entities respectively and this data indicates that significant numbers of women with these defects may be helped by microsurgery. Failure to recognize these abnormalities may otherwise result in patients being diagnosed as idiopathic infertility, a decision which may exclude them from the possibility of undergoing a successful form of microsurgical treatment.

Cysts↗
PubMed1987

Temperature dependence of the molecular dynamics of platelet membranes in Alzheimer's disease.

The biophysical properties of platelet membranes from five patients with Alzheimer-type dementia and five neurologically healthy controls, matched for age and sex, were examined by fluorescence spectroscopy employing the fluorescent probes DPH and TMADPH. The anisotropy of DPH has previously been observed to be reduced in platelet membranes of patients with Alzheimer-type dementia. However, Alzheimer's disease was not associated with a significant change in the flow activation energy at either deep or superficial regions of platelet membranes. In addition, the temperature-dependent phase transition observed with TMADPH occurred at the same mean temperature in platelet membranes from the demented and control groups.

Aged↗