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Biomedical subjects

B M Cohen

Publications and source records attributed to B M Cohen.

At least 73 records · Page 4Linked to original sources
PubMed1994

Greater hemodynamic response to photic stimulation in schizophrenic patients: an echo planar MRI study.

Functional echo planar magnetic resonance imaging (MRI) probably will be of importance in assessing brain abnormalities in psychiatric disorders. The authors used functional MRI to measure the relative magnitude of the change in image signal intensity, reflecting changes in regional neuronal activity caused by photic stimulation, in eight patients with schizophrenia and nine normal comparison subjects. The mean signal intensity change in the primary visual cortex was significantly greater in patients with schizophrenia (mean = 4.6%, SD = 1.5%) than in normal comparison subjects (mean = 3.1%, SD = 1.3%). These results may reflect a variety of factors, including diffuse structural brain changes as well as primary or iatrogenic impairment of mitochondrial function or energy metabolism.

Adult↗
PubMed1994

Antidepressant-associated mania: a controlled comparison with spontaneous mania.

OBJECTIVE: Antidepressants have been associated with the induction of mania and rapid cycling. This study examined whether antidepressant-associated manic states differ in any way from spontaneous mania. METHOD: Forty-nine consecutive inpatients with antidepressant-associated manic states were compared with 49 matched inpatients with spontaneous mania in a blind, retrospective chart review. RESULTS: Across virtually every clinical measure examined, the patients with antidepressant-associated manic states experienced milder and more time-limited manic episodes than the patients with spontaneous mania. The patients with antidepressant-associated manic states were subject to frequent checking by nurses and hall restriction for a significantly shorter period of time than the patients with spontaneous mania. The patients with antidepressant-associated manic states also had significantly less severe levels of delusions, hallucinations, psychomotor agitation, and bizarre behavior, according to a standard rating instrument, than the patients with spontaneous mania. For further study the patients with antidepressant-associated mania were divided into subgroups taking four individual classes of antidepressant drugs: tricyclics (N = 19), fluoxetine (N = 13), monoamine oxidase inhibitors (MAOIs) (N = 8), and bupropion (N = 6); three patients taking combinations of drugs were not included in these analyses. The patients with MAOI- and bupropion-associated mania had a slightly lower overall rating of severity of psychopathology at admission than the subgroups with fluoxetine- and tricyclic-associated mania. CONCLUSIONS: Antidepressant-associated mania appears to be a milder and more time-limited syndrome than spontaneous mania and may represent a distinct clinical entity. MAOIs and bupropion may be associated with milder manic states than either tricyclic drugs or fluoxetine.

Adult↗
PubMed1994

Neurologic factors predict a favorable valproate response in bipolar and schizoaffective disorders.

The hypothesis that neurologic factors influence the response to valproate (divalproex sodium) in bipolar and schizoaffective disorders was tested. In 115 predominantly lithium-refractory inpatients, neurologic findings were recorded, and blind raters assessed valproate response from the medical record. Patients with a seizure history were much more likely to have a robust response to valproate (70%), when compared with patients without such history (34.6%). History of head injury and abnormal electroencephalographic findings also tended to be more common in those patients with good response. Overall, the group of patients with any neurologic abnormality exhibited a significantly higher rate of good response to valproate (43.6%) than did the neurologically normal group (24.3%). Bipolar or schizoaffective patients with abnormal neurologic features may represent a distinct subtype of illness and appear to be good candidates for valproate therapy.

Bipolar Disorder↗
PubMed1994

Percutaneous coronary rotational atherectomy: New Jersey experience.

Complex coronary lesions can be approached percutaneously with rotational atherectomy. The first 70 procedures were performed at Newark Beth Israel Medical Center with a success rate of 94 percent. Despite treating a high-risk patient population, the complication rate was low.

Atherectomy, Coronary↗
PubMed1993

Tissue concentrations of clozapine and its metabolites in the rat.

Clozapine (CLZ) and its metabolites norclozapine (NOR) and clozapine-N-oxide (NOX) were assayed in rat serum and brain tissue after intraperitoneal injection of CLZ. Clozapine levels rose with dose, averaging 28 ng/ml (87 nmol/L) serum per milligram/kilogram dose. Brain- and serum-CLZ levels correlated closely, averaging 24-fold higher in brain. Norclozapine and NOX averaged approximately 58% and 13% of CLZ in serum, respectively, whereas in brain, NOR was detected only at doses greater than or equal to 10 mg/kg (approximately 5.6% of CLZ) and NOX was undetectable. Levels peaked within 30 minutes, and elimination of CLZ from brain and CLZ or NOR from blood was very rapid (half-life = 1.5 to 1.6 hours). A week of daily dosing with CLZ led to no accumulation of drug in brain; a week of fluoxetine pretreatment increased analyte concentrations (serum, 86%; brain, 61%), but valproate had little effect.

Animals↗
PubMed1993

Everything activates c-fos--how can it matter?

It is probably safe to say that the regulation of c-fos expression by drug treatment and other stimulus paradigms has biological specificity and mechanistic significance. However, as this brief essay makes clear, the immunohistochemical detection of c-fos is only the tip of the biological iceberg. IEGs deserve to be studied as critical components of the intracellular signaling machinery that may transduce intercellular signals, including those produced by drugs of abuse, into longer term changes in cellular function. However, the study of IEG expression must be related to biologically significant target genes and must be complemented by the study of phosphorylation of constitutively expressed transcription factors. Moreover, as illustrated by the proenkephalin gene, the regulation of genes that play important roles in differentiated cell function may differ depending on which cell types and stimulus conditions are investigated. Finally, attention must be paid to the complexities of gene regulation under conditions of repetitive and chronic stimulation if phenomena such as the neural substrates of drug dependence are to be understood.

Animals↗
PubMed1992

The human brain resonance of choline-containing compounds is similar in patients receiving lithium treatment and controls: an in vivo proton magnetic resonance spectroscopy study.

Lithium specifically and potentially inhibits membrane transport of choline. However, the effect of lithium on human neuronal choline content is unknown. This study was performed to determine if lithium alters the human brain choline concentration in vivo. In vivo proton magnetic resonance spectroscopy was used to compare the relative brain concentration of choline-containing compounds in seven lithium-treated patients and six lithium-free controls. No significant difference was observed in the mean relative choline resonance between the patient and control groups. Lithium treatment did not appear to alter the overall brain content of choline-containing compounds. It remains possible that a component of these compounds, particularly free choline, is elevated during lithium treatment.

Adult↗
PubMed1992

Drug distribution between blood and brain as a determinant of antipsychotic drug effects.

Concentrations of the neuroleptics haloperidol, bromperidol, fluphenazine, chlorpromazine and its metabolites nor-1- and nor-2-chlorpromazine, thioridazine and its metabolites mesoridazine, sulforidazine, and northioridazine, and promazine were estimated in serum and brain of rats by high performance liquid chromatography (HPLC) with electrochemical detection following 5 days of chronic administration of drug at typical doses (haloperidol, bromperidol, and fluphenazine 1 mg/kg/day; chlorpromazine, promazine, and thioridazine 25 mg/kg/day). The observed ratio of brain-to-serum concentration of drug varied widely (0.18-62.5) among neuroleptics studied. High potency agents had more favorable brain-to-blood distribution than low potency agents, and a strong correlation (r = 0.734, p < 0.05) was observed between the brain-to-serum ratios of the neuroleptics and standard clinical doses of drug. This finding suggests that drug distribution is a significant determinant of clinical potency. For most neuroleptics, including drugs with high (fluphenazine, haloperidol) and low potency (thioridazine) such as dopamine D2 antagonists, concentration of drug in the brain was similar. If the results are applicable to patients, they suggest that the degree of dopamine D2 blockade achieved during treatment may vary by drug. Chlorpromazine and promazine were notable for producing high concentrations of drug in the brain at typical doses, suggesting that optimal doses might be lower than those in common use. These results may be important in designing and interpreting studies of the effects of neuroleptic drugs in animals and patients.

Animals↗
PubMed1992

Differential expression of c-fos and zif268 in rat striatum after haloperidol, clozapine, and amphetamine.

Antipsychotic drugs are monoamine receptor antagonists. However, the mechanisms by which these direct actions are translated into therapeutic effects are unknown. Candidate mechanisms include receptor-mediated regulation of gene expression in target neurons. Inducible transcription factors, including certain immediate early genes (IEGs), may mediate between receptor-activated second messenger systems and expression of genes involved in the differentiated functions of neurons. We examined the specificity of induction of the IEGs c-fos and zif268 after acute administration of several antipsychotic drugs and, for comparison, the stimulant amphetamine, which has pharmacologic effects relatively opposite to those of antipsychotics. Antipsychotic drugs with potent dopamine D2 receptor antagonist properties, such as haloperidol, induced both c-fos and zif268 mRNA in the caudate-putamen; however, the atypical antipsychotic drug clozapine induced zif268 but not c-fos mRNA in that region. Similarly, haloperidol, but not clozapine, induced c-Fos-like immunoreactivity in the caudate-putamen. In contrast, both drugs induced c-Fos-like immunoreactivity in the nucleus accumbens. Like haloperidol, amphetamine induced both c-fos and zif268 mRNA in the caudate-putamen, but the anatomic patterns of induction of c-Fos-like immunoreactivity by the two drugs were dramatically different. Haloperidol and amphetamine induced AP-1 binding activity in cell extracts from the caudate-putamen, indicating that drug-induced IEG expression results in protein products that may function in the regulation of target gene expression. Thus these data demonstrate that inductions of IEG expression by haloperidol, clozapine, and amphetamine are specific, may be biologically relevant, and suggest avenues for further investigation.

Amino Acid Isomerases↗
PubMed1992

Differences between antipsychotic drugs in persistence of brain levels and behavioral effects.

After a single dose of the butyrophenone neuroleptic haloperidol, behavioral effects and detectable drug levels in rat brain can last for several weeks. To determine if such persistence is a general property of neuroleptics, we compared drug levels and effects after IP administration of two butyrophenones (haloperidol and bromperidol), a high potency (fluphenazine) and a low potency (chlorpromazine) phenothiazine. Drug levels in brain tissue were measured by high pressure liquid chromatography and behavioral effects monitored as inhibition of apomorphine-induced stereotypy. Estimated near terminal elimination half-lives (t 1/2) from brain for acutely administered chlorpromazine (20 mg/kg) and fluphenazine (1 mg/kg) were 0.41 and 0.62 days, respectively, and neither drug was detectable after 4 days. Fluphenazine given daily for 5 days showed an only slightly slower elimination (t 1/2 = 1.1 days). In contrast, near-terminal elimination half-lives from brain for haloperidol and bromperidol (both at 1 mg/kg, IP) were much longer (6.6 and 5.8 days, respectively), and each was detectable for 21 days after dosing. Inhibition of apomorphine-induced stereotypy correlated highly (r = 0.95) with brain levels of haloperidol. For fluphenazine, given once or repeatedly, early inhibition was replaced within 1 week by supersensitivity to apomorphine which persisted for up to 3 weeks. These findings, indicating marked differences in clearance and recovery times after dosing with butyrophenones and phenothiazines, have clear implications for studies of the effects of neuroleptic drugs in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Do central antiadrenergic actions contribute to the atypical properties of clozapine?

Full neuropharmacological understanding of the atypical antipsychotic agent clozapine remains elusive. Antidopaminergic actions of most neuroleptics probably contribute to their antipsychotic benefits, but also to neurological side-effects. Clinical evidence of abnormalities of dopamine (DA) and serotonin (5-HT) in psychotic disorders is inconsistent, but there is substantial metabolic and post-mortem evidence for hyperactivity of noradrenaline (NA). Clozapine is only weakly antidopaminergic but is a potent antagonist at brain alpha 1-adrenergic, 5-HT2-serotonergic, and muscarinic receptors. Its apparent limbic-over-extrapyramidal neurophysiological selectivity can be mimicked by combining a typical neuroleptic with a central alpha 1 antagonist. Clozapine strongly upregulates alpha 1, but not DA, receptor abundance, and may supersensitise alpha 1 but not DA receptors in rat brain. Clozapine also selectively increases activity of NA neurons and metabolic turnover in NA more than DA areas of rat brain, and also increases NA, but not DA or 5-HT, metabolites in human CSF. Potential psychotropic effects of selective central antiadrenergic agents may deserve reconsideration.

Clozapine↗
PubMed1992

Sonographic assessment of late proliferative phase endometrium during ovulation induction.

Late proliferative phase endometrium was assessed sonographically in 400 patients undergoing ovulation monitoring or stimulation. Endometrial evaluation was classified in relation to its widest diameter (quantity) and by the presence or absence of a double-layered (outer echogenic/inner hypoechoic) pattern (quality). No patient conceived if the endometrium was totally echogenic and less than 8 mm in diameter. All patients who conceived had an endometrium that was double-layered or greater than 9 mm in diameter. Positive, double-layered patterns correlated with correction of hormonal aberrations such as hypoestrogenism, hyperprolactinemia or hyperandrogenism. Such a positive pattern was also accomplished after discontinuation of clomiphene citrate in certain low-body weight/low-body fat women and administration of human menopausal gonadotropins to those patients. Application of the principles described to ensure the development of an adequate, double-layered (follicular phase) endometrium at midcycle were found to coincide with a higher incidence of pregnancy and viable gestation.

Chorionic Gonadotropin↗
PubMed1991

Dopamine blocking activity of clomipramine in patients with obsessive-compulsive disorder.

While many data suggest that Obsessive-Compulsive Disorder (OCD) is an illness accompanied by dysregulation of the serotonergic system, interesting clinical evidence and animal studies also suggest possible dysregulation of the dopaminergic (DA) system. In order to determine whether clomipramine (CMI), an antiobsessional agent, is capable of altering DA function, we performed a neuroleptic radioreceptor assay (NRRA) on plasma samples from OCD patients before and after treatment in a double-blind, placebo controlled trial of CMI. CMI produced mild but significant DA D-2 receptor binding activity in an in vitro assay. The degree of dopamine binding activity did not correlate with clinical response to clomipramine. Because it has been suggested that another drug with antiobsessional efficacy, fluoxetine, may also have dopamine blocking properties, it may be speculated that antidopaminergic activity in combination with serotonergic effects is involved in antiobsessional activity of effective agents for some patients.

Adolescent↗