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B M Cohen

Publications and source records attributed to B M Cohen.

At least 55 records · Page 3Linked to original sources
PubMed1996

Abnormal cerebral metabolism in polydrug abusers during early withdrawal: a 31P MR spectroscopy study.

Phosphorus magnetic resonance spectroscopy (31P MRS) at 1.5 T was performed on nine polysubstance abusing men. All nine patients met DSM-III-R criteria for concurrent cocaine and heroin dependence, were neurologically normal, were negative for the human immunodeficiency virus, and had normal clinical brain MRI scans. Patients were scanned 2-7 days after admission to a drug treatment unit. Eleven age-matched control subjects also were studied. The ISIS localized phosphorus spectra were obtained from a 5-cm thick axial brain slice and a 100-cc white matter volume. In the brain slice, the phosphorus metabolite signal expressed as a percentage of total phosphorus signal was 15% higher for phosphomonoesters, 10% lower for nucleotide triphosphates (beta-NTP), and 7% lower for total nucleotide phosphates in polydrug abusers compared with those in controls. Phosphodiesters, inorganic phosphate, phosphocreatine, total phosphorus, pH, and free magnesium concentration were unchanged. None of these parameters correlated with the methadone dose or the number of days abstinence. Single photon emission computed tomographic imaging of a subgroup of the patients revealed abnormal cerebral perfusion in 80% of the patients scanned. These data suggest that cerebral high energy phosphate and phospholipid metabolite changes result from long term drug abuse and/or withdrawal and that these changes can be detected and studied by 31P MRS.

Adult↗
PubMed1996

A technique for detecting GABA in the human brain with PRESS localization and optimized refocusing spectral editing radiofrequency pulses.

A proton magnetic resonance spectral editing technique is presented that uses PRESS excitation to achieve spatially localized measurements of brain gamma-aminobutyric acid (GABA). The homonuclear difference spectroscopy technique employs a frequency selective inversion pulse to suppress the creatine resonance at 3.0 ppm. The timing of this pulse is optimized to maximize the suppression of creatine by minimizing the effect of the editing pulse on the 3.0 ppm resonances. The PRESS excitation achieves three dimensional spatial localization in a single acquisition making it less sensitive to patient motion than multiple acquisition techniques. The performance and utility of this technique were evaluated by phantom experiments and by in vivo measurements of brain GABA concentration in 10 normal subjects.

Brain↗
PubMed1996

Differential effect of CDP-choline on brain cytosolic choline levels in younger and older subjects as measured by proton magnetic resonance spectroscopy.

Phosphatidylcholine (PtdCho), which is essential for membrane integrity and repair, is reduced in brain cell membranes with age. Evidence from both animal and in vitro studies indicates that cytidine 5' diphosphate choline (CDP-choline) can increase the synthesis of PtdCho; however, the effect of CDP-choline on brain choline metabolism has not previously been studied in human subjects. In this study, in vivo proton magnetic resonance spectroscopy (1H-MRS) was used to measure brain levels of cytosolic, choline-containing compounds before and after single oral doses of CDP-choline. Three hours after dosing, plasma choline increased similarly in younger (mean age 25 years) and older subjects (mean age 59 years). However, while the choline resonance in brain increased by 18% on average in younger subjects, it decreased by almost 6% in older subjects (P = 0.028). These results may be explained by a previously observed decrease in brain choline uptake, but not cytidine uptake, in older subjects. Additional intracellular cytidine following the administration of CDP-choline should lead to the increased incorporation of choline already present in brain into membrane PtdCho, which is not MRS-visible, consequently lowering the brain choline resonance below that of pre-treatment values. These results suggest that the cytidine moiety of CDP-choline stimulates phosphatidylcholine synthesis in human brain cell membranes in older subjects.

Adult↗
PubMed1996

Proton magnetic resonance spectroscopy of the temporal lobes in schizophrenics and normal controls.

Previous research has found structural and functional abnormalities in the temporal lobes of schizophrenic patients, often with greater impairment on the left side. This study applied proton MRS to both right and left temporal lobes of schizophrenic patients and normal control subjects. Reductions in the NAA/Cr ratio were found bilaterally for schizophrenic patients as compared to normal controls, and may be associated with reduced neuronal integrity. These results strengthen the evidence for biochemical abnormalities in the temporal lobes in schizophrenia.

Adult↗
PubMed1996

Treatment of negative symptoms in schizophrenia and schizoaffective disorder by selegiline augmentation of antipsychotic medication. A pilot study examining the role of dopamine.

It has been suggested that schizophrenic negative symptoms may be manifestations of regionally deficient CNS dopaminergic activity. We sought to test this hypothesis by openly treating patients on chronic antipsychotic medication who showed prominent negative symptoms with low-dose selegiline (5 mg b.i.d.), a monoamine oxidase-B inhibitor that selectively enhances dopaminergic activity. Twenty-one patients meeting DSM-III-R criteria for chronic schizophrenia (N = 14) or schizoaffective disorder (N = 7) with prominent negative symptoms were studied. Subjects had been kept at their current antipsychotic and antiparkinsonian medication dose levels for at least a month before the study, which was continued unchanged throughout the trial. Over 6 weeks of selegiline treatment, a 34.7% reduction in negative symptoms was demonstrated on the Scale for the Assessment of Negative Symptoms. There were also reductions in depressive symptoms (21-item Hamilton Depression Scale dropped 36.8%) and extrapyramidal symptoms (Simpson-Angus Extrapyramidal Symptom Scale scores dropped 27.7%), but no change was observed in the severity of positive symptoms as measured by the Brief Psychiatric Rating Scale. Global clinical improvement was demonstrated, with mean Clinical Global Impressions Scale score rising 17.6%. These findings support the hypothesis that negative symptoms, as well as extrapyramidal symptoms and certain depressive symptoms, may be manifestations of regionally deficient dopaminergic activity.

Adult↗
PubMed1996

The thalamus as a site of action of antipsychotic drugs.

OBJECTIVE: Because recent data suggest that there are abnormalities of the thalamus in schizophrenia, the authors tested the effects of antipsychotic drugs on thalamic sites. METHOD: Nine rats were given acute doses of the typical neuroleptic haloperidol (N = 3), the atypical neuroleptic clozapine (N = 3), or a drug-free vehicle (N = 3). Cellular activation was assessed by using immunohistochemistry to determine expression of the immediate response gene c-fos. RESULTS: Both antipsychotic drugs induced increased Fos immunoreactivity, suggesting increased activity in cells of the midline nuclei of the thalamus. CONCLUSIONS: The shared clinical effects of antipsychotic drugs may be mediated in part through actions on the thalamus.

Animals↗
PubMed1996

Functional magnetic resonance imaging of schizophrenic patients and comparison subjects during word production.

OBJECTIVE: This study was undertaken to test the feasibility of using functional magnetic resonance imaging (MRI) to examine changes in cortical activation in response to verbal tasks in two brain regions. METHOD: Twelve schizophrenic patients and 11 comparison subjects underwent functional MRI of the frontal and temporal lobes. Stimulus sequences were divided into five 30-second segments by using a task-activation paradigm that alternated between resting and stimulated states. Functional images were collected every 30 seconds by using a gradient echo pulse sequence. RESULTS: Schizophrenic subjects demonstrated significantly less left frontal activation and greater left temporal activation than comparison subjects during a word fluency task. CONCLUSIONS: These preliminary data suggest that functional MRI has the sensitivity to detect differences in activation between comparison subjects and schizophrenic patients during higher cortical functions. These findings are in agreement with PET studies that reported reduced left frontal activation during challenge paradigms for the schizophrenic patients.

Adult↗
PubMed1996

Coronary perforation complicating rotational ablation: the U.S. multicenter experience.

This study retrospectively analyzed the data within the U.S. Multicenter Registry for Rotational Ablation to determine the incidence of coronary perforation during rotational ablation, its angiographic predictors and clinical outcomes during 2953 consecutive patients, 3717 lesions. Patients were categorized into Group A (without perforation, N = 2931) and Group B (with perforation, N = 22 patients). Perforation occurred in 0.7% of procedures, and in 0.6% of lesions treated and was more frequent within the right (12/ 1105, 1.1%) and circumflex (9/761, 1.2%) arteries than the left anterior descending artery [1/1727, 0.06%; (P < 0.001)]. Morphologic features associated with increased perforation rates were eccentricity, tortuousity, and lesion length > 10 mm. Group B was assessed with regard to major complications, including death, surgery, myocardial infarction, or tamponade (type I); and minor complications; sealing with balloon angioplasty and without clinical sequelae (type II). There were 15 type I: emergency surgery in nine, of whom two died, and six infarctions (5 non-Q wave and one Q wave); and 7 type II patients. Coronary perforation, although a rare complication of rotational ablation, is seen more frequently in the right and circumflex coronary arteries than the left anterior descending artery, and occurs more frequently with lesion eccentricity, tortuousity, and length > 10 mm.

Atherectomy, Coronary↗
PubMed1996

Cocktail attenuation of rotational ablation flow effects (CARAFE) study: pilot.

Although rotational ablation has been successful in the treatment of complex coronary lesions, periprocedural complications of microvascular-mediated ischemia (slow flow or no reflow) and coronary vasospasm may occur. In an attempt to reduce such complications, a drug cocktail consisting of a combination of verapamil 10 micrograms/ml, nitroglycerin 4 micrograms/ml, and heparin 20 U/ml was infused in 21 consecutive patients with AHA/ACC Type B2 and C lesion morphology. A total of 27 lesions were treated, with a procedural success rate of 95%. One patient required emergency bypass surgery. Coronary vasospasm occurred in 7% (2/27 lesions). Only one lesion (3.7%) was associated with a transient reduction in TIMI flow that resolved within 5 min, and none had classical no-reflow. No patient developed intraluminal thrombus, and none had hypotension requiring inotropic support. All patients had prophylactic temporary pacemakers inserted. All RCA and circumflex lesions and 50% of LAD stenoses required transient pacing. A "cocktail" infusion of verapamil, nitroglycerin, and heparin mixed in pressurized saline delivered through the 4-French Teflon sheath of the Rotablator system during rotational ablation is associated with high success and low complication rates. Transient AV block is frequent, especially when treating RCA and circumflex arteries; therefore, prophylactic pacing is indicated.

Aged↗
PubMed1995

Decreased brain choline uptake in older adults. An in vivo proton magnetic resonance spectroscopy study.

OBJECTIVE: To test the hypothesis that uptake of circulating choline into the brain decreases with age, because alterations in metabolism of choline may be a factor contributing to age-related degenerative changes in the brain. DESIGN: Cohort comparison in younger and older adults. PARTICIPANTS: Subjects were chosen consecutively from lists of healthy volunteers screened by medical and psychiatric interviews and laboratory tests. Younger adults (n = 12) were between the ages of 20 and 40 years (mean age, 32 years), and older adults (n = 16) were between the ages of 60 and 85 years (mean age, 73 years). INTERVENTIONS: After fasting overnight, subjects received choline, as the bitartrate, to yield free choline equal to 50 mg/kg of body weight. Blood was drawn for determination of plasma choline concentration by high-performance liquid chromatography, and proton magnetic resonance spectroscopy (1H-MRS) was performed to determine the relative concentration of cytosolic choline-containing compounds in the brain at baseline and after ingestion of choline. MAIN OUTCOME MEASURES: Plasma choline and cytosolic choline-containing compounds in the brain, estimated as the ratio of the choline resonance to the creatine resonance on 1H-MRS scans of the basal ganglia, were compared following blinded analyses of data from subject cohorts studied at baseline and 3 hours after choline ingestion. RESULTS: Levels of plasma choline and cytosolic choline-containing compounds in brain were similar at baseline in younger and older subjects. Following ingestion of choline, plasma choline concentration increased by similar proportions (76% and 80%) in both younger and older subjects. Brain cytosolic choline--containing compounds increased substantially in younger subjects (mean increase, 60%; P < .001 vs baseline). Older subjects showed a much smaller increase in brain choline-containing compounds (mean, 16%; P < .001 vs the increase in younger subjects). CONCLUSION: Uptake of circulating choline into the brain decreases with age. Given the key role of choline in neuronal structure and function, this change may be a contributing factor in onset in late life of neurodegenerative, particularly dementing, illnesses in which cholinergic neurons show particular susceptibility to loss.

Adult↗
PubMed1995

Acute administration of typical and atypical antipsychotic drugs induces distinctive patterns of Fos expression in the rat forebrain.

Fos expression in the rat brain was investigated by immunohistochemistry after i.p. administration of single doses of a wide range of typical neuroleptic antipsychotic drugs (including the potent dopamine D2 antagonist haloperidol and the mixed monoamine antagonist chlorpromazine) and atypical antipsychotic drugs (including the weak dopamine D2 antagonists clozapine and thioridazine, the relatively pure D2 antagonist raclopride and the mixed D2 and serotonin S2 antagonist risperidone). For comparison to the effects of the antipsychotic drugs and also because the unique clinical therapeutic effects of clozapine have been attributed to S2 blockade, the S2 antagonist ritanserin was also studied. The single shared effect of all antipsychotic drugs tested was the induction of significantly increased Fos immunoreactivity in the nucleus accumbens (NAc). Fos-positive neurons in the NAc were mostly localized in patches throughout its rostrocaudal extent. Haloperidol, chlorpromazine, raclopride and risperidone all significantly increased Fos expression in the medial and lateral striatum. Fos-positive neurons in the striatum were distributed more lateral than medial and declined from rostral to caudal levels. Haloperidol, thioridazine and risperidone also markedly increased Fos expression in the lateral septum. Distinguishing it from the other neuroleptics, clozapine did not increase Fos expression in the lateral striatum, but induced a significant increase in Fos expression in the prefrontal cortex. Ritanserin did not induce Fos expression in any brain region examined, suggesting that S2 antagonism is not responsible for the effects of antipsychotic drugs observed here. Our results suggest that there are distinctive patterns of Fos expression in the forebrain induced by typical and atypical antipsychotic drugs. Notably, Fos expression in the NAc, as a shared property of all the antipsychotic drugs, may be related to the actions mediating the therapeutic effects of these drugs in the treatment of psychotic disorders. The density of Fos-positive neurons stimulated by antipsychotic drugs in the striatum appeared to be correlated with the relative severity of extrapyramidal side-effects produced by these drugs and may be related to the mechanisms mediating these effects.

Analysis of Variance↗
PubMed1995

Choline ingestion increases the resonance of choline-containing compounds in human brain: an in vivo proton magnetic resonance study.

Choline is a crucial intermediate in several clinically relevant neurochemical processes. In this study, choline-containing compounds in human brain (principally phosphocholine, glycero-phosphocholine, and choline) were measured by 1H-magnetic resonance spectroscopy, before and after the ingestion of 50 mg/kg choline in four normal control subjects. Substantial and remarkably similar increases in the brain choline resonance occurred in each subject, with a nearly two-fold rise in the choline resonance observed 3 hr following choline ingestion (p = 0.008 versus baseline). One subject also received a dose of 200 mg/kg choline, and exhibited a proportionally larger increase in the brain choline resonance. The results are consistent with animal data reporting a rise in choline-containing compounds following choline administration. This is the first study to our knowledge where an oral nutrient has been shown to produce a detectable change in human brain composition in vivo. Studying choline transport and biotransformation in human brain may have relevance to several neuropsychiatric disorders, including affective disorders and dementia.

Acetylcholine↗
PubMed1995

Sequential dynamic susceptibility contrast MR experiments in human brain: residual contrast agent effect, steady state, and hemodynamic perturbation.

The stability and reproducibility of the dynamic susceptibility contrast (DSC) MRI method for sequential relative cerebral blood volume (relCBV) measurements was evaluated to validate the method for use in quantitative studies of cerebral hemodynamics in humans. A spin echo echo planar imaging protocol was used in conjunction with multiple bolus injections of the susceptibility contrast agent gadoteridol (GD). The effects of variation in interbolus interval (10 min to 4 h), the number of injections (two to four), and the effect of the cerebral vasodilating agent acetazolamide (ACZ) were evaluated in 44 experiments performed with 22 normal subjects. Two fundamental observations were made. First, with multiple injections of GD, the change in MR signal over time was not consistent from first to subsequent boluses. A second bolus administered 10 min to 2 h after an initial bolus resulted in signal change of greater amplitude and duration, resulting in artifactually elevated estimates of relCBV, consistent with a residual effect of GD. Second, a relative steady state could be reached with serial injections of GD, such that the profile of subsequent boluses closely paralleled those of previous ones. This facilitates the reliable measurement of relCBV during activation, as demonstrated by use of ACZ.

Acetazolamide↗
PubMed1995

Abnormalities of regional distribution of cerebral vasculature in schizophrenia detected by dynamic susceptibility contrast MRI.

OBJECTIVE: The authors tested the hypothesis that the regional distribution of cerebral vasculature is anomalous in schizophrenia. METHOD: Dynamic susceptibility contrast magnetic resonance imaging was used to evaluate cerebral blood volume in the right and left occipital cortex, basal ganglia, and cerebellum of 10 subjects with schizophrenia and 10 healthy comparison subjects. RESULTS: Cerebral blood volume was greater in the schizophrenic subjects in every region studied. CONCLUSIONS: The findings suggest an abnormality of the configuration of cerebral blood vessels in schizophrenia.

Adult↗
PubMed1995

Temporal lobe proton magnetic resonance spectroscopy of patients with first-episode psychosis.

OBJECTIVE: The authors measured the ratio of N-acetyl aspartate (a putative neuronal marker) to creatine-phosphocreatine in patients with first-episode psychosis by using proton magnetic resonance spectroscopy (MRS). METHOD: Temporal lobe 1H MRS was performed bilaterally on 13 patients with first-episode psychosis and 15 comparison subjects. The N-acetyl aspartate/creatine-phosphocreatine and choline/creatine-phosphocreatine ratios were determined. RESULTS: The N-acetyl aspartate/creatine-phosphocreatine ratio of the psychotic patients was significantly lower than that of the comparison subjects. CONCLUSIONS: These preliminary data suggest that abnormalities in temporal lobe N-acetyl aspartate concentration are present early in psychotic illness.

Adult↗
PubMed1994

Association of the apolipoprotein E epsilon 4 allele with clinical subtypes of autopsy-confirmed Alzheimer's disease.

Consistent with previous reports, we observed a significant association of the APOE epsilon 4 allele with Alzheimer's Disease (AD) in a series of 91 autopsy-confirmed cases. The epsilon 4 allele frequency was higher in cases with a family history of AD-like dementia (0.54 +/- 0.07), although the epsilon 4 allele frequency in the AD cases with a negative family history (0.38 +/- 0.05) remained significantly greater than that for the non-AD control group (0.13 +/- 0.03). A similar increase in epsilon 4 allele frequency (0.54 +/- 0.07) was observed in the AD cases with amyloid angiopathy, compared to those who did not have amyloid angiopathy (0.36 +/- 0.04). Contrary to previous reports, no effect of the dosage of the epsilon 4 allele was found on the age of onset of dementia among the AD cases and, contrary to reports suggesting an association of epsilon 4 and atherosclerosis, the epsilon 4 allele frequency was similar in cases with or without concurrent brain infarcts. Modest but consistent correlations were observed between the dosage of epsilon 4 alleles and the cortical density of senile plaques, but not neurofibrillary tangles. The last finding suggests that the pathogenic events mediated by the epsilon 4 allele may be more directly involved in the formation of senile plaques, the identifying lesions in AD, than neurofibrillary tangles. A robust association of both the presence of an epsilon 4 allele and a family history of AD-like dementia with concurrent amyloid angiopathy occurred within our sample of AD cases. This association arose from an interaction of the epsilon 4 allele with a separate familial factor for which a family history of dementia served as a surrogate. These results suggest that amyloid angiopathy may be a common or central feature of a form of familial AD that is associated with the transmission of the APOE epsilon 4 allele.

Aged↗
PubMed1994

Persistent reduction of immediate early gene mRNA in rat forebrain following single or multiple doses of cocaine.

Stimulus-induced expression of immediate early genes (IEGs) is believed to be involved in the transduction of extracellular stimuli into prolonged modifications of cellular function. Previous studies have demonstrated that the IEGs NGFI-A (zif268) and c-fos are each rapidly induced in the caudate putamen (CP) by treatment with the indirect dopamine agonist cocaine. The short-term course of this induction has been well studied. However, the consequences of cocaine use are not limited to immediate pharmacological effects. Withdrawal, especially from prolonged or repeated use, can produce extended physiological and behavioral changes. At the cellular level, these longer-term effects may be mediated by or reflected in changes in the expression of IEGs. For this reason, we have investigated long-term perturbations in IEG expression during withdrawal from intravenously (IV) or intraperitoneally (IP) administered cocaine. Levels of NGFI-A and c-fos were measured in the CP of rats by Northern blot analysis, which confirmed that cocaine-induced increases of NGFI-A and c-fos mRNA lasts for several hours after drug administration. Immediately following this induction, however, there is a prolonged period during which a marked reduction in the relative amount of mRNA for both NGFI-A and c-fos is observed in cocaine-treated animals when compared to matched, vehicle-treated controls. This repression persisted for several hours after a single injection and as long as several days following multiple injections, strongly suggesting a cumulative effect for repeated exposures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗