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Biomedical subjects

M Buchsbaum

Publications and source records attributed to M Buchsbaum.

At least 19 recordsLinked to original sources
PubMed2001

Sleep deprivation as a model experimental antidepressant treatment: findings from functional brain imaging.

This paper reviews the functional brain imaging studies in depressed patients treated with sleep deprivation. Sleep deprivation is an excellent experimental model of antidepressant treatments which offer new opportunities to understand the basic neural mechanisms. Its antidepressant effects are efficacious and rapid; sleep deprivation is easy to administer, inexpensive, and relatively safe; it can be studied in patients, normal controls, and animals; and it may lead to new treatments and new paradigms for antidepressant therapies. Seven published papers, coming from five different research centers, using either positron emission tomography (PET) with 18fluorodeoxyglucose (FDG) or single photon emission computerized tomography (SPECT) with Technetium-99-bexamethyl propyleneamine oxime (HMPAO) have relatively consistent findings. First, before sleep deprivation, responders have significantly elevated metabolism compared with non-responders, and usually the normal controls, in the orbital medial prefrontal cortex, and especially in the ventral portions of the anterior cingulate cortex. Secondly, after sleep deprivation, these hyperactive areas normalize in the responders. The magnitude of the clinical improvement was significantly correlated with decreased local glucose metabolic rate or cerebral blood flow in three studies. The results are consistent with some but not all functional brain imaging studies of antidepressant medications in depressed patients. Finally, a SPECT study using a radioactively labeled D2 receptor antagonist suggests that the antidepressant benefits of sleep deprivation are correlated with endogenous release of dopamine.

Brain↗
PubMed2001

Clinical neurochemical implications of sleep deprivation's effects on the anterior cingulate of depressed responders.

The antidepressant and cerebral metabolic effects of total sleep deprivation (TSD) or partial sleep deprivation (PSD) for one night has been studied with functional neuroimaging in seven publications from five different groups. Despite the variations in methods and techniques, the over-all findings were relatively consistent. First, before sleep deprivation, responders have significantly elevated metabolism compared with non-responders and normal controls, in the orbital medial prefrontal cortex, and especially the ventral portions of the anterior cingulate cortex. Second, after sleep deprivation, these hyperactive areas normalize in the responders. One functional imaging study suggested that synaptic dopamine release was associated with the antidepressant effects of TSD. The neurochemical implications of these findings are explored. Possible dopaminergic and serotonergic mechanisms are discussed.

Cerebral Cortex↗
PubMed2001

Emergency department evaluation of chest pain using exercise stress echocardiography.

OBJECTIVE: Patients with a low risk of coronary artery disease (CAD) presenting to the emergency department (ED) with chest pain pose a diagnostic dilemma because a small percentage will suffer an acute myocardial infarction (MI) and sudden death. The authors conducted this study to determine whether exercise stress echocardiography (ESE) could be used to further support the safe discharge of these low-risk patients. METHODS: A convenience sample of patients > or =30 years of age without a prior cardiac history who presented to an academic community hospital with chest pain, normal initial creatine kinase, and electrocardiography without ischemic changes underwent ESE within 6 +/- 1.7 hours (mean +/- SD). Abnormal ESE was defined as regional wall motion abnormality at rest or after exercise. The ED disposition and three- and six-month follow-up for cardiac events were recorded. This was a prospective observational cohort study. RESULTS: Of a total of 149 eligible patients, 145 completed the study. The mean age (+/-SD) was 47 +/- 9 years; 56% were male. No adverse events were noted during ESE. Seven patients (5%) had abnormal ESE (2 with rest wall motion abnormalities and 5 with exercise-induced wall motion abnormalities). Five of the seven underwent cardiac catheterization; three had CAD. All patients received telephone follow-up at three months and six months. Of the 138 patients with a normal ESE, all were free of cardiac events at three months. One patient had a non-Q-wave MI at six months (negative predictive value = 99.3%, 95% CI = 97.8% to 100%). CONCLUSIONS: Exercise stress echocardiography can be used to evaluate low-risk chest pain patients in the ED. Patients with a normal ESE may be considered for discharge with minimal risk of sequelae.

Adult↗
PubMed2001

Temporal lobe deficits in murderers: EEG findings undetected by PET.

This study evaluates electroencephalography (EEG) and positron emission tomography (PET) in the same subjects. Fourteen murderers were assessed by using both PET (while they were performing the continuous performance task) and EEG during a resting state. EEG revealed significant increases in slow-wave activity in the temporal, but not frontal, lobe in murderers, in contrast to prior PET findings that showed reduced prefrontal, but not temporal, glucose metabolism. Results suggest that resting EEG shows empirical utility distinct from PET activation findings.

Adult↗
PubMed1999

Progressive catatonia.

We present the case of a young man with a diagnosis of a childhood-onset pervasive developmental disorder who developed a progressive neurologic deterioration with persistent catatonia and right hemiparesis. On his initial evaluation approximately three years after the onset of mutism, he manifested right hemiparesis and catalepsy. Two years later, although catalepsy had subsided, motor function had deteriorated so that he could not use his hands to feed or dress himself. Oral-facialbuccal dyskinesia manifested by blepharospasm and grimacing were present constantly during waking hours. Quantitative electroencephalography demonstrated markedly decreased amplitude, a finding associated with catatonia. Left sural nerve biopsy indicated large axon cylinder degeneration. Left deltoid biopsy demonstrated perimysial fibrosis and type II fiber predominance. Although magnetic resonance imaging of the head without contrast was normal, positron emission tomography indicated hypometabolism of the right cerebral and the right cerebellar hemispheres. The patient continues to deteriorate despite a course of 25 electroconvulsive treatments. He continues to manifest criteria for catatonia including motoric immobility, mutism, and peculiarities of voluntary movement such as prominent grimacing. We suspect an inherited neurodegenerative disorder. Since catatonia is a treatable condition frequently associated with medical and neurological diseases, examination for the features of catatonia must be included in the assessment of patients with progressive brain degeneration. This report is an attempt to clarify the traits of a serious variant of progressive brain degeneration.

Activities of Daily Living↗
PubMed1998

Prefrontal glucose deficits in murderers lacking psychosocial deprivation.

Previous research has suggested that links between autonomic nervous system functioning and violence are strongest in those who come from benign home backgrounds, but there appears to be no similar research using brain-imaging measures of central nervous system functioning. It was hypothesized that murderers who had no early psychosocial deprivation (e.g., no childhood abuse, family neglect) would demonstrate lower prefrontal glucose metabolism than murderers with early psychosocial deprivation and a group of normal controls. Murderers from a previous study, which showed prefrontal deficits in murderers, were assessed for psychosocial deprivation and divided into those with and without deprivation. Murderers without any clear psychosocial deficits were significantly lower on prefrontal glucose metabolism than murderers with psychosocial deficits and controls. These results suggest that murderers lacking psychosocial deficits are characterized by prefrontal deficits. It is argued that among violent offenders without deprived home backgrounds, the "social push" to violence is minimized, and consequently, brain abnormalities provide a relatively stronger predisposition to violence in this group.

Adult↗
PubMed1997

Brain abnormalities in murderers indicated by positron emission tomography.

Murderers pleading not guilty by reason of insanity (NGRI) are thought to have brain dysfunction, but there have been no previous studies reporting direct measures of both cortical and subcortical brain functioning in this specific group. Positron emission tomography brain imaging using a continuous performance challenge task was conducted on 41 murderers pleading not guilty by reason of insanity and 41 age- and sex-matched controls. Murderers were characterized by reduced glucose metabolism in the prefrontal cortex, superior parietal gyrus, left angular gyrus, and the corpus callosum, while abnormal asymmetries of activity (left hemisphere lower than right) were also found in the amygdala, thalamus, and medial temporal lobe. These preliminary findings provide initial indications of a network of abnormal cortical and subcortical brain processes that may predispose to violence in murderers pleading NGRI.

Adult↗
PubMed1993

Preparation and preliminary biological evaluation of [18F]NCQ-115: a new selective reversible dopamine D2 receptor ligand.

18F-labeled dopamine D2 antagonist, NCQ-115 ((+)-(R)-5-bromo-N-((1-(fluorobenzyl)-2-pyrrolidinyl)-methyl-2,3- dimethoxybenzamide), was successfully prepared using a remotely controlled system. [18F]Fluoride was reacted with the trifluoromethanesulfonate salt of 4-(trimethylamino)benzaldehyde. The product was first reduced with LAH, and then reacted with thionyl bromide to yield 18F-labeled 4-fluorobenzylbromide. [18F]4-Fluorobenzylbromide was then reacted with the pyrrolidie precursor (NCQ-282) to yield the product [18F]NCQ-115 contaminated with unreacted starting material. The product was purified by reverse phase chromatography yielding [18F]NCQ-115 with a specific activity of more than 1400 Ci/mmol. Autoradiographic and biodistribution data following injection of [18F]NCQ-115 in rats revealed the regional uptake of striatum/cerebellum to be 3.2 at 30 min post-injection.

Animals↗
PubMed1993

Novel interactions between dermal dendrocytes and mast cells in human skin. Implications for hemostasis and matrix repair.

BACKGROUND: Dermal dendrocytes are a newly-recognized cell type in human skin. They express coagulation Factor XIIIa (FXIIIa), also known as fibrin stabilizing factor, and their number is increased in certain inflammatory dermatoses. Current dogma suggests that these recently described cells may represent a subset of antigen-presenting macrophages. The present study therefore was undertaken to examine further the phenotype and potential function of these novel cells. EXPERIMENTAL DESIGN: Conventional ultrastructure, single and dual label immunofluorescence and immunocytochemistry, confocal laser scanning microscopy, and immunoelectron microscopy were used to define structure and potential heterogeneity among dermal dendrocytes. Human neonatal foreskin organ culture exposed to mast cell secretagogues, inhibitors, and relevant recombinant cytokines (tumor necrosis factors alpha) was employed to gain insight into functional characteristics of FXIIIa expression. RESULTS: We found that dermal dendrocytes are phenotypically unique dermal cells, separate from conventional macrophages, with antigenic heterogeneity of FXIIIa and CD34 expression related to their microanatomical location in the dermis. Moreover, they express specialized membrane-matrix plaques that may stabilize their placement in various dermal strata. Finally, superficial subpopulations of dermal dendrocytes are closely-associated with mast cells and show enhanced FXIIIa expression in response to mast cell degranulation, an event that appears to result from liberation of mast cell tumor necrosis factor in the dendrocyte microenvironment. CONCLUSIONS: These new insights establish dermal dendrocytes as distinctive fixed skin cells with potential functional capacity for mast cell-dependent facilitation of fibrin cross-linking and matrix remodeling. These previously unrecognized phenotypic and functional characteristics of dermal dendrocytes therefore may be relevant to cellular interactions responsible for cutaneous wound healing and hemostasis.

Cell Communication↗
PubMed1989

Clinical, psychophysiological, and neurological characteristics of volunteers with impaired smooth pursuit eye movements.

Two hundred eighty-five volunteers from a community college were screened on campus for accuracy of their smooth pursuit eye movements (SPEM) by electrooculograph (EOG). Those volunteers with the least and the most accurate SPEM were recalled to the laboratory for a comprehensive evaluation of clinical and demographic characteristics, family history, neurological status, and psychophysiological and biological measures, including SPEM [repeat EOG test and infrared (IR) test], an electroencephalogram, auditory and visual evoked potentials, reaction time (RT), the continuous performance task (CPT), platelet monoamine oxidase (MAO), plasma amine oxidase, and dopamine-beta-hydroxylase (DBH). Low-accuracy SPEM was associated with social isolation, inadequate rapport, eccentricity, and a variety of related schizotypal or schizophrenia-like characteristics, but not with generalized psychopathology or other demographic/medical/clinical history variables. Low-accuracy SPEM also was associated with neurological and psychophysiological abnormalities frequently observed in schizophrenic patients. These results suggest that impaired SPEM may reflect an underlying central nervous system dysfunction that is specifically associated with clinical and biological characteristics related to schizophrenia, even in the absence of overt schizophrenia.

Adult↗
PubMed1989

Intercellular adhesion molecule expression in the evolving human cutaneous delayed hypersensitivity reaction.

Intercellular adhesion molecule-1 (ICAM-1), putatively expressed by antigen-presenting or target skin cells, is a ligand for the lymphocyte function-associated antigen (LFA-1) present on circulating lymphocytes. Immunohistochemistry of normal adult human skin using monoclonal antiserum to ICAM-1 demonstrated focal reactivity restricted to endothelium lining the dermal microvasculature. Delayed hypersensitivity responses elicited with dinitrochlorobenzene in the skin of the same subject were evaluated sequentially over a 96 h period using immunohistochemical and ultrastructural techniques. The first alteration observed consisted of mast cell degranulation within perivenular foci in the superficial dermis at 4 h after antigen challenge. Sparse superficial perivascular T-cell infiltrates were present by 24 h. Progressive staining for ICAM-1 was observed in microvascular endothelium and in dermal dendritic cells between 24 and 48 h. ICAM-1 expression was documented focally within the lower epidermis at 48 h and diffusely within the lower and upper epidermal layers at 96 h. ICAM-1 expression by keratinocytes was consistently associated with T-cell migration into the epidermis, whereas migration was never observed in the absence of ICAM-1 reactivity. Immunoelectron microscopy confirmed ICAM-1 to be exclusively present on endothelial cells, dermal dendritic cells, mononuclear cells, and keratinocytes, and permitted characterization of the patterns of membrane reactivity. ICAM-1 expression by epidermal cells appears to be closely linked to the progressive migration of T cells from the dermis into the epidermis that characterizes cutaneous delayed hypersensitivity.

CD4-Positive T-Lymphocytes↗
PubMed1988

Assessment of young men at risk for alcoholism with P300 from a visual discrimination task.

A visual discrimination paradigm was used to elicit the P3 (P300) component of the event-related brain potential (ERP) in a large group (N = 196) of male undergraduate volunteers. Comparison of P3 amplitude and latencies between individuals with a positive family history for alcoholism (FH +) and those without such a history (FH -) obtained no differences between the groups. No associations between P3 latency or amplitude and the amount of alcohol typically consumed were found. Differences between the present and previous P3 family history studies using visual stimuli are attributed to the cognitive demands of ERP task.

Adult↗
PubMed1985

Phenotypic and functional analysis of T cells cloned directly from the blood and cerebrospinal fluid of patients with multiple sclerosis.

A single-cell cloning technique was used to analyze both phenotype and function of individual T cells in patients with multiple sclerosis (MS). Blood and cerebrospinal fluid (CSF) lymphocytes were plated at 1 cell per well, stimulated with phytohemagglutinin followed by interleukin 2, and expanded to 3 X 10(6) cells per "clone." More than 90% of the T8 clones generated from patients with MS and controls in both blood and CSF were cytotoxic precursors. There was also a slight decrease in cytotoxic T4 clones in the blood of patients with MS. The cytotoxic precursor frequencies of T cells in the CSF generally reflected those in the blood. In separate experiments, antigen reactivity was examined in lines established from blood or CSF. No reactivity to myelin basic protein or white matter was found in patients with MS or controls. Myelin basic protein-reactive clones could, however, be generated after first stimulating lymphocytes with antigen before cloning. These results suggest that changes in the T8 population from the blood of patients with MS involve cytotoxic as well as suppressor cells. Sequestration of myelin basic protein- or white matter-reactive T cells was not seen in the CSF of patients with MS, unlike reports of viral meningoencephalitis, in which large numbers of antigen-specific cells were found in the CSF. Direct single-cell clonal analysis of the CSF should provide a more sophisticated approach to the study of T cell abnormalities in patients with MS.

Brain↗
PubMed1985

Decreased autologous mixed lymphocyte reaction in multiple sclerosis.

The autologous mixed lymphocyte reaction (AMLR) measures the T-cell response to antigens on the surface of autologous non-T-cells. Studies have shown a decreased ability of T-cells to proliferate during the AMLR in a number of autoimmune and viral disorders. The AMLR was studied in 56 patients with multiple sclerosis (MS), a presumed autoimmune disease of the central nervous system, and the response was correlated with T-cell subsets. The AMLR was decreased in active MS patients (3 117 +/- 573 cpm) as compared to inactive patients (5 896 +/- 1 800 cpm) (P less than 0.05) and normal controls (7 782 +/- 1 725 cpm) (P less than 0.01). There was no significant difference between inactive patients and normal controls (P greater than 0.1). A more pronounced difference was also seen when patients with active disease associated with peripheral blood T4/T8 ratios greater than 3.0 (1 045 +/- 223 cpm) were compared with normal controls (P less than 0.01). In addition, MS patients with T4/T8 ratios of less than 1.0 had an increased AMLR (9 256 +/- 1 762 cmp) as compared to patients with either a high T4/T8 ratio (P less than 0.001) or normal ratio (P less than 0.05). Thus, multiple sclerosis patients with clinically active disease have a decreased AMLR which correlates with high T4/T8 ratios in a subgroup of patients.

Adolescent↗
PubMed1985

Alternative statistical models for the examination of clinical positron emission tomography/fluorodeoxyglucose data.

This article describes a method for partitioning metabolic variability found in positron emission tomography/[18F]fluorodeoxyglucose studies. For the 15 subjects examined, 74.8% of the total metabolic variability could be ascribed to individual differences in global metabolic rate, whereas 15.8% of the total variability was consistent regional variation or pattern across subjects. Subsequently, the method of Q-component analysis is described for the identification of strong- and weak-pattern subjects. In addition, a standardization procedure that amplifies the observed pattern by removing systematic individual differences is described. Finally, the implications of these findings and methods for future and clinical studies are discussed.

Adolescent↗
PubMed1984

ERPs and psychopathology. II. Biological issues.

We have briefly covered important issues and considerations in four topic areas likely to be of use to the ERP researcher who is also interested in biological psychiatry. We cannot ignore diagnosis because of its basic role in the field of psychiatry. Although there are reliability problems, especially in the field of psychiatric diagnosis, ERPs may help in the painstaking task of validating diagnosis based on behavioral observation. In addition, the ERP researcher can use diagnosis to obtain potentially more homogeneous samples of patients so as to reduce between-subject error variance in studies. We have considered research areas like PET scan and CT scan which provide data of more anatomical precision than ERPs for deep neurological sites. While the potential may be there, it is essentially unrealized as yet. Finally, neurochemistry and psychopharmacology seem to be the areas most likely to bear fruit in the immediate future. If this potential is to be realized, it is necessary to formulate new questions and a new methodology to handle these questions. An important question, for example, is whether a biological profile is a more useful criterion than a behavioral profile for predicting response to pharmacological intervention. In biological psychiatry, this question is a human suffering issue of considerable importance.

Antipsychotic Agents↗