Search PubMed⌕ Search

Biomedical subjects

A Breier

Publications and source records attributed to A Breier.

At least 145 records · Page 8Linked to original sources
PubMed1993

Quantitative electroencephalographic correlates of steroid administration in man.

Elevated levels of circulating corticosteroids are frequently associated with behavioral alterations in man, although the mechanisms by which corticosteroids may affect behavior are poorly understood. To evaluate possible effects of exogenous corticosteroids on brain electrophysiological functioning and the relationship of such effects to behavioral and biochemical changes, we administered prednisone (80 mg p.o. daily for 5 days) in a double-blind manner to 11 medically healthy volunteers. Quantitative electroencephalogram analysis was performed following 4 days of prednisone administration and during the preceding and ensuing placebo administration periods. Central theta wave brain electrical activity significantly increased following prednisone administration and returned to baseline following prednisone withdrawal. This effect was directly correlated with prednisone-induced increases in subjective sadness ratings and with decreases in self-rated energy and well-being. Prednisone-induced reductions in peak alpha wave activity were also directly correlated with increases in subjective sadness and Symptom Checklist-90 ratings and with decreases in self-rated 'hypomanic' symptoms. Further, prednisone-induced increases in theta activity were significantly correlated with prednisone-induced decreases in CSF levels of somatostatin-like immunoreactivity, and prednisone-induced decreases in peak alpha activity were significantly correlated with decreases in CSF levels of norepinephrine and with relative increases (or lesser decreases) in CSF levels of beta-endorphin and beta-lipotropic hormone. This preliminary report of the concomitant development of prednisone-induced changes in brain electrical activity, neurochemistry and behavior highlights areas for future exploration in the study of corticosteroid effects on behavior in man.

Adult↗
PubMed1993

Structural abnormalities in deficit and nondeficit schizophrenia.

OBJECTIVE: Previous studies have suggested the involvement of the frontal and parietal cortices and thalamus in a neural circuit underlying the production of primary enduring negative or deficit symptoms of schizophrenia. The purpose of this study was to examine whether structural changes in the proposed circuit are associated with the production of deficit symptoms. METHOD: Magnetic resonance imaging was used to measure the volume of selected circuit brain regions (i.e., the prefrontal region and caudate) and noncircuit brain regions (i.e., the amygdala/hippocampus complex) in 17 deficit and 24 nondeficit schizophrenic outpatients and 30 normal comparison subjects. RESULTS: Right and left total prefrontal volumes discriminated deficit from nondeficit patients, with prefrontal volumes being smaller in nondeficit patients. There were no differences between the two schizophrenic subgroups in left caudate or right and left amygdala/hippocampus complex volumes. The right caudate was larger in deficit patients, but the difference between the two schizophrenic subgroups was not significant. There were no differences between deficit and normal subjects on any prefrontal region measure. Nondeficit patients had smaller total right and left prefrontal volumes than normal subjects. Both schizophrenic subgroups had larger left caudate volumes and smaller right and left amygdala/hippocampus complex volumes than the normal subjects. There was a trend for deficit patients to have larger right caudate volumes. CONCLUSIONS: These results suggest that structural changes in the prefrontal region are not responsible for deficit symptoms. The caudate, particularly the right caudate, may be associated with the production of these symptoms.

Frontal Lobe↗
PubMed1993

Clozapine treatment of outpatients with schizophrenia: outcome and long-term response patterns.

OBJECTIVE: The purpose of the study was to examine the effects of clozapine in treating moderately ill schizophrenic outpatients and to determine the length of medication trial needed to identify responders and nonresponders. METHODS: Rates of clinical responses, relapses and hospitalizations, and levels of symptomatology and functioning were assessed for 30 chronic schizophrenic outpatients who received clozapine for one year. For some patients, data on relapse and hospitalization during treatment were compared with data from the year before treatment. RESULTS: Eighteen of the 30 patients met criteria for sustained response; 17 of the responders were identified within the first four months of treatment. Patients experienced significantly fewer relapses and hospitalizations during treatment than in the previous year. Improvement in positive symptoms, general symptomatology, and levels of functioning reached a plateau during the first six months of treatment and remained at that level during the second six months. Negative symptoms and quality of life showed nonsignificant improvements at 12 months. CONCLUSIONS: Results support the use of clozapine in treating chronic, residually symptomatic schizophrenic outpatients. A four-month clozapine trial may be adequate to detect clinical responders in this population.

Adult↗
PubMed1993

Hospital vs. community.

Explore the source record for details and available documents.

Community Mental Health Services↗
PubMed1993

Overcoming of vincristine resistance in L1210/VCR cells by several corticosteroids. Collateral sensitivity of resistant cells.

Five corticosteroids were tested to determine whether they are able to overcome the multidrug resistance of vincristine resistant mouse leukemia cells L1210/VCR. The most effective in reversing multidrug resistance were cortisone and dexamethasone, less effective as reversing agents were 11-deoxycorticosterone, 1-dehydrocortisone and hydrocortisone. By testing of collateral sensitivity of vincristine resistant cell line to these corticosteroids it was found that only 11-deoxycorticosterone and dexamethasone were toxic to multidrug resistant cells at doses much lower than required for toxicity to the drug-sensitive L1210/S cells. Using thin layer chromatography the polarity of tested corticosteroids was estimated, and good correlation was found between polarity of corticosteroids and their increased toxicity to vincristine resistant cells.

17-Hydroxycorticosteroids↗
PubMed1992

Plasma prolactin as a predictor of relapse in drug-free schizophrenic outpatients.

A low plasma prolactin concentration has been reported to be associated with an increased risk of subsequent relapse in patients with schizophrenia. Prolactin concentration was measured in samples from stable schizophrenic men who were outpatients just prior to neuroleptic withdrawal. No relationship between prolactin concentration and time to subsequent relapse was found. Prolactin concentration may predict time to relapse only in populations characterized by specific demographic features or medication history.

Administration, Oral↗
PubMed1992

Effects of alprazolam on pituitary-adrenal and catecholaminergic responses to metabolic stress in humans.

Concurrent effects of benzodiazepines on stress-induced activation of the three classical "stress" systems: pituitary-adrenal, adrenomedullary, and sympathoneural systems have not been extensively investigated in humans. In the present study, the effects of alprazolam (1.5 mg) on plasma levels of adrenocorticotropin hormone (ACTH), epinephrine, norepinephrine, dihydroxyphenylglycol (DHPG, the intraneuronal metabolite of norepinephrine), and mood states were examined in 10 healthy volunteers undergoing glucoprivic stress. Glucoprivic stress was induced by intravenous administration of the glucose analog, 2-deoxyglucose (2DG), at a dose (50 mg/kg) that impairs cellular glucose metabolism and produces a state comparable to hypoglycemia. Alprazolam and 2DG were administered in a double-blind, placebo-controlled manner. 2DG produced robust elevations in plasma ACTH and epinephrine levels, modest elevations in plasma norepinephrine levels, and decreases in plasma DHPG levels. Alprazolam significantly attenuated the 2DG-induced increases in plasma ACTH and epinephrine, but did not significantly effect plasma norepinephrine and DHPG. These data suggest that benzodiazepines attenuate metabolic stress-induced activation of the pituitary-adrenal and adrenomedullary systems but do not effect 2DG-related effects on peripheral sympathoneural function. The possible mechanisms involved are discussed.

Adrenocorticotropic Hormone↗
PubMed1992

Brain morphology and schizophrenia. A magnetic resonance imaging study of limbic, prefrontal cortex, and caudate structures.

We used magnetic resonance imaging to examine the morphologic characteristics of the amygdala/hippocampus, prefrontal cortex, and caudate nucleus in 29 healthy volunteers matched for age, gender, and head of household socioeconomic status and 44 patients with chronic schizophrenia. Total volumes of these structures were determined from 3-mm contiguous coronal sections. Schizophrenic patients, compared with healthy controls, had significantly smaller right and left amygdala/hippocampal complex volumes, smaller right and left prefrontal volumes, and larger left caudate volumes. A secondary analysis revealed reductions in the right and left amygdala and the left hippocampus. In addition, prefrontal white matter, but not gray matter, was reduced in the schizophrenic patients. Moreover, the right white matter volume in schizophrenic patients was significantly related to right amygdala/hippocampal volume (r = .39), data that provide preliminary support for a hypothesis of abnormal limbic-cortical connection in schizophrenia. We studied the implications of these data for the pathophysiology of schizophrenia.

Adult↗
PubMed1992

Plasma levels of catecholamines and corticotrophin during acute glucopenia induced by 2-deoxy-D-glucose in normal man.

Acute cellular glucopenia after 2-deoxy-D-glucose administration profoundly stimulates hypothalamic-pituitary-adrenocortical and adrenomedullary activity. Whether glucopenia stimulates sympathoneural release of noradrenaline is unclear. We studied 20 healthy subjects who received 2-deoxy-D-glucose (50 mg/kg in 100 ml isotonic saline) or isotonic saline (100 ml) i.v. for 30 min on each of 2 test days. Heart rate and blood pressure were measured with antecubital venous blood obtained via an indwelling catheter for assays of plasma catecholamines (noradrenaline; adrenaline; dihydroxyphenylalanine; dihydroxyphenylglycol; and dihydroxyphenylacetic acid), corticotrophin, cortisol, and glucose. 2-deoxy-D-glucose decreased diastolic blood pressure by 20% (from 69 +/- 2 to 55 +/- 2 mmHg) and increased adrenaline levels by 30-fold [21 +/- 6 (SEM) to 634 +/- 73 pg/ml], corticotrophin by sevenfold (5.1 +/- 1.2 to 35.8 +/- 4.9 pg/ml), glucose and cortisol by two-fold (82 +/- 5 to 163 +/- 9 mg/dl and 15 +/- 2 to 31 +/- 2 micrograms/dl), and noradrenaline by about 30% (224 +/- 15 to 295 +/- 24 pg/ml, p < 0.05), whereas plasma dihydroxyphenylglycol levels decreased (765 +/- 56 to 628 +/- 42 pg/ml). Small decreases in dihydroxyphenylalanine and dihydroxyphenylacetic acid levels after 2-deoxy-D-glucose did not differ from those after saline. Responses of adrenaline levels were positively correlated with those of noradrenaline (r = 0.47, p < 0.05) and glucose (r = 0.45, p = 0.06), but not of corticotrophin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1992

Anxiogenic properties of yohimbine. I. Behavioral, physiological and biochemical measures.

The anxiogenic effects of yohimbine, a specific alpha-2-receptor antagonist were examined by administering 20 mg yohimbine orally to 8 panic patients on placebo treatment, 7 panic patients on alprazolam treatment and 12 controls using a double-blind randomized design, instructions that minimized the expectancy of experiencing a panic attack and two additional structured situations. Yohimbine induced more pronounced increases in anxiety and panicky ratings, norepinephrine secretion, maximum heart rate and high heart rate variability and decreases in skin temperature in panic patients compared with controls. However, possibly owing to an instructional set and experimental design that distracted patients from unpleasant bodily sensations no panic attacks were observed.

Adult↗
PubMed1992

Anxiogenic properties of yohimbine. II. Influence of experimental set and setting.

To study the pharmacological induction of stress along with psychological stress and their possible interaction, 20 mg yohimbine and placebo orally were administered to 8 panic patients on placebo treatment, 7 panic patients on alprazolam treatment and 12 controls in a double-blind crossover design. Two structured situations which can be considered as 'neutral' stressors were included: a mental arithmetic task and a continuous performance task. Mental arithmetic induced robust increases in ratings of panicky, anxiety, nervousness, heart rate and electrodermal activity, while the continuous performance task induced increases exclusively in skin conductance reaction. Patients responded to these tasks less than controls with regard to subjective ratings and electrodermal activity. Yohimbine did not potentiate the response to the tasks in the patients. In controls, heart rate during the mental arithmetic task, but not during rest, was increased after yohimbine. In contrast to other yohimbine challenge studies no panic attacks were observed. It is hypothesized that the experimental design together with an instructional set that reduces expectancy factors and the inclusion of structured and time-limited tasks in a challenge paradigm is able to reduce the anxiogenic effects of yohimbine.

Adaptation, Psychological↗
PubMed1992

The effects of metabolic stress on plasma progesterone in healthy volunteers and schizophrenic patients.

A number of preclinical studies suggest that progesterone may play an important role in the stress response, however, the effects of stress on progesterone in humans has not been established. Also, several lines of evidence indicate that schizophrenia may be associated with abnormal neurobiological responses to stress, but the effects of stress on progesterone in schizophrenia has not been investigated. The purpose of the present study was to examine the effects of stress on plasma progesterone and cortisol in healthy subjects and to determine if schizophrenic patients have altered stress-induced plasma progesterone levels compared to normal controls. Stress was induced through administration of 2-deoxyglucose (2DG), a glucose analog that impairs glucose metabolism resulting in a clinical state comparable to hypoglycemia. There were significant increases in plasma progesterone and cortisol levels following 2DG-induced glucoprivic stress in healthy controls. There was no relationship between stress related progesterone and cortisol elevations. Schizophrenic patients, in comparison to controls, had significantly greater 2DG-induced elevations in progesterone levels but no differences in stress-related cortisol levels. There was evidence that basal progesterone and cortisol levels were elevated in the schizophrenic patients. The implications of these data are discussed.

Adaptation, Physiological↗
PubMed1992

[Multidrug resistance and the P-glycoprotein].

A survey is presented on the information concerning the nature and molecular mechanism of multi drug resistance, a phenomenon involving the resistance of tumor cells to different types of chemotherapeutic agents. P-glycoprotein is by its enzymatic activity directly responsible for expelling xenobiotics from the intracellular space and thus also for the development of MDR. Its detection provided new possibilities for causal studies of this type of resistance as well as for its in vitro modelling. In the presented survey, the function of P-glycoprotein is characterized also in cells of normal nontumorous tissue.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Adaptation of mouse leukemia cells L1210 to vincristine. Evidence for expression of P-glycoprotein.

A vincristine resistant cell line was obtained from mouse leukemia cells L1210 by long-term adaptation in a medium with stepwise increasing concentrations of vincristine. By Western blotting using monoclonal antibody C219, positive signal on the presence of P-glycoprotein was observed in the resistant cells. Moreover, hybridization of mRNA from vincristine resistant cells with radiolabeled MDR1 cDNA probe gave evidence about the expression of MDR1 gene. The observed resistance may be depressed by application of "chemosensitizers" such as (1) calcium entry blockers (verapamil and nifedipine); (2) neuroleptics (trifluorperasine) and (3) local anesthetics (lidocaine) directly to the grow medium. Any significant effect in O2 consumption as well as incorporation of [U-14C]-glucose by the sensitive or resistant cells was not detected in the absence of vincristine. Presence of vincristine induced increasing velocity of O2 consumption by resistant cells from 2.5 +/- 0.3 to 3.3 +/- 0.2 microliters/min.10(6) cells, and, on the other hand, decreasing O2 consumption by sensitive cells from 2.3 +/- 0.2 to 1.7 +/- 0.1 ml/min.10(6) cells. The presence of vincristine induced less potent decrease in glucose incorporation by resistant cells in comparison with values which were observed in sensitive cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Carbamazepine maintenance treatment in outpatient schizophrenics.

A double-blind crossover trial was used to evaluate carbamazepine as the sole maintenance treatment of chronic, nonmanic schizophrenic outpatients whose conditions had been stabilized with the use of neuroleptics prior to study. Criteria of treatment effectiveness included the number of patients relapsing and time to relapse over a 95-day neuroleptic-free period during which either carbamazepine or placebo was administered. Relapse was determined by the concordance of psychiatric ratings and independent clinical judgements indicating significant worsening. Results for 27 patients (13 receiving carbamazepine and 14 receiving placebo) involved in the first phase of this treatment comparison were nondifferentiating. Corroborating descriptive findings in the second phase were available for 14 of these patients. There was no evidence supporting the existence of a treatment-relevant subgroup defined by episodic dyscontrol phenomena.

Adult↗
PubMed1991

National Institute of Mental Health longitudinal study of chronic schizophrenia. Prognosis and predictors of outcome.

We performed a longitudinal study of chronic schizophrenic patients who were hospitalized for research purposes at the National Institute of Mental Health (NIMH) Intramural Program in the 1970s and early 1980s. We assessed present course, outcome and predictor data from the initial cohort of 58 young chronic schizophrenic patients who were followed up for 2 to 12 years following their NIMH index hospitalization. At follow-up, the sample showed substantial functional impairment and levels of symptoms with only about 20% of the sample demonstrating a good outcome. In addition, strong intercorrelation was noted among the symptom and functioning indexes at follow-up. Moreover, neuropsychologic tests of frontal cortical functioning were significantly correlated with outcome levels of negative symptoms and social functioning but not with levels of positive symptoms. During the period from the index hospitalization to the follow-up assessment, 78% of the sample suffered a relapse, 38% attempted suicide and 24% had episodes of major affective illness. Furthermore, levels of positive and negative symptoms ascertained when patients received optimal neuroleptic treatment during the index hospitalization significantly predicted outcome levels of symptoms and functioning and time spent hospitalized during the follow-up period. In contrast, levels of index positive and negative symptoms ascertained during the drug-free state did not predict outcome symptoms or functioning. These data suggest that treatment response is a critical predictor variable. We examined the implication of these data for the course of illness in schizophrenics.

Adult↗
PubMed1991

Alprazolam attenuates metabolic stress-induced neuroendocrine and behavioral effects in humans.

The effects of benzodiazepine drugs and the role of their recognition site, the GABAA/benzodiazepine receptor, in acute glucoprivic stress are not known. In the present study, the effects of acute glucoprivation were examined in ten healthy human subjects. Glucoprivation was induced by infusion of the glucose analog, 2-deoxyglucose (2DG), at doses sufficient (50 mg/kg) to competitively inhibit glucose metabolism. In addition, the effects of the triazolobenzodiazepine alprazolam (1.5 mg) on the 2DG-induced stress response was assessed. 2DG produced significant elevations in plasma cortisol (P = 0.0001) and glucose (P = 0.0003) levels. Alprazolam pretreatment attenuated the 2DG-related cortisol elevations (P = 0.05) but did not effect 2DG-induced glucose increases. In addition, 2DG caused significant increases in hunger (P = 0.01) and thirst (P = 0.001), and alprazolam significantly blunted both of these responses. Lastly, 2DG had significant effects on heart rate, diastolic blood pressure and body temperature (P less than 0.05). Alprazolam did not effect these physiologic indices. The significance of these data for the mechanisms involved in acute glucoprivic stress are examined and the implications of the data for the pathophysiology of affective illness and eating disorders are discussed.

Adult↗