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Biomedical subjects

S Gabriel

Publications and source records attributed to S Gabriel.

At least 55 records · Page 3Linked to original sources

Hostility is associated with a heightened prolactin response to meta-chlorophenylpiperazine in abstinent cocaine addicts.

The prolactin (PRL) response to the administration of serotonin (5HT) agonists is an index of central nervous system 5HT activity. This index is blunted in association with hostile aggression in personality and depressive disorder patients without substance abuse. We tested whether the PRL response to the oral administration of the partial 5HT agonist meta-chlorophenylpiperazine (MCPP), 0.35 mg/kg, was associated with a measure of trait hostility, the Buss Durkee Hostility Inventory (BDHI), in cocaine addicts who were completing a 3-week detoxification and rehabilitation program. We also tested whether the cocaine addicts differed from healthy volunteers on their PRL, cortisol (CORT) or temperature responses to MCPP. The PRL response to MCPP was positively associated with the total score on the BDHI. There were, however, no differences in the neuroendocrine or temperature responses to MCPP between the cocaine-dependent group and the healthy volunteers once age effects were controlled for.

Adult↗

Effects of barium on stimulus-induced changes in [K+]o and field potentials in dentate gyrus and area CA1 of human epileptic hippocampus.

The effects of barium on stimulus-induced rises in [K+]o were studied in the dentate gyrus (DG) and area CA1 of human hippocampal slices. Rises in [K+]o elicited by repetitive stimulation of the hilus, stratum moleculare, alveus, or stratum radiatum were dependent on stimulus intensity and frequency. Barium augmented rises in [K+]o in the DG by about 120% but failed to do so in area CA1. In both DG and area CA1 barium had no effects on population spikes whereas stimulus-induced slow field potentials were reduced. Since barium interferes with K+ uptake and redistribution by blocking leak conductances and inwardly-rectifying currents in astrocytes, our findings suggest that glial cells in the sclerotic hippocampal area CA1 may contribute less to K+ regulation.

Adult↗

Effects of barium on stimulus induced changes in extracellular potassium concentration in area CA1 of hippocampal slices from normal and pilocarpine-treated epileptic rats.

Laminar profiles of rises in [K+]o and slow field potentials induced by alvear stimulation were recorded in area CA1 of hippocampal slices from control and pilocarpine-treated rats in absence and presence of Ba2+. In control animals, Ba2+ augmented rises in [K+]o in stratum pyramidale (SP) as well as in stratum radiatum (SR). In pilocarpine-treated animals an augmentation of rises in [K+]o was restricted to SP and its immediate vicinity. Moreover, the effect of Ba2+ in SP was small or missing in eight out of 15 slices of pilocarpine-treated animals. In these slices laminar profiles of rises in [K+]o were not affected by Ba2+. It is suggested that spatial K+-buffering is reduced in area CA1 of epileptic animals.

Animals↗

Cost-effectiveness of ultrasound-guided liver biopsy.

The risk of a major complication from "blind" percutaneous liver biopsy is reported to be in the range of 0.24% to 3.8%. In a recent randomized trial, patients whose liver biopsies were performed with ultrasonography had a significant reduction in complications requiring hospitalization compared with patients without ultrasound-guided biopsies (0.5% vs. 2.2%, P < .05). Despite this, routine use of ultrasonography for liver biopsies has not been implemented because of controversies with respect to cost-effectiveness. The aim of our study was to analyze the relative cost-effectiveness of performing ultrasound-guided liver biopsies using decision analysis. A decision tree was constructed to compare a strategy of liver biopsy using ultrasonography with a strategy without ultrasonography. The major outcomes included were minor complications such as pain requiring analgesics and major complications, which require hospitalization. Costs included were direct medical costs from the payer's perspective. In our baseline model, the cost from complications per patient with and without ultrasonography was $62 and $129, respectively. The marginal effectiveness expressed as the number of major complications avoided was 1.2/100 liver biopsies. The incremental cost to avoid one major complication was $2,731. The model was most sensitive to the frequency of major complications and the additional cost of ultrasonography. Our decision analysis model suggests that ultrasound-guided liver biopsy is cost-effective. Future studies assessing the efficacy of image-guided liver biopsies should be conducted.

Biopsy, Needle↗

Serotonin function and risk for alcoholism in boys with attention-deficit hyperactivity disorder.

Data in animals and adults indicate that central serotonergic (5-HT) function may be involved in the development of alcohol abuse. Despite this, studies exploring this mechanism in individuals at risk for alcoholism are scant. This study used a fenfluramine (FEN) challenge procedure to investigate the relationship between risk for alcoholism and 5-HT function in 7- to 11-year-old boys with attention-deficit hyperactivity disorder (ADHD). The prolactin (PRL) and cortisol (CORT) responses to FEN were examined in 10 sons of alcoholic fathers (FA+) and 30 sons of nonalcoholic fathers (FA-). The FA+ group had a significantly greater CORT, but not PRL, response to FEN relative to the FA- group. The discrepancy between the CORT and PRL responses may be due to the different mechanisms that underlie their 5-HT stimulated release. This suggests that, among ADHD boys, those at familial risk for alcohol abuse may differ from those who are not at risk in 5-HT function.

Alcoholism↗

Age-related changes in the association between serotonergic function and aggression in boys with ADHD.

The results of several studies have indicated an inverse relationship between central serotonergic (5-HT) mechanisms and aggression in animals and adults, but studies in children have yielded conflicting results. This study assessed 5-HT function, using a fenfluramine (FEN) challenge procedure, in an attempt to replicate a previously reported enhancement of the prolactin (PRL) response to FEN in aggressive relative to nonaggressive ADHD boys. The study failed to replicate the previous finding. Samples from both studies were then examined to reconcile the discrepant findings. The samples differed significantly in age. The entire group (n = 50) was then divided into older and younger subgroups and reanalyzed using a two-way (age-group x aggression) analysis of covariance (ANCOVA) controlling for plasma medication level. The ANCOVA generated a significant age-group x aggression interaction. Young aggressive boys had a significantly greater PRL response to FEN than young nonaggressive boys, but no such difference existed in the older age-group. These findings raise the possibility of different developmental trajectories in 5-HT function between aggressive and nonaggressive boys.

Aggression↗

Bacterial translocation during portal clamping for liver resection. A clinical study.

OBJECTIVE: To determine the incidence and the clinical importance of gut-bacterial translocation after portal triad clamping for liver resection. DESIGN: Cohort study. SETTING: Multispecialty referral center. PATIENTS: Five cirrhotic and 10 noncirrhotic patients requiring liver resection. INTERVENTIONS: Elective liver resection under normothermic ischemic conditions (mean +/- SD duration, 40.2 +/- 13.1 minutes). Simultaneous sampling for qualitative culture of the systemic and portal blood, the upper gastrointestinal tract fluid, and a mesenteric lymph node (MLN) before and after liver resection. MAIN OUTCOME MEASURES: Positive culture rate, type of organism isolated, and septic complications rate. RESULTS: Before resection, blood cultures and MLNs were sterile in all but 1 patient; this culture-positive patient had had a recent colon resection for occlusive carcinoma and was excluded from further analysis. After resection, systemic and portal blood cultures were sterile in all cases. Conversely, the MNLs were culture positive in 6 (43%) of 14 patients. Coagulase-negative staphylococci were the most common isolates. A weak correlation was observed between the organisms isolated from the MLNs and those simultaneously present in the upper gastrointestinal tract fluid. There was no relationship between bacterial translocation and the outcome as patients with culture-positive MLNs showed no evidence of intraperitoneal septic complications and the only patient with a septic complication (a subphrenic abscess) had negative cultures after resection. CONCLUSION: A significant bacterial translocation in the MLNs occurs after portal triad clamping and liver resection, although not clinically relevant.

Adult↗

Plasma cortisol and aggression in boys with ADHD.

OBJECTIVE: The results of several studies suggest an inverse relationship between cortisol secretion and aggressive behavior. This study examined basal plasma cortisol levels in aggressive and nonaggressive boys with attention-deficit hyperactivity disorder (ADHD). METHOD: The subjects were 23 aggressive and 27 nonaggressive boys with ADHD, aged 7 to 11 years. After 3 days of a low monoamine diet and an overnight fast, an indwelling catheter was inserted into a forearm vein. Samples for plasma cortisol levels were obtained 105 and 115 minutes after insertion of the catheter. RESULTS: A one-way analysis of covariance (ANCOVA) controlling for body mass revealed no significant difference in plasma cortisol between the aggressive and nonaggressive boys. Furthermore, when the children were alternatively divided on the basis of the presence or absence of a DSM-III-R diagnosis of conduct disorder, a one-way ANCOVA again revealed no significant difference in cortisol levels. CONCLUSIONS: The hypothesized inverse relationship between cortisol secretion and aggressive behavior in boys with ADHD was not found. These findings are consistent with a large body of literature indicating that the biological substrate of aggression is complex and that the identification of biological laboratory markers of aggressive behavior is not a clinically useful strategy at this time.

Aggression↗

Distal extremity swelling with pitting edema in polymyalgia rheumatica. Report on nineteen cases.

OBJECTIVE: To determine the frequency and clinical characteristics of diffuse distal extremity swelling with pitting edema occurring in polymyalgia rheumatica (PMR). METHODS: Clinical features and laboratory findings were recorded for all 245 residents of Olmsted County, Minnesota who developed PMR over a 22-year period (1970-1991). Those who exhibited > or = 1 episode of diffuse distal extremity edema with pitting were selected for this study, and were evaluated further. RESULTS: Thirteen women and 6 men in this incidence cohort of PMR had > or = 1 episode of distal extremity swelling with pitting edema. Giant cell arteritis was also identified in 5 patients. In 11 patients, the swelling and edema development concurrently with proximal PMR symptoms. In 2 patients, the distal swelling was the initial manifestation, and in 6 patients, the distal symptoms developed during relapses or recurrences of PMR. Both upper and lower extremities were affected, usually in a symmetric manner. Other peripheral manifestations were also common. The distal swelling and pitting edema responded promptly to corticosteroids, and slowly or incompletely to nonsteroidal anti-inflammatory drugs; a similar response was observed in the proximal symptoms. The distal swelling appeared to represent tenosynovitis and synovitis of regional structures. CONCLUSION: Distal extremity swelling with pitting edema represents a manifestation of PMR that has not been well described in previous studies. Awareness of this finding will help facilitate the proper diagnosis and institution of appropriate therapy for this disease.

Adrenal Cortex Hormones↗

Effects of cholecystokinin on Y, X, and W cells in the dorsal lateral geniculate nucleus of rats.

The role of the cholecystokinergic input to the rat's dorsal lateral geniculate nucleus (dLGN) was studied by examining the effect of iontophoretically administered CCK-8S on the neuronal response to stimulation of the receptive field center. Peristimulus activity was recorded extracellularly from 108 neurons grouped according to the type of receptive field (OFF, ON, or ON-OFF) and classified with respect to their Y, X, or W properties by means of discriminant analysis. CCK affected the response to a center-sized spot of light in two thirds of the neurons investigated. The center response decreased in 50 of 73 CCK-sensitive neurons (69%), predominantly in Y OFF and X OFF center cells (17 of 19). In the remaining 23 cells the center response increased, most consistently (11 of 17) in W ON center cells. Center and surround responses were similarly influenced. Inhibitions and excitations induced by CCK-8S were reproducible, dose dependent, and receptor mediated. The CCKB antagonist PD 135158 reduced the CCK effects in 10 of 14 cells; the CCKA antagonist KL 1001 reduced the CCK effects in 17 of 36 cells. The CCK-induced inhibition was B-receptor specific in 4 of 8 cells, A-receptor specific in 2 of 8 cells, and partially mediated by each of the two types of receptor in the remaining 2 cells. Blocking by the CCKA antagonist was more frequently observed in W cells than in cells with Y or X characteristics. The data show that CCK modifies the activity of dLGN cells in a variable direction depending on the specific cell type (Y, X, W) and response pattern (OFF, ON). The effects of CCK are discussed in relation to proposed functions of the superior collicular input to the dLGN.

Animals↗

Interaction of cholecystokinin and glutamate agonists within the dLGN, the dentate gyrus, and the hippocampus.

The interaction of sulfated cholecystokinin (CCK-8S) with excitatory amino acids (EAA) was studied on single units of the dorsal lateral geniculate nucleus (dLGN), the dentate gyrus, and the hippocampal CA3 region in rats anaesthetized with urethane. lontophoretic co-administration of small, individually ineffective currents of CCK-8S and kainic acid or N-methyl-D-aspartate repeatedly elicited an increase of the discharge rate in nearly all geniculate and half of the dentate neurons but not in those of the CA3 region. The effect could be reduced by the CCKB receptor antagonist PD 135,158 more often than by the CCKA antagonist KL 1001. The increased firing due to co-administration of CCK and kainate could also be suppressed by the non-NMDA antagonist CNQX but not by the NMDA antagonists CPP or AP-5, which were otherwise able to prevent the neuron from responding to co-administration of CCK and NMDA. It is suggested that in distinct brain regions the effectivity of the "low level" EAA transmission may be enhanced by small amounts of CCK-8S. This is thought to be mediated by a coactivation of CCK and EEA receptors.

Animals↗

The dielectric properties of biological tissues: I. Literature survey.

The dielectric properties of tissues have been extracted from the literature of the past five decades and presented in a graphical format. The purpose is to assess the current state of knowledge, expose the gaps there are and provide a basis for the evaluation and analysis of corresponding data from an on-going measurement programme.

Adipose Tissue↗

The dielectric properties of biological tissues: II. Measurements in the frequency range 10 Hz to 20 GHz.

Three experimental techniques based on automatic swept-frequency network and impedance analysers were used to measure the dielectric properties of tissue in the frequency range 10 Hz to 20 GHz. The technique used in conjunction with the impedance analyser is described. Results are given for a number of human and animal tissues, at body temperature, across the frequency range, demonstrating that good agreement was achieved between measurements using the three pieces of equipment. Moreover, the measured values fall well within the body of corresponding literature data.

Adipose Tissue↗

The dielectric properties of biological tissues: III. Parametric models for the dielectric spectrum of tissues.

A parametric model was developed to describe the variation of dielectric properties of tissues as a function of frequency. The experimental spectrum from 10 Hz to 100 GHz was modelled with four dispersion regions. The development of the model was based on recently acquired data, complemented by data surveyed from the literature. The purpose is to enable the prediction of dielectric data that are in line with those contained in the vast body of literature on the subject. The analysis was carried out on a Microsoft Excel spreadsheet. Parameters are given for 17 tissue types.

Adipose Tissue↗

Hostility is associated with a low prolactin response to meta-chlorophenylpiperazine in abstinent alcoholics.

The prolactin response to the administration of serotonin agonists is an index of central nervous system serotonin (5HT) activity. This index is blunted in association with hostile aggression in personality-disordered individuals without substance abuse. We tested whether prolactin response to the partial 5HT agonist meta-chlorophenylpiperazine (MCPP) (0.35 mg/kg po) was associated with measures of trait hostility in alcoholics who were completing a 3-week rehabilitation program after medical detoxification. We also tested whether the same 5HT index differed in the group of alcoholics compared with the healthy volunteers. The prolactin response to MCPP was inversely associated with the main index of trait hostility and was similarly inversely associated with an index of depression. There was, however, no difference in neuroendocrine or temperature responses to MCPP between the alcohol-dependent group and the healthy volunteers.

Adult↗

Engineering, expression and renaturation of targeted TGF-beta fusion proteins.

This study reports the expression, purification, and renaturation of biologically active Transforming Growth Factor-beta 1 (TGF-beta 1) fusion proteins from Escherichia coli (E. coli). A prokaryotic expression vector was engineered to produce tripartite fusion proteins consisting of (i) a purification tag, (ii) a protease-sensitive linker/collagen binding domain, and (iii) a cDNA sequence encoding the active fragment of human TGF-beta 1. The expressed fusion proteins TGF-B1-F1 and TGF-B1-F2, located in inclusion bodies, were solubilized with 8 M urea and renatured using a glutathione redox-coupled system and protracted dialysis under several experimental conditions. The purification of the recombinant proteins was achieved by binding the His-tag of the fusion proteins on a Ni-NTA metal chelate column. The biological activity of the recombinant growth factor was demonstrated by its ability to inhibit mink lung (Mv1Lu) cell proliferation and/or to stimulate proliferation of NIH-3T3 mouse fibroblasts, where purified human platelet TGF-beta 1 served as a positive control. Purified TGF-B1-F1 and TGF-B1-F2 (collagen-binding) constructs exhibited anti-proliferative activities comparable to purified platelet TGF-beta 1, but at lower specific activities. Binding of the renatured TGF-B1-F2 fusion protein to collagen was demonstrated by stable binding on a collagen-conjugated Sephadex-G15 column. The high affinity binding was also demonstrated by the binding of 3H-collagen to the TGF-B1-F2 protein immobilized on a Ni-NTA column. The TGF-B1-F2 fusion protein bound to collagen coated surfaces with high affinity but exhibited comparatively lower biological activity than the fusion protein in solution, suggesting a potentially latent configuration. Taken together, these results demonstrate that biologically active TGF-beta 1 fusion proteins can be recovered from transformed bacteria by oxidative refolding; thus, providing a means for its high-yield production, purification, and renaturation from microorganisms. Furthermore, these results support the concept that auxiliary domains may be used to modulate and/or target TGF-beta 1 for specific applications.

3T3 Cells↗

Diurnal neuroendocrine and autonomic function in acute and remitted depressed male patients.

This study evaluated diurnal data gathered hourly (1000 to 1800 hours) in males during acute depression and during remission of depression and in age-range/gender-matched normal controls. Mean, peak, variability, and time-course of the noradrenergic metabolite, plasma 3-methoxy, 4-hydroxyphenylglycol [MHPG]), plasma cortisol, and autonomic (mean arterial blood pressure [MAP] and heart rate) variables were examined. Compared to controls, acutely depressed, but not remitted depressed, patients had 1) an earlier plasma MHPG peak, 2) a greater intragroup variability of plasma MHPG, 3) a higher plasma cortisol concentration, 4) a lower MAP, and 5) tended to increase MAP more slowly than did the normal controls. The time course of diurnal heart rate also differed in acutely depressed patients from controls: acutely depressed patients started higher and converged by midday to normal levels. These diurnal data lend limited support to the dysregulation hypotheses of depression that suggest normal circadian rhythmicities are altered or disrupted in acute depression and that peripheral manifestations of central dysregulation normalize in remission of depression.

Adult↗

Neurochemical correlates of dementia severity in Alzheimer's disease: relative importance of the cholinergic deficits.

Cholinergic markers, neuropeptides, and amines and their metabolites were sampled from identical specimens across 10 neocortical regions in a large sample of Alzheimer's disease (AD) cases and controls. Levels of choline acetyltransferase, acetylcholinesterase, somatostatin, corticotropin-releasing factor, serotonin, and 5-hydroxyindoleacetic acid were significantly reduced in AD versus controls. After data reduction, the most descriptive neurochemical indices were used to examine the relationship of neurochemical measures and dementia severity within the AD sample, controlling for age effects. Dementia severity ratings were based on antemortem assessments (46.9% of AD sample) and postmortem chart review (53.1% of the AD sample). Choline acetyltransferase activity was highly correlated with clinical dementia ratings across the neocortex of the AD cases. Somatostatin and corticotropin-releasing factor levels were correlated with dementia severity only when control cases were included in the analyses. None of the amines, their metabolites, or the neuropeptides quantified related significantly to dementia severity in the AD cohort. These data (a) confirm the strong association of cholinergic deficits with functional impairment in AD and show that this association is independent of age and (b) suggest that of all the neurochemical species quantified, the cholinergic indices may be unique in their association with dementia severity.

Aged↗