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Biomedical subjects

D T George

Publications and source records attributed to D T George.

At least 19 recordsLinked to original sources
PubMed2001

Serotonin, testosterone and alcohol in the etiology of domestic violence.

In a previous study we administered the panicogenic agent sodium lactate to a select group of perpetrators of domestic violence and comparison groups. Results of that study showed that perpetrators exhibited exaggerated lactate-induced fear, panic and rage. In this current study, we compared the cerebral spinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and testosterone obtained from perpetrators of domestic violence and a group of healthy comparison subjects. All subjects were assessed for DSM-III-R diagnoses. Perpetrators with alcohol dependence (DV-ALC) (n=13), perpetrators without alcohol dependence (DV-NALC) (n=10) and healthy comparison subjects (HCS) (n=20) were clinically assessed using the Spielberger Trait Anxiety, Brown-Goodwin Aggression Scale, Buss Durkee Hostility Inventory and Straus Conflict Tactics. Following an overnight fast and bed rest, subjects received a lumbar puncture to obtain CSF concentrations of 5-HIAA and testosterone. Perpetrators scored significantly higher on measures of aggression than HCS. DV-NALC had significantly lower concentrations of CSF 5-HIAA and higher Straus Conflict Tactics (CT) physical violence scores than DV-ALC and HCS. DV-ALC had significantly higher concentrations of CSF testosterone than DV-NALC. DV-ALC also had significantly higher Straus CT physical violence scores than HCS. DV-NALC and DV-ALC differed on 5-HIAA concentrations, testosterone concentrations, Straus CT physical violence scores and alcohol dependence. These results suggest that DV-NALC and DV-ALC groups could have different biological mechanisms mediating domestic violence.

Adult↗
PubMed2001

The time-course of electrocardiographic interbeat interval dynamics in alcoholic subjects after short-term abstinence.

Alcohol dependence has been correlated with decreases in heart rate variability. However, the time course of recovery of heart rate variability after cessation of alcohol consumption is unknown. We used electrocardiogram (ECG) data serially obtained from a population of detoxifying alcoholic subjects to determine the Hurst exponent of the ECG interbeat interval time series. Higher values of the Hurst exponent are associated with decreased heart rate variability when H< or =0.5. We tested a series of response-surface models relating the Hurst exponent (H) thus obtained to the following independent variables: the time interval T (days since last use of alcohol), A (age in years at time of admission), and gender. The best-fit model was: H(T)=(KA+H(m)T+H(f)T)/(1+T), F=5.2, P(F)</=0.01. Model parameters were: K=0.008+/-0.002 (mean+/-SEM); asymptotic H-values for males and females: H(m)=0.24+/-0.02 and H(f)=0.16+/-0.03, respectively, significantly different at P< or =0.05. Age was the strongest predictor of initial H-values in this alcoholic population sample.

Adult↗
PubMed2001

Increased coronary artery blood flow with aortomyoplasty in chronic heart failure.

BACKGROUND: We hypothesized that diastolic counter-pulsation using aortomyoplasty will increase coronary blood flow. METHODS: In dogs (n = 6, 20 to 25 kg), the left latissimus dorsi muscle was isolated, wrapped around the descending thoracic aorta, and conditioned by chronic electrical stimulation. Heart failure was induced by rapid ventricular pacing. In a terminal study, left ventricular and aortic pressures, and blood flow in the left anterior descending coronary artery and descending aorta were measured. The endocardial-viability ratio was calculated. RESULTS: Aortomyoplasty increased mean diastolic aortic pressure (70 +/- 5 to 75 +/- 5 mm Hg, p < 0.05) and reduced peak left ventricular pressure (86 +/- 4 to 84 +/- 4 mm Hg, p < 0.05), leading to a 16% increase in endocardial-viability ratio (1.29 +/- 0.05 to 1.49 +/- 0.05, p < 0.05). Coronary blood flow was increased by 15% (8.2 +/- 1.5 to 9.4 +/- 1.6 mL/min, p < 0.05). During muscle contraction, 2.7 +/- 0.5 mL was ejected from the wrapped aortic segment. CONCLUSIONS: These data demonstrate that aortomyoplasty provides successful diastolic counterpulsation after muscle conditioning and heart failure.

Animals↗
PubMed2000

Lactate-induced rage and panic in a select group of subjects who perpetrate acts of domestic violence.

BACKGROUND: Perpetrators of domestic violence frequently report symptoms of autonomic arousal and a sense of fear and/or loss of control at the time of the violence. Since many of these symptoms are also associated with panic attacks, we hypothesized that perpetrators of domestic violence and patients with panic attacks may share similar exaggerated fear-related behaviors. To test this hypothesis, we employed the panicogenic agent sodium lactate to examine the response of perpetrators to anxiety fear induced by a chemical agent. METHODS: Using a double-blind, placebo-controlled design, we infused 0.5 mol/L sodium lactate or placebo over 20 min on separate days to a select group of subjects who perpetrate acts of domestic violence and two nonviolent comparison groups. We compared their behavioral, neuroendocrine, and physiologic responses. RESULTS: Lactate administration elicited intense emotional responses in the perpetrators of domestic violence. Perpetrators evidenced more lactate-induced rage and panic and showed greater changes in speech, breathing, and motor activity than did nonviolent control subjects. There were no significant differences between the groups for any neuroendocrine or physiologic measure. CONCLUSIONS: These results are consistent with our hypothesis that some perpetrators of domestic violence have exaggerated fear-related behavioral responses.

Adult↗
PubMed2000

Plasma total cholesterol concentrations do not predict cerebrospinal fluid neurotransmitter metabolites: implications for the biophysical role of highly unsaturated fatty acids.

Low concentrations of a metabolite of serotonin found in cerebrospinal fluid (CSF), 5-hydroxyindolacetic acid (5-HIAA), are strongly associated with suicidal and violent behaviors. Although lowering of plasma total cholesterol has been suggested to increase mortality from suicide and violence by decreasing concentrations of CSF 5-HIAA via changes in membrane biophysical properties, highly unsaturated fatty acids may play a more important role. Violent and nonviolent comparison groups, early- and late-onset alcoholics, and healthy comparison subjects were studied to control for alcohol use and predisposition to violence. Fasting plasma total cholesterol and CSF were assayed under stringently controlled conditions. When all groups were combined (n = 234), plasma cholesterol concentrations had a weak positive correlation with CSF 5-HIAA (r = 0.18, P < 0.01). However, age correlated with both plasma total cholesterol and CSF 5-HIAA concentrations. When age was included in multiple regression models, the correlation between cholesterol and CSF 5-HIAA concentrations was not significant. Cholesterol correlated weakly with CSF 5-HIAA concentrations only in late-onset alcoholics after age was controlled for, but the relation was not significant after correction for multiple testing. CSF homovanillic acid did not correlate with plasma total cholesterol in any group. Plasma total cholesterol had no apparent relation to CSF neurotransmitter metabolites in any group of subjects. Highly unsaturated essential fatty acids, which are also critical determinants of membrane biophysical properties and may be linked to brain serotonin concentrations, should also be considered in studies examining the effect of lowering fat intake on the incidence of suicide and violence.

Adult↗
PubMed1999

Buspirone treatment of alcoholism: age of onset, and cerebrospinal fluid 5-hydroxyindolacetic acid and homovanillic acid concentrations, but not medication treatment, predict return to drinking.

Disturbances in central nervous system serotonin (5-HT) have been implicated in the pathophysiology of alcoholism. To test the hypothesis that increasing 5-HT function could promote treatment compliance, we randomized patients who had completed a 5-week inpatient treatment program for alcoholism to receive either buspirone or placebo for 1 year. Ten of the 49 patients remained in the study for the entire year. The days to relapse did not differ significantly between patients receiving buspirone or placebo. Regardless of the medication, late-onset alcoholics had a longer time to relapse than early-onset alcoholics. Cerebrospinal fluid showed that patients with high concentrations of both the 5-HT metabolite, 5-hydroxyindoleacetic acid, and the dopamine metabolite, homovanillic acid, were more likely to relapse, compared with patients with low concentrations of cerebrospinal fluid 5-hydroxyindoleacetic acid and homovanillic acid.

Adult↗
PubMed1998

Essential fatty acids predict metabolites of serotonin and dopamine in cerebrospinal fluid among healthy control subjects, and early- and late-onset alcoholics.

BACKGROUND: Impulsive violence, suicide, and depression are strongly associated with low concentrations of cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA). Increased suicide and trauma reported in some cholesterol-lowering trials may be related to altered concentrations of polyunsaturated fatty acids rather than cholesterol, a possible surrogate marker. METHODS: CSF 5-HIAA and homovanillic acid (HVA), total cholesterol, and plasma fatty acid concentrations were examined in 176 subjects, including 49 healthy volunteers, and 88 early- and 39 late-onset alcoholics. RESULTS: Among each group, polyunsaturated fatty acids predicted both CSF 5-HIAA and CSF HVA concentrations, but total cholesterol was unrelated to either neurotransmitter metabolite. The relationships between plasma 22: 6n3 and CSF 5-HIAA were significantly different when healthy volunteers (r = .35) were compared to early-onset alcoholics (r = -.38) (p < .0002). CONCLUSIONS: Dietary studies are indicated to determine if essential fatty acid supplementation can influence central nervous system serotonin and dopamine metabolism and modify impulsive behaviors related to these neurotransmitters.

Adult↗
PubMed1998

A replication study of violent and nonviolent subjects: cerebrospinal fluid metabolites of serotonin and dopamine are predicted by plasma essential fatty acids.

BACKGROUND: Among an independent group of subjects selected for their history of violent, impulsive behaviors and nonviolent control subjects, we attempted to replicate the finding that plasma docosahexaenoic acid concentrations were negatively correlated with cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA) concentrations. METHODS: CSF 5-HIAA and homovanillic acid (HVA), fasting total cholesterol, and plasma fatty acid concentrations were examined in violent and nonviolent subjects matched for their severity of alcohol dependence. RESULTS: Violent subjects had significantly higher lifetime violence and hostility ratings and lower concentrations of CSF 5-HIAA than nonviolent subjects. Plasma docosahexaenoic acid was negatively correlated with CSF 5-HIAA only among violent subjects. CONCLUSIONS: This observational study suggests that dietary essential fatty acids may change neurotransmitter concentrations. Prospective dietary intervention trials will be required to determine if increasing dietary intake of docosahexaenoic acid will increase or decrease either CSF 5-HIAA concentrations or impulsive and violent behaviors.

Adult↗
PubMed1998

Triazolam-induced changes in alcoholic thought processes.

This study was designed to examine and contrast cognitive effects (explicit memory and access to semantic knowledge) of the benzodiazepine Halcion (triazolam) in ten normal volunteers and ten cognitively un-impaired detoxified alcoholics. The two groups were indistinguishable from one another under placebo conditions on all measures of cognitive functioning. Under Halcion test conditions (0.375 mg p.o.), both groups were about equally impaired in their recall of to-be-remembered information. However, alcoholics, were more likely to recall information that they were not asked to remember (intrusion errors) on all measures of explicit remembering. Alcoholics also generated relatively uncommon (low frequency) responses from semantic memory, rather than common, categorically related associations in response to stimuli such as types of vegetables, flowers, and fruit following the administration of Halcion, but were not different from normal volunteers in the types of responses generated under placebo conditions. These findings suggest that a drug challenge that simulates many of the effects of acute alcohol administration induces alcoholics to think and remember differently (qualitatively) from normal volunteers.

Adult↗
PubMed1998

A versatile microprocessor-based multichannel stimulator for skeletal muscle cardiac assist.

A versatile, microprocessor-based stimulator for skeletal muscle cardiac assist (SMCA) has been designed, constructed, and used in several studies. The stimulator uses multiple bipolar electrodes to deliver arbitrarily specified electrical stimulus sequences to three nerve branches of the latissimus dorsi muscle. The electrodes are electrically isolated to effect regional stimulation of the muscle. The width, amplitude, and interpulse interval of each pulse in the stimulus sequence are independently variable, and the three channels are independently programmable, allowing a wide variety of stimulus patterns. Battery powered units have been used in studies for up to one year. In this paper, the stimulator and sample applications in SMCA are described.

Analog-Digital Conversion↗
PubMed1997

Effect of alcoholism on the incidence of lactate-induced panic attacks.

BACKGROUND: Chronic alcohol use is associated with higher than expected rates of panic disorder. METHODS: To study the relationship between alcoholism and panic disorder, we administered the panicogenic agent, sodium lactate, to 26 alcoholics with either panic disorder or frequent panic attacks (ALCPAN), 20 nonalcoholics with panic disorder (PAN), 14 alcoholics without a history of panic attacks, and 14 healthy volunteers. RESULTS: PAN were significantly more likely to have a lactate-induced panic attack (65%) than ALCPAN (23%). ALCPAN who had the onset of panic attacks prior to alcoholism also had a reduced frequency of lactate-induced panic attacks (26.7%) compared to PAN. CONCLUSIONS: There is a reduced incidence of lactate-induced panic attacks in ALCPAN. This reduction does not appear to be explained by the relative onset of panic attacks to alcoholism. The role of excessive alcohol consumption in the decreased frequency of lactate-induced panic attacks seen in ALCPAN needs further study.

Adult↗
PubMed1997

Beta-adrenoreceptor coupling to GS protein in alcohol dependence, panic disorder, and patients with both conditions.

Ethanol may downregulate G-protein-coupled beta-adrenoreceptors (beta AR). beta AR may also be dysregulated in panic disorder (PD). In clinical samples, many patients have comorbid alcohol dependence (AD) and PD. Therefore, we investigated beta AR coupling in patients with these disorders. We harvested polymorphonuclear leukocytes from 24 healthy volunteers (Vs), and from 22 abstinent AD patients, 7 PD patients, and 9 patients with comorbid AD/PD. beta AR were assayed using saturation and agonist-displacement experiments. Group differences were tested using one-way analysis of variance (ANOVA). All beta AR binding parameters were similar in AD patients and Vs. The ratio of the agonists' dissociation constant from the receptor in the low affinity state (KL) to that in the high affinity state (KH) was significantly higher in PD patients than in AD patients and Vs (930.97 +/- 440.80 vs. 226.2 +/- 94.47 vs. 197.05 +/- 61.03, respectively, p < .01). This finding suggests that beta AR are supercoupled to GS in patients with PD. There was a trend for higher total receptor density (RT) in AD/PD and PD patients (Vs = 39.06 +/- 42.57 vs. AD = 27.93 +/- 23.07 vs. AD/PD = 66.85 +/- 79.02 vs. PD = 68.36 +/- 49.20, p < .08). There were no differences between AD/PD and PD patients, who combined had a significantly higher RT than Vs and AD patients (Vs = 38.95 +/- 8.81 vs. AD = 29.63 +/- 5.07 vs. AD/PD = 67.51 +/- 17.00, fmol/mg protein, p < .04). Finally, AD/PD patients had a significantly higher receptor density in the low-affinity conformational state than Vs and AD patients, but not PD patients (25.96 +/- 11.59 vs. 10.69 +/- 1.53 vs. 7.62 +/- 1.08 vs. 17.07 +/- 5.26 fmol/mg protein, respectively, p < .005). beta AR function in polymorphonuclear leukocytes is normal in abstinent alcoholics. The previously reported abnormal beta AR regulation in alcoholism may be state dependent. The higher RT and KL/KH ratio in AD/PD and PD, but not in AD patients, suggest that increased beta AR function may be important in the pathophysiology of PD.

Adrenergic beta-Agonists↗
PubMed1997

Effects of triazolam and ethanol on proactive interference: evidence for an impairment in retrieval inhibition.

The effects of two memory-impairing drugs, ethanol and triazolam, on proactive interference (PI) in memory were studied. Following ingestion of either one of these drugs or a placebo, subjects studied an A-B list (e.g., BEE-WASP) of paired associates, followed by an A-C list (e.g., BEE-HONEY) on the interference trial, and a D-E list (e.g., KING-QUEEN) followed by an A-C list on the control trial. A PI effect was found in the data, such that subjects produced fewer correct second list targets on the interference trial than on the control trial. Neither ethanol nor triazolam was found to influence the size of the PI effect. However, both drugs were found to increase B intrusions on the test of the A-C list, to impair subjects' ability to produce more than one studied response for each cue word, and to impair the subjective experience of retrieved memory information. These data suggest that ethanol and triazolam impair an inhibitory process that normally operates as one component of intentional retrieval, playing an important role in the suppression of unwanted information during a memory task.

Adult↗
PubMed1997

Variable-frequency train stimulation of canine latissimus dorsi muscle during shortening contractions.

In cardiomyoplasty, the latissimus dorsi muscle (LDM) is wrapped around the heart ventricles and electrically activated with a constant-frequency train (CFT). This study tested the hypotheses that increased mechanical performance from the LDM could be achieved by activating the muscle with variable-frequency trains (VFTs) of shorter duration or containing fewer stimulus pulses than the CFT now used. The mechanical performance of the canine LDM (n = 7) during shortening contractions was measured while the muscle was stimulated with 5- and 6-pulse CFTs (of duration 132 and 165 ms, respectively) and 5- and 6-pulse VFTs (of duration 104 and 143 ms, respectively) that were designed to take advantage of the catchlike property of skeletal muscle. Measurements were made from fresh and fatigued muscles. For the fresh muscles, the VFTs elicited significantly greater peak power than did the 6-pulse CFT. When the muscles were fatigued, VFT stimulation significantly improved both the peak and mean power produced compared with stimulation by CFTs. These results show that stimulation of the LDM with shorter duration VFTs is potentially useful for application in cardiomyoplasty.

Animals↗
PubMed1997

Behavioral and neuroendocrine responses to m-chlorophenylpiperazine in subtypes of alcoholics and in healthy comparison subjects.

OBJECTIVE: The purpose of this study was to explore central serotonergic functions in subgroups of alcoholics and in healthy comparison subjects. METHOD: The mixed serotonin (5-HT) agonist/antagonist m-chlorophenylpiperazine (m-CPP) was administered to male alcoholic patients who were classified according to the criteria of von Knorring et al. as type I alcoholics (late onset) (N = 16) or type II alcoholics (early onset with antisocial traits) (N = 24) and to 22 healthy comparison subjects. Psychological, physiological, and neuroendocrine measures were obtained before and after the m-CPP infusion. RESULTS: m-CPP elicited subtype-related differential effects among the alcoholics; the type I alcoholics reported more anger and anxiety, and the type II alcoholics reported increased euphoria and a greater likelihood of drinking. The healthy comparison subjects exhibited a greater increase in plasma ACTH response to the m-CPP infusion than the alcoholics regardless of subtype. CONCLUSIONS: Differences in certain 5-HT receptor functions may explain some of the clinical characteristics that differentiate the type II and type I subgroups of alcoholic patients. Furthermore, alcoholics may have reduced sensitivity of 5-HT2C receptors in comparison with healthy subjects.

Adrenocorticotropic Hormone↗
PubMed1997

Optimizing muscle-to-cardiac timing for aortomyoplasty.

A new surgical approach to support failing hearts is known as aortomyoplasty-a technique in which the latissimus dorsi muscle is wrapped around the aorta and stimulated during cardiac diastole to provide chronic diastolic counterpulsation. We hypothesized that the timing of muscle contraction within the cardiac cycle effects the amount of diastolic augmentation during counterpulsation. In dogs (n = 9, 20-25 kg), the effect of muscle-to-cardiac timing on hemodynamic outcome of aortomyoplasty was measured. Muscle stimulation was initiated at the dicrotic notch and stimulus durations were systematically increased. Mean diastolic aortic pressure was maximized when stimulation terminated at the ensuing R-wave. Peak left-ventricular pressure was minimized when muscle stimulation terminated before the ensuing R-wave. The endocardial-viability ratio (a ratio of aortic diastolic pressure augmentation to left-ventricular pressure reduction) was maximized when stimulus terminated at the ensuing R-wave. Muscle-to-cardiac timing influences the effectiveness of counterpulsation during aortomyoplasty.

Animals↗
PubMed1996

Early-onset alcoholics have lower cerebrospinal fluid 5-hydroxyindoleacetic acid levels than late-onset alcoholics.

BACKGROUND: We investigated the interrelationships of age at onset of excessive alcohol consumption, family history of alcoholism, psychiatric comorbidity, and cerebrospinal fluid monoamine metabolite concentrations in abstinent, treatment-seeking alcoholics. METHODS: We studied 131 recently abstinent alcoholics. Supervised abstinence was maintained on a research ward at the National Institutes of Health Clinical Center for a minimum of 3 weeks. All alcoholics received a low-monoamine diet for a minimum of 3 days before lumbar puncture. Lumbar punctures were performed in the morning after an overnight fast. Monamine metabolites and tryptophan in cerebrospinal fluid were quantified with liquid chromatography by means of electrochemical detection. Psychiatric diagnoses were established from blind-rated Schedule for Affective Disorders and Schizophrenia-Lifetime version interviews administered by a research social worker. Severity and age at onset of excessive alcohol consumption were documented with a structured lifetime drinking history questionnaire and with selected alcoholism screening questionnaires (CAGE and Michigan Alcoholism Screening Test). Family history of alcoholism was obtained from the probands. RESULTS: A majority of the treatment-seeking, primarily white male alcoholics had a lifetime history of psychiatric disorders other than alcoholism. None fulfilled criteria for antisocial personality disorder. Early-onset alcoholics (onset of excessive consumption before 25 years of age) had a more severe course of alcoholism and lower mean cerebrospinal fluid 5-hydroxyindoleacetic acid concentration than late-onset alcoholics. Patients who reported both parents to be alcoholics had particularly low mean cerebrospinal fluid 5-hydroxyindoleacetic acid, homovanillic acid, and tryptophan concentrations. CONCLUSION: Among treatment-seeking alcoholics, early age at onset is generally associated with a more severe course of alcoholism and lower cerebrospinal fluid 5-hydroxyindoleacetic acid concentration.

Adult↗