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Biomedical subjects

D T George

Publications and source records attributed to D T George.

At least 55 records · Page 3Linked to original sources
PubMed1990

Altered cerebrospinal fluid neuropeptide Y and peptide YY immunoreactivity in anorexia and bulimia nervosa.

The related central nervous system peptides neuropeptide Y and peptide YY have been found to be among the most potent endogenous stimulants of feeding behavior. We measured these neuropeptides in cerebrospinal fluid to determine whether they contributed to the pathophysiologic characteristics of anorexia and bulimia nervosa. Cerebrospinal fluid neuropeptide Y concentrations were significantly elevated in underweight anorectic patients and in many of the anorectic patients studied at intervals after weight restoration. These levels normalized in long-term weight-restored anorectic patients who had a return of normal menstrual cycles. Increased neuropeptide Y activity may contribute to several characteristic disturbances in anorexia, including menstrual dysregulation. Cerebrospinal fluid peptide YY concentrations were significantly elevated in normal-weight bulimic patients abstinent from pathological eating behavior for a month compared with themselves when actively bingeing and vomiting or compared with healthy volunteers. Increased peptide YY activity may contribute to a drive to overfeed in normal-weight bulimic patients.

Adult↗
PubMed1990

Altered norepinephrine regulation in bulimia: effects of pharmacological challenge with isoproterenol.

While abnormalities in central norepinephrine regulation may contribute to abnormal eating patterns in bulimia nervosa, alterations in function of the peripheral sympathetic nervous system could contribute to the decreased metabolic rate and increased anxiety responses previously reported in these patients. To assess beta-adrenergic receptor sensitivity in bulimic patients, we studied cardiovascular and hormonal responses to acute pharmacological challenge with intravenously administered isoproterenol. In comparison to healthy controls, binge-abstinent bulimic patients had significantly reduced mean baseline plasma norepinephrine level, pulse rate, and systolic blood pressure, and significantly increased chronotropic responses to isoproterenol infusion. Decreased sympathoneural activity may contribute to a tendency for bulimic patients to maintain body weight despite low caloric intake.

Adult↗
PubMed1990

Penetration of [3H]T-2 mycotoxin through abraded and intact skin and methods to decontaminate [3H]T-2 mycotoxin from abrasions.

Penetration of 50 muCi of [3H]T-2 mycotoxin through abraded and intact skin was studied in anesthetized rats sacrificed at 5, 15, 30, 45, 60 and 90 min post-exposure. The greatest penetration was through abraded skin (49 +/- 7%) at 90 min post-exposure, whereas penetration through intact skin (2 +/- 3%) was substantially less (P less than 0.0015). Methods to decontaminate [3H]T-2 mycotoxin from abraded skin over time were studied. Treatment of [3H]T-2 contaminated abrasions by applying Trau + Medic dressing, applying Charcoal Cloth-Anti-bacterial Field Dressing (Charcoal Dressing), or swabbing with povidone-iodine 30 min post-exposure removed 17-32% of the applied [3H]T-2. Immediate blotting with immediate removal of the dressings absorbed 103 +/- 4% (Trau + Medic) and 87 +/- 4% (Charcoal Dressing) of the applied [3H]T-2, while immediate blotting and leaving the dressing in place for 30 min removed 91 +/- 5% (Trau + Medic) and 76 +/- 3% (Charcoal Dressing). It appears that immediate blotting with either dressing followed by immediate removal before application of a clean dressing is an effective method for decontaminating [3H]T-2 from abrasions.

Adsorption↗
PubMed1990

A cerebrospinal fluid study of the pathophysiology of panic disorder associated with alcoholism.

In order to investigate the neurochemistry of panic disorder in alcoholics, we measured various cerebrospinal fluid (CSF) parameters in subjects with both conditions and compared them with an age- and sex-matched population of alcoholics and normal controls. When height, age and weight were covaried, subjects with panic disorder had higher levels of B-endorphin in CSF. There were no differences in other CSF measures between the groups. Alcoholics with panic disorder had higher plasma MHPG concentrations compared with alcoholics without panic disorder but these were not statistically different from controls.

Adult↗
PubMed1990

Cerebrospinal fluid monoamine metabolites in alcoholic patients who attempt suicide.

Reduced cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindoleacetic acid have been reported to be commonly associated with suicidal behaviour. Alcoholics are known to often manifest suicidal behaviour. Therefore, we compared cerebrospinal fluid levels of monoamine metabolites in alcoholics who had (n = 20) and had not (n = 108) attempted suicide and healthy volunteers (n = 30). There were no significant differences among the 3 groups for CSF levels of either 5-hydroxyindoleacetic acid, the dopamine metabolite homovanillic acid, norepinephrine, or the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol.

Adult↗
PubMed1990

Alcoholism and panic disorder: is the comorbidity more than coincidence?

Studies on alcoholic patients have found a higher than expected prevalence of panic disorder, and suggest a positive correlation between the level of alcohol consumption and severity of anxiety. Conversely, there is an increased prevalence of alcoholism among patients with panic disorder and their blood relatives. A comparison of symptoms, physiological and neurochemical changes known to occur in both alcohol withdrawal and panic disorder reveals a degree of similarity between the 2 conditions. Based on the data, we propose that the chemical and cognitive changes occurring as the result of repeated alcohol withdrawals may kindle and condition coincidence of panic attacks in susceptible individuals. Implications of our postulates for treatment of alcohol withdrawal and panic disorder in alcoholics and for future studies are discussed.

Alcoholism↗
PubMed1990

Isoproterenol infusion test in anorexia nervosa: assessment of pre- and post-beta-noradrenergic receptor activity.

Anorexia nervosa is associated with alterations in sympathetic activity and metabolism that persist during and after weight recovery. This study assessed beta-adrenergic receptor activity, an important modulator of vascular and metabolic function, in anorexic patients studied when underweight and at intervals during recovery, in comparison with healthy volunteer women. An increase in heart rate, in response to increasing doses of isoproterenol, served as an index of postsynaptic activity. Anorexic patients, during refeeding and weight gain, needed a significantly higher dose of isoproterenol to increase basal heart rate by 25 beats/minute, compared with underweight anorexic patients. Down-regulated postsynaptic cardiac beta-adrenoceptors during weight gain may protect against refeeding-induced exaggerated sympathetic activity. Because presynaptic beta-adrenoceptors serve as a positive feedback loop for synaptic catecholamine secretion, the increase in plasma norepinephrine concentrations during the isoproterenol infusion served as an index of presynaptic activity. We found that increasing doses of isoproterenol were associated with a linear increase in plasma norepinephrine in each healthy volunteer. In contrast, anorexic patients at any state had a significantly more erratic secretion of plasma norepinephrine in response to increasing doses of isoproterenol. Altered regulation of presynaptic adrenoceptors may explain, in part, the large variance and little consensus between previous studies as to whether anorexic patients have reduced or normal plasma norepinephrine levels.

Anorexia Nervosa↗
PubMed1989

The effect of bingeing and vomiting on hormonal secretion.

Women who are of normal weight and have bulimia nervosa have multiple neuroendocrine disturbances. The reasons for these neuroendocrine abnormalities are not known, but there are reasons to suspect that bingeing and vomiting behavior could be contributory. It is well known that food consumption in healthy volunteers increases plasma insulin, cortisol, and prolactin secretion and suppresses growth hormone secretion, whereas activation of the emetic reflex increases plasma arginine vasopressin (AVP) secretion. The purpose of this study was to investigate the effects of bingeing and vomiting on these hormones. In comparison with healthy control women consuming a large meal, bulimic patients, when bingeing and vomiting, had an exaggerated secretion of either the amount and/or the duration of insulin, cortisol, and prolactin. Vasopressin secretion was not increased during or after bingeing and vomiting, probably because bulimic subjects do not become nauseated. In addition, bulimic patients had significantly reduced baseline plasma prolactin and possibly elevated baseline cortisol compared with controls. In summary, this study supports the presence of neuroendocrine disturbances in bulimia and raises a question as to whether or not excessive and prolonged food consumption (and/or vomiting) are contributory.

Adult↗
PubMed1989

Central and peripheral ACTH and cortisol levels in anorexia nervosa and bulimia.

To explore the relationship of central and peripheral adrenocorticotropic hormone (ACTH, or corticotropin) levels to hypothalamo-pituitary-adrenal axis dysfunction in patients with eating disorders, levels of cerebrospinal fluid (CSF) and plasma ACTH, cortisol, and 24-hour urinary free cortisol were measured in 16 patients with anorexia nervosa (60% +/- 1.1% of ideal body weight), 14 patients with bulimia (93.2% +/- 4.6% of ideal body weight), and 11 healthy age-matched women volunteers. The CSF, plasma, and urinary free cortisol levels were elevated in underweight anorexic patients and showed declines following weight recovery. Cortisol-binding globulin levels were similar in anorexics and controls. In contrast, underweight anorexics showed low CSF ACTH levels that returned to normal following weight recovery, and their plasma ACTH levels were normal. On hospital admission, bulimic patients demonstrated normal ACTH and cortisol levels. After their abstinence from binge-purge episodes, the CSF ACTH levels decreased significantly. Positive relationships were found among CSF, plasma, and urinary cortisol levels, and inverse relationships were seen between cortisol measures and CSF ACTH levels in patients with eating disorders. Secretion of ACTH into the CSF may respond to feedback by cortisol or, alternatively, may be suppressed by the hypersecretion of corticotropin-releasing hormone, leading to the depletion of the pro-opiomelanocortin molecule.

Adolescent↗
PubMed1989

Lactate and hyperventilation substantially attenuate vagal tone in normal volunteers. A possible mechanism of panic provocation?

Many aspects of panic attacks, eg, palpitations, tremor, sweating, and an emotional sense of "fear," have been theorized to arise from sympathetic nervous system activation. However, most studies have not demonstrated clearly increased levels of catecholamines during an attack, which is contrary to this hypothesis. To explore another possible cause for the physiological changes known to occur during a panic attack, we assessed parasympathetic nervous system activity by measuring vagal tone during treatments known to produce panic symptoms: sodium lactate administration and hyperventilation. Our findings showed a marked reduction in vagal tone during both procedures. We postulate that withdrawal of parasympathetic activity may explain some of the physiological changes occurring in panic attacks and be contributing to the origin of panic.

Adult↗
PubMed1989

Decreased caloric intake in normal-weight patients with bulimia: comparison with female volunteers.

Patients with bulimia (binge-purge syndrome) frequently complain that they consume a very restrictive diet to avoid gaining weight. To investigate this claim, 23 hospitalized bulimic patients were assessed daily for body weight, caloric intake, macronutrient diet content, activity measures, and body composition estimates during weight-stable periods. Bulimic patients ate fewer kilocalories per kilogram body weight (22.1 +/- 4.6 kcal/kg) than did age-matched normal women (29.7 +/- 6.5 kcal/kg) but had similar activity levels and body composition. Clinical variables, such as history of laxative abuse, anorexia, or obesity, and physiological characteristics, such as body weight, activity level, or dietary content, could not account for this difference in caloric consumption. Bulimic patients tended to eat a diet lower in fat and higher in protein than did control subjects. These results agree with observations of increased efficiency of caloric utilization in obese patients and support patient complaints of a tendency to gain weight easily.

Adolescent↗
PubMed1989

Aggressive thoughts and behavior: another symptom of panic disorder?

We report on 3 individuals who describe aggressive thoughts and behaviors that frequently occurred in association with panic symptoms. It is theorized that the seemingly paradoxical emotions of fear and aggression may actually share a similar etiology. Of clinical interest, the subjects improved in both their panic and aggressive symptoms when they were treated with antidepressant medication.

Adult↗
PubMed1989

Panic response to lactate administration in alcoholic and nonalcoholic patients with panic disorder.

The authors administered lactate to 12 abstinent alcoholics with panic disorder, 10 nonalcoholic patients with panic disorder, and eight control subjects. They found that the alcoholic patients had fewer panic attacks in response to lactate infusion than the nonalcoholic patients. This finding was not attributable to differences in baseline anxiety or the change in plasma chemical values brought about by sodium lactate administration. The authors suggest that there may be subgroups of patients with panic disorder who need further characterization to meaningfully elucidate the pathophysiology of the disorder.

Adult↗
PubMed1989

Hyperamylasemia and its relationship to binge-purge episodes: development of a clinically relevant laboratory test.

Hyperamylasemia and parotid hypertrophy are conditions found in bulimic patients. The authors studied serum amylase levels in 56 underweight anorectics, 24 weight-recovered anorectics, 23 normal-weight bulimics, and 31 volunteer women. Normal-weight bulimic patients had significantly higher admission serum amylase values (mean +/- SE = 73.4 +/- 8.0 IU/L) than controls (40.8 +/- 2.4 IU/L). Additionally, the serum amylase test distinguished between restrictor anorectics (N = 31, 44.7 +/- 4.7 IU/L) and bulimic anorectics (N = 25, 68.8 +/- 8.6 IU/L, p less than .05) with a high degree of specificity and a fair degree of sensitivity. A subsample (N = 7) of bulimics showed twofold to fourfold increases in serum amylase values after a controlled period of binge eating and vomiting, whereas normal volunteers showed no change in serum amylase values (p less than .001) after ingesting a large meal. Serum amylase values declined significantly within 6 to 15 days of admission. However, after passes off the unit, serum amylase values returned to admission values, presumably as a result of binge-vomit episodes. The authors observe that modest increases of serum amylase values appear to be a consequence of binge-vomit behavior and suggest that serial serum amylase determination may be useful in monitoring the degree of patient abstinence in therapeutic programs.

Adult↗
PubMed1989

Contribution of CNS neuropeptide (NPY, CRH, and beta-endorphin) alterations to psychophysiological abnormalities in anorexia nervosa.

Patients with anorexia nervosa have neuroendocrine and behavioral alterations that starvation and weight loss are thought to cause, or contribute to, since they are reversed by weight restoration. We have found that anorexics have starvation-related disturbances of neuropeptide Y (NPY), corticotropin-releasing hormone (CRH), and beta-endorphin, as determined by their measurements in cerebrospinal fluid. The relationship between these neuropeptides and several symptoms in anorexia, together with findings in experimental animals, raise a possibility that changes in the activity of these neuropeptides contribute to neuroendocrine and behavioral alterations in anorexia. Specifically, a disturbance of central nervous system CRH activity is likely to be responsible for hypercortisolemia, while a disturbance of central nervous system NPY may contribute to amenorrhea. In addition, disturbances of these neuropeptides could contribute to other symptoms such as increased physical activity, hypotension, reduced sexual interest, depression, and pathological feeding behavior.

Adult↗
PubMed1988

Lymphocyte beta-adrenergic receptor modification in bulimia.

beta-Adrenergic receptor binding on circulating lymphocytes was evaluated in young female bulimic patients (n = 12) and age- and sex-matched normal control volunteers (n = 10). Using iodine 125-labeled cyanopindolol, antagonist binding was evaluated (number of receptors [Bmax] and dissociation constant [KD]), and using isoproterenol competition of cyanopindolol binding, the concentration required to inhibit binding by 50% (IC50) for isoproterenol and the agonist affinity measure of KL/KH (ratio of dissociation constants for the low- and high-affinity states of the receptor) were determined. Plasma norepinephrine (NE) level was also measured. There was a trend toward lower plasma NE levels in the bulimic patients. The KL/KH ratio in bulimic patients was significantly greater than that for the normal volunteers, indicating increased receptor coupling. The KL/KH ratio was not significantly correlated with plasma NE level. Neither Bmax nor KD was different between the two groups. These findings suggest that beta-adrenergic receptors in bulimic patients may be more responsive than in normal subjects, without alteration of the traditional measures of receptor responses, a difference that cannot be explained on the basis of plasma NE. These findings provide another line of evidence for altered regulation of the noradrenergic system in bulimic patients during a controlled phase of their illness.

Adult↗