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Biomedical subjects

M Irwin

Publications and source records attributed to M Irwin.

At least 109 records · Page 6Linked to original sources

TSH response to TRH and family history of alcoholism.

The thyrotropin (TSH) response to intravenous thyrotropin-releasing hormone (TRH) was evaluated in 10 sons of alcoholic fathers (FHP group) and 10 matched controls (FHN group). No differences were observed between the two groups in basal TSH, peak TSH levels, on the incidence of TSH-blunting to TRH. Though there was a trend for a less intense TSH response over time after the TRH infusion, the difference between the family groups was not significant. These results are not consistent with some previous reports of an increased percentage of blunted TSH response to TRH for children of alcoholics. The clinical and research implications of these findings are discussed.

Adolescent↗

Growth hormone response to intravenous diazepam and placebo in 82 healthy men.

Growth hormone (GH) response to placebo and two different doses of diazepam (0.12 mg/kg and 0.20 mg/kg) were evaluated in 82 healthy young men. Both diazepam doses had a significant effect on the growth hormone secretion, with peak values occurring between 30 and 60 min postinfusion, after which levels returned to baseline. There was also a small but significant change in this hormone over time after placebo, but this was reflected by a slow rise following the saline infusion. Individual GH responses to diazepam were variable and, when a cut-off point of 7.5 ng/ml GH increase before 90 min postdrug administration was used, 1% of the men demonstrated a response after placebo, 17% after low-dose diazepam, and 37% following high-dose diazepam. The clinical implications and limitations of these findings are discussed.

Adolescent↗

EEG sleep studies in "pure" primary alcoholism during subacute withdrawal: relationships to normal controls, age, and other clinical variables.

Electroencephalogram (EEG) sleep recordings were compared in 34 normal controls and 31 inpatients with relatively pure primary alcoholism who had been abstinent for about 17 days. Compared with normal controls, primary alcoholics took longer to fall asleep, slept less, and had poor sleep efficiency. Sleep loss reflected reduced non-rapid eye movement (NREM) sleep, especially stage 2 sleep, stage 4 sleep, and total delta (stage 3 and 4) sleep. Alcoholic patients had higher REM density of the first REM period. Sleep deteriorated with age in both normal controls and patients, with younger alcoholics showing sleep patterns typical of older controls. Among other clinical-demographic variables examined, the shorter the duration of sobriety at the time of the study, the later patients went to bed and fell asleep. The number of drinks per drinking day in the 3 months before admission was directly related to the duration of the first REM period. In addition, the maximum number of withdrawal symptoms the patient had ever experienced was inversely related to the amount of delta sleep. Sleep measures were not correlated with depression rating, liver enzymes, or other measures of alcohol consumption.

Adult↗

Reduction of immune function in life stress and depression.

Reduced cell-mediated immune function has been found in depressed patients and in distressed persons undergoing threatening life events. The present study examines the interaction between severe life stress and major depression to produce immune alterations in 36 matched pairs of hospitalized depressed patients and nondepressed controls. Both major depressive disorder and the presence of threatening life events in control subjects are independently associated with a 50% reduction of natural killer (NK) cytotoxicity. A decrease in natural cytotoxicity is significantly associated with depressive symptoms but not with age, alcohol consumption, or tobacco smoking. These findings of altered immunity provide further evidence that the physiological responses in chronic stress parallel those found in the syndrome of depression.

Adult↗

Clinical importance of age at onset in type 1 and type 2 primary alcoholics.

Alcoholics have been proposed to be comprised of subtypes who differ in their age at onset and in type 1 vs type 2 characteristics. This study examined whether the clinical course of primary alcoholics was associated with age at onset as well as the type 1-vs-type 2 classification scheme. Interviews with 171 consecutive primary alcoholic men entering an alcohol treatment program revealed that age at onset of alcoholism was correlated with alcohol, drug, and childhood criminality problem histories. Neither classification of these alcoholics into discrete type 1 and type 2 categories nor placing them along a continuum of type 2 characteristics was consistently associated with severity of clinical histories. These findings underscore the clinical importance of age at onset and suggest the possibility that the type 2 prototype might represent a separate diagnosis, antisocial personality disorder, and not alcoholism itself.

Adult↗

Major depressive disorder, alcoholism, and reduced natural killer cell cytotoxicity. Role of severity of depressive symptoms and alcohol consumption.

Depression and alcohol abuse have been associated with alterations in cell-mediated immune function. This study directly compared the effects of depression, alcoholism, and their joint contribution to reduce natural killer cell cytotoxicity. Natural killer cell activity was significantly lower in both depressed (n = 18) and alcoholic (n = 19) patients compared with control subjects (n = 50). In addition, patients with a dual diagnosis of either alcohol abuse and secondary depression (n = 9) or depression with a history of alcohol abuse (n = 26) demonstrated a further decrease in natural killer cell activity compared with that found in patients with either depression or alcoholism alone. While both depression and alcoholism are separately associated with a reduction of natural killer cell activity, subgroups of patients in whom the diagnoses of alcoholism and depression coexist show a further decrement in natural killer cell function.

Adult↗

Short REM latency in primary alcoholic patients with secondary depression.

Primary alcoholic patients with secondary depression had significantly shorter REM latency and less non-REM sleep than alcoholics without other psychiatric diagnoses and normal control subjects. Both patient groups had significantly longer sleep latency and less sleep efficiency, total sleep time, and delta sleep than control subjects.

Adult↗

Tridimensional Personality Questionnaire scores of sons of alcoholic and nonalcoholic fathers.

The authors studied 33 men whose fathers had severe alcohol-related problems and 33 subjects with no family history of alcoholism. The former supplied information about the course of their fathers' alcohol problems; all 66 men answered questions about their own drinking and drug use and completed the Tridimensional Personality Questionnaire. There were no significant relationships between any of the 18 questionnaire scores and a subject's quantity/frequency of drinking or his family history of alcoholism. There was only one significant correlation between the alcoholic fathers' type 2 characteristics, according to the type 1/type 2 theory, and the sons' questionnaire scores. The relevance of these findings to the theory is discussed.

Adult↗

Central corticotropin-releasing factor mediates the suppressive effect of stress on natural killer cytotoxicity.

CRF acts within the brain to elicit changes in neuroendocrine, autonomic, and behavioral activity similar to that observed after stress. A reduction of splenic natural killer (NK) activity has also been described after the central administration of CRF. In this study we examined whether the central release of CRF plays a physiological role in mediating stress-induced suppression of NK cytotoxicity. Four sessions of footshock stress (1.5 mamp; 1-sec duration; 60-Hz sine wave; delivered randomly twice per min for 30 min) over a 48-h period significantly (P less than 0.001) reduced splenic NK activity in the rat. Pretreatment of the animals by central administration of polyclonal CRF antibodies completely antagonized the stress-induced suppression of NK cell activity. In contrast, the peripheral immunoneutralization of CRF was ineffective. Measurement of circulating levels of ACTH and corticosterone demonstrated that stress-induced elevations of ACTH and corticosterone were significantly (P less than 0.05) attenuated by peripheral anti-CRF serum, but not by centrally administered anti-CRF. These findings suggest that endogenous brain CRF coordinates the suppressive effect of footshock stress on NK cytotoxicity independently of pituitary-adrenal activation.

Adrenocorticotropic Hormone↗

The history of anxiety symptoms among 171 primary alcoholics.

This study used patient and resource person face-to-face interviews to explore the history of anxiety symptoms and syndromes in 171 primary alcoholic male veterans on an alcohol treatment program. Almost all men (98%) reported at least one symptom of anxiety during drinking or withdrawal, including 80% who related problems with palpitations and/or shortness of breath. In addition, seven men (4%) described at least one episode of panic lasting from 1 to 4 or more hours, although only two of these individuals experienced three or more panic attacks in a 3-week period in the context of heavy drinking or withdrawal. No men evidenced repetitive panic attacks either before the onset of heavy drinking or in the context of a protracted period of abstinence. Seven individuals (4%) fulfilled criteria for generalized anxiety symptoms when dry for 3 or more months. The histories of treatment by mental health workers or in psychiatric facilities taken together with the symptom picture generated from patient and resource person interviews do not indicate an elevated incidence of either panic disorder or generalized anxiety that is independent of heavy drinking.

Adaptation, Psychological↗

Sympathetic nervous system mediates central corticotropin-releasing factor induced suppression of natural killer cytotoxicity.

Corticotropin-releasing factor (CRF) acts within the brain to elicit changes in neuroendocrine, autonomic and behavioral activity similar to those observed after stress. A reduction of cellular immune function as measured by splenic natural killer cell activity has also been described following the central administration of CRF. In this study we evaluated the role of the sympathetic nervous system in mediating CRF-induced suppression of natural killer (NK) cytotoxicity. Synthetic rat CRF (1.0 microgram) microinjected into the lateral ventricle increased noradrenergic function and reduced NK activity in the rat spleen. Pretreatment of the animals by chemical sympathectomy (6-hydroxy-dopamine, 100 mg/kg i.p. daily over 10 days) produced a greater than 95% reduction of splenic norepinephrine concentration and abolished completely both the CRF-induced increase in plasma catecholamine levels and the reduction in splenic NK activity. In addition, beta adrenergic receptor blockade (either propranolol, 10 mg/kg i.p., or butoxamine, 25 mg/kg i.p. 30 min before i.c.v. infusion) antagonized the CRF-induced reduction in NK activity. Measurement of circulating levels of adrenocorticotrophic hormone and corticosterone demonstrated that activation of the pituitary adrenal axis by CRF was dissociated from changes in NK activity. These findings suggest that the sympathetic nervous system mediates the suppression of splenic NK cytotoxicity after i.c.v. CRF.

Animals↗

Subjective feelings of anxiety in young men after ethanol and diazepam infusions.

Self-reported feelings of anxiety after separate administrations of ethanol (0.75 mL/kg), low-dose diazepam (0.12 mg/kg), high-dose diazepam (0.20 mg/kg), and placebo were evaluated over four laboratory sessions in the same 90 male volunteers, who used the Spielberger State Anxiety Inventory (STAI). Significant increases in the state anxiety scores were observed after administrations of diazepam and ethanol, while a significant decrease in the feelings of tension was reported after administration of placebo. Consistent with previous work from our laboratory, there were similarities in the intensity and time course of change observed for a number of measures following low-dose diazepam and ethanol infusions. The potential importance of these findings to the understanding of intoxication and abuse of benzodiazepines is discussed.

Adult↗

Plasma levels of tetrahydrobiopterin and folate in major depression.

Plasma levels of tetrahydrobiopterin (BH4) and the related pterin folate were concurrently measured in 20 pairs of depressed patients and age-matched controls. The mean values of plasma BH4 in depressed patients was significantly elevated to a level about 150% of that found in the controls. Folate levels were not different between groups. These findings emphasize that BH4, a required cofactor in the biosynthesis of catecholamines and indolamines, is altered in depression.

Adult↗

Central corticotropin releasing factor reduces natural cytotoxicity. Time course of action.

Corticotropin-releasing factor (CRF) administered intracerebroventricularly produced both a rapid, greater than 50% reduction in splenic natural killer (NK) cytotoxicity and a prolonged elevation in plasma corticosterone levels. In the first 60 minutes following CRF, fivefold increases in corticosterone levels were associated with the suppression of NK activity. However, NK activity returned to control levels at later time points even though elevated plasma corticosterone levels persisted. These data augment the findings that central CRF reduces natural cytotoxicity and establish a time course for the effect in acutely treated rats.

Animals↗

An analysis of the clinical relevance of type 1 and type 2 alcoholics.

Predictions inherent in the proposed Type 1/Type 2 continuum of alcoholic subtypes were indirectly explored in 31 sons of primary alcoholic fathers. The fathers' alcoholism was rated on a 0-5 scale utilizing characteristics typical of the Type 2 extreme of the continuum. If a predisposition to Type 2 alcoholism is genetically transmitted, then we would have predicted that the sons of Type 2 alcoholics would be more likely than the sons of Type 1 men to show an earlier onset of drinking, as well as more alcohol and substance intake and associated problems. The results did not support any consistent trend in the correlation between the FHP fathers' alcoholic characteristics and the sons' problem picture. Potential explanations for this finding are discussed including the possibility that the Type 2 extreme might represent a separate diagnostic entity, the antisocial personality disorder, and not alcoholism itself.

Adult↗

The measurement of villus cell population size in the mouse small intestine in normal and abnormal states: a comparison of absolute measurements with morphometric estimators in sectioned immersion-fixed material.

From a functional viewpoint, the most important part of the small intestinal mucosa is the villus epithelium; in the experimental study of intestinal adaptation it is often necessary to estimate the size of the population. For these reasons, a systematic study of methods of measuring the size of the villus cell population was undertaken in villi of normal morphology from control animals, and in villi of abnormal morphology as produced by treatment of mice with cytosine arabinoside (Ara-C). The villus cell population can be measured with precision and accuracy in both normal and abnormal mucosal states, with a relative standard error usually less than 5%, with good reproducibility, and with very low counting errors. In the mouse a practically linear relationship between the villus cell population size and position in the small intestine can be shown. In normal, control animals, linear estimates of villus population, for example the villus height, the villus core height, and the villus row count measured in sections of immersion-fixed material, were found to be rough approximations as indicators of the villus cell population, and were highly correlated with it. Product variables, comprising the products of a height with a width measurement, show a large improvement over the linear variables as estimators of villus cell population. In populations of abnormally shaped villi produced by Ara-C, both linear and product variables showed a considerable decrease in correlation with the villus cell population. Consequently, indirect, linear measurements of the villus population size do not accurately reflect the size of the villus population in abnormal villi. Finally, a method comparing theoretical and measured surface: volume indices was used to indicate that the most appropriate shape for normal mouse villi is a simple cylinder; this method would also be applicable for other villus cell populations.

Animals↗

Graded neuropsychological impairment and elevated gamma-glutamyl transferase in chronic alcoholic men.

This study hypothesizes that distinct biochemical and metabolic disturbances associated with liver injury may be related to specific cognitive changes in alcoholics. In 132 alcoholic men admitted to an alcohol treatment program, increases in gamma-glutamyl transferase (GGT) values were correlated with impairment in several measures of visuoperceptual and visuoconceptual functioning. The association between plasma levels of GGT and neuropsychological performance was independent of the relative contribution of other laboratory measures of liver injury and of alcohol consumption histories. These observations support the hypothesis that elevated levels of GGT are distinctly associated with neuropsychological deficits and suggest that possible mechanisms beyond severe hepatic dysfunction and alcohol consumption underlie cognitive deficits in alcoholics.

Adult↗

Behavioral hyporeactivity to physostigmine in detoxified primary alcoholics.

Changes in anergia/inhibition, mood, and pulse rate induced by intravenous physostigmine were significantly less pronounced in 26 patients with primary alcoholism than in 36 normal control subjects. These results suggest possible abnormalities in central cholinergic functioning in primary alcoholics.

Adolescent↗