Biomedical subjects

M Irwin

Publications and source records attributed to M Irwin.

At least 19 recordsLinked to original sources

PubMed1992

Lack of association between an RFLP near the D2 dopamine receptor gene and severe alcoholism.

Blum et al (1990) have recently examined a restriction fragment length polymorphism (RFLP) detected by TaqI RFLP to the dopamine D2 receptor gene (DRD2) in deceased alcoholics and nonalcoholics, and reported an association between alcoholism and the A1 allele. Subsequent studies, however, by other investigators have failed to confirm this. We have examined the DRD2 TaqI RFLP in 47 living Caucasian males with severe alcoholism. All alcoholic subjects were thoroughly characterized by a structured interview, and met DSM-III-R criteria for alcohol dependence. Only 9/47 (19%) (1990) of these alcoholics had the AI allele compared to 14/22 (64%) reported by Blum et al. This rate was not significantly different from the rates reported in control populations by Blum et al (1990), CEPH, or Bolos et al (1990), and differed only slightly from those reported by Grandy et al (1990). Alcoholics selected for severe medical complications also displayed a similar rate. Our data do not support an association between alcoholism and the D2 dopamine receptor gene in this population.

Adult↗

PubMed1992

Central corticotropin-releasing hormone reduces cellular immunity.

Corticotropin-releasing hormone (CRH) acts within the brain to elicit changes in neuroendocrine, autonomic, and behavioral activity similar to those observed after stress. A reduction of splenic natural killer (NK) activity has also been described following the central administration of CRH. In this study, we examined whether other in vitro measures of cellular immunity, including peripheral and splenic NK activity, lymphocyte responses to mitogen stimulation, and numbers of splenic T and NK cell subpopulations, are altered following CRH. Synthetic rat CRH (1.0 microgram) microinjected into the lateral ventricle reduced splenic and peripheral blood NK activity, lymphocyte responses to mitogenic stimulation, and percentage of splenic NK cell numbers. Numbers of splenic lymphocytes and T cell subpopulations were not altered by central CRH. These findings suggest that central CRH acts to reduce a number of in vitro cellular immune measures similar to the effects of inescapable stress.

Animals↗

PubMed1992

Depression and reduced natural killer cytotoxicity: a longitudinal study of depressed patients and control subjects.

Cross-sectional studies have demonstrated that natural killer (NK) cell activity is reduced in depression. To extend these observations and examine further the association between severity of depressive symptoms and values of NK activity, this study used a longitudinal case-control design and assessed NK cytotoxicity at intake and at follow-up 6 months after discharge from the hospital in depressed patients and control subjects. From acute hospitalization to follow-up, depression scores significantly (P < 0.01) decreased following treatment in the depressed patients but did not change in the control subjects. NK activity significantly (P < 0.05) increased from intake to follow-up in the depressives while lytic activity did not change in the controls. At intake NK activity was significantly (P < 0.01) reduced in the depressed patients as compared to values in the controls, while at follow-up cytotoxicity was similar between the two groups. These longitudinal data suggest that a reduction of NK cytotoxicity is temporally associated with the state of acute depression.

Adult↗

PubMed1992

Evaluation of a disposable patient-controlled analgesia device in children.

A disposable patient-controlled analgesia (PCA) device was evaluated in 20 children after major abdominal, urological and orthopaedic surgery. All patients were given a high dependency level of nursing care in general wards. Efficacy (as assessed by hourly pain scores) was comparable to that achieved in a matched control group of 20 children who used the Graseby PCA system. Safety was confirmed by monitoring arterial oxygen saturation, sedation scores and ventilatory frequency. Morphine consumption was similar with the two techniques, but varied widely between patients. The disposable device has a complementary role to play in the provision of a comprehensive pain relief service for children.

Adolescent↗

PubMed1992

A multicenter experience with a bipolar tined polyurethane ventricular lead.

A multicenter study was undertaken to determine the failure rate of a specific polyurethane bipolar tined pacing lead, the Medtronic 4012 pacing lead. Six centers in the United States and Canada implanted 1,190 Medtronic 4012 pacing leads. The study was designed to determine the probability and clinical manifestations of lead failure. Only failures compatible with an insulation problem were included. The probability of a 4012 lead failure by Kaplan-Meier analysis was 20.9% at 6 years after implantation. Failures were manifested as sensing abnormalities, failure to capture, early battery depletion, and significant decrease in measured impedance compared with the previous impedance measurements. Of the 95 definite lead failures, 16 (16.8%) were associated with symptoms similar to those experienced before pacemaker placement. The observed failure rate is unacceptable, and strong consideration should be given to replacing the 4012 pacing lead in pacemaker-dependent patients and closely monitoring nondependent patients.

Aged↗

PubMed1992

Sympathetic and immune interactions during dynamic exercise. Mediation via a beta 2-adrenergic-dependent mechanism.

BACKGROUND: The relation between the sympathetic nervous system and the immune system has not been fully defined. Recent investigations have suggested an adrenergically driven efflux of specific beta 2-receptor-rich lymphocyte subsets into the circulation with either exercise or infusion of exogenous catecholamines. METHODS AND RESULTS: To determine whether acute sympathetic stimulation mediates immunoregulatory cell traffic and function via a beta 2-receptor mechanism, we exercised 20 healthy volunteers before and after 1 week of treatment with either the nonselective beta-antagonist propranolol or the beta 1-selective antagonist metoprolol. Before treatment, exhaustive exercise according to the Bruce protocol led to a marked lymphocytosis. Tsuppressor/cytotoxic (Ts/c) and natural killer cells, subtypes with the largest density of beta-receptors, showed the most pronounced increases after exercise, with less impressive elevations in T(helper) and B cells. With respect to function, exhaustive exercise led to a decrease in concanavalin A-stimulated IL-2 receptor expression and [3H]thymidine incorporation while enhancing natural killer cell activity. One week of propranolol therapy blunted the exercise-induced increases in circulating Ts/c and natural killer subpopulations as well as the previously observed alterations in cellular immune function. Treatment with the beta 1-selective antagonist metoprolol, however, did not impair the influence of exercise on any of the above parameters. CONCLUSIONS: Acute sympathetic stimulation by exhaustive exercise leads to selective release of immunoregulatory cells into the circulation with subsequent alterations in cellular immune function, either secondary to subset changes or as a result of direct catecholamine effects on function. These changes are attenuated by propranolol but not metoprolol, suggesting a beta 2-mediated mechanism.

Adult↗

PubMed1992

Central corticotropin-releasing hormone activates the sympathetic nervous system and reduces immune function: increased responsivity of the aged rat.

CRH acts within the brain to activate the sympathetic nervous system and reduce cellular immune function. To determine the effects of age on CRH-induced elevations of sympathetic activity and suppression of immunity, we examined the responses of plasma catecholamines, neuropeptide-Y (NPY), corticosterone, and splenic natural killer (NK) activity after microinjection of rat CRH (200 pmol) into the lateral ventricle of aged (24-month-old) Fischer 344 (F344) rats compared to those in young (4-month-old) F344 rats. Basal concentrations of plasma norepinephrine and NPY were higher in the aged than in the young animals. In addition, CRH produced a greater elevation of plasma levels of catecholamines and NPY, which persisted for a longer period of time in the aged rats compared to responses in the young animals. Splenic NK activity showed an age-related decrement at baseline, and CRH induced a further significant (P less than 0.01) reduction of lytic activity in the aged rats, but did not alter cytotoxicity in the young rats. Corticosterone basal levels and responses were similar in the aged and young rats. These results show an age-related increase in autonomic outflow and suppression of NK activity after central CRH administration. In aged animals, the central nervous system may have a role in abnormal regulation of sympathetic activity and suppression of natural cytotoxicity in vivo.

Aging↗

PubMed1992

Importance sampling. I. Computing multimodel p values in linkage analysis.

In linkage analysis, when the lod score is maximized over multiple genetic models, standard asymptotic approximation of the significance level does not apply. Monte Carlo methods can be used to estimate the p value, but procedures currently used are extremely inefficient. We propose a Monte Carlo procedure based on the concept of importance sampling, which can be thousands of times more efficient than current procedures. With a reasonable amount of computing time, extremely accurate estimates of the p values can be obtained. Both theoretical results and an example of maturity-onset diabetes of the young (MODY) are presented to illustrate the efficiency performance of our method. Relations between single-model and multimodel p values are explored. The new procedure is also used to investigate the performance of asymptotic approximations in a single model situation.

Diabetes Mellitus, Type 2↗

PubMed1991

Reduced natural killer cell cytotoxicity in depression but not in schizophrenia.

A reduction of natural killer (NK) cell activity has been found in hospitalized patients with major depressive disorder. To examine whether a reduction of NK activity is found in other psychiatric patients or related to the nonspecific effects of hospitalization, NK cell cytotoxicity was compared in hospitalized depressed patients, schizophrenic inpatients, and two groups of controls separately age matched to each patient group. NK activity was significantly (p less than 0.01) lower in depressed inpatients than control subjects. However, in the hospitalized schizophrenic patients values of natural cytotoxicity did not differ from controls. These findings suggest that reduced NK cytotoxicity in depression is independent of the effects of hospitalization.

Adult↗

PubMed1991

Adapting milieu therapy to short-term psychiatric hospitalization of children.

Traditional concepts of long-term residential treatment of children are adapted for use on short-term psychiatric units. A model of milieu therapy is proposed which emphasizes the fostering of discriminate interpersonal attachments. Specific interventions, the use of limits, and the role of other therapies are discussed in the context of this model.

Child↗

PubMed1991

Neuropeptide Y and natural killer cell activity: findings in depression and Alzheimer caregiver stress.

A reduction in immune function has been found in patients with a major depressive disorder and in persons undergoing severe life stress. This study investigated the association between increased sympathetic nervous system activity and reduced natural killer (NK) cytotoxicity in depression and Alzheimer caregiver stress. NK activity and plasma concentrations of epinephrine, norepinephrine, and neuropeptide Y were measured in depressed patients (n = 19) and age- and gender-matched controls (n = 19), and in Alzheimer spousal caregivers (n = 48) and matched noncaregiver controls (n = 17). Plasma levels of neuropeptide Y, but not circulating basal levels of catecholamines, were significantly (P less than 0.01) elevated in the depressed patients and in the caregivers compared with respective controls. NK activity was significantly (P less than 0.001) lower in the depressed patients than in their controls, but not different between the caregivers and the noncaregiver controls. Circulating concentrations of neuropeptide Y, but not catecholamines, were inversely correlated (r = -0.31, P less than 0.001) with NK activity. In addition, multiple regression analyses demonstrated that the significant (P less than 0.01) association between neuropeptide Y and natural cytotoxicity was independent of the relative contribution of age and basal and dynamic levels of epinephrine and norepinephrine. These findings suggest that increased sympathetic nervous system activity and the release of neuropeptide Y may be associated with the modulation of NK cytotoxicity.

Alzheimer Disease↗

PubMed1991

Both genes for EF-1 alpha in Candida albicans are translated.

In previous work, we showed that Candida albicans has two genes, TEF-1 and TEF-2, which encode identical polypeptides for the highly conserved, essential, protein synthesis factor EF-1 alpha (Breviario et al., 1988). This result prompted questions as to whether C. albicans preferentially uses one of the genes over the other and whether both genes are actually translated into protein. Gene-specific sequence differences in the untranslated portion of each gene made it possible to prepare gene-specific oligonucleotide hybridization probes. Results with the probes showed that the relative steady-state mRNA levels of the two genes were equivalent and that the mRNA for each gene was present in active translation complexes.

Blotting, Northern↗

PubMed1991

Reduced cerebral grey matter observed in alcoholics using magnetic resonance imaging.

Twenty-eight chronic alcoholics and 36 age- and sex-matched non-alcoholic controls were examined with magnetic resonance imaging and brain morphometric analyses. Results confirmed large increases in subarachnoid cerebrospinal fluid (CSF) volume and mild ventricular enlargement in the alcoholics and revealed associated volume reductions of localized cortical and subcortical cerebral structures. Volume losses in the diencephalon, the caudate nucleus, dorsolateral frontal and parietal cortex, and mesial temporal lobe structures were the most prominent. Significant correlations between increments in cortical and ventricular CSF and decrements in the volume of cortical and subcortical grey matter were noted. Although there was little evidence for relationships between performance on neuropsychological tests and volume of grey matter structures, significant correlations between some cognitive measures and subcortical and cortical fluid volumes were found. The parallels between this pattern of affected structures and recent neuropathological findings are discussed.

Adult↗

PubMed1991

Response of three hormones to diazepam challenge in sons of alcoholics and controls.

This study evaluates the hypothesis that the decreased reaction to ethanol reported for sons of alcoholics will also be observed following infusions of a benzodiazepine. The investigation compared 37 men who were family history positive for alcoholism with 37 family history negative controls on postinfusion levels of cortisol, prolactin, and growth hormone following 0.12 and 0.20 mg/kg of diazepam given IV over 7 minutes. The results demonstrated no evidence of a decreased response for the sons of alcoholics on the levels of these three hormones.

Adult↗

PubMed1991

Cognitive performance of alcoholics: a longitudinal evaluation of the role of drinking history, depression, liver function, nutrition, and family history.

To assess the role of drinking history, depression, liver function, nutrition, and family history on cognitive performance, 171 detoxified male alcoholics were administered a brief neuropsychological examination at admission and discharge from an inpatient treatment program and at a 3-month follow-up evaluation. Regression analyses showed that at admission, depression and liver function were significant predictors of neuropsychological performance, whereas at discharge 3 to 4 weeks later only age and an estimate of premorbid intelligence were significant predictors. At the 3-month follow-up, estimates of drinking following discharge and severity of depressive symptoms were major significant predictors of neuropsychological performance. Indices of drinking prior to admission to the treatment program, nutrition, and family history for alcoholism did not predict performance on any of the three test occasions. These findings indicate that in addition to the chronic neurotoxic effect of alcohol a number of different medical and psychiatric factors, as well as the acute effects of alcohol, contribute to the cognitive scores of patients at various points in the clinical course.

Adult↗

PubMed1991

Reactions to ethanol and diazepam in healthy young men.

The reactions to oral ethanol (0.75 ml/kg), IV low-dose diazepam (0.12 mg/kg) and IV high-dose diazepam (0.2 mg/kg) were evaluated over four test sessions in the same 48 healthy young men. The data demonstrated similar subjective feelings after the low-dose diazepam and ethanol, but significantly greater effect after high-dose diazepam. Despite the similarities on subjective feelings, the low-dose diazepam challenge resulted in significantly more impairment than did ethanol on measures of memory, body sway and the evaluation of the passage of time. The similarities in subjective aspects of intoxication for ethanol and low-dose diazepam have potential implications for increasing our understanding of possible enhanced vulnerabilities for abuse of benzodiazepines among alcohol-abusing patients. The trend for similarities in subjective intoxication but greater impairment in motor and cognitive performance after low-dose diazepam compared to ethanol might indicate that subjects might be less aware of their actual levels of performance difficulties after the benzodiazepine. It is hoped that these data will help clinicians understand more about the quality of intoxication with benzodiazepines and the types of impairments likely to be observed.

Adult↗

PubMed1991

Changes in anxiety among abstinent male alcoholics.

Symptoms of anxiety are prevalent features of alcoholics seeking treatment. In the present study levels of state anxiety among male primary alcoholics (with no preexisting major psychiatric disorders) were examined 3 times per week during inpatient treatment for alcoholism and again at 3 months following treatment. The 171 male alcoholics also completed the trait scale of the State Trait Anxiety Inventory upon admission to an inpatient program and at 3 months following treatment. Results indicate that recently detoxified males experience multiple anxiety symptoms, with 40% reporting significantly elevated levels of state anxiety at admission (greater than or equal to 75th percentile). By the second week of treatment state anxiety scores typically returned to the normal range although symptoms continued to decrease significantly with each week of continued abstinence. Elevated levels of anxiety symptoms were more common among primary alcoholics with a history of panic episodes or generalized anxiety disorder symptoms. While abstainers and relapsers did not differ in level of anxiety observed during treatment, the relapsers report significantly higher state and trait anxiety scores at follow-up.

Adult↗

PubMed1991

Subjective feelings and changes in body sway following diazepam in sons of alcoholics and control subjects.

The possible generalization to diazepam of the dampened response to ethanol in sons of alcoholic fathers was evaluated in 62 sons of alcoholics (family history positive [FHP] subjects) and 62 family history negative (FHN) controls (124 men). Following challenges with placebo, .12 and .2 mg/kg of diazepam in three separate sessions, evaluation of subjective feelings and increases in body sway revealed no decreased reaction for FHPs.

Adult↗