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Biomedical subjects

M R Irwin

Publications and source records attributed to M R Irwin.

At least 19 recordsLinked to original sources
PubMed2005

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

Aged↗
PubMed2001

Propranolol affects stress-induced leukocytosis and cellular adhesion molecule expression.

In this study, the impact of the beta-adrenergic antagonist propranolol on resting and acute psychological- and physical-stress-induced circulating leukocyte numbers and the density of cellular adhesion molecules was investigated. In a randomized double-blind crossover design, 45 healthy volunteers performed a 15-min public speaking task and 21 subjects performed a 16-min bicycle exercise after 5 days of ingesting a placebo and after 5 days of ingesting 100 mg/day propranolol. One week of ingesting propranolol modestly elevated the numbers of CD62L+ (P<0.019) but not CD62L- T-lymphocytes. Moreover, propranolol preferentially blunted-psychological stress-induced increases in naïve T-helper (CD4+CD62L+; P<0.049) and naïve T-cytotoxic lymphocytes (CD8+CD62L+; P<0.003), as well as activated T-cytotoxic lymphocytes (CD8+CD29+; P<0.005). However, exercise-induced increases in leukocyte numbers were enhanced following propranolol treatment (P<0.04). In contrast to the effect on the numbers of adhesion-molecule-bearing cells, there was only a modest effect of propranolol on stress-induced alterations of the density of CD62L, CD54 and CD11a. In this study, propranolol treatment interfered with the adrenergic regulation of circulating leukocyte numbers by blunting psychological stress effects but enhancing exercise effects. Propranolol affected the cell activation status to a lesser extent, as reflected by the density of adhesion molecules.

Adrenergic beta-Antagonists↗
PubMed2000

Leukocyte adhesion molecule expression and T cell naïve/memory status following isoproterenol infusion.

This study examined adhesion molecules on peripheral leukocytes following a 30-min infusion of the beta-adrenergic agonist isoproterenol in 23 healthy subjects. In response to isoproterenol, the number of CD8 +CD62L- T cells and both CD62L+ and CD62L-natural killer (NK) (CD3 CD16+ 56+) cells increased markedly in circulation (p < 0.001). In addition, the surface density of CD62L was significantly lower on both CD8+ and CD4+ T cells (p < 0.001). Plasma levels of soluble CD62L remained unchanged, arguing against an isoproterenol-induced shedding of L-selectin. In contrast to CD62L, the surface density of the beta2 integrin LFA-1 (CD11a) was higher on circulating lymphocytes (p < 0.001) (but not monocytes or lymphocytes) post-infusion. Isoproterenol also led to a mobilization of memory/activated CD8+CD29high T cells (p < 0.01), but had no significant effect on the number of circulating CD8+ CD45RA+ CD62L+ naïve T cells. beta blockade with the non-specific antagonist propranolol eliminated these isoproterenol-induced effects.

Adrenergic beta-Agonists↗
PubMed1997

Longitudinal analysis of multiple indicators of health decline among spousal caregivers.

The hazards for experiencing major health events were studied longitudinally among 150 spousal caregivers of Alzheimer's disease (AD) patients and 46 married control participants. Based on longitudinal assessments from one to six years, the hazards of reaching any of three health events (extended physical illness or disability > 1 month, unhealthy medical rating from a nurse interview, or hospitalization) were not significantly different in a group comparison of caregivers to controls (Cox proportional hazards assumption, p > .05). However, there was a trend [X2(1, N = 107) = 3.13, p = .08] for caregivers to have a greater hazard for serious illness. Among caregivers only, a greater hazard for reaching at least one of these health events was associated with providing more activities of daily living (ADL) assistance [X2(1, N = 125) = 3.83, p = .05] but not with problem behaviors of the AD patient (p > .05). These results suggest that providing extensive ADL assistance may have health implications for spousal AD caregivers, while caregiving, per se, does not. Furthermore, these physical health impacts of caregiving may be best characterized using multidimensional assessments. Contrary to our guiding hypothesis, caregivers encountering more problem behaviors of their AD spouse were less likely to be hospitalized, X2(1, N = 145) = 5.88, p = .02. This finding may reflect a reluctance by caregivers to schedule necessary medical care when their spouses are most problematic, and this may have further long-term health implications for caregivers.

Activities of Daily Living↗
PubMed1997

Modulation of immune cell function by the autonomic nervous system.

This review discusses some of the major findings implicating the autonomic nervous system in the regulation of immune function. The sympathetic nervous system, the primary focus of this line of research, directly innervates the major lymphoid organs, and physiological release of sympathetic neurohormones at these sites has been documented. Leukocytes have been shown to express receptors for catecholamines, as well as neuropeptide Y, and studies in vitro and in vivo have indicated that occupation of these receptors by the appropriate ligands produces functional changes in immunological cells. Finally, altered sympathetic regulation may underlie some of the immunological abnormalities observed in chronic stress, clinical depression, and ageing.

Animals↗
PubMed1996

Macrophages can recognize and kill tumor cells bearing the membrane isoform of macrophage colony-stimulating factor.

NBXFO hybridoma cells produced both the membrane and secreted isoforms of macrophage colony-stimulating factor (M-CSF). Murine bone marrow cells stimulated by the secreted form of M-CSF (sM-CSF) became Mac1+, Mac2+, Mac3+, and F4/80+ macrophages that inhibited the growth of NBXFO cells, but not L1210 or P815 tumor cells. In cytotoxicity studies, M-CSF activated macrophages and freshly isolated macrophages killed NBXFO cells in the presence of polymyxin B, eliminating the possibility that contaminating lipopolysaccharide (LPS) was responsible for the delivery of the cytotoxic signal. Retroviral-mediated transfection of T9 glioma cells with the gene for the membrane isoform of M-CSF (mM-CSF), but not for the secreted isoform of M-CSF, transferred the ability of macrophages to kill these transfected T9 cells in a mM-CSF dose-dependent manner. Macrophage-mediated killing of the mM-CSF transfected clone was blocked by using a 100-fold excess of recombinant M-CSF. Catalase, superoxide dismutase, and the nitric oxide inhibitor, N-omega-nitro-arginine methyl ester (NAME), did not effect macrophage cytotoxicity against the mM-CSF transfectant T9 clones. T9 parental cells when cultured in the presence of an equal number of the mM-CSF transfectant cells were not killed, indicating specific target cell cytotoxicity by the macrophages. Electron microscopy showed that macrophages were capable of phagocytosizing mM-CSF bearing T9 tumor cells and NBXFO hybridoma cells; this suggested a possible mechanism of this cytotoxicity. This study indicates that mM-CSF provides the necessary binding and triggering molecules through which macrophages can initiate direct tumor cell cytotoxicity.

Animals↗
PubMed1996

Natural and cellular immune responses in Flinders sensitive and resistant line rats.

Major depression is associated with impairments in natural and cellular immune responses. This study characterized baseline natural and cellular immune function in the Flinders Sensitive Line (FSL) genetic animal model of depression and in Flinders Resistant Line (FRL) controls. Splenic natural cytotoxicity per natural killer (NK) cell was significantly lower in the FSL rats, suggesting that NK cells are less activated at rest in the FSL rats than in the FRL controls. Neither lymphocyte proliferative responses nor interleukin-2 production differed between the two strains. Resting baseline concentrations of plasma adrenocorticotropic hormone and corticosterone were similar between the FSL and FRL rats, indicating that hypothalamo-pituitary adrenal axis activation did not mediate immunological differences. FSL rats show abnormalities in natural immunity similar to those found in clinically depressed human beings, indicating that this animal model may be useful in understanding the neural and neuroendocrine mechanisms associated with immune alterations in depression.

Animals↗
PubMed1995

A role for CRH and the sympathetic nervous system in stress-induced immunosuppression.

Central CRH coordination of the behavioral and physiologic sequelae of stress has been well established, and so it is parsimonious to suggest that CRH might also coordinate the immunologic sequelae. The studies presented here lend support to this suggestion. CRH administration into the brain was shown to modulate aspects of both cellular and humoral immune function, and the inhibition of CRH release in the brain following stress inhibited stress-associated immunosuppression. The effects of CRH appear to be mediated by the sympathetic branch of the autonomic nervous system, as chemical sympathectomy and pharmacological blockade of beta-adrenergic receptors both reversed the effects of CRH on immune function. In contrast, removal of the adrenal glands did not alter the immunologic effects of CRH. These links among CRH in the brain, sympathetic activation, and immune function suggest the possibility that immune function may be altered in other conditions characterized by elevated sympathetic tone, such as depression and aging, and that these alterations may be attributed to CRH dysregulation in the brain. These studies shed light on the intricate relationship between the brain and the immune system, and also illuminate its complexity. The differential regulation of CRH in the brain and the periphery is one example of the latter. These findings also set the stage for potential clinical intervention with CRH antagonists, for example, to treat compromised immune function associated with chronic stress, depression, or aging.

Animals↗
PubMed1995

Neuropeptide Y inhibits in vivo specific antibody production in rats.

The sympathetic neurotransmitter neuropeptide-Y (NPY) is hypothesized to play a role in the in vivo modulation of immune responses. This study examined the effects of intraperitoneal administration of NPY on specific antibody responses to keyhole limpet hemocyanin (KLH) in rats. Antibody levels were repeatedly measured by enzyme-linked immunosorbent assay before and after intraperitoneal immunization with KLH. NPY induced a dose-dependent inhibition of IgM and IgG antibody responses following immunization with either physiologic or supraphysiologic doses of antigen. These in vivo results suggests that NPY may be involved in endogenous modulation of immune responses.

Animals↗
PubMed1995

Alcoholism and affective disorder: clinical course of depressive symptoms.

OBJECTIVE: This study compared the severity of and the change in depressive symptoms among men with alcohol dependence, affective disorder, or both disorders during 4 weeks of inpatient treatment. METHOD: After their primary and secondary psychiatric disorders were defined with the use of criteria based on chronology of symptoms, 54 unmedicated men entering treatment for alcohol dependence or affective disorder were assessed for 4 consecutive weeks with the Hamilton Depression Rating Scale. RESULTS: The findings indicate that the rate of remission of depressive symptoms was consistent with the primary diagnosis. Depressive symptoms remitted more rapidly among the men with primary alcoholism than among those with primary affective disorder. However, a minimum of 3 weeks of abstinence from alcohol appeared to be necessary to consistently differentiate the groups with dual diagnoses on the basis of their current depressive symptoms. Alcohol dependence occurring in conjunction with primary affective disorder did not intensify presenting depressive symptoms or retard the resolution of such symptoms. CONCLUSIONS: Diagnoses of alcohol dependence and affective disorder based on symptom chronology appear to have prognostic significance with respect to remission of depressive symptoms in men with both diagnoses. Depressive symptoms of dysphoric mood, dysfunctional cognitions, vegetative symptoms, and anxiety/agitation showed different rates and levels of remission across the primary diagnostic groups.

Adult↗
PubMed1994

Characteristics of men with alcoholic hallucinosis.

The goal of this study was to evaluate the characteristics of primary alcoholics with alcoholic hallucinosis. Six hundred and forty-three primary alcoholic men were recruited from a 28-day Alcohol and Drug Treatment Program at the San Diego VA Medical Center. Subjects only experiencing perceptual abnormalities during alcohol withdrawal, drug-related hallucinosis, as well as those having abnormal sensations that did not meet criteria for hallucinations were excluded from the present study. The remaining 532 subjects were divided into Group 1 (n = 48), which consisted of subjects with a DSM-IIIR and ICD-10 diagnosis of alcoholic hallucinosis, and Group 2 (n = 484) which consisted of those without any history of hallucinations. A comparison of the two groups revealed that Group 1 men were younger at the onset of alcohol problems, consumed more alcohol per occasion, developed more alcohol-related life problems, and had higher rates of drug experimentation as well as more different types of drugs used. This study suggests that primary alcoholics who consume more drugs and/or alcohol might be at an increased risk for developing alcoholic hallucinosis.

Adult↗
PubMed1994

A comparative study of criteria for subgrouping alcoholics: the primary/secondary diagnostic scheme versus variations of the type 1/type 2 criteria.

OBJECTIVE: This study compared three methods for identifying type 1 and type 2 alcoholism to determine how well the methods agree. It also evaluated the comparability of each of these schemes to the primary/secondary approach to subgrouping alcoholics. METHOD: Fifty male alcoholic inpatients were given diagnoses of primary alcoholism without antisocial personality disorder or primary antisocial personality disorder with secondary alcoholism on the basis of data from structured interviews. Operationalized criteria for type 1 and type 2 alcoholism from three groups of researchers (Gilligan et al., von Knorring et al., and Sullivan et al.) were also used to designate subgroups of the same subjects. RESULTS: Subgroups of subjects classified as having type 1 or type 2 alcoholism according to the criteria of von Knorring et al. and of Sullivan et al. showed good levels of agreement, but the criteria of Gilligan et al. yielded poor agreement with those of the other two schemes. Subgroups with type 1 or type 2 alcoholism according to the criteria of Sullivan et al. showed significant overlap with subgroups diagnosed according to the primary/secondary alcoholism scheme: there was 73% concordance between the type 1 subgroup and the subgroup with primary alcoholism and 73% concordance between the type 2 subgroup and the subgroup with primary antisocial personality disorder and secondary alcoholism. CONCLUSIONS: There is variability in assigning diagnoses of type 1 and type 2 alcoholism with the use of current methods. Also, type 1/type 2 classifications based primarily on age-at-onset factors significantly overlap with the primary/secondary classifications of alcoholics.

Adolescent↗
PubMed1993

High intracerebral levels of CRH result in CRH receptor downregulation in the amygdala and neuroimmune desensitization.

Corticotropin-releasing hormone (CRH) acts at the pituitary level to increase ACTH secretion and, within the central nervous system, to stimulate the sympathoadrenomedullary axis and behavioral activity. In addition, the central administration of CRH has been reported to reduce cellular immunity in the periphery. This study investigated the temporal relationship between CRH receptor regulation and the changes in splenic natural killer (NK) cell and pituitary-adrenocortical hormone responses to a single intracisternal (IC) CRH challenge (acute CRH) 24 h after chronic CRH pretreatment (5 nmol/day IC CRH for 4 days). Chronic CRH significantly decreased by 44.2 +/- 7.8% (P < 0.01) the CRH receptor concentration (beta max) in the amygdala. In contrast, the CRH receptor concentration of the anterior pituitary in the chronic CRH group was similar to the pituitary CRH receptor concentration in chronic saline controls. The immunoreactive-CRH concentration of the amygdala measured 24 h after the last IC CRH injection was not different from brain CRH levels in controls receiving chronic saline pretreatment. Consequently, the downregulation of amygdala CRH receptors occurred after transient increases in intracerebral CRH levels and did not result from ex vivo receptor occupancy by residual exogenous CRH sequestrated in brain tissue at the time of the CRH binding assay. Pretreatment with chronic CRH completely abolished the ability of a central CRH injection to suppress splenic NK activity; whereas, pituitary-adrenal responses to a superimposed acute CRH challenge were not significantly altered by chronic CRH pretreatment. These results suggest that the desensitization of the brain processes mediating CRH-induced suppression of splenic NK cytotoxicity is temporally correlated with CRH receptor downregulation in the amygdala but independent of pituitary-adrenal activation. These findings represent the first in vivo demonstration of homologous downregulation of extrahypothalamic CRH receptors and provide further evidence for the role of central CRH in the modulation of immune function.

Amygdala↗
PubMed1992

Plasma beta-endorphin and natural killer cell activity in major depression: a preliminary study.

Low concentrations of beta-endorphin have been found to enhance human natural killer (NK) cell activity in vitro. Both beta-endorphin and NK activity are changed by clinical depression. To evaluate whether circulating concentrations of beta-endorphin have a role in the in vivo modulation of cellular immunity in humans, we measured plasma beta-endorphin and NK cell activity in 14 depressed patients and 14 age-matched control subjects. In the depressed patients, both plasma beta-endorphin and NK cell activity were reduced to 76% and 57%, respectively, of the mean levels in the control subjects. In addition, beta-endorphin showed a significant positive correlation with lytic units of NK cell activity in the combined group of all subjects and in the patient group (p = 0.04), but not in the control group. The study supports the hypothesis that circulating endorphin is correlated with NK cell activity in vivo. This correlation may be higher in the depressed patient group.

Adult↗
PubMed1992

The relationship of life adversity, social support, and coping to hospitalization with major depression.

We evaluated the relationship between life events, social support, coping, and depression in 27 male inpatients meeting the requirements for Research Diagnostic Criteria major depressive disorder and in 35 age- and sex-matched nonpatients. Overall, the hospitalized depressed patients reported significantly more events and difficulties than did the controls, but this difference in statistical significance disappeared after excluding from analysis "non-independent" happenings which could have been brought on by depression. More hospitalized depressed patients (23 of 27, or 85%) than controls (8 of 35, or 22.9%) experienced markedly threatening events and difficulties ("marked adversities") in the 6 months before their interview. The depressed group also reported having significantly fewer social supports, being less satisfied with the emotional component of this support, and using more emotion-focused coping than the controls. A discriminant analysis predicted depressive status from a combination of marked adversities, reduced number of social supports, and greater use of emotion-focused coping. The results indicate that the relationship of life events to depression is complex. The excess number of events might be partly a product of dysfunctional behavior that "produces" depression-related events which might, in turn, exacerbate depression; simultaneously, patients are more likely to experience highly adverse events which might precipitate the depression in the first place. Reduced social supports and the use of emotion-focused coping appear to also be associated with hospitalization for major depression.

Adaptation, Psychological↗
PubMed1990

Severity of psychosocial stress and outcome of alcoholism treatment.

We examined the relation between stressful life events and drinking outcome among 129 male alcoholics who had completed an alcohol treatment program. Life events were assessed for the year prior to treatment and for the 3 months after treatment and were rated on the Psychiatric Epidemiology Research Interview and the Contextual Rating System. Approximately 40% of the pretreatment stressors were found to be directly or indirectly related to alcohol use. When stressors related to drinking were excluded from consideration, we found that men who returned to drinking after treatment experienced more severe or highly threatening stress before their relapse than men who remained abstinent during the follow-up period. These data suggest that although less severe stress may not increase risk for relapse, acute severe stressors and highly threatening chronic difficulties may be associated with elevated relapse risk.

Adult↗
PubMed1989

Individual behavioral and neuroendocrine differences in responsiveness to audiogenic stress.

A relatively wide range of individual differences in neuroendocrine, immune and behavioral components of the audiogenic stress response has been found. In this study, an analysis of the association between the physiological and behavioral measures revealed that the degree of noise-induced suppression of both general activity and ingestive behaviors was significantly correlated with activation of adrenal steroid secretion following both acute and repeated noise exposures. Splenic natural killer cytotoxicity was not correlated with the behavioral measures of the stress response. Characterization of individual behavioral response profiles may be needed to evaluate accurately the neuroendocrine effects of stress.

Animals↗