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Biomedical subjects

M Irwin

Publications and source records attributed to M Irwin.

158 records · Page 9Linked to original sources
PubMed1980

Biliary secretion of methadone and methadone metabolites in man.

A method for the simultaneous quantitative analysis of human bile for methadone, and two of its metabolites: pyrrolidine, the major metabolite formed by N-demethylation, and pyrroline, formed by a second N-demethylation, using gas liquid chromatography and both radiolabeled methadone and pyrrolidine as standards for determinations of recovery has been developed. This method has been applied to the quantitative analysis of methadone and its metabolites in bile collected over three days from T-tube drainage in a methadone-maintained patient who had undergone cholecystectomy and common bile duct exploration but who had no liver disease. The concentrations and total amounts of the pyrrolidine metabolite far exceeded those of methadone and of the pyrroline metabolite. The amounts of unchanged methadone found in bile (as in previous studies of feces) were found to be very low. Therefore, at least in this patient, a significant enterohepatic circulation of unchanged methadone is unlikely.

Bile↗
PubMed1979

Biochemical genetics of Chinese hamster cell mutants with deviant purine metabolism: isolation and characterization of a mutant deficient in the activity of phosphoribosylaminoimidazole synthetase.

A new purine-requiring mutant of Chinese hamster ovary cells (CHO-Kl) is described. This mutant, Ade-G, grows on aminoimidazole carboxamide, hypoxanthine, or adenine. It complements all eight of our other previously described Ade- mutants. Biochemical analysis of de novo purine synthesis in whole cells suggests that Ade-G is capable of the first four reactions of de novo purine biosynthesis and that it synthesizes and accumulates phosphoribosylformylglycinamidine (FGAM). Direct enzyme assay in cell-free extracts confirms that Ade-G is defective in phosphoribosylaminoimidazole synthetase activity and does not convert FGAM to phosphoribosylaminoimidazole (AIR), the next intermediate in the de novo biosynthetic pathway.

Animals↗
PubMed1976

Effects of maternal nutrition on fetal growth and infant development.

The results of a food supplementation study conducted in four chronically malnourished rural villages in Guatemala were analyzed to determine possible effects on the study children's early mental and physical development. One of two food supplements, atole and fresco, were given to pregnant and lactating mothers and the infants born to them up to three years of age. The level of supplement received was noted and the subsequent course of the children's development observed. Food supplementation of pregnant mothers was found to correlate with higher weights of their babies at birth. No other major maternal variables--home diet, body height and/or weight, morbidity, obstetric characteristics, or socioeconomic status--could account for this association. At 36 months of age the children who had received a large amount of food supplementation showed a far lower prevalence of growth retardation than did those who received smaller quantities. Again, this correlation could not be attributed to any other major maternal variables. In regard to mental development, food supplementation was found to correlate with better performance in psychological tests beginning at six months of age. At 36 months the correlations were significant in five different tests. The results of this analysis have wide-ranging implications for public health. Given the recognized association between low birthweight and infant mortality, they point especially to the importance of maternal nutrition during pregnancy in programs aimed at reducing this serious problem.

Child, Preschool↗
PubMedDate not supplied

Screening for depression in the older adult: criterion validity of the 10-item Center for Epidemiological Studies Depression Scale (CES-D)

BACKGROUND: The Center for Epidemiological Studies Depression Scale (CES-D) has been widely used in studies of late-life depression. While the CES-D is convenient to use in most settings, it can present problems for elderly respondents who may find the response format confusing, the questions emotionally stressful, and the time to complete burdensome. A briefer 10-item version has been proposed, but there are few data on its properties as a screening instrument. METHODS: The 10-item CES-D was administered in 2 studies. In study 1, a stratified sample of middle-aged depressed patients (n = 40) and comparison controls (n = 43) were administered the CES-D to determine an optimal cutoff score. In study 2, the accuracy of the CES-D optimal cutoff score was tested in a sample of adults older than 60 years (n = 68). Major depression diagnoses were derived from the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, with consensus diagnoses using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. RESULTS: Reliability statistics with the 10-item CES-D were found to be comparable to those reported for the original CES-D. Using an optimal cutoff score of 4 in study 1, the sensitivity of the 10-item CES-D was 97%; specificity, 84%; and positive predictive value, 85%. In the study 2 sample of older adults, the sensitivity of the CES-D was 100%; specificity, 93%; and positive predictive value, 38%. CONCLUSION: The 10-item CES-D has excellent properties for use as a screening instrument for the identification of major depression in older adults.

Aged↗
PubMedDate not supplied

Propranolol treatment affects parameters of human immunity.

Elevated sympathetic activity can modulate parameters of immunity. We investigated the role of the low sympathetic activity in resting healthy volunteers by treating them with the beta-adrenergic antagonist propranolol (3 x 40 mg/d for 7 days). Propranolol treatment increased the number of circulating T cells but not that of other white blood cells. Similarly, Con A-stimulated lymphocyte proliferation and IL-2 formation were enhanced. Although the number of circulating NK cells did not change, NK-cell activity was reduced markedly after propranolol treatment. These alterations are not a mirror image of the changes observed under conditions of elevated sympathetic activity but demonstrate that withdrawal of the endogenous sympathetic tone by drugs such as propranolol can modulate parameters of human immunity.

Adult↗
PubMedDate not supplied

Assessment of olfactory deficits in detoxified alcoholics.

Olfactory functioning was evaluated in 37 male detoxified alcoholics and in 21 age-matched nonalcoholic controls using the University of Pennsylvania Smell Identification Test (UPSIT). Of the original subjects, 23 alcoholics and 14 controls returned for reevaluation 3-4 months following initial testing. The results showed that alcoholics had significantly lower UPSIT scores than did the controls, both at baseline and follow-up testing. Thirty-two percent of the alcoholics' UPSIT scores, in comparison to five percent of the controls' scores, fell into the clinically impaired range. Although current smoking patterns correlated significantly with UPSIT indices, comparisons limited to nonsmokers still indicated that the alcoholics were significantly impaired on this olfactory task. Correlational analyses indicated that olfactory performance was unrelated to alcoholics' scores on visuoconceptual and language tasks. Correlations with MR-derived indices of CSF volume showed a highly significant relationship between UPSIT scores and cortical sulcal volumes. Additionally, alcoholics (N = 15) who remained abstinent had significantly higher scores at follow-up than those who were not abstinent (N = 8). These findings demonstrate that alcoholism is associated with basic olfactory impairments which are only partially reversible with abstinence and that cortical structures play an important role in this sensory loss.

Adult↗
PubMedDate not supplied

Olfactory loss in alcoholics: correlations with cortical and subcortical MRI indices.

The relationship between olfactory identification ability and MRI volumetric indices of specific cortical and subcortical brain regions was investigated in 36 recently detoxified male alcoholics. The results of correlational analyses between MRI indices and score on the University of Pennsylvania Smell Identification Test (UPSIT) revealed that impairment in olfactory identification was associated with elevated cortical and ventricular CSF volumes as well as with reduced tissue volumes in the cortical and subcortical grey matter. The volume of the thalamus was found to be a significant unique predictor of UPSIT score, even after accounting for variance shared with other MRI indices. These findings provide the first empirical support for existing hypotheses that olfactory loss in alcoholic subjects may be mediated by both cortical and subcortical structures.

Alcoholism↗
PubMedDate not supplied

Polysomnography and depressive symptoms in primary alcoholics with and without a lifetime diagnosis of secondary depression and in patients with primary major depression.

BACKGROUND: There is evidence suggesting that there is: (1) additive polysomnographic effects of alcoholism and depression; and (2) elevated baseline REM density in primary alcoholics with (PASD) and without lifetime history of secondary depression (NPA). METHODS: 23 PASDs, 59 NPAs, and 23 primary major depression patients (PMD) underwent polysomnography. Any drinking within 3 months after a 1-month inpatient alcohol rehabilitation defined relapse. RESULTS: PASDs' polysomnography was more like NPAs than PMDs. Polysomnography reflected 3-month sobriety status more than diagnosis. LIMITATIONS: Not all PASD's met full major depression criteria upon admission. CONCLUSIONS: Alcoholism affected polysomnography more than depression. Elevated admission REM density predicted 3-month relapse in PASDs and NPAs.

Adult↗
PubMedDate not supplied

Electroencephalographic sleep and natural killer activity in depressed patients and control subjects.

Insomnia is associated with a reduction of natural killer (NK) activity in depression independent of the severity of other depressive symptoms. This study extends these findings by exploring the relationship between objective electroencephalographic (EEG) assessment of sleep and values of NK activity in depressed patients (n = 23) and in control subjects (n = 17). The sleep EEG parameters total sleep time, sleep efficiency, and duration of nonREM sleep were each positively correlated with NK activity in the depressed patients and in the control subjects, demonstrating similar relationships between the amount of sleep and NK activity in the separate groups. These observations support the hypothesis that sleep measures are associated with NK cytotoxicity, independent of the effects of severity of depressive symptoms or the presence of a mood disorder.

Adult↗
PubMedDate not supplied

Partial sleep deprivation reduces natural killer cell activity in humans.

Sleep disturbance, measured by either subjective report or electroencephalographic (EEG) assessment of sleep, correlates with a reduction of natural killer (NK) cell activity in major depression. To test whether sleep loss independent of mood disturbance alters daytime values of cellular immune function, the effect of late-night partial sleep deprivation on NK cell activity was studied in 23 medically and psychiatrically healthy male volunteers. After a night of sleep deprivation between 3 and 7 AM, NK cell activity was reduced in 18 of the 23 subjects with average lytic activity reduced significantly (p < .01) to a level 72% of the mean of three separate baseline values. After a night of resumed nocturnal sleep, NK cell activity had returned to baseline levels. These data implicate sleep in the modulation of natural immunity and demonstrate that even modest disturbances of sleep produce a reduction of NK cell activity.

Adult↗
PubMedDate not supplied

Plasma catecholamine and lymphocyte beta 2-adrenergic receptor alterations in elderly Alzheimer caregivers under stress.

OBJECTIVE: The purpose of this study was to determine the effects of chronic stress on beta-adrenergic physiology in elderly spousal caregivers to Alzheimer patients. METHODS: Thirty-seven elderly spousal caregivers and matched noncaregiver controls (mean age 73 years, SD = 6) were studied. Life stress categorization (presence of marked threat) covering the previous 6 months was determined using a semistructured interview based on the Psychiatric Epidemiological Research Inventory and the Life Events and Difficulties Schedule. beta 2-adrenergic receptor sensitivity (isoproterenol-stimulated cyclic AMP accumulation) and density were determined in lymphocytes. RESULTS: Caregivers with high life stress had higher plasma norepinephrine levels (p < .04) but no change in plasma cortisol. For beta-receptor sensitivity, 30% of the variance was accounted for by high life stress rating, increased age, being male, and lower norepinephrine (p = .018); 17% of the variance in beta-receptor density was accounted for by plasma norepinephrine (p = .03). CONCLUSIONS: The findings demonstrate that chronic high stress may be associated with changes in adrenergic physiology and may provide a mechanism through which chronic stress alters cellular immunity.

Adult↗
PubMedDate not supplied

Reduction of natural killer cytotoxic activity in major depression: interaction between depression and cigarette smoking.

OBJECTIVE: Epidemiological data suggest that the presence of a depressed mood combined with cigarette smoking increases the risk of cancer at sites associated with smoking and at sites not associated with smoking. This study tested the hypothesis that major depression and smoking together contribute to a decline of natural killer cell (NK) activity, an immune parameter thought to be important in immune surveillance. METHODS: A sample of 245 men were stratified into four groups: control subjects who were not smokers, control subjects who were smokers, subjects with major depression who were not smokers, and subjects with major depression who were smokers. Blood samples were obtained for measurement of total white blood cell (WBC) counts, differential cell counts, and assay of NK activity. RESULTS: Major depression and cigarette smoking interact and were together associated with changes in WBC counts and NK activity. Depressed subjects who were smokers had higher WBC counts (p < .001) and lower NK activity (p < .01) than depressed nonsmoking subjects. However, WBC counts and NK activity were similar in control smokers and nonsmokers. Backward elimination regression analyses showed that the interaction of depression and smoking significantly (p < .001) predicted WBC counts and NK activity. CONCLUSIONS: This study extends previous findings of immune alterations in patients with major depression. Major depression and smoking interact and together contribute to an elevation of total WBC count and a decline of NK activity.

Adult↗