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Biomedical subjects

M T Murphy

Publications and source records attributed to M T Murphy.

33 records · Page 2Linked to original sources

Maternal and fetal plasma atrial natriuretic peptide concentrations during elective caesarean section.

Atrial natriuretic peptide (ANP) is stored in the atrial cardiocyte and is capable of exerting potent, selective, and transient effects on fluid and electrolyte balance and on blood pressure. Because fluid shifts and hemodynamic adjustments occur during parturition, ANP might play a homeostatic role in the parturient and fetoplacental unit. We measured maternal and fetal plasma ANP concentrations in 19 parturients during elective caesarean section. Plasma ANP levels were also measured in seven nonpregnant women of the same age group. The baseline ANP concentration in parturients was significantly higher (29.77 +/- 6.06 pg/ml vs 7.37 +/- 2.1 pg/ml; mean +/- s.e.mean) than in their nonpregnant counterparts. The umbilical artery (UA) ANP concentration was significantly higher than the umbilical vein concentration (91.91 +/- 14.91 pg/ml vs. 40.04 +/- 9.71 pg/ml). Factors under the anaesthesiologist's control may influence maternal and fetal plasma ANP levels. There was a significant correlation between the volume of maternal Ringer's lactate infusion received and maternal ANP concentration. A significant correlation was seen between the total dose of ephedrine administered acutely prior to delivery and the UA ANP concentration. These data suggest that: 1) increased blood volume during pregnancy is associated with increased maternal plasma ANP levels, and 2) the fetus can produce its own ANP, and is thereby capable of responding to ANP stimulating factors.

Anesthesia, Obstetrical↗

Operation, anesthesia, and the endorphin system.

Endogenous opioid peptides regulate a multitude of neuronal pathways and extraneural targets (e.g., white blood cells). Acting in the periphery and at central sites of afferent integration within multiple compartments at multiple levels, they modify the secretion of other hormones yet are themselves secreted during stress to produce important biological effects. Usually quiescent, the opioid system becomes active during a host of stresses to optimize, integrate, and buffer bodily responses. During stress, endorphins act to limit sympathetically driven responses such as tachycardia and vasoconstriction; however, if given to resting subjects, opiates may evoke the very responses they inhibit during stress. As the roles of individual opioid peptides and opiate receptors are studied in increasing depth, an amazing degree of functional heterogeneity and detail has emerged. Such knowledge has barely begun to be exploited in creating the next generation of therapeutics.

Anesthesia↗

Postanesthetic shivering in primates: inhibition by peripheral heating and by taurine.

There has been little research on the cause(s) of postanesthetic shivering (PAS) and on specific interventions. Therefore, the authors investigated PAS in eight unoperated squirrel monkeys anesthetized with halothane-nitrous oxide mixture. Shivering developed in all monkeys in which body temperature was allowed to decrease (mean +/- SEM, 2.8 +/- 0.6 degrees C) during anesthesia. Shivering occurred in 25% of animals in which body temperature was actively maintained at preanesthetic levels during anesthesia. No shivering occurred in animals warmed both during and after anesthesia. Application of radiant heat to the skin stopped PAS immediately, even though deep body temperature remained low; shivering resumed within seconds after this heating was discontinued. Intracerebroventricular (0.1-2 mg) and intravenous (100 mg/kg) administration of the putative inhibitory neurotransmitter taurine also stopped the shivering in preliminary experiments, but central injection of alpha-melanocyte stimulating hormone (100-300 micrograms), an endogenous antipyretic, did not. The results implicate reduced body temperature and activation of central heat production pathways as major factors in PAS and suggest that halothane-nitrous oxide anesthesia per se, elevation of the thermal set-point, and surgical procedures are not essential to the shivering phenomenon. The results suggest for future study two methods to control PAS: application of radiant heat or administration of taurine.

Anesthesia, General↗

Beta-endorphin: effect on thermoregulation in aged monkeys.

In previous experiments small doses of the opiate morphine produced greater hyperthermia in aged than in younger sub-human primates. To test whether this augmented response is due to enhanced sensitivity of CNS opioid receptors with age, beta-endorphin (0.625-5 micrograms), an endogenous opioid peptide, was injected into the lateral cerebral ventricle (ICV) of young (less than 9 years) and aged (greater than 9 years) squirrel monkeys. Significantly greater hyperthermias developed in the older primates after each dose. In the aged monkeys, all but the smallest dose increased core temperature about 1.5 degrees C within 1 hr after injection. Mean rectal temperature in the younger animals rose 0.5-0.7 degrees after all but the largest dose (1-1.5 degrees C rise). Both groups maintained an elevated body temperature after central beta-endorphin throughout the 5 hr recording period. 1.25 micrograms beta-endorphin given ICV in a hot environment (30 degrees C) caused greater hyperthermia in older animals. This dose given in the cold (18 degrees C) caused large changes in temperature of the aged monkeys, either hyperthermia or marked decreases, whereas the young primates developed only moderate rises in body temperature. The same dose of morphine sulfate (1.25 micrograms) ICV produced similar changes in core temperature in the two age groups in each ambient temperature. These results indicate that: (1) stimulation of CNS opioid receptors influences thermoregulation and (2) aging increases responsiveness to such stimulation.

Age Factors↗

Effects of morphine on body temperature of squirrel monkeys of various ages.

Increased sensitivity to certain drugs is believed to contribute to dysthermia in the elderly. To learn whether the temperature-altering effects of an opiate are increased in aged primates, injections of morphine sulfate (0.5-4 mg/kg) were given SC in randomly assigned order to squirrel monkeys ranging in age from 3.5 to over 17 years. Hyperthermia was the predominant response with no clear relationship to age, although hypothermic and biphasic responses also occurred, most commonly after the highest dose. Lateral cerebral ventricular injections of 0.625 and 1.25 micrograms morphine sulfate evoked hyperthermia in monkeys over 8 years of age but did not affect the temperature of animals less than 5 years old. Doses of 2.5 and 5 micrograms usually elicited hyperthermia regardless of age, but 10 micrograms induced hypothermia in a majority of monkeys. Naloxone was given intraventricularly to several monkeys to limit the degree of hypothermia after high doses of morphine given peripherally or centrally. Thus in these primates, as in other species such as the rat, lower doses of morphine usually evoked hyperthermia, but sufficiently high doses caused body temperature to fall. Unlike the case in the squirrel monkey with diazepam and with endogenous substances such as leukocytic pyrogen and taurine, there was not a strong or consistent relationship between age and morphine-induced temperature changes.

Aging↗

Effects of alcohol on thermoregulation in aged monkeys.

Ethanol ingestion has been implicated in accidental hypothermia of the elderly, but there is no prior data on the relative sensitivity to alcohol of aged homeotherms that might account for disproportionate dysthermia in this age group. To assess their sensitivity, ethanol (0.5-2.0 g/kg) or H20 was given by gavage to squirrel monkeys less than 4 yrs old, 4-9 yrs of age and over 9 yrs old. Dose-related decreases in body temperature occurred in all three groups in a 25.5 degrees C environment, with the greatest decreases in the oldest animals. In an 18.5 degrees C environment the hypothermias caused by 0.5 and 1.0 g/kg ethanol were greatly augmented in old monkeys and in some cases their temperatures fell to potentially life-threatening levels. In a 30.5 degrees C environment, 1.0 g/kg ethanol given to monkeys caused approximately equal temperature reductions in the three groups. When determined after 1.0 g/kg ethanol, peripheral vasomotor tone increased significantly in animals of each age group in all three environments. Decreases in rectal temperature were associated with parallel decreases in oxygen consumption. These results indicate that: 1) aging is associated with an increased sensitivity to the hypothermic action of ethanol in thermoneutral and cold environments, 2) ethanol in the doses tested inhibits heat production mechanisms without suppressing compensatory vasoconstriction in response to decreased body temperature.

Aging↗

Prediction by surveillance cultures of bacteremia among neutropenic patients treated in a protective environment.

One hundred seventy-five consecutive marrow transplant patients who were treated in a protective environment for at least two weeks were studied to determine the usefulness of bacteriologic surveillance cultures for the prediction of bacteremia due to Staphylococcus aureus or aerobic gram-negative bacilli. Bacteremia with these organisms occurred in 15 patients (9%), and all patients were colonized with the respective organism before bacteremia occurred. Bacterial colonization was associated with a 17- to 174-fold increase in the relative risk of bacteremia. Negative predictive values were high, but positive predictive values were low owing to the infrequent occurrence of bacteremia. Surveillance cultures also predicted antibiotic sensitivities for all but one organism causing bacteremia. Bacteriologic surveillance cultures in the protective environment are thus useful both for the identification of patients at higher risk of bacteremia with certain types of organisms and for the identification of those who may fail to respond to antibiotic therapy as a result of infection with resistant organisms.

Adolescent↗

Peripheral administration of alpha-MSH reduces fever in older and younger rabbits.

In these experiments IV, ICV and intra-gastric administration of alpha-MSH reduced fever caused by injections of leukocytic pyrogen (LP). 2.5 micrograms alpha-MSH injected IV reduced fever caused by IV LP, more so in rabbits over 3 yrs old than in those under 2 yrs of age; 5 mg of acetaminophen given IV had no antipyretic effect in either age group. ICV administration of 25 ng alpha-MSH reduced fever caused by IV LP injection in the older but not in the younger rabbits, alpha-MSH given IV (2.5 micrograms) also lowered fever induced by ICV injection of LP in older but not in younger animals. Both older and younger rabbits showed reductions in fever evoked by IV LP after 2.5 mg alpha-MSH was given by gastric tube. The results indicate that this peptide which occurs naturally within the brain has potent antipyretic properties when given systemically, presumably as a result of a central antipyretic action. Greater sensitivity to central alpha-MSH in the older rabbits may account for the reduced febrile response seen in the aged. The findings support previous data which suggest that central alpha-MSH has a physiological role in the limitation of fever.

Acetaminophen↗

The role of self-directed in vivo exposure in combination with cognitive therapy, relaxation training, or therapist-assisted exposure in the treatment of panic disorder with agoraphobia.

The effects of self-directed in vivo exposure in the treatment of panic disorder with agoraphobia were examined. Seventy-four chronic and severe agoraphobic subjects were randomly assigned to Cognitive Therapy plus graded exposure. Relaxation Training plus graded exposure, or therapist-assisted graded exposure alone. Treatment consisted of 16 weekly 2.5-hour sessions. All subjects received programmed practice instructions for engaging in self-directed exposure as a concomitant strategy to their primary treatment. All subjects were instructed to keep systematic behavioral diary recordings of all self-directed exposure practice. The diary data were analyzed across and within treatments and assessment phases. Statistically significant findings were obtained across all diary measure domains with powerful repeated measures effects observed across all treatments. Significant between group effects and treatment x repeated measures interactions were obtained across the diary measure domains. Multiple linear regressions of in vivo anxiety levels and, to a lesser extent, frequency of self-directed exposure practice were found to be significantly associated with global assessment of severity at posttreatment and 3-month follow-up assessments. Furthermore, depression and marital satisfaction were significantly associated with in vivo anxiety. These and other findings are discussed with regard to their conceptual and clinical implications.

Adult↗

Murine monoclonal antibody with anti-e-like specificity: suitability for screening for e-negative cells.

A directly agglutinating murine monoclonal antibody of the IgG3 isotype has been produced after mice were immunized with papain-treated Bombay phenotype, e-positive red cells (RBCs). The antibody strongly agglutinated all e-positive RBCs and gave negative reactions with RBCs from Rhnull persons and those homozygous for Rh deletion genes. Variable reactivity was found with e-negative RBCs, ranging from weak to negative with R2R2, slightly stronger with r"r", and stronger still with RzRz. These reactions, together with results from tests with a large panel of Rh-variant RBCs, suggested a specificity for an epitope that is part of the e mosaic but is also expressed at least partially on e-negative RBCs and is influenced by the presence of C. This antibody has been standardized for use as a screening reagent for R2R2 cells by a microplate technique, and over 6000 donations have been screened in this way. No discrepancies have been found in confirmatory tests for e-negative status using human anti-e.

Animals↗