Analgesic doses of fentanyl impair oxidative metabolism of neonatal hepatocytes

BACKGROUND/PURPOSE: Studies in human surgical neonates have shown that intraoperative fentanyl analgesia results in greater fall in perioperative body core temperature compared with morphine analgesia. The aim of the study was to compare in a neonatal animal model the biochemical effect of fentanyl and morphine on hepatocyte oxidative metabolism. METHODS: Hepatocytes were isolated from suckling rats and the oxygen consumption from palmitate was measured polarographically. In experiment A, fentanyl and morphine within the respective analgesic serum ranges were added to hepatocytes to assess the effect on oxygen consumption. In experiment B, fentanyl was added to hepatocytes in the presence of inhibitors of mitochondrial respiration to investigate its site of action. In experiment C, hepatocytes were incubated with either fentanyl or morphine, centrifuged, and then examined ultrastructurally by electron microscopy. RESULTS: In experiment A, fentanyl inhibited oxygen consumption by up to 40% (P < .01). Morphine inhibited oxygen consumption to a maximum of 25% (P < .01). In experiment B, in the presence of oligomycin, fentanyl increased the inhibition of oxygen consumption; however, in the presence of myxothiazol, no further inhibition by fentanyl occurred. In experiment C, mild ultrastructural alterations to hepatocytes were observed after incubation with fentanyl but not with morphine. CONCLUSIONS: This study demonstrates that therapeutic doses of two commonly used analgesic drugs impair neonatal hepatic oxidative metabolism. Fentanyl exerts a greater effect than morphine by diminishing liver oxygen consumption by up to 40%. The inhibitory effect of fentanyl occurs directly on the mitochondrial respiratory chain, either on substrate oxidation or on the thermogenic proton leak. The findings of this study are relevant to the perioperative management of surgical neonates.     

Describing traumatic responses and distress of community residents directly and indirectly exposed to an aircraft crash.

This study described the traumatic responses and the extent of psychological distress among residents who had been exposed directly or indirectly to an aircraft crash in Coventry, U.K. The direct exposure group consisted of 62 residents who were on the housing estate at the time of the accident and 20 who were not. They were interviewed on their subjective responses to the crash and then asked to fill in two distress measures: the Impact of Event Scale (IES) and the General Health Questionnaire (GHQ). The results showed a contrast between the responses of the two groups at the time of the crash. They also showed that the direct exposure group had a significantly higher score in the IES item of avoidance, the IES total, the GHQ items of somatization, social dysfunction, and the total score than the indirect exposure group had. Associations were then made between subjective responses and distress measures. Stepwise multiple regression analyses showed that for the direct exposure residents, the IES total was predicted by "whether they received professional help" and "whether they were worried about their safety after the crash." The GHQ total of the direct exposure residents was predicted by "anger about what had happened to them." For the indirect exposure residents, the IES total was predicted by "their present feelings when they heard planes flying over." There were no predictions found between responses and the GHQ total.     

Secretaries, depression and absenteeism.

This study examines the prevalence of Major Depressive Disorder; missed work; and mental health services use among secretaries and other women employed full-time. In a random sample of 3,484 women employed full-time, women employed as secretaries were significantly more likely to be depressed than other women even after controlling for socio-demographic characteristics (odds ratio = 1.69, 95% confidence interval = 1.05, 2.73). Secretaries were significantly more likely to report missing work in the last three months (odds ratio = 1.77, confidence interval = 1.01, 3.11); a finding not attributable to depression. Secretaries were also more likely to seek mental health services, but this finding was not significant (odds ratio = 1.78, confidence interval = 0.55, 5.78). It is possible that these findings are attributable to a selection effect whereby depressed women, and women who are likely to miss work, become secretaries. A second possibility is that women employed as secretaries have more "nonwork role stress" than other employed women. Alternatively, job conditions which result in dissatisfaction and stress may lead to depression and absenteeism. We believe our findings warrant further investigation into the work environment of secretaries.     

Albumin-binding surfaces for implantable devices.

Surfaces of implantable and blood contact-devices accumulate adsorbed and denatured proteins. This anomalous layer of proteins may help trigger unwanted events such as activation of coagulation systems and, perhaps, chronic inflammation. Because, in many experimental systems, the purposeful coating of surfaces with albumin will biologically "passivate" materials, we have attempted to develop polymers which, when exposed to blood or body fluids, will spontaneously, selectively, and reversibly adsorb host albumin. We report here a novel derivatization technique for increasing the albumin affinity of implantable polyetherurethane (PU). The technique is based on the incorporation of high-molecular-weight dextran to which the albumin-binding dye Cibacron Blue is covalently attached. Somewhat surprisingly, the amounts of human albumin adsorbed by Blue Dextran-modified and unmodified PU are quite similar. There are, however, important differences. First, the binding of albumin to derivatized PU is specific and not readily blocked by proteins in albumin-depleted human serum. Second, the majority of albumin associated with derivatized PU appears to be reversibly bound. Third, the binding of albumin to derivatized PU evidently is mediated primarily through ligand-specific binding of the protein to the albumin-binding dextran-dye conjugate. We conclude that it is possible to produce implantable polymers having surfaces which display albumin-binding dyes that selectively and reversibly bind albumin. Materials with this property, when implanted or exposed to blood, should form an infinitely renewable coating of albumin derived from physiologic fluids. This surface modification strategy may spawn a new generation of implantable materials with improved biologic compatibility.     

Sensory Excitatory Postsynaptic Potentials Mediated by NMDA and non-NMDA Receptors in the Thalamus in vivo

Excitatory amino acid neurotransmitters, such as l-glutamate, act at several receptors in the brain, which are sometimes referred to as N-methyl-d-aspartate (NMDA) and non-NMDA receptors. Extensive in vitro work indicates that both NMDA receptors and non-NMDA receptors contribute to excitatory postsynaptic potentials (epsps). The contribution of NMDA receptors to epsps in vivo under physiological conditions is, however, almost unknown. The receptors that mediate the epsps evoked in thalamic relay cells by natural stimulation of sensory afferents have been investigated in anaesthetized rats, and we report the first pharmacological characterization of an excitatory amino acid receptor-mediated epsp in vivo involving both non-NMDA receptors and, in particular, NMDA receptors.     

Boundary encroachment: pharmacists in the clinical setting

Summary This paper discusses the relationship between pharmacy and medicine in the light of recent claims that occupations such as pharmacy, whose central tasks arc organised around those of medicine, have gained increasing control over their sphere of work, thus contributing to a decline in medical hegemony. We discuss the process by which on the one hand, para-medical groups may extend their boundaries into areas officially the responsibility of the medical profession, and on the other, the medical profession may willingly delegate or indeed relinquish control over certain tasks. However, we argue from data collected from those groups in medicine and pharmacy concerned with the problems of drug use, that this does not necessarily indicate a decline in medical hegemony.     

Incorporation of 75Se-selenomethionine into human apoproteins. II. Characterization of metabolism of very-low-density and low-density lipoproteins in vivo and in vitro.

This investigation is designed to explore the potential role of apo VLDL as a precursor of a polypeptide component of human LDL. Attention was directed to the chromatography-defined Sf-I polypeptide fraction of apo VLDL, which has been previously shown to be immunologically and chemically indistinguishable from the major component of apoLDL.1-3 In VLDL isolated from bloow drawn within two hours following 75Se-SM injection, the Sf-I polypeptide fraction of apo VLDL was highly enriched with isotope, providing an appropriate preparation for in-vitro tracer studies. Conversion of 75Se-VLDL to 75Se-LDL occurred in vitro in the presence of normal plasma at 37 degrees C., and this conversion was augmented by post-heparin plasma. No conversion to HDL lipoproteins could be detected. Injection of heparin in vivo resulted in acute reciprocal changes in the radioactivity contained within serum apo VLDL and apoLDL. These findings suggest that a component of the Sf-I polypeptide fraction of apo VLDL can be metabolized into the apoprotein of LDL in man. Thus, the biochemical and immunologic similarities between the Sf-I fractions of apoVLDL and apoLDL may result from a physiologic "precursor-product" relationship between the apoprotein moieties of these two lipoprotein species. A method for further investigation of the metabolism of human apoprotein is suggested.     

A comparison of self-report and clinical diagnostic interviews for depression: diagnostic interview schedule and schedules for clinical assessment in neuropsychiatry in the Baltimore epidemiologic catchment area follow-up

BACKGROUND: The field of psychiatric epidemiology continues to employ self-report instruments, but the low degree of agreement between diagnoses achieved using these instruments vs. that achieved by psychiatrists in the clinical modality threatens the credibility of the results. METHODS: In the Baltimore Epidemiologic Catchment Area follow-up, 349 individuals who had a Diagnostic Interview Schedule (DIS) interview were blindly examined by psychiatrists using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN). Comparisons were made at the level of diagnosis, syndrome, and DSM-IV symptom group. Indexes of agreement were computed and characteristics of discrepant cases were identified. RESULTS: Agreement on diagnosis of major depressive disorder was only fair (kappa = 0.20), with the DIS missing many cases judged to meet criteria for diagnosis using the SCAN (29% sensitivity). A major source of discrepancy was respondents with false-negative diagnoses who repeatedly failed to report DIS symptoms attributed to life crises or medical conditions. Older age, male sex, and lower impairment were associated with underdetection by the DIS, using logistic regression analysis. In spite of the diagnostic discrepancy, there was substantial correlation in numbers of symptom groups in the 2 modalities (r = 0.49). Agreement was highest (about 55% sensitivity and 90% specificity) when both the SCAN and DIS thresholds were set at the level of depression syndrome instead of diagnosis. CONCLUSIONS: Weak agreement at the level of diagnosis continues to threaten the credibility of estimates of prevalence of specific disorders. A bias toward underreporting, as well as stronger agreement at the level of the depression syndrome and on ordinal measures of depressive symptoms, suggests that associations with risk factors are conservative.