Aldehyde dehydrogenase activities in hepatocyte nodules and hepatocellular carcinomas from Wistar rats

The activities of aldehyde dehydrogenases using benzaldehydeand propionaldehyde as substrates and NADP and NAD as coenzymeswere determined in normal liver, hepatocyte nodules and hepatocellularcarcinomas from male Wistar rats. Hepatocyte nodules were producedby intermittent exposure of rats to 0.05% 2-acetylaminofluoreneor by initiation with diethylnitrosamine followed by selectionusing 2 weeks of dietary exposure to 0.02% 2-acetylaminofluoreneand partial hepatectomy. The activities of propionaldehyde:NAD and benzaldehyde: NADP aldehyde dehydrogenases were increasedin hepatocyte nodules of all types as well as in most hepatocellularcarcinomas. The most prominent elevation of enzyme activitywas found in the cytosol of persistent hepatocyte nodules (35–60times) and some hepatocellular carcinomas (92 times) using benzaldehydeand NADP. The benzaldehyde: NADP aldehyde dehydrogenase activityvaried considerably between different nodules suggesting theexistence of a subpopulation of hepatocyte nodules with veryhigh enzymatic activities. The activity of propionaldehyde:NAD aldehyde dehydrogenase activity as well as of -glutamyltransferasedid not show substantial internodular variations. The activityof benzaldehyde: NADP aldehyde dehydrogenase in individual carcinomasinvestigated in these experiments varied extensively. The datadid not support the idea that all hepatomas had been developedfrom pre-neoplastic nodules with very high activity of thisenzyme.     

Clotrimazole induction of cytochrome P-450: dose-differentiated isozyme induction

Treatment of male rats for 3 days with the N-substituted imidazole, clotrimazole, produced up to a 4-fold induction of hepatic microsomal cytochrome P-450. The monooxygenase activities induced varied with the dose administered. At low doses (less than 25 mg/kg), p-nitroanisole demethylase and aniline hydroxylase activities were induced. Only at higher doses were other monooxygenase activities (erythromycin and ethylmorphine demethylases and cytochrome P-450 metabolic-intermediate complex formation from troleandomycin) induced. Microsomal UDP-glucuronosyltransferase activity toward morphine was induced at low doses in a manner similar to that of p-nitroanisole demethylase. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of microsomes indicated that low doses of clotrimazole caused the intensification of a 48,000 molecular weight protein band, whereas at high doses, there was a marked intensification of an additional 50,500 molecular weight protein, the same molecular weight band as was intensified in phenobarbital- and dexamethasone-induced microsomes. The observations suggest a phenomenon of "dose-differentiated" isozyme induction for cytochrome P-450.     

Long-term follow-up of the Indiana conservative resurfacing hip arthroplasty

Sixty-four Indiana conservative (Depuy, Warsaw, IN) hip arthroplasties performed in 61 patients were reviewed for loosening, mechanisms of loosening, and revision rate. Mean follow-up time was 6.8 years. There were revisions in 26 hips (40.6%) with 4 hips awaiting revision, yielding a total of 30 hips (47%) defined as failures. Acetabular failure occurred in 20 hips, femoral failure in 18, and combined failure in 13. Failure of this prosthesis persists over time. There seems to be little or no place for this design in contemporary hip joint arthroplasty.     

A comparative trial of anti-glycoconjugate antibody assays: IgM antibodies to GM1

IgM class antibodies against the ganglioside GM1 have been found in a subgroup of patients with lower motor neuron syndromes and multifocal motor neuropathies (MMN). The pathogenic relevance of these antibodies is still unclear, but some MMN patients with IgM antibodies against GM1 seem to profit from immunosuppressive therapy. A reliable test for IgM antibodies against GMl may be useful for identifying these patients. We have assessed the comparability of the ELISA tests used for the determination of IgM against GM1 by sending coded serum samples to nine laboratories. In three samples high-titre IgM antibodies against GM1 were detected by all laboratories. This result was confirmed by dot blot immunodetection and thin-layer chromatography immuno-overlay. Seven samples were read as negative by nearly all laboratories. Major discrepancies between laboratories were noted in the analysis of one sample with results ranging from negative to high titre. Participating laboratories: N. Baumann and A. Ben Younes-Chennoufi, Neurobiologie cellulaire moleculaire et clinique, INSERM U134, Hôpital de la Sâpetrière, Paris, France; P. Fredman and L. Svennerholm, Department of Psychiatry and Neurochemistry, Goteborg University, Sweden; N. Gregson and R. A. C. Hughes, Department of Neurology, Guy's and St. Thomas's Medical and Dental School, London, UK; A. A. Ilyas, Department of Neurosciences, University of Medicine & Dentistry of New Jersey, New Jersey Medical School, Newark, N. J., USA; A. Pestronk, Division of Neuromuscular Diseases, Washington University School of Medicine, St. Louis, Mo., USA; A. J. Steck, Service de Neurologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland (current address: Department of Neurology, University of Basle); H. Willison, Department of Neurology, University of Glasgow, Glasgow, UK     

Cholecystokinin: proofs and prospects for involvement in control of food intake and body weight

Evidence that CCK participates in the control of meal size is compelling, but the avenues by which CCK may affect daily food intake and body weight regulation are still uncertain. Although participation of brain CCK in control of food intake is acknowledged, our focus here is on participation of peripheral CCK in the control of food intake. Therefore, in this article we (1) review evidence for CCK's participation in control of meal size, (2) document involvement of CCK-A receptors located on vagal sensory neurons in control of food intake by exogenous and endogenous CCK, (3) point out apparent discrepancies in the experimental record, which auger for non-endocrine sources of CCK and non-vagal sites of CCK action, and (4) summarize recent observations, suggesting mechanisms by which CCK could participate in the control of daily food intake and body weight regulation.     

The lifetime of automatic semantic priming effects may exceed two seconds

The N400 component of event-related potentials (ERPs) was obtained in a modified version of the Neely [J.H. Neely, Semantic priming and retrieval from lexical memory: Roles of inhibitionless spreading activation and limited-capacity attention, Journal of Experimental Psychology: General, Vol. 106 (1977), pp. 226-254.] paradigm which permits unconfounding of semantic priming effects due to automatic and attentional processes. It was found that a short stimulus onset asynchrony (SOA) of 250 ms between the prime and the target was associated with automatic but not expectancy effects on the amplitude of N400. At a long SOA of 2000 ms between prime and target, semantic priming effects on N400 were obtained associated with both automatic and expectancy processes. Moreover, there was no significance difference in the magnitude of the automatic effects at the two SOAs, suggesting that automatic processing had not decayed within the 2000 ms interval between the prime and target. The results support the two-processing interpretation of semantic priming advanced by Posner and Synder [M.I. Posner, C.R.R. Snyder, Attention and cognitive control, in: R.L. Solso (Ed.), Information Processing and Cognition: The Loyola Symposium, Erlbaum, Hillsdale, NJ (1975).] and concur with the results of Neely [J.H. Neely, Semantic priming and retrieval from lexical memory: Roles of inhibitionless spreading activation and limited-capacity attention, Journal of Experimental Psychology: General, Vol. 106 (1977), pp. 226-254], with the exception of indicating a longer persistence of automatic processes.     

Changes in sensitivity to stimulus deviance in Alzheimer's disease: an ERP perspective

The mismatch negativity (MMN) of the event-related brain potential (ERP) reflects the storage of information in sensory memory. MMNs were recorded from eight patients with Alzheimer's disease (AD) and eight controls to small (delta50 Hz), large (delta300 Hz), and a variety of highly deviant, environmental sounds. Both old controls and patients showed robust MMNs to all three classes of deviant events, and robust P3 compounds (indicative of active attention) to the environmental sounds. The data suggest that patients with mild AD have an intact sensory memory mechanism that responds similarly to that of controls to systematic increases in deviance. However, for both older controls and patients, only highly deviant acoustic events are likely to involuntary capture attention.     

Morbidity and mortality in elderly trauma patients

BACKGROUND: Despite an increasing incidence, relatively few studies have examined the factors that predict morbidity and mortality in older patients and several reports have found standard predictors such as the Injury Severity Score to be less useful in this patient population. Similarly, the effect of skeletal injury has not been examined with regard to complications and mortality. The purpose of this study was to review a large multicenter experience with elderly trauma patients to isolate factors that might predict morbidity and mortality. The potential effect of skeletal long-bone injury was of particular interest. METHODS: The charts of all patients older than 60 years who were admitted to one of four Level I trauma centers after sustaining blunt trauma were reviewed. Mechanisms of injury included in the study were motor vehicle crash, pedestrian struck, fall from a height, and crush injury. Slip-and-fall injuries were excluded. A total of 326 patients met inclusion criteria. Variables studied included age, sex, mechanism of injury, Injury Severity Score (ISS), Revised Trauma Score, Glasgow Coma Scale (GCS) score, blood transfusion, fluid resuscitation, surgery performed (laparotomy, long-bone fracture stabilization, both), and timing of surgery. Outcome variables measured included incidence of adult respiratory distress syndrome, pneumonia, sepsis, myocardial infarction, deep venous thromboembolism, gastrointestinal complications, and death. chi2, logistic regression, t test, and nonparametric analyses were done as appropriate for the type of variable. RESULTS: The average age of the patients was 72.2+/-8 years. Overall, 59 patients (18.1%) died, of whom 52 of 59 survived at least 24 hours. Statistical significance for continuous variables (p < 0.05) using univariate analysis was reached for the following factors for the patients who died: higher ISS (33.1 vs. 16.4), lower GCS score (11.5 vs. 13.9), greater transfusion requirement (10.9 vs. 2.9 U), and more fluid infused (12.4 vs. 4.9 L). Logistic regression analysis was performed to determine the factors that predicted mortality. They included (odds ratios and p values in parentheses) transfusion (1.11, p = 0.01), ISS (1.04, p = 0.008), GCS score (0.87, p = 0.007), and fluid requirement (1.06, p = 0.06). Regarding surgery, orthopedic surgery alone had an odds ratio of 0.53, indicating that orthopedic patients was less likely to die than patients who did not undergo any surgery. Patients who underwent only a general surgical procedure were 2.5 times more likely to die (p = 0.03) and patients who underwent both general and orthopedic procedures were 1.5 times more likely to die (p = 0.32) than patients who did not require surgery. Early (< or =24 hours) versus late (>24 hours) surgery for bony stabilization did not have a statistical effect on mortality (11% early vs. 18% late). Two patients in need of bony stabilization, however, died before these procedures were performed. With regard to complications, regression analysis revealed that ISS predicted adult respiratory distress syndrome, pneumonia, sepsis, and gastrointestinal complications; fluid transfusion predicted myocardial infusion; and need for surgery and transfusion requirements predicted sepsis. These complications, in turn, were significant risk factors for mortality. This large series of elderly patients demonstrates that mortality correlates closely with ISS and is influenced by blood and fluid requirements and by GCS score. The institution-specific mortality was the same when adjusted for ISS. The need for orthopedic surgery and the timing of the surgery was not a risk factor for systemic complications or mortality in this series. CONCLUSION: Mortality is predicted by ISS and by complications in older patients. Seventy-seven percent of the orthopedic injuries were stabilized early, but the timing of surgery did not have any statistical effect on the incidence of complications or mortality. (ABSTRACT TRUNCA