Mechanism of adrenal insufficiency following trauma and severe hemorrhage: role of hepatic 11beta-hydroxysteroid dehydrogenase

BACKGROUND: Although adrenal insufficiency may not occur with moderate hypotension, it does occur with severe hemorrhage. Since hepatocellular function is depressed following severe hemorrhage, it remains unknown whether the liver plays any role in regulating adrenal function after trauma and hemorrhagic shock. HYPOTHESIS: Hepatic 11beta-hydroxysteroid dehydrogenase (11beta-HSD), a microsomal enzyme responsible for the degradation of bioactive corticosterone, plays a major role in the development of adrenal insufficiency following trauma and severe hemorrhage. DESIGN, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Male rats underwent laparotomy to induce trauma before hemorrhage. They were then bled to and maintained at a blood pressure of 40 mm Hg until 40% of the maximal bleed-out volume was returned in the form of Ringer lactate. The rats were then resuscitated with 4 times the volume of maximal bleed-out with Ringer lactate during a 60-minute period. Plasma levels of corticosterone and corticotropin were measured at various intervals. In additional groups, corticotropin-induced corticosterone release, adrenal contents of corticosterone and cyclic adenosine monophosphate (cAMP), hepatic 11beta-HSD activity, and plasma levels of corticosterone-binding globulin were determined at 1.5 hours after resuscitation. Moreover, a model of moderate hypotension (blood pressure, 80 mm Hg) was used to determine whether adrenal function is depressed under such conditions. RESULTS: At the time of maximal bleed-out, plasma corticosterone and corticotropin levels increased by 245% (P<.001) and 293% (P<.001), respectively. Despite corticotropin levels being similar to those of the animals undergoing sham operation after resuscitation, corticosterone levels in hemorrhaged animals remained elevated up to 4 hours after resuscitation (by 158%-207%; P<.001). In addition, corticotropin-induced corticosterone release decreased by 78% at 1.5 hours after resuscitation (P = .009). In contrast, moderate hypotension did not reduce corticotropin-induced corticosterone release. Adrenal corticosterone content and cAMP levels (i.e., the second messenger of corticotropin action) decreased by 55% (P<.001) and 25% (P = .03), respectively. Hepatic 11beta-HSD activity decreased significantly at 1.5 hours after resuscitation (P<.001). CONCLUSIONS: Sustained increase in plasma corticosterone levels following hemorrhage and resuscitation may be, in part, due to the decreased hepatic 11beta-HSD activity. The high level of corticosterone negatively regulates corticotropin release, further reducing adrenal responsiveness to corticotropin stimulation. Thus, the liver appears to play an important role in regulating adrenal function following trauma and severe hemorrhage.     

Expression of 25-hydroxyvitamin D3-1alpha-hydroxylase in the human kidney

The secosteroid hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) plays a vital role in calcium metabolism, tissue differentiation, and normal bone growth. Biosynthesis of 1,25(OH)2D3 is catalyzed by the mitochondrial cytochrome P450 enzyme 25-hydroxyvitamin D3 1alpha-hydroxylase (1alpha-hydroxylase). Although activity of this enzyme has been described in several tissues, the kidneys are recognized to be the principal site of 1,25(OH)2D3 production. To date, enzyme activity studies using vitamin D-deficient animals have suggested that 1alpha-hydroxylase is expressed exclusively in proximal convoluted tubules. With the recent cloning of 1alpha-hydroxylase, specific cRNA probes and in-house polyclonal antiserum have been used to determine the distribution of 1alpha-hydroxylase along the human nephron. Immunohistochemistry and in situ hybridization studies indicated strong expression of 1alpha-hydroxylase protein and mRNA in the distal convoluted tubule, the cortical and medullary part of the collecting ducts, and the papillary epithelia. Lower expression was observed along the thick ascending limb of the loop of Henle and Bowman's capsule. Weaker and more variable expression of 1alpha-hydroxylase protein and mRNA was seen in proximal convoluted tubules, and no expression was observed in glomeruli or vascular structures. These data show for the first time the distribution of alpha1-hydroxylase expression in normal human kidney. In contrast to earlier enzyme activity studies conducted in vitamin D-deficient animals, our data indicate that the distal nephron is the predominant site of 1alpha-hydroxylase expression under conditions of vitamin D sufficiency.     

Measurement of initial N-acetyl aspartate concentration by magnetic resonance spectroscopy and initial infarct volume by MRI predicts outcome in patients with middle cerebral artery territory infarction.

BACKGROUND AND PURPOSE: (1)H MR spectroscopy can be used to study biochemical changes occurring in the brain in stroke. We used it to examine the relationship between metabolite concentration (N-acetyl aspartate [NAA], lactate, cholines and creatines), size of infarct, clinical deficit, and 3-month clinical outcome in patients with middle cerebral artery (MCA) territory infarction. METHODS: Thirty-one patients with acute MCA territory infarction were recruited within 72 hours of the onset of symptoms. Single-voxel short echo time stimulated echo acquistion mode spectroscopy was used to obtain metabolite data from the infarct core. Metabolite concentrations were determined with use of variable projection time domain-fitting analysis. Infarct size was determined with T2-weighted images. Patient outcome groups at 3 months were "independent," "dependent," or "dead." RESULTS: All patients (100%; 95% CI 75% to 100%) who had an infarct >70 mL did poorly. Eighteen of 20 patients (90%; 95% CI 68% to 99%) with a core NAA concentration <7 mmol/L did poorly at 3 months, whereas 7 of 11 patients (64%; 95% CI 31% to 89%) with an initial NAA concentration >7 mmol/L did well. Combining these results showed that all patients who had an initial infarct volume >70 mL did poorly, irrespective of the NAA concentration. Of those patients with infarcts <70 mL, those who had a core NAA concentration >7 mmol/L did well (88%; 95% CI 47% to 100%), whereas those with a lower NAA concentration did poorly (80%; 95% CI 44% to 97%). There was no association between other metabolite concentrations and outcome. CONCLUSIONS: Infarct volume and NAA concentration can together predict clinical outcome in MCA infarction in humans.     

Hippocampal theta-related cellular activity in the superior colliculus of the urethane-anesthetized rat

In the present study, 93 cells in the superior colliculus (SC) were recorded extracellularly during the simultaneous occurrence of spontaneous theta field activity, sensory-induced (tail pinch) theta field activity, and large amplitude irregular (LIA) field activity, recorded from an electrode located in the stratum moleculare of the hippocampal formation (HPC). The effect of the intravenous administration of atropine sulfate (ATSO4) was also tested on SC cellular activity. The field activities of theta and LIA were recorded from all layers of the SC and were found to be temporally coherent with the same activities recorded simultaneously from the HPC, during all conditions tested. By using the criteria of Colom and Bland (1987) for the classification of theta-related cells, 75 of 93 cells (81%) were found to be related to the generation of theta field activity in the HPC and 18 of 93 (19%) were nonrelated. All cells recorded discharged in a tonic, nonrhythmic pattern during the theta HPC field states. Of the 75 theta-related cells, 61 (81%) were classified as tonic theta-ON cells and 14 (19%) as tonic theta-OFF cells. Although these cell types were found in all three layers of the SC, the majority of tonic theta-ON cells were recorded in the intermediate layer, and the tonic theta-OFF cells were dispersed evenly between the intermediate layer and the deep layer of the SC. The intravenous administration of ATSO4 abolished theta field activity in the HPC and SC, and the theta-related increase in the discharge rate of all tonic theta-ON cells tested. However, the same treatment did not have any effect on the discharge properties of tonic theta-OFF cells. The same stimuli that resulted in the inhibition of the discharge rates of these cells (tail pinch and electrical stimulation of the PH) in the predrug condition did so after the administration of ATSO4.     

Prognosis in schizophrenia. Prognostic predictors and outcome

Eighty-eight of 92 first-admission schizophrenics from 1963, an incidence by first admission cohort, were followed up in 1974 and 1975. Epidemiologically the sample was more comparable to lower European rates and expectancy rather than to higher American figures. Prior to follow-up, factors said to predict outcome were scored. This prognostic information was complete for 79 cases. Outcome was measured on a variety of criteria. The patients fell into a "poor prognosis" group based on the prognostic indicators, which were of little value in predicting prognosis within this group. However, patients who received extensive service during the follow-up period had poorer outcomes. Outcome was better than in most earlier studies of schizophrenia, but similar to that in some other recent studies of first-admission patients; also, the use of phenothiazines, short-term hospitalization, and community services may play a part. The failure of prognostic indicators to predict more than about 25% of the outcome variance for this group of "poor prognosis" patients supports the viewpoint that "good" and "poor" prognosis schizophrenia are two different entities.     

Environmental health impact in the hospital laundry

The task of surveying the hospital laundry is often dismissed by public health officials as unnecessary because the laundry cycle is generally considered to be capable of destroying all pathogens. Even though a properly operated laundry can produce a relatively bacteria free product, there are a number of variables that have an impact on the bacterial quality of the linen before it reaches the patient. It is vital that surveillance personnel understand these factors during processing, transporting, or sorting linen so that the final product is aesthetically, chemically, and bacteriologically acceptable for patient use. At the U. S. Public Health Service Hospital laundry in New Orleans, surveillance by the Environmental Health Department has identified potential problem areas. Operational improvements have been instituted at this laundry that would not have been possible without a thorough understanding of the laundry cycle. The authors describe the laundry cycle, including potential problem areas; identify useful microbial and chemical surveillance methods; and discuss process control procedures. This information will help the environmental health worker in discussions with laundry personnel regarding contamination control and operational efficiency.     

Bacteriologic and endotoxin analysis of salvaged blood used in autologous transfusions during cardiac operations.

Autologous blood transfusion is a common method of reducing the need for heterologous blood transfusion during cardiac operations. Recently we investigated an outbreak of severe, nonsurgical postoperative bleeding among patients undergoing heart operations and receiving intraoperative transfusion of blood from a cell conservation device (Cell Saver System, Haemonetics Corp., Braintree, Mass.). As a result of this investigation, we conducted a prospective study to determine if bacterial or endotoxin contamination of the blood collected in the Cell Saver System and used for reinfusion during heart operations contributes to postoperative bleeding complications. Patients' blood samples were collected immediately before operation, at the end of cardiopulmonary bypass, 1 hour postoperatively, and from the Cell Saver System. All blood samples were cultured for bacteria, and all plasma samples were assayed for endotoxin. Preoperatively all patients having heart operations were without signs of infection, 33 of 37 blood cultures taken were negative, and none of the plasma samples had detectable endotoxin. After discontinuance of cardiopulmonary bypass but before delivery of blood from the Cell Saver System, bacteria and endotoxin were detected in 11 of 36 (30.6%) and five of 35 (14.3%) of the patients' blood samples, respectively. The blood aspirated from the open chest and collected by the Cell Saver System was culture positive in 30 of 31 (96.8%) samples, and seven of 29 (24.1%) contained endotoxin. One of 28 blood samples collected 1 hour postoperatively was culture positive, and five of 25 samples contained endotoxin. Of 61 total microorganisms isolated, 50 (82%) were coagulase-negative staphylococci, four (6.6%) aerobic diphtheroids, five (8.2%) anaerobic "diphtheroids" (Propionibacterium acnes), and two (3.2%) gram-negative bacilli. Plasma endotoxin concentrations ranged from 10 to 765 pg/ml. No signs of endotoxemia or unusual bleeding were observed intraoperatively or postoperatively in any of the 38 patients. Although blood collected in the Cell Saver System and used for reinfusion during heart operations often was contaminated with gram-positive bacterial commensals of the skin and low concentrations of endotoxin, no adverse effects were noted in the patients.     

In vivo intrahippocampal microinfusion of carbachol and bicuculline induces theta-like oscillations in the septally deafferented hippocampus.

In their laboratory the authors have previously demonstrated that hippocampal slices could be induced to generate trains of "theta-like" oscillations by whole-bath perfusions of carbachol. Until recently, it has not been possible to generate similar activity in the septally deafferented hippocampus of an otherwise intact brain by microinfusions of carbachol. This study presents a full report of the first demonstration of a theta-like oscillation in the in vivo, septally deafferented hippocampal formation. Rats were anesthetized with urethane and implanted with microinfusion cannulae in the region of the medial septum/vertical limb of the diagonal band of Broca (MS/vDBB) and at single or multiple sites in the stratum moleculare of the fascia dentata. The MS/vDBB was microinfused with procaine hydrochloride to produce a reversible suppression lasting for approximately 20 minutes. Intrahippocampal microinfusions of carbachol or bicuculline alone (in the postprocaine condition of the MS/vDBB) failed to produce any theta-like oscillations. The combination of carbachol and bicuculline produced trains of theta-like oscillations during suppression of the MS/vDBB very similar to those seen in the slice preparations. The oscillations were blocked by intravenous administration of atropine sulfate, and they had the same depth profile as that of theta. Theta-on cells were shown to discharge in rhythmic bursts in synchrony with the oscillations. Thus, it would appear that the essential nature of the medial septal input to the hippocampal formation, for the generation of theta field activity in the intact brain, consists of a critical balance between cholinergic and GABAergic circuitry.     

The value of the history in the diagnosis of carpal tunnel syndrome

Details of the clinical history were elicited by questionnaire from 8,223 patients with suspected carpal tunnel syndrome and compared with the neurophysiological findings. Distribution of symptoms to the radial part of the hand and nocturnal exacerbation of symptoms showed the strongest individual correlations with positive nerve conduction studies. The regression model derived from the complete questionnaire achieved an overall sensitivity of 79% and specificity of 55% for the diagnosis of carpal tunnel syndrome when compared with the nerve conduction study results as a gold standard. A simple regression model for evaluating the history compares favourably with widely used clinical signs in its ability to predict the findings of nerve conduction studies.