Trauma systems and emergency medicine

The impact of trauma is a major public health challenge which is likely to escalate in the early 21st century. A systematic approach to this problem is required. This review explains the conceptual framework that defines a trauma system, gives a brief historical perspective and describes some of the essential elements of the system which should make a difference to patient outcome. Emergency physicians are well placed to play a leading role in the development and implementation of trauma systems.     

Anxiety and hippocampus volume in the rat.

In depressed patients as well as healthy controls, a positive relationship between hippocampal volume and trait anxiety has been reported. This study sought to explore the possible inter-relation between hippocampal volume and trait anxiety further. Magnetic resonance imaging at 7 T was used to measure hippocampal volumes in a rat model of extremes in trait anxiety (experiment 1) and in a Wistar population with normal anxiety-related behavior (experiment 2). In addition to anxiety-related behavior, potentially confounding factors (depression-like, exploratory, and locomotor behavior) were assessed. Experiment 1 globally supported the hypothesis of a positive relationship between hippocampus volume and trait anxiety but did not allow for ruling out possible confounds arising from cosegregation of other behavioral traits. Experiment 2 yielded strong evidence for a negative relationship which was specific for trait anxiety. Thus, the relationship between hippocampal volume and anxiety may be more complex than expected. Interestingly, anxiety-related behavior in experiment 2 had a stronger influence on hippocampal volume than depression-like behavior. In the light of hippocampal volume loss in anxiety disorder and frequent comorbidity of anxiety and depression, this finding suggests that further research into the relationship between anxiety and hippocampal volume may be critical for understanding hippocampal contributions to normal and pathological behavior.     

Human xenoreactive natural antibodies of the IgM isotype activate pig endothelial cells

Abstract: Preformed, xenoreactive natural antibodies (XNA) and complement (C) are involved in the initiation of vascular rejection of organs transplanted between discordant species, presumably by stimulating donor organ endothelial cells (EC). Although C is known to play a role in the activation of EC, it has not been clear whether the antibodies serve only to anchor the initial components of C, and thus permit the C cascade to proceed, or whether the antibodies themselves deliver a signal to the EC. We have tested affinity-purified human IgM containing XNA (IgM-XNA) for its ability to stimulate in vitro the up-regulation of genes in pig EC. Northern blot analysis shows that IgM, which contains XNA, stimulates mRNA accumulation for certain genes (including IL-8, PAI-1, and ECI-7, a new gene that we have found is associated with EC activation), but not others known to be up-regulated in response to TNF, IL-1 or LPS. Our results show that XNA provide a signal to EC, and thus may themselves participate in activation of EC and consequent vascular rejection.     

Hypothalamic-pituitary-gonadal function in two infants with Smith-Lemli-Opitz syndrome

We report on the hypothalamic-pituitary-gonadal function in 2 male infants with the Smith-Lemli-Opitz (SLO or RSH) syndrome. Both infants had abnormal external genitalia. Basal and LHRH stimulated plasma gonadotropins were normal for age (1 month). Plasma testosterone, androstenedione, and dehydroepiandrosterone sulfate were normal for age and sex. Some forms of congenital adrenal hyperplasia (17,20-desmolase deficiency, 17α-hydroxylase deficiency, and 3β-hydroxysteroid dehydrogenase deficiency) were ruled out by hormonal studies. The endocrinological findings indicate a normal hypothalamic-pituitary-gonadal function and a normal adrenal steroid biosynthesis in these 2 patients. A partial androgen receptor defect causing the genital malformations seems possible in one patient. Whether 5α-reductase deficiency is the cause of the male pseudohermaphroditism in SLO syndrome remains the subject of future studies. © 1992 Wiley-Liss, Inc.     

Reference and target region modeling of [11C]-(R)-PK11195 brain studies.

PET with [(11)C]-(R)-PK11195 is currently the modality of choice for the in vivo imaging of microglial activation in the human brain. In this work we devised a supervised clustering procedure and a new quantification methodology capable of producing binding potential (BP) estimates quantitatively comparable with those derived from plasma input with robust quantitative implementation at the pixel level. METHODS: The new methodology uses predefined kinetic classes to extract a gray matter reference tissue without specific tracer binding and devoid of spurious signals (in particular, blood pool and muscle). Kinetic classes were derived from an historical database of 12 healthy control subjects and from 3 patients with Huntington's disease. BP estimates were obtained using rank-shaping exponential spectral analysis (RS-ESA) (both plasma and reference input) and the simplified reference tissue model (SRTM). Comparison between plasma- derived BPs and those produced with the new reference methodology was performed using 6 additional healthy control subjects. Reliability of the new methodology was performed on 4 test-retest studies of patients with Alzheimer's disease. RESULTS: The new algorithm selected reference voxels in gray matter tissue avoiding regions with specific binding located, in particular, in the venous and arterial circulation. Using the new reference, BP values obtained using a plasma input and a reference input were in excellent agreement and highly correlated (r = 0.811, P < 10(-5)) when calculated with RS-ESA and less so (r = 0.507, P < 0.005) when SRTM was used. In the production of parametric maps, SRTM was used with the new reference extraction, resulting in test-retest variability (10.6%; mean ICC = 0.878) that was superior to that obtained using the previous unsupervised clustering approach (mean ICC = 0.596). CONCLUSION: Reference region modeling combined with supervised reference tissue extraction produces a robust and reproducible quantitative assessment of [(11)C]-(R)-PK11195 studies in the human brain.     

Effect of early and late antibiotic treatment in experimental acute pancreatitis in rats

Background The clinical course in acute necrotizing pancreatitis is mainly determined by bacterial infection of pancreatic and peripancreatic necrosis. The effect of two antibiotic regimens for early and late treatment was investigated in the taurocholate model of necrotizing pancreatitis in the rat. Materials and methods Seventy male Wistar rats were divided into five pancreatitis groups (12 animals each) and a sham-operated group (10 animals). Pancreatitis was induced by intraductal infusion of 3% taurocholate under sterile conditions. Animals received two different antibiotic regimes (20 mg/kg imipenem or 20 mg/kg ciprofloxacin plus 20 mg/kg metronidazole) early at 2, 12, 20, and 28 h after induction of pancreatitis or late at 16 and 24 h after induction of pancreatitis or no antibiotics (control). Animals were examined after 30 h for pancreatic and extrapancreatic infection. Results Early and late antibiotic treatment with both regimes could significantly reduce pancreatic infection from 58 to 8–25%. However, extrapancreatic infection was only reduced by early antibiotic therapy. While quinolones also reduced bacterial counts in small and large bowel, imipenem did not. Conclusions In our animal model of necrotizing pancreatitis, early and late treatment with ciprofloxacin/metronidazole and imipenem reduce bacterial infection of the pancreas. Extrapancreatic infection, however, is reduced significantly only by early antibiotic treatment. The effectivity of early antibiotic treatment in the clinical setting should be subject to further investigation with improved study design and sufficient patient numbers.     

Release of vasopressin from supraoptic neurons within the median eminence in vivo. A combined microdialysis and push-pull perfusion study in the rat

The present study was designed to investigate whether or not arginine vasopressin (AVP) is released from magnocellular neurons within the median eminence (ME) in vivo. Urethane-anesthetized adult male Wistar rats were equipped with a microdialysis probe aimed at the supraoptic (SON) or paraventricular nucleus (PVN), a push-pull perfusion probe resting in the ME, and a blood microdialysis probe within the jugular vein. Dialysis of the SON (but not the PVN) with Ringer's solution containing 56 mmol l⁻¹ K⁺ resulted in an increase in AVP release within the ME (to 492 ± 192% of release during basal conditions,P < 0.05) and into blood (to 138 ± 9%,P < 0.01) whereby the release probably occurred from axonal swellings and nerve terminals of supraoptic neurons which project through the internal zone of the ME to the posterior pituitary. The calculated amount of AVP released into the extracellular fluid of the ME was high enough (approximately 1 pg/μ1) to hypothesize that the neuropeptide could enter the portal blood capillaries in physiologically relevant concentrations. Taken together, the present study indicates that activation of magnocellular neurons is accompanied by release of AVP within the median eminence. We assume that AVP released in this way might mediate a communication between the hypothalamic-neurohypophysial system and the hypothalamic-pituitary-adrenal axis in response to selected stressful stimuli.