Approach to the poisoned patient

Routine poison management involves the following: (1) stabilization, (2) toxidrome recognition, (3) decontamination, (4) antidote administration, (5) enhanced elimination of toxin, and (6) supportive care. Stabilization involves airway, ventilation, and circulation support. In the patient with altered mental status, oxygen, naloxone, glucose, and thiamine should be administered. Symptom complexes that relate to specific classifications of toxins are referred to as toxidromes. Emesis by means of syrup of ipecac is rarely used for in-hospital gastric decontamination. Activated charcoal is a useful adsorbent for gastric decontamination. Whole bowel irrigation is useful for iron, lead, and lithium poisoning and for the body packer phenomenon. Enhancement of elimination may involve multiple doses of activated charcoal, hemodialysis, or charcoal hemoperfusion.     

The effect of the immunomodulator neurotropin on the learning of active defensive behavior by rats

Rats were intraperitoneally injected with neurotropin (NSP), a substrate extracted from the inflammatory dermis of rabbits inoculated with Vaccine virus. Active avoidance behaviour of rats was studied. After NSP administration rats demonstrated higher levels of conditioning and true responses compared with control. In NSP-treated rats relationship between the time of beginning of intersignal run during learning and success of the avoidance trial differed from that in the control group. The results suggest that neurotropin administration activates the retrieval processes and leads to stronger consolidation of avoidance behaviour.     

5-HT1C receptor-mediated phosphoinositide hydrolysis in the rat choroid plexus after chronic treatment with clozapine

Chronic treatment with clozapine (14 days; 10 and 25 mg/kg/day) decreases 5-HT1C receptor density but not affinity in rat choroid plexus measured with [3H]mesulergine. We now report the effects of the same clozapine treatment regimens on the function of 5-HT1C receptors (measured by maximal stimulation of 5-HT1C receptor-mediated phosphoinositide hydrolysis) in relation to receptor changes in rat choroid plexus. Quantitative 5-HT1C receptor autoradiography indicated that chronic clozapine treatment decreased, in a dose-related manner, 5-HT1C receptor binding sites labeled by antagonist ([3H]mesulergine) and agonist ([125I](+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, [125I]DOI) radioligands. However, only the higher dose of clozapine decreased statistically significantly the maximal 5-HT1C receptor-mediated phosphoinositide hydrolysis response. Chronic administration of haloperidol (0.5 mg/kg/day) did not change any of the 5-HT1C receptor parameters. In conclusion, chronic clozapine treatment is able to modulate the function of 5-HT1C receptors. This further strengthens the possibility that 5-HT1C receptors may contribute to some of the atypical effects of clozapine.     

The induction of cyclooxygenase-2 by interleukin-4 in human umbilical vein endothelial cells: a possible role in regulation of fetal vascular tone

In immunocytes from the mollusc Mytilus galloprovincialis, the major pathway followed by platelet-derived growth factor (PDGF)-AB and transforming growth factor (TGF)-beta1 in provoking the release of norepinephrine, epinephrine and dopamine into cell-free hemolymph (serum) is mediated by a corticotropin-releasing hormone-adrenocorticotropin hormone (CRH-ACTH) biogenic amine axis. This axis not only annulled the inhibiting properties of PDGF-AB, it even reversed the latter's effect, while the inducing effect of TGF-beta1 was amplified. These findings show that non-classical immune-neuroendocrine molecules, such as PDGF-AB and TGF-beta1, are involved in building stress response, using the same conserved mechanisms present from invertebrates to vertebrates.     

In vivo studies on the role of the peripheral benzodiazepine receptor (PBR) in steroidogenesis

In various steroidogenic cell models, mitochondrial preparations and submitochondrial fractions, the expression of the mitochondrial 18 kDa peripheral-type benzodiazepine receptor (PBR) protein confers the ability to take up and release, upon ligand activation, cholesterol. Thus, cholesterol becomes available to P450scc on the inner mitochondrial membrane. These in vitro studies were validated by in vivo experiments. Treatment of rats with ginkgolide B (GKB), specifically reduced the ligand binding capacity, protein, and mRNA expression of the adrenocortical PBR and circulating glucocorticoid levels. Treatment with GKB also resulted in inhibition of PBR protein synthesis and corticosterone production by isolated adrenocortical cells in response to ACTH. The ontogeny of both PBR binding capacity and protein directly paralleled that of ACTH-inducible steroidogenesis in rat adrenal cells and in rats injected with ACTH. In addition, the previously described suppression of luteal progesterone synthesis in the pregnant rat by continuous in vivo administration of a gonadotropin-releasing hormone agonist may be due to decreased luteal PBR ligand binding and mRNA. These results suggest that (i) PBR is an absolute prerequisite for adrenocortical and luteal steroidogenesis, (ii) regulation of adrenal PBR expression may be used as a tool to control circulating glucocorticoid levels and (iii) the stress hypo-responsive period of neonatal rats may result from decreased adrenal cortical PBR expression.     

Brachial plexus injury during cardiac catheterisation in children. Report of two cases

The arm is particularly vulnerable to neurological injury, due to the intimate anatomical relationship between the brachial plexus and the traction zones. Severe injuries of the brachial plexus can be caused by compression, traction or laceration. Fortunately, many deficits are superficial and permanent neurovascular deficits are rare. Nevertheless, it is important to identify the probable cause of the injury since the prognosis for recovery directly depends on the underlying nature of the neurological deficit. Two anaesthetised children who suffered brachial plexus injury during cardiac catheterisation are reported. The first, with Ebstein's anomaly and significant pulmonary valve stenosis, presented, after the procedure, with a right arm motor deficit with proximal predominance. The second patient, with tetralogy of Fallot and pulmonary atresia, presented difficulty in left arm abduction and external rotation on awakening. The risk factors for brachial plexus lesions during anaesthesia are discussed. These include improper positioning, anaesthetic agents, extreme variations of body mass index and anatomical anomalies. Prevention, evolution and treatment of the brachial plexus injury are also considered. With proper care by the cardio-radiologist and anaesthesiologist the frequency of this injury can be reduced.     

Evolution and resolution of long-term cardiac memory

BACKGROUND: Cardiac memory (CM) refers to T-wave changes induced by ventricular pacing or arrhythmia that accumulate in magnitude and duration with repeated episodes of abnormal activation. We report herein the kinetics of long-term CM and its association with the ventricular action potential. METHODS AND RESULTS: Dogs were paced from the ventricles at rates of 110 to 120 bpm for approximately 3 weeks. CM characterized by gradual sinus rhythm T vector rotation toward the paced QRS vector evolved in all dogs regardless of pacing site (left ventricular [LV] anterior apex or base, posterior LV, or right ventricular free wall). Cardiac hemodynamics and myocardial flow (microsphere studies) were unaltered by the pacing. Recovery time for the memory T wave to return to control increased with duration of the previous pacing. The protein synthesis inhibitor cycloheximide markedly (P<.05) and reproducibly attenuated evolution of CM. When pacing was performed from the atrium, CM did not occur. Standard microelectrode techniques were used to study action potential from the LV free wall of control and CM dogs. CM was associated with increased action potential duration in epicardial and endocardial but not midmyocardial cells, significantly altering the transmyocardial gradient for repolarization. CONCLUSIONS: CM is a dynamic process for which the final T vector is predicted by the paced QRS vector and which is associated with significant changes in epicardial and endocardial but not midmyocardial cell action potential duration, such that the transmural gradient of repolarization is altered. It is unaccompanied by evidence of altered hemodynamics or flow, requires a change in pathway of activation, and appears to require new protein synthesis.     

Three-dimensional structure of the plant photosystem II reaction centre at 8 A resolution

Photosystem II is a multisubunit enzyme complex involved in plant photosynthesis. It uses solar energy to catalyse the breakdown of water to reducing equivalents and molecular oxygen. Native photosystem II comprises more than 25 different subunits, and has a relative molecular mass of more than 600K. Here we report the three-dimensional structure of a photosystem II subcomplex, containing the proteins D1, D2, CP47 and cytochrome b-559, determined by electron crystallography. This CP47 reaction centre, which has a relative molecular mass of 160K, can perform light-mediated energy and electron-transfer reactions but is unable to oxidize water. The complex contains 23 transmembrane alpha-helices, of which 16 have been assigned to the D1, D2 and CP47 proteins. The arrangement of these helices is remarkably similar to that of the helices in the reaction centres of purple bacteria and of plant photosystem I, indicating a common evolutionary origin for these assemblies. The map suggests that redox cofactors in the D1-D2 complex are located in positions analogous to those in the bacterial reaction centre, but the distance between the chlorophylls corresponding to the bacterial 'special pair' is significantly larger.