DSP4-induced noradrenergic lesions increase beta-adrenergic receptors and hippocampal electrophysiological responsiveness

Following profound (greater than 90%) depletions of norepinephrine (NE) by the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4), the numbers of beta-adrenergic receptors were significantly increased (20-25%) in rat hippocampal and somatosensory cortical membranes; however, the numbers of alpha 1-adrenergic receptors and the affinities of both types of receptors were unaffected. This selective up-regulation of beta-adrenergic receptors was evident 1 week after DSP4 administration and was maintained for at least 2 more weeks. In electrophysiological experiments in the hippocampal slice preparation, responses to threshold as well as maximal concentrations of isoproterenol were enhanced 150% and 33%, respectively, in the DSP4-lesioned animals. The results demonstrate that nearly complete depletion of brain NE produced by administration of DSP4, like that produced by 6-hydroxydopamine, results in increased numbers of beta- but not alpha-adrenergic receptors, and suggest that the density of the former are regulated by afferent noradrenergic fibers. Furthermore, the functional significance of the increased number of hippocampal beta-adrenergic receptors is directly manifested in a greater electrophysiological responsiveness to an exogenously administered beta-adrenergic receptor agonist.     

Pulmonary angiography with iopamidol: patient comfort, image quality, and hemodynamics

The choice of a contrast agent for pulmonary angiography has important implications for patient comfort, image quality, and perhaps the safety of the procedure, particularly for "high-risk" patients. In a prospective study the nonionic, low-osmolality agent iopamidol eliminated the problem of image degradation due to coughing, and patients showed excellent tolerance for it. However, pressure measurements obtained within 3-5 minutes of injection of iopamidol and diatrizoate sodium meglumine 76% showed no significant difference in the hemodynamic effects of the two contrast agents, either for normotensive or for pulmonary hypertensive patients. Contrary to a common presumption, pulmonary hypertension by itself did not appear to increase the risk of pulmonary angiography. The theoretic presumption of greater hemodynamic stability with low-osmolality contrast agents was not clinically evident in this trial with iopamidol. At present, enhanced patient comfort and improved image quality remain the only confirmed bases for choosing this contrast agent for pulmonary angiography.     

AN ATYPICAL CASE OF ATYPICAL PNEUMONIA

SUMMARY A 23-year-old man, previously fit and well, presented with an atypical pneumonia, associated with microangiopathic anaemia, thrombocytopenia, rhabdomyolysis and renal impairment. Despite administration of intravenous fluids and antibiotics, his condition rapidly deteriorated, and the possibility of an aggressive connective tissue disorder was raised. Thus he was treated with high-dose oral steroids and plasma exchange until autoantibodies were shown to be negative. At this stage it transpired that the patient had swallowed water from a stream three weeks earlier, and leptospira antibody titres were subsequently found to be elevated. Antibiotics were continued, and after a protracted course he made a full recovery. Leptospirosis should be remembered as a rare cause of atypical pneumonia, particularly if there is associated hepatic or renal impairment.     

Kernicterus in an adult who is heterozygous for Crigler-Najjar syndrome and homozygous for Gilbert-type genetic defect

Gilbert syndrome is a common genetic disorder associated with mild unconjugated hyperbilirubinemia and no clinical illness. In contrast, Crigler-Najjar syndrome types I and II are rare genetic disorders associated with severe unconjugated hyperbilirubinemia and a life-long risk of kernicterus. Patients with Gilbert syndrome have low levels of a normal form of uridinediphosphoglucuronate glucuronosyltransferase because of a defect in the promoter region of both alleles, whereas patients with Crigler-Najjar syndrome are homozygous for a defect that yields an abnormal form of the enzyme that has limited or no activity. This case report describes a young adult with Crigler-Najjar syndrome type II in whom kernicterus developed after a laparoscopic cholecystectomy. The development of kernicterus was the result of a largely preventable series of events that lead to an increase in the free fraction of his serum bilirubin. Analysis of his genetic defect showed that he was homozygous for the mutation associated with Gilbert syndrome and heterozygous for a second mutation in the open reading frame of one allele of the bilirubin uridinediphosphoglucuronate glucuronosyltransferase gene. The combined defect leads to severe hyperbilirubinemia and shows how seemingly benign genetic defects, when combined, can cause serious clinical disease. (Gastroenterology 1997 Jun;112(6):2099-103)     

SAFETY,EFFECTIVENESS AND COST EFFICACY OF DIAGNOSTIC ELECTROPHYSIOLOGY AND RADIOFREQUENCY ABLATION IN A DISTRICT GENERAL HOSPITAL

Electrophysiological studies (EPS) are now being performed in district general hospitals (DGH) in the UK. In order to audit our results, a prospective database was established for all patients undergoing EPS and radiofrequency (RF) ablation at Eastbourne District General Hospital, East Sussex. Between 1 January 1997 and 1 July 2000, 300 EPS procedures were performed, resulting in 155 RF ablations. The average RF ablation procedure time was 119.3 minutes with an average fluoroscopy time of 19.1 minutes. Cost per RF ablation procedure was £1166.79 excluding use of facilities, pacemaker devices, medical nursing and radiography staffing costs. The overall success rate for RF ablation was 93.6% with a major complication rate of 0.6%, a total complication rate of 3.9% and no associated mortality. We have shown that RF ablation can be performed safely, effectively and economically in a DGH setting with a high rate of success and a low complication rate.     

Methodology for coupling local application of dopamine and other chemicals with rapid in vivo electrochemical recordings in freely-moving rats

Methodology is presented for constructing and using an electrode/microcannulae assembly that allows in vivo electrochemical measurements coupled with local application of dopamine (DA) and other chemicals in the unanesthetized freely-moving rat. Rats were implanted with a voltammetric electrode constructed of a carbon fiber sealed in fused silica tubing attached to a pair of stainless steel guide cannulae, into which fused silica injection cannulae were inserted for local application of DA and other chemicals. Precise delivery of nanoliter volumes was accomplished using a syringe drive combined with a fluid swivel to deliver the solutions to the injection cannulae. A newly-designed miniature potentiostat connected to a commutator via a modular telephone jack assembly allowed for high-speed chronoamperometric electrochemical recordings in freely-moving rats. Initial experiments characterized the in vitro electrochemical recording characteristics of the voltammetric electrode. In vivo studies were also carried out to study clearance of locally-applied DA and of potassium-evoked endogenous DA in the striatum and nucleus accumbens of freely-moving rats. In addition, the effects of chloral hydrate anesthesia on DA clearance signals in the nucleus accumbens were investigated. Moreover, the stability and reproducibility of this recording technique for measuring exogenous DA clearance was verified over a period of 5 days. Finally, the concurrent effects of systemic cocaine injection on DA uptake in nucleus accumbens and locomotor activity were examined. These studies support the conclusion that the methodology described herein allows for rapid chronoamperometric electrochemical recordings in freely-moving rats with precise microapplications of DA and other chemicals combined with concurrent measures of animal behavior.     

Teenage mothering, admission to hospital, and accidents during the first 5 years

One thousand and thirty-one singleton children of teenage mothers were compared with 10 950 singleton children of older mothers in a national longitudinal cohort study. Children born to teenage mothers and living with them during the first 5 years were more liable to hospital admissions, especially after accidents and for gastroenteritis, than were children born to and living with older mothers. Frequent accidents, poisoning, burns, and superficial injuries or lacerations were more often reported by teenage mothers. The association of teenage mothering with greater likelihood that children would have accidents or be admitted to hospital remained highly significant even after controlling for social and biological confounding influences. Although in part a marker for adverse socioeconomic circumstances, low maternal age appears to be a health hazard for children.