An electrophysiological investigation of the properties of a murine recombinant 5-HT3 receptor stably expressed in HEK 293 cells.

1. The pharmacological and biophysical properties of a recombinant 5-HT3 receptor have been studied by use of patch-clamp techniques applied to HEK 293 cells stably transfected with the murine 5-HT3 R-A cDNA. 2. At a holding potential of -60 mV, 77% of cells investigated responded to ionophoretically applied 5-HT with an inward current. Such currents were unaffected by methysergide (1 microM), or ketanserin (1 microM), but were antagonized in a concentration-dependent and reversible manner by the selective 5-HT3 receptor antagonist, ondansetron (IC50 = 440 pM) and the non-selective antagonists (+)-tubocurarine (IC50 = 1.8 nM) and metoclopramide (IC50 50 nM). 3. The 5-HT-induced current reversed in sign (E5-HT) at approximately -2mV and exhibited inward rectification. The influence of extra- and intracellular ion substitutions upon E5-HT indicates the 5-HT-evoked current to be mainly mediated by a mixed monovalent cation conductance. 4. Calcium and magnesium (0.1-10 nM) produced a concentration-dependent, voltage-independent, inhibition of the 5-HT-induced response. Zinc (0.3-300 microM) exerted a biphasic effect with low concentrations enhancing, and high concentrations depressing, the 5-HT-evoked current. 5. Fluctuation analysis of inward currents evoked by a low (1 microM) concentration of 5-HT suggests the current to be mediated by the opening of channels with a conductance of 420 fS. 6. The pharmacological and biophysical properties of the 5-HT3 R-A are similar to those previously described for 5-HT3 receptors native to murine neuroblastoma cell lines, with the exception that the function of the recombinant receptor was enhanced by low concentrations of zinc. This observation suggests that the properties of the native receptor are not completely represented by the 5-HT3 R-A subunit alone.     

Single dose ciprofloxacin for the eradication of pharyngeal carriage of Neisseria meningitidis

Single dose oral ciprofloxacin was given to all personnel in a naval training establishment as part of the management of an outbreak of meningococcal meningitis. Two thousand one hundred personnel received the drug and Neisseria meningitidis was eradicated from the pharynx of 97% of 570 who were swabbed two to four days later. In a cohort of 277 personnel who were followed for up to nine weeks, pharyngeal carriage was eliminated from 93% of 104 carriers. The overall prevalence of carriage fell from 19% to less than 1.5% as a result of the use of ciprofloxacin. Few side effects were encountered, compliance was good and meningococci resistant to the antibiotic were not found after therapy. A single oral dose of ciprofloxacin 500 mg eliminates pharyngeal carriage of N. meningitidis effectively and has few adverse reactions.     

Cellular and molecular effects of trimethyltin and triethyltin: Relevance to organotin neurotoxicity

Many of the neurotoxic aspects of organotin exposure have been described. Organotin exposure culminates in its accumulation in the CNS and PNS. The clinical picture is dominated by neurological disturbances; yet, the primary basis for their neurotoxicity is unknown. Trimethyltin (TMT) is primarily a CNS neurotoxin affecting neurons within the hippocampal pyramidal band and the fascia dentata. Triethyltin (TET) is a neurotoxin that produces a pathological picture dominated by brain and spinal cord edema. The first part of this review summarizes the current understanding of the interaction of TMT and TET with biologically active sites in the induction of neurotoxicity. In the second part, several hypotheses for the differential neurotoxic effects of these organotins and their shortcomings are discussed.     

A comparison of the Outcome Questionnaire‐45 and Outcome Questionnaire‐30 in classification and prediction of treatment outcome

Recent research has found that measuring, monitoring and providing therapists with feedback about their clients' treatment progress improves treatment outcome. This study assessed the level of agreement between two outcome measures used to measure and monitor treatment progress. The Outcome Questionnaire (OQ‐45) was compared with a shorter, derivative measure, the OQ‐30. Each measure has an associated feedback system, which provides therapists with feedback about their clients' treatment progress. The OQ‐45 and the OQ‐30 demonstrated high levels of agreement in measurement of client outcome. The OQ‐45 feedback system emerged as the most accurate and clinically useful method for providing therapists with feedback about their clients' predicted treatment outcomes. Copyright © 2006 John Wiley & Sons, Ltd.     

Preliminary experience with inhaled milrinone in cardiac surgery

Background: Inhaled administration of milrinone reduces pulmonary artery pressure. Pulmonary hypertension (PH) and right heart failure are associated with difficult separation from cardiopulmonary bypass (CPB). Therefore, inhaled milrinone could facilitate separation from CPB. Objective: To determine the impact and timing of administration of inhaled milrinone. Methods: A retrospective analysis of our experience on high-risk patients receiving inhaled milrinone was conducted to evaluate the postoperative course after administration of the drug. Results: Seventy-three patients received inhaled milrinone from June 2002 to February 2005. Mean age was 64 ± 13 years, with a mean preoperative Parsonnet score of 27 ± 14. Inhaled milrinone (5 mg) was administered before (n = 30) or after (n = 40) CPB, three patients had off-pump procedures and were excluded. CPB time was 145 ± 78 min with cross-clamping times of 91 ± 56 min without any significant difference between groups. Fifty-four patients (74%) had difficult separation from CPB, 14 patients (19%) required an intra-aortic balloon pump and 10 patients (14%) needed emergency reinitiation of CPB for hemodynamic instability. Ten patients died in the perioperative period (13.7%). Patients receiving inhaled milrinone prior to CPB initiation had a lowering pulmonary artery pressure after CPB (p < .01) and had less emergency reinitiation of CPB after weaning (3% vs 23%, p = .02) as compared to those with administration after CPB. No detectable side effects were directly linked to the administration of the drug. Conclusion: In this high-risk cohort, use of inhaled milrinone was well tolerated. Administration before initiation of CPB could help weaning from CPB.     

Qualitätssicherung und Hygiene beim ambulanten Operieren

BACKGROUND: According to the German Law on Infectious Diseases (Infektionsschutzgesetz or IfSG) German outpatient centres must provide evidence of maintaining certain standards of hygiene and record their nosocomial infection rates. To fulfill their legal obligations, the Commission for Hospital Hygiene and the Prevention of Infection recommends surveillance modules such as that known as AMBU-KISS. MATERIALS AND METHODS: The AMBU-KISS project centre implemented a survey to evaluate all procedures relevant to hygiene, surveillance of surgical site infections, and facilities available at centres participating in the AMBU-KISS surveillance programme. The questionnaire was returned by 99 of 110 participants. RESULTS AND DISCUSSION: All the centres possess cleaning and disinfection schemes, and practically all of them use written instructions on the processing of instruments and surgical hand disinfection procedure. Many of the participants spend too much time on surgical hand disinfection and presurgical skin disinfection. CONCLUSION: The survey demonstrates that hygienic conditions at centres participating in AMBU-KISS are largely satisfactory. However, there is nevertheless a need to optimise infection control measures.     

Growth hormone effects on hypertrophic scar formation: a randomized controlled trial of 62 burned children

The hypercatabolism after massive pediatric burns has been effectively treated with recombinant human growth hormone, an anabolic agent that stimulates protein synthesis and abrogates growth arrest. While experimental studies have shown increased potential for fibrosis induced by growth hormone therapy, adverse effects on human scars have not been investigated. Our aim was to evaluate hypertrophic scar formation in 62 patients randomized to receive injections of 0.05 mg/kg/day of recombinant human growth hormone or placebo, from discharge until 1 year after burn. Scar scales were used to evaluate scar-severity at discharge, 6, 9, 12, and 18-24 months after burn, by three observers blinded to treatment. Computer-assisted planimetry allowed quantification of percentage of hypertrophic scar formation. Types I and III collagens were localized and quantified in scars and normal skin of patients from both groups, using immunohistochemistry with confocal laser microscopy analysis. Insulin-like growth factor-1 blood levels helped assess compliance. Statistical analysis showed that scar hypertrophy significantly increased from 6 to 12 months after injury in both groups, while decreasing at 18-24 months postburn. Types I and III collagens were statistically increased in the reticular layer of scars from both groups when compared to paired normal skin. Insulin-like growth factor-1 was significantly increased in the recombinant human growth factor-treated group. No differences were seen when recombinant human growth factor and control groups were compared using the scar scales, planimetry, or immunohistochemistry. We concluded that recombinant human growth hormone therapy did not adversely affect scar formation and should not contraindicate the administration of recombinant human growth hormone as a therapeutic approach to severely burned children.