Adjustment of metabolism,catecholamines and β-adrenoceptors to 90 min of cycle ergometry

Adrenaline infusion of 0.1 g · kg^–1 · min^–1 in healthy volunteers results in an increase of hepatic glucose production, an increase of the absolute number of occupied -adrenoceptors and specific changes in metabolism. To compare these effects with the changes induced by an endogenous catecholamine release, we investigated healthy volunteers during cycle ergometry. After fasting at least 14 h seven healthy subjects exercised for 90 min at an intensity of 20% below their individual anaerobic threshold. The rate of glucose production as well as the turnover rates of alanine and leucine were calculated using stable isotope tracers. High and low affinity -adrenergic binding sites on lymphocytes were determined by an equilibrium binding assay with (–)¹²⁵ Iodocyanopindolol. After 90 min of cycling the rate of appearance of glucose increased significantly from means of 2.0 (SD 0.2) to 2.65 (SD 0.50) mg · kg^–1 · min^–1 with unchanged blood concentrations of glucose and lactate. The flux of the amino acids alanine and leucine decreased significantly from means of 0.91 (SD 0.21) to 0.62 (SD 0.14) mg · kg^–1 · min^–1 and from 0.40 (SD 0.05) to 0.32(SD 0.04) mg · kg^–1 · min^–1, respectively. The mean free fatty acid concentration increased significantly from 0.65 (SD 0.33) to 1.27 (SD 0.45) mmol · l^–1 during the endurance trial. The increase of glucose turnover and the decrease of amino acid flux point to a metabolic shift towards enhanced utilization of free fatty acids. Adrenaline and noradrenaline concentrations showed a moderate but significant increase from means of 0.61 (SD 0.20) to 0.99 (SD 0.36) nmol · l^–1 and from 2.27 (SD 0.75) to 3.46 (SD 0.38) nmol · 1^–1, respectively. The number of high affinity -adrenergic binding sites per cell (-adrenoceptors) nearly doubled from 770 (SD 130) to 1490 (SD 150) during 90 min of cycling. The observed endogenous plasma catecholamine concentrations were not sufficient to change significantly the relative receptor occupancy. This would seem to indicate that the aerobic exercise induced effects depended more on the absolute number of occupied -adrenoceptors than on their relative receptor occupancy. When compared to the results of the adrenaline infusion experiment the increases of the hepatic glucose production and the increase of -adrenoceptors were very similar in both groups despite ten times higher adrenaline plasma concentrations in the infusion group. This would seem to indicate that -adrenoceptors mediated effects do not correlate with catecholamine plasma concentrations.     

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP)

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.      

Osteopetrosis: MR characteristics at 1.5 T

Four patients with proved osteopetrosis (three with the infantile malignant form and one with the benign form) were examined with magnetic resonance imaging at 1.5 T. All patients were studied in the coronal and sagittal planes using both short and long repetition time/echo time sequences. The infantile malignant form was characterized by a complete lack of signal from the marrow alternating with a signal intensity equivalent to that of the intervertebral disks, resulting in a "stepladder" appearance. In the benign form or after successful marrow transplantation in the infantile malignant form, intermediate or high signal intensity in the vertebrae was noted, suggesting the presence of some marrow elements.     

Direct versus indirect transfer for traumatic brain injury to James Cook University Hospital: a retrospective study

IntroductionPatients with traumatic brain injury are referred to the neurosurgical unit at James Cook University Hospital, Middlesbrough, either from local accident and emergency departments (direct transfer from the scene) or from other hospitals (indirect transfer). This study looked at the outcome in both groups.Material and methodsThis was a retrospective observational study using trauma audit research network data for patients treated for traumatic brain injury at the neurosurgery department at the neurosurgical unit at James Cook University Hospital.ResultsA total of 356 patients with traumatic brain injury were admitted under the care of neurosurgeons; 143 (40%) of these patients had a neurosurgical procedure. Of the patients undergoing a neurological procedure, 111 patients were transferred directly while 32 were indirect transfers; 213 patients were managed conservatively. Of those managed conservatively, 165 were transferred directly while 48 were indirect transfers.We compared the length of hospital stay and Glasgow Outcome Scale score for the patients based on whether they were conservatively managed or required surgery in the direct and indirect transfer groups. The difference in the length of stay in the surgical and conservative groups following direct and indirect transfer was insignificant (p = 0.07). The time to the operation in direct and indirect transfer was also not statistically significant (p = 0.06).ConclusionPatients are as safe, if not safer, by reaching the nearest trauma unit with facilities for resuscitation and imaging.     

IMPACTED RIGHT UPPER CENTRAL INCISOR AND TRANSPOSITION OF TWO OTHER ANTERIOR TEETH ON THE SAME SIDE (A Case Report)

A young boy presented with an uncommon finding of impaction of upper right central incisor and transposition of canine and lateral incisor on the same side. Esthetic management of his cosmetic problem which included fixed appliance therapy followed by light cure restorations is discussed.KEY WORDS: Impaction, Transposition     

Einfluß verschiedener niedriger Droperidol-Dosierungen auf postoperative Angst, innere Anspannung, allgemeine Befindlichkeit und PONV

Background: Droperidol even in low doses such as 0,5?mg to 1,25?mg can increase postoperative anxiety and state of tension. The aim of this study was to determine whether these side effects occur frequently following low-dose droperidol and to see whether these are dose related. Methods: 184 female in- and outpatients ASA grade 1 and 2 undergoing gynaecological laparoscopy were recruited to this prospective, double-blind study. General anaesthesia was standardized (induction with thiopentone, fentanyl 2?µg/kg and vecuronium 0,1?mg/kg, tracheal intubation, maintainance with enflurane in N₂O/O₂). Patients were randomly allocated to receive saline (n=45), 0,625?mg (n=46), 1,25?mg (n=47) or 2,5?mg (n=46) droperidol i.v. 10 minutes before the end of surgery. 1, 3, 6, and 24 hours postoperatively, the patients’ anxiety, state of tension and overall mood was evaluated using two psychological questionnaires which had been tested for the perioperative period (Erlanger anxiety and tension-scale / BSKE-EWL-test). Sedation was evaluated by the staff of the recovery room. In addition, postoperative nausea and vomiting (PONV) was assessed using a 100?mm visual analogue scale and by counting the episodes of retching or vomiting. PONV was then rated over the whole observation period as none, mild, moderate or severe using a fixed scoring algorithm. Statistical analysis was performed using the ANOVA and the chi²-test. Results: The patients did not differ with regard to biometric data, duration of surgery and anaesthesia. The postoperative scores for anxiety, state of tension and overall mood were not different between the groups at any observation time (Fig.?1: anxiety and tension: P=0,5687; figure 2: overall mood: P=0,0647). Quality of sleep in the first night after surgery was the same in all groups (Table?2 and 3). Sedation was not significantly different (Table?4; P=0,0704). Furthermore, duration of stay in the recovery room did not differ (P=0,4353). On the other hand, three patients from the 2,5?mg droperidol group had to stay unexpectedly on the ward overnight, because they had been too much sedated to be discharged at home. This was not the case with any patient from the other groups. Compared to placebo, PONV over the whole 24?h observation period was significantly reduced by droperidol (Fig.?3; P=0,0338): completely free from PONV: placebo: 41,3%, 0,625?mg droperidol: 67,4%, 1,25?mg droperidol: 53,2%, 2,5?mg droperidol: 71,7%. Also the severity of PONV was reduced. Conclusion: In gynaecological laparoscopy under general anaesthesia with tracheal intubation, we recommend droperidol 0,625?mg in the prevention of PONV, as it reduces PONV as well as 2,5?mg with no severe sedation in this dosage. Psychological side effects did not occur more frequently after droperidol compared to placebo in any of the investigated dosages.     

Entwicklung eines neuen Closed-Loop Systems Regelung einer Mivacurium-induzierten neuromuskulären Blockade

There are many closed-loop control systems for muscle relaxants reported, but only a few could cope with the introduction of the latest shorter acting neuromuscular blocking drugs. These new muscle relaxants such as mivacurium require a fast adapting closed-loop system for controlling an adequate infusion. METHODS: After approval of the local ethics committee and having the patients' informed consent a total number of 75 patients [ASA I and II] were included in the study and assigned either to a training-, prediction-, prediction-/feedback- or a validation phase, as needed. Anaesthesia was induced and maintained with propofol in a TCI-mode with a plasma level of 3 to 5 micrograms/ml and 0.1 mg fentanyl boli as needed in all patients. In the last validation phase, having 20 patients, the prediction error and the error of the whole system was taken and analysed. RESULTS: A closed-loop system using a neural network as a predictor could be established. In the final validation phase consisting of 20 patients the mean square prediction error was found to be 0.1% +/- 0.2% [mean +/- SD]. The mean square error of the whole system was 0.55% +/- 0.59% [mean +/- SD]. CONCLUSIONS: A closed-loop system for control of a mivacurium infusion could be established. The system proofed to be reliable for a closed-loop infusion of mivacurium in order to maintain a predefined degree of neuromuscular blockade of 95% during routine surgery. The performance of the described controller is comparable to all recent attempts and could therefore be useful for scientific studies. It should be further validated and established for other muscle relaxants, as well.