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Biomedical subjects

A Urwyler

Publications and source records attributed to A Urwyler.

At least 19 recordsLinked to original sources
PubMed1997

In vitro contracture test for diagnosis of malignant hyperthermia following the protocol of the European MH Group: results of testing patients surviving fulminant MH and unrelated low-risk subjects. The European Malignant Hyperthermia Group.

BACKGROUND: Determination of sensitivity and specificity of the in vitro contracture test (IVCT) for malignant hyperthermia (MH) susceptibility using the European MH Group (EMHG) protocol has been performed in some laboratories but only on a small sample from the combined EMHG. Thus, the purpose of the present study was to determine combined EMHG sensitivity and specificity of the test. METHODS: Results of IVCT of patients with previous fulminant MH and normal, low-risk subjects (controls) were collected from 22 centres of the EMHG. IVCT was performed according to the EMHG protocol. Patients were included in the study if the clinical crisis had a score of at least 50 points with the Clinical Grading Scale. Low-risk subjects were included provided they did not belong to a family with known MH susceptibility, they had not developed any signs of MH at previous anaesthetics, and they did not suffer from any neuromuscular disease. For inclusion of both MH patients and low-risk subjects, at least 1 muscle bundle in the IVCT should have twitches of 10 mN (1 g) or more. For evaluation of individual tests, only muscle bundles with twitch heights of 10 mN (1 g) or more were used. RESULTS: A total of 1502 probands had undergone IVCT because of a previous anaesthesia with symptoms and signs suggestive of MH. Of these, 119 had clinical scores of 50 and above. From these 119 MH-suspected patients and from 202 low-risk subjects, IVCT data were collected. Subsequently, 14 MH-suspected patients were excluded from further analysis for the following reasons: In 3 patients, the suspected MH episode could be fully explained by diseases other than MH; in 11 MHS patients, IVCT was incomplete (n = 1), data were lost (n = 3), or none of the muscle bundles fulfilled twitch criteria (n = 7). Of the remaining 105 MH-suspected patients, 89 were MHS, 10 MHEh, 5 MHEc, and one MHN. Thus, we observed a diagnostic sensitivity of the IVCT of 99.0% if the MHE group is considered susceptible (95% confidence interval 94.8-100.0%). Of the 202 low-risk subjects, 3 were MHS, 5 MHEh, 5 MHEc, and 189 MHN. This gives a specificity of the IVCT of 93.6% (95% confidence interval 89.2-96.5%). CONCLUSION: The IVCT for diagnosis of MH susceptibility in Europe has a high sensitivity and a satisfactory specificity.

Adolescent↗
PubMed1996

Effects of intravenous lidocaine and/or esmolol on hemodynamic responses to laryngoscopy and intubation: a double-blind, controlled clinical trial.

STUDY OBJECTIVES: To evaluate the efficacy of intravenous lidocaine and two doses of esmolol for attenuating the cardiovascular responses to laryngoscopy and intubation, and to assess whether a combination of both drugs is more effective than either drug alone. DESIGN: Randomized, prospective, double-blind, placebo-controlled study. SETTING: University hospital. PATIENTS: 90 ASA status I and II normotensive women scheduled for elective gynecologic procedures with general anesthesia. INTERVENTIONS: Induction of anesthesia was standardized for all patients. The first group received lidocaine 1.5 mg/kg (Group LID); the second and third groups received esmolol 1 mg/kg and 2 mg/kg, respectively (Groups E1 and E2, respectively); the fourth group received lidocaine 1.5 mg/kg and esmolol 1 mg/kg (Group LID-E1); the fifth group received lidocaine 1.5 mg/kg and esmolol 2 mg/kg (Group LID-E2); the sixth group received saline as a placebo (Group PLAC). MEASUREMENTS AND MAIN RESULTS: Systolic blood pressure and heart rate (HR) were recorded before induction, before injection of the first test drug, immediately before laryngoscopy, and 1, 2, and 5 minutes following intubation. Duration of laryngoscopy was recorded. Only patients receiving placebo had increased HR values after intubation compared with baseline values (p < 0.05). The proportion of patients with a maximum HR exceeding 90 beats/min was significantly higher in the placebo group (8 of 15 patients) than in both esmolol groups (E1 2 of 15; E2 2 of 15) (p < 0.05). Systolic blood pressure values after tracheal intubation did not differ among groups except for those receiving the combinations of lidocaine and esmolol, and they had significantly lower blood pressure (BP) values compared with placebo (p < 0.05). CONCLUSIONS: Esmolol 1 to 2 mg/kg is reliably effective in attenuating HR response to tracheal intubation. Neither of the two doses of esmolol tested nor that of lidocaine affected the BP response. Only the combination of lidocaine and esmolol attenuated both HR and BP responses to tracheal intubation.

Adolescent↗
PubMed1995

Bee venom immunotherapy results in decrease of IL-4 and IL-5 and increase of IFN-gamma secretion in specific allergen-stimulated T cell cultures.

The mechanisms of bee venom immunotherapy (VIT) are largely unknown. The aim of this study was to follow the changes of T cell cytokine secretion during the course of VIT. Ten bee venom-allergic patients with a history of severe systemic reactions, positive skin tests, and bee venom (BV)-specific serum IgE Abs were treated as follows: on the first day, a cumulative dose of 111 micrograms, starting with 0.1 microgram, was administered s.c. under intensive care conditions. Further injections of 100 micrograms BV were given on day 7, day 21, and thereafter at intervals of 4 wk. Blood samples were obtained just before the initiation of VIT, after the last injection on the same day, and before the subsequent BV injections on days 7, 21, and 50 of VIT. Peripheral blood mononuclear cells (PBMC) were stimulated with phospholipase A (PLA), the major BV allergen, or with a control Ag tetanus toxoid (TT). Cytokine secretion was measured 24 h after restimulation of the cultures with solid-phase bound OKT3 F(ab')2 mAbs after 7 days of culture. In PLA-stimulated cultures, VIT resulted in decreased IL-4 and IL-5 and increased IFN-gamma secretion. In TT-stimulated cultures, we observed similar levels of cytokines before and during VIT. We conclude that ultra-rush VIT changes allergen-specific T cell reactivity.

Allergens↗
PubMed1995

Paravascular lumbar plexus block: block extension after femoral nerve stimulation and injection of 20 vs. 40 ml mepivacaine 10 mg/ml.

The goal of this prospective randomized study was to assess the extension of the "three-in-one" paravascular lumbar plexus block after femoral nerve stimulation and injection of 20 vs. 40 ml mepivacaine 10 mg/ml. Three-in-one blocks were achieved in 12 of 39 (31%) patients given 20 ml of 1% mepivacine (group 1), and 17 of 41 (41%) patients given 40 ml (Group 2) of the same solution (n.s.). The level of successful blockade at each nerve did not differ between groups. The femoral nerve was blocked in 92% vs. 93% of patients in groups 1 and 2, respectively; the obturator nerve in 62% vs. 78%; and the lateral cutaneous femoral nerve in 41% vs. 44%. We conclude that femoral nerve stimulation is effective in faciliating blockade in the femoral nerve but not the obturator or lateral cutaneous femoral nerve with the tested solution and volumes, and therefore not particularly effective for achieving complete 3-in-1 blockade. Within the clinically relevant range of 20-40 ml, the volume of mepivacaine 10 mg/ml does not appear to influence the extent of blockade.

Adult↗
PubMed1994

Neuropeptides are potent modulators of human in vitro immunoglobulin E synthesis.

We determined the effect of adrenocorticotropin hormone (ACTH) on the regulation of IgE synthesis. Depending on the concentration, ACTH enhanced or inhibited IgE synthesis in a culture system where IgE synthesis was induced with interleukin-4 (IL-4) and anti-CD40 monoclonal antibody in peripheral blood mononuclear cells. Similar effects on IgE synthesis were observed by adding ACTH-related peptides, e.g. corticotropin-releasing factor (CRF), the inducer of ACTH, or alpha-melanocyte stimulating hormone (alpha-MSH), a cleavage product of ACTH. However, ACTH had no effect on IgG or IgM synthesis in this culture system. ACTH did not act directly on either B or T cells as there was no influence on IgE synthesis in a system using purified B cells alone or co-cultured with T cells. The effect of ACTH on IgE synthesis was mediated by accessory cells. This was shown by priming purified CD14-positive monocytes with ACTH and reconstitution experiments. Therefore, these findings suggest that ACTH and the related peptides CRF and alpha-MSH can influence the microenvironment modulating an IL-4 and anti-CD40 monoclonal antibody driven class switching to IgE via accessory cells.

Adrenocorticotropic Hormone↗
PubMed1994

[Malignant hyperthermia].

Malignant hyperthermia (MH) is a rare, life-threatening pharmacogenetic disease. The genetic incidence is estimated to be 1:10,000. In predisposed individuals, MH is triggered by volatile anaesthetics and/or depolarizing muscle relaxants by an abnormal increase of intracellular calcium concentration in skeletal muscle cells. The clinical presentation may vary from abortive MH to the fulminant MH crisis. Early diagnosis, the use of electrocardiography and capnography for anaesthetic monitoring, immediate cessation of trigger agents and dantrolene treatment are essential components of an effective MH therapy. In some MH families, a genetic alteration of the ryanodine receptor gene (a calcium channel of the sarcoplasmic reticulum) on chromosome 19 has been identified as the potential cause of MH susceptibility. Recent molecular biological findings support the view of MH being a heterogenetic disease. At present, the diagnosis in potentially MH-susceptible individuals is still made using the in vitro halothane and caffeine muscle contracture test.

Anesthesia↗
PubMed1994

Are laboratory values in bone marrow aspirate predictable for venous blood in paediatric patients?

In an emergency situation, early laboratory results are important, but often difficult to obtain. If venous access cannot be established, the intraosseous route may be used as an alternative. This study investigated the predictive value of bone marrow aspirate in performing laboratory studies. Thirty children underwent general anaesthesia for bone marrow aspiration (iliac crest) for oncologic or haematologic reasons. The aspirate and a peripheral venous blood sample, which was obtained simultaneously, were subjected to different laboratory tests and the results were compared by means of confidence interval analyses of the individual ratios of venous/bone marrow values. Based on these analyses, a high predictability of bone marrow values were found for haemoglobin, sodium, chloride, glucose, bilirubin, urea, creatinine, pH, and standard bicarbonate. Moderate, but clinically useful predictability was found for haematocrit, potassium, and total protein, while bone marrow values of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, PCO2, PO2, thrombocytes and leukocytes were systematically different from values in venous blood. Our data suggest that the intraosseous route is not only an important emergency alternative to intravenous access for administering fluids and drugs but may also serve as a reliable alternative for obtaining initial diagnostic laboratory studies when intravascular access is not obtainable.

Analysis of Variance↗
PubMed1994

Detection of a novel RYR1 mutation in four malignant hyperthermia pedigrees.

Malignant hyperthermia (MH) is a potentially fatal autosomal dominant disorder of skeletal muscle and is triggered in susceptible people by all commonly used inhalational anaesthetics and depolarizing muscle relaxants. To date, six mutations in the skeletal muscle ryanodine receptor gene (RYR1) have been identified in malignant hyperthermia susceptible (MHS) and central core disease (CCD) cases. Using SSCP analysis, we have screened the RYR1 gene in affected individuals for novel MHS mutations and have identified a G to A transition mutation which results in the replacement of a conserved Gly at position 2433 with an Arg. The Gly2433Arg mutation was present in four of 104 unrelated MHS individuals investigated and was not detected in a normal population sample. This mutation is adjacent to the previously identified Arg2434His mutation reported in a CCD/MH family and indicates that there may be a second region in the RYR1 gene where MHS/CCD mutations cluster.

Amino Acid Sequence↗
PubMed1994

Genetic effects on the variability of the halothane and caffeine muscle contracture tests.

BACKGROUND: The spectrum of the clinical presentation of malignant hyperthermia (MH) and the results of recent linkage studies suggest that there is a degree of heterogeneity in MH susceptibility. In the current study, we analyzed in vitro muscle contracture tests from members of large families with MH to evaluate if the results of these tests could be related to genetic influences. METHODS: Forty-seven subjects from four families with an MH-related death and with at least five clinically MH-susceptible individuals per family, as diagnosed by an in vitro muscle contracture test according to the protocol of the European MH Group, were included in the current analysis. We compared the strength of muscle contractures to challenges of halothane, caffeine, or both and the effect of these two drugs on twitch potentiation in response to supramaximal electrical stimulation among the families. RESULTS: Clinical MH susceptibility was confirmed in 36 individuals, and 11 individuals were diagnosed as MH-negative. In MH-susceptible individuals, muscle contractures to the 2% halothane challenge were significantly higher in family 1 (n = 15; 16.2 +/- 2.9 mN, mean +/- standard error of the mean) and in family 4 (n = 5; 16.4 +/- 5 mN) than in family 2 (n = 9; 5.8 +/- 1.5 mN) or family 3 (n = 7; 6.0 +/- 1.1 mN). Muscle contractures to the caffeine challenge (2 mM) were significantly increased in family 1 (7.3 +/- 1.4 mN) compared with those in family 3 (1.3 +/- 1.0 mN). In addition, we found a dose-dependent twitch potentiation to the halothane challenge in family 2 (P < 0.01) and to the caffeine challenge in families 2 (P < 0.001) and 3 (P < 0.01), whereas there was no twitch potentiation in families 1 and 4. CONCLUSIONS: The differences of in vitro muscle contracture tests among several families with MH provide evidence for genetic influences on the variability of this test procedure. However, it is not known if the observed differences are caused by heterogeneity of the MH gene mutation(s) or by other genetic factors that might modify muscle contractures in vitro.

Adult↗
PubMed1994

Effects of ondansetron in the prevention of postoperative nausea and vomiting in children.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a commonly observed adverse effect of general anesthesia. Recently, ondansetron, a new serotonin3 (5-hydroxytryptamine3) receptor antagonist was shown to be effective in the prophylaxis and prevention of chemotherapy-induced nausea and vomiting in children and adults as well as of PONV in adults. The aim of the current study was to evaluate the capacity of ondansetron to prevent PONV in pediatric patients. METHODS: Two hundred children (132 boys and 68 girls) 2-10 yr of age received general inhalational anesthesia for surgical procedures (the extremities; ear, nose, and throat; inguinal hernia and phimosis; and dentistry) of an expected duration of less than 90 min. This study was divided into two phases: prophylaxis and rescue treatment. For prophylaxis, patients were randomly assigned to two groups: one group received an intravenous injection of 0.1 mg/kg ondansetron, and the other group received a placebo before surgical incision under double-blind conditions. For rescue treatment, only placebo patients were included; as a rescue medication they received an intravenous injection of 0.1 mg/kg ondansetron or 0.02 mg/kg droperidol according to a prestudy randomization under double-blind conditions. Incidence and severity of PONV (PONV score 0 = no nausea and no retching; 1 = complaining of sickness and retching; 2 = vomiting one or two time in 30 min; 3 = vomiting more than two times in 30 min) was recorded over a 4-h period in the postanesthesia care unit. Within 72 h of the procedure, a follow-up nurse interviewed the parents for late-onset nausea in the children. RESULTS: With regard to prophylaxis, 10% of patients receiving ondansetron had PONV during the 4-h observation period versus 40% of those receiving placebo (P < 0.001). The incidence of vomiting alone (PONV score > or = 2) was 5% and 25%, respectively (P < 0.001). There were no significant differences between ondansetron and droperidol in the treatment of PONV. However, at the end of the 4-h period, ondansetron patients were less sedated than were patients who had received droperidol (P < 0.01). Interviews with parents could be performed for 143 of 200 children (76 ondansetron and 67 placebo). Twenty-four children (15 ondansetron and 9 placebo) showed late-onset PONV after the 4-h observation period but within 24 h of the procedure (19.7% vs. 13.4%; P not significant). CONCLUSIONS: Ondansetron is effective in the prevention of PONV in pediatric patients for the first 4 h after general anesthesia. Lower sedation scores with ondansetron compared with droperidol may be an advantage, especially in ambulatory surgery. However, the incidence of late-onset PONV (> 4-24 h) was not influenced by prophylactic treatment with one dose of ondansetron preoperatively.

Anesthesia, General↗
PubMed1993

In vitro effect of ephedrine, adrenaline, noradrenaline and isoprenaline on halothane-induced contractures in skeletal muscle from patients potentially susceptible to malignant hyperthermia.

We have measured the effects of ephedrine, adrenaline, noradrenaline and isoprenaline on halothane-induced contractures in muscle biopsies from patients potentially susceptible to malignant hyperthermia (MH). At concentrations of 4-24 mmol litre-1, ephedrine induced in vitro contractures in halothane 0.44 mmol litre-1-prechallenged muscle, whilst adrenaline, noradrenaline and isoprenaline had no effect. There was a shift of the ephedrine concentration-response curve to the left and an increased maximum muscle contracture in the MH susceptible group compared with the MH negative group (P < 0.001). We conclude that ephedrine increased halothane-induced muscle contractures in vitro either by an unknown pharmacological mechanism or by an adrenergic stimulation which was different from those of the other investigated adrenoceptor agonists.

Dose-Response Relationship, Drug↗
PubMed1993

Effects of three different types of management on the elimination kinetics of volatile anaesthetics. Implications for malignant hyperthermia treatment.

The effectiveness of three types of management on the elimination kinetics of volatile anaesthetics was studied prospectively in 45 patients randomised to one of three groups. Patients were anaesthetised using isoflurane. Inspiratory and expiratory isoflurane concentrations were measured. After reaching a steady-state isoflurane concentration, the vaporizer was turned off. In group 1, only the fresh gas flow was increased from 40 to 120 ml.kg-1 x min-1. Patients in group 2, in addition to the increase in the fresh gas flow, had a charcoal filter connected in the inspiratory limb of the circuit. Patients in group 3 had the fresh gas flow increased and the anaesthetic machine and breathing system changed. There was a statistically significant difference in the isoflurane washout from the anaesthetic machines between group 1 (90% elimination time 39 [10] s) and group 2 (90% elimination time 25 [5] s) (p < 0.01). However, there was no significant difference in the isoflurane washout from the patients in any of the groups. Thus the use of a charcoal filter or a change of the anaesthetic machine and breathing system proved to be of no clinical advantage.

Adult↗
PubMed1992

Lumbovertebral syndrome after extradural blood patch.

We describe a patient who developed an immobilizing lumbovertebral syndrome after an extradural blood patch and who was hospitalized with a suspected extradural abscess. An infectious aetiology of the persistent backache could be excluded and the patient recovered with analgesics and physiotherapy. The probable aetiology is discussed.

Adult↗
PubMed1992

Laryngospasm during transtracheal high frequency jet ventilation.

A 74-year-old woman developed severe cardiovascular depression during percutaneous transtracheal high frequency jet ventilation for laser surgery of the epiglottis. This was found to be caused by acute airway obstruction secondary to severe laryngospasm. We recommend profound neuromuscular blockade during percutaneous transtracheal jet ventilation, in order to prevent this complication.

Aged↗
PubMed1992

B lymphoblasts show oxidase activity in response to cross-linking of surface IgM and HLA-DR.

Human B lymphocytes express components of the superoxide generating system of phagocytes, NADPH oxidase. We studied regulation of this 'B-cell oxidase' during in vitro blast transformation, using Lucigenin-amplified chemiluminescence (CL) to detect superoxide release. While freshly isolated tonsil B lymphocytes showed no CL responses, culture with phorbol myristate acetate (PMA) and ionomycin induced susceptibility to CL triggering by anti-IgM and anti-HLA-DR. Maximal effects were observed after 3 days of culture with 0.4 ng/ml PMA + 1 microgram/ml ionomycin. Cells from such B lymphoblast cultures showed no CL responses to opsonized zymosan. In contrast, peripheral blood mononuclear cells, where monocytes are the predominant oxidant source, showed CL responses to opsonized zymosan but not to anti-IgM and anti-HLA-DR, either before or after culture with PMA + ionomycin. Culture of B cells with the surface immunoglobulin cross-linking agent staphylococcus aureus Cowan I also led to emergence of a CL, response to anti-IgM, which was enhanced by interferon-gamma. Interestingly, markedly fewer B blasts than freshly isolated B lymphocytes expressed cytochrome b-558 surface antigen. Thus, the B-cell oxidase is up-regulated during blast transformation and can be triggered via surface IgM and HLA-DR; however, this appears to be restricted to a subset of B lymphoblasts.

B-Lymphocytes↗
PubMed1992

Effect of halothane equilibration kinetics on in vitro muscle contractures for malignant hyperthermia screening.

In vitro muscle contracture tests for malignant hyperthermia screening are routinely performed using standardized protocols. In the present study on-line monitoring of halothane concentrations in the gas phase was demonstrated to be an improved test standard. The kinetics of halothane concentration and their effect on in vitro muscle contracture tests were evaluated in two test baths, I and II, which contained 3 and 18 ml Krebs-Ringer solution, respectively. The equilibration kinetics for halothane was significantly faster in bath I (t1/2 = 8.2 s) compared with bath II (t1/2 = 25.6 s). Twenty-one pairs of muscle bundles from 21 potentially malignant hyperthermia susceptible patients were investigated, each test bath receiving one bundle from each pair. The variance of muscle contractures was significantly increased in test bath I compared with test bath II. However, there was no influence on malignant hyperthermia diagnosis, suggesting that, within the ranges of t1/2 = 8.2 s-25.6 s, the test bath volumes need not be standardized.

Disease Susceptibility↗
PubMed1992

[Neonatal resuscitation in the delivery room. What role does the anesthetist play?].

Neonatal resuscitation in the delivery room of small obstetric units is problematic because of the lack of on-site personnel with adequate training and experience. In large university hospitals this task is usually fulfilled by neonatologists who are present 24 h/day. However, in medium-sized and small obstetric units neonatal resuscitation is performed by a variety of professionals: paediatricians, obstetricians, anaesthetists, midwives, nurses, and nurse anaesthetists. The degree of responsibility and involvement of the anaesthesia specialist in the resuscitation of the newborn in Switzerland is unknown, and therefore an investigation was conducted. METHOD. After a telephone inquiry at all the hospitals in Switzerland, a total of 175 obstetric units were identified. A questionnaire with items regarding organisation, responsibilities, and the extent of involvement of the anaesthesia department of the particular hospital was sent to each of the appropriate anaesthetists. RESULTS. Of the 175 questionnaires, 163 (93%) were returned; 14 could not be analysed (5 were sent to hospitals where there was in fact no obstetric unit and 9 were sent to anaesthetists who shared responsibilities for one unit). In 1988, 76,505 babies were born in Switzerland; two-thirds of these were delivered in hospitals with an annual birth rate of less than 600 births per year. Of the 149 questionnaires that were eligible for further analysis, 118 (79%) documented participation of the anaesthetic team in the resuscitation of the newborn. However, only 22% of these departments had an official contract with the hospital administration. Ninety-nine per cent of all responders agreed that every anaesthetist should have the knowledge--both theoretical and practical--to resuscitate a newborn infant. However, reservations were expressed on how to acquire and how to maintain this competence. The initial evaluation of the newborn was done by an anaesthetist in 3% (2250/76,505) of all deliveries in Switzerland in 1988; 1.2% (882/76,505) of these babies needed bag-and-mask ventilation and in 0.4% (308/76,505) endotracheal intubation was performed by the anaesthetist. Proceeding on the assumption that 5% of all newborns need some sort of resuscitation immediately after birth, it is estimated that in 1988 approximately one-third of resuscitations were performed by anaesthetists. It is therefore concluded that anaesthetists play an important role in the resuscitation of newborns in Switzerland.

Anesthesiology↗