ISSN:0003-3022    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundAltered Ca2+homeostasis in skeletal muscle is a key molecular event triggering malignant hyperthermia (MH) in malignant hyperthermia-susceptible (MHS) individuals. Genetic studies have shown that mutations in the type 1 ryanodine receptor (RYR1) are associated with MH susceptibility. Because human B lymphocytes express theRYR1, it is hypothesized that Ca2+homeostasis in B lymphocytes is altered in MHS individuals.MethodsThis study investigated the Ca2+response of B cells to caffeine and 4-chloro-m-cresol in 13 MHS and 21 MH-negative (MHN) individuals who had been diagnosed by caffeine halothane contracture test (CHCT) and 18 healthy volunteers. Changes in [Ca2+]iin B cells were measured directly in fluo-3 loaded cells using a dual-color flow cytometric technique. Further, B cell phenotype was correlated with CHCT results in a family with the Val2168Met (G6502A) mutation.ResultsCaffeine-induced (50 mm) increases in [Ca2+]iin B cells were significantly greater in MHS than in MHN (P= 0.0004), control (P= 0.0001) or non-MHS (MHN and control) individuals (P< 0.0001). The 4-chloro-m-cresol-induced (400 &mgr;m) increases in [Ca2+]iwere also significantly different between MHS and controls (P= 0.003) or between MHS and non-MHS (MHN and control) individuals (P= 0.0078). A study of a family with the Val2168Met mutation demonstrated expression of theRYR1mRNA mutant in B cells from the family members with MHS phenotype and a clear segregation of genotype with B-cell phenotype.ConclusionThe Ca2+responses to caffeine or 4-chloro-m-cresol in B lymphocytes showed significant differences between MHS and MHN (or control) individuals. Although the molecular mechanisms of these alterations are currently undetermined, the results suggest that the enhanced Ca2+responses are associated with mutations in theRYR1gene in some MHS individuals.

ISSN:0003-3022    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundMalignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle. During general anesthesia, a life-threatening hypermetabolic state may occur resulting from increased release of Ca2+from the sarcoplasmic reticulum in skeletal muscle. Diagnosis of MH susceptibility requires surgical muscle biopsies to measure force in response to chemical stimulation (in vitrocontracture test, IVCT). Here, the authors investigated an alternative way of discriminating MH-susceptible (MHS) from normal (MHN) subjects by using cultured human myotubes and measuring proton release as an indicator of cellular metabolism.MethodsMyotubes were stimulated with the Ca2+release channel agonist 4-chloro-m-cresol (4-CmC), leading to metabolic activation and proton secretion. The rate of extracellular acidification was recorded with a silicon sensor chip.ResultsA stepwise increase in 4-CmC concentration led to a phasic–tonic increase in the acidification rate. The response, measured at different concentrations of 4-CmC, was considerably larger in cultures from MHS compared with MHN subjects and correlated well with the force response in the IVCT.ConclusionsThe enhanced metabolism of cultured skeletal myotubes, likely originating from an increased myoplasmic Ca2+concentration, can be monitored by studying the proton secretion rate. Because the method seems to be able to distinguish normal from pathologic phenotypes, it is a promising technique for possible future use in less invasive MH testing.

ISSN:0003-3022    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundMalignant hyperthermia susceptibility (MHS), an uncommon syndrome often inherited as an autosomal dominant trait, is characterized by a genetic and clinical heterogeneity. In this article, the authors described six pedigrees in which both parents of MHS patients were diagnosed with MHS by anin vitrodiagnostic test. Haplotype and mutation analysis revealed that more than one MHS genetic trait was present in these families.MethodsA panel of 104 MHS families were investigated with a caffeine halothane contracture test on muscle biopsy specimens. When possible, blood creatine kinase concentrations of MHS patients were measured. Haplotyping studies were conducted with chromosome 19q13.2 polymorphic markers and mutations were searched for in patients’ DNA.ResultsIn six families, thein vitrodiagnostic test and genetic studies demonstrated that both, apparently unrelated, parents of MHS patients were MHS. In three families, homozygous or compound heterozygous individuals for RYR1 mutations were characterized at a molecular level. In one family, a compound heterozygous patient harboring a RYR1 mutation and a CACNA1S mutation was identified. While patients with two mutated alleles did not show differences in their muscle response to halothane or caffeine, their creatinine kinase concentrations were significantly elevated compared with the heterozygous patients.ConclusionsBased on genetic andin vitrodiagnostic test data, more than one MHS allele associated with the MHS phenotype was evidenced in four families. These data should be considered in view of the use of genetics for the diagnosis of MHS and when reaching conclusions of genetic heterogeneity in MHS families. Taking into account the usual dominant mode of transmission of MHS and the size of the investigated population, the authors propose an evaluation of the incidence of the MHS in the general population based on genetic data.

ISSN:0003-3022    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundAntiemetic drugs are costly, are associated with variable efficacy, and can produce unwanted side effects when used for prophylaxis against postoperative nausea and vomiting. This clinical study was designed to compare the efficacy of transcutaneous electrical acupoint stimulation using a ReliefBand®to ondansetron (Zofran®) when utilized alone or in combination for preventing postoperative nausea and vomiting after plastic surgery.MethodsA single-center, randomized, double-blind, placebo- and sham-controlled study design was conducted to compare three prophylactic antiemetic treatment regimens in 120 outpatients undergoing plastic surgery procedures with routine low-dose droperidol prophylaxis: (1) ondansetron (n = 40), 4 mg intravenous ondansetron and a sham ReliefBand®; (2) acustimulation (n = 40), 2 ml intravenous saline and an active ReliefBand®; and (3) combination (n = 40), 4 mg intravenous ondansetron and an active ReliefBand®. The incidences of postoperative nausea and vomiting, as well as the need for “rescue” antiemetics, were determined at specific time intervals for up to 72 h after surgery. The outcome variables assessed included recovery times, quality of recovery score, time to resumption of normal diet, and patient satisfaction with the prophylactic antiemetic therapy.ResultsUse of the ReliefBand®in combination with ondansetron significantly reduced nausea (20vs.50%), vomiting (0vs.20%), and the need for rescue antiemetics (10vs.37%) compared with ondansetron alone at 24 h after surgery. Furthermore, the ability to resume a normal diet (74vs.35%) within 24 h after surgery was significantly improved when the ReliefBand®was used to supplement ondansetron (vs.ondansetron alone). Finally, the quality of recovery (90 ± 10vs.70 ± 20) and patient satisfaction (94 ± 10vs.75 ± 22) scores were significantly higher in the combination groupversusthe ondansetron group. There were no significant differences between the ReliefBand®and ondansetron when administered as adjuvants to droperidol for antiemetic prophylaxis.ConclusionsThe ReliefBand®compared favorably to ondansetron (4 mg intravenously) when used for prophylaxis against postoperative nausea and vomiting. Furthermore, the acustimulation device enhanced the antiemetic efficacy of ondansetron after plastic surgery.

ISSN:0003-3022    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundThe pharmacokinetics and pharmacodynamics of succinylcholine were studied simultaneously in anesthetized patients to understand why the drug has a rapid onset and short duration of action. A quantitative model describing the concentration–effect relation of succinylcholine was proposed. The correlation betweenin vitrohydrolysis in plasma andin vivoelimination was also examined.MethodsBefore induction of anesthesia, blood was drawn forin vitroanalysis in seven adults. Anesthesia was induced with propofol and remifentanil. Single twitch stimulation was applied at the ulnar nerve every 10 s, and the force of contraction of the adductor pollicis was measured. Arterial blood was drawn frequently after succinylcholine injection to characterize the front-end kinetics. Plasma concentrations were measured by mass spectrometry, and pharmacokinetic parameters were derived using compartmental and noncompartmental approaches. Pharmacokinetic–pharmacodynamic relations were estimated.ResultsThe meanin vitrodegradation rate constant in plasma (1.07 ± 0.49 min−1) was not different from thein vivoelimination rate constant (0.97 ± 0.30 min−1), and an excellent correlation (r2= 0.94) was observed. Total body clearance derived using noncompartmental (37 ± 7 ml · min−1· kg−1) and compartmental (37 ± 9 ml · min−1· kg−1) approaches were similar. The plasma–effect compartment equilibration rate constant (keo) was 0.058 ± 0.026 min−1, and the effect compartment concentration at 50% block was 734 ± 211 ng/ml.ConclusionSuccinylcholine is a low-potency drug with a very fast clearance that equilibrates relatively slowly with the effect compartment. Itsin vivodisappearance is greatly accountable by a rapid hydrolysis in plasma.

ISSN:0003-3022    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundA significant number of children undergoing anesthesia and surgery exhibit new-onset sleep-related problems postoperatively. The aim of this longitudinal cohort study was to expand previous research in this area by using a new objective technology.MethodsThis study compared children undergoing general anesthesia and outpatient surgery (n = 92) to a community-based control group of children (n = 77). Data regarding coping, temperament, anxiety, surgical procedures, and postoperative pain were collected. Subjects underwent actigraphy sleep monitoring for at least 3 nights before surgery and 5 postoperative days (POD). Sleep assessment was performed with actigraphy sleep monitoring and the Post Hospitalization Behavioral Questionnaire (PHBQ).ResultsForty-three children (47%) in the surgery group experienced postoperative sleeping disturbances as determined by either the actigraphy or the PHBQ. Only 13 children (14.4%), however, experienced a decrease of at least 1 SD in percentage sleep as assessed by actigraphy. Postoperative pain scores on POD 1 and POD 2 were significantly higher among children who exhibited sleep problems as diagnosed by actigraphy (F = 4.283;P= 0.047). Also, children who exhibited actigraph-based sleep problems scored lower sociability-temperament (14.1 ± 4.3vs.17.5 ± 3.4;P= 0.04) scores compared with the community group and had a higher rate of change in their perioperative anxiety levels (group × time interaction, F = 5.1;P= 0.03).ConclusionA significant number of children undergoing outpatient surgery experience postoperative sleep-related problems. The clinical significance of this finding, however, is unclear.

ISSN:0003-3022    

出版商:OVID    

年代:2002

数据来源: OVID