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Biomedical subjects

T Girard

Publications and source records attributed to T Girard.

At least 19 recordsLinked to original sources

Ropivacaine versus bupivacaine 0.125% with fentanyl 1 microg/ml for epidural labour analgesia: is daily practice more important than pharmaceutical choice?

UNLABELLED: Ropivacaine might be superior to bupivcaine for epidural labour analgesia because it appears to induce less lower extremity motor blockade. The clinical relevance of this difference is not yet clear. METHODS: In a double-blind randomised trial bupivacaine and ropivacaine each at 0.125% with 1 microg/ml fentanyl were compared for epidural labour analgesia. This study was performed in two university hospitals. RESULTS: Sixty-three nulliparous women with singleton pregnancies at term were included. There were no differences between bupivacaine and ropivacaine as far as motor blockade, analgesic outcome, mode of delivery and neonatal outcome are concerned. However, the clinical management of epidural analgesia differed significantly between the two institutions involved. Parturients of one institution had their epidural catheter placed earlier, needed less top-up medication, and had more successful mobilisations, when compared to the other institution. CONCLUSIONS: Institutional clinical practice can be significantly different. Pharmacological differences between bupivacaine and ropivacaine at 0.125% with 1 microg/ml fentanyl seem to be less important than differences between institutions in terms of clinical practice.

Adjuvants, Anesthesia↗

Predictors of long-term mortality and cardiac events in patients with known or suspected coronary artery disease who survive major non-cardiac surgery.

The aim of this prospective study was to assess predictors of long-term outcome in patients with documented or suspected coronary artery disease who survive major non-cardiac surgery. The impact of patients' comorbidities, pre-operative heart rate variability and postoperative increase in cardiac troponin I on all-cause mortality and major cardiac events within 2 years was explored using multivariable logistic regression. Six of 173 patients died within the first month after surgery and were excluded from the study. Thirty-four of 167 patients (20%) died 1-24 months after surgery. Independent predictors of all-cause mortality were history of congestive heart failure (odds ratio 6.4 [95%, confidence interval 1.7-24]), pre-operatively depressed heart rate variability (odds ratio 6.4 [95%, confidence interval 1.9-21]), and age > 70 years (odds ratio 4.5 [95%, confidence interval 1.2-16]). In contrast, postoperative elevation of cardiac troponin I did not independently predict all-cause mortality or major cardiac events.

Aged↗

Similar susceptibility to halothane, caffeine and ryanodine in vitro reflects pharmacogenetic variability of malignant hyperthermia.

BACKGROUND AND OBJECTIVE: To analyse the use of standardized application of ryanodine for in vitro muscle contracture testing to define cut-off values separating malignant hyperthermia susceptible from malignant hyperthermia negative subjects. Furthermore, we compared the results of in vitro muscle-contracture tests following the halothane, caffeine and ryanodine challenges. METHODS: In 113 subjects, halothane, caffeine and ryanodine muscle-contracture tests were performed according to the protocol of the European Malignant Hyperthermia Group. RESULTS: Malignant hyperthermia susceptible subjects (n = 77) had significantly shorter onset times in the ryanodine in vitro muscle-contracture test (1 micromol ryanodine) compared with malignant hyperthermia negative subjects (n = 36), median 4.8 vs. 20.1 min, respectively, without any influence of age or gender. The best cut-off value was 10 min (sensitivity 0.78 and specificity 0.94, respectively). Shorter cut-off values had greater specificity, but lower sensitivity. Groups could not be separated without an overlap. In susceptible subjects, we found a correlation between onset time and threshold concentrations for halothane and caffeine (p = 0.47 and 0.52, respectively). In addition, muscle bundles with high susceptibility to halothane and caffeine also showed high susceptibility to ryanodine. CONCLUSIONS: The ryanodine in vitro muscle-contracture test confirmed the malignant hyperthermia status that was determined using the halothane and caffeine in vitro muscle-contracture tests. Due to an overlap between the two groups, discrimination ability was not always perfect and short cut-off values with higher specificity had reduced sensitivity and vice versa. The correlation of contractures following the halothane, caffeine and ryanodine challenges points towards a similar individual pharmacogenetic effect rather than a specific, different pharmacological action between the three agents.

Adolescent↗

Intra-vascular large B-cell lymphoma revealed by a nephrotic syndrome: a one year remission induced by a high frequency CHOP and rituximab.

Intra-vascular lymphoma is usually reported as a rare and fatal disorder. We describe here the first case of an intra-vascular lymphoma revealed by a nephrotic syndrome for which a durable remission has been obtained by 8 cycles of bi-mensual CHOP and Rituximab therapy. In this report, 18 fluorodesoxyglucose tomoscintigraphy is discussed as a tool for intra-vascular lymphoma extension and follow-up.

Aged↗

Bibliometric analysis of original molecular biology research in anaesthesia.

Molecular biology has expanded the horizons of anaesthesia during the last 20 years and has led to an increase of basic science articles that are published in the specialised anaesthetic journals or originate in anaesthetic institutions. We searched for and analysed the specific features, such as year of publication, publishing journal, and country of origin, of all such molecular biology articles stored in the MEDLINE database during the period 1986-2002. We identified 1265 original articles that used molecular biology techniques; 223 (18%) of these articles were published in anaesthetic journals and 1042 (82%) articles in 556 other biomedical journals. While in the late 1980s only a few molecular biology articles were published each year by anaesthetic institutions, worldwide this number reached approximately 200 basic science articles by the end of 2002. The USA clearly dominates the field of anaesthesia with respect to molecular biology research with 839 (66%) such articles.

Anesthesia↗

Diagnosis of malignant hyperthermia susceptibility during CABG surgery.

A 55-year-old man presented for coronary artery bypass graft (CABG) surgery. Malignant hyperthermia (MH) was suspected in his family. This case report describes a diagnostic approach to obtain a definite MH diagnosis by performing an in vitro contracture test at the time of CABG surgery in combination with molecular genetic investigations.

Adult↗

Recent advances in the diagnosis of malignant hyperthermia susceptibility: how confident can we be of genetic testing?

Malignant hyperthermia (MH) is a condition that manifests in susceptible individuals only on exposure to certain anaesthetic agents. Although genetically heterogeneous, mutations in the RYR1 gene (19q13.1) are associated with the majority of reported MH cases. Guidelines for the genetic diagnosis for MH susceptibility have recently been introduced by the European MH Group (EMHG). These are designed to supplement the muscle biopsy testing procedure, the in vitro contracture test (IVCT), which has been the only means of patient screening for the last 30 years and which remains the method for definitive diagnosis in suspected probands. Discordance observed in some families between IVCT phenotype and susceptibility locus genotype could limit the confidence in genetic diagnosis. We have therefore assessed the prevalence of 15 RYR1 mutations currently used in the genetic diagnosis of MH in a sample of over 500 unrelated European MH susceptible individuals and have recorded the frequency of RYR1 genotype/IVCT phenotype discordance. RYR1 mutations were detected in up to approximately 30% of families investigated. Phenotype/genotype discordance in a single individual was observed in 10 out of 196 mutation-positive families. In five families a mutation-positive/IVCT-negative individual was observed, and in the other five families a mutation-negative/IVCT-positive individual was observed. These data represent the most comprehensive assessment of RYR1 mutation prevalence and genotype/phenotype correlation analysis and highlight the possible limitations of MH screening methods. The implications for genetic diagnosis are discussed.

Chromosomes, Human, Pair 19↗

Phenotyping malignant hyperthermia susceptibility by measuring halothane-induced changes in myoplasmic calcium concentration in cultured human skeletal muscle cells.

BACKGROUND: Malignant hyperthermia (MH) is a potentially lethal disease triggered by volatile anaesthetics and succinylcholine in genetically predisposed individuals. Because of the heterogenetic nature of MH, a simple genetic-based diagnostic test is not feasible and diagnosis requires an invasive open muscle biopsy followed by the in vitro contracture test (IVCT). Our aim was to establish if measurements of halothane-induced increases in intracellular calcium ion concentration [Ca(2+)](i) in cultured human skeletal muscle cells can be used to phenotype MH susceptibility and if different mutations in the ryanodine receptor (RYR1) gene affect halothane-induced increases in [Ca(2+)](i). METHODS: Primary cultures of human skeletal muscle cells were established from 54 individuals diagnosed by the IVCT according to the protocol of the European MH Group as: MH susceptible (n=22), MH negative (n=18) or MH equivocal (n=14). All individuals were screened for the presence of the most common mutations in the RYR1 gene. [Ca(2+)](i) was measured by fluorescent digital microscopy using fura-2/AM in 10 cells from each patient at five different halothane concentrations. RESULTS: The halothane-induced increase in [Ca(2+)](i) differed significantly between the three diagnostic groups. Different mutations of the RYR1 gene did not have a specific impact on halothane-induced increases in [Ca(2+)](i). CONCLUSIONS: Measurements of [Ca(2+)](i) in human skeletal muscle cells can be used to phenotype MH susceptibility; however, we did not observe a specific effect of any mutation in the RYR1 gene on the halothane-induced increase in [Ca(2+)](i).

Adolescent↗

B-lymphocytes from malignant hyperthermia-susceptible patients have an increased sensitivity to skeletal muscle ryanodine receptor activators.

Malignant hyperthermia (MH) is a pharmacogenetic disease triggered by volatile anesthetics and succinylcholine in genetically predisposed individuals. The underlying feature of MH is a hypersensitivity of the calcium release machinery of the sarcoplasmic reticulum, and in many cases this is a result of point mutations in the skeletal muscle ryanodine receptor calcium release channel (RYR1). RYR1 is mainly expressed in skeletal muscle, but a recent report demonstrated the existence of this isoform in human B-lymphocytes. As B-cells can produce a number of cytokines, including endogenous pyrogens, we investigated whether some of the symptoms seen during MH could be related to the involvement of the immune system. Our results show that (i) Epstein-Barr virus-immortalized B-cells from MH-susceptible individuals carrying the V2168M RYR1 gene mutation were more sensitive to the RYR activator 4-chloro-m-cresol and (ii) their peripheral blood leukocytes produce more interleukin (IL)-1beta after treatment with the RYR activators caffeine and 4-chloro-m-cresol, compared with cells from healthy controls. Our result demonstrate that RYR1-mediated calcium signaling is involved in release of IL-1beta from B-lymphocytes and suggest that some of the symptoms seen during an MH episode may be due to IL-1beta production.

B-Lymphocytes↗

Genotype-phenotype comparison of the Swiss malignant hyperthermia population.

Malignant hyperthermia (MH) is a potentially lethal pharmacogenetic disease, triggered by inhalative anesthetics or depolarizing muscle relaxants in genetically predisposed individuals. Linkage analysis have revealed MH to be a heterogenetic disease with about 50% of MH families linked to the locus of the ryanodine receptor calcium channel (RYR1). We investigated the frequency of the 23 published MH linked RYR1 gene mutations in the Swiss MH population and compared our findings to the results of the in vitro contracture test (IVCT). IVCT was performed following the protocol of the European MH Group and mutation screening was done by PCR amplification of genomic DNA followed by restriction enzyme digestion or SSCP. We identified RYR1 gene mutations in 40% of unrelated MH families (19/48) with a high incidence of the mutation V2168M (27%). IVCT results revealed a significantly stronger functional effect of mutations R614C and V2168M as compared to mutations G2434R and R2458C. This is the first time that such a high incidence of RYR1 gene mutations in an MH population has been found, supporting the use of molecular genetic testing for the diagnosis of MH susceptibility in suitable families. In addition our data show that different RYR1 gene mutations are associated with different IVCT phenotypes.

Caffeine↗

Are antineutrophil cytoplasmic antibodies a marker predictive of relapse in Wegener's granulomatosis? A prospective study.

OBJECTIVES: To investigate the predictive value of testing for antineutrophil cytoplasmic antibodies (ANCA) in 55 patients with systemic Wegener's granulomatosis (WG) included in a randomized, prospective trial comparing corticosteroids and oral or pulse cyclophosphamide. METHODS: All 55 patients received corticosteroids. A cyclophosphamide pulse of 0.7 g/m2 was given at the time of diagnosis. After the first pulse, the patients were assigned at random to receive either pulse or oral cyclophosphamide (2 mg/kg/day), independently of ANCA results. ANCA were sought using an immunofluorescence assay and an attempt was made to correlate them with relapse of WG. ANCA were monitored throughout the study. RESULTS: At the time of diagnosis, ANCA were detected in 48 (87%) patients, with a cytoplasmic labelling pattern in 44 and a perinuclear pattern in four. ANCA follow-up was available for 50 patients. ANCA disappeared in 34 patients and persisted in nine. For 79% of the patients, the clinical course improved with the disappearance of ANCA and deteriorated with their persistence or increased titre. Among the patients who were initially ANCA-positive, 23 relapses occurred. Relapses were more frequent when ANCA remained positive or reappeared [13/19 ANCA-positive patients vs 3/29 ANCA-negative patients (P<0.01)]. Nine relapses (39%) occurred in patients with persistent ANCA, and ANCA reappearance preceded relapse in eight (35%). The mean time between inclusion and relapse did not differ between the patients who became ANCA-negative and those who were persistently ANCA-positive (14.6+/-13.2 vs 14.4+/-8.2 months). The mean time to ANCA disappearance was similar for the patients who relapsed and those who did not. Corticosteroids and pulse or oral cyclophosphamide did not significantly modify the time to ANCA disappearance. Throughout the study, seven patients were ANCA-negative. CONCLUSION: Although ANCA positivity was associated with relapse, discordance between cytoplasmic ANCA and disease activity was not unusual. In the absence of clinical manifestations, ANCA titres alone can serve as a warning signal but not indicate whether to adjust or initiate treatment.

Antibodies, Antineutrophil Cytoplasmic↗

Analysis of factors predictive of survival based on 49 patients with systemic Wegener's granulomatosis and prospective follow-up.

OBJECTIVES: This prospective study attempted to determine factors predictive of survival in systemic Wegener's granulomatosis (WG) based on 49 patients. Patients and methods. All patients had previously untreated systemic WG. Treatment was with oral or pulse cyclophosphamide plus corticosteroids. Univariate and multivariate analyses of survival were performed using 13 parameters evaluated at diagnosis. RESULTS: The mortality rate was 37% during a mean follow-up period of 1.9 yr. Among the 13 parameters evaluated, univariate analysis selected the following factors as predictors of a poor outcome: serum creatinine > or =18.1 mg/dl, age > or =57 yr, and erythrocyte sedimentation rate (ESR) > or =90 mm/1st h. The absence of ear, nose and throat (ENT) involvement also tended to predict a greater risk of mortality. Glomerulonephritis, when present and regardless of creatininaemia, and pulmonary involvement had no significant effect. Multivariate analysis retained serum creatinine > or =18.1 mg/dl and age > or =57 yr as significant predictors of poor prognosis. CONCLUSIONS: Our results suggest that impaired renal function and older age are independent factors predicting poor outcome in WG. ESR proved to be a good marker of disease severity. Conversely, univariate analysis indicated that patients with ENT involvement tended to have a better outcome, suggesting a more benign evolution of granulomatous disease compared with more aggressive vasculitis.

Administration, Oral↗

[Abdominal tuberculosis: deceptive and still encountered].

BACKGROUND: Extrapulmonary manifestations of tuberculosis are increasing in incidence. Abdominal tuberculosis may mimic a variety of gastrointestinal disorders. The diagnosis of abdominal tuberculosis is still difficult to establish before surgery. CASE REPORTS: We report 3 cases of abdominal tuberculosis in immunocompetent individuals. One patient presented with an ileocecal mass mimicking cancer. The second one presented with fever, ileocecal mass and ascites leading to the diagnosis of appendiceal peritonitis. The last patient was admitted for ascites, ovarian mass and high CA 125 serum level simulating ovarian cancer with peritoneal carcinomatosis. COMMENTS: In cases of abdominal tuberculosis when standard investigations are unhelpful, a PCR should be performed. Estimation of adenosine deaminase in ascitic fluid is an easy and reliable method for diagnosing tuberculous ascites. With these non invasive diagnostic procedures, surgery should be reserved only to patients with complications.

Adenosine Deaminase↗

Favorable outcome of gemcitabine-induced respiratory distress syndrome.

Gemcitabine, a deoxycytidine analog, is used to treat solid tumors, like non-small-cell lung carcinoma. The most commonly reported adverse effects are reversible and generally not fatal. However, among the five cases of acute respiratory distress syndrome (ARDS) secondary to gemcitabine treatment reported since 1997, four were fatal despite corticosteroid therapy. We describe here a patient who received gemcitabine for bronchial epidermoid carcinoma and developed ARDS which spontaneously regressed after gemcitabine withdrawal.

Aged↗