Biomedical subjects

M Girard

Publications and source records attributed to M Girard.

At least 73 records · Page 4Linked to original sources

PubMed1998

[Mitomycin-vinorelbine combination as second-line chemotherapy in metastatic cancer of the breast].

Fourty-six patients (41 evaluable) were treated in second line chemotherapy of metastatic breast cancer (MBC) by an association of mitomycin (M), vinorelbine (V) (M 8 mg/m2 D1, V 25 mg/m2 D1 and DI 8 every 4 weeks). Median age was 58 years (36-78), median performance status 1 (0-3). Thirty-seven per cent of the tumors were estrogen receptors positive and 17% progesterone receptors positive. Seventeen patients received an adjuvant chemotherapy and 39 a first line chemotherapy with anthracycline (A). The median number of metastatic sites was 2 (1-4) and 27 patients (67%) had visceral metastases. Twelve patients were refractory to anthracyclines and 5 resistant. No toxic death nor hemolytic uremic syndrome were observed. Seven (3.7%) febrile neutropenias happened responsible for 4 hospitalizations. A grade 3 or 4 neutropenia was noted in 34% of the cycles but no other clinic toxicity nor grade 3 or 4 thrombopenia. The rate of objective response (OR) was 37.5% with 2 complete responses (CR) and 13 partial responses (PR). Seven patients had stable disease and 18 progressed. The rate of hepatic OR was 31%. Five (40%) A-refractory patients responded but no resistant patient. Median OR time was 10 weeks (8-12) and median OR duration was 5 months (3-6). Median survival was 11.5 months. MV association is well tolerated and effective in second line chemotherapy for MBC even with hepatic metastasis and in patients refractory to anthracyclines.

Adult↗

PubMed1997

Chimpanzee CXCR4 and CCR5 act as coreceptors for HIV type 1.

Chemokine receptors are molecules involved in the fusion of immunodeficiency viruses after their attachment. As chimpanzees are the animal model for infection by HIV-1, we cloned and sequenced chimpanzee CXCR4 and CCR5 from PBMCs. Chimpanzee CXCR4 was found to be identical to human CXCR4, which provides an explanation for the sensitivity of chimpanzees to lymphotropic isolates of HIV-1. Chimpanzee CCR5 showed two substitutions with respect to human CCR5. However, we show that the macrophage-tropic isolate HIV-1-Ba-L can use chimpanzee CCR5 as a fusion receptor. Therefore, the resistance of chimpanzee PBMCs to infection by macrophage-tropic isolates of HIV-1 is unlikely to be due to substitutions in CCR5.

Amino Acid Sequence↗

PubMed1997

IgA immunity in HIV type 1-infected chimpanzees. I. Systemic immunity.

HIV infection in humans causes various aberrancies in both the cellular and humoral immune systems, including functional abnormalities of B lymphocytes. In many instances, dysfunction occurs in the regulation of serum IgA, resulting in elevated concentrations of this immunoglobulin isotype. To determine whether HIV-1-infected chimpanzees develop IgA abnormalities similar to those observed in humans, we quantified total IgA, IgG, and IgM levels in sera collected longitudinally from six HIV-infected chimpanzees and one uninfected control animal. In comparison to immunoglobulin levels in the uninfected animal, two of the six infected chimpanzees exhibited increases in serum immunoglobulins following infection with HIV. Two other infected animals showed a marked decrease in the three isotypes within 10 months of exposure to HIV, followed by a return to baseline levels. The remaining two HIV-infected chimpanzees displayed serum immunoglobulin levels that paralleled the baseline levels and did not show great deviation over a period of 20 to 45 months postinfection. ELISA analyses of the IgA subclasses revealed possible abnormalities of the IgA2 subclass within the two animals that did not display irregular IgA, IgG, or IgM responses to HIV-1. Specific IgG, IgA, IgA1, and IgA2 antibodies to HIV antigens were detected by an enzyme immunoassay (EIA) kit and by Western blot analysis with IgA, IgA1, and IgA2 antibodies directed against the env, gag, and pol gene products. Because IgG can mask the detection of HIV-specific IgA antibodies in infected humans, Western blots and EIAs were also performed on IgG-depleted chimpanzee sera. The results demonstrated that in some instances, IgA reactivity against HIV antigens can be enhanced on removal of IgG. This study indicates that HIV-1 is capable of inducing abnormalities in serum IgA expression in chimpanzees. These results might further understanding of how HIV affects humoral responses in infected humans.

Animals↗

PubMed1997

IgA immunity in HIV type 1-infected chimpanzees. II. Mucosal immunity.

Vaginal wash fluids from chimpanzees cervically infected with HIV-1 and saliva from intravenously and cervically infected chimpanzees were analyzed for total IgA, IgA1, IgA2, IgG, and albumin concentrations and for reactivity against HIV-1. No overt abnormalities were detected in salivary immunoglobulin or albumin concentrations in either group of animals. Anti-HIV IgA and IgA subclass antibodies were demonstrated in saliva from five of six intravenously infected chimpanzees and in two of four cervically infected animals, with titers ranging from 1:5 to 1:20. HIV-specific IgG antibodies could be detected in saliva from half of the systemically infected group, the highest titer being 1:2560, whereas the highest anti-HIV IgG titer in the mucosally infected group was 1:20. Western blot analyses of the first saliva samples obtained after initial virus exposure revealed IgG, IgA, and IgA subclass antibodies directed at the env, gag, or pol gene products in both groups of chimpanzees. Examination of IgG, IgA, IgA1, and IgA2 concentrations in vaginal washes from cervically infected animals showed that IgG levels were highest, but IgA and IgA subclass reactivities against HIV-1 were more prominent than that of IgG. These results demonstrate that systemic infection of chimpanzees with HIV-1 elicits mucosal responses specific for HIV, and vaginal infection of chimpanzees induces a common mucosal immune response reminiscent of that in humans.

Albumins↗

PubMed1997

Antibodies to several conformation-dependent epitopes of gp120/gp41 inhibit CCR-5-dependent cell-to-cell fusion mediated by the native envelope glycoprotein of a primary macrophage-tropic HIV-1 isolate.

The beta-chemokine receptor CCR-5 is essential for the efficient entry of primary macrophage-tropic HIV-1 isolates into CD4(+) target cells. To study CCR-5-dependent cell-to-cell fusion, we have developed an assay system based on the infection of CD4(+) CCR-5(+) HeLa cells with a Semliki Forest virus recombinant expressing the gp120/gp41 envelope (Env) from a primary clade B HIV-1 isolate (BX08), or from a laboratory T cell line-adapted strain (LAI). In this system, gp120/gp41 of the "nonsyncytium-inducing," primary, macrophage-tropic HIV-1BX08 isolate, was at least as fusogenic as that of the "syncytium-inducing" HIV-1LAI strain. BX08 Env-mediated fusion was inhibited by the beta-chemokines RANTES (regulated upon activation, normal T cell expressed and secreted) and macrophage inflammatory proteins 1beta (MIP-1beta) and by antibodies to CD4, whereas LAI Env-mediated fusion was insensitive to these beta-chemokines. In contrast soluble CD4 significantly reduced LAI, but not BX08 Env-mediated fusion, suggesting that the primary isolate Env glycoprotein has a reduced affinity for CD4. The domains in gp120/gp41 involved in the interaction with the CD4 and CCR-5 molecules were probed using monoclonal antibodies. For the antibodies tested here, the greatest inhibition of fusion was observed with those directed to conformation-dependent, rather than linear epitopes. Efficient inhibition of fusion was not restricted to epitopes in any one domain of gp120/gp41. The assay was sufficiently sensitive to distinguish between antibody- and beta-chemokine-mediated fusion inhibition using serum samples from patient BX08, suggesting that the system may be useful for screening human sera for the presence of biologically significant antibodies.

Antibodies, Viral↗

PubMed1997

Characterisation of human serum albumin heterogeneity by capillary zone electrophoresis and electrospray ionization mass spectrometry.

Human serum albumin (HSA) preparations and HSA-containing recombinant human erythropoietin (rhEPO) formulations were analyzed by capillary zone electrophoresis. HSA was separated into several components by the addition of 1,4-diaminobutane to 20 mM sodium phosphate, pH 6.0 as electrophoretic buffer. Resolution was improved by increasing the buffer pH to 8.5. A comparative analysis of HSA preparations from three manufacturers provided evidence that this method can be used to differentiate individual preparations. The analysis of rhEPO formulations, composed largely of HSA, showed levels of heterogeneity comparable to that of HSA preparations. Electrospray ionisation mass spectrometry was used as an independent method to confirm the heterogeneous nature of HSA.

Blood Protein Electrophoresis↗

PubMed1997

Challenge of chimpanzees immunized with a recombinant canarypox-HIV-1 virus.

To evaluate the potential protective efficacy of a live recombinant human immunodeficiency virus type 1 (HIV-1) canarypox vaccine candidate, two chimpanzees were immunized five times with ALVAC-HIV-1 vCP250, a recombinant canarypox virus that expresses the HIV-1[IIIB(LAI)] gp120/TM, gag, and protease gene products. One month after the last booster inoculation, the animals were challenged by intravenous injection of cell-associated virus in the form of peripheral blood mononuclear cells from an HIV-1[IIIB(LAI)]-infected chimpanzee. One chimpanzee with a neutralizing antibody titer to HIV-1[IIIB(LAI)] of 128 at the time of challenge was protected, whereas both the second animal, with a neutralizing antibody titer of 32, and a naive control animal became infected. At 5 months after challenge, the protected chimpanzee and a third animal, previously immunized with various HIV-1[MN] antigens, were given a booster inoculation. The two animals were challenged intravenously 5 weeks later with twenty 50% tissue culture infectious doses of cell-free HIV-1[DH12], a heterologous subtype B isolate. Neither chimpanzee had neutralizing antibodies to HIV-1[DH12], and neither one was protected from infection with this isolate. The immune responses elicited by vaccination against HIV-1[IIIB(LAI)] or HIV-1[MN] did not, therefore, protect the animals from challenge with the heterologous cell-free HIV-1[DH12].

AIDS Vaccines↗

PubMed1997

Characterization and titration of an HIV type 1 subtype E chimpanzee challenge stock.

A subtype E human immunodeficiency virus type 1 (HIV-1) isolate from the Central African Republic (E/90CR402) was adapted to growth on chimpanzee peripheral blood mononuclear cells (PBMCs) by cocultivation of irradiated, infected human PBMCs with chimpanzee PBMCs. The resulting virus was passaged in chimpanzee PBMCs to generate a stock of chimpanzee-adapted virus. Although its V3 region sequence was identical to that of the parental isolate, the chimpanzee-adapted virus had a syncytium-inducing phenotype as opposed to the non-syncytium-inducing phenotype of the parental virus. After demonstrating in one animal each that the passaged virus could infect chimpanzees following intravenous (i.v.) or cervical inoculation, the i.v. infectious titer of the stock was determined. Exposure of three chimpanzees to different doses of the virus indicated that the titer was between 2 and 5 TCID50. Thus, the HIV-1 E/90CR402 chimpanzee challenge stock established persistent infections in chimpanzees by both the i.v. and genital routes and should be valuable for future HIV-1 vaccine studies to evaluate cross-protection between HIV-1 subtypes.

Animals↗

PubMed1997

Comparison of picornaviral IRES-driven internal initiation of translation in cultured cells of different origins.

We recently compared the efficiency of six picornaviral internal ribosome entry segments (IRESes) and the hepatitis C virus (HCV) IRES for their ability to drive internal initiation of translationin vitro. Here we present the results of a similar comparison performed in six different cultured cell lines infected with a recombinant vaccinia virus expressing the T7 polymerase and transfected with dicistronic plasmids. The IRESes could be divided into three groups: (i) the cardiovirus and aphthovirus IRESes (and the HCV element) direct internal initiation efficiently in all cell lines tested; (ii) the enterovirus and rhinovirus IRESes are at least equally efficient in several cell lines, but are extremely inefficient in certain cell types; and (iii) the hepatitis A virus IRES is incapable of directing efficient internal initiation in any of the cell lines used (including human hepatocytes). These are the same three groups found when IRESes were classified according to their activitiesin vitro, or according to sequence homologies. In a mouse neuronal cell line, the poliovirus and other type I IRESes were not functional in an artificial bicistronic context. However, infectious poliovirions were produced efficiently after transfection of these cells with a genomic length RNA. Furthermore, activity of the type I IRESes was dramatically increased upon co-expression of the poliovirus 2A proteinase, demonstrating that while IRES efficiency may vary considerably from one cell type to another, at least in some cases viral proteins are capable of overcoming cell-specific translational defects.

Amino Acid Sequence↗

PubMed1997

Analysis of recombinant human erythropoietin in drug formulations by high-performance capillary electrophoresis.

A high-performance capillary electrophoresis (HPCE) method was developed for the analysis of recombinant human erythropoietin (rhEPO) in final drug preparations. All products examined were formulated with large amounts of human serum albumin (HSA) which is used as a protein excipient. Due to their similar physical characteristics in solution, rhEPO and HSA could not be resolved under HPCE conditions previously developed for the separation of bulk rhEPO. Addition of 1 mM nickel chloride to the electrophoretic buffer allowed complete separation of the two proteins as well as separation of rhEPO into several glycoform populations. The method was linear over the concentration range of 0.03-1.92 mg/ml, with limits of detection and of quantitation of 0.01 and 0.03 mg/ml, respectively. The precision of the method was evaluated from intra- and inter-day replicate injections of both rhEPO standard solution and formulation. Components of within- and between-batch variances were consistently below 5%, which constituted an acceptable level of variation. Products from two manufacturers were analyzed and showed little qualitative but appreciable quantitative lot-to-lot variations for rhEPO content when expressed in terms of units of biological activity. The method also revealed qualitative differences between the two products.

Blotting, Western↗

PubMed1997

Differences in caffeine 3-demethylation activity among inbred mouse strains: a comparison of hepatic Cyp1a2 gene expression between two inbred strains.

The 3-demethylation of caffeine can be used as an index of cytochrome P450 CYP1A2 activity in vivo. We compared the plasma levels of caffeine and the 3-demethylated metabolite. 1,7-dimethylxanthine, in six common inbred strains (A/J, P/J, BALB/cJ, C3H/HeJ, AKR/J, and SWR/J) and one inbred strain (APN) derived in our laboratory from outbred Swiss-Webster mice on the basis of its relative susceptibility to acetaminophen-induced hepatotoxicity. We found significant variations between a number of the common strains, all of which produced significantly higher caffeine 3-demethylation indices than our APN strain. In three of the six common strains, there was a significant difference between males and females, with the females having consistently lower 1,7-xanthine/caffeine ratios. Hepatic Cyp1a2 expression was compared between APN and C3H/HeJ males. Microsomal methoxyresorufin O-demethylation, acetanilide 4-hydroxylation, and CYP1A2 immunoreactive protein levels were significantly higher in C3H/HeJ relative to APN mice, as were hepatic CYP1A2 mRNA levels. These results indicate the importance of strain and gender to the outcome of pharmacological or toxicological studies involving CYP1A2-mediated metabolism, as well as the suitability of the plasma 1,7-dimethylxanthine/caffeine ratio as a marker of CYP1A2 activity in the mouse. The striking differences observed between the APN and C3H/HeJ mice suggest that these strains may be suitable for a genetic analysis of the regulation of the basal expression of CYP1A2, a key enzyme in procarcinogen activation.

Acetaminophen↗

PubMed1997

Direction of injection does not affect the spread of spinal bupivacaine in parturients.

PURPOSE: One of the factors that can affect the distribution of local anaesthetic solutions in the subarachnoid space is the direction of the spinal needle through which injections are made. This study investigated the effect of the direction of the aperture of the Whitacre needle on the spread of hyperbaric bupivacaine in parturients undergoing elective caesarean section. METHODS: Forty healthy term parturients scheduled for caesarean delivery under spinal anaesthesia with 12 mg hyperbaric bupivacaine + 0.2 mg morphine were randomly assigned to one of two groups: needle orifice cephalad (I) or caudad (II). Spinal blocks were administered in the sitting position with patients being positioned supine immediately after. A blinded observer assessed the dermatome level of analgesia to ice every minute for the first 10 minutes, every three minutes for the following 35 min, then every 15 min until the sensory level regressed to T10. RESULTS: There was no difference between the groups regarding the maximal number of segments blocked cephalad to T11 (11.4 +/- 3.4: group I and 12.0 +/- 3.4: group II), time to highest cephalad spread of sensory block (22 +/- 10: group I and 19 +/- 10 min: group II), or time to regression to T10 (164 +/- 26: group I and 153 +/- 24 min: group II). The maximum decrease in blood pressure (33.9 +/- 9.6: group I and 36.8 +/- 11.8 mmHg: group II) and dosage of ephedrine administered (14.7 +/- 10.7: group I and 16.2 +/- 11.0 mg: group II) did not differ. CONCLUSION: The direction of the aperture of the Whitacre needle does not influence the spread of hyperbaric bupivacaine in the term parturient.

Adult↗

PubMed1997

Comparison of rocuronium and d-tubocurarine for prevention of succinylcholine-induced fasciculations and myalgia.

PURPOSE: We compared d-tubocurarine and rocuronium for the prevention of succinylcholine-induced fasciculations and postoperative myalgia (POM) and evaluated the influence of both drugs on the speed of onset and recovery of succinylcholine. METHODS: Seventy-five women undergoing surgery of short duration were studied. They were randomized to one of three groups: group SAL received normal saline followed three minutes later by 1.0 mg.kg-1 succinylcholine; group ROC received 0.05 mg.kg-1 rocuronium + 1.5 mg.kg-1 succinylcholine; group DTC received 0.05 mg.kg-1 d-tubocurarine + 1.5 mg.kg-1 succinylcholine. Single-twitch stimulation was applied to the ulnar nerve every 10 sec and the EMG response of the adductor pollicis was recorded. Fasciculations were assessed by a blinded observer on a scale of 0-3. Patients were asked 24 and 48 hr later to rate POM using a scale of 0-10. RESULTS: The interval needed for twitch height to decrease to 10% of initial value after succinylcholine was longer in group ROC (58 +/- 20 sec) (mean +/- SD) compared with group SAL (44 +/- 13 sec) (P < 0.05). Recovery to 20% occurred faster in group ROC (324 +/- 83 sec) than in groups SAL (456 +/- 103 sec) and DTC (450 +/-132 sec) (P < 0.05). Fasciculations were more intense in groups SAL than in groups ROC and DTC (P < 0.001). Patients rated POM as less intense 24hr postoperatively only in group ROC (1.2 +/- 2.4) compared with group SAL (3.3 +/- 3.5) (P < 0.05). CONCLUSION: Rocuronium prevents succinylcholine-induced fasciculations and POM. Rocuronium also delays the onset of succinylcholine and shortens its duration compared with d-tubocurarine.

Adolescent↗

PubMed1997

Bupivacaine decreases epidural meperidine requirements after abdominal surgery.

PURPOSE: The purpose of this study was to determine the optimal of three concentrations of bupivacaine (0.0%, 0.05%, 0.10%) to add to an epidural infusion of meperidine (1 mg.ml-1) for postoperative pain relief. METHODS: In this prospective, double blind study, 60 patients undergoing abdominal surgery with general anaesthesia were randomized into three groups to receive for postoperative epidural analgesia: 1) 1 mg.ml-1 meperidine (0% group), 2) bupivacaine 0.05% and 1 mg.ml-1 meperidine (0.05% group), 3) bupivacaine 0.10% and 1 mg.ml-1 meperidine (0.10% group). Postoperatively, the epidural infusion rate was titrated to produce adequate analgesia and pain was assessed at rest and on movement. RESULTS: There were no differences in demographic data, average pain scores or side effects among the three groups. However, there was improvement of pain relief at rest over time in the three groups (P < 0.05). Postoperative epidural analgesic infusion rates increased over time for the three groups (P < 0.05) and were lower in the 0.10% group (mean of 10.0 ml.hr-1) than in the 0% group (mean of 12.6 ml.hr-1) (P < 0.05). More than half of the 0% group had serum meperidine concentrations > 400 g.L-1 to control moderate postoperative pain. CONCLUSION: Although analgesia was identical among groups, the lower serum concentrations of meperidine support the addition of bupivacaine 0.10% to meperidine when administered as a continuous infusion following abdominal surgery.

Abdomen↗

PubMed1997

The addition of continuous intravenous infusion of ketorolac to a patient-controlled analgetic morphine regime reduced postoperative myocardial ischemia in patients undergoing elective total hip or knee arthroplasty.

This double-blind randomized trial assessed the effect of adding an intravenous continuous infusion of ketorolac to a patient-controlled analgesia (PCA) morphine regimen on analgesia, heart rate, arterial blood pressure, and postoperative myocardial ischemia. Patients having elective total hip or knee replacement were randomized to receive ketorolac 30 mg bolus, followed by an infusion of 5 mg/h for 24 h or placebo. All patients had access to PCA morphine (20 microg/kg bolus, with a lockout of 6 min). Patients were monitored for pain visual analog scale, blood pressure, heart rate, and ST segment depression via a continuous Holter monitor. ST depression of 1 mm 60 ms after the J point was considered significant if it lasted more than 1 min. There was no difference in demographics, risk factors, or cardiac medications between the groups. Ketorolac-treated patients had significantly better pain control at 2, 6, and 24 h. There was significant morphine sparing at all times after 3 h. There was no difference in the number of ischemic events between the groups. The ischemic episodes of the patients who received ketorolac occurred at slower heart rates (97 +/- 15 vs 114 +/- 16 bpm, P = 0.001) than those of patients in the placebo group. The duration of ST depression was shorter in ketorolac-treated patients (24 +/- 35 vs 76 +/- 95 min, P < 0.05). All ST depressions were clinically silent. Logistic regression of factors predicting ischemia included the use of calcium channel blockers and low pain score. These results suggest that analgesia with ketorolac reduces the duration of ischemic episodes in the first 24 h postoperatively.

Aged↗

PubMed1997

Increased basal expression of hepatic Cyp1a1 and Cyp1a2 genes in inbred mice selected for susceptibility to acetaminophen-induced hepatotoxicity.

Susceptibility to acetaminophen-induced hepatotoxicity was found to vary widely in an outbred colony of Swiss Webster mice. Some acetaminophen-treated male mice showed a significant elevation in serum levels of the hepatic enzyme alanine aminotransferase at a normally non-hepatotoxic oral dose. A selective breeding program over 17 generations produced inbred mice which were either susceptible or nonsusceptible to the hepatotoxic effects of acetaminophen. Liver microsomes from the susceptible group showed a statistically significant increase in the ability to metabolize acetaminophen to a reactive intermediate which covalently binds N-acetylcysteine. Microsomal cytochrome P450 activities associated with CYP1A2 (acetanilide 4-hydroxylation and methoxyresorufin O-demethylase) were significantly increased in the susceptible group. Ethoxyresorufin O-deethylase activity, associated with both CYP1A1 and CYP1A2, was also significantly elevated in this group. Further examination of both CYP1A isoforms revealed that hepatic CYP1A1 and CYP1A2 mRNA and protein levels were significantly elevated in animals from the susceptible group. In vivo caffeine 3-demethylation, which is associated with CYP1A2 activity, co-segregated with acetaminophen susceptibility and showed a significant positive correlation (r = 0.626, p < 0.005) with CYP1A2 mRNA expression in animals from both the susceptible and nonsusceptible groups. The co-segregation of elevated basal Cyp1a1 and CYP1a2 gene expression levels in animals selected for susceptibility to acetaminophen-induced hepatotoxicity suggested a common heritable basis for regulation of basal expression of both of these CYP1A isoforms. This was supported by the correlated expression of both CYP1A mRNAs within individual mice (r = 0.644, p < 0.02).

Acetaminophen↗

PubMed1997

Human immunodeficiency virus type 1 intersubtype (B/E) recombination in a superinfected chimpanzee.

Genetic characterization of a large number of human immunodeficiency virus type 1 (HIV-1) isolates indicates that at least 10% of all strains have mosaic genomes generated by recombination between viruses of the same or different subtypes or clades. What is not known, however, is the time between infection with the first and second HIV-1 strains as well as the time between infection with the second strain and the recombinational event. After 32 months of infection with HIV-1(LAI(IIIB)), a chimpanzee was inoculated intravenously and became infected with a subtype E strain, HIV-1(90CR402). With PCR amplification, DNA heteroduplex analysis, and DNA sequencing, both parental strains and two distinct recombinant proviruses were found in genomic DNA from lymph node tissue obtained 24 weeks after exposure to HIV-1(90CR402). These results show (i) that antiviral immune responses established by long-term infection with an HIV-1 subtype B strain did not prevent infection by a subtype E strain and (ii) that both strains actively replicated and produced sufficient quantities of virus to coinfect the same cell(s), resulting in recombinant viruses.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Anesthetic and surgical complications in 219 cases of myotonic dystrophy.

The objective of this study was to assess the frequency, type, and severity of perioperative complications after a first surgery under general anesthesia in patients with myotonic dystrophy (DM) and to measure the association with suspected risk factors. Numerous cases of perioperative complications in DM patients have been reported. Hazards have been associated with the use of thiopentone, suxamethonium, neostigmine, and halothane. A retrospective study of perioperative complications was conducted for 219 DM patients who had their first surgery under general anesthesia at the Chicoutimi Hospital. The overall frequency of complications was 8.2% (18 of 219). Most complications (16 of 18) were pulmonary, including five patients with acute ventilatory failure necessitating ventilatory support, four patients with atelectasis, and three patients with pneumonia. Using multivariate analysis, we found that the risk of perioperative pulmonary complications (PPC) was significantly higher after an upper abdominal surgery (odds ratio (OR), 24.4; 95% CI, 4.0 to 149.3) and for patients with a severe muscular disability, as assessed by the presence of proximal limb weakness (OR, 14.1; 95% CI, 1.5 to 134.4). The likelihood of PPC was not related to any specific anesthetic drug. Because of the increased risk of PPC, careful monitoring during the early postoperative period, protection of upper airways, chest physiotherapy, and incentive spirometry are mandatory in all symptomatic DM patients, particularly those with a severe muscular disability or those who have undergone an upper abdominal surgery.

Adolescent↗