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Biomedical subjects

R Leger

Publications and source records attributed to R Leger.

13 recordsLinked to original sources
PubMed2001

Identification and characterization of inhibitors of multidrug resistance efflux pumps in Pseudomonas aeruginosa: novel agents for combination therapy.

Whole-cell assays were implemented to search for efflux pump inhibitors (EPIs) of the three multidrug resistance efflux pumps (MexAB-OprM, MexCD-OprJ, MexEF-OprN) that contribute to fluoroquinolone resistance in clinical isolates of Pseudomonas aeruginosa. Secondary assays were developed to identify lead compounds with exquisite activities as inhibitors. A broad-spectrum EPI which is active against all three known Mex efflux pumps from P. aeruginosa and their close Escherichia coli efflux pump homolog (AcrAB-TolC) was discovered. When this compound, MC-207,110, was used, the intrinsic resistance of P. aeruginosa to fluoroquinolones was decreased significantly (eightfold for levofloxacin). Acquired resistance due to the overexpression of efflux pumps was also decreased (32- to 64-fold reduction in the MIC of levofloxacin). Similarly, 32- to 64-fold reductions in MICs in the presence of MC-207,110 were observed for strains with overexpressed efflux pumps and various target mutations that confer resistance to levofloxacin (e.g., gyrA and parC). We also compared the frequencies of emergence of levofloxacin-resistant variants in the wild-type strain at four times the MIC of levofloxacin (1 microg/ml) when it was used either alone or in combination with EPI. In the case of levofloxacin alone, the frequency was approximately 10(-7) CFU/ml. In contrast, with an EPI, the frequency was below the level of detection (<10(-11)). In summary, we have demonstrated that inhibition of efflux pumps (i) decreased the level of intrinsic resistance significantly, (ii) reversed acquired resistance, and (iii) resulted in a decreased frequency of emergence of P. aeruginosa strains that are highly resistant to fluoroquinolones.

Anti-Infective Agents↗
PubMed1999

[Pain therapy after thoracoscopic interventions. Do regional analgesia techniques (intercostal block or interpleural analgesia) have advantages over intravenous patient-controlled opioid analgesia (PCA)?].

Systemic opioids and thoracic epidural analgesia are common techniques used to provide post-operative analgesia following thoracoscopy (video-assisted thoracic surgery). The aim of the present prospective randomised study was to evaluate the efficacy of two less invasive analgesic techniques, intercostal blocks (ICB) and interpleural analgesia (IPA). After approval from the ethics committee and informed consent from the patients, 36 patients scheduled for thoracoscopic surgery were randomly assigned to a group for postoperative pain management: group ICB: intercostal blocks of the segments involved with 5 ml 0.5% bupivacaine at the end of surgery and 6 h later; group IPA: interpleural analgesia with 20 ml 0.25% bupivacaine applied every 4 h using a catheter placed during surgery near the apex of the interpleural space; control group: IV-opiod-PCA with piritamide. Patients in the ICB and IPA groups had access to pain relief by PCA with piritramide as well. Additional medication for all groups if the analgesia was insufficient consisted of metamizol. There were no significant differences in piritramide consumption between the two regional analgesia groups and the control group up to the 3rd and 7th postoperative day. Up to the 7th day piritramide consumption in group ICB was 78 mg, in group IPA 75 mg and 80 mg in the control group. Patients in group ICB showed significantly less pain at rest measured by the visual analogue scale (VAS) on the 1st postoperative day (U-test, P < 0.05), but otherwise there were no statistical differences regarding pain scores. Respiratory parameters such as forced vital capacity, forced expiratory volume, peak flow and the Tiffeneau test (FVC, FEV1, PF, FEV1/FVC) were reduced significantly after thoracoscopy and showed a slow recovery in all three groups without significant intergroup differences. Thoracoscopic surgery causes less and shorter lasting pain in comparison to thoracotomy. Nevertheless, effective pain management is necessary. We could not demonstrate a significant reduction in piritramide consumption for the techniques of regional analgesia tested here (ICB, IPA). We conclude that the use of these techniques is not complementary after thoracoscopy, since an opioid (PCA with piritramide) combined with a non-opioid (metamizol) resulted in satisfactory analgesia.

Adult↗
PubMed1997

[Pain therapy after thoracotomies--systemic patient-controlled analgesia (PCA) with opioid versus intercostal block and interpleural analgesia].

Both regional analgesia and systemic opioid therapy (e.g. PCA) are commonly used for pain relief following thoracic surgery. Many anaesthesiologists are reluctant to use thoracic epidural analgesia on general surgical wards. Therefore, we investigated in a prospective randomised study the efficacy of intercostal blocks (ICB) or interpleural analgesia (IPA) compared to PCA with systemic opioids (PCA). Following ethics committee approval and informed consent, 45 thoracotomy patients were randomised for postoperative pain management: group 1: intravenous PCA with piritramide (PCA-control), group 2: intercostal blocks of the segments concerned with 5 ml bupivacaine 0.5% at the end of surgery and 6 hours thereafter (ICB), group 3: interpleural analgesia with 20 ml bupivacaine 0.25% applied every 4 hours using a catheter placed during surgery near the apex of the pleural space (IPA). Patients in the ICB and IPA groups were able to obtain additional pain relief by PCA with piritramide. Alternative medication for all groups in case of insufficient analgesia was metamizol. Both regional analgesia groups used significantly less piritramide up to the 3rd (IPA) or 7th (ICB) postoperative day than the control group (p < 0.05). The consumption of metamizol was lower as well (n. s.). No significant differences between the study groups were observed with regard to pain scores (visual analogue scale VAS) at rest, during deep inspiration, coughing or mobilisation. Respiratory parameters as forced vital capacity, forced expiratory volume (1 sec) and peak flow (FVC; FEV1; PF) were reduced significantly following thoracotomy and showed a slow restitution in all three study groups without major inter-group differences. Intercostal blocks and interpleural analgesia significantly reduce opioid demand following thoracotomy and are effective means of postoperative pain management. Nevertheless, in contrast to epidural analgesia, both methods have to be supplemented by, or combined with, systemic analgesics in most patients. On the other hand, compared to epidural analgesia, ICB and IPA are less invasive and easier to manage on general surgical wards.

Adult↗
PubMed1995

A novel common Kell antigen, TOU, and its spatial relationship to other Kell antigens.

A 47-year-old native American (TOU) was admitted to hospital for hip surgery. His serum agglutinated all red blood cells (RBCs) tested except Ko and DTT-treated RBCs and was weakly reactive with RBCs known to have a weak expression of Kell antigens, namely Kmod, McLeod, Kp(a+b-) (KEL:3,-4) and K:-13 (KEL:-13) phenotypes. RBCs from three siblings, a son and a daughter were incompatible with TOU's antibody. TOU's RBCs had the common Kell phenotype: K-k+Kp(a-b+c-)Ku+Js(a-b+)Ul(a-)K:11,-17K:14,-24K:12,13,18,19, 22,-23(KEL:-1,2,-3,4,5,-6,7,-10,11,12,13,14,-17,18,19,-21,22,-23,-24). Since TOU's RBCs were not agglutinated by an unidentified Kell-related antibody (IAN), tests were performed to show that TOU and IAN were mutually compatible. IAN is a Latino female hospitalised for a hysterectomy. The TOU antigen was shown to be located on the Kell glycoprotein by a monoclonal antibody immobilisation of erythrocyte antigen (MAIEA) assay. The unique pattern of reactivity obtained with TOU and IAN antibodies using this assay indicated the TOU epitope to be in an area remote from other Kell antigens, namely K, k, Kpa, Kpb, Kpc, Ku, Jsa, Jsb, U1a, K11, K12, K13, K14, Wka, K18, K19, K22 and K24 (KEL1, KEL2, KEL3, KEL4, KEL5, KEL6, KEL7, KEL11, KEL12, KEL13, KEL14, KEL17, KEL18, KEL4, KEL5, KEL6, KEL7, KEL11, KEL12, KEL13, KEL14, KEL17, KEL18, KEL19, KEL21, KEL22 and KEL24) but close to the low-incidence antigen K23 (KEL23).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1993

[Results of cementless implantation of 150 "Erlangen Model" hip prostheses of titanium alloy Ti Al5 Fe2.5].

Between March 17, 1984 and August 20, 1987, 142 patients with osteoarthritis of one or both hips were treated by joint replacement with the uncemented "Erlangen" hip prosthesis (Prof. H. Beck/P. Brehm Chirurgie-Mechanik GmbH). The causes of the osteoarthritis varied. Hip replacement was carried out for the following conditions: rheumatoid arthritis including ankylosing spondylitis, aseptic necrosis of the femoral head, including posttraumatic and idiopathic forms, osteoarthritis of unknown origin, osteoarthritis following dysplasia or subluxation of the hips, and loosened cemented hip prostheses (131 primary implantations and 19 revisions). Full weight-bearing was not permitted for 50 days postoperatively, but mobilization and isometric exercises were started 2 days after operation and isotonic exercises were introduced later. Complications included fracture of the femoral shaft during operation and aseptic loosening. Our results in the 142 patients (150 joints) at 32-65 months (average 44 months) after surgery are encouraging. Good results based on patient satisfaction were obtained in 92.7% (81.3% after revision) and poor results in 7.3% (18.7% after revision). Most (90.2%) of the patients can walk without a stick (50.0% after revision), and 90.2% of the patients can walk more than 1000 m (68.8% after revision).

Alloys↗
PubMed1991

Synthetic peptides homologous to human glycophorins of the Miltenberger complex of variants of MNSs blood group system specify the epitopes for Hil, SJL, Hop, and Mur antisera.

The antigenic epitopes of the MNSs blood groups are localized on alpha and delta glycophorins (glycophorins A and B) of the erythrocyte surface. Hil, SJL, Mur, and Hop antisera define the Miltenberger (Mi) complex of MiV, MiJ.L., MiIII, and MiVI variant serologic phenotypes of this blood group system. We report here the location of the epitopes for antibodies in these antisera. The antigens of these Mi classes are variant glycophorins that are hybrids of alpha and delta glycophorins in alpha-delta and delta-alpha-delta arrangements. The hybrid junctions give rise to novel polypeptide sequences not present in the parent glycophorins; in MiIII and MiVI this also includes an expressed sequence of the delta pseudoexon. These sequences are identical in the above Mi-glycophorins occurring in erythrocytes that share a common Mi determinant. Four peptides of 10 to 14 amino acids each were constructed to be homologous to the identical sequences; they were designated, "Hil", "SJL", "Mur", and "Hop" to reflect the common determinant. The peptides were tested for inhibition of reaction of appropriate cells with the relevant antisera. The Hil peptide, outlining the alpha-delta s junction region in MiIII, MiV, and MiVI glycophorins, inhibited the reaction of respective erythrocytes (red blood cells [RBCs]) with anti-Hil. The SJL peptide, which differs from the Hil peptide by a single Thr----Met substitution, was specific for inhibition of the reaction of MiJ.L. RBCs with anti-SJL (an example of anti-S specific for such RBCs). The Hop peptide, which corresponds to the delta-alpha junction in MiVI glycophorin, inhibited the hemagglutination of MiVIII RBCs by anti-Hop. MiVI and MiVIII glycophorins share an identical sequence at that site. The Mur peptide, corresponding to a portion of the expressed pseudoexon sequence in MiIII and MiVI glycophorins, was specific for inhibition of the reaction of MiIII and MiVI RBCs with anti-Mur. The peptides had no effect on the hemagglutination of control MNSs RBCs by their respective antisera nor of unrelated Mi classes RBCs by antisera that distinguish these classes. We conclude that the alpha-delta junction in MiIII, MiV, and MiVI glycophorins outlines the epitopes for anti-Hil, the alpha-delta junction in MiJ.L. outlines the epitope for anti-SJL, the delta-alpha junction in MiVI constitutes the epitope for anti-Hop, and the expressed delta pseudoexon sequence in MiIII and MiVI constitutes the epitope for anti-Mur.

Amino Acid Sequence↗
PubMedDate not supplied

Cholestasis as a side effect of bupivacaine?

BACKGROUND AND OBJECTIVES: Cholestasis has been proposed as a side effect of interpleural bupivacaine. Therefore, the effects of various application techniques on liver enzymes were studied following ethics committee approval and informed patient consent. METHODS: Patients following scheduled thoracotomy and laparoscopic cholecystectomy were prospectively studied and randomized to the following application techniques of bupivacaine: Thoracic surgery. T0: Control (systemic analgesia only: patient-controlled analgesia with opioids; n = 26); T1: Repetitive intercostal blocks (10-20 mL 0.5% bupivacaine, 2-4 times per day for 3-6 days; n = 17); T2: Interpleural injections via a catheter placed intraoperatively (20 mL 0.25%, 4-6 times per day for 3-6 days, right: n = 25 or left: n = 12). Laparoscopic cholecystectomy. Intraperitoneal application (single injection). L0: 50 mL saline (Control) (n = 21). L1: 50 mL 0.125% bupivacaine (n = 18); L2: 50 mL 0.25% (n = 20). The serum concentrations of bilirubin, gamma-GT, alkaline phosphatase, leucine amino peptidase, glutamate oxalacetate transaminase, and glutamate pyruvate transaminase were measured preoperatively and on day 1, 3, and 7 postoperatively. RESULTS: Neither application of plain bupivacaine was associated with significant changes in the postoperative concentration of hepatic enzymes. In particular, there was no difference between left- and right-sided interpleural application. Although increases in hepatic enzyme concentrations were observed in some patients postoperatively, this was similar in the bupivacaine and control groups. CONCLUSION: Perioperative interpleural, intercostal, and intraperitoneal administration of bupivacaine was not associated with findings indicative of cholestasis in the early postoperative course.

Adult↗