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Biomedical subjects

L Gutmann

Publications and source records attributed to L Gutmann.

At least 19 recordsLinked to original sources
PubMed2006

Occurrence of qnrA-positive clinical isolates in French teaching hospitals during 2002-2005.

Bacteria harbouring the novel qnrA plasmid-mediated mechanism of quinolone resistance have been described in different countries, but the frequency of their occurrence has not been investigated. In total, 1,468 clinical isolates of Enterobacteriaceae with quinolone resistance or extended-spectrum beta-lactamase (ESBL) phenotypes were collected from eight teaching hospitals in France during 2002-2005 and screened for qnrA. Overall, 28 isolates (22 Enterobacter cloacae, three Klebsiella pneumoniae, one Citrobacter freundii, one Klebsiella oxytoca and one Proteus mirabilis) were positive for qnrA, representing 1.9% of all isolates, 3.3% of ESBL-producing isolates (22% of the E. cloacae isolates) and 0% of non-ESBL-producing isolates. The prevalence of qnrA among consecutive ESBL-producing isolates in 2004 from the eight hospitals was 2.8% (18/639). Of the qnrA-positive isolates, 100% were intermediately-resistant or resistant to nalidixic acid, and 75% to ciprofloxacin. Twenty-one of the 22 qnrA-positive E. cloacae isolates were obtained from two hospitals in the Paris area, and molecular typing and plasmid content analysis showed clonal relationships for five, three and two isolates, respectively. The qnrA genetic environment was similar to that of the In36 integron. The remaining two isolates had qnrA variants (30 and 29 nucleotide differences, respectively, compared with the original sequence) and an unknown genetic environment. The ESBL gene associated with qnrA was bla(SHV-12) in most of the isolates, but bla(PER-1) and bla(SHV-2a) were found in two isolates. In France, it appears that qnrA-positive isolates are predominantly E. cloacae isolates producing SHV-12, and may be associated with the dissemination of an In36-like integron.

Bacterial Proteins↗
PubMed2003

Fulminant invasive pulmonary aspergillosis in immunocompetent patients--a two-case report.

Two cases of invasive aspergillosis (IA) in immunocompetent patients with a fulminant fatal outcome are reported. Both patients were elderly and had a history of chronic lung disease treated with prolonged inhaled corticosteroids and a short course of systemic corticosteroids. They presented with dyspnea and fever, their respiratory function deteriorated rapidly, and they died 7 days after admission. Aspergillus fumigatus was cultured from respiratory samples. IA was confirmed in one case by necropsy that showed diffuse bilateral necrotizing pneumonitis and myocarditis. In the other case, IA diagnosis was established by thoracic CT scan plus detection of Aspergillus antigen in two blood samples. These two cases demonstrate that short-term corticosteroid therapy in immunocompetent patients with underlying chronic lung conditions is a risk factor for IA, and that its evolution can be fulminant.

Administration, Inhalation↗
PubMed2001

Persistent facial myokymia associated with K(+) channel antibodies.

A 58-year-old woman developed bilateral facial myokymia in 1978, persisting for the next 23 years and associated with high titers of voltage-gated K(+) channel (VGKC) antibodies. Brain imaging failed to show a pontine lesion. The clinical facial myokymia and electromyographic doublets and multiplets (43 to 250 Hz) were milder and more restricted than those seen in generalized neuromyotonic disorders with VGKC antibodies. This case and another reported recently represent a focal VGKC antibody syndrome.

Autoantibodies↗
PubMed2001

Current management of ALS: comparison of the ALS CARE Database and the AAN Practice Parameter. The American Academy of Neurology.

BACKGROUND: The American Academy of Neurology (AAN) ALS Practice Parameter was published in April 1999. The ALS CARE Database has been collecting data on the management of patients with ALS in North America since 1996. OBJECTIVE: To compare the management of patients with ALS in North America as recorded in the ALS CARE Database with the recommendations of the AAN ALS Practice Parameter. METHODS: Data were analyzed from 2018 patients at enrollment and from 373 of these patients who died between enrollment and May 1999. RESULTS: Eighty-two percent of the enrolled patients reported that they had been given enough information about ALS. Only 54% of patients with drooling were receiving medication for this problem. Only 41% of those who reported being depressed most of the time were receiving antidepressant medications. Only 28% of those with dyspnea and only 9.2% of those with a forced vital capacity <40% predicted were receiving noninvasive positive pressure ventilator support. Only 30% of those with moderate to severe dysphagia had a gastrostomy tube. Half of the patients who died did so at home, but only 47% of them received residential hospice services. Although 89% of patients who died were recorded as having done so peacefully, 17% were reported to have had breathing difficulties (i.e., respiratory distress), 8% anxiety, 3.3% pain, and 2.5% choking. Advance directives were in place for 90% of the patients who died, and in 97% of cases these directives were followed. CONCLUSIONS: These findings indicate that in the 3-year period prior to the publication of the AAN Practice Parameter, many but not all patients received the care that is recommended in that parameter; there were deficiencies, particularly in the key areas of gastrostomy and noninvasive positive pressure ventilation.

Amyotrophic Lateral Sclerosis↗
PubMed2001

New mutation in parE in a pneumococcal in vitro mutant resistant to fluoroquinolones.

For an in vitro mutant of Streptococcus pneumoniae selected on moxifloxacin four- to eightfold-increased MICs of new fluoroquinolones, only a twofold-increased MIC of ciprofloxacin, and a twofold-decreased MIC of novobiocin were observed. This phenotype was conferred by two mutations: Ser81Phe in GyrA and a novel undescribed His103Tyr mutation in ParE, outside the quinolone resistance-determining region, in the putative ATP-binding site of topoisomerase IV.

Adenosine Triphosphate↗
PubMed2001

Penicillin-binding protein 5 and expression of ampicillin resistance in Enterococcus faecium.

We report a structural and transcriptional analysis of the pbp5 region of Enterococcus faecium C68. pbp5 exists within a larger operon that includes upstream open reading frames (ORFs) corresponding to previously reported psr (penicillin-binding protein synthesis repressor) and ftsW (whose product is a transmembrane protein that interacts with PBP3 in Escherichia coli septum formation) genes. Hybridization of mRNA from C68, CV133, and four ampicillin-resistant CV133 mutants revealed four distinct transcripts from this region, consisting of (i) E. faecium ftsW (ftsW(Efm)) alone; (ii) psr and pbp5; (iii) pbp5 alone; and (iv) ftsW(Efm), psr, and pbp5. Quantities of the different transcripts varied between strains and did not always correlate with quantities of PBP5 or levels of ampicillin resistance. Since the psr of C68 is presumably nonfunctional due to an insertion of an extra nucleotide in the codon for the 44th amino acid, the region extending from the ftsW(Efm) promoter through the pbp5 gene of C68 was cloned in E. coli to facilitate mutagenesis. The psr ORF was regenerated using site-directed mutagenesis and introduced into E. faecium D344-SRF on conjugative shuttle vector pTCV-lac (pCWR558 [psr ORF interrupted]; pCWR583 [psr ORF intact]). Ampicillin MICs for both D344-SRF(pCWR558) and D344-SRF(pCWR583) were 64 microg/ml. Quantities of pbp5 transcript and protein were similar in strains containing either construct regardless of whether they were grown in the presence or absence of ampicillin, arguing against a role for PSR as a repressor of pbp5 transcription. However, quantities of psr transcript were increased in D344-SRF(pCWR583) compared to D344-SRF(pCWR558), especially after growth in ampicillin; suggesting that PSR acts in some manner to activate its own transcription.

Ampicillin Resistance↗
PubMed2001

Role of penicillin-binding protein 5 in expression of ampicillin resistance and peptidoglycan structure in Enterococcus faecium.

The contribution of penicillin-binding protein 5 (PBP 5) to intrinsic and acquired beta-lactam resistance was investigated by constructing isogenic strains of Enterococcus faecium producing different PBP 5. The pbp5 genes from three E. faecium clinical isolates (BM4107, D344, and H80721) were cloned into the shuttle vector pAT392 and introduced into E. faecium D344S, a spontaneous derivative of E. faecium D344 highly susceptible to ampicillin due to deletion of pbp5 (MIC, 0.03 microg/ml). Immunodetection of PBP5 indicated that cloning of the pbp5 genes into pAT392 resulted in moderate overproduction of PBP 5 in comparison to wild-type strains. This difference may be attributed to a difference in gene copy number. Expression of the pbp5 genes from BM4107 (MIC, 2 microg/ml), D344 (MIC, 24 microg/ml), and H80721 (MIC, 512 microg/ml) in D344S conferred relatively low levels of resistance to ampicillin (MICs, 6, 12, and 20 microg/ml, respectively). A methionine-to-alanine substitution was introduced at position 485 of the BM4107 PBP 5 by site-directed mutagenesis. In contrast to previous hypotheses based on comparison of nonisogenic strains, this substitution resulted in only a 2.5-fold increase in the ampicillin MIC. The reversed-phase high-performance liquid chromatography muropeptide profiles of D344 and D344S were similar, indicating that deletion of pbp5 was not associated with a detectable defect in cell wall synthesis. These results indicate that pbp5 is a nonessential gene responsible for intrinsic resistance to moderate levels of ampicillin and by itself cannot confer high-level resistance.

Ampicillin Resistance↗
PubMed2001

Identification of the UDP-MurNAc-pentapeptide:L-alanine ligase for synthesis of branched peptidoglycan precursors in Enterococcus faecalis.

Many species of gram-positive bacteria produce branched peptidoglycan precursors resulting from the transfer of various L-amino acids or glycine from amino acyl-tRNA to the epsilon-amino group of L-lysine. The UDP-MurNAc-pentapeptide:L-alanine ligase and alanyl-tRNA synthetase genes from Enterococcus faecalis were identified, cloned, and overexpressed in Escherichia coli. The purified enzymes were necessary and sufficient for tRNA-dependent addition of L-alanine to UDP-MurNAc-pentapeptide in vitro. The ligase belonged to the Fem family of proteins, which were initially identified genetically as factors essential for methicillin resistance in Staphylococcus aureus.

Alanine↗
PubMed2000

Selection of drug-resistant variants in the female genital tract of human immunodeficiency virus type 1-infected women receiving antiretroviral therapy.

We investigated human immunodeficiency virus (HIV) type 1 RNA, proviral DNA, and antiretroviral drug-resistant variants in cervicovaginal secretions of HIV-1-infected women receiving antiretroviral therapy. The prevalence of detectable HIV-1 RNA in genital secretions was inversely related to the number of antiretroviral drugs taken by the patients. Proviral DNA was detected in approximately half of all samples of cervicovaginal secretions from HIV-1-infected women, regardless of the presence or absence of HIV-1 RNA in cervicovaginal secretions and of the antiretroviral regimen. In cervicovaginal secretions of most women with persisting genital viral replication, HIV variants exhibiting mutations associated with drug resistance against protease and reverse-transcriptase pol genes were found. Our observations indicate that antiretroviral therapy is not effective in purging the female genital tract of cell-associated provirus and that antiretroviral drugs that penetrate the female genital tract at suboptimal concentrations exert a potent selective pressure on genital HIV variants when local replication of free HIV-1 RNA persists.

Adult↗
PubMed2000

Novel mechanism of beta-lactam resistance due to bypass of DD-transpeptidation in Enterococcus faecium.

The peptidoglycan structure of in vitro selected ampicillin-resistant mutant Enterococcus faecium D344M512 and of the susceptible parental strain D344S was determined by reverse phase high performance liquid chromatography and mass spectrometry. The muropeptide monomers were almost identical in the two strains. The substantial majority (99.3%) of the oligomers from the susceptible strain D344S contained the usual d-alanyl --> d-asparaginyl (or d-aspartyl)-l-lysyl cross-link (d-Ala --> d-Asx-l-Lys) generated by beta-lactam-sensitive DD-transpeptidation. The remaining oligomers (0.7%) were produced by beta-lactam-insensitive LD-transpeptidation, because they contained l-Lys --> d-Asx-l-Lys cross-links. The muropeptide oligomers of the ampicillin-resistant mutant D344M512 contained only these l-Lys --> d-Asx-l-Lys cross-links indicating that resistance was due to the bypass of the beta-lactam-sensitive DD-transpeptidation reaction. The discovery of this novel resistance mechanism indicates that DD-transpeptidases cannot be considered anymore as the sole essential transpeptidase enzymes.

Amino Acid Sequence↗
PubMed2000

The cumulative occurrence of resistance mutations in the HIV-1 protease gene is associated with failure of salvage therapy with ritonavir and saquinavir in protease inhibitor-experienced patients.

Salvage therapy with ritonavir (RTV) and saquinavir (SQV) failed to achieve virological and immunological improvement in 24 HIV-infected patients who discontinued triple therapy with RTV or indinavir (IDV) because of failure or intolerance to treatment. Changes in the HIV-1 protease gene sequence were analyzed prospectively in 14 patients. No primary protease mutation was found prior to the use of protease inhibitors. After 7 months of treatment with IDV or RTV, primary resistance mutations at codons pol 46 and/or pol 82 were observed in 11 of 13 patients. After 16 weeks on RTV-SQV, novel primary mutations related to SQV emerged in 7 of 13 patients, together with an increase in the number of secondary resistance mutations. Our observations indicate that the cumulative occurrence of resistance mutations in the protease gene was associated with failure of antiretroviral therapy. The presence of mutations to a first protease inhibitor may represent a risk factor for the failure of a subsequent treatment with a second line protease inhibitor.

Adult↗
PubMed2000

Periodic paralyses.

The periodic paralyses are a group of muscle diseases with abnormalities of channels. These abnormalities result in paralysis or weakness with or without poor relaxation of muscle. Hypokalemic periodic paralyses, potassium-sensitive periodic paralyses, and paramyotonia congenita are reviewed. The clinical findings, pathophysiologic abnormalities, diagnostic evaluations, and possible treatments are included in this article.

Biopsy↗