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Biomedical subjects

L Gutmann

Publications and source records attributed to L Gutmann.

At least 235 records · Page 13Linked to original sources

Reversible ipecac myopathy.

The abuse of ipecac syrup for three years resulted in painless, nonfatigable, chiefly proximal weakness in a 27-year-old woman. Electromyography (EMG) and a muscle biopsy revealed features of a myopathy similar to those previously reported in experimental emetine myopathy. Clinical weakness and EMG abnormalities improved after discontinuation of ipecac administration. A direct toxic action of ipecac (acting through its active alkaloid, emetine hydrochloride) on muscle fibers seemed to be responsible for the weakness in this patient.

Adult↗

Cross-resistance to nalidixic acid, trimethoprim, and chloramphenicol associated with alterations in outer membrane proteins of Klebsiella, Enterobacter, and Serratia.

We studied in vitro mutants of Klebsiella, Enterobacter, and Serratia cross-resistant to nalidixic acid, trimethoprim, and chloramphenicol that were similar to mutants found in vivo. The sole mechanism for this type of resistance appeared to be a reduction in permeability of the cell envelope. The mutants had significantly lower rates of uptake of glucose and chloramphenicol, but binding of chloramphenicol to ribosomes was normal. In addition, the amounts of dihydrofolate reductase were similar in both wild-type and cross-resistant mutants of Klebsiella. Examination of the bacterial outer membrane revealed that the amount of at least one major protein, with a molecular size of approximately 40 kilodaltons, was decreased in the mutants. Therefore the resistance seemed likely to be due to the reduction in quantity of these outer membrane proteins, possibly porins, in the mutant bacteria.

Anti-Bacterial Agents↗

In-vitro susceptibility of Nocardia asteroides to 21 beta-lactam antibiotics, in combination with three beta-lactamase inhibitors, and its relationship to the beta-lactamase content.

Twelve strains of Nocardia asteroides were studied for their susceptibility to 21 beta-lactam antibiotics, alone or in combination with clavulanic acid, sulbactam, or BLP 2013, and for their content of beta-lactamase. Eleven strains were shown to have beta-lactamase activities, which gave three different patterns after analytical isoelectric focusing. The only strain with no detectable beta-lactamase was the most susceptible to the antibiotics tested. The other strains containing beta-lactamases showed almost the same susceptibility profile. Clavulanic acid was the only beta-lactamase inhibitor to show a significant synergistic effect when combined with penicillins.

Anti-Bacterial Agents↗

Sch 34343 activity against streptococci and beta-lactam-resistant Enterobacteriaceae.

The in-vitro activity of Sch 34343 was compared with that of cefotaxime, ceftazidime, latamoxef (moxalactam), aztreonam and ampicillin. Against pneumococci, Sch 34343 was as active as ampicillin, whereas against the other streptococci it was less active than ampicillin but significantly better than the other antibiotics against enterococci. With clinical isolates of Enterobacteriaceae resistant to cefotaxime, Sch 34343 had MICs generally less than 2 mg/l. After introduction of plasmid-mediated beta-lactamases into Escherichia coli Cla. there were no significant changes in the MICs of Sch 34343. Mutants of Enterobacter cloacae, Citrobacter freundii and Morganella morganii with derepressed cephalosporinases had susceptibilities equal to or less than 1 mg/l, which were generally lower than those of the other compounds tested. Comparison of parental strains and permeability mutants of E. coli, Ent. cloacae, and Serratia marcescens showed that the increase in MICs of Sch 34343 were lower than those found for the other antibiotics.

Anti-Bacterial Agents↗

One or two low affinity penicillin-binding proteins may be responsible for the range of susceptibility of Enterococcus faecium to benzylpenicillin.

Three benzylpenicillin-resistant, clinical isolates of Enterococcus faecium (MIC values 16-64 micrograms ml-1) contained six penicillin-binding proteins (PBPs), of which PBP5 was the most abundant and had the lowest affinity for the antibiotic. Four benzylpenicillin-susceptible strains (MIC values 0.031-0.5 microgram ml-1) were obtained as spontaneous derivatives from these above organisms. There were significant decreases in the amounts of PBP5 in each of the derivatives, with the concomitant appearance of a new, higher affinity PBP (5*) in three strains. Increased amounts of PBP5, with no changes in PBP5*, were found in several mutants with intermediate-level benzylpenicillin-resistance (MIC values 1-8 micrograms ml-1) selected from two of the susceptible strains. Examination of 18 other clinical isolates, with a wide range of susceptibilities to benzylpenicillin (MIC values 0.062-128 micrograms ml-1), showed that PBP5* was present in 13 strains, and PBP5 in all of them, but in differing amounts. The results concerning the relative amounts and relative affinities of PBPs 5* and 5 allowed the categorization of the various strains into six groups, within which organisms had somewhat similar susceptibilities to benzylpenicillin.

Bacterial Proteins↗

Characterization of nutritionally variant streptococci by biochemical tests and penicillin-binding proteins.

A comparative study of 60 strains of nutritionally variant streptococci (NVS) with 34 strains of Streptococcus mitis and 37 strains of Streptococcus sanguis II showed the presence of a red chromophore which was absent in the other streptococcal species. By using the conventional microbiological tests, only small differences were found between the NVS and the two other related species. In contrast a clear-cut delineation was found by the API 20 Strep system of identification. All NVS contained pyrrolidonylarylamidase, an enzyme which was absent in S. mitis and S. sanguis II strains, and lacked the alkaline phosphatase enzyme which was present in 56% of S. mitis strains and 62% of S. sanguis II strains. According to the additional enzymatic and biochemical tests of the API 20 Strep system, there were three biotypes among NVS. The major biotype included 33 of 60 strains which were characterized by the presence of both alpha- and beta-galactosidases and the capacity to hydrolyze trehalose. This biotype also showed a specific pattern of penicillin-binding proteins. These results show that NVS are recognized as a separate variety distinct from S. mitis and S. sanguis II species, despite some common biochemical properties. Moreover, the delineation of 33 strains with a specific biotype and a specific penicillin-binding protein pattern strongly suggests that a large part of NVS strains belong to an individual species.

Bacterial Proteins↗

Inclusion body myositis and chronic immune thrombocytopenia.

We report a case of inclusion body myositis and chronic immune thrombocytopenia with serum platelet antibodies and circulating immune complexes. Although immune mechanisms probably play an important role in the pathogenesis of inclusion body myositis, a viral etiology cannot be excluded.

Antibodies↗

Different mechanisms of resistance to latamoxef (moxalactam) in Serratia marcescens.

Three pairs of latamoxef (moxalactam)-resistant and -sensitive strains of Serratia marcescens were isolated either in vivo or in vitro. Multiple mechanisms of resistance were found, and these mechanisms involved: a decrease in permeability in each case, associated with modification of the protein composition of the outer membrane in two cases; a variable increase (two-to-six-fold) in the amount of beta-lactamase; and in one case only, some modification of the penicillin binding proteins. Thus, it may be necessary for multiple mechanisms to be present to give resistance to latamoxef in this species.

Bacterial Proteins↗

Recovery period after exposure of Staphylococcus aureus to sub-inhibitory and bactericidal concentrations of rifampicin: clinical implications.

The effects of rifampicin, at subinhibitory and bactericidal concentrations, were examined in the presence of and after the removal of the drug. After exposure to subinhibitory concentrations as low as one-tenth of the MIC an extended recovery period was observed. Incubation of exponential or stationary phase cultures for 30 min or 4 h with a bactericidal concentration also caused a significantly prolonged recovery period.

Colony-Forming Units Assay↗

An evaluation of the bacteriolytic and biochemical properties of ceftiolene (42980RP).

Ceftiolene (42980RP) is a new cephalosporin with a broad antibacterial spectrum similar to cefotaxime or ceftriaxone. The characteristics of ceftiolene have been tested in a variety of assays involving various biochemical aspects of the mode of action of beta-lactam antibiotics. The affinities of ceftiolene for penicillin-binding proteins were very comparable with those of ceftriaxone and cefotaxime for Escherichia coli, and generally greater than those of latamoxef (moxalactam) for the higher molecular weight PBPs of E. coli. Enterobacter cloacae. Proteus mirabilis and Pseudomonas aeruginosa. The affinity of ceftiolene for PBP1 of Staphylococcus aureus was greater than those of cefotaxime or latamoxef, but comparable with these antibiotics for PBP3. The bacteriolytic activity of ceftiolene at defined concentrations against Gram-negative organisms was similar to that of ceftriaxone, and significantly better than that of the other third-generation cephalosporins tested. Introduction of plasmid-encoded beta-lactamases into E. coli reduced the wide variation in bacteriolytic effect of the different cephalosporins, and a significant inoculum effect was observed for the bacteriolysis. Chloramphenicol was less antagonistic against ceftiolene- or ceftriaxone-induced lysis than was observed for cefotaxime or latamoxef. Growth of Staph. aureus at low concentrations of ceftiolene caused the bacteria to become more sensitive to lysis by lysostaphin than organisms grown with cefotaxime or latamoxef under the same conditions. These observations confirm the necessity to use techniques other than routine MIC determinations to distinguish between antibiotics which would otherwise appear very similar.

Anti-Bacterial Agents↗

Development of resistance to beta-lactam antibiotics with special reference to third-generation cephalosporins.

The resistance mechanisms associated with changes in the outer membrane permeability and in beta-lactamase and penicillin-binding-protein production are reviewed. The prevalence of membrane permeability- and chromosome-mediated beta-lactamase-related resistance in Gram-negative bacteria, and of PBP-related resistance in Gram-positive bacteria, with respect to third-generation cephalosporins, is outlined. The frequency of overall resistance to these compounds in two Parisian hospitals during 1983 did not exceed 2% in Enterobacteriaceae but was close to 15% in Pseudomonas sp.

Bacteria↗

Mitochondrial encephalomyopathy with decreased succinate-cytochrome c reductase activity.

We report two siblings with a mitochondrial encephalomyopathy. The syndrome was characterized by ataxia, intellectual impairment, myoclonic jerks, rare seizures, and small stature. Muscle biopsy specimens showed abnormal accumulations of mitochondria and lipid droplets. Biochemical studies on muscle demonstrated decreased succinate-cytochrome c reductase activity in the mitochondrial respiratory chain.

Brain Diseases↗