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Biomedical subjects

L Gutmann

Publications and source records attributed to L Gutmann.

At least 145 records · Page 8Linked to original sources
PubMed1991

Myotonia congenita.

There are two types of MC, autosomal dominant and autosomal recessive (also called recessive generalized myotonia), both with the predominant clinical feature of diffuse myotonia. Recessive MC patients have more weakness than patients with dominant MC. MC patients of both types have a normal life span. Ongoing genetic studies have not as yet identified any chromosomal linkage. Electrophysiologically and pathophysiologically, there is no difference between these two types. The major pathophysiologic abnormality is decreased membrane chloride conductance. Treatment of myotonia is not always necessary, but when it is, the most effective medications are those that stabilize the muscle membrane. Phenytoin is frequently the first choice because it has more benign side effect profile than other drugs and a reasonable response rate.

Diagnosis, Differential↗
PubMed1991

Triple-combination penicillin-vancomycin-gentamicin for experimental endocarditis caused by a moderately penicillin- and highly glycopeptide-resistant isolate of Enterococcus faecium.

An in vitro bacteriostatic synergy between beta-lactam and glycopeptide antibiotics has been recently described against isolates of Enterococcus faecium moderately resistant to penicillin and highly resistant to vancomycin. The relevance of this synergy in a rabbit endocarditis model was evaluated. Penicillin was tested at low- (LoD) and high-dose (HiD) regimens, alone or combined with vancomycin and/or gentamicin. Compared with controls, after a 5-day treatment: LoD penicillin, vancomycin, gentamicin, LoD penicillin plus gentamicin or vancomycin, and vancomycin-gentamicin were not effective; LoD penicillin-vancomycin caused a small reduction of bacterial titers in vegetations that was strongly enhanced by adding gentamicin; HiD penicillin-gentamicin, the most effective regimen, was not significantly better than LoD penicillin-vancomycin-gentamicin. These results suggest that the relative in vivo inefficacy of penicillin-vancomycin might be related to the fact that this combination was poorly bactericidal, and the triple combination of LoD penicillin-vancomycin-gentamicin or the combination of HiD penicillin-gentamicin should be considered in the treatment of serious infections due to beta-lactam- and glycopeptide-resistant enterococci.

Animals↗
PubMed1991

Mechanisms of quinolone resistance in a clinical isolate of Escherichia coli highly resistant to fluoroquinolones but susceptible to nalidixic acid.

Two associated resistance mechanisms were found in a nalidixic acid-susceptible (4 micrograms/ml) but fluoroquinolone-resistant (8 to 16 micrograms/ml) strain of Escherichia coli Q2 selected under norfloxacin therapy. As compared with the susceptible E. coli Q1 isolated before treatment, changes in outer membrane proteins and lipopolysaccharides in Q2 were associated with a 1.5- to 3-fold decrease in the uptake of fluoroquinolones but not nalidixic acid. A 50% inhibition of DNA synthesis in toluene-permeabilized cells of the resistant strain E. coli Q2 required up to 500-fold increased quantities of fluoroquinolones, whereas such inhibition was obtained in both E. coli Q1 and Q2 with similar amounts of nalidixic acid. Selection from E. coli Q1 on norfloxacin of one-step resistant mutants resembling E. coli Q2 was unsuccessful. From these results we infer that a decrease in outer membrane permeability, associated with a peculiar alteration of the DNA gyrase, was responsible for the unusual quinolone resistance phenotype of E. coli Q2.

Anti-Infective Agents↗
PubMed1991

Synergistic killing of vancomycin-resistant enterococci of classes A, B, and C by combinations of vancomycin, penicillin, and gentamicin.

Using both high and low inocula for time-kill curves, we examined the antibiotic killing of clinical isolates of glycopeptide-resistant enterococci (Enterococcus faecium, E. faecalis, and E. gallinarum) belonging to phenotypic resistance classes A, B, and C. None were resistant to high levels (greater than 500 mg/liter) of gentamicin. Vancomycin-penicillin-gentamicin resulted in 2 or more logs of killing above that of the most effective two-antibiotic combination for all strains except two of three E. gallinarum (VanC) strains and a constitutive mutant of a VanB strain. This strategy may be useful clinically.

Drug Resistance, Microbial↗
PubMed1991

Association of two resistance mechanisms in a clinical isolate of Enterobacter cloacae with high-level resistance to imipenem.

Carbapenem resistance was studied in a clinical isolate of Enterobacter cloacae, strain 201 (MIC of imipenem and meropenem, 16 micrograms/ml). This strain was analyzed comparatively with the carbapenem-susceptible parent strain 200, an equally susceptible revertant, 201-Rev, and in vitro-selected mutants with different levels of carbapenem resistance. All strains produced similarly high amounts of the same cephalosporinase (pIapp = 8.8). Strain 201 apparently lacked two major outer membrane proteins of ca. 37 and 38 kDa, while 201-Rev produced only the 37-kDa protein. The permeability coefficient, determined with cephaloridine, was reduced up to ninefold in the resistant strains which also showed a substantial reduction in the uptake of [14C]meropenem. The introduction of the plasmid-borne ampD gene (whose product decreases the expression of ampC) resulted in almost complete cessation of cephalosporinase production in all strains and a substantial decrease in the MICs of the carbapenems which remained, however, 8- to 16-fold higher than those determined for the susceptible strains containing the ampD gene. This "residual" resistance was attributed to reduced outer membrane permeability. The contribution of cephalosporinase production was verified in a reverse experiment, in which the introduction of ampC into a low-level cephalosporinase producer resulted in a fourfold increase in the carbapenem MICs. From these results, we infer that reduced outer membrane permeability and high-level cephalosporinase production can operate in conjunction in clinical isolates of E. cloacae to confer imipenem resistance.

Bacterial Outer Membrane Proteins↗
PubMed1991

Lytic effect of two fluoroquinolones, ofloxacin and pefloxacin, on Escherichia coli W7 and its consequences on peptidoglycan composition.

Examination of biochemical changes in Escherichia coli W7 after exposure to ofloxacin or pefloxacin revealed distinct concentration-dependent responses. At levels close to the MIC, extensive filamentation was followed by a lytic event, which involved an active protein synthesis. This lysis was correlated with changes in the peptidoglycan composition, particularly a decrease in the average glycan chain length, involving the action of the autolysines. At higher concentrations, no lysis occurred and the growth was totally inhibited as well as the protein synthesis. The peptidoglycan composition exhibited an increase in the average glycan chain length, suggesting an apparent reduced activity of the lytic transglycosylase. These results show that exposure to low concentrations of quinolones leads to the induction of lysis and peptidoglycan modifications which might contribute to the bactericidal effects of quinolones.

Bacterial Proteins↗
PubMed1991

Interplay of cell wall barrier and beta-lactamase activity determines high resistance to beta-lactam antibiotics in Mycobacterium chelonae.

We calculated the target access index, which reflects the probability that a drug will reach its target at an effective concentration, and the predictive MICs of cephaloridine, cephalothin, and cefazolin for Mycobacterium chelonae from the drug concentrations inhibiting the binding of benzylpenicillin to penicillin-binding proteins, the permeability coefficients, and the beta-lactamase properties. Despite a low level of beta-lactamase activity and because of a very effective permeability barrier, the target access indices were very low, e.g., 100 times lower than for penicillinase-producing Escherichia coli. The predicted MICs were within one to three twofold dilutions of the experimentally determined values (which ranged between 512 and greater than or equal to 2,048 micrograms/ml). These results demonstrate that the interplay of the cell wall barrier and beta-lactamase activity determines high resistance of M. chelonae to beta-lactam antibiotics.

Cefazolin↗
PubMed1991

Pick's disease: a case clinically resembling amyotrophic lateral sclerosis.

A 50-year-old woman with a progressive neurologic illness clinically resembling amyotrophic lateral sclerosis had Pick's disease verified at autopsy. This case represents another example of Pick's disease in which the early manifestations were not those of dementia. This patient also showed some unusual histopathologic features, including degeneration of the substantia nigra and occasional "compound Pick bodies."

Amyotrophic Lateral Sclerosis↗
PubMed1990

Comparison of vancomycin-inducible proteins from four strains of Enterococci.

Vancomycin-inducible proteins of 39.5 and 39 kDa from respectively, low-level and high-level resistant Enterococci were compared. Electrophoretic, immunoblot and peptide analysis revealed three types of protein, one in a low-level resistant strain of E. faecium, one in 2 high-level-resistant strains of E. faecium, and one in a high-level resistant strain of E. faecalis. The inducible proteins of E. faecium and E. faecalis, of 39.5 and 39 kDa respectively, which may function in a similar fashion (Al-Obeid et al. (1990) Antimicrob. Agents Chemother. 34, 252-256), are not related immunologically.

Bacterial Proteins↗
PubMed1990

Amoxicillin-clavulanic acid therapy of spontaneous bacterial peritonitis: a prospective study of twenty-seven cases in cirrhotic patients.

Spontaneous bacterial peritonitis in cirrhosis is a serious complication that demands urgent attention. We report here a prospective study of the treatment of 27 episodes of spontaneous bacterial peritonitis in 22 cirrhotic patients with amoxicillin and clavulanic acid. The infection of ascitic fluid was diagnosed by a positive culture plus an ascitic neutrophil count exceeding 75/microliters, or by an ascitic neutrophil count exceeding 500/microliters. The infection was treated with 1 gm amoxicillin and 0.2 gm clavulanic acid every 6 hr for 14 days. In 17 cases (63%), bacteria were isolated from the ascitic fluid. All the bacteria isolated were sensitive to amoxicillin and clavulanic acid, whereas in five cases they were resistant to amoxicillin alone (Escherichia coli in two cases, Klebsiella pneumoniae in two cases and Bacteroides fragilis in one case). Cure of the infection was achieved in 23 episodes (85%) after 14 days' treatment; 17 patients (63%) were able to leave the hospital. Fourteen of 20 patients (70%) treated for the first episode of infection died within 1 yr: eight from infection, two from gastrointestinal hemorrhage, one from infection and hemorrhage and three from tumors. One patient who had repeated infections underwent liver transplantation and has not had any infectious complications 1.5 yr after surgery. Amoxicillin and clavulanic acid may be an effective first-line therapy for ascitic fluid infection in cirrhosis. Nevertheless, the 1-yr prognosis continues to be grave and the severity of the underlying liver disease remains the most important determinant for survival.

Adult↗
PubMed1990

A phasmid shuttle vector for the cloning of complex operons in Salmonella.

Phasmid (phage plasmid hybrid) P4 vir1 can be propagated in Escherichia coli as a helper-dependent lytic phage, as a plasmid, or as a prophage. On the basis of an understanding of these modes of propagation, derivatives of P4 have been constructed for use as cloning vectors. In this report we demonstrate that phasmid P4 (i) will propagate as a helper-dependent lytic phage and as a plasmid in Salmonella spp. and (ii) can be used as a high efficiency phage shuttle vector for the reversible transfer of cloned genes between Salmonella spp. and E. coli. For both E. coli and Salmonella spp., P4 phage-mediated gene transfer proved to be only 10-fold lower than plaquing efficiency. For the case of Salmonella spp., this frequency is ca. 10(4)-fold more efficient than is typically found for the transformation of DNA molecules. The usefulness of this cloning vector system for analyses of pathogenic virulence factors is demonstrated by the cloning and expression of both the P pilus adhesin operon and the hemolysin operon of uropathogenic E. coli.

Cloning, Molecular↗
PubMed1990

Modification of penicillin-binding proteins of penicillin-resistant mutants of different species of enterococci.

Mutants resistant to penicillin G were selected in a stepwise manner from nine different species of enterococci. Mutants with the highest level of resistance showed cross-resistance to all beta-lactams tested. For eight of the nine species, resistance correlated with increased production of a low molecular weight penicillin-binding protein (PBP). Two of these species produced a new PBP of low molecular weight, while two other species produced an additional PBP of high molecular weight. With the exception of Enterococcus faecium, no difference was observed in terms of lysis or bactericidal effect when the sensitive strains and their resistant mutants were tested at ten times their respective MICs of penicillin G. With E. faecium an increased lytic and bactericidal effect was observed for the resistant mutant.

Bacterial Proteins↗