Search PubMed⌕ Search

Biomedical subjects

L Gutmann

Publications and source records attributed to L Gutmann.

At least 19 recordsLinked to original sources
PubMed1992

A silent carbapenemase gene in strains of Bacteroides fragilis can be expressed after a one-step mutation.

High-level carbapenem-resistant (CpmR) mutants, with MICs for imipenem and carbapenem of greater than 128 micrograms/ml, were selected in vitro from four carbapenem-susceptible (CpmS) clinical isolates of Bacteroides fragilis. The CpmS strains produced very low levels of beta-lactamase activity, which was increased approx. 50- to 100-fold in the CpmR mutants. Isoelectric focussing and enzyme kinetic analysis (Km and Vrel) of the 'carbapenemases' from the CpmR mutants and similarly resistant clinical isolates suggested a close relatedness of the enzymes. A probe covering most of the cfiA gene encoding such an enzyme (Thompson, J.S. and Malamy, M.H. (1990) J. Bacteriol. 172, 2584-2593) hybridized with DNA from the CpmR mutants, their CpmS parental strains as well as clinical CpmR isolates, but not from randomly chosen carbapenem-susceptible strains. The possibility is considered that mutations leading to expression of the silent carbapenemase gene, and thereby to clinically relevant carbapenem resistance, may also occur in the clinical setting.

Bacterial Outer Membrane Proteins↗
PubMed1992

Replacement of the essential penicillin-binding protein 5 by high-molecular mass PBPs may explain vancomycin-beta-lactam synergy in low-level vancomycin-resistant Enterococcus faecium D366.

The mechanism of synergy between vancomycin and penicillin, as well as other beta-lactam antibiotics, was examined in a penicillin-resistant E. faecium (D366) expressing an inducible low-level resistance to vancomycin. It was demonstrated that penicillin per se was not able to reduce the inducible expression of the 39.5-kDa protein (VANB) or the carboxypeptidase activity which are involved in the mechanism of vancomycin resistance of this strain. Assays of competition between 3H-benzylpenicillin and diverse beta-lactam antibiotics suggested as the most likely explanation of the synergy that, once vancomycin resistance has been induced, the high-molecular mass penicillin-binding proteins (PBPs), and possibly PBP1 in particular, which have a high affinity for beta-lactam antibiotics, take over the role of the low-affinity PBP5 which is, in the non-induced strain, responsible for beta-lactam resistance.

Bacterial Proteins↗
PubMed1992

Impaired neuromuscular transmission during partial inhibition of acetylcholinesterase: the role of stimulus-induced antidromic backfiring in the generation of the decrement-increment phenomenon.

Neuromuscular transmission was studied in the rat phrenic nerve-hemidiaphragm preparation with acetylcholinesterase (AChE) partially inactivated. Enzyme inhibition resulted in (1) increased single-twitch tension of the diaphragm; (2) compound muscle action potential (CMAP) containing repetitive discharges; (3) stimulus-induced antidromic backfiring (SIAB) seen in the phrenic nerve; and (4) repetitive nerve stimulation (RNS) eliciting a decrement-increment (D-I) phenomenon (i.e., amplitude reduction maximal with the second CMAP). Using a high-calcium and low-magnesium solution, SIAB and the decrement of the second CMAP during RNS were intensified, whereas closely spaced trains and (+)-tubocurarine (TC) abolished SIAB and simultaneously prevented the decrement of the second CMAP. Importantly, low concentrations of (+)-TC prevented SIAB in the phrenic nerve, while the repetitive discharges of the CMAP and the increase in twitch tension remained unaffected. This observation suggests that preterminal nicotinic receptors stimulated by released acetylcholine induce SIAB, whereas postsynaptic events are less important in the generation of SIAB. SIAB, a presynaptic event, appears to be responsible for the transient impairment of the neuromuscular transmission, i.e., the D-I phenomenon.

Acetylcholinesterase↗
PubMed1992

Diffusion of beta-lactam antibiotics into proteoliposomes reconstituted with outer membranes of isogenic imipenem-susceptible and -resistant strains of Enterobacter cloacae.

The influence of outer membrane (OM) permeability on carbapenem susceptibility was studied in strains of Enterobacter cloacae, a species in which carbapenem resistance depends upon the conjunction of overproduction of the chromosomal cephalosporinase and reduction of OM permeability. Relative trans-OM diffusion rates were measured using the liposome swelling assay. Proteoliposomes were reconstituted with OM from the members of an isogenic set of E. cloacae strains, selected in vivo or in vitro, which produced either porins F and D (wild-type), or F or D only, or neither. For all but one mutant, and compared with the wild-type strain, the respective increases in MICs and decreases in trans-OM diffusion of carbapenems were: nil and 13 to 18%; 4- to 32-fold and 33 to 50%; > or = 64-fold and > or = 90%. Our results suggest (i) that carbapenems (and other beta-lactam antibiotics) diffuse through porins F and D, but more rapidly through porin F, and (ii) that OM permeability is the critical factor in determining the level of MICs of carbapenems for cephalosporinase-overproducing strains of E. cloacae. The OM of one particular low-level carbapenem-resistant and porin F- and D-deficient mutant was at least five times more permeable to carbapenems than the similarly porin-deficient high-level resistant mutants. We infer from this observation the possible existence of an alternative carbapenem penetration pathway which could be associated with two as yet uncharacterized overproduced OM proteins of about 22 and 47 kDa.

Anti-Bacterial Agents↗
PubMed1992

Inducible carboxypeptidase activity in vancomycin-resistant enterococci.

Vancomycin was found to coinduce DD-carboxypeptidase activity, together with resistance, in eight low- or high-level glycopeptide-resistant strains of enterococci. The constitutively resistant mutant (MT10) of a low-level-resistant strain of Enterococcus faecium (D366) spontaneously expressed a level of carboxypeptidase similar to that of the induced strain D366. Pentapeptide, UDP-MurNac-pentapeptide, as well as D-alanyl-D-alanine were in vitro substrates for the carboxypeptidase which was not inhibited by penicillin. The level of vancomycin resistance correlated roughly with the level of carboxypeptidase activity. We infer from these results that the carboxypeptidase is one component of the glycopeptide resistance mechanism.

Anti-Bacterial Agents↗
PubMed1992

Daptomycin or teicoplanin in combination with gentamicin for treatment of experimental endocarditis due to a highly glycopeptide-resistant isolate of Enterococcus faecium.

Using an experimental endocarditis model, we studied the activity of daptomycin used alone or in combination with gentamicin against an Enterococcus faecium strain that was highly resistant to glycopeptides and susceptible to gentamicin. In vitro, the MIC of daptomycin was 1 micrograms/ml. In vivo, daptomycin appeared to be effective only when it was used in a high-dose regimen, i.e., 12 mg/kg of body weight every 8 h (-2.5 log10 CFU/g versus controls; P < 0.05), particularly when it was combined with gentamicin (-5.0 log10 CFU/g versus controls; P < 0.01). Since the distribution of daptomycin into cardiac vegetations, as evaluated by autoradiography, appeared to be homogeneous, the poor in vivo activity of daptomycin was considered to be related to its high degree of protein binding, as suggested by killing curves studies. Since the MIC of teicoplanin for the vancomycin-resistant E. faecium strain used in the study was only 64 micrograms/ml and since an in vitro synergy between teicoplanin at high dose and gentamicin was observed, a high-dose regimen of teicoplanin, i.e., 40 mg/kg every 12 h, was also assessed in vivo. This treatment provided marginal activity only when it was combined with gentamicin (-2.3 log10 CFU/g versus controls; P < 0.05). These results suggest that the levels of daptomycin or teicoplanin in serum required to cure experimental endocarditis caused by a highly glycopeptide-resistant strain of E. faecium would not be achievable in humans.

Animals↗
PubMed1992

Analysis of peptidoglycan precursors in vancomycin-resistant enterococci.

Analysis by high-pressure liquid chromatography of the cytoplasmic peptidoglycan precursors of a high- and a low-level vancomycin-resistant Enterococcus spp. was performed before and after induction of resistance. This analysis showed a decrease of the D-Ala-D-Ala and UDP-MurNac-pentapeptide pools, an increase of the UDP-MurNac-tripeptide pool, and the appearance of new UDP-MurNac-containing material. These results lead us to suggest that the vancomycin-induced carboxypeptidase activity cleaves the D-Ala-D-Ala (L. Gutmann, D. Billot-Klein, S. Al-Obeid, I. Klare, S. Francoul, E. Collatz, and J. van Heijenoort, Antimicrob. Agents Chemother. 36:77-80, 1992), which in turn would prevent formation of the normal UDP-MurNac-pentapeptide and thereby of the vancomycin target. The novel UDP-MurNac-containing material is thought to correspond to peptidoglycan precursors which might be synthesized by an alternate pathway (T. D. H. Bugg, G. D. Wright, S. Dutka-Malen, M. Arthur, P. Courvalin, and C. T. Walsh, Biochemistry 30:10408-10415, 1991) and which would be unable to bind vancomycin in glycopeptide-resistant enterococci.

Cells, Cultured↗
PubMed1992

Persistent unilateral tibialis anterior muscle hypertrophy with complex repetitive discharges and myalgia: report of two unique cases and response to botulinum toxin.

Unilateral enlargement of the tibialis anterior muscle associated with complex repetitive discharges occurred over several months in two patients and was preceded by pain and numbness in the lower leg. Neuroradiologic investigations excluded a compressive radiculopathy, but pharmacologic and neurophysiologic studies suggested a neurogenic basis for the muscle hypertrophy. Botulinum toxin A injection into the hypertrophied muscles led to a decreased muscle volume and cessation of muscle pain.

Adult↗
PubMed1992

Trends in the association of Lambert-Eaton myasthenic syndrome with carcinoma.

The Lambert-Eaton myasthenic syndrome (LEMS) is often associated with carcinoma. The exact number of patients with tumor has been reported to be as high as 70%. Recent clinical experience suggests that the actual number of patients with tumor may be substantially lower. We combined data from the clinical experience of the neuromuscular services at West Virginia University and the University of Virginia to determine the rate of occurrence of cancer in this disorder. We identified 28 patients with LEMS, and 14 had cancer. There is a distinct trend for a lower tumor frequency over the past decade, which suggests that the clinical manifestations of the disease may be changing.

Adult↗
PubMed1992

[Autoimmune diseases after unusual exposure to silica or silicones. 3 cases].

A woman, who had intensively used an abrasive cleansing powder rich in silica for 12 years, developed a connective tissue disease consisting of destructive inflammatory oligoarthritis, Gougerot-Sjögren's syndrome, Raynaud's syndrome, anti-nuclear antibodies and hypocomplementemia. Another woman, who had sprayed silicone-glaze on cables for 15 years, suffered from edematous scleroderma. A man, who had sprayed the same silicone-glaze on cables over a 20 year period, had a subluxing arthropathy. These autoimmune syndromes were compared with diseases classically induced by exposure to silica and silicone. To the best of our knowledge, these means of exposure have not been reported previously and merit being known in the aim of prevention.

Adult↗
PubMed1991

Pupil-sparing oculomotor nerve palsy due to midbrain infarction.

Vasculopathic oculomotor nerve palsies with pupillary sparing are thought to be due to ischemic damage to the nerve in the subarachnoid space or the cavernous sinus. We present two cases of patients with isolated pupil-sparing oculomotor nerve palsies due to midbrain infarcts. Focal ischemic midbrain lesions should be considered in cases of pupil-sparing oculomotor nerve palsies.

Adult↗
PubMed1991

Midbrain vs. pontine medial longitudinal fasciculus lesions: the utilization of masseter and blink reflexes.

Masseter (MR) and blink reflexes (BL) were investigated in 51 patients with internuclear ophthalmoplegia (INO) due to multiple sclerosis (28) and lacunar infarction (23). The MR was abnormal in 20 of 23 cases with bilateral INO and in 21 of 28 with unilateral INO. The R1 component of the BL (BL-R1) was abnormal in 7 of 23 patients with bilateral INO and 10 of 28 with unilateral INO. Combined MR and BL-R1 changes occurred in 8 of 28 cases with unilateral INO and 7 of 23 with bilateral INO. The findings provide evidence for a rostral/caudal localization of lesions within the medial longitudinal fasciculus causing INO on the basis of MR and BL-R1 abnormalities. An abnormality limited to MR suggests a midbrain location in 58.8% of patients while abnormal BL-R1 with or without an associated MR change suggests a rostral pontine location in 35.3%.

Blinking↗
PubMed1991

Paradoxical lid elevation with sustained upgaze: a sign of Lambert-Eaton syndrome.

Myasthenia gravis and Lambert-Eaton myasthenic syndrome are causes of acquired extraocular muscle weakness and ptosis. Exacerbation of ptosis after sustained upgaze is a clinically useful sign in the diagnosis of myasthenia gravis. A 54-year-old woman with established Lambert-Eaton myasthenic syndrome exhibited transient improvement of her ptosis after sustained upgaze. We suggest that paradoxical lid elevation after sustained upgaze may be a clinically useful sign in distinguishing Lambert-Eaton myasthenic syndrome from myasthenia gravis.

Blepharoptosis↗
PubMed1991

AAEM minimonograph #37: facial and limb myokymia.

Myokymia is a clinical phenomenon associated with characteristic electromyographic activity referred to as myokymic discharges. These are spontaneously generated bursts of individual motor unit potentials with each burst recurring rhythmically or semirhythmically, usually several times per second. It involves facial muscles more commonly than those of the extremities, and is most often seen in association with Guillain-Barré syndrome, multiple sclerosis, radiation plexopathy, pontine tumors, and timber rattlesnake envenomation. An alteration in the biochemical microenvironment of axon membranes at one of the various sites along the motor axon is the likely basis for the altered membrane excitability that underlies the myokymic discharges in most cases. The similarity of these discharges to those seen with hypocalcemic tetany, and the ability to manipulate myokymic discharges by altering serum-ionized Ca++, suggests that decrease in the ionized Ca++ in the microenvironment of the axon may play an important role.

Electromyography↗