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Biomedical subjects

M Picard

Publications and source records attributed to M Picard.

At least 109 records · Page 6Linked to original sources
PubMed1992

Molecular basis of the efficacy of cefaclor against Haemophilus influenzae.

Cefaclor sustained its inhibitory activity against a beta-lactamase-producing strain of Haemophilus influenzae. Although a relatively high permeability coefficient was calculated for ampicillin compared with that calculated for cefaclor, the resulting periplasmic concentration of cefaclor was 5.7 times that of ampicillin. The efficacy of cefaclor may be due to its higher beta-lactamase resistance, which allows it to achieve a greater periplasmic concentration and adequate binding to crucial penicillin-binding proteins.

Anti-Bacterial Agents↗
PubMed1992

Molecular basis of the non-beta-lactamase-mediated resistance to beta-lactam antibiotics in strains of Haemophilus influenzae isolated in Canada.

A study recently conducted across Canada showed that 64 of 2,503 clinical isolates of Haemophilus influenzae were resistant to beta-lactams without production of a beta-lactamase (L. D. Tremblay, J. L'Ecuyer, P. Provencher, M. G. Bergeron, and Canadian Study Group, Can. Med. Assoc. J. 143:895-900, 1990). The beta-lactamase-negative strains formed three distinct groups, with ampicillin MICs of 0.5 to 1, 2 to 4, and greater than or equal to 8 micrograms/ml for groups I, II, and III, respectively. We have investigated the mechanisms of resistance for eight strains originating from different infections and geographic areas. These strains were representative of groups I to III. Five strains were nontypeable, two were type B, and one was non-B. Chromosomal DNA extracted from each strain was used to transform the laboratory strain Rd. Transformants were selected on beta-lactam-containing plates and showed the same level of resistance to ampicillin as the donor strains. Differences in outer membrane proteins, porins, and lipopolysaccharide profiles on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) did not change with resistance. Functional analyses of purified porins in artificial lipid bilayer experiments did not explain resistance. Peptidoglycan synthesis was measured by incorporation of [14C]alanine into trichloroacetic acid-insoluble cell wall material in the presence of chloramphenicol. The growth rate and the rate of peptidoglycan synthesis observed for the transformants of the isogenic set did not correlate with resistance. Whole-cell labeling with 125I-penicillin revealed modifications in penicillin-binding proteins (PBPs) among the transformants. In particular, PBPs 3A and 3B (65 and 63 kDa, respectively) showed a decrease in affinity for beta-lactams in all transformants (groups I, II, and III) and correlated with an increased MIC except in the transformant of group III, which showed higher levels of resistance. Partial purification and proteolytic digestion of 125I-penicillin-labeled PBP 3B led to two types of CnBr peptide profiles on SDS-PAGE, the profiles of the transformed strains from groups I and II being different from those of the control group and group III. Finally, electron microscopy revealed a distinct cell filamentation for the group III transformants. These data clearly indicate that changes in PBPs are a common mechanism that results in a significant level of non-beta-lactamase-mediated beta-lactam resistance in H. influenzae despite serotype, origin of isolation, or geographic distribution.

Adolescent↗
PubMed1992

[Multivariate study of auditory perception using multi-electrode cochlear implants].

The goal of this study was to determine the influence of auditory and cognitive factors in hearing or listening mechanisms with the Nucleus multielectrode cochlear implant. Accordingly, hearing sensitivity, psycho-acoustical masking functions and measures of temporal resolution were obtained from 14 adults with acquired deafness. In addition, six measures of open-set speech discrimination were introduced to represent a possible contribution of cognitive factors. Results indicated the contribution of both auditory and cognitive factors to speech understanding. Cognitive factors were most influential. Differences were also found in the relative importance of various cognitive factors, both before and after an intensive aural rehabilitation program. Initially, subjects relied more heavily on their ability to make efficient use of the linguistic redundancy of speech. At the end of the program, they paid more attention to speech acoustics, as a result of enhanced auditory spectral analysis and temporal resolution at about 2 kHz.

Adolescent↗
PubMed1992

Scintigraphic aspect of Rotor's disease with technetium-99m-mebrofenin.

A 28-yr-old male with Rotor's disease was studied with 99mTc-mebrofenin. The scintigraphic pattern was that of a slow liver uptake with unimpaired excretion and persistent visualization of the cardiac blood pool, kidneys and urinary tract up to 6 hr. The gallbladder was visualized at 55 min postinjection.

Adult↗
PubMed1991

A site-specific deletion in mitochondrial DNA of Podospora is under the control of nuclear genes.

In the filamentous fungus Podospora anserina, the association of two nuclear genes inevitably leads to a "premature death" phenotype consisting of an early end of vegetative growth a few days after ascospore germination. Mycelia showing this phenotype contain a mitochondrial chromosome that always bears the same deletion. One of the break points is exactly at the 5' splice site of a particular mitochondrial intron, suggesting that the deletion event could result from molecular mechanisms also involved in intron mobility. One of the nuclear genes involved in triggering this site-specific event belongs to the mating-type minus haplotype; the other is a mutant allele of a gene encoding a cytosolic ribosomal protein.

Ascomycota↗
PubMed1991

Metabolism of 99mTc-L,L-ethyl cysteinate dimer in healthy volunteers.

99mTc-L,L-Ethyl cysteinate dimer (ECD) is a brain-perfusion imaging agent, which exhibits selective retention in brain and rapid renal excretion. The pharmacokinetics and metabolism of ECD were studied in vivo in healthy humans and its metabolism in vitro was evaluated in tissue from human brain. In vitro studies showed 99mTc-L,L-ECD to be metabolized to a polar 99mTc-complex. It has been shown previously that most of the activity of 99mTc retained in the brain of the monkey in vivo is in the form of a polar 99mTc complex (Walovitch, Hill, Garrity, Cheesman, Burgess, O'Leary, Watson, Ganey, Morgan and Williams, 1989). Whole body images of the distribution of 99mTc-L,L-ECD (10 mCi i.v.) in four adult males showed good uptake in brain, with slow elimination (6.8 +/- 0.3% injected dose [mean +/- SE] at 5 min), with less than 25% decrease in activity during 4 hr of imaging. Background areas in the head and lungs washed out rapidly, providing ideal imaging conditions. Elimination of 99mTc from venous blood was biphasic, with a plateau of activity between 2-15 min (7-8% injected dose) before a terminal phase, with a t1/2 of a few hours. Organic extraction of whole venous blood showed greater than 50% of the 99mTc-L,L-ECD to be in the form of polar metabolite(s) at 5 min. They were identified in the urine as the 99mTc ethylenediylbis-L-cysteine, monoethyl ester complex (ECM) and the 99mTc-ethylenediylbis-L-cysteine complex (EC). These metabolites were excreted rapidly (75% injected dose in urine within 6 hr). The results of this study support the hypothesis that the selective retention in brain, rapid blood elimination and renal excretion of 99mTc-L,L-ECD is due to its metabolic transformation to polar end products.

Adult↗
PubMed1991

Multivariate clinical models and quantitative dipyridamole-thallium imaging to predict cardiac morbidity and death after vascular reconstruction.

Patients with peripheral vascular disease have a high prevalence of coronary artery disease and are at increased risk for cardiac morbidity and death after vascular reconstruction. The present study was undertaken to assess the value of 18 clinical parameters, of 7 clinical scoring systems, and of quantitative dipyridamole-thallium imaging for predicting the occurrence of postoperative myocardial infarction or cardiac death. Vascular surgery was performed in 125 patients. Thirteen postoperative cardiac events occurred, including 10 cardiac deaths and 3 nonfatal infarctions. Clinical parameters were not useful in predicting postoperative outcome. All 63 patients with normal scan results or fixed perfusion defects underwent surgery uneventfully, whereas 21% (13/62) of patients with reversible defects had a postoperative cardiac complication. By use of quantitative scintigraphic indexes we found that patients with reversible defects could be stratified into intermediate and high-risk subgroups with postoperative event rates of 5% (2/47) and 85% (11/13), respectively, despite intensive postoperative monitoring and antianginal medication. Thus in patients unable to complete a standard exercise stress test, postoperative outcome cannot be predicted clinically, whereas dipyridamole-thallium imaging successfully identified all patients who had a postoperative cardiac event. By use of quantification we found that patients with reversible defects can be stratified into an intermediate risk subgroup that can undergo surgery with minimal complication rate and a high-risk subgroup that requires coronary angiography.

Canada↗
PubMed1991

Cloning the mating types of the heterothallic fungus Podospora anserina: developmental features of haploid transformants carrying both mating types.

DNAs that encode the mating-type functions (mat+ and mat-) of the filamentous fungus Podospora anserina were cloned with the use of the mating-type A probe from Neurospora crassa. Cloning the full mat information was ascertained through gene replacement experiments. Molecular and functional analyses of haploid transformants carrying both mating types lead to several striking conclusions. Mat+ mat- strains are dual maters. However, the resident mat information is dominant to the mat information added by transformation with respect to fruiting body development and ascus production. Moreover, when dual mating mat+ mat- strains are crossed to mat+ or mat- testers, there is strong selection, after fertilization, that leads to the loss from the mat+ mat- nucleus of the mat information that matches that of the tester. Finally, the mat locus contains at least two domains, one sufficient for fertilization, the other necessary for sporulation.

Ascomycota↗
PubMed1991

Macrophage- and oxidant-mediated inhibition of the ability of live Blastomyces dermatitidis conidia to transform to the pathogenic yeast phase: implications for the pathogenesis of dimorphic fungal infections.

Conidia, produced by the mycelial phase of dimorphic fungi, are thought to represent the infectious form of the organism but must complete a transition to the tissue-invasive, yeast-like phase for infection to ensue. Preventing such transition should effectively eliminate pathogenicity. Using Blastomyces dermatitidis as a target, murine bronchoalveolar macrophages preferentially blocked phase transition after 4 h of incubation with conidia, relatively sparing the ability of conidia to produce hyphae. H2O2, in relatively high concentrations, demonstrated the same activity. The effects of H2O2 seem irreversible, since H2O2-treated conidia that germinated at 48 h at 25 degrees C were still unable to produce yeasts over the next 5 days when incubated at 37 degrees C. Catalase could not reverse the macrophage-induced inhibition of phase transition, suggesting that nonoxidative defense mechanisms may be operative in vivo. Since conidia do not form mycelia at temperatures found in mammalian hosts, these effects may represent a novel host defense mechanism against dimorphic fungal pathogens.

Animals↗
PubMed1991

Treatment of murine invasive candidiasis with amphotericin B and cilofungin: evidence for enhanced activity with combination therapy.

The in vivo interactions of cilofungin, an echinocandin antifungal agent, and amphotericin B, a polyene derivative, in a murine model of disseminated candidiasis have been investigated. While single therapy with either drug alone prolonged survival of infected mice, kidney colony counts were not appreciably reduced. In contrast, combination therapy, especially at higher doses of both drugs, resulted in significant prolongation of survival and suppression of growth of yeast cells in the kidneys. Combination therapy of experimental candidiasis with cilofungin and amphotericin B did not result in antagonism; rather, additive or synergistic effects were seen. Future preclinical work with other echinocandin and polyene derivatives should include studies evaluating the in vivo interactions of both classes of compounds.

Amphotericin B↗
PubMed1991

[Clinical study of speech understanding in noise].

The goal of this study was to determine the extent to which the difficulty frequently experienced by hearing-impaired listeners in understanding noisy speech can be clinically described in terms of the auditory site of lesion. To this end, shifts of speech reception threshold in noise, using standardized franco-québécois bisyllabic word lists, were obtained from noise-exposed workers and compared to Plomp's model to ascertain content validity. Shifts resulted from monaural listening to a broad-band speech spectrum noise held constant at 0 dB signal-to-noise ratio. In this manner, increasing the presentation levels of both speech and noise was expected to progressively minimize the contribution of Plomp's class A attenuation component to speech hearing loss and eventually show an unequivocal manifestation of its distortion component (class D speech hearing loss). Listeners were 457 noise-exposed workers giving a total of 914 observations. Rejection of those ears with suspected middle-ear pathology led to a reduction to a total of 709 observations representing various degrees of permanent hearing impairment. An additional 98 observations showed normal hearing sensitivity in spite of noise exposure averaging 9.6 years. Results indicated the presence of five categories of speech threshold shifts varying independently of hearing sensitivity. 59.8% of those observations with permanent hearing impairment (424/709) simultaneously showed a problem understanding speech in noise. On 78 occasions, listening in noise was so disturbed that the 50% performance level corresponding to the speech threshold could no longer be established within reasonable limits, that is up to 65 dB above the speech threshold in a quiet environment. Conversely, 26.5% of the observations with essentially normal hearing sensitivity (26/98) showed reduced speech reception in noise. Fitting Plomp's model confirmed our expectations for two of the five categories of scores. A principal component analysis identified similar behaviour of speech threshold shifts in noise compared with Plomp's class D speech hearing loss. Hence, these speech threshold shifts in noise were interpreted as predominantly reflecting peripheral auditory disorders, that is defective frequency selectivity and temporal resolution. The remaining categories were found to be under the predominant influence of two other mechanisms: (1) band width reduction resulting from impaired hearing; (2) disorders associated with certain non-auditory cognitive factors, namely selective attention and the ability to make use of the redundancy of the message.

Adult↗
PubMed1990

Transient left ventricular cavitary dilation during dipyridamole-thallium imaging as an indicator of severe coronary artery disease.

Transient left ventricular (LV) cavitary dilation during dipyridamole-thallium imaging was reported in 45 of 510 (9%) consecutive patients referred for dipyridamole-thallium imaging. Clinical and hemodynamic effects observed during dipyridamole infusion were not predictive of transient cavitary dilation on the thallium images. Coronary angiography was performed in 32 of the 45 patients: 75% had either left main, 3-vessel or "high-risk" 2-vessel coronary artery disease. Although 25 of 45 patients (56%) with transient cavitary dilation were either asymptomatic or had only grade 1/4 effort angina, 16 of 25 patients (64%) not referred for coronary revascularization sustained a cardiac event during a mean follow-up of 12 months. Most events were cardiac deaths (75%) and 87% of events occurred within 4 months of the test. Noncardiac surgery was performed in 187 of the 510 patients. The postoperative cardiac event rate was 2% in the 101 patients with normal scans or fixed defects, 19% in 75 patients with reversible perfusion defects and 58% in 12 patients with reversible cavitary dilation (p less than 0.0001). Thus, transient LV dilation during dipyridamole-thallium imaging is a marker of severe underlying coronary artery disease, denotes a poor prognosis and predicts a high risk of postoperative cardiac complications in patients who undergo noncardiac surgery.

Coronary Angiography↗
PubMed1990

Attachment of Blastomyces dermatitidis conidia to murine bronchoalveolar macrophages: characterization of binding and elicitation of respiratory burst.

We studied the mechanisms of adherence of Blastomyces dermatitidis conidia to murine bronchoalveolar macrophages and the ability of the conidia to elicit an increase in macrophage O2- production, using an avirulent fungal strain. The number of cell associated conidia was counted by visual inspection of 2 hour macrophage monolayers incubated with conidia and O2- was measured by reduction of ferricytochrome c. Adherence of conidia to bronchoalveolar macrophages was time dependent and reached a plateau after 30 min (36 +/- 5%, 51 +/- 22%, and 36 +/- 17% macrophages with adherent conidia after 15, 30, and 60 min, respectively). Both Ca+2 and Mg+2 were required. The carbohydrates mannose, mannan, fucose, alphamethylmannoside, beta-glucan, galactose, N-acetylglucosamine and chitotriose (100-1000 micrograms/ml) did not inhibit adherence of conidia to macrophages. Trypsin treatment of macrophages or conidia did not affect binding. Conidia did not stimulate bronchoalveolar macrophage production of O2- above baseline concentrations (2.0 +/- 0.9 vs 0.8 +/- 0.5 nmol O2-, p greater than 0.05). We conclude that murine bronchoalveolar macrophage--B. dermatitidis conidia interactions occur primarily by a non-lectin-like attachment and do not result in the production of macrophage derived O2-.

Animals↗
PubMed1990

Postoperative myocardial infarction and cardiac death. Predictive value of dipyridamole-thallium imaging and five clinical scoring systems based on multifactorial analysis.

Sixty-six patients unable to complete a standard preoperative exercise test because of physical limitations were studied to determine the predictive value of individual clinical parameters, of clinical scoring systems based on multifactorial analysis, and of dipyridamole-thallium imaging before major general and vascular surgery. Study endpoints were limited to postoperative myocardial infarction or cardiac death before hospital discharge. There were nine postoperative cardiac events (seven deaths and two nonfatal infarctions). There was no statistical correlation between cardiac events and preoperative clinical descriptors, including individual clinical parameters, the Dripps-American Surgical Association score, the Goldman Cardiac Risk Index score, the Detsky Modified Cardiac Risk Index score, Eagle's clinical markers of low surgical risk, and the probability of postoperative events as determined by Cooperman's equation. There were no cardiac events in 30 patients with normal dipyridamole-thallium scans or in nine patients with fixed myocardial perfusion defects. Of 21 patients with reversible perfusion defects who underwent surgery, nine had a postoperative cardiac event (sensitivity, 100%; specificity, 43%). In the six other patients with reversible defects, preoperative angiography showed severe coronary disease or cardiomyopathy. Thus in patients unable to complete a standard exercise stress test, postoperative outcome cannot be predicted clinically before major general and vascular surgery, whereas dipyridamole-thallium imaging successfully identified all patients who sustained a postoperative cardiac event.

Aged↗
PubMed1990

Demonstration of abnormal peritoneal communication in patients with ascites.

Patients with ascites are known to have complications such as pleural effusions and hernias. Special diagnostic procedures are occasionally necessary to determine the nature of the abnormality and to determine the corrective medico-surgical approach. The two cases described illustrate the usefulness of intraperitoneal as well as intrapleural injection of a radionuclide in diagnosing the leakage of ascitic fluid.

Adult↗
PubMed1990

Technetium-99m HMPAO imaging in Sturge-Weber syndrome.

The Tc-99m HMPAO brain imaging confirmed marked hypoperfusion secondary to anomalous cerebral venous drainage of the Sturge-Weber syndrome. Until now, this had been a hypothesis suggested by results obtained from conventional brain scans and cerebral arteriography.

Angiomatosis↗
PubMed1990

Treatment of murine pulmonary blastomycosis with SCH 39304, a new triazole antifungal agent.

SCH 39304, a broad-spectrum azole derivative, was evaluated in an experimental mouse model of blastomycosis pneumonia. Five days after being inoculated with Blastomyces dermatitidis, infected mice were treated with either oral SCH 39304, fluconazole, or intraperitoneal amphotericin B. A dose response protective effect was observed with SCH 39304 at 5 to 100 mg/kg of body weight per day, with 5 mg of SCH 39304 per kg per day providing activity similar to that of 100 mg of fluconazole per kg per day. Colony counts of yeasts in the lungs of mice sacrificed while on therapy with SCH 39304 were consistently below those of controls, and several lungs were sterile. We conclude that SCH 39304 is effective in murine blastomycosis treatment and deserves to be evaluated in the treatment of human blastomycosis.

Amphotericin B↗