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Biomedical subjects

Michel Cormier

Publications and source records attributed to Michel Cormier.

9 recordsLinked to original sources

Effect of delivery parameters on immunization to ovalbumin following intracutaneous administration by a coated microneedle array patch system.

Immunization to the model antigen ovalbumin was investigated using a novel intracutaneous delivery system consisting of antigen-coated microneedle arrays. The influence of the following parameters on the resulting immune responses was investigated: depth of vaccine delivery, dose of vaccine delivered, density of microneedles on the array, and area of application. The immune response was found to be dose dependent, and mostly independent of depth of delivery, density of microneedles, or area of application. Our studies show that the shortest, most tolerable microneedle arrays can be used for achieving consistent and high antibody titers. Overall, the microneedle array proves to be a very versatile delivery technology, allowing easy and reproducible antigen delivery to skin for efficient vaccination without the use of a needle and syringe.

Administration, Cutaneous↗

Peracetic acid stress-induced genetic rearrangements in Escherichia coli H10407 detected by RAPD and RFLP analyses.

The discriminatory powers of random amplified polymorphic DNA (RAPD) analysis and restriction fragment length polymorphism (RFLP) were assessed for the detection and comparison of DNA modifications caused by an oxidative stress. DNA extracted from peracetic acid (PAA)-treated Escherichia coli H10407 was randomly amplified with the 10-mer primer OPZ14, which generated one stress-induced fragment. RFLP and RAPD profiles were hybridized by Southern blotting with the digoxigenin-labelled RAPD product. Untreated and PAA-treated cells had difference band profiles. The results indicate that RAPD analysis could be used as a discriminatory tool for investigating genetic rearrangements in E. coli caused by oxidative stress and that RFLP analysis could be used to confirm the rearrangements.

DNA Fingerprinting↗

Prevalence of oropharyngeal beta-lactamase-producing Capnocytophaga spp. in pediatric oncology patients over a ten-year period.

BACKGROUND: The aim of this study was to evaluate the prevalence of beta-lactamase-producing Capnocytophaga isolates in young children hospitalized in the Pediatric Oncology Department of Hôpital Sud (Rennes, France) over a ten-year period (1993-2002). METHODS: In neutropenic children, a periodic survey of the oral cavity allows a predictive evaluation of the risk of systemic infections by Capnocytophaga spp. In 449 children with cancer, 3,053 samples were collected by oral swabbing and plated on TBBP agar. The susceptibility of Capnocytophaga isolates to five beta-lactams was determined. RESULTS: A total of 440 strains of Capnocytophaga spp. were isolated, 309 (70%) of which were beta-lactamase producers. The beta-lactamase-producing strains were all resistant to cefazolin, 86% to amoxicillin, and 63% to ceftazidime. The proportion of strains resistant to third-generation cephalosporins remained high throughout the ten-year study, while susceptibility to imipenem and amoxicillin combined with clavulanic acid was always conserved. CONCLUSION: These results highlight the risk of antibiotic failure in Capnocytophaga infections and the importance of monitoring immunosuppressed patients and testing for antibiotic susceptibility and beta-lactamase production.

Capnocytophaga↗

Tenosynovitis of the wrist due to resistant Mycobacterium tuberculosis in a heart transplant patient.

Tubercular tenosynovitis is now rare, which can delay diagnosis of this disease. We report a case of tenosynovitis of the wrist in a heart transplant patient caused by an isoniazid- and streptomycin-resistant Mycobacterium tuberculosis strain. Despite immunosuppression therapy, which can lead to a smoldering evolution, molecular biology analysis of biopsies allowed a rapid diagnosis.

Anti-Bacterial Agents↗

Transdermal delivery of desmopressin using a coated microneedle array patch system.

Desmopressin is a synthetic peptide hormone chiefly used for treatment of enuresis in young children. It is available in injectable, intranasal, and oral formulations. While administration by injection is poorly suited for routine use in young children, intranasal and oral administration result in low and variable bioavailability. This study therefore explored the feasibility of administering desmopressin transdermally using Macroflux technology, which uses a microneedle array to overcome the skin barrier. The tips of microneedles in 2-cm2 arrays were covered with a solid coating of various amounts of desmopressin and applied to the skin of hairless guinea pigs for 5 or 15 min. Pharmacologically relevant amounts of desmopressin were delivered after 5 min. Bioavailability was as high as 85% and showed acceptable variability (30%). Immunoreactive serum desmopressin reached peak levels after a Tmax of 60 min. Elimination kinetics for serum desmopressin was similar after transdermal and intravenous (IV) delivery, suggesting the absence of a skin depot. Only 10% of the desmopressin dose loaded onto the microneedle array was found on the skin surface after application. Additionally, the patches were well tolerated. These results suggest that transdermal delivery of desmopressin by Macroflux is a safe and efficient alternative to currently available routes of administration.

Administration, Cutaneous↗

Genetic analysis of an ambler class A extended-spectrum beta-lactamase from Capnocytophaga ochracea.

A beta-lactamase gene (cfxA3, 966 bp) was isolated from a beta-lactam-resistant Capnocytophaga ochracea clinical isolate and amplified using primers from the cfxA gene of Bacteroides vulgatus. The MICs of third-generation cephalosporins were much higher than those of the transconjugant Escherichia coli strain. The deduced protein sequence, by comparison with CfxA2 of Prevotella intermedia, had a Y239D substitution and possessed the characteristics of a class A, group 2e beta-lactamase.

Amino Acid Substitution↗

Microbiology of mandibular third molar pericoronitis: incidence of beta-lactamase-producing bacteria.

OBJECTIVES: The purpose of this study was to evaluate the predominant flora associated with pericoronitis in third molars and to investigate the presence of beta-lactamase-producing strains. STUDY DESIGN: The third molars in 26 adults were evaluated by cultures with nonselective media and with selective media containing amoxicillin, pristinamycin, spiramycin, metronidazole, and spiramycin plus metronidazole. RESULTS: In the majority of cases (19/26), the flora found in an anaerobic atmosphere predominated. Obligate anaerobes were present in 21 of the 26 samples. The bacteria most commonly detected were alpha-hemolytic streptococci (26/26) and the genera Prevotella (15/26), Veillonella (15/26), Bacteroides (9/26), and Capnocytophaga (9/26). Amoxicillin and pristinamycin were the most active in reducing the anaerobic cultivable counts. beta-Lactamase-producing strains were detected in 9 samples and were mostly bacteria of the genera Prevotella, Staphylococcus, and Bacteroides. CONCLUSIONS: These results highlight (1) the diversity of the microflora associated with pericoronitis and the importance of the anaerobic flora and (2) the existence of selection pressure related to the use of beta-lactams that may culminate in failure of prescribed penicillins.

Adolescent↗

Evaluation of the mandibular third molar pericoronitis flora and its susceptibility to different antibiotics prescribed in france.

This work assessed the polymicrobial flora of mandibular third molar pericoronitis. Obligate anaerobes were found in almost all cases (32 of 35). Amoxicillin and pristinamycin were the most effective against the flora, particularly aerobic organisms. Metronidazole alone or combined with spiramycin was the most effective drug against obligate anaerobes.

Anti-Bacterial Agents↗

Macroflux microprojection array patch technology: a new and efficient approach for intracutaneous immunization.

PURPOSE: We evaluated the Macroflux microprojection array patch technology as a novel system for intracutaneous delivery of protein antigens. METHODS: Macroflux microprojection array systems (330-microm micro-projection length, 190 microprojections/cm2, 1- and 2-cm2 area) were coated with a model protein antigen, ovalbumin (OVA), to produce a dry-film coating. After system application, microprojection penetration depth, OVA delivery, and comparative immune responses were evaluated in a hairless guinea pig model. RESULTS: Macroflux microprojections penetrated into hairless guinea pig skin at an average depth of 100 microm with no projections deeper than 300 microm. Doses of I to 80 microg of OVA were delivered via 1- or 2-cm2 systems by varying the coating solution concentration and wearing time. Delivery rates were as high as 20 microg in 5 s. In a prime and boost dose immune response study, OVA-coated Macroflux was most comparable to equivalent doses injected intradermally. Higher antibody titers were observed when OVA was administered with the microprojection array or intradermally at low doses (1 and 5 microg). Macroflux administration at 1- and 5-microg doses gave immune responses up to 50-fold greater than that observed after the same subcutaneous or intramuscular dose. Dry coating an adjuvant, glucosaminyl muramyl dipeptide, with OVA on the Macroflux resulted in augmented antibody responses. CONCLUSIONS: Macroflux skin patch technology provides rapid and reproducible intracutaneous administration of dry-coated antigen. The depth of skin penetration targets skin immune cells; the quantity of antigen delivered can be controlled by formulation, patch wearing time, and system size. This novel needle-free patch technology may ultimately have broad applications for a wide variety of therapeutic vaccines to improve efficacy and convenience of use.

Administration, Cutaneous↗