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Biomedical subjects

M Boucherat

Publications and source records attributed to M Boucherat.

At least 19 recordsLinked to original sources

Change in nasopharyngeal carriage of Streptococcus pneumoniae resulting from antibiotic therapy for acute otitis media in children.

BACKGROUND: Acute otitis media is the leading reason for antibiotic prescriptions in childhood. The increase in antibiotic resistance of Streptococcus pneumoniae is generally attributed to the extensive use of antibiotics and the selective pressure on the bacterial strains of the nasopharyngeal flora. OBJECTIVE: To evaluate the change in nasopharyngeal carriage of S. pneumoniae during antibiotic therapy prescribed for acute otitis media. METHODS: Between October, 1993, and March, 1994, we conducted a clinical trial comparing cefpodoxime-proxetil and amoxicillin-clavulanate in acute otitis media. From 364 children, 4 months to 4.5 years old, a nasopharyngeal sample was obtained before and after treatment. Antibiotic susceptibility was established by determining minimal inhibitory concentrations by the agar dilution method. Serotype and randomly amplified polymorphic DNA analysis were used to compare pre- and posttreatment S. pneumoniae strains. RESULTS: The risk for a child to carry penicillin-resistant S. pneumoniae (MIC > or = 0.125 mg/l) did not increase after antibiotic treatment: 84 of 364 (23.1%) before, 70 of 364 (19.2%) after. There was a significant decrease of penicillin-susceptible S. pneumoniae carriage, 117 of 364 (32.1%) before treatment compared with 24 of 364 (6.6%) (P = 0.0001) after treatment. However, among the children carrying S. pneumoniae at the end of the treatment there was an increase in the percentage of penicillin-resistant pneumococci: 84 of 201 (41.8%) before treatment and 70 of 94 (74.5%) after treatment. Among the 94 children carrying S. pneumoniae at the end of the treatment, 22 did not harbor pneumococcus before, 16 carried another genotypically different serotype and 56 harbored the same serotype. Among these 56 children 2 patients harbored strains that had increased MICs for the tested beta-lactam antibiotics. The randomly amplified polymorphic DNA analysis showed that in one case, the strains were genetically different. CONCLUSIONS: These data illustrate that antibiotic therapy did not increase the rate at which children carried penicillin-resistant S. pneumoniae, but there was an increase in the rate of resistance among the children carrying pneumococci at the end of the treatment, mainly as a result of reduction of susceptible strains.

Acute Disease

New mutations in the X-linked form of Charcot-Marie-Tooth disease.

Mutations in the gene for connexin 32 are associated with a chromosome X-linked form of Charcot-Marie-Tooth disease. The prevalence of this form is probably underestimated. We screened 12 candidate families and found 7 missense mutations of which 4 are new. These mutations are located in intra- and extramembraneous parts of the protein. Some mutations are probably present with a higher frequency. This study further confirms variation of connexin 32 mutations with scarcity in the second transmembrane domain and, so far, absence in the fourth transmembrane domain and in the carboxy-terminal region.

Charcot-Marie-Tooth Disease

Incidence of primary ciliary dyskinesia in children with recurrent respiratory diseases.

The goal of the study was to evaluate the incidence of primary ciliary dyskinesia (PCD) in children suffering from recurrent respiratory tract infections (RRIs) by means of noninvasive method. Respiratory ciliated cells were collected by nasal brushing in 118 children (4.6 +/- 2.5 years) with RRIs. The ciliary beat frequency (CBF) was measured with a stroboscopic method, and when the CBF was abnormal, the ciliary ultrastructure was analyzed by a quantitative method. The CBF could be measured in 106 patients (90%) and was abnormal in 15 patients. The ciliary ultrastructure was found to be abnormal in 11 of 15 patients: PCD was diagnosed in 6 cases, and acquired ciliary defects were observed in the remaining 5 patients. Our conclusion, that PCD is rare but net exceptional (5.6%) in children with RRIs, justifies the systematic investigation of ciliated cells in such patients. For this purpose, nasal brushing can be used to sample ciliated cells even in young children.

Algorithms

Six-day amoxicillin vs. ten-day penicillin V therapy for group A streptococcal tonsillopharyngitis.

OBJECTIVE: To compare the efficacy and safety of amoxicillin (50 mg/kg/day divided twice daily) for 6 days and penicillin V (45 mg/kg/day divided into three doses/day) for 10 days in children with group A streptococcal (GAS) tonsillopharyngitis. METHODS: In a prospective, comparative, open, randomized, multicenter trial, children were scheduled to return for visits 4 days (main end point) and 1 month after the completion of treatment for clinical and bacteriologic assessment. Total DNA restriction fragment length polymorphism was used to compare pre- and posttreatment GAS isolates. RESULTS: Between September, 1993, and February, 1995, 321 children (161 amoxicillin, 160 penicillin V) were enrolled, among whom 318 (160 amoxicillin, 158 penicillin V) were evaluable for safety, and 277 were evaluable for efficacy. Four days after the completion of treatment, pretreatment GAS were eradicated from 118 of the 141 children receiving amoxicillin (83.7%) and 116 of the 136 (85.3%) taking penicillin. One month after the outset of treatment, bacteriologic relapses were observed in 9.9% (n = 11) of the children receiving amoxicillin and 5.7% (n = 6) of those treated with penicillin V, bacteriologic recurrences in 5 and 3 patients, respectively. Adverse events related to the study medications were reported in 4 patients in the amoxicillin group and 8 in the penicillin V group. Drug-related adverse events leading to treatment discontinuation occurred in 3 patients, all in the penicillin V group. Compliance, based on diary cards and the weight of study drugs returned, was significantly better in the amoxicillin group. CONCLUSIONS. The efficacy and safety of amoxicillin (50 mg/kg/day twice daily) for 6 days were not statistically different from those of penicillin (45 mg/kg/d three times a day) for 10 days in the treatment of GAS tonsillopharyngitis.

Adolescent

Molecular diagnosis of Charcot-Marie-Tooth 1A disease and hereditary neuropathy with liability to pressure palsies by quantifying CMT1A-REP sequences: consequences of recombinations at variant sites on chromosomes 17p11.2-12.

The most frequent form of Charcot-Marie-Tooth disease (CMT1A; OMIM118.220) is the result of a duplication on chromosome 17 in pll.2-p12. This region contains PMP22, a gene expressed in peripheral myelin. The mutation results from an unequal crossing-over involving repeated sequences, CMT1A-REP, located on both sides of the duplicated region. The reciprocal product of this recombination is a deletion of the same region, which is associated with hereditary neuropathy with liability to pressure palsies (HNPP; OMIM162.500). Proximal and distal CMT1A-REP sequences can be distinguished by the presence of a variant EcoRI site. We quantified the number of these repeat sequences in 36 CMT1A and 40 HNPP patients. CMT1A-REP sequences are involved in almost all of the mutations. The majority of recombination breakpoints occur distally from the variant EcoRI site. However, a few have a breakpoint proximal to this site, which creates the risk of misinterpretation with respect to a duplicated/deleted status.

Charcot-Marie-Tooth Disease

In vitro influence of plasma steroid-binding proteins on androgen metabolism in human leukocytes.

The purpose of this study was to investigate the influence of plasma steroid-binding proteins on androgen metabolism in intact leukocytes prepared from normal male and female blood samples. Leukocyte preparations were incubated for 24 h at 37 degrees C with either labeled or unlabeled testosterone (T), 5 alpha-dihydrotestosterone (5 alpha-DHT), and androstenedione (A). After extraction, the formed labeled metabolites were first identified by high performance liquid chromatography, then, using unlabeled substrates, metabolite concentrations were measured by specific radioimmunoassays. The conversion ratios of substrate to metabolite were calculated for each preparation using either labeled or unlabeled substrates. In the absence of steroid-binding proteins, the mean conversion ratios of T to A, A to T, T to 5 alpha-DHT, and 5 alpha-DHT to 3 alpha-androstanediol (3 alpha-D) were, in males and females, respectively, 5.6% and 6.1% (n = 11), 5.6% and 5.6% (n = 5), 2.8% and 2.2% (n = 11), 43.1% and 40.0% (n = 5), these sex differences being non-significant. The presence of increasing amounts of plasma, purified albumin or sex hormone binding-globulin (SHBG) in the incubation media reduced metabolite formation dose-dependently. However, a 1000-fold greater concentration of albumin than of SHBG was necessary for 50% inhibition of androgen metabolism by leukocytes, showing SHBG to have the main protective effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Treatment failure in otitis media: an analysis.

An epidemiological study was conducted in order to monitor the involvement of penicillin-resistant pneumococci (PRP) in treatment failure in acute otitis media (AOM), in an area of France where resistance to antibiotics is high. A total of 293 children presenting to 12 ear, nose and throat (ENT) specialists were included in the study. The mean age of the patients was 15.3 months and most of the children (58.7%) were attending day care centres. Bacteriological sampling demonstrated that in 146 cases (49.8%), no pathogen was present at the time of treatment failure. In the remaining patients Streptococcus pneumoniae was the most frequently recovered pathogen, being isolated from 81/147 (55.1%) of bacteriologically documented cases. Serotype 23F was the predominant strain, representing 53% of all S. pneumoniae isolates recovered. Resistance or reduced susceptibility to the prescribed antibiotic was seen in 70/81 (86.4%) of the S. pneumoniae isolates. In 32 out of 49 children administered a beta-lactam antibiotic, treatment failure involved PRP. Amoxycillin seemed to be the most active oral beta-lactam against these pathogens. The multiresistance of S. pneumoniae poses a serious therapeutic problem and should make myringotomy and bacteriological sampling obligatory in cases of antibiotic treatment failure.

Acute Disease

[Evaluation of the brushing technique in nasal cytology].

Analysis of nasal cytology provides useful information for the diagnosis of rhinitis. This analysis represents an interesting tool for objective assessment of nasal pathology. The purpose of this study was to describe the brushing method for obtaining nasal cytologic specimen. Samples were carried out from nine adult patients with chronic nasal obstruction. In all cases, the cytologic specimen had a good amount of well-preserved cells, easy to identify on morphological criteria. A differential cell count was performed on the different epithelial cell types present in the specimen and the results are reported in the present study. In conclusion, brushing method is non invasive and allows to precisely evaluate both epithelial and inflammatory cells present in the nasal mucosa.

Adult

Do nasal ciliary changes reflect bronchial changes? An ultrastructural study.

Ciliary dyskinesia is characterized by recurrent respiratory tract infections secondary to abnormal ciliary structure and function. The diagnosis of ciliary dyskinesia is based on the detection of axonemal ultrastructural abnormalities (AUA) is respiratory mucosa samples. In most cases, the diagnosis of AUA is made on samples obtained from nasal ciliated cells with little discomfort to the patient. However, no studies have been performed in the same patient to confirm whether nasal samples reflect bronchial ciliary changes. To answer this question and to determine whether it is necessary to sample bronchial cells for the diagnosis of ciliary dyskinesia, we investigated 12 patients (between the age of 5 and 63 yr) with chronic sputum production. The presence of situs inversus, bronchiectasis, chronic sinusitis, and sterility was investigated to determine an inherited disorder. Two groups were established: Group 1 = six patients with an inherited disorder and Group 2 = six patients without evidence of an inherited disorder. Samples were obtained by brushing or biopsy of nasal and bronchial mucosa and were processed for transmission electron microscopy. In Group 1, the mean AUA was 65.2 +/- 11.4%. The following predominant axonemal defects were found: absence of dynein arms (DA) (four patients), central complex abnormalities (CC) (one patient), and various AUA (one patient). Nasal and bronchial samples correlated significantly for total AUA (r' = 1, p < 0.01) and for outer DA defects (r' = 0.96, p < 0.05). A good but not significant correlation was found for inner DA (r' = 0.83) and peripheral microtubule (PM) defects (r' = 0.71). In Group 2, the mean AUA was 9.6 +/- 2.3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

[Prevention of acute otitis media. Amoxicillin versus glycoproteins from Klebsiella pneumoniae. Study in children under 5 years of age].

Several studies in the English language literature have shown that continuous antibiotic prophylaxis is more effective than a placebo in preventing recurrent otitis media. In this prospective, randomized trial the effectiveness of continuous amoxicillin therapy was compared with that of glycoproteins from Klebsiella pneumoniae (GKP). The two treatments were administered during 3 months to children aged 1 to 5 years, who had at least 3 episodes of otitis media within the 3 months preceding their admission to the trial. The trial lasted from February 1989 to July 1990. It involved 60 children (mean age: 22.6 months) who had been seen as out-patients and had recovered from their latest episode of otitis. Thirty-three children received amoxicillin 25 mg/kg/day divided into two doses, during 3 months. Twenty-seven children were given GKP 2 tablets per day during 8 days in the 1st month and 1 tablets per day during 8 days in the following 2 months. During the study period, 14 cases of otitis media were observed in children under amoxicillin, as against 22 cases in children under GKP. When the type of day-nursery was taken into account as adjustment factor, the results showed a significantly lower percentage of failures in the amoxicillin group (P less than 0.03). Both treatments were well tolerated (no child was excluded from the trial for intolerance). No Clostridium difficile toxin developed in the amoxicillin group.

Acute Disease

[Brush technique in cytological analysis of the nasal mucosa. A critical and comparative analysis].

The cytological study of the nasal mucosa is one the essential steps toward a better understanding of the physicopathological mechanisms involved in chronic affections of the nose. The development of a reliable, reproducible noninvasive technique to obtain cells in the prerequisite for this analysis. The brush technique is based on the use of a small cylindric nylon brush which is rotated as it is moved back and forth across the nasal mucosa to harvest the various cell types present on the surface of the mucosa. The specimen obtained is centrifuged and examined under an optical microscope. A semi-quantitative analysis is carried out to determine the relative richness of the specimen in epithelial cells (ciliated, qoblet and basal cells) and in inflammatory cells (neutrophils, basophils, eosinophils, lymphocytes, and monocytes). A precise differential cell count is then performed. According to the results obtained, an immunologic marker study of lymphocyte subsets may also be done using the same specimen. This technique may be used in both children and adults and permits cell harvest from various sites within the nasal fossa. Already tested in the study of the activity of cilia, this method is promising for the cytological study of the nasal mucosa. The brush method and other techniques of cell harvest are described and compared.

Adolescent

Determination of plasma delta-aminolaevulinic acid levels. Applications.

Determination of plasma delta-aminolaevulinic acid levels is of interest for the diagnosis of disorders of heme biosynthesis. We describe a reliable method for the determination of this parameter, based on a modification of the original method of Mauzerall and Granick. Analytical criteria are defined and the reference range used, established using data from 40 subjects, was 0.30 to 1.20 mumol/l. Results in patients with porphyria or lead poisoning and in those treated with haemodialysis or anticonvulsants indicate that this determination could be used principally in the diagnosis and management of acute porphyrias and in the early laboratory diagnosis of lead poisoning.

Aminolevulinic Acid

Determination of debrisoquine and metabolites in human urine by gas chromatography-mass spectrometry.

A gas chromatographic-mass spectrometric analysis has been developed for the determination of debrisoquine and its metabolites in the urine of healthy individuals (controls) and patients with chronic renal failure. The sensitive and specific assay comprises selected-ion monitoring of the drug and the metabolites 4-hydroxydebrisoquine and 8-hydroxydebrisoquine using guanoxan as the internal standard. The limit of detection is ca. 0.2 microgram/ml. The clinical study shows that the healthy individuals and patients with chronic renal failure can be divided in two groups of extensive metabolizers and poor metabolizers, respectively. The extensive metabolizers excreted large amounts of 4-hydroxydebrisoquine and minor amounts of 8-hydroxydebrisoquine. The poor metabolizers excreted small amounts of 4-hydroxy metabolite, and no 8-hydroxydebrisoquine was detected in the urine.

Debrisoquin

Inherited factors in diffuse bronchiectasis in the adult: a prospective study.

To evaluate the prevalence of inherited respiratory ciliary structure and underlying mucus abnormalities in the diffuse bronchiectasis syndrome, we investigated 53 subjects comprising 38 patients with diffuse bronchiectasis confirmed by high-resolution thoracic computed tomography, ten with chronic bronchitis and no diffuse bronchiectasis and five healthy nonsmoking control subjects. The clinical history was determined by means of a standardized questionnaire. Axonemal abnormalities of respiratory cilia were evaluated on bronchial or nasal mucosa samples by transmission electron microscopy (structure) and stroboscopic observation (function). Cystic fibrosis (CF) and Young's syndrome were detected by means of the sweat test and semen analysis when male infertility was suspected. Among the 38 patients with diffuse bronchiectasis, a primary ciliary dyskinesia (PCD) was detected in five (13%) with a high proportion (range: 55-100%) of cilia showing axonemal ultrastructural abnormalities always involving the dynein arms. The prevalence of this inherited condition was higher in North African (36%) than in European patients (4%) (p less than 0.01). After exclusion of the five patients with PCD, the patients with diffuse bronchiectasis showed axonemal ultrastructural abnormalities similar to those with chronic bronchitis. The diagnosis of underlying mucus disorders was based on two types of criterion, i.e. for CF, sweat chloride levels greater than 80 mmol.l-1, or the combination of diagnostic criteria proposed by Stern et al. Respectively, five (three Young's syndrome and two CF) and seven (one Young's syndrome and six CF) cases of inherited mucus disorders were suspected. Our results showed that PCD was highly prevalent among the adult North African patients with diffuse bronchiectasis but relatively rare in the Europeans.

Adult

[Cefaclor versus penicillin V in staphylococcal infections in children].

Although rheumatic fever virtually no longer occurs in France, pharyngitis due to group A beta-hemolytic streptococci (ABHS) remains a common pediatric problem. American studies have underscored the high rate of bacteriologic treatment failures and recurrences of ABHS pharyngitis. Furthermore, several comparative studies have demonstrated that cephalosporins provide better results on these two parameters. This prospective randomized study compared the effectiveness of penicillin V (50,000 to 100,000 IU/kg/day in three divided doses) and Cefaclor (20 to 40 mg/kg/day in three divided doses), each given for ten consecutive days. From September 1989 through October 1990, 117 children (mean age 5.7 years) were entered into the study. All study subjects were seen as outpatients and found to have ABHS pharyngitis on the basis of a rapid screening test and confirmatory bacteriologic studies. Cefaclor was given to 56 patients and penicillin V to 61. Reevaluation with a repeat bacteriologic study was performed in all patients at the end of the treatment period, or earlier in the event of new clinical manifestations, and towards D40. Among patients given penicillin V, bacteriologic failure rate at completion of therapy was 19.6%, clinical failure rate on D10 was 8%, and recurrence rate on D40 was 16.5%. Cefaclor exhibited greater bacteriologic and clinical effectiveness, with 3.4% bacteriologic failures on D10 (p less than 0.01), 1.7% clinical failures on D10, 8.9% clinical recurrences between D10 and D40, and an overall 10.6% rate of failure or recurrence (p = 0.05).

Adolescent

[An open randomized trial, Pediazole versus cefaclor in the treatment of acute otitis media in children].

The combination of erythromycin ethylsuccinate and acetyl sulfafuroxazole (Pediazole = ES) is effective against Hemophilus influenzae, including beta-lactamase-producing strains, and against Streptococcus pneumoniae, including macrolide-resistant strains. In this study, mean daily dosage was 40-50 mg/kg for cefaclor and 50 mg/kg ES + 150 mg/kg sulfamide for Pediazole. Both products were given in three divided doses per day for ten days. Tolerance was evaluable in 106 children and effectiveness in 103 children including 52 in the ES group and 51 in the cefaclor group. Mean age was 23.5 months and both groups were comparable as concerns age, weight, previous ENT disease, and severity of the otitis media. Tolerance was satisfactory in both groups. Clinical results were as follows: failures before or at completion of the course, 5/52 in the ES group versus 13/51 in the cefaclor for the treatment of children with acute otitis media.

Acute Disease

Dissimilar expression of axonemal anomalies in respiratory cilia and sperm flagella in infertile men.

Infertility by sperm immotility may be a consequence of axonemal defects, and it is sometimes associated with respiratory disease as in the primary ciliary dyskinesia. The purpose of this study was to investigate the respiratory epithelium of 13 infertile patients with flagellar ultrastructural anomalies whether they suffered or not from respiratory disease. Only one patient had severe respiratory disease. The beat frequency of nasal cilia (9 to 13 Hz) was considered normal in 11 of the 13 patients. All the cilia were found abnormal in one patient. In 12 of 13 infertile men (92.3%), significant ultrastructural cilia anomalies were found (greater than 7%) even though the men did not suffer from any respiratory disease. Axonemal anomalies were found at both levels either of the same type (four cases) or only partially similar (two cases) or totally different (six cases). The most frequently abnormal substructure of cilia was the central complex (10 of 12) even in cases exhibiting a different abnormal pattern at the flagellar level. Findings are discussed according to those found in animal mutants. Our results suggest that ciliary and flagellar axonemes should be controlled both by common and by different groups of genes.

Adult