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Biomedical subjects

M Boucherat

Publications and source records attributed to M Boucherat.

At least 19 recordsLinked to original sources

Relationship between clinical signs and symptoms and nasopharyngeal flora in acute otitis media.

Possible links between the clinical signs and symptoms of acute otitis media and the composition of the nasopharyngeal flora were investigated by reviewing the files of 1807 children enrolled in four randomised, multicentre trials. A standard protocol was used, nasopharyngeal samples were cultured, and signs and symptoms were recorded. Carriage of Haemophilus influenzae was associated positively with conjunctivitis (OR 4.83, 95% CI 3.76-6.20) and negatively with fever (OR 0.69, 95% CI 0.56-0.86). Carriage of pneumococci was associated positively with fever (OR 1.32, 95% CI 1.08-1.63) and negatively with conjunctivitis (OR 0.50, 95% CI 0.40-0.63).

Carrier State↗

[French paediatrician and general practitioner's survey about actual and future BCG use].

Within the context of future multipuncture withdrawal, we managed, in April 2005, a survey on BCG vaccine habits. During April 2005, 636 paediatricians and 192 GP took part in a survey about BCG, practices managed by InfoVac-France, InVS and AFPA. Most of physicians (73.6%) don't use Mantoux test before BCG vaccination in children less than 6 months old, and the Monovax is the most frequent vaccine used (93.7%). Less than 30% physicians are thinking to be ready to systematically vaccine children after prospected withdrawal of multipuncture vaccination, and almost 1 pediatrician of 5 and one GP of 7 don't want to vaccine anymore. In future, preferred option after Monovax withdrawal is to vaccinate with BCG only the high risk population for tuberculosis (59%). About 60% physicians think that parents could be opposed to intradermal immunization. More than 2/3 of physicians have not an assistant (except the parents) to contain the children during the intradermal injection (71.6%). It seems not acceptable for 2/3 of physicians to address their patients to colleagues or to specialized structures.

Adult↗

[Recurrent respiratory tract infections: how should we investigate and treat?].

Recurrent respiratory tract infections are a common reason for visits to primary care practitioners or hospital physicians. They are placed at the junction of several medical specialities: paediatrics, ENT, pneumology, allergology, immunology, infectiology. The great diversity of the laboratory tests requested and on the other hand the proposed treatments, are the consequences of the diversity of the patients encountered and the paucity of the evidence based-medicine studies in this setting. The dilemma is how to identify the child for which recurrent respiratory tract infections are the witness of underlying condition, without performing repeated medical examinations, laboratory tests and treatments for normal children for which immunologic development occurs normally. The essential tools are the history analysis, physical examination and few laboratory tests. The other questions are how to include, for these patients, influenza and pneumococcal vaccines in the immunization program and how to assess the benefit/risk ratio and the cost of surgical treatments. This paper presents the thought of an expert group trying to define the situations where biological tests or treatments are useful.

Child↗

[Pneumococcal meningitis in France: age and medical risk factors in children].

Streptococcus pneumoniae (Sp) is an important cause of morbidity and mortality among paediatric infectious diseases. The aim of this study is to analyse specific data on Sp meningitis out of the Bacterial Meningitis (BM) French Surveillance Network about mean age of BM cases and clinical features. Overall 367 Sp BM were reported between January 2001 to January 2004 (sex ratio M/F: 1.3), 69.7% were < 2 years old, median age 0.8 year (minmax 0-16.8 years). Before two years old children, 94.1% had no medical risk factor and no underlying conditions: on the other hand, after two years old, these factors were reported in 27% cases (P < 0.001). Mortality rate was 10.9%. On account of a Sp BM's pic at five months, data of the BM French Surveillance Network confirm the necessity of an early vaccination. The vaccine administration at two, three, four months with a booster during the second year, recommended in the vaccinal french calendar, seems particularly adapted to the Sp BM in France.

Adolescent↗

Polymorphic short tandem repeats for diagnosis of the Charcot-Marie-Tooth 1A duplication.

BACKGROUND: A 1.5-Mb microduplication containing the gene for peripheral myelin protein 22 (PMP22) on chromosome 17p11.2-12 is responsible for 75% of cases of the demyelinating form of Charcot-Marie-Tooth disease (CMT1A). Methods for molecular diagnosis of CMT1A use Southern blot and/or amplification by PCR of polymorphic poly(AC) repeats (microsatellites) located within the duplicated region, or the detection of junction fragments specific for the duplication. Difficulties with both strategies have led us to develop a new diagnostic strategy with highly polymorphic short tandem repeats (STRs) located inside the CMT1A duplicated region. METHODS: We tested 10 STRs located within the duplication for polymorphic behavior. Three STRs were selected and used to test a set of 130 unrelated CMT1A patients and were compared with nonduplicated controls. The study was then extended to a larger population of patients. Alleles of interest were sequenced. A manual protocol using polyacrylamide electrophoresis and silver staining and an automated capillary electrophoresis protocol to separate fluorescently labeled alleles were validated. RESULTS: We identified three new STRs covering 0.55 Mb in the center of the CMT1A duplication. One marker, 4A, is located inside the PMP22 gene. The two others, 9A and 9B, more telomerically positioned, have the highest observed heterozygosity reported to date for CMT1A markers: 0.80 for 9A, and 0.79 for 9B. Tetra- and pentanucleotide repeats offered clear amplification, accurate sizing, and easy quantification of intensities. CONCLUSIONS: Combined use of the three STRs allows robust diagnosis with almost complete informativeness. In our routine diagnosis for CMT1A, they have replaced the use of other polymorphic markers, either in a manual adaptation or combined with fluorescence labeling and allele sizing on a DNA sequencer.

Charcot-Marie-Tooth Disease↗

Impact of antimicrobial therapy on nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, and Branhamella catarrhalis in children with respiratory tract infections.

We conducted a multicenter prospective study to document changes in nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, and Branhamella catarrhalis during antibiotic therapy. A cohort of 629 children with respiratory tract infections underwent nasopharyngeal sampling before and after antibiotic treatment. Susceptibility testing, serotyping, arbitrarily primed polymerase chain reaction, and pulsed-field gel electrophoresis were used to compare pretreatment and posttreatment strains of S. pneumoniae. A significant decrease in carriage of all 3 species (especially S. pneumoniae and B. catarrhalis) was recorded. The increase in the proportion of penicillin-resistant pneumococci (PRP; 66% vs. 44%) was due to the decreased carriage of penicillin-susceptible pneumococci (71 of 629 vs. 176 of 629). The risk of PRP carriage in a given child did not increase. None of the children was found to harbor genetically related strains with increased minimum inhibitory concentrations. Given the multiple resistance of PRP, beta-lactam antibiotic therapy also increased the incidence of macrolide-resistant strains, whereas macrolides selected both macrolide- and penicillin-resistant strains.

Anti-Bacterial Agents↗

Five vs. ten days of antibiotic therapy for acute otitis media in young children.

BACKGROUND: Many publications in recent years have argued in favor of shortened therapy for acute otitis media. However, doubt persists regarding children younger than 2 years, and some authors therefore restrict short course therapy to children older than 2 years. METHODS: In a prospective, comparative, double blind, randomized, multicenter trial we compared cefpodoxime-proxetil, 8 mg/kg/day in two divided doses for 10 days, with an identical 5-day regimen followed by a 5-day placebo period. RESULTS: Between October, 1996, and April, 1997, 450 children (mean age, 14.3 months) were enrolled, 227 in the 5-day group and 223 in the 10-day group. In the per protocol analysis clinical success was obtained on Days 12 to 14 after the beginning of treatment (main analysis) in 175 (84.1%) of the 208 children receiving the 5-day regimen and 194 (92.4%) of the 210 children receiving the 10-day regimen (P = 0.009). The superiority of the standard regimen was more marked among children cared for outside their homes (92.5% vs. 81.5%). Clinical success persisted on Days 28 to 42 among 134 (85.4%) of the 157 assessable patients in the 5-day group and 144 (83.7%) of the 172 assessable patients in the 10-day group (P = 0.68). CONCLUSIONS: The 10-day regimen resulted in a higher success rate at the conclusion of therapy, but there were no differences between the two study groups 4 to 6 weeks after enrollment in the study protocol.

Acute Disease↗

One dose ceftriaxone vs. ten days of amoxicillin/clavulanate therapy for acute otitis media: clinical efficacy and change in nasopharyngeal flora.

OBJECTIVE: To compare the efficacy and the safety of a single intramuscular dose of ceftriaxone, 50 mg/kg, vs. a 10-day course of amoxicillin/clavulanate (amox/clav) therapy, 80 mg/kg/day of amoxicillin: 10 mg/kg/day of clavulanate in three divided doses, in children with acute otitis media (AOM) and to evaluate the changes in nasopharyngeal flora after treatment. METHODS: In a prospective, comparative, open randomized, multicenter trial, children were scheduled to return for visits on Days 12 to 14 (main end point) and Days 28 to 42 after the beginning of treatment for AOM. A nasopharyngeal swab for bacterial culture was obtained before the treatment and at Days 12 to 14. RESULTS: Between February, 1995, and May, 1996, 513 children with a mean age of 14.2 +/- 6.7 months were enrolled. All the patients were evaluable for the safety and intent-to-treat analyses and 463 for the per protocol efficacy. At Days 12 to 14 clinical success was obtained in 186 of the 235 children (79%) given ceftriaxone and in 188 of the 228 children (82.5%) treated with amox/clav. Among the patients with clinical success on Days 12 to 14, the success was maintained at Days 28 to 42 for 108 of 183 (59%) patients in the ceftriaxone group and 103 of 187 (55%) patients in the amox/clav group. Before the antibiotic treatment the percentages of children carrying Streptococcus pneumoniae (59.1%), Haemophilus influenzae (39.4%), Moraxella catarrhalis (55.7%) and the rate of penicillin-resistant S. pneumoniae (52.2%) were comparable between the 2 groups. At Days 12 to 14 the carriage of S. pneumoniae and M. catarrhalis was significantly different between the patients treated with ceftriaxone, 43.9 and 42.2, respectively, and the patients treated with amox/clav, 17.4 and 11.1%, respectively. Among the children carrying S. pneumoniae at Days 12 to 14, the percentage of penicillin-resistant strains reached 63.4% in the ceftriaxone treatment group and 83.0% in the amox/clav treatment group, (P = 0.02). Adverse events (mainly diarrhea) related to the study medication were reported more frequently (P < 0.0001) in the amox/clav treatment group. CONCLUSIONS: In an area with a high rate of penicillin-resistant S. pneumoniae, a single dose of ceftriaxone is as efficient as a 10-day course of amox/clav in the treatment of AOM in young children. There was for the two regimens an increased rate of penicillin-resistant strains among the pneumococci carried, whereas the chance for a child to carry a penicillin resistant S. pneumoniae did not increase after treatment.

Acute Disease↗

[Utilization of rapid diagnostic tests for group A streptococcus and and bacteriologic and clinical correlations with acute angina in general medicine].

OBJECTIVES: A prospective study was conducted between November 1995 and May 1996 by 130 general practitioners in France to assess feasibility of a rapid routine diagnostic test for group A streptococcus infection in a general medicine setting and to search for bacteriological and clinical correlations. METHODS: A routine diagnostic test was performed in all patients presenting acute pharyngitis and cultures were ordered in case of positive tests. Among the 2,800 patients included, there were 563 children under 14 years and 2,226 adults. The routine diagnostic test was positive in 393 cases (14%). A culture was obtained in 375 case and isolated group A streptococcus in 324 (11.5% of the total population). The positive predictive value of the routine diagnostic test was 86.4% in this general medicine setting. RESULTS: Comparing clinical signs with the results of the routine diagnostic test showed that an erythematous pultaceous aspect of the pharynx, severe dysphagia and the presence of enlarged nodes were more frequent in patients with streptococcal pharyngitis. The association of these 3 clinical signs with fever > 38 degrees C was also more frequent in patients with a positive routine diagnostic test (OR = 3.3; 95% CI = 2.5-4.4). The triad hoarseness + cough + rhinorrhea was more frequent in subjects with a positive routine diagnostic test (22.7% versus 9%; OR = 2.6; 95% CI = 2.1-4.3). CONCLUSION: The general practitioners who participated in this study found the routine diagnostic test for group A streptococcal pharyngitis was easy to use and compatible with everyday practice. This diagnostic tool was seen as a progress in the management of acute pharyngitis, but only 53.7% of the practitioners were willing to use antibiotics only for cases where a highly specific routine diagnostic test performed during the consultation identifies group A streptococcus. Lack of reimbursement by the national health assurance however makes it impossible to use this test routinely in the general medicine setting.

Acute Disease↗

A multicenter, randomized, double-blind trial of 5 versus 10 days of antibiotic therapy for acute otitis media in young children.

BACKGROUND: All but 2 of the 15 published trials have failed to show a difference in efficacy between short (3 to 5 days) and standard (7 to 10 days) antibiotic regimens for acute otitis media (AOM). These studies involved relatively few patients under 2 years of age, who are at a higher risk for treatment failure. METHODS: In a prospective, comparative, double-blind, randomized, multicenter trial, we compared amoxicillin/clavulanate in 3 divided doses for 10 days with an identical 5-day regimen, followed by a 5-day placebo period. RESULTS: Between February 1995 and May 1996, 385 children (mean age, 13.3 months) were enrolled, 194 in the 5-day treatment group and 191 in the 10-day treatment group. In the per protocol analysis, clinical success was obtained on days 12 to 14 after the beginning of treatment (main analysis) in 125 (76.7%) of the 163 children receiving the 5-day regimen and 148 (88.1%) of the 168 receiving the 10-day regimen (P = .006). Clinical success persisted on days 28 to 42 among 57 (40.4%) of the 141 assessable patients in the 5-day group and 64 (46%) of the 139 assessable patients in the 10-day group. (P = .34). Multivariate analysis showed that the 10-day course was statistically superior only among children cared for outside their homes (86.8% vs 70.8%; P = .008). CONCLUSIONS: When assessed on days 12 to 14 after the outset of treatment, a 5-day regimen is not equivalent to a 10-day regimen among young children with AOM.

Acute Disease↗

Mutations in the X-linked form of Charcot-Marie-Tooth disease in the French population.

The present study reports eight additional mutations in the connexin32 gene associated with the X-linked form of Charcot-Marie-Tooth disease. One of these mutations was found twice in two apparently unrelated families. This form of the disease is demyelinating and dominant. However, patient selection for mutational screening should not be limited to these criteria since presentation can either be familial or sporadic, and some patients may be incorrectly classified as suffering from an 'axonal' form. These new mutations complete our previously published work on 12 other mutations and enable meaningful observation in a representative sample of the French population. Mutations are found in all regions of the gene. The most frequently observed mutations were those affecting arginines and mainly involved CpG sequences. Compared with other sources, some of the mutations were present at a higher frequency in the French population.

Adolescent↗

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↗