Pierre Gehanno

Hyperbaric Oxygen Therapy for Radionecrosis of the Jaw: A Randomized, Placebo-Controlled, Double-Blind Trial From the ORN96 Study Group

PURPOSE To determine the efficacy and safety of hyperbaric oxygen therapy (HBO) for overt mandibular osteoradionecrosis. PATIENTS AND METHODS This prospective, multicenter, randomized, double-blind, placebo-controlled trial was conducted at 12 university hospitals. Ambulatory adults with overt osteoradionecrosis of the mandible were assigned to receive 30 HBO exposures preoperatively at 2.4 absolute atmosphere for 90 minutes or a placebo, and 10 additional HBO dives postoperatively or a placebo. The main outcome measure was 1-year recovery rate from osteoradionecrosis. Secondary end points included time to treatment failure, time to pain relief, 1-year mortality rate, and treatment safety. RESULTS At the time of the second interim analysis, based on the triangular test, the study was stopped for potentially worse outcomes in the HBO arm. A total of 68 patients were enrolled and analyzed. At 1 year, six (19%) of 31 patients had recovered in the HBO arm and 12 (32%) of 37 in the placebo arm (relative risk = 0.60; 95% CI, 0.25 to 1.41; P = .23). Time to treatment failure (hazard ratio = 1.33; 95% CI, 0.68 to 2.60; P = .41) and time to pain relief (hazard ratio = 1.00; 95% CI, 0.52 to 1.89; P = .99) were similar between the two treatment arms. CONCLUSION Patients with overt mandibular osteoradionecrosis did not benefit from hyperbaric oxygenation.

In vivo correlates for Streptococcus pneumoniae penicillin resistance in acute otitis media.

Eighty-four children suffering from acute otitis media caused by Streptococcus pneumoniae were treated prospectively with cefuroxime axetil suspension (30 mg/kg of body weight twice daily for 8 days). The high incidence of isolates with decreased susceptibilities to penicillin (42 of 84 isolates) allowed us to establish a relationship between clinical success and the penicillin MICs for pneumococcal isolates. It was found that cefuroxime axetil is clinically effective in the treatment of acute otitis media caused by penicillin-susceptible and penicillin-intermediate strains of S. pneumoniae. The results indicate that the risk of treatment failure with cefuroxime axetil was increased in children with otitis media caused by S. pneumoniae when the penicillin MIC were greater than or equal to 2 mg/liter.

Evaluation of nasopharyngeal cultures for bacteriologic assessment of acute otitis media in children.

BACKGROUND The recent emergence of penicillin-resistant Streptococcus pneumoniae, particularly in acute otitis media (AOM), has increased interest in the development of noninvasive procedures that might help to predict the bacterial etiology of this condition. We conducted an open multicenter study to evaluate the predictive value of the nasopharyngeal (NP) sampling in children with AOM by comparing the bacteriologic results of NP cultures with those of pus collected by myringotomy in the same patients. METHODS The NP secretions and the pus obtained by myringotomy were collected concomitantly in 354 children younger than 6 years of age with clinical signs of AOM. The clinical usefulness of NP culture was determined by calculating its sensitivity and specificity, and especially its positive and negative predictive values for the three main pathogens responsible for AOM, Haemophilus influenzae, S. pneumoniae and Moraxella catarrhalis. RESULTS A positive NP culture was found to have little predictive value for H. influenzae (52%), S. pneumoniae (43%) and M. catarrhalis (19%). In contrast the negative predictive value of NP cultures was much greater and was accompanied by negative middle ear fluid cultures in more than 95% of children, especially for S. pneumoniae. Furthermore the incidence of beta-lactamase-producing strains of H. influenzae at both sampling sites was similar (30 and 35%, respectively), as was the incidence of penicillin-resistant S. pneumoniae (50 and 54%). CONCLUSION It appears that the correlation between results of NP and middle ear fluid cultures in children with AOM is too weak to allow NP culture to be recommended for the bacteriologic documentation of this disease. However, these results should not overshadow the considerable epidemiologic value of NP cultures, particularly with reference to the monitoring of pneumonococcal susceptibility in children. The collection of NP cultures should therefore be promoted for their collective epidemiologic value.

Microbiology of otitis media in the Paris, France, area from 1987 to 1997.

PURPOSE OF THE STUDY To investigate epidemiologic trends in the bacteriology of acute otitis media, data were recorded during a 10-year period by the same group of investigators during clinical studies in pediatric outpatients. METHODS Bacterial samples were obtained before antibiotic treatment from 2149 children (age 3 to 36 months) with acute otitis media. All samples were transported, handled and cultured in the same way throughout the 10-year period. RESULTS From the study patients 1862 samples of middle ear secretion were collected by tympanocentesis and 287 samples were collected from spontaneous otorrhea occurring within 24 h. Pathogens were isolated from 70% of patients. Pathogens included Haemophilus influenzae (40%), Streptococcus pneumoniae (31%) and Moraxella catarrhalis (8%). The incidence of beta-lactamase-producing H. influenzae was approximately 20% from 1987 to 1989, was approximately 35% from 1990 to 1995 and increased to 60 and 70% during the last 2 years. The rate of S. pneumoniae with decreased susceptibility to penicillin gradually increased from 7% in 1987 to 70% in 1996 and 1997. CONCLUSION The very high incidence of antimicrobial resistant strains reached during a short period in pediatric acute otitis media in our area, emphasizes the need for frequent epidemiologic studies.

Prognostic Value of Lymph Node Involvement in Oral Cancers: A Study of 137 Cases

Objective The aim of this study was to assess the prognostic value of lymph node involvement in patients with squamous cell carcinoma of the oral cavity.

Pathogens isolated during treatment failures in otitis

OBJECTIVES A prospective study in the Paris region to evaluate the clinical and bacteriologic epidemiology of acute otitis media in infants in whom oral antibiotic therapy resulted in clinical failure. METHODS The study included 186 children with a mean age of 17.5 +/- 13.1 months. Two-thirds of them attended a day-care center and 40.8% had a history of recurrent otitis media. The most frequently prescribed prior antibiotics were amoxicillin-clavulanic acid (43% of cases), an oral third generation cephalosporin (22.6%), erythromycin-sulfisoxazole (11.8%) and a first generation cephalosporin (10.2%). The average duration of antibiotic therapy was 6.9 +/- 2.65 days. Specimens for bacterial cultures included 188 samples of middle ear fluid obtained by tympanocentesis and 37 collected from otorrhea fluid. RESULTS One hundred forty-one samples (62.7%) from 126 children yielded 170 bacterial isolates. In 60 children (32.3%) the culture of the ear pus was sterile. Among the 170 bacterial isolates: 67 (39.4%) were Streptococcus pneumoniae (59 patients), of which 77.6% had reduced susceptibility to penicillin (PRSP with penicillin MIC > or = 0.125 mg/l); 61 (35.9%) were Haemophilus influenzae (56 patients) of which 49.2% were beta-lactamase producers; and 8 were Moraxella catarrhalis (8 patients), of which 87.5% were beta-lactamase producers. Thirty-six patients were infected by S. pneumoniae with penicillin MIC > or =1 mg/l. In our study attending day-care center (P = 0.04), temperature >38 degrees C with signs of otalgia (P = 0.02), age <2 years (P = 0.048) and prior antibiotic treatment with erythromycin-sulfisoxazole (P = 0.006) were independently predictive risk factors for patients infected with penicillin-resistant S. pneumoniae. Pneumococcal serogroups 23, 14 and 19 were predominant (25.4, 25.4 and 23.8%, respectively). Penicillin resistance was mainly associated with serogroups 23 and 14. CONCLUSIONS Penicillin-resistant S. pneumoniae isolates are frequently responsible for therapeutic failure in cases of acute otitis media in the Paris region.

Immunohistochemical localization of plakophilins (PKP1, PKP2, PKP3, and p0071) in primary oropharyngeal tumors: correlation with clinical parameters

Plakophilins (PKPs) are members of the armadillo multigene family. Armadillo-related proteins function in both cell adhesion and signal transduction, and also play a central role in tumorigenesis. Here we report the immunohistochemical localization of PKPs in 37 cases of human primary squamous cell carcinoma of the oropharynx lacking overt distant metastases that were followed clinically for 3 years. Immunoreactivity for the PKPs PKP1, PKP2, PKP3, and p0071 (also known as PKP4) was assessed on frozen unfixed sections using a semiquantitative scoring system. Results were correlated with tumor grade, clinicopathologic parameters, and patient survival. Only p0071 was associated with tumor growth, demonstrating an inverse correlation with tumor size. PKP1 and PKP3 immunoreactivity was inversely correlated with tumor histological grade and was observed only in tumors that did not metastasize. In contrast, strong PKP2 immunoreactivity was observed in 85.7% of metastatic tumors. Interestingly, patients with tumors in which PKP1 and PKP3 immunoreactivity was reduced or absent exhibited local recurrences or metastases, or both, as well as poor survival. Correlation of the subcellular localization of PKPs with routine histological and clinical parameters suggests that these proteins may serve as useful markers for predicting the clinical outcome of the disease. Although the 4 PKPs displayed different levels and patterns of subcellular distribution in tumors, there was a positive correlation between immunoreactivity for PKP2 and PKP3, as well as for PKP2 and p0071, suggesting possible functional similarities associated with differentiation, tumor growth, and disease prognosis. Nevertheless, the mechanisms involved in altering the subcellular localization in tumors compared with normal epithelium are unknown, and further investigation is needed to determine whether PKPs are causative factors for oral carcinogenesis or are merely characteristic of the phenotype.

Effect of increased dosages of amoxicillin in treatment of experimental middle ear otitis due to penicillin-resistant Streptococcus pneumoniae.

A gerbil model of acute middle ear otitis was used to evaluate the efficacy of increased dosages of amoxicillin in eradicating infection induced by penicillin-resistant Streptococcus pneumoniae. Three different strains were used: (i) a serotype 23 penicillin-susceptible strain; (ii) a serotype 23 penicillin-resistant strain (MIC of penicillin, 2 micrograms/ml); and (iii) a serotype 19 highly penicillin-resistant strain (MIC of penicillin, 4 to 8 micrograms/ml). Animals were inoculated bilaterally with 10(7) CFU per ear by transbulla challenge and treated 2 to 4 h postinfection by amoxicillin administrated subcutaneously. The course of the disease was monitored bacteriologically on days 2, 4, and 8 postinfection. The three strains had a similar pathogenicity in untreated animals in terms of the duration of the disease, bacterial counts in middle ear (ME) fluid, and systemic complications. Infection due to the penicillin-susceptible strain was cured after two injections of 2.5 mg/kg of body weight. No bacteria were recovered at day 2 after two injections at 10 and 25 mg/kg with the penicillin-resistant and highly penicillin-resistant strains, respectively. Under these experimental conditions, increased does of amoxicillin consistent with MICs were able to clear ME infection. Pharmacokinetic parameters of amoxicillin in serum and ME fluid were within the clinical range at the doses used in the study.

Otogenic intracranial infections in adults.

Objective: To assess the type and bacteriology of otologic diseases associated with bacterial meningitis in adults. Method: Retrospective review of 79 patients over an 18‐year period. Results: Acute otitis media was diagnosed in 32 patients, chronic otitis in 29 (16 with cholesteatoma), and cerebrospinal fluid leak in 18. Streptococcus pneumoniae was a common cause of meningitis‐complicating acute otitis media (69%) or cerebrospinal fluid leak (50%), whereas other bacteria or negative cultures were found in the cerebrospinal fluid of patients with chronic otitis. Surgery was performed promptly in 26 patients; four patients died. Conclusions: Early diagnosis of otogenic bacterial meningitis is essential to allow appropriate antimicrobial treatment. Antimicrobials active on gram negative bacilli and anaerobes should be used in patients with chronic otitis. An emergency surgical procedure is required in patients whose neurologic or infectious status fails to improve under antimicrobial treatment.

Epidemiologic study of conjunctivitis-otitis syndrome

We conducted a prospective cross-sectional epidemiologic study of conjunctivitis-otitis syndrome during two 3-week periods of consecutive winters. A representative sample of 184 pediatricians and ear, nose and throat specialists in the Paris area recruited 2901 children from 6 to 36 months of age presenting with acute otitis media, of whom 465 (16%) also had purulent conjunctivitis. In sampled children, the culture of the conjunctival exudate yielded bacterial pathogens in 419 patients: Haemophilus influenzae, 371 (89%); Streptococcus pneumoniae, 72 (17%); and Branhamella catarrhalis, 23 (5%). Pulsed field gel electrophoresis analysis of paired H. influenzae isolates from the conjunctival exudate and middle ear fluid of 21 patients showed identical strains in each patient.