Differential selection of multidrug efflux mutants by trovafloxacin and ciprofloxacin in an experimental model of Pseudomonas aeruginosa acute pneumonia in rats.

The ability of trovafloxacin and ciprofloxacin to select efflux mutants in vivo was studied in a model of acute Pseudomonas aeruginosa pneumonia in rats. Twelve hours after intratracheal inoculation of 10(6) CFU of P. aeruginosa strain PAO1 enmeshed in agar beads, two groups of 12 rats were treated by three intraperitoneal injections of each antibiotic given every 5 h. Dosing regimens were chosen to obtain a comparable area under the concentration-time curve from 0 to infinity/MIC ratio of 27.9 min for trovafloxacin (75 mg/kg of body weight) and of 32.6 min for ciprofloxacin (12.5 mg/kg). Twelve rats were left untreated and served as controls. Rats were sacrificed 12 h after the last injection (34 h after infection) for lung bacteriological studies. Selection of resistant bacteria was determined by plating lung homogenates on Trypticase soy agar plates containing antibiotic. In untreated animals, the frequency of resistant colonies was 10-fold higher than in agar beads. Compared to controls, both treatment regimens resulted in a 2-log reduction of lung bacterial load. The frequency of resistant colonies was 10-fold less with trovafloxacin than with ciprofloxacin at twice the MIC (7.4 x 10(-5) versus 8.4 x 10(-4), respectively) (P < 0.05) and at four times the MIC (6.2 x 10(-4) versus 5.0 x 10(-5), respectively) (P < 0.05). A multidrug resistance phenotype typical of efflux mutants was observed in all 41 randomly tested colonies obtained from treated and untreated rats. In agreement with in vitro results, trovafloxacin and ciprofloxacin preferentially selected MexCD-OprJ and MexEF-OprN overproducers, respectively. These results demonstrate the differential ability of trovafloxacin and ciprofloxacin to select efflux mutants in vivo and highlight the rapid emergence of those mutants, even without treatment.

[Effect of prolonged treatment with proton pump inhibitors on serum gastrin levels and the fundus mucosa. Preliminary results]. / Influence des traitements prolongés par inhibiteurs de la pompe à protons sur la gastrinémie et la muqueuse fundique. Résultats préliminaires.

OBJECTIVES: To evaluate the evolution of fundic argyrophil cell density and hyperplasia grading, fundic chronic gastritis grading and serum gastrin levels in patients treated with proton pump inhibitors. METHODS: Thirty-two patients treated with proton pump inhibitors for gastroesophageal reflux and/or duodenal ulcer were studied. No patient had a gastric ulcer. The studied parameters were serum gastrin levels, fundic argyrophil cell density, the degree of fundic argyrophil cell hyperplasia, the grade of fundic atrophic gastritis and the presence of Helicobacter pylori. The first point of the study was 7 months (range: 0-42 months) and the last point 33 months (range: 7-72 months) after the beginning of the treatment. RESULTS: Serum gastrin levels significantly increased with treatment. Fundic argyrophil cell density did not change significantly. In 3 patients (9%), serum gastrin levels were twice the normal upper limit. The highest serum gastrin levels (249 and 665 pg/mL) were noted in the 2 patients treated with the highest doses of proton pump inhibitors. Micronodular hyperplasia of the fundic argyrophil cells was observed in 2 patients treated with omeprazole 20 mg/d for 4 years and lansoprazole 90 mg/d for 6 years, respectively. Non active superficial chronic gastritis was noted in 2 patients. Serum gastrin levels were significantly correlated with cell densities. CONCLUSION: There were minor modifications of fundic argyrophil cell population and of gastrinaemia during the study period. They were not related to chronic atrophic gastritis. However, survey is mandatory in patients treated with high dose proton pump inhibitors, in those in whom gastrinaemia is elevated and when treatment duration is longer than 5 years.

Assessment of dysplasia, mucosal mucins, p53 protein expression, and DNA content in ulcerative colitis patients with colectomy and ileorectal anastomosis.

BACKGROUND: Patients with ileorectal anastomosis after colectomy for ulcerative colitis remain at risk of developing rectal malignancy. Detection of mucosal dysplasia has been used for regular screening but is difficult in inflammatory mucosa, prompting the search for complementary markers. METHODS: This prospective study aimed to assess the prevalence of dysplasia, the predominance of sialomucin, DNA aneuploidy, and p53 overexpression as possible predictors of colorectal tumourigenesis, in the rectal mucosa of an unselected group of 27 patients with ileorectal anastomosis performed for ulcerative colitis. Patients had neither neoplastic nor dysplastic lesions on the colectomy specimen and the retained rectum at the time of surgery. One biopsy specimen of each lateral rectal wall was studied, using routine histology, mucin histochemistry, DNA flow cytometry, and the streptavidin-biotin complex method with D07 monoclonal antibodies directed towards the p53 protein. RESULTS: Seventeen, seven, and three patients showed inflammatory lesions of inactive, moderate, and severe active colitis, respectively. Dysplasia, sialomucin predominance, DNA aneuploidy, and p53 overexpression were not detected. CONCLUSIONS: The risk of malignant transformation of the rectal mucosa after ileorectal anastomosis seemed to be low in this ulcerative colitis group without high-grade dysplasia or carcinoma in the previous colectomy specimen, carefully followed up endoscopically and histologically. It remains to be evaluated which of the methods studied above will optimize the histopathologic surveillance of the rectal mucosa of ulcerative colitis patients with ileorectal anastomosis.

[Stapedo-vestibular ankylosis associated with osteopathy of the promontory (author's transl)]. / Ankylose stapédo-vestibulaire associée à une ostéopathie du promontoire. (A propos de deux observations).

The authors present two unusual operative findings during surgery for stapedo-vestibular ankylosis, of which no similar cases would appear to be found in the literature. The first case posed the problem of stapedo-vestibular ankylosis as a sequel of clinically latent otitis, the only manifestations of which were radiological opacity of the mastoid and an area of osteitis of the promontory, still active, in the absence of any other progressive inflammatory phenomena or sequelae. Surgery required curettage and opening of the promontory, associated with total stapedectomy and a Teflon-inter-position. The functional result was very good. The second case of typical bilateral stapedo-vestibular ankylosis suggested the possibility of "malignant" otospongiosis, or at all events, markedly progressive. Surgery led to opening of the labyrinth. After platinectomy and excision of a bony sequestrum, there remained only a large fossa with an area equivalent to 3 times that of a usual fenestra ovale. A Teflon-interposition piston was performed with a good result. These rare forms lead to discussion of:--Lobstein's disease, Paget's disease and parathyroid osteosis. Finally, the authors approach the problem of the therapeutic attitude to be adopted in the presence of such rare conditions.