[Glassy cell carcinoma of the uterine cervix: An aggressive type of cancer]. / Glassy cell carcinoma du col de l'utérus : une maladie tumorale agressive.

INTRODUCTION: Cervical cancer is the twelfth most frequent cancer in women in France. Glassy cell carcinoma is a rare histological entity, rapidly aggressive, associated with a poor prognosis. CASE REPORT: A 30-year-old woman was admitted in an internal medicine department for polyarthralgia with high grade fever, evolving for 3 weeks. There was an inflammatory syndrome. The 18-FDG-PET-scan showed inflammatory lymph nodes as well as disseminated osteolytic lesions, and a primitive pelvic tumor. A 3cm tumor of the cervix was found during the gynaecologic examination. Histological analysis elicited a high-index mitotic carcinoma, glassy cell carcinoma type. Despite chemotherapy, the outcome was poor, with early death occurring after three months of follow-up. CONCLUSION: The glassy cell carcinoma of the cervix should be considered as an aetiology of bone metastases in young female patients.

Treatment of asthma by the inhaled corticosteroid ciclesonide given either in the morning or evening.

The study addressed the question whether the novel inhaled prodrug corticosteroid ciclesonide is equally effective when inhaled in the morning compared to the evening. For this purpose a double-blind, randomized, parallel group study was initiated in which 209 asthmatic patients (forced expiratory volume in one second = 50-90% predicted) inhaled either 200 microg ciclesonide in the morning or in the evening, for 8 weeks. Efficacy was assessed by means of spirometry as well as daily recordings of morning and evening peak expiratory flow (PEF), symptoms and use of rescue medication. The 24-h urinary cortisol excretion was measured to evaluate any effect on hypothalamic-pituitary-adrenol axis. Ciclesonide significantly improved asthma control. Morning and evening administration was shown to be equally effective for the different spirometry variables, evening PEF, symptoms, use of rescue medication and number of asthma exacerbations. Regarding morning PEF, the improvements after evening dosing were more prominent and equivalence of morning and evening administration could not be demonstrated. No relevant influence on cortisol excretion was found. Overall, the study indicates that ciclesonide can be given either in the morning or in the evening to meet the patients' preference and individual medical needs, although evening administration may lead to a more pronounced improvement in morning peak expiratory flow.

[Medical demography: the portrait of pathologic anatomy and cytology]. / Démographie médicale: le portrait de l'anatomie et cytologie pathologiques.

Assessment of care supply in terms of medical labor force is difficult because of the disparity of available data. Using the medical specialty of pathology as an example, we present for the first time a demographic analysis based on the confrontation of main data sources. This study underlines some of the structural and dynamic problems which threaten the demographic stability of the specialty. The public service suffers from a lack of practitioners, especially in regional hospitals. Whereas one third of French pathologists work in the larger hospitals around Paris, in some other regions private services constitute the main component of the supply. Projections based on the aging phenomenon and a reduction in entry indicate a future problem in the renewal of generations of pathologists. The consequences of this programmed decrease in the number of French pathologists will be further exacerbated by the movement of the sex ratio in favor of women.

[Comparison of databases of the medical profession: an example in anatomy and pathological cytology]. / Comparaison des bases de donnees de la profession medicale: l'exemple de l'anatomie et cytologie pathologiques.

Medical demographic regulation policy is supported by statistical descriptive and prospective studies on the actual and future supply of medical practitioners. Two main data bases are available in France for these analyses one at the Ministry of Health and the other at the French Medical Council. While both are supposed to be exhaustive and reliable, the official publications of the two institutions provide different data. It is difficult to assess the actual number of French doctors. The task is even more problematic for each individual medical or surgical specialty. Using the medical specialty Pathology as an example, this article compares the quality of the different data bases and underlines some of the structural and dynamic problems which could interfere with the validity of the information. Better cooperation between the different institutions involved would be helpful to contribute to the quality of the data bases and the organization of the medical specialty.

Penetration of lomefloxacin into bronchial secretions following single and multiple oral administration.

The bronchial penetration of lomefloxacin, a new difluorinated quinolone, was evaluated in 36 patients who underwent bronchoscopies for diagnostic purposes. Patients were randomized into two groups, with 18 patients (Group I) receiving a single oral dose of 400 mg lomefloxacin and 18 patients (Group II) receiving 400 mg twice daily. Samples of serum and bronchial secretions were collected simultaneously in both groups at 1, 2, or 4 hours after lomefloxacin administration. The results of this study showed that bronchial penetration of lomefloxacin was rapid and yielded high concentrations; the mean bronchial levels of the drug reached 2.78 +/- 3.64 micrograms/mL in Group I 1 hour after the dose, and 2.84 +/- 1.73 micrograms/mL in Group II at the fourth hour. The ratio between bronchial and simultaneous serum concentrations was 89% at the first and second hours after the dose for Group I, and it was 77% 4 hours after oral administration in Group II. In comparing these results to previous reports of lomefloxacin penetration into bronchial mucosa or of concentrations of other new fluoroquinolones into bronchial secretions, it is to be noted that the local concentrations of the newer quinolones are of very similar values, ranging from 2.7 micrograms/mL (ofloxacin) to 4.46 micrograms/mL (pefloxacin). This study confirms that lomefloxacin achieves high tissue concentrations in the respiratory tree; this characteristic, together with lomefloxacin's antibacterial spectrum, indicates promise in the treatment of many respiratory infections.

[Diffusion of piperacillin into bronchial secretions]. / Etude de la diffusion de la pipéracilline dans les sécrétions bronchiques.

Piperacillin is a ureido-penicillin characterized by the presence of a piperazine group at the position 6 of the beta-lactam ring. This group confers a broader spectrum that includes Pseudomonas. In vitro studies have shown that piperacillin is active against clinical strains recovered from intensive care unit patients with severe lower respiratory tract infections. The purpose of our study was to investigate the usefulness of piperacillin in such patients by evaluating the drug's diffusion into bronchial secretions. A single 4 g dose of piperacillin was given intravenously over three minutes to each of 6 intensive care unit patients. Serum and bronchial secretion samples (obtained through a tracheal intubation or tracheostomy tube) were taken 1/2 hour, 2 h, 4 h and 6 h after the injection to evaluate piperacillin kinetics. Serum piperacillin concentrations were maximal 30 mn after the IV (mean value: 90.6 +/- 23.8 micrograms/ml) and thereafter fell gradually (mean value after 4 hours: 40.4 +/- 27.5 micrograms/ml). Peak concentrations in bronchial secretions were recorded at 2 hours (12.2 +/- 8.5 micrograms/ml); the mean residual value at 6 hours was 4.9 +/- 8.7 micrograms/ml. The diffusion ratio (ratio of bronchial secretion concentration to simultaneous serum concentration) was 15.5% to 24.5%. Our results show that the diffusion of piperacillin into bronchial secretions is outstanding and support the use of this drug in severe respiratory tract infections.

Study of the diffusion of cefmenoxime into the bronchial secretions.

The wide spectrum of antibacterial activity of cefmenoxime as well as its resistance to beta-lactamase degradation, confers upon this drug a probable efficacy in the treatment of common respiratory infections. The objective of this study was to evaluate the penetration of cefmenoxime into bronchial secretions taken in patients, mostly with chronically superinfected bronchial pathology. Bronchial samples were collected by means of fiber-optic bronchoscopy; simultaneous serum samples were also taken after bolus intravenous injection of 1 g of cefmenoxime, after a single dose in 12 patients (group I); after multiple doses in 12 patients (group II). Concentrations of cefmenoxime were determined by means of microbiological procedure. The results showed: bronchial kinetics of cefmenoxime similar to those of other cephalosporins studied previously; after multiple doses a bronchial steady state with a slow decrease of bronchial levels as a function of time; no difference between levels measured after single or multiple doses; a ratio between bronchial levels (B) and simultaneous serum (S) levels (B/S, %) of about 10% at the 2nd hour, 20% at the 4th hour. Due to the extremely low MICs for most bacteria responsible for respiratory infections, cefmenoxime might be expected as the drug of choice in the treatment of bronchopulmonary infections.

The penetration of macrolides into bronchial secretions.

Macrolides have shown efficacy in the treatment of a large range of respiratory infections. These antibiotics are well tolerated, have a narrow antibacterial spectrum, and excellent diffusion properties. We have studied the penetration into bronchial secretions of three macrolides, erythromycin, josamycin and oleandomycin. The bronchial concentrations of erythromycin reached an average of 1 mg/l 2 h after oral administration of 1 g; they were lower for josamycin (0.52 mg/l) but the ratio between bronchial and simultaneous serum concentrations was similar for both drugs. Bronchial levels of oleandomycin were rapidly higher than the serum levels, reaching 3 to 4 mg/l, a ratio of more than 100%. Other studies on tissue concentrations of erythromycin and josamycin showed local levels of 4 to 6 mg/l, whereas in bronchial secretions the concentrations were identical to those measured in our study. On the whole, the good diffusion of macrolides into respiratory tissues and secretions as well as in-vitro antibacterial activity against most species responsible for respiratory infections confirm their indication in the treatment of these infections.

Influence of a fluidifying agent (bromhexine) on the penetration of antibiotics into respiratory secretions.

The authors report the results of a study designed to evaluate the possible increase of penetration into bronchial secretions of antibiotics when combined with a fluidifying agent: bromhexine. The study was carried out in a double-blind experiment: erythromycin in 22 patients (group I) or amoxycillin in 26 patients (group II) were administered orally; in both groups several patients were given a placebo, instead of bromhexine. Antibiotics were administered at the usual dosage: 0.5 g X 2 for erythromycin (3 days); 1 g X 2 for amoxycillin (7 days); with the latter, two different doses of bromhexine were administered simultaneously: 48 mg/day and 96 mg/day in ten and eight patients respectively. Samples of bronchial secretions were collected by means of fibreoptic bronchoscopy at the second hour for erythromycin and for amoxycillin; simultaneous serum samples were also collected. The results of the study showed in both groups a significant increase of the ratios between bronchial levels and simultaneous serum concentrations when combined with bromhexine; in patients receiving amoxycillin with 96 mg of bromhexine the percentage penetration was noticeably higher (7.5%) than in those treated with 48 mg bromhexine (4.3%). These results confirm the efficacy of bromhexine as a drug able to disrupt mucopolysaccharides of bronchial secretions and, as a result, to increase the bronchial penetration of antimicrobial drugs as evaluated on the basis of percentage penetration ratio.

[Bronchial diffusion of new anti-pseudomonal beta-lactams. Clinical significance]. / Diffusion bronchique des nouvelles beta-lactamines anti-pseudomonas. Signification clinique.

In treating severe respiratory infections due to Pseudomonas aeruginosa and in patients with cystic fibrosis, new anti-pseudomonal beta-lactams constitute a good alternative to the traditional aminoglycoside antibiotic therapy. Among several criteria for the choice of an antibiotic, estimation of intrabronchial levels is to be taken into account. The authors report the results of the study of a new semi-synthetic penicillin, apalcillin, and two cephalosporins (cefsulodin, ceftazidime), active in vitro against Pseudomonas; their penetration into respiratory secretions was evaluated in 48 patients, intubated, tracheostomized, or undergoing fiberoptic bronchoscopy. Antibiotic concentrations were measured by the microbiological procedure. Bronchial penetration of apalcillin was early and noticeable, reaching a bronchial peak representing 20% of the simultaneous seric concentration. The local levels of cefsulodin and of ceftazidime did not differ from those achieved with cephalosporins studied previously; the bronchial peak reached 5,6 micrograms/ml for both drugs 2 hours after administration; this bronchial level corresponded to 15 to 20% of the serum concentration. The clinical response could not be evaluated due to the severe underlying pathology which compromised the outcome of the disease in the patients of this study. However, at least for apalcillin, a significant correlation was noted between bronchial levels, susceptibility of bacteria isolated in patients, and eradication of susceptible organisms.

Penetration of cefsulodin into bronchial secretions.

The objective of this study was to evaluate the penetration of cefsulodin, a new cephalosporin active against Pseudomonas aeruginosa, into the bronchial secretions. The study was carried out in 28 patients with respiratory infections; 11 patients received a single dose of 1 g i.v. (bolus); 17 patients received multiple doses of 1 g every 8 h for 48 h. Simultaneous samples of blood and bronchial secretions were collected 30 min and 1, 2, 4 and 6 h after injection. Bronchial secretions were obtained from 23 patients by means of fiberoptic bronchoscopy and in 5 tracheostomized patients (with severe respiratory insufficiency) through a tracheostomy cannula. The assays of cefsulodin were performed by means of the microbiological agar diffusion technique. The results of the study showed a noticeable penetration of the drug into the bronchial secretions, with a mean peak reaching 3.1-5.3 micrograms/ml at the 3rd or 4th hour, a slow elimination and residual levels at 6 h ranging between 2.0 and 6.0 micrograms/ml. The rate of penetration was not influenced by the administration of multiple doses of the drug. The ratios between bronchial concentrations and simultaneous serum concentrations ranged between 10 and 30%, corresponding to the usual values found for other cephalosporins. In conclusion, this study provides satisfactory results and confirms the presence of bronchial levels capable of inhibiting P. aeruginosa.

[penetration of fosfomycin into bronchial secretions]. / Etude de la pénétration de la fosfomycine dans les sécrétions bronchiques.

The objective of this study was to evaluate the penetration of fosfomycin in bronchial secretions in 11 tracheostomized patients which allowed sampling at successive times, following intravenous injection of 4 gr of the drug during 4 hours. In simultaneous samples of serum and bronchial secretions, the measurement of fosfomycin was performed according to the agar diffusion microbiological method. The results of the study showed a worthwhile penetration of fosfomycin, with a mean bronchial concentration reaching 13,1 micrograms/ml, half an hour after the end of the injection, decreasing slowly with 7,04 micrograms/ml remaining two hours after the injection. The ratio between bronchial levels and corresponding serum levels reached 13% two hours after the injection. Fosfomycin diffusion from serum to bronchial secretions realizes significant amounts that are superior to the MICs of fosfomycin for most bacteria responsible for serious broncho-pulmonary infections in intensive care units.

Study of the diffusion of cefotiam in the bronchial secretions.

The objective of this study was to evaluate the concentration in the bronchial secretions of a new injectable cephalosporin, cefotiam, which is characterized by an excellent antibacterial activity, stability against beta-lactamases and interesting pharmacokinetic properties. 30 patients suffering from acute exacerbation of a chronic bronchitis or bronchiectasis with expectoration, received either 1 g i. v. of cefotiam in a single dose or four doses of 1 g each over a period of 3 days. The bronchial secretion samples were obtained by fibroscopy, 1, 2, or 4 h after the last dose, in order to evaluate the kinetics of the bronchial concentration of cefotiam. Blood samples were taken simultaneously in order to establish a possible correlation between the bronchial and serum levels of the drug. The results of the study show a rapid and significant transfer of the drug through the bronchoalveolar capillaries, elevated bronchial concentrations starting from the 2nd h, reaching 10 micrograms/ml (or more) in certain cases, slow elimination with bronchial concentrations persisting at high levels for up to 4 h and a ratio between bronchial and serum concentrations of 25-60% at the 2nd h and more than 100% at the 3rd and 4th h. These results confirm the excellent diffusion of cefotiam, especially in the respiratory tract, allowing bronchial levels largely superior to the minimum inhibitory concentrations required to kill the bacteria usually responsible for lower respiratory tract infections.

Penetration of ampicillin into human bronchial secretions.

Ampicillin concentrations in serum and bronchial secretions after oral administration of bacampicillin were evaluated. Twenty-eight hospitalized patients with acute bronchopulmonary infections received a single dose of 800 mg of bacampicillin. Samples of bronchial secretions were obtained during diagnostic bronchoscopy and blood samples were drawn simultaneously. Significant concentrations of ampicillin were found in bronchial secretions, the peak level, reached after approximately two hours, being 0.27 micrograms/ml on an average. The penetration of ampicillin into the bronchial secretions after the administration of bacampicillin could be correlated with the degree of bronchial inflammation, as illustrated either by macroscopic purulence or protein concentration in the secretions. The results suggest that bacampicillin is a useful drug in acute bronchopulmonary infections.

[Pharmacokinetic study of antibiotics in human respiratory tract (author's transl)]. / Pharmacocinétique des antibiotiques dans les voies respiratoires.

We report the results of the study of the bronchial concentrations of several antibiotics. The experiment included 280 patients and the concentrations achieved in bronchial secretions were measured for 11 antibiotics. The samples of bronchial secretions were taken in situ by fibroscopy or through the tracheostomy cannula. The results of the study show that the rate of penetration is variable according to the different drugs; even in the same antibiotic family such as beta-lactam antibiotics the rate of penetration is variable. The bronchial levels of aminoglycosides, macrolides and tetracyclines are worthwhile, and are often superior to the MIC of the infecting organisms; the penetration is also dependant of the inflammatory conditions of the bronchi. Otherwise the sampling conditions were the best possible since samples taken by fibroscopy or by tracheostomy are not contaminated by saliva which is a factor of dilutional error. The methodology used in this study is an approach of pharmacokinetics of antibiotics in respiratory tract.