Pretherapeutic laparoscopic staging of locally advanced cervical carcinomas: technique and results.
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Biomedical subjects
Publications and source records attributed to F Leblanc.
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In view to prepare Mars human exploration, it is necessary to promote and lead, at the international level, a highly interdisciplinary program, involving specialists of geochemistry, geophysics, atmospheric science, space weather, and biology. The goal of this program will be to elaborate concepts of individual instruments, then of integrated instrumental packages, able to collect exhaustive data sets of environmental parameters from future landers and rovers of Mars, and to favour the conditions of their implementation. Such a program is one of the most urgent need for preparing human exploration, in order to develop mitigation strategies aimed at ensuring the safety of human explorers, and minimizing risk for surface operations. A few main areas of investigation may be listed: particle and radiation environment, chemical composition of atmosphere, meteorology, chemical composition of dust, surface and subsurface material, water in the subsurface, physical properties of the soil, search for an hypothesized microbial activity, characterization of radio-electric properties of the Martian ionosphere. Scientists at the origin of the present paper, already involved at a high degree of responsibility in several Mars missions, and actively preparing in situ instrumentation for future landed platforms (Netlander--now cancelled, MSL-09), express their readiness to participate in both ESA/AURORA and NASA programs of Mars human exploration. They think that the formation of a Mars Environment working group at ESA, in the course of the AURORA definition phase, could act positively in favour of the program, by increasing its scientific cross-section and making it still more focused on human exploration.
MOTIVATION: One particular application of microarray data, is to uncover the molecular variation among cancers. One feature of microarray studies is the fact that the number n of samples collected is relatively small compared to the number p of genes per sample which are usually in the thousands. In statistical terms this very large number of predictors compared to a small number of samples or observations makes the classification problem difficult. An efficient way to solve this problem is by using dimension reduction statistical techniques in conjunction with nonparametric discriminant procedures. RESULTS: We view the classification problem as a regression problem with few observations and many predictor variables. We use an adaptive dimension reduction method for generalized semi-parametric regression models that allows us to solve the 'curse of dimensionality problem' arising in the context of expression data. The predictive performance of the resulting classification rule is illustrated on two well know data sets in the microarray literature: the leukemia data that is known to contain classes that are easy 'separable' and the colon data set.
One hundred and forty-three non-repetitive strains of Pseudomonas aeruginosa were collected in 13 French hospitals in 1997. A decreased susceptibility or resistance to ticarcillin (MIC > 16 mg/L) was found in 61 isolates (43%) and this was attributed to three major mechanisms: (i) overexpression of OprM and hence related efflux components such as MexAB or MexXY (42.6%), (ii) production of acquired beta-lactamase (29.5%) and (iii) overexpression of chromosomally encoded AmpC cephalosporinase (21.3%). Four of seven 'intrinsically' resistant strains (11.5%) with normal amounts of OprM were shown to produce low levels of AmpC, whereas in three isolates no resistance mechanism to beta-lactams could be identified. Overproduction of OprM thus appears as an important mechanism of ticarcillin resistance in French isolates of P. aeruginosa.
A prospective survey was carried out during three three-weeks periods in May, October 1997 and October 1998 in 13 teaching hospitals. All non-repetitive isolates of P. aeruginosa collected were subject to serotypage and determination of the inhibiting minimal concentrations for ticarcillin, piperacillin, piperacillin + tazobactam, ceftazidime, imipenem, amikacin, ciprofloxacin and fosfomycin. Identification of the betalactamases and quantification of the cephalosporinase were done for the strains intermediate or resistant to ticarcillin. The most frequent serotypes were O: 6 (17%), O: 11 (13%), O: 1 (10%) and O: 12 (9%). Serotype O: 12 was the least susceptible to antibiotics except for fosfomycin. Whatever the serotype, 76% of P. aeruginosa strains with bla PSE-1 are susceptible to fosfomycin, when only 29.8% of non bla PSE-1 producing strains were susceptible to this antibiotic. Integron encoding bla PSE-1 could be implicated in susceptibility to fosfomycin of P. aeruginosa strains. The associations fosfomycin + imipenem or fosfomycin + ceftazidime could be proposed in case of infections due to P. aeruginosa O: 12.
A prospective survey was carried out in october 1999 in 15 french teaching hospitals. Average susceptibility rates, determined by minimal inhibitory concentrations, for the 738 non-repetitive strains of P. aeruginosa isolated were: ticarcillin, 58%, ticarcillin + clavulanic acid, 56%, piperacillin, 73%, piperacillin + tazobactam, 82%, ceftazidime, 76%, cefepime, 53%, cefpirome, 36%, aztreonam, 58%, imipenem, 81%, amikacin, 62%, tobramycine, 71% and, ciprofloxacin, 60%. Among the 75% serotypable strains, the most frequent serotypes were: O:6 (15.3%), O:11 (14.5%), O:1 (10.4%), O:3 (7.9%), O:4 (6.1%) and O:12 (6.1%). The serotype O:12 was the most resistant to antibiotics. Forty-two percent of the strains were resistant or presented an intermediate susceptibility to ticarcillin. Mechanisms were as follow: 14.5% non enzymatic mechanism, 12.5% overproduction of the constitutive cephalosporinase, 7.1% transferable betalactamase and, 6.9% combination of these mechanisms. Among the 67 transferable betalactamases: 48 (71.6%) were PSE-1, 12 (19.4%) TEM-2 and 6 (7.5%) oxacillinases. One extended spectrum betalactamase was characterized. Among the cephalosporines tested, cefepime was less affected by the overproduction of constitutive cephalosporinase. Ceftazidime, remained the best cephalosporin except against the strains overexpressing the chromosomal type 1 beta-lactamase. Resistance to tobramycin was mainly due to enzymatic mechanisms with a high level of resistance. Decreased susceptibility was more frequent for amikacin than for tobramycin. This was probably related with non enzymatic mechanisms.
A total of 1310 consecutive strains of Pseudomonas aeruginosa were collected in 11 French hospitals in 1996. The percentages of susceptible isolates measured by the agar dilution method were: ticarcillin (53%), piperacillin (69%) (MIC 16 mg/L), ceftazidime (77%), cefepime (55%), cefpirome (40%), aztreonam (57.5%), imipenem (81.5%) (MIC 4 mg/L), amikacin (64.5%) (MIC 8 mg/L) and ciprofloxacin (58%) (MIC 1 mg/L). Resistance to beta-lactams was linked to the production of transferable beta-lactamases (30%), overproduction of cephalosporinase (29%) and to non-enzymic mechanisms (38%).
In a prospective study carried out during a three-week period in October 1998 in 13 teaching hospitals, 735 non-repetitive isolates of Pseudomonas aeruginosa were collected. In patients presenting cystic fibrosis (70 strains), the main serotypes isolated were O:6 (14.3%) and O:1 (14.3%). Serotypes O:11 and O:12 were exceptional. In other patients (665 strains), the most frequent serotypes were O:6 (15.9%), O:11 (15.6%), O:1 (10.7%) and O:12 (9.2%). The antibiotic susceptibility rates were as follows (respectively, non-cystic fibrosis and cystic fibrosis strains): ticarcillin, 55 and 59%, piperacillin, 71 and 67%, ceftazidime, 75 and 67%, cefepime, 56 and 43%, cefpirome, 37 and 21%, aztreonam, 57 and 56%, imipenem, 83 and 70%, amikacin, 69 and 33%, ciprofloxacin, 56 and 61% and fosfomycin, 33 and 43%. Serotype O:12 was the least susceptible to antibiotics. Forty-five percent of the non-cystic fibrosis strains presented intermediate susceptibility or resistance to ticarcillin. The most frequent mechanisms of resistance were: non-enzymatic resistance (14.3%), overproduction of the constitutive cephalosporinase (13.8%), production of transferable beta-lactamase (8.6%) and a combination of these mechanisms (4.2%). Among cystic fibrosis strains, resistance to beta-lactam antibiotics was mainly due to overproduction of the constitutive cephalosporinase (18.6%), whereas production of a transferable beta-lactamase was rare (1.4%). Susceptibility to aminoglycosides and fluoroquinolones was less frequent in isolates producing transferable beta-lactamases and/or overproducing cephalosporinase. Decreased susceptibility to imipenem was more frequent in strains presenting a high level of cephalosporinase production. Among the cephalosporins, cefepime was the least affected by the overproduction of constitutive cephalosporinase. Ceftazidime remained the most efficient antibiotic against both susceptible isolates and strains presenting a non-enzymatic or PSE-1 penicillinase-producing mechanism.
The in-vitro activity of grepafloxacin, a new oral fluoroquinolone antibiotic, was compared with those of three other fluoroquinolones and two unrelated antimicrobials, doxycycline and erythromycin, against various Mycoplasma spp. For 65 mycoplasma and 42 ureaplasma strains, grepafloxacin (MIC range 0.03-2 mg/L) was some two to 16 times more active than ofloxacin and ciprofloxacin, showing similar activity to that of sparfloxacin. MBCs of grepafloxacin increased two- to 16-fold when compared with MICs and were comparable to those of sparfloxacin, and lower than those of ofloxacin and ciprofloxacin.
Infections caused by non-tuberculous mycobacteria and multidrug-resistant Mycobacterium tuberculosis are difficult to treat. New compounds potentially active against these bacteria are therefore constantly being sought. Among them is grepafloxacin, a new C5 fluoroquinolone. A panel of 130 isolates of mycobacteria including 33 M. tuberculosis isolates and 97 isolates of different species of atypical mycobacteria were analysed for susceptibility to grepafloxacin, ofloxacin and ciprofloxacin. The MICs of these fluoroquinolones were determined using the agar-dilution method. Different mycobacterial species showed different degrees of susceptibility to grepafloxacin, ofloxacin and ciprofloxacin but little difference was observed between the MICs of the three antibiotics against strains of the same mycobacterial species. In addition, to evaluate the intracellular activity of these drugs, six strains of mycobacteria were studied using a human-macrophage infection model. Preliminary results of macrophage experiments showed that grepafloxacin was more active than ofloxacin and ciprofloxacin, particularly against Mycobacterium kansasii and, to a lesser degree, against Mycobacterium avium complex and Mycobacterium marinum. However, the three fluoroquinolones had comparable activities against M. tuberculosis.
BACKGROUND: Otitis media is a common infection of childhood. Increasing antibiotic resistance rates among the principal causative pathogens, Streptococcus pneumoniae and Haemophilus influenzae, are associated with failure of first line agents. OBJECTIVE: This open, randomized, multicenter study compared the clinical efficacy of a short 5-day course of cefuroxime axetil (CAE) suspension with that of amoxicillin/clavulanate (A/CA) suspension for 8 or 10 days. METHODS: Children age 6 to 36 months with acute otitis media with effusion, diagnosed by tympanocentesis and microbiologic culture, were randomized to receive CAE (30 mg/kg/day in two divided doses for 5 days) or A/CA 40 mg/kg/day in three divided doses for 10 days (A/CA-10). In French centers A/CA was given at 80 mg/kg/day in three divided doses for 8 days (A/CA-8). Patients were assessed 1 to 4 days after completing the course (posttreatment) and followed up at 21 to 28 days after completing the course. RESULTS: Of the 716 patients randomized, 252 were treated with CAE, 255 with A/CA-10 and 209 with A/CA-8. In the clinically evaluable population, the proportions of patients with clinical cure at posttreatment were 175 of 203 (86%), 181 of 205 (88%) and 145 of 164 (88%) in the CAE, A/CA-10 and A/CA-8 groups, respectively, demonstrating equivalence among the three treatments. For patients <18 months old, clinical cures were 111 of 134 (83%), 116 of 131 (89%) and 83 of 99 (84%) in the CAE, A/CA-10 and A/CA-8 groups, respectively; equivalence was also demonstrated. At follow-up, 130 of 175 (74%) CAE, 121 of 172 (70%) A/CA-10, and 112 of 142 (79%) A/CA-8 had maintained cure. A total of 837 pretreatment pathogens were isolated from middle ear fluid in 73% (522 of 716) patients, the majority of isolates were S. pneumoniae (30%) and H. influenzae (27%). The most common adverse events were gastrointestinal, the incidence of drug-related diarrhea being higher in the A/CA-10 group (18%) than in either the CAE or A/CA-8 groups (10%). CONCLUSIONS: A 5-day course of CAE, given twice daily, was shown to be equivalent to the two regimens of A/CA for treatment of acute otitis media with effusion in children.
BACKGROUND: A prospective cost-effectiveness analysis undertaken as part of the CAESAR (Canada, Australia, Europe, South Africa) placebo-controlled clinical trial showed that the addition of lamivudine to zidovudine-containing regimens for 1 year reduced progression of HIV infection to AIDS or death, as well as significantly reducing the number of hospitalisations, outpatient visits and the requirement for medications for HIV-related illness and adverse events. Data from all 1840 patients included in the 'intent-to-treat' population of the CAESAR trial were used for the present analysis. A Canadian third-party payer perspective was adopted, and all costs were adjusted to 1997 prices. RESULTS: The savings associated with reduced healthcare resource use in the CAESAR study were estimated to be 1123 Canadian dollars ($Can) per patient, over the year. These savings partly offset the cost of lamivudine. The analysis showed that the addition of lamivudine to zidovudine-containing regimens resulted in an incremental cost-effectiveness ratio of $Can 14,225 [95% confidence interval (CI): $Can4383 to $Can29,577] for progression to AIDS/death avoided and of $Can5631 (95%CI: $Can2010 to $Can12,929) for HIV-related illness avoided. CONCLUSIONS: Our findings indicate that treatments that slow the progression of HIV infection to AIDS or death have the potential to facilitate healthcare savings, which partly offset the drug acquisition costs. The results also demonstrate that it is possible to undertake economic evaluations in parallel with a major clinical end-point study.
The bacteriological eradication rates of Streptococcus pneumoniae from sputum of patients experiencing acute exacerbations of chronic bronchitis (WHO definition) have been compared following therapy with either cefuroxime axetil 250 mg b.d. or cefixime 200 mg b.d. All patients were hospitalised for an acute exacerbation of chronic bronchitis. The study design was a multicentre, double-blind, randomised, parallel group with patients giving written informed consent initially. Patients were recruited to the study if they met the WHO definition of chronic bronchitis, were aged 30-75 years and had a high probability of S. pneumoniae infection based on initial sputum Gram stain. All S. pneumoniae isolates were serotyped and susceptibility tested at the National Reference Centre, Paris. S. pneumoniae was eradicated more rapidly following cefuroxime axetil administration than after cefixime and this difference was statistically significant (p = 0.002) at 2-4 days post-treatment. Clinical endpoints showed a similar trend--94% response to cefuroxime axetil compared with 71% response to cefixime (RR 6.39:1). Cefuroxime eradicated S. pneumoniae significantly more rapidly than cefixime and patients in the cefuroxime axetil arm had favourable clinical criteria. The data suggest that focused antibacterial studies may be helpful in evaluating antibiotics in acute exacerbation of chronic bronchitis.
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