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Biomedical subjects

A C Crémieux

Publications and source records attributed to A C Crémieux.

At least 19 recordsLinked to original sources
PubMed2001

Prevalence of high-grade dysplasia and cancer in the anal canal in human papillomavirus-infected individuals.

BACKGROUND & AIMS: The incidence of anal cancer is higher in patients with anal canal condyloma, a sexually transmitted disease, than in the general population. We determined the prevalence of anal dysplasia and cancer in patients with anal canal condyloma with respect to human immunodeficiency virus (HIV) status, immunity status, and human papillomavirus types. METHODS: In 174 consecutive patients (114 HIV positive, 60 HIV negative) with anal canal condyloma, lesions were cured, and the patients were then followed up prospectively. Langerhans cells (LCs) in normal anal mucosa were quantified, and viruses (Epstein-Barr virus, cytomegalovirus, human simplex virus 1, and various human papillomavirus [HPV] types) were characterized on inclusion. During follow-up (median 26 months), relapsed condylomas were resected and examined histologically. HIV load and CD4 T-lymphocyte counts in serum were determined at each visit. RESULTS: Several factors differed significantly between HIV-positive and HIV-negative patients: LCs/mm anal tissue (15 vs. 30), oncogenic HPV (27% vs. 13%), other current anal infections (44% vs. 0%), and sex ratio (93% vs. 73% male). During follow-up, condylomas relapsed in 75% of the HIV-positive patients, with 19 high-grade dysplasias (HGDs) and 1 invasive carcinoma, but in only 6% of HIV-negative patients, with 1 HGD. Male sex, HIV positivity, and <15 LCs/mm tissue were independent risk factors for condyloma relapse. HIV positivity, HGD before inclusion, and condyloma relapse were independent risk factors for HGD and cancer. Serum HIV load was associated with relapse, whereas CD4 T-lymphocyte counts were not. CONCLUSIONS: The prevalence of HGD and carcinoma is higher in HIV-positive than in HIV-negative patients, probably because of HPV activity. HIV-positive patients with high serum HIV load and/or a history of anal dysplasia should be examined by anoscopy, and condylomas should be analyzed histologically.

Adult↗
PubMed2001

A comparison of the steady-state pharmacokinetics and safety of abacavir, lamivudine, and zidovudine taken as a triple combination tablet and as abacavir plus a lamivudine-zidovudine double combination tablet by HIV-1-infected adults.

STUDY OBJECTIVE: To investigate the steady-state pharmacokinetics of a triple combination tablet containing abacavir (ABC) 300 mg, lamivudine (3TC) 150 mg, and zidovudine (ZDV) 300 mg taken twice/day, and those of ABC 300 mg twice/day plus a double combination tablet containing 3TC 150 mg and ZDV 300 mg twice/day (ABC-COM). DESIGN: Open-label, crossover study. SETTING: Two hospital-based clinical research units. PATIENTS: Twelve men infected with human immunodeficiency virus-1. INTERVENTION: Steady-state pharmacokinetics of ABC, 3TC, and ZDV were assessed after dosing with ABC-COM and the triple combination tablet. MEASUREMENTS AND MAIN RESULTS: Steady-state pharmacokinetics of ABC, 3TC, and ZDV were similar for the triple combination tablet versus ABC-COM for the following: geometric mean (GM) area under the serum concentration-time curve, ABC 6.08 versus 5.87, 3TC 5.51 versus 5.53, and ZDV 1.38 versus 1.46 microg x hr/ml; GM maximum serum concentration (Cmax-ss), ABC 3.09 versus 3.19, 3TC 1.26 versus 1.40, and ZDV 1.19 versus 1.15 microg/ml; median time to Cmax-ss, ABC 0.75 versus 0.75, 3TC 1.50 versus 1.24, and ZDV 0.75 versus 0.75 hours; and GM oral clearance, ABC 51 versus 49, 3TC 27 versus 27, and ZDV 217 versus 206 L/hour. The GM half-lives of ABC and ZDV were similar for both treatments, 1.69 versus 1.58 and 2.30 versus 2.08 hours, respectively. CONCLUSION: Steady-state pharmacokinetics of ABC, 3TC, and ZDV were similar in patients who took them as ABC-COM or as a triple combination tablet.

Adult↗
PubMed1999

Prosthetic joint infection: when can prosthesis salvage be considered?

Management of prosthetic joint infection (PJI) remains a therapeutic challenge. We retrospectively studied 69 infected total hip or knee arthroplasties managed between 1980 and 1996 in our institution. Treatment failure, defined as relapse of PJI in the first year following the last antimicrobial treatment, occurred for 14 patients (20.3%). None of the potentially contributive parameters analyzed was significantly predictive of treatment failure. Of the subgroup of 34 patients with PJI who initially underwent debridement with retention of the prosthesis, the 13 (38.2%) who did not require further surgical treatment had symptoms for a significantly shorter duration before debridement (4.85 vs. 54.24 days; P < .0001). Because debridement with retention of the prosthesis rarely enables control of PJI, this therapeutic approach should be considered only when the duration of symptoms is very short.

Adult↗
PubMed1998

Efficacy of teicoplanin and autoradiographic diffusion pattern of [14C]teicoplanin in experimental Staphylococcus aureus infection of joint prostheses.

Prosthesis infections are difficult to cure. Infection with methicillin-resistant staphylococci is becoming more common in patients with orthopedic implants. Using a recently developed model of methicillin-resistant Staphylococcus aureus (MRSA) infection of a knee prosthesis, we compared the efficacies of teicoplanin and vancomycin. [14C]teicoplanin diffusion in this model was also studied by autoradiography. A partial knee replacement was performed with a silicone implant fitting into the intramedullary canal of the tibia, and 10(7) CFU of MRSA was injected into the knee. Treatment with teicoplanin or vancomycin (20 or 60 mg/kg of body weight, respectively, given intramuscularly twice daily) was started 7 days after inoculation and was continued for 7 days. The teicoplanin and vancomycin MICs for MRSA were 1 microg/ml. Mean peak and trough levels in serum were 39.1 and 23.5 microg/ml, respectively, for teicoplanin and 34.4 and 18.5 microg/ml, respectively, for vancomycin. Fifteen days after the end of therapy, the animals were killed and their tibias were removed, pulverized, and quantitatively cultured. Teicoplanin and vancomycin significantly reduced (P < 0. 05) the bacterial density (2.7 +/- 1.3 and 3.3 +/- 1.6 log10 CFU/g of bone, respectively) compared to those for the controls (5.04 +/- 1.4 log10 CFU/g of bone). The bacterial covents of teicoplanin- and vancomycin-treated rabbits were comparable. The [14C]teicoplanin autoradiographic diffusion patterns in rabbits with prostheses, two of which were uninfected and two of which were infected, were studied 15 days after inoculation. Sixty minutes after the end of an infusion of 250 microCi of [14C]teicoplanin, autoradiography showed that in the infected animals, the highest levels of radioactivity were located around the prosthesis and in the periosteum, bone marrow, and trabecular bone. Radioactivity was less intense in epiphyseal disk cartilage, femoral cartilage, articular ligaments, and muscles and was weak in compact bone. A similar distribution pattern was seen in uninfected rabbits. Thus, teicoplanin may represent an effective alternative therapy for the treatment of these infections.

Animals↗
PubMed1997

[Beta-lactamase inhibitors].

UNLABELLED: BETA-LACTAMASE: The capacity to produce beta-lactamase, an enzyme which hydrolyses penicillin and cephalosporines, is the main source of bacterial resistance to beta-lactamines, thus the important contribution of beta-lactamase inhibitors (clavanulanic acid, sulbactam and tazobactam). MECHANISM OF ACTION: Beta-lactamase inhibitors inactivate these enzymes and, in association with beta-lactamines, offer wide spectrum bactericidal action (Gram negative bacilli, anaerobic germs, methicillin-sensitive staphylococci and streptococci) and can be used as first-line treatment in certain community-acquired and nosocomial infections. SIDE EFFECTS: Widespread use of these inhibitors selects intermediate or resistant strains. Toxicity is low. Undesirable effects (poor digestive tolerance for oral formulations) are dose-dependent. RIGOROUS PRESCRIPTION: Recent development of bacterial resistance emphasizes the importance of rational use of these associations and the need for a better definition of the optimal doses. Prescriptions must avoid underdosing and excessively long treatments. Treatment should be simplified if sensitivity to an antibiotic with a narrower spectrum is recognized.

Anti-Bacterial Agents↗
PubMed1997

Experimental models of bone and prosthetic joint infections.

Bone and joint infections are difficult to cure. The difficulty is related to the presence of bacteria adherent to foreign material in many cases and also to the limited activity of antibiotics in infected bones. Clinical trials are difficult to design because of the heterogeneity of the disease and the number of factors that could influence the therapeutic response. To control for these multiple variables, attempts have been made to develop reliable animal models of osteomyelitis and prosthetic joint infections that closely mimic the different infections seen in orthopedic surgery and that allow evaluation of the efficacy of surgical procedures as well as local or systemic antibiotic therapy. These models will continue to provide us information on the pathogenesis and management of such infections.

Animals↗
PubMed1996

[Tuberculosis. Current therapeutics].

Due to the constant decline in incidence up to the mid eighties, eradication of tuberculosis appeared to be an attainable objective in developed countries. Since then multiple factors (HIV epidemic, poor social conditions in certain unfavored areas, population migrations, urbanization) have led to an increased frequency, making an excellent knowledge of tuberculosis a priority for all physicians. Multi-resistant mycobacteria have also made their appearance leading to numerous clinical and experimental studies which provide new insights into the correct management of patients with tuberculosis. Despite these recent changes, the classical treatment for tuberculosis remains the same in most cases, allowing nearly-certain cure when applied correctly in patients infected with a susceptible bacteria, including those with HIV infection or extrapulmonary localizations. On the contrary, the spontaneous aggravation of multi-resistant tuberculosis, even in some cases being treated, emphasizes the need to test the strain's susceptibility to the antituberculous agents used. Certain new antibiotics, including fluoroquinolones, may play an important role in some cases. The contribution of surgery, isolation and strict compliance must also be emphasized. Resistant strains may also led to renewed indications for the Calmette-Guérin vaccine.

AIDS-Related Opportunistic Infections↗
PubMed1996

[Treatment of cytomegalovirus infections in HIV infection].

Cytomegalovirus (CMV) infections are common in patients with AIDS. Retinal localizations predominate, although digestive and neurological and more rarely pulmonary localizations are sometimes seen. Functional prognosis is poor in case of retinal infection requiring early treatment. Standard therapy is based on intravenous administration of two antiviral agents with similar actions: ganciclovir and foscarnet. Maintenance therapy, aimed at delaying recurrence, is clearly indicated for retinitis and may be so for other localizations. The parenteral route is recommended although in case of contraindications, oral ganciclovir and local treatments (intravitreal injections, intravireal implants) may be used. Recurrence is observed earlier after oral treatment, local treatments cannot prevent other localizations and retinal detachment is more frequent with vitreal implants. Other drugs are under study. Cygalovir would be an interesting alternative due to its long half-life allowing fewer injections. Primary prophylaxy for CMV infection is an important perspective. Quantitative PCR will help better define risk groups of patients who could benefit from preventive therapy. The choice between oral or intravenous administration and the correct dose remain to be determined for the most effective preventive treatment and to avoid the emergence of resistance.

AIDS-Related Opportunistic Infections↗
PubMed1996

A new model of experimental prosthetic joint infection due to methicillin-resistant Staphylococcus aureus: a microbiologic, histopathologic, and magnetic resonance imaging characterization.

Partial knee arthroplasty was done in rabbits with a silicone-elastomer implant. Immediately after closing the surgical wound, 5 x 10(6) cfu of methicillin-resistant Staphylococcus aureus was injected into the joint. Disease evolution was studied at different stages of infection up to 8 weeks. Prosthetic infection developed in all animals. Gross pathology and histopathologic changes were characteristic of joint and bone infection. Quantitative bacterial counts from infected bone confirmed disease chronicity. The mean number of colony-forming units per gram of bone +/- SD 1 week after infection was 4.84 +/- 0.24 log10 cfu/g and remained stable from week 1 to week 8. Magnetic resonance imaging showed evidence of prosthetic infection as of week 1, while only mild radiologic changes of bone were seen 2 weeks after infection. This model produces a prosthetic infection that is reproducible and close to that of human prosthetic infection.

Animals↗
PubMed1996

Efficacy of sparfloxacin and autoradiographic diffusion pattern of [14C]Sparfloxacin in experimental Staphylococcus aureus joint prosthesis infection.

Using a new rabbit model of methicillin-susceptible Staphylococcus aureus knee prosthesis infection, we compared the efficacies of sparfloxacin (50 mg/kg of body weight subcutaneously, twice a day) and pefloxacin (50 mg/kg subcutaneously, twice a day). A partial knee replacement was performed with a silicone implant fitted into the intramedullary canal of the tibia, and 5 x 10(7) CFU of methicillin-susceptible S. aureus was injected into the knee. The 7-day treatment regimen was started 15 days later. The MICs and MBCs of sparfloxacin and pefloxacin were, respectively, 0.06 and 0.25 microgram/ml (MIC) and 0.25 and 1 microgram/ml (MBC). The peak levels of sparfloxacin and pefloxacin in serum were 3.6 and 21 micrograms/ml, respectively. Three weeks after the end of treatment, animals were sacrificed and tibias were removed, pulverized, and quantitatively cultured. In contrast to pefloxacin (3.61 +/- 1.64 log10 CFU/g of bone), sparfloxacin significantly reduced the bacterial density (2.12 +/- 1.1 log10 CFU/g of bone) (P = 0.01) in comparison with the level in controls (4.59 +/- 1.21 log10 CFU/g of bone), without selection of resistant variants. Sparfloxacin was significantly more effective than pefloxacin (P = 0.025). The autoradiographic pattern of [14C]sparfloxacin diffusion was studied in noninfected animals with prostheses and in infected animals 15 days after inoculation. Sixty minutes after completion of infusion of 250 microCi of [14C]sparfloxacin, in infected animals the highest levels of radioactivity were detected around the prosthesis, in femoral cartilage, and in articular ligaments. Radioactivity was slightly less intense in bone marrow and muscles and was very weak in compact bone. The distribution of sparfloxacin in uninfected rabbits was similar. Thus, sparfloxacin may represent a valid alternative therapy in these infections provided that it is carefully monitored for potential side effects.

Animals↗
PubMed1994

Evaluation of a rabbit model for osteomyelitis by high field, high resolution imaging using the chemical-shift-specific-slice-selection technique.

The rabbit model of osteomyelitis introduced by C.W. Norden, based on injection of an infecting solution (Staphylococcus aureus, sodium morrhuate) into the tibia, was studied at 4.7 Tesla with a time-efficient chemical shift selective imaging technique, Chemical Shift Specific Slice Selection (C4S). The evolution of the disease over several weeks was followed on water-selective, fat-selective, and sum images obtained simultaneously with this imaging sequence. Experiments were performed either on different groups of rabbits at different times after infection with subsequent sacrifice of the animal and microbiological analysis of the infected tibia or on the same group of animals imaged several times after infection. Associated analysis of the water and fat selective images revealed marrow modifications very early (Day 5 after inoculation) demonstrating the high sensitivity of the employed imaging technique. Later on, bone modifications were best identified on the sum images. Additional experiments performed on animals injected with a noninfecting solution containing only sodium morrhuate showed however that the sclerosing agent alone can yield images similar to those produced by infection at early stages after inoculation. Therefore, the Norden model would not be suitable for monitoring quantitatively outcome of therapy by magnetic resonance imaging. It is however well adapted for the evaluation and optimization of MRI techniques or protocols intended to detect early changes of bone marrow produced by septic or aseptic infarct.

Adipose Tissue↗
PubMed1993

Influence of the pre-treatment duration of infection on the efficacies of various antibiotic regimens in experimental streptococcal endocarditis.

The influence of the pre-treatment duration of infection on the efficacies of three different antibiotic regimens was investigated in a rabbit model of subacute endocarditis caused by a novel, nutritionally-variant species, Streptococcus adjacens strain GaDT. Treatment was initiated either 6 or 10 days after bacterial inoculation (days 7 and 11 respectively) and comprised procaine penicillin (150,000 IU/kg bd), alone or combined with tobramycin (12 mg/kg od), teicoplanin (10 mg/kg bd), all administered by the intramuscular route for 4 days. The MICs and MBCs of penicillin, tobramycin and teicoplanin were 0.015 and 1 mg/L, 8 and 16 mg/L and 0.25 and 256 mg/L respectively. In the control rabbits, the mean (+/- S.D.) weights of the vegetations were 25 +/- 16 mg on day 7 and 45 +/- 34 mg on day 11 (P = 0.06). The mean (+/- S.D.) reductions in the number of cfu in the vegetations of the treated groups of animals after completion of therapy which had been started on days 7 and 11, compared with the mean numbers of cfu in the vegetations of the untreated controls on days 7 and 11 (delta log10 cfu/g), were 4.0 +/- 1.3 and 2.1 +/- 1.5 respectively for penicillin (P < 0.05), 3.2 +/- 1.8 and 2.4 +/- 1.8 respectively for teicoplanin and 5.4 +/- 1.2 and 5.2 +/- 1.2 respectively for the combination of penicillin and tobramycin. The increase in the size of the vegetations and changes in the metabolism of the bacteria within the vegetations between days 7 and 11, as demonstrated by electron microscopy, might explain why penicillin was more effective earlier in the course of the disease and why the influence of the duration of infection before treatment was initiated, varied according to the antibiotic regimen. These results suggest that the use of bactericidal regimens, such as the combination of penicillin and tobramycin, which are equally effective in reducing the bacterial counts in vegetations which have been infected for both long and short periods could minimize the risk of relapse in patients with endocarditis in whom there have been long delays before initiating treatment and/or who have large vegetations.

Animals↗
PubMed1993

Pharmacokinetic and pharmacodynamic aspects of therapy of experimental endocarditis.

Bacterial endocarditis is difficult to cure because of poor penetration of antibiotics into infected vegetations, altered metabolic state of bacteria within the lesion, and absence of adequate host-defense cellular response, that could cooperate with antibiotic action. Two main aspects are discussed for their effect on human therapy: (1) the kinetics of antibiotic diffusion into vegetations, with a special reference to the data obtained with autoradiography, and (2) the specificity of some pharmacodynamic aspects of antibiotics in endocarditis, including the clinical consequences of these two parameters on antibiotic dosing regimens and length of therapy.

Animals↗
PubMed1991

Ceftriaxone diffusion into cardiac fibrin vegetation. Qualitative and quantitative evaluation by autoradiography.

Heterogeneous diffusion of some antibiotics into fibrin rich infectious processes is one explanation of the difficulty to cure infections such as endocarditis. Ceftriaxone is a beta lactam antibiotic, potentially useful due to a broad spectrum of activity and its long elimination half-life. We investigated by means of autoradiography the diffusion of labelled ceftriaxone into large infected cardiac vegetations obtained in a rabbit model of endocarditis. Ten d after infection 250 microCi 14C ceftriaxone was injected over 30 min. Thirty min after the end of infusion (T30) vegetation/blood radioactivity ratio was 0.58 +/- 0.4 (n = 3). At T200, radioactivity decreased approximatively 3-fold, in blood and in vegetations simultaneously. Autoradiography showed that at T30, ceftriaxone was 20-30 times more concentrated at the periphery of vegetation than in the core. Autoradiography obtained at T200 showed a progressive diffusion toward the core. The diffusion gradient may explain the fact that high local concentrations are necessary to sterilize vegetations. The pattern of diffusion of antibiotics in fibrin is an important pharmacokinetic parameter for predicting in vivo activity.

Animals↗