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Biomedical subjects

M F Michel

Publications and source records attributed to M F Michel.

At least 91 records · Page 5Linked to original sources

Evaluation of an enzyme immunoassay for the diagnosis of chlamydial infections in urogenital specimens.

A total of 194 male urethral and 402 cervical specimens were obtained from patients at the venereal disease outpatient clinic of University Hospital, Rotterdam, The Netherlands, to evaluate the IDEIA test (Boots Celltech) for the detection of chlamydial infections. The prevalences of culture-positive males and females were 17.5 and 8.2%, respectively. The respective overall sensitivities and specificities found were 67.6 and 93.7% for the males and 63.6 and 93.8% for the females. The highest sensitivity (83.3%) was found in male patients with more than 20 leukocytes per field in the sediment of the first-voided urine (magnification, X250) and in women with more than 10 leukocytes per field in a cervical Gram stain (magnification, X800). However, in men without urethritis and in women with fewer than 10 leukocytes per field in the Gram stain, sensitivities of 44.4 and 40%, respectively, were found. Culture-positive, IDEIA-negative results were predominantly observed in samples with few inclusions in the culture.

Antibodies, Monoclonal↗

Comparison of oral treatment of uncomplicated urogenital and rectal gonorrhoea with cefuroxime axetil ester or clavulanic acid potentiated amoxycillin (Augmentin).

In a randomised study of two drugs for the oral treatment of uncomplicated urogenital and rectal gonorrhoea the therapeutic effect of cefuroxime axetil ester (CAE) and amoxycillin plus clavulanic acid (A + C) was compared. Cefuroxime axetil ester 1.5 g was given to 129 men and 118 women. Amoxycillin 3.0 g and clavulanic acid 0.25 g was given to 131 men and 122 women. Both treatments were combined with probenecid 1.0 g and administered in a single oral dose. Of the 500 patients thus treated, 376 were assessable. In the group taking CAE, failure rates were 0.9% for the men and 0% for the women; and the overall failure rate was 0.5%. In the group taking A + C the equivalent failure rates were 4.6%, 1.2%, and 3.1%. The differences were not significant. Penicillinase producing Neisseria gonorrhoeae (PPNG) was isolated from 5.6% of the assessable patients. All 10 PPNG infections in the group taking CAE and four of 11 PPNG infections in the group taking A + C were cured. These numbers were too small to draw a definite conclusion about the efficacy of both drugs in this type of infection. Postgonococcal urethritis was observed in 35% of the men in the group taking CAE and in 32% of those in the group taking A + C. Side effects were noted in 38% of the group taking CAE and 28% of the group taking A + C. Nausea and vomiting were more commonly observed in the group taking CAE; and diarrhoea was more commonly observed in the group taking A + C.

Administration, Oral↗

Bactericidal effect of combinations of cephalosporins with tobramycin on clinical isolates of Escherichia coli, Klebsiella and Staphylococcus aureus.

The antimicrobial activities of the cephalosporins cefazolin, cefotaxime, moxalactam or ceftazidime in combination with tobramycin against clinical isolates of E. coli, of Klebsiella, of beta-lactamase-negative and beta-lactamase-producing S. aureus strains were compared in vitro by the checkerboard technique. Antibiotic dilutions differed by small arithmetic increments. Favourable interactions occurred with each bacterial species. This trend applied to third-generation cephalosporins against E. coli and Klebsiella as well as to cefazolin against S. aureus. The antibiotics with already the highest intrinsic activity generally exhibited also the most favourable interaction.

Cephalosporins↗

Amiodarone-induced enhancement of doxorubicin and 4'-deoxydoxorubicin cytotoxicity to rat colon cancer cells in vitro and in vivo.

The mechanisms of the resistance of intestinal cancer to anthracyclines were studied on an experimental model of rat colon cancer cells. The accumulation of anthracyclines in the nucleus of living cancer cells was observed by fluorescence microscopy. This accumulation depended on both the capacity of anthracyclines to penetrate into the cell and the activity of an efflux mechanism extruding the drug from the cell. We found that 4'-deoxydoxorubicin was superior to 4 other anthracyclines in its capacity to penetrate into confluent colon cancer cells. Amiodarone, an antiarrhythmic agent used in cardiology, inhibited the efflux mechanism efficiently and increased the toxicity of anthracyclines to the colon cancer cells. Association of amiodarone and 4'-deoxydoxorubicin was able to cure 5 of 13 rats that had been inoculated i.p. previously with syngeneic colon cancer cells. This association could be of interest in the treatment of human colon cancer.

Adenocarcinoma↗

Interaction between two cellular subpopulations of a rat colonic carcinoma when inoculated to the syngeneic host.

From a single, chemically-induced rat colonic carcinoma, two subpopulations of tumor cells have been isolated. When injected into syngeneic rats, TR cells give rise to progressive tumors in most of the animals, whereas TS cells give rise to no tumors or to tumors which regress in less than 30 days. TS cells inhibit the growth of TR tumors, whether they are injected before TR cells or simultaneously, at a different site or mixed with the TR cells. Lymph nodes and spleen lymphocytes from animals having rejected TS tumors also inhibit TR-cell growth. On the other hand, TS cells are able to give rise to progressive tumors when they are injected into rats bearing established TR tumors. Lymph nodes and spleen cells of TR tumor-bearing rats are able to enhance TS cell growth. These results suggest that subpopulations of cancer cells contained in the same tumor interact with each other through their effect on the host immune system. The growth of a whole tumor probably depends not only on the growth potential of each constituent subpopulation, but also on the interaction between the subpopulations themselves.

Adenocarcinoma↗

Evaluation of the direct fluorescent antibody test for diagnosis of chlamydial infections.

The direct fluorescent antibody test and two culture methods were compared for accurate diagnosis of chlamydial infections. Using the same samples, 109 were found to be positive in the microtitre method with the direct confirmation test without subpassage, whereas 66 were positive in the vial method with Giemsa staining and subpassage. The direct test was evaluated for accuracy using cervical and male urethral specimens. Specimens for culture were obtained prior to sampling for the direct test. For cervical samples the sensitivity of the direct test, with the vial method taken as reference, appeared to be 72.2% with a specificity of 93.5%. With the microtitre method as standard, these values were 55.9% and 91.3%, respectively for females, and for male patients 49% and 95.6%, respectively. For cervical samples, in which sampling for the direct test was carried out prior to sampling for culture, the values were 46.3% and 93.2% respectively. Both culture method and study population influenced the sensitivity of the direct test. According to our findings, the direct test cannot replace the culture method for diagnosis of chlamydial infections.

Antigens, Bacterial↗

Solid-phase enzyme immunoassay for detection of Chlamydia trachomatis.

The prototype of a solid-phase enzyme immunoassay for the detection of Chlamydia trachomatis antigen was tested in 403 men and 135 women attending a venereal disease clinic. Culture on HeLa 229 cells was used as reference method. In men the overall sensitivity and specificity of the enzyme immunoassay was 70% and 98.5% respectively. In the 158 men with non-gonococcal urethritis the sensitivity and specificity was 73% and 96.5% respectively, in the 31 men with post-gonococcal urethritis 82% and 100%, in the 48 men with gonococcal urethritis 67% and 100%, in the 125 men with discharge but normal urinary sediment 54% and 99.1% and in the 41 men with no signs or symptoms 50% and 100%. In women the sensitivity and specificity of the assay was 70% and 92% respectively. On account of the low degree of sensitivity in both men and women and the low degree of specificity in women the prototype of the enzyme immunoassay is not yet considered suitable for clinical use. An improved model is being developed.

Antigens, Bacterial↗

Free versus liposome-entrapped ampicillin in treatment of infection due to Listeria monocytogenes in normal and athymic (nude) mice.

Efficacy of liposomal as compared with free ampicillin in treatment of infection due to Listeria monocytogenes was studied in normal and congenitally athymic (nude) mice. After intravenous injection the multilamellar vesicles used were taken up mainly by liver and spleen, the target organs of L. monocytogenes. Injection of empty liposomes in two doses of 2 mumol of vesicle lipid each, administered at 40 and 112 hr after bacterial inoculation, did not influence the course of listerial infection in normal and nude mice. In normal mice liposomal entrapment of ampicillin resulted in significant improvement in the antibiotic's therapeutic index. The use of liposomal ampicillin at a total dose of 0.54 mg (two doses of 0.27 mg each) resulted in a therapeutic effect similar to that resulting from a total dose of 48 mg of free ampicillin (eight doses of 6 mg each). However, neither ampicillin treatment schedules cured infections in nude mice.

Ampicillin↗

Therapeutic efficacy of continuous versus intermittent administration of ceftazidime in an experimental Klebsiella pneumoniae pneumonia in rats.

An experimental Klebsiella pneumoniae pneumonia in rats was used to study the influence of continuous or of intermittent (8-hr intervals) administration of ceftazidime on therapeutic efficacy. Antimicrobial response was evaluated with respect to the calculated total daily dose that protected 50% of the animals from death (PD50) until 16 days after termination of a four-day treatment. When antibiotic treatment was started 5 hr after bacterial inoculation, the PD50 values after continuous and after intermittent administration of ceftazidime were 0.36 and 1.42 mg/kg per day, respectively (P less than .001). With a delay in the administration of the antibiotic to 34 hr after inoculation, the respective PD50 values were 1.08 and 13.06 mg of ceftazidime/kg per day (P less than .001). These studies show an improved therapeutic efficacy that increased with a delay in treatment when ceftazidime was administered by continuous infusion as compared with administration at 8-hr intervals. Continuous administration of PD50 doses of ceftazidime resulted in serum levels that were constantly below the MIC of the infecting Klebsiella strain.

Animals↗

Relevance of serum protein binding of cefoxitin and cefazolin to their activities against Klebsiella pneumoniae pneumonia in rats.

An experimental Klebsiella pneumoniae pneumonia in rats was used to study the effect of protein binding of cefoxitin and cefazolin on their therapeutic activity. Both cephalosporins were similar with respect to their antimicrobial activity against the K. pneumoniae in vitro, but they differed in their degree of protein binding, being 34% for cefoxitin and 89 to 93% for cefazolin in uninfected rats and 24 and 71 to 83%, respectively, in infected rats. Various doses of these agents were administered by continuous infusion, which started 5 h after bacterial inoculation and continued for 65 h. Antimicrobial response was evaluated with respect to the numbers of bacteria recovered from lung and blood at the end of treatment. An inhibitory effect of protein binding on the in vivo antimicrobial activity was demonstrated. Cefoxitin was therapeutically effective at a constant plasma level that reached the MIC. To obtain a similar effect with cefazolin the plasma level of that drug had to be increased to a concentration more than three times the MIC.

Animals↗

Prevalence of antibodies to Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma hominis in infertile women.

A total of 57 infertile women, who had been referred for in vitro fertilisation or for diagnostic laparoscopy, were tested for the presence of antibodies to Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma hominis. Four were excluded from the study. Of the remaining 53, 33 had laparoscopically obvious tubal disorders, such as adhesions, distal occlusions and strictures, and 20 did not. Antibodies to C trachomatis were found in 7/33 (21.2%) v 0/20, antibodies to N gonorrhoeae in 20/38 (60.6%) v 5/20 (25%), and antibodies to M hominis in 18/24 (75%) women with tubal disorders v 13/19 (68.4%) of those with no disorder. Antibodies to C trachomatis and N gonorrhoeae were significantly (p less than 0.05) more common in women with tubal disorders. The high prevalence of antibodies to N gonorrhoeae in infertile women without tubal disorders suggests that ciliated tubal epithelium is damaged after inflammation without this being laparoscopically visible. Our results confirm the important role of N gonorrhoeae and C trachomatis in the aetiology of infertility after tubal inflammation.

Adult↗

Pharmacokinetics of tobramycin in patients with cystic fibrosis. Implications for the dosing interval.

The pharmacokinetics of tobramycin were evaluated in 15 patients (8 to 22 years of age) with cystic fibrosis (CF). A dose of 3.0 to 3.3 mg/kg of body weight was given intravenously over 20 minutes, and concentrations in serum were followed up to eight hours after initiation of the infusion. In the calculation of pharmacokinetic parameters, a two-compartment open model was used. The elimination half-life of the drug was highly inversely correlated with age (p less than 0.0004), and body weight (p less than 0.00002). Total body clearance (TBC), and volume of distribution at steady state (VDSS) were directly correlated with age and body weight. However, when TBC and VDSS were corrected for BSA, no correlation could be demonstrated. The mean one-hour and eight-hour serum concentrations of tobramycin were 5.40 and 0.45 microgram X ml-1, respectively. Between patients, considerable differences were found in the time after administration at which the serum concentration decreased below 1 microgram X ml-1. This interpatient variation has clinical implications for tobramycin therapy in CF, in particular for the dosing interval.

Adolescent↗

Efficacy of continuous versus intermittent administration of penicillin G in Streptococcus pneumoniae pneumonia in normal and immunodeficient rats.

An experimental Streptococcus pneumoniae pneumonia was used to study the influence of continuous versus intermittent administration of penicillin G on therapeutic efficacy in normal rats and in rats whose phagocytic capacities were impaired by decomplementation with cobra venom factor. Response to antibiotic treatment was evaluated with respect to numbers of bacteria in left lung, blood and pleural fluid. Penicillin treatment was started 36 h after bacterial inoculation, and continued for four days. With intermittent intramuscular administration of penicillin normal rats were cured after daily doses of 4 mg/kg at 12 h intervals, whereas decomplemented rats recovered only after daily doses of 100 or 102 mg/kg at 12 h or 8 h intervals, respectively. When penicillin was administered by way of continuous infusion, daily doses of 3.5 mg/kg were required for a cure of infections in both normal rats and in decomplemented rats. This treatment resulted in a constant level of 0.05 micrograms of penicillin per ml, which was slightly above the minimum bactericidal concentration for the infecting strain. These findings show that maintenance of bactericidal levels of penicillin were particularly important in curing severe infection in rats with impaired defense.

Animals↗

Treatment of non-complicated urogenital, rectal and oropharyngeal gonorrhoea with intramuscular cefotaxime 1.0 g or cefuroxime 1.5 g.

In an open randomized study in a large Rotterdam male and female population (n = 1500), suffering from uncomplicated urogenital, rectal and oropharyngeal gonorrhoea treatment with cefotaxime 1.0 g proved to be more effective than with cefuroxime 1.5 g in all patients studied. However, statistically significant differences between the failure rates of the cefotaxime and the cefuroxime treatment were found only for all male and female patients, in urethral or urogenital and rectal infections in this group, for all male patients, and in urethral infections in men. Failure rates were low (1.7 and 5.6%, respectively for cefotaxime and cefuroxime). Oropharygeal gonorrhoea responded less well than urethral or urogenital and rectal gonorrhoea. Both drugs were very effective in the eradication of uncomplicated gonococcal infections caused by both non-beta-lactamase producing and beta-lactamase producing gonococci. High (greater than 30%) post-gonococcal urethritis rates were observed. Side-effects were minor.

Cefotaxime↗

Tolerance percentage as a criterion for the detection of tolerant Staphylococcus aureus strains.

In this study, the degree of tolerance was determined in several populations of Staphylococcus aureus isolates. The degree of tolerance of a staphylococcal strain can be established in a reproducible way by exposing the strain to increasing concentrations of a beta-lactam antibiotic and determining the number of surviving bacteria at each concentration. The number of surviving bacteria was expressed as a fraction of the initial inoculum. By this technique, it appears that for each strain the value of the surviving fraction stabilized above a certain concentration of the antibiotic. This value was called the tolerance percentage of the strain. In 64 S. aureus strains isolated from blood cultures in 1982, the tolerance percentages, after exposure to methicillin, varied from less than or equal to 0.1 to 6; 28% of the strains showed a tolerance percentage of less than or equal to 0.1, and 12.5% showed a tolerance percentage of greater than or equal to 2. Similar tolerance percentages were found with cloxacillin, nafcillin, cephalothin, and penicillin. Strains with a tolerance percentage of greater than or equal to 2 showed slow killing and lysis in the presence of a high methicillin concentration. A tolerance percentage of 2 appeared to be the breakpoint between susceptible and tolerant strains. Older collections of S. aureus strains, dating from the years 1951 to 1953 and 1957 to 1958, also included strains with a survival percentage of greater than or equal to 2, thus indicating that tolerance of S. aureus to beta-lactam antibiotics is not a new phenomenon.

Cephalothin↗