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Biomedical subjects

M Boeckh

Publications and source records attributed to M Boeckh.

11 recordsLinked to original sources

Cytomegalovirus antigen detection in peripheral blood leukocytes after allogeneic marrow transplantation.

Detection of cytomegalovirus (CMV) antigenemia was compared with shell vial centrifugation cultures for rapid detection of CMV infection. In a prospective study, 59 CMV seropositive patients were monitored weekly during the first 100 days after allogeneic marrow transplantation for virus excretion from urine, throat, and blood and for antigenemia by direct staining of peripheral leukocytes using an antibody pool directed against pp 65. Antigenemia was present in 21 of 22 patients with culture-proven CMV infection and in 3 of 37 without culture-proven CMV infection (sensitivity 95%, specificity 91%). The median time of onset of antigenemia and shell vial cultures was day 47 and 55 after transplant, respectively (P = .0006). Among patients who developed CMV disease without preceding cultures, antigenemia was detected in all patients with CMV pneumonia (N = 6) and in two of three patients with gastrointestinal disease by a median of 10 and 7 days, respectively, before the onset of disease (P = .0002). Levels of antigenemia were significantly higher in patients with disease or viremia than in patients with excretion from urine or throat (P less than .05). Whether the antigenemia assay is more sensitive than rapid culture methods to focus antiviral prophylaxis in marrow transplant patients must be determined in controlled studies.

Antigens, Viral

Pharmacokinetics of loracarbef and interaction with acetylcysteine.

A study was conducted to evaluate the pharmacokinetics of loracarbef, a new synthetic oral carbacephem antibiotic, following administration of 400 mg in normal male volunteers. The influence of food and possible interaction with acetylcysteine, a commonly used mucolytic agent, was also studied. Twelve healthy volunteers participated in the study and randomly received an oral dose of 400 mg loracarbef in the fasting state, 400 mg loracarbef following a standard breakfast or 400 mg loracarbef together with 200 mg acetylcysteine in granular form. Serum and urine concentrations were determined over 24 h by means of a bioassay. Loracarbef was well tolerated. Four volunteers complained of mild, transient headache. The substance was well absorbed with a mean peak level of 19.21 +/- 3.94 mg/l in the fasting state; it was primarily excreted in active form via the kidneys (urine recovery/24 h: 86-92%). The elimination half-life ranged from 70.3 to 102.0 min. Acetylcysteine had no effect on the absorption of loracarbef. The intake together with food delayed the absorption time, but had no influence on the bioavailability.

Acetylcysteine

Pharmacokinetics of roxithromycin and influence of H2-blockers and antacids on gastrointestinal absorption.

The pharmacokinetics of roxithromycin (300 mg orally) and the influence of the antacid aluminum magnesium hydroxide and the H2-blocker ranitidine on bioavailability of roxithromycin in ten healthy volunteers were studied. Pharmacokinetics after a single dose of roxithromycin were characterized by high peak serum levels (9.1 +/- 2.1 mg/l) and a long elimination half-life (7.2 +/- 2.5 h), resulting in a large area under the curve (116.9 +/- 32.7 mg h/l). High inter- and intraindividual variations were found for both the absorption time and the elimination half-life. The bioavailability of roxithromycin was not affected by coadministration with antacids or ranitidine.

Adult

Comparison of MRC-5 and U-373MG astrocytoma cells for detection of cytomegalovirus in shell vial centrifugation cultures.

U-373MG astrocytoma cells are susceptible to human cytomegalovirus (CMV) infection and offer the advantage of a continuous cell line for clinical laboratory use. U-373MG to MRC-5 cells for detection of CMV by centrifugation culture were therefore compared. At 20 h, 10 (6.1%) versus 12 (7.4%) of 163 clinical specimens were positive for CMV, and at 40 h, 12 (7.4%) versus 17 (10.4%) were positive in U-373MG and MRC-5 cells, respectively. Substantial toxicity was found in U-373MG cells (84%) when inoculated with blood specimens. For detection of CMV in centrifugation culture, MRC-5 cells are superior due both to higher sensitivity and lesser toxicity.

Astrocytoma

Pharmacokinetics and serum bactericidal activities of quinolones in combination with clindamycin, metronidazole, and ornidazole.

To enhance the antimicrobial spectrum of the quinolones against anaerobic organisms and gram-positive bacteria, we investigated in two studies the parenteral combinations of ciprofloxacin (200 mg) and ofloxacin (200 mg) with metronidazole (500 mg) or clindamycin (600 mg) and the oral combinations of enoxacin (400 mg) and fleroxacin (400 mg) with metronidazole (400 mg), clindamycin (300 mg), or ornidazole (500 mg) (only with fleroxacin). The pharmacokinetics and serum bactericidal activities (SBAs) against 5 aerobic and 2 anaerobic species (total, 58 strains) were determined in two groups of 10 healthy volunteers by using a randomized crossover study design. The additions of metronidazole, clindamycin, and ornidazole did not affect the pharmacokinetics of the quinolones. The combination of clindamycin with ciprofloxacin, ofloxacin, and, to a lesser extent, fleroxacin resulted in an increase of the SBA against gram-positive strains (mean peak titers): Staphylococcus aureus, ciprofloxacin alone, 1:5.5; ciprofloxacin-clindamycin, 1:19.9; ofloxacin alone, 1:3.6; ofloxacin-clindamycin, 1:17.5; fleroxacin alone, 1:4.3; fleroxacin-clindamycin, 1:8.1; Streptococcus pneumoniae (fleroxacin and enoxacin were not tested), ciprofloxacin alone, 1:2.0; ciprofloxacin-clindamycin, 1:53; ofloxacin alone, 1:2.6; and ofloxacin-clindamycin, 1:49.2. The high SBA of quinolones against gram-negative bacteria was not affected by the combinations; however, relatively low activities against Pseudomonas aeruginosa were detected. In general, against anaerobic bacteria, low bactericidal activities were determined in both studies (mean peak titers ranged from 1:2.1 to 1:3.1; mean trough titers range from 1:2.0 to 1:2.9). In clinical settings with severe mixed infections, a parenteral therapy consisting of modern quinolones together with clindamycin or imidazole derivatives seems to be active and offers no obvious interactions.

4-Quinolones

Comparative pharmacokinetics of glycopeptide antibiotics, and the influence of teicoplanin on granulocyte function.

The glycopeptide antibiotics teicoplanin and vancomycin differ in their pharmacokinetic properties. Teicoplanin is characterized by a high and prolonged serum concentration as a result of its long elimination half-life, which can be explained by high serum protein binding and renal tubular resorption. The apparent volume of distribution of teicoplanin is much larger than the extracellular space of the human body, indicating intracellular accumulation in different tissues. Elimination is primarily via the kidneys, though 15-20% is eliminated by non-renal mechanisms. Vancomycin has a shorter elimination half-life and lower protein binding than teicoplanin. At therapeutically relevant serum concentrations, teicoplanin has no influence on superoxide anion production and enzyme release by granulocytes.

Cells, Cultured

Combination effects of ciprofloxacin, clindamycin, and metronidazole intravenously in volunteers.

Despite the broad antibacterial spectrum of ciprofloxacin, most anaerobic organisms are resistant to the drug, whereas several gram-positive organisms are only moderately susceptible. Thus, in some clinical situations, combined treatment with ciprofloxacin and metronidazole or clindamycin could be useful. Therefore, the pharmacokinetics and serum bactericidal activities of ciprofloxacin in combination with clindamycin or metronidazole were investigated using a randomized crossover study design in 10 healthy volunteers. Ciprofloxacin (200 mg) was administered alone and in combination with clindamycin (600 mg) or metronidazole (500 mg); all drugs were given intravenously over 30 minutes. Serum and urine concentrations of the substances were measured using standard methods (high-performance liquid chromatography or gas chromatography). Blood samples for determination of serum bactericidal activity against five different aerobic and two anaerobic bacterial species (a total of 58 strains) were obtained one hour and six hours after drug infusion. All values were statistically analyzed by use of the Student t test.

Adult

Quinine dosage in severe malaria with renal failure necessitating haemodialysis.

For therapy of severe malaria with renal failure, a 2/3 reduction in the usual intravenous dose of quinine is recommended (600 mg per 24 h instead of 600 mg per 8 h). Two patients with severe malaria and renal failure requiring dialysis have been treated. The half-life was not prolonged (15 h). Quinine proved to be nondialysable. It was shown that this dose of quinine tended to lead to a low level in blood (under 10 mg.l-1). A normal dose of quinine (2 x 15 mg/kg per day) is therefore recommended for malaria therapy, even in cases with renal failure requiring haemodialysis, in order to attain the desired plasma level (5 to 15 mg.l-1).

Chromatography, High Pressure Liquid

Pharmacokinetics and serum bactericidal activity of vancomycin alone and in combination with ceftazidime in healthy volunteers.

The pharmacokinetics and serum bactericidal activity of vancomycin alone and in combination with ceftazidime were investigated in 10 healthy volunteers. The pharmacokinetic parameters showed no significant differences (P less than 0.05) between single and combined administration. No antagonistic effects were observed in serum bactericidal activity with the combination against 20 gram-positive and 20 gram-negative locally isolated bacteria. A titer of greater than or equal to 1:8 was generated by the combination against all test strains except enterococci. Seven of ten volunteers developed a typical "red man's syndrome" during the administration of 1.0 g of vancomycin.

Adult