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Biomedical subjects

M Boeckh

Publications and source records attributed to M Boeckh.

At least 55 records · Page 3Linked to original sources
PubMed1996

Cytomegalovirus pp65 antigenemia-guided early treatment with ganciclovir versus ganciclovir at engraftment after allogeneic marrow transplantation: a randomized double-blind study.

To determine whether cytomegalovirus (CMV) antigenemiaguided ganciclovir treatment may be as effective, may require less treatment, and thus may cause less marrow toxicity than ganciclovir administered at engraftment, 226 marrow transplant recipients were randomized at engraftment to receive placebo (antigenemia-ganciclovir group) or ganciclovir (ganciclovir group) until day 100 in a double-blind study. In patients with antigenemia of 3 or more positive cells in 2 slides and/or viremia, study drug was discontinued and ganciclovir was started for at least 3 weeks or until negative CMV antigenemia and resumed only if antigenemia recurred. More patients in the antigenemia-ganciclovir group developed CMV disease before day 100 after transplantation compared with the ganciclovir group (14% v 2.7%, P = .002). Of the 16 patients with CMV disease before day 100 in the antigenemia-ganciclovir group, 10 (8.8%) had disease before or during the first episode of antigenemia and 6 (5.3%) developed disease after discontinuation of ganciclovir. Untreated low-grade antigenemia progressed to CMV disease in 19% of patients with grade 3-4 compared with 0% of patients with grade 0-2 acute graft-versus-host disease (P = .04). There was no significant difference in CMV disease by day 180 after transplantation and thereafter. CMV-related death, transplant survival, and neutropenia were not significantly different between the groups. In the ganciclovir group, more invasive fungal infections occurred (P = .03) and more ganciclovir was used (P < .0001). Thus, delaying the start of ganciclovir until highgrade antigenemia and discontinuing ganciclovir based on negative antigenemia results in more CMV disease by day 100 than ganciclovir administered at engraftment. However, ganciclovir at engraftment is associated with more early invasive fungal infections and more late CMV disease resulting in similar survival rates.

Adolescent↗
PubMed1996

Hepatic mucormycosis in a bone marrow transplant recipient who ingested naturopathic medicine.

This case report describes a bone marrow transplant recipient in whom hepatic zygomycosis developed after ingestion of multiple naturopathic medicines. Mucor was isolated from the patient's liver aspirate and from one of the naturopathic medicines. Arbitrary-primed polymerase chain reaction (PCR) analyses were performed on the Mucor isolates from the patient's liver aspirate and from his naturopathic medicine to see if they were genotypically related. Mucor indicus was the species identified in both the patient's liver aspirate and the naturopathic medicine. Arbitrary-primed PCR analysis revealed that these isolates were genotypically identical. We conclude that this bone marrow transplant recipient acquired hepatic mucormycosis from ingestion of a naturopathic medicine containing Mucor.

Adult↗
PubMed1996

Cytomegalovirus pp65 antigenemia after autologous marrow and peripheral blood stem cell transplantation.

In a prospective study, the cytomegalovirus (CMV) pp65 antigenemia assay was compared with detection of CMV by blood culture in 67 consecutive CMV-seropositive patients undergoing autologous marrow or peripheral blood stem cell transplantation. Antigenemia occurred in 26 patients (38.8%) a median of 33 days (range, 12-74) after transplant. Viremia was detected in 5 patients (7.5%) a median of 30 days (range, 12-74) after transplant and was treated with ganciclovir in 3. Antigenemia occurred sporadically at low levels (< 5 positive cells/slide) in 19 patients (28.4%) and never resulted in CMV disease. Two of 7 patients who presented with or progressed to antigenemia of > 5 positive cells/slide developed fatal CMV pneumonia 8 days later. Neither patient had CMV viremia before onset of pneumonia. Thus, quantitative CMV pp65 antigenemia may be useful in guiding antiviral treatment in seropositive autograft recipients.

Adult↗
PubMed1996

High-level sensitivity of quantitative pp65 cytomegalovirus (CMV) antigenemia assay for diagnosis of CMV disease in AIDS patients and follow-up.

Cytomegalovirus (CMV) antigenemia was evaluated in 174 patients positive for human immunodeficiency virus. Antigenemia could be detected in 96.7% of patients with CMV disease, 76.9% of patients suffering from a relapse of the disease, and 11.4% of asymptomatic patients with CD4 levels of < 100 cells per microliter. No antigenemia was detected in patients with CD4 levels of 250 to 500 cells per microliter. Specificity and the positive predictive value for CMV disease were increased only if more than 5 positive cells per slide were considered. However, CMV disease may also occur in patients with low-grade antigenemia.

AIDS-Related Opportunistic Infections↗
PubMed1995

Failure of high-dose acyclovir to prevent cytomegalovirus disease after autologous marrow transplantation.

In a retrospective study, the strategy of giving high-dose acyclovir (500 mg/m2 every 8 h intravenously) from day 5 before transplantation to day 30 after transplantation was evaluated in 266 cytomegalovirus (CMV)-seropositive autograft recipients. the incidence of CMV pneumonia was compared with that in 85 control patients who did not receive high-dose acyclovir. There was no significant difference in the incidence of CMV pneumonia between groups at day 100 (Kaplan-Meier estimates, 6.3% [acyclovir] vs. 7.7% [controls], P = .63) and day 200 after transplantation (7.6% vs. 13.1%, P = .32). The overall rate of patients who presented with CMV disease without preceding excretion from blood, urine, or throat was 77%. CMV pneumonia was fatal in 9 (56%) of 16 acyclovir recipients compared with 5 (63%) of 8 controls (P = 1.0). Survival after transplantation was not different between groups (P = .68). Thus, high-dose acyclovir does not appear to be effective for prevention of CMV disease after autologous transplantation.

Acyclovir↗
PubMed1994

Strategies for the prevention of cytomegalovirus disease after marrow transplantation.

The purposes of this review are to examine the epidemiology of disease due to cytomegalovirus (CMV) in recipients of autologous and allogeneic marrow transplants and to compare different antiviral regimens used for the prevention of such disease in recipients of allogeneic marrow transplants, with an emphasis on ganciclovir. In seven studies, ganciclovir reduced the incidence of CMV infection and disease after allogeneic marrow transplantation. In one study mortality after transplantation was reduced because of a decreased rate of CMV-related death among ganciclovir-treated patients. Ganciclovir was effective when given to all CMV-seropositive patients (prophylaxis) or to patients who were considered at high risk for CMV disease on the basis of a positive surveillance culture (early treatment). The effectiveness of ganciclovir for the prevention of CMV infection and disease is limited by drug-induced neutropenia. Experience with other antiviral agents, such as foscarnet, has been limited. Initial studies of the adoptive transfer of CMV-specific CD8+ cytotoxic T cells have been conducted. In short, ganciclovir is currently effective for the prevention of CMV disease in allogeneic marrow transplant recipients, but its usefulness is limited by neutropenia. Future studies must be aimed at confining the toxicity of ganciclovir to patients at the highest risk for CMV disease.

Bone Marrow Transplantation↗
PubMed1994

Frequency distribution of cytomegalovirus envelope glycoprotein genotypes in bone marrow transplant recipients.

Using restriction analysis of polymerase chain reaction (PCR)-amplified DNA, the cytomegalovirus (CMV) envelope glycoprotein (gB and gH) genotypes were determined for virus isolates from 128 bone marrow transplant recipients with fatal or nonfatal CMV. All isolates could be assigned to one of four gB and gH genotypes previously identified by DNA sequencing studies. Isolates of gB type 1 were more commonly found to be of gH type 2, whereas gB types 2-4 were more commonly linked to gH type 1. A small frequency of recombination with gB was detected by restriction analysis of DNA from variable regions of the gp55 and gp116 domains. Multiple isolates from various sites of 29 patients were typed and, with three exceptions, the gB genotype remained constant in all isolates from a single patient. Patients who survived CMV infection more commonly shed virus of gB type 1 than those who died (P = .003). This significant difference of gB types among patient subsets is unexplained but raises the possibility that gB genotypes may serve as a marker for pathogenicity of CMV strains in marrow transplant patients.

Adolescent↗
PubMed1994

Factors influencing detection of quantitative cytomegalovirus antigenemia.

Of 20 blood specimens testing positive for cytomegalovirus antigen after immediate processing, 19 (95%) remained positive when kept at room temperature for 24 h before processing. Quantitative antigenemia decreased by an average of 44% after storage. Compared with acetone fixation, formaldehyde fixation showed improved readability, fewer artifacts, and a higher degree of sensitivity.

Acetone↗
PubMed1994

Early detection and treatment of cytomegalovirus infections in marrow transplant patients: methodological aspects and implications for therapeutic interventions.

Major advances have been made in the early detection of CMV infection after marrow transplant by the introduction of the polymerase chain reaction (PCR) and the CMV antigenemia assay. Numerous studies have established clinical correlations of these techniques but there is a need for technical standardization as assay sensitivity may vary considerably with different modifications. Current prevention strategies for CMV disease after marrow transplantation, including options on how the antigenemia assay and PCR assays may be used in early treatment strategies, are discussed.

Acyclovir↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗