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Biomedical subjects

C Bührer

Publications and source records attributed to C Bührer.

65 records · Page 4Linked to original sources
PubMed1990

Central nervous system relapse prevention in 1165 standard-risk children with acute lymphoblastic leukemia in five BFM trials.

In treatment of childhood ALL, prevention of CNS relapse by cranial irradiation is followed by considerable long-term sequelae. In the three ALL-BFM (Berlin-Frankfurt-Münster) trials 70, 76, and 79, employing radiotherapy (8.5 Gy craniospinal, 18 or 24 Gy cranial irradiation) in all arms, the incidence of CNS relapses (isolated and combined) in standard-risk patients (SR, 60% of all children) was consistently less than 6%. A risk factor (RF) calculated from absolute blast number, liver, and spleen size at diagnosis was used to stratify patients in the subsequent trials ALL-BFM 81 and 83. In ALL-BFM 81, SR patients (RF less than 1.2) were randomized to receive 18 Gy cranial irradiation or intermediate-dose i.v. methotrexate (ID-MTX) (4 x 0.5 g/m2). In ALL-BFM 83, the SR group was further subdivided into group SR low (SR-L, RF less than 0.8) and group SR high (SR-H, RF 0.8 - less than 1.2). SR-L patients received no irradiation, and were tested by randomization for the effectiveness of an intensive reinduction regimen (protocol III). SR-H patients were randomized for 12 or 18 Gy. The results were as follows: In patients of both trials with RF less than 0.8, radiotherapy could be replaced by ID-MTX plus protocol III. Without protocol III, relapses increased from 15.7% to 31.7%. Concomitantly, the fraction of relapses with CNS involvement increased from 26.7% to 36.4%. However, SR patients with RF between 0.8 and 1.2 could not be protected by reinduction alone (isolated/overall CNS relapse rate with irradiation, 4%/5%; without irradiation, 11%/22%). Dosages of 12 and 18 Gy were found to be equally protective.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Acute onset deafness in a 4-year-old girl after a single infusion of cis-platinum.

Dose-dependent reduction of auditory function mainly in the high frequency range has been described as a common adverse side effect of cis-platinum. Here we report on a 4-year-old girl with osteosarcoma of the right distal femur who developed acute bilateral deafness 3 days after a single infusion of high-dose cis-platinum (150 mg/m2) during preoperative chemotherapy. Sudden disabling ototoxicity should be considered when administering high-dose cis-platinum to young children.

Acute Disease↗
PubMed1990

Lymphocyte activation and expression of the human leucocyte-endothelial cell adhesion molecule 1 (Leu-8/TQ1 antigen).

The Leu-8/TQ1 antigen, recently shown to be the human equivalent of the murine MEL-14 lymph node homing receptor and now designated as leucocyte-endothelial cell adhesion molecule, LECAM-1, has been used to dissect T, B and natural killer (NK) cells into various subpopulations with different functional properties, such as suppressor-inducer (CD4+ Leu-8/TQ1+) or helper (CD4+ Leu-8/TQ1-) T lymphocytes. Diminished Leu-8/TQ1 antigen density has been reported after lymphocyte activation with B- or T-cell specific stimuli for several days. In the present study, we sought to determine the signal requirements for altered Leu-8/TQ1 expression. Exposure of freshly isolated peripheral blood lymphocytes to phorbol 12-myristate 13-acetate (PMA) and/or calcium ionophores was found to cause rapid down-regulation of the Leu-8 antigen, with little or no Leu-8 reactivity remaining 1 hr after simultaneous addition of PMA and calcium ionophores to the culture medium. TQ1 reactivity was changed in parallel with that of Leu-8. Leu-8 expression of T and B cells was sensitive to both PMA and calcium ionophores, whereas Leu-8 expression of NK cells was affected by PMA but not by the calcium ionophore A23187. The effect of PMA on Leu-8/TQ1 expression could be antagonized by pretreatment with the protein kinase C inhibitor, H7, whereas that of A23187 could not. Partial re-expression of the Leu-8 antigen was seen 3 days after addition of PMA alone but not when it was given together with calcium ionophores. After Leu-8 down-regulation induced by 1 hr treatment with PMA or calcium ionophores. Leu-8 re-expression was observed within 24 hr when stimuli were removed by washing. Activation of T cells with anti-CD3 antibody resulted in a partial reduction of Leu-8/TQ1 expression, first detectable after 1-3 hr of stimulation and maximal at 24 hr. Fully mitogenmic concentrations of concanavalin A (Con A) did not affect Leu-8 expression within the first hours of culture. Transient reduction of Leu-8 expression was seen 24 hr after supraoptimal dosages of Con A, but Con A-stimulated lymphocytes cultured for 4-12 days with interleukin-2 (IL-2) retained Leu-8/TQ1 reactivity to a similar degree as fresh cells. In contrast to Leu-8/TQ1, CD45RA expression was not altered after 1 hr treatment with PMA and/or calcium ionophores but gradually disappeared during 1 week after Con A stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens, CD↗
PubMed1990

A highly sensitive quantitative bioassay for human granulocyte-macrophage colony-stimulating factor.

Based on the granulocyte-macrophage colony-stimulating factor (GM-CSF) dependency of a newly established human myeloid cell line GM/SO, we developed a highly specific and sensitive bioassay for human GM-CSF. The presence of bioactive GM-CSF could be determined by measuring the formazan concentration produced from MTT by the cells that survived and proliferated in the presence of either natural or recombinant human GM-CSF. With this assay we were able to quantify the level of GM-CSF in two human sera as well as in conditioned media from human bladder cell carcinoma cell line 5637, a human fibroblast line, and phytohemagglutinin-stimulated peripheral blood mononuclear cells. The sensitivity of the assay allows measurement of concentrations of GM-CSF as low as 0.1 U/ml.

Biological Assay↗
PubMed1989

Immunophenotypic demonstration of two natural killer surface markers, H25 and H366, on fresh human leukemic cells.

Using a modified alkaline-phosphatase/antialkaline-phosphatase method for phenotyping fresh human leukemias, we could demonstrate peripheral blood and bone marrow-derived blast cells to specifically react with two monoclonal antibodies (MoAbs), H25 and H366, previously shown to recognize natural killer cells, activated T lymphocytes and a proportion of normal hematopoietic precursor cells. MoAbs H25 and H366 were found to identify the majority of leukemic cells in patients presenting with T-ALL, LGL leukemia, pre-B-ALL, CML, and AML, respectively.

Animals↗
PubMed1988

Anti-tumor efficacy of interleukin-2-activated killer cells in human neuroblastoma ex vivo.

We studied the ex vivo sensitivity of continuously cultured neuroblastoma cells from 3 different patients towards interleukin-2-induced cell-mediated cytotoxicity. A mean (+/- SD) target cell lysis (4 h 51Cr release) of 49 +/- 11, 46 +/- 8, and 32 +/- 11% in SMS-SAN, LA-N-1, and SK-N-BE2 cell lines, respectively, was achieved when neuroblastoma cells were co-cultured at an effector-to-target (E:T) ratio of 50:1 with peripheral blood mononuclear cells (PBMC) that had been preincubated for 4 days in the presence of recombinant interleukin-2 (rIL-2; 100 U/ml). Under identical conditions, 93 +/- 9% of Daudi cells (a standard target for rIL-2-activated killer cells) were lysed. Preincubation of rIL-2-induced PBMC cultures in the presence of irradiated neuroblastoma targets (LA-N-1, SK-N-BE2) resulted in a significant cytolytic augmentation. At E:T ratios of 50:1 and 10:1, day-4 rIL-2/LA-N-1-stimulated PBMC produced 69 +/- 7 and 41 +/- 11% lysis of LA-N-1 cells, as compared to 46 +/- 8 and 22 +/- (mean +/- SD) 7% lysis by untargeted PBMC that were preincubated with rIL-2 (100 U/ml) in the absence of LA-N-1 target cells (p less than 0.05). Co-incubation of rIL-2-induced PBMC preparations with irradiated LA-N-1 and SK-N-BE2 cells, respectively, did not significantly enhance the cytolytic activity against other neuroblastoma targets and the standard Daudi cell line (p greater than or equal to 0.3).(ABSTRACT TRUNCATED AT 250 WORDS)

Cytotoxicity, Immunologic↗
PubMed1988

Ewing's sarcoma: ex vivo sensitivity towards natural and lymphokine-activated killing.

We studied the ex vivo cell-mediated cytotoxicity of natural killer (NK) and lymphokine-activated killer (LAK) cells against continuously cultured Ewing's sarcoma cells from 3 different patients. Target cell lysis was measured in a 4-hour 51Cr radioisotope release assay. At an effector to target (E:T) ratio of 50:1, the mean (+/- 1 SD) cytolysis by fresh purified large granular lymphocytes (NK cells) was 20 +/- 8, 25 +/- 2, and 21 +/- 3% in Ewing's sarcoma cell lines 6647, 5838, and A4573, respectively. Under identical conditions, NK cells lysed 56 +/- 7% of K562 (a standard NK target), and 3 +/- 3% of Daudi (a standard NK-resistant LAK target). When compared to fresh unseparated peripheral blood mononuclear cells (PBMC), purified NK cells did not exhibit an enhanced cytotoxic reactivity against either Ewing's sarcoma target. In contrast, LAK cells (i.e., PBMC that were preincubated for 4 days in the presence of rIL-2) were highly cytotoxic against all three Ewing's sarcoma targets. LAK activity was dependent on the concentration of rIL-2 used in PBMC cultures. Optimum cell-mediated toxicity against the standard LAK target Daudi (99 +/- 10% cytolysis at 50:1 E:T ratio) was achieved at rIL-2 concentrations of 1,000 u/ml. LAK cells grown under these conditions were also effective against Ewing's sarcoma cells. At an E:T ratio of 50:1, 86 +/- 16, 85 +/- 16, and 67 +/- 13% inhibition was observed in 6647, 5838, and A4573 cells, respectively, as compared to 17 +/- 10, 19 +/- 15, and 29 +/- 11% cytolysis by fresh uninduced PBMC. In summary, our results suggest that rIL-2-induced LAK-type immune effector cells may be of some therapeutic value in the treatment of poor prognosis Ewing's sarcoma.

Cell Line↗
PubMedDate not supplied

[Inhaled nitric oxide therapy in preterm infants].

According to a number of recently published, randomized controlled trials, treatment of persistent pulmonary hypertension of the newborn (PPHN) by the use of inhaled nitric oxide (iNO) has emerged as an established procedure in neonatology. The situation in premature infants appears to be more complicated than in the term infant. Due to the fact that nitric oxide interferes with platelet aggregation, the risk of intraventricular hemorrhage or its aggravation during iNO therapy is being discussed in a controversial manner. Since most studies are aimed at endpoints like oxygenation parameters, the presently available studies report extremely variable incidences of intraventricular hemorrhages (IVH). Meanwhile two large studies could demonstrate that clinical application of iNO in preterm infants is not associated with an increased incidence of IVH. Further randomized controlled trials of iNO in preterm neonates are highly desirable in order to establish the future role of this therapy and its indications.

Cerebral Hemorrhage↗
PubMedDate not supplied

Meta-analysis of inhaled nitric oxide in premature infants: an update.

INTRODUCTION: The role of inhaled nitric oxide (iNO) in the treatment of severe hypoxemic respiratory failure of term neonates has been firmly established in several randomized trials. In contrast, the use of iNO in premature newborns has remained controversial. We performed a meta-analysis of five published randomized controlled trials involving a total of 808 infants below 34 weeks of gestation. RESULTS: The rates of major intracranial hemorrhage (ICH) were similar in both groups (42 of 208 infants receiving iNO vs 52 of 185 controls, relative risk (RR) 0.72, 95 % confidence interval (CI) 0.50-1.02) as was the mortality rate (169 of 415 receiving iNO vs 155 of 393 controls, RR 1.03, 95 % CI 0.87-1.22). Of 415 infants receiving iNO, 188 infants were diagnosed as having chronic lung disease (CLD), compared to 215 of 393 control infants. The RR in favor of iNO was 0.83, 95 % CI 0.72-0.95, p = 0.0092. Treatment failure, defined as death or CLD was significantly reduced in the iNO group (iNO: 126 of 208 infants versus control: 139 of 185, RR in favor of iNO 0.81, 95 % CI 0.70-0.93, p = 0.0025). CONCLUSIONS: We conclude that the use of iNO may decrease the CLD and the combined endpoint CLD and mortality in preterm infants with hypoxemic respiratory failure. However, the most recent and by far largest study was terminated due to an increase in severe ICH. Therefore a cautious use of iNO in preterm infants at risk for ICH is mandatory. Further studies with appropriate neurodevelopmental follow-up need to elucidate if the reduction of CLD in very low birth weight infants is potentially associated with modifications in neurodevelopmental outcome.

Administration, Inhalation↗
PubMedDate not supplied

Fosfomycin does not reduce cytostatic activity of cis-platinum against human osteosarcoma cell lines in vitro.

Fosfomycin has been shown to ameliorate the dose-limiting ototoxicity and nephrotoxicity associated with the antineoplastic agent cis-platinum. Clinical use of fosfomycin in cis-platinum-treated tumor patients critically depends on retaining therapeutic efficacy of cis-platinum while designing modalities to reduce side effects. This study uses two independent assay systems for cell viability and proliferation; we demonstrate that cytocidal activity of cis-platinum against human osteosarcoma cell lines is not affected by various concentrations of fosfomycin up to 0.1 mg/ml in vitro. This suggests that in these cells there is no direct pharmacodynamic interaction of cis-platinum and fosfomycin with respect to mechanisms crucial for tumor kill.

Antineoplastic Combined Chemotherapy Protocols↗