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Biomedical subjects

O Burkhard

Publications and source records attributed to O Burkhard.

14 recordsLinked to original sources

Randomized phase III study of high-dose fluorouracil given as a weekly 24-hour infusion with or without leucovorin versus bolus fluorouracil plus leucovorin in advanced colorectal cancer: European organization of Research and Treatment of Cancer Gastrointestinal Group Study 40952.

PURPOSE: This trial was conducted to determine whether high-dose fluorouracil (FU) given as a weekly 24-hour infusion is more active than bolus FU + leucovorin (LV), and whether high-dose infusional FU can be modulated by LV. PATIENTS AND METHODS: A total of 497 patients with previously untreated metastatic colorectal cancer were randomly assigned to receive bolus FU 425 mg/m2 intravenously + LV 20 mg/m2 on days 1 to 5 and repeated on day 28 (FU + LV), or FU 2600 mg/m2 as a 24-hour infusion alone (FU24h) or in combination with 500 mg/m2 LV (FU24h + LV)-all given weekly x6 followed by a 2-week rest period. Survival was the major study end point. RESULTS: With a median follow-up of more than 3 years, survival did not differ among the treatment groups (median FU + LV, 11.1 months [95% CI, 10.2 to 15.0 months]; FU24h, 13.0 months [95% CI, 10.4 to 15.4 months]; FU24h + LV, 13.7 months [95% CI, 12.0 to 16.4 months]; P =.724). Progression-free survival (PFS) was significantly longer for FU24h + LV (median FU + LV, 4.0 months [95% CI, 3.4 to 4.9]; FU24h, 4.1 months [95% CI, 3.4 to 5.0]; FU24h + LV 5.6 months [95% CI, 4.4 to 6.7]; P =.029). The response rates in the subgroup of patients with measurable disease were 12%, 10%, and 17% for FU + LV, FU24h, and FU24h + LV, respectively (not significant). Occurrence of grade 3 and 4 diarrhea was higher in the FU24h + LV arm (22%) compared with the FU24h (6%) or FU + LV (9%) arms; however, stomatitis (11% in FU + LV v 3% in FU24h v 5% in FU24h + LV arms) and hematologic toxicity were higher in the bolus FU + LV arm. Global quality of life did not differ within the three arms. CONCLUSION: Neither FU24h + LV nor FU24h prolong survival, relative to bolus FU + LV. Leucovorin increases PFS if added to FU24h, but increases toxicity.

Adult↗

Reduced-dose cladribine (2-CdA) plus mitoxantrone is effective in the treatment of mantle-cell and low-grade non-Hodgkin's lymphoma.

Cladribine (2-chlorodeoxyadenosine) (2-CdA) has been shown to be effective in mantle-cell (MCL) and low-grade lymphomas (lgNHL). The aim of this multicentre study was to evaluate the rate and duration of remissions and to examine the toxicity of the combination of reduced-dose 2-CdA and mitoxantrone (CdM) in MCL and lgNHL as first-line therapy or for patients in their relapse. A total of 285 courses, median of five courses per patient, were administered to 62 evaluable patients (42 previously untreated, 20 relapsed) with 5 mg/m(2) 2-CdA per day given as an intermittent 2-h infusion over 3 consecutive days combined with 8 mg/m(2) mitoxantrone on days 1 and 2 for the untreated patients or 12 mg/m(2) mitoxantrone on day 1 for patients in their first relapse for a maximum of six cycles every four weeks. 32 follicular, 18 MCL, 9 lymphoplasmacytoid, 2 marginal zone and 1 unclassified low-grade B-cell lymphoma were involved in the study. 56 of the 62 patients responded to CdM resulting in an overall response rate of 90% (95% confidence interval (CI), 80-96%) with a complete remission (CR) rate of 44% (95% CI, 31-57%) and a median duration of remission of 25 months (range 6-42+). The overall survival rate at 48 months was 80%. For 42 previously untreated patients, the overall response rate was 88% (95% CI, 74-96%) with a CR rate of 38% (95% CI, 24-54%), whereas the response rate for the group of 20 previously treated patients was similar with a 95% overall response (95% CI, 75-100%) and a CR rate of 55% (95% CI, 32-77%). In MCL, CdM showed a high activity, achieving a response rate of 100% (95% CI, 81-100%) with a CR rate of 44% and a median duration of remission of 24 months (range 6-35+). Myelosuppression was the major toxicity with 23% grade 3 granulocytopenia and 50% grade 4. Thrombocytopenia was less commonly observed, with only 8% grades 3 and 4. These results demonstrate that the combination of reduced-dose 2-CdA and mitoxantrone is a highly active regimen in the treatment of low-grade lymphomas, and in particular of MCL.

Adult↗

[An innovative procedure of oxygen detection in medicine, biology, environmental research and biotechnology based on luminescence quenching].

For most (aerobic) animal organisms, oxygen is a mandatory and global substrate. The accurate measurement of oxygen is therefore of importance in the fields of medicine, biology, environmental research and biotechnology. The fact that oxygen is not readily soluble in aqueous media makes its detection more difficult. In contrast to the technique of polarography, the use of luminescence quenching by paramagnetic oxygen, does not consume the oxygen. Another problem of oxygen detection in connection with respiration is the need for very short response times. A third problem, which is associated with luminescence itself, is the fading of the dyes, which results in long-term signal instability. The last two problems can be optimally resolved by adsorbing the luminescence dye onto chromatographic materials--in particular hydrophobic material--having a very large internal surface area, and using the decay time in accordance with the Stern-Volmer equation as oxygen signal. For this, continuous evaluation of the signal is necessary. The carrier material doped with dye is incorporated in a single-grain layer. For measurements in liquids, the detector layer is protected by a black silicone membrane. Two designs are possible for the oxygen detector: (I) a special form using glass fibres, and (II) a miniature detector utilizing optoelectronic solid state technology. Both fluorescence and phosphorescence can be employed, the dye used being excited by light, obviating the need for quartz. The detector layers may be either of high sensitivity for small oxygen concentrations, or have equal sensitivity over the entire oxygen concentration range. There is an optimal figure for the specific amount of adsorbed dye. Application examples are given for respiration and for the determination of oxygen uptake by suspended cells.

Animals↗

Low viscosity of densely and highly polymerized human hemoglobin in aqueous solution--the problem of stability.

The viscosity of highly and densely polymerized human hemoglobin is low enough in reasonable concentrations to serve as an effective oxygen carrying blood substitute. But polymerisation with glutardialdehyde leads to instable polymers. In contrast polymerisation with diisocyanate gives stable polymers which can be fractionated. Fractionation reduces viscosity. The viscosity of the fractionated polymers is at 5 g/dl as low as the viscosity of plasma.

Cross-Linking Reagents↗

Dependence of visible spectrum [epsilon (lambda)] of fully oxygenated hemoglobin on concentration of hemoglobin.

Lambert-Beer's law assumes that the extinction coefficient of a dye is not influenced by its concentration. Some experiments of Barnikol (Proc. Int. Congr. Physiol. Sci. 27th Paris 1977; Respiration 36: 86-95, 1978) led to the presumption that especially at highly concentrated hemoglobin (Hb) solutions Lambert-Beer's law does not hold. To further elucidate this problem we have measured the extinction coefficient of completely oxygenated hemoglobin (epsilon HbO2) over a wide range of Hb concentrations (CHbO2). Our results prove clearly that epsilon HbO2 in visible range as well as in the Soret region depends on CHbO2. In our opinion the invalidity of Lambert-Beer's law is caused by the self-association of the Hb molecules. This concept is a powerful tool to explain the high n values (n greater than 4) which were obtained by some authors in animal blood (bird, frog, trout, earthworm). Furthermore the influence of the self-association on the physicochemical properties of concentrated solutions of human hemoglobin is discussed.

Chemical Phenomena↗