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Biomedical subjects

M Baumann

Publications and source records attributed to M Baumann.

At least 127 records · Page 7Linked to original sources
PubMed1998

[Brief preoperative radiotherapy in surgical therapy of rectal carcinoma. Long-term results of a prospective randomized study].

To ascertain whether preoperative short-term radiotherapy can improve local tumor control and the long-term survival of patients with operable rectal cancer, a prospective randomised trial was performed from 1988 to 1993. Ninety-three patients with rectal cancer were either directly treated with surgery (n = 46) or underwent preoperative radiotherapy with 5 x 3.3 Gy irradiation and operation within 48 h (n = 47). If indicated (T4, UICC stage III) patients also received postoperative irradiation. Comparison of the methods of operation (abdominoperineal amputation versus anterior resection) revealed no significant difference in 5-year survival rate (P = 0.393). Local control of R0-resected tumors was improved after preoperative irradiation (P = 0.08). The 5-year survival rate was significantly higher after preoperative short-term radiotherapy (P = 0.027). Preoperative radiotherapy is not an independent factor according to overall survival (P = 0.078) and local recurrence (P = 0.07). In agreement with the results of other authors the present study indicates improved local tumor control of rectal cancer after preoperative radiation therapy. The 5-year survival rate was significantly better after preoperative radiotherapy than after surgery alone.

Adult↗
PubMed1998

Hyperfractionated radiotherapy in head and neck cancer: a second look at the clinical data.

Hyperfractionated radiation therapy (HF) is one of the most promising modifications of conventional fractionation (CF). However, two recent reviews on the efficacy of HF reached opposite conclusions: Stuschke and Thames (Int. J. Radiat. Oncol. Biol. Phys. 37: 259-267, 1997) concluded that the effectiveness of radiotherapy is consistently higher for HF than for CF, whereas Beck-Bornholdt et al. (Radiother. Oncol. 43: 1-21, 1997) concluded that evidence for a consistent therapeutic gain from HF is lacking and it cannot be ruled out that HF in head and neck tumors is detrimental. To clarify this issue, some important discrepancies between the two reviews are highlighted and a second look is taken at the clinical data published on HF in head and neck cancer. The most convincing prospective study so far is the EORTC trial 22791. This trial supports that HF allows escalation of the biologically effective dose to the tumor without a significant increase in late complications.

Head and Neck Neoplasms↗
PubMed1998

Changes in biochemical markers and bone mass after withdrawal of ibandronate treatment: prediction of bone mass changes during treatment.

The study was a 1 year randomized, double-blind, placebo-controlled study of ibandronate treatment in postmenopausal, osteopenic women. Participants were followed for 1 year after withdrawal of treatment. All women were at least 10 years past menopause and had a baseline bone mineral density (BMD) at the distal forearm at least 1.5 standard deviations below the premenopausal mean peak value. A total of 141 women (78%) completed the first year, and 119 women (66%) the second year of the study. The dose-response data of the first year have been published previously (Ravn et al. Bone 19:527-533;1996). In this study, we analyzed the biochemical markers as predictors of response in bone mass during ibandronate treatment, and report withdrawal data from the last year of the study, when ibandronate was discontinued. The relative change in the biochemical markers was significantly correlated to the response in BMD. At 12 months, the r values ranged from -0.29 to -0.47 (p < 0.01) and were highest for CrossLaps (uCL) and osteocalcin (OC(N-MID)). The quartiles of women with the most reduced concentrations of uCL and OC(N-MID) during treatment showed a 360-430% higher response in BMD compared to quartiles with less reduced concentrations (p < 0.01). During the withdrawal period, uCL and alkaline phosphatase (AP) returned to baseline values 12 months after discontinuation of treatment in all groups, whereas OC(N-MID) and bone-specific AP were still reduced 10%-25% in the groups previously treated with the highest doses of ibandronate (1.0-5.0 mg) (p < 0.01). In the withdrawal period, BMD decreased equally in all groups (analysis of variance; not significant); with a linear rate of 2%/year on average (p < 0.05 to < 0.001) at the spine and femur. In conclusion, uCL and OC(N-MID) can be used to predict the response in bone mass during ibandronate treatment. The bone loss that resumes after withdrawal of ibandronate treatment is of a magnitude similar to that of normal postmenopausal bone loss.

Aged↗
PubMed1998

Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis.

Neutrophil elastase (NE) is a potent serine proteinase whose expression is limited to a narrow window during myeloid development. In neutrophils, NE is stored in azurophil granules along with other serine proteinases (cathepsin G, proteinase 3 and azurocidin) at concentrations exceeding 5 mM. As a result of its capacity to efficiently degrade extracellular matrix, NE has been implicated in a variety of destructive diseases. Indeed, while much interest has focused on the pathologic effects of this enzyme, little is known regarding its normal physiologic function(s). Because previous in vitro data have shown that NE exhibits antibacterial activity, we investigated the role of NE in host defense against bacteria. Generating strains of mice deficient in NE (NE-/-) by targeted mutagenesis, we show that NE-/- mice are more susceptible than their normal littermates to sepsis and death following intraperitoneal infection with Gram negative (Klebsiella pneumoniae and Escherichia coli) but not Gram positive (Staphylococcus aureus) bacteria. Our data indicate that neutrophils migrate normally to sites of infection in the absence of NE, but that NE is required for maximal intracellular killing of Gram negative bacteria by neutrophils.

Animals↗
PubMed1998

Flow cytometric identification of candidate normal stem cell populations in CD45-negative B-cell precursor acute lymphoblastic leukaemia.

CD45-negative B-cell precursor acute lymphoblastic leukaemia (ALL) provides a unique model to study the stem cell compartment in ALL as leukaemic CD34-positive cells, unlike their normal counterparts, do not express CD45. By increasing the number of events analysed to 10(6), storing only the events in the region of interest (storage gate), using appropriate isotype controls and stringent washing procedures, a flow cytometric protocol was established to characterize rare CD34+ CD19- events. In eight of 12 patients (67%) with CD45-negative B-cell precursor ALL, a distinct CD34+ CD19- CD45+ candidate normal stem cell population could be detected. In one patient analysed by four-colour staining, the CD34+ CD19- CD45+ cells, unlike the CD45-negative leukaemic cells, expressed CD117 (c-kit), providing further evidence that these cells represent residual nonleukaemic normal cells. By multiparameter analysis, this population of candidate normal stem cells could be separated from contaminating leukaemic CD34+ CD19- CD45- cells, which were detected in 11 of the 12 patients within the CD34+ CD19- compartment.

Acute Disease↗
PubMed1998

Fractionation effect on radiation-induced growth retardation of tibia in rabbits and rats.

A study of the sensitivity to fractionation of the growing tibia of rabbits and rats was conducted by comparing the growth of the treated right bone to that of the untreated left side in each individual animal using radiographic measurements. The experimental endpoint was the percentage of normal growth 24 weeks after irradiation in rabbits and 14 weeks after treatment in rats. The results show clear dose-response relationships in all experimental arms. A clear-cut fractionation effect was demonstrated in both species. The alpha/beta-ratios determined by maximum likelihood analysis according to the LQ-model with graded responses were 3.2 Gy (95% C.I. 1.1; 5.6) in rabbits and 6.9 Gy (5.3; 8.7) in rats, when all data were included in the calculations. When single-dose data were excluded the alpha/beta-values were -0.6 Gy (-3.1; 2.3) in rabbits and 5.0 Gy (3.5; 7.0) in rats. Our data provide further evidence that low doses per fraction should be used when irradiation of the epiphysis cannot be avoided in pediatric patients.

Animals↗
PubMed1998

Linear-quadratic analysis of tumour response to fractionated radiotherapy: a study on human squamous cell carcinoma xenografts.

PURPOSE: To compare values for the alpha/beta ratio in experimental tumours irradiated either under conditions of clamping and short overall time or under more 'clinically realistic' conditions. MATERIALS AND METHODS: Human squamous cell carcinomas, FaDu and GL, were grown in nude mice. Alpha/beta values were determined from local tumour control data after treatment with single doses and 2, 4, and 8 fractions under clamp hypoxia in 3.5 days, using maximum likelihood analysis. Effective alpha/beta values (alpha/beta(eff)) were determined from treatment with 12, 30, and 60 fractions under ambient conditions in a constant overall treatment time of 6 weeks. RESULTS: After correction for an oxygen enhancement ratio of 2.7 the alpha/beta values were 15 Gy (95% CI 9; 24) for FaDu and 49 Gy (26; 122) for GL. In FaDu the TCD50 values after 12 to 60 fractions were not significantly different, the alpha/beta(eff) value was infinite (52; inf.). Unexpected from the high alpha/beta value, the TCD50 values of GL tumours increased from 37 Gy (28; 47) after 12 fractions to 59 Gy (52; 67) after 60 fractions: the alpha/beta(eff) value was 3 Gy (0.6; 12 Gy). CONCLUSIONS: The results support the view that mechanisms other than recovery from sublethal radiation damage and repopulation of clonogenic tumour cells may importantly impact on treatment outcome when the number of fractions is changed in clinical radiotherapy.

Animals↗
PubMed1998

Activation of the Epstein-Barr virus transcription factor BZLF1 by 12-O-tetradecanoylphorbol-13-acetate-induced phosphorylation.

BZLF1 is a member of the extended AP-1 family of transcription factors which binds to specific BZLF1 sequence motifs within early Epstein-Barr virus (EBV) promoters and to closely related AP-1 motifs. BZLF1's activity is regulated at the transcriptional level as well as through protein interactions and posttranslational modifications. Phorbol esters or immunoglobulin cross-linking both reactivate EBV from latently infected B cells via transactivation of BZLF1. We report here that the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) is capable of inducing BZLF1's activity even further. The induction occurs at the posttranscriptional level and depends on a single serine residue located in the DNA binding domain of BZLF1. This serine residue (S186) is phosphorylated by protein kinase C in vitro and in vivo after stimulation with TPA. Phosphorylation of S186 per se interferes with the DNA binding affinity of BZLF1 in vitro but is mandatory for TPA-induced increase in DNA binding of BZLF1, as shown in gel retardation assays and reconstruction experiments with cellular extracts. In transcriptional reporter assays, S186 is essential for the activation of BZLF1 by TPA. Presumably, a yet-to-be-identified cellular factor restores the DNA binding affinity and enhances the transcriptional activity of S186-phosphorylated BZLF1, which is required to induce the lytic phase of EBV's life cycle.

Amino Acid Sequence↗
PubMed1998

Rapid, automated assay for progesterone on the Abbott AxSYM analyzer.

We describe an automated assay for progesterone (P4) in human serum and plasma with the Abbott AxSYM random-access immunoassay analyzer. In this one-step competitive assay, P4 immobilized onto latex microparticles competes with sample P4 for binding to a conjugate of alkaline phosphatase (AP) and anti-P4 antibody. Total CVs ranged from 3.4% to 8.2% in multiple precision studies conducted according to the 20-day NCCLS EP5-T protocol. The detection limit (zero calibrator + 2 SD) was 0.10 microg/L across 36 experiments. Values for diluted samples were 83-116% of expected. Recovery of P4 added to serum specimens was 92-115%. Cross-reactivities with 43 natural and synthetic steroids were 0-6.3%. No significant interference was detected from bilirubin, protein, erythrocytes, hemoglobin, triglycerides, or cholesterol. In a multisite correlation study, AxSYM P4 results compared well with results from a commercial RIA method (n = 1156; r = 0.976; slope = 1.03; y-intercept = 0.04). Assay throughput is >80 tests per hour in batch mode, 60 tests per hour with mixed load list configurations.

Autoanalysis↗
PubMed1998

Reproducibility of retinal thickness measurements in normal eyes using optical coherence tomography.

BACKGROUND AND OBJECTIVE: To determine the reproducibility of retinal thickness measurements in normal eyes using optical coherence tomography (OCT). PATIENTS AND METHODS: Multiple 3.20-mm vertical cross-sectional images through the center of fixation of consecutive patients with normal results on ocular examinations were obtained. Each image was divided into seven 320-micron segments. Regional retinal thicknesses for each section were measured using both the manually assisted (requiring observer localization of reflectivity peaks) and the automated modes (observer-independent measurement) of the computer software. RESULTS: Eighteen right eyes were studied. The mean coefficient of variation was less than 10% for all locations using the manually assisted method (average standard deviation less than 17 microns [range 9 to 16 microns]). The automated method was less reliable, with a coefficient of variation greater than 10% for locations within 500 microns of fixation. Automated measurements at fixation were the least reproducible because of poor internal limiting membrane reflectivity. CONCLUSION: OCT is capable of reproducible measurement of retinal thickness in normal eyes. Computer-driven, automated measurement of retinal thickness within 500 microns of fixation needs to be refined and its reproducibility reassessed in this region.

Adult↗
PubMed1998

[Program planning of pragmatic/professional actions and evaluations in the context of humanitarian actions].

Health action programme planning is an approach that attempts to resolve the public health problems that are defined as priority. It is upon this approach that the determination of strategies, planning of objectives, the operational plan of activities and the pragmatic/professional evaluation of results, process, resources, community participation, partnerships and staff, are based. The goal concerning this is to provide the foundation of a conceptual and methodological reflection on humanitarian interventions as a planning approach within a community, and to propose elements of methods for programme planning and comprehensive, quantitative evaluation. The approach and tool presented here were tested within the context of humanitarian missions carried out in other countries, and result from a two year collaboration with Médecins du Monde.

Community Participation↗
PubMed1998

Lactated Ringer's solution versus hydroxyethyl starch for volume replacement in autologous blood donors with cardiovascular disease: a controlled, randomized trial.

BACKGROUND AND OBJECTIVES: The study was designed to evaluate whether volume replacement following blood donation can prevent arterial hypotension in autologous blood donors with cardiovascular disease. MATERIALS AND METHODS: One hundred nineteen autologous blood donors with known cardiovascular disease were randomly allocated to receive, following withdrawal of 500 ml of blood, either no infusion (control group) or a 25 ml/min intravenous infusion of either 1,500 ml of lactated Ringer's solution (LRS) or 500 ml of 6% hydroxyethyl starch (HES). Starting before phlebotomy, arterial blood pressure was measured oscillometrically every 5 min until 90 min after donation. RESULTS: Group means showed little difference between the groups in blood pressure throughout the monitoring period. The proportion of patients who at least once had a > or = 20% decrease from baseline in systolic blood pressure was 3-5 times greater in the control group than in the LRS and the HES group (50 vs. 10 and 15%, respectively; p < 0.001 on chi 2 analysis for a 2 x 3 table). Systolic hypertensive episodes (> or = 20% increase over baseline) were observed more frequently in the LRS group than in the control and the HES group (41 vs. 10 and 18%, respectively; p = 0.003). CONCLUSION: Both LRS and HES, administered at a volume ratio to blood loss of 3:1 and 1:1, respectively, significantly reduced the incidence of systolic hypotensive episodes in autologous blood donors with cardiovascular disease. LRS at a 3:1 volume ratio to blood loss was associated with a high rate of systolic hypertension.

Adult↗
PubMed1998

Effects of intensive endurance exercise on DNA damage in leucocytes.

OBJECTIVE: It has been shown that highly intensive anaerobic exercise induces DNA damage in leucocytes (LEU). The present study was designed to investigate whether intensive endurance exercise is capable of inducing comparable effects. EXPERIMENTAL DESIGN: A prospective study. PARTICIPANTS: Twelve men (aged 27.3 +/- 4.1 years) who undertook a regular training of different extent (running volume 45 +/- 25 km.week-1) volunteered in the study. INTERVENTIONS: The subjects competed in a half marathon (HM) of 21.1 km, 93.0 +/- 10.4 min. MEASUREMENTS: Blood was taken at rest, 1 and 24 hrs after HM for determination of creatine kinase, neutrophil (PMN), lymphocyte and monocyte counts. DNA damage in LEU at rest and 24 hrs after HM was quantified using the single cell gel-electrophoresis (SCG) assay. RESULTS: PMN increased from 2.81 +/- 0.69 to 13.13 +/- 2.91 1 hrs after HM (p < 0.01) and returned to 3.26 +/- 0.47 10(9) cells.l-1 by 24 hr recovery. DNA migration (image length, IL) reflecting the extent of DNA damage was elevated significantly in 10 of 12 subjects one day after HM. IL rose from 32.7 +/- 2.2 to 40.7 +/- 3.9 microns (p < 0.01). Correlation analysis revealed a relationship between DNA migration 24 hrs after HM and PMN count 1 hr post-exercise (r = 0.67, p < 0.05). CONCLUSIONS: The results confirm the hypothesis that DNA damage in LEU occurs after intensive endurance exercise. We suppose our observation of exercise-induced DNA damage in LEU is affected by reactive oxygen species which are released from PMN. It is quite unclear whether DNA damage in LEU is causal involved in exercise-induced modifications of the immune system.

Adult↗