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Biomedical subjects

H Müller

Publications and source records attributed to H Müller.

At least 37 records · Page 2Linked to original sources

Cytoreductive surgery plus intraperitoneal hyperthermic perfusion is an effective treatment for metastasized malignant mixed mesodermal tumours (MMMT)--report of six cases.

BACKGROUND: Malignant mixed mesodermal tumours (MMMT) of the female genital tract are rare and heterogeneous malignancies that impart grim prognosis. These tumours are characterized by an admixture of malignant epithelial and stromal elements comprising carcinomatous and sarcomatous neoplastic cells. Thus far, almost 350 cases of MMMT have been recorded in the international medical literature. Due to its rarity, there is no agreement on the best treatment strategy in women with metastasized MMMT. METHODS: Six women (mean age 59 years) with metastasized MMMT defined to the peritoneal cavity have been treated by cytoreductive surgery plus hyperthermic peritoneal perfusion plus postoperative adjuvant chemotherapy. All patients have been pre-treated by surgery for primary tumour and one by systemic chemotherapy. As cytostatics for hyperthermic peritoneal perfusion, we have used Mitomycin in a dosage of 18 mg/m2 plus Melphalan in a dosage of 25 mg/m2. As adjuvant treatment CDDP 40 mg/m2/dl, Mitomycin 7 mg/md2/dl and Ifosfamid 100 mg/kg 24 h/dl was applicated via intraaortic catheter three times with a treatment free interval of 3 weeks. RESULTS: A complete cytoreduction without remnant tumour formations in the peritoneal cavity could be carried out in all six patients. The postoperative course was uneventful in all cases except for one where a spontaneous small bowel perforation and prolonged gall secretion had to be treated by re-operation. One patient died 4 months later by pneumonia without evidence of disease. Four patients are without evidence of disease after 2, 4, 14 and 19 months, whereas one patient developed liver metastases after 9 months still treated by systemic chemotherapy. CONCLUSION: Complete cytoreduction plus hyperthermic peritoneal perfusion plus adjuvant chemotherapy seems to be an effective treatment for recurrent or metastasized MMMT. Further studies have to define the value of this new treatment strategy for this rare tumour entity.

Adult↗

[A perioperative screening for metastatic disease is not indicated in patients with primary breast cancer and no clinical signs of tumor spread].

OBJECTIVE: Is a perioperative metastatic screening programme indicated in patients presenting with primary operable breast cancer and no signs of distant metastases? PATIENTS AND METHODS: The impact of staging results (chest X-ray, bone scanning, liver ultrasound) for prognosis, treatment, quality of life and costs was retrospectively analysed in 1 076 patients with an operable breast cancer and no clinical signs of metastases. RESULTS: Staging examinations revealed 30 (2.8 %) distant metastases, 130 (12.1 %) suspect findings and excluded metastases in 916 (85.1 %) patients. Further diagnostic procedures confirmed distant metastases in 7 (5.4 %) and excluded them in 123 (94.6 %) out of 130 patients with suspect findings. Distant metastases were detected more frequently with increasing tumor size (pT < or = 2.0 cm: 1.6 %, pT 2.1-5.0 cm: 3.0 %, respectively pT > 5.0 cm: 15.1 %; p < 0.001) and increasing number of involved axillary lymph nodes (pN0: 1.4 %, pN1-3 +: 1.8 %, pN4-9 +: 4.0 %, pN > 10 +: 12.5 %; p < 0.001). Due to false positive findings 123 (11.4 %) patients had to live for a significant period of time with the psychological distress of suspected metastatic disease. The abandonment of a perioperative screening in 1 076 patients saves costs of at least euro 259,366.68. CONCLUSIONS: In breast cancer patients without clinical signs of tumor spread perioperative screening for metastases is not warranted because of low frequency of metastases, false positive findings, missing therapeutic consequences and high costs.

Adult↗

Reversion of molecularly engineered, partially attenuated, very virulent infectious bursal disease virus during infection of commercial chickens.

A molecularly cloned, tissue culture-adapted infectious bursal disease virus (BD-3tc) was generated from a very virulent strain by the reverse genetics approach following site-directed mutagenesis (Q253H and A284T in VP2). The pathogenicity of BD-3tc was tested in commercial chickens. The wild-type strain (BD-3wt) and the molecularly cloned parental strain (BD-3mc) were included for comparison. The subclinical course of the disease, with delayed and milder pathological lesions followed by quick follicular regeneration in the bursa of Fabricius in BD-3tc-inoculated birds, suggested that these amino acid substitutions made BD-3tc partially attenuated. However, severe bursa atrophy was observed at 14 days after inoculation. Reverse transcription-polymerase chain reaction coupled with restriction enzyme analysis revealed that both point mutations in BD-3tc had reverted 14 days after inoculation. Further investigations demonstrated that the codon for amino acid at position 284 had already reverted to the wild-type phenotype (T284A) 3 days after inoculation.

Animals↗

Assessment of genetic, antigenic and pathotypic criteria for the characterization of IBDV strains.

The aim of this work was the selection and comparison of representative infectious bursal disease virus (IBDV) strains. Nine strains of IBDV, isolated at different times and from different geographic regions of Europe and China, were characterized. Batches of all strains were prepared following standardized protocols and checked for the absence of contaminating viruses. Criteria used for their characterization were: (i) the nucleotide sequence of the VP2 variable region, (ii) binding to a panel of neutralizing monoclonal antibodies in antigen capture enzyme-linked immunosorbent assays, and (iii) virulence in specific pathogen free chickens after infection with a standardized number of median embryo infective doses. Based on the first two criteria, two of nine strains were classified as classical virulent (cv) IBDV (F52/70, Cu-1wt), and five as very virulent (vv) IBDV (849VB, 96108, HK46, GX, Harbin). Remarkably, although a clear-cut difference was demonstrable between European cvIBDV (F52/70 and Cu-1wt) and vvIBDV (849VB and 96108) strains, there was a continuum in the pathogenicity of Chinese vvIBDVs. Our results indicate the probable existence of differences in virulence within IBDV lineages determined on the basis of antigenic typing using monoclonal antibodies and the alignment of the VP2 sequences. This indicates limitations in the analysis of IBDV pathotypes based on the VP2 variable region and emphasizes that these criteria may not be sufficient for the classification of IBDV strains.

Amino Acid Sequence↗

Thoracic stop-flow perfusion in the treatment of refractory non small cell lung cancer.

This study was undertaken to determine the survival of patients with unresectable and refractory non small cell lung cancer (NSCLC) submitted to thoracic stop-flow perfusion (TSP). Forty-five patients with NSCLC confined to thoracic region entered the study. All 45 patients had been pretreated with some form of chemotherapy and had progression of disease. The cytostatic regimen was mitomycin 10 mg/m2, navelbine 25 mg/m2 and cisplatin 60 mg/m2. In 39/45 patients, immediately after TSP, hemofiltration was performed to reduce systemic side effects There were 16/45 responses to the first TSP (CR 0; PR 16): a response rate of 35.6%. Median time to progression was 4 months. Median survival was 7.5 months.1-year survival rate was 36.4%, 2-year survival rate was 14%, and 3-year survival rate was 5.7%.

Adult↗

Muscular adaptations to computer-guided strength training with eccentric overload.

AIMS: In order to investigate the muscular adaptations to a novel form of strength training, 18 male untrained subjects performed 4 weeks of low resistance-high repetition knee extension exercise. METHODS: Nine of them trained on a conventional weight resistance device (Leg curler, CON/ECC group), with loads equivalent to 30% of the concentric one-repetition maximum (1RM) for both the concentric and eccentric phase of movement. The other nine trained on a newly developed computer-driven device (CON/ECC-OVERLOAD group) with the concentric load equivalent to 30% of the concentric 1RM and the eccentric load equivalent to 30% of the eccentric 1RM. RESULTS: Training resulted in significantly (P < or = 0.05) increased peak torque and a tendency (P=0.092) to increased muscle cross-sectional area for the CON/ECC-OVERLOAD but not the CON/ECC group, while strength endurance capacity was significantly (P < or = 0.05) increased in the CON/ECC group only. RT-PCR revealed significantly increased myosin heavy chain (MHC) IIa and lactate dehydrogenase (LDH) A mRNAs, a tendency for increased MHC IIx mRNA (P = 0.056) and high correlations between the changes in MHC IIx and LDH A mRNAs (r=0.97, P=0.001) in the CON/ECC-OVERLOAD group. CONCLUSIONS: These results indicate a shift towards a more type II dominated gene expression pattern in the vasti laterales muscles of the CON/ECC-OVERLOAD group in response to training. We suggest that the increased eccentric load in the CON/ECC-OVERLOAD training leads to distinct adaptations towards a stronger, faster muscle.

Adaptation, Physiological↗

Registration of biplane angiography and intravascular ultrasound for 3D vessel reconstruction.

UNLABELLED: If planned and applied correctly, intra-vascular brachytherapy (IVB) can significantly reduce the risk of restenosis after interventional treatment of stenotic arteries. OBJECTIVES: In order to facilitate computer-based IVB planning, a three-dimensional reconstruction of the stenotic artery based on intravascular ultrasound (IVUS) sequences is desirable. METHODS: To attain a 3D reconstruction, the frames of the IVUS sequence are properly aligned in space and completed with additional intermediate frames generated by interpolation. The alignment procedure uses additional information that is obtained from biplane X-ray angiography performed simultaneously during the capturing of the IVUS sequence. After IVUS images and biplane angiography data are acquired from the patient, the vessel-wall borders and the IVUS catheter are detected by an active contour algorithm. Next, the twist between adjacent IVUS frames is determined by a sequential triangulation method combined with stochastic analysis. RESULTS: The above procedure results in a 3D volume-model of the vessel, which also contains information from the IVUS modality. This data is sufficient for computer-based intravascular brachytherapy planning. CONCLUSION: The proposed methodology can be used to improve the current state-of-the-art IVB treatment planning by enabling computerized dosage computations on a highly accurate 3D model.

Algorithms↗

Discrimination of patients with and without vertebral fractures as measured by ultrasound and DXA osteodensitometry.

This study compares dual X-ray absorptiometry (DXA) measurements of the hip and spine with quantitative ultrasound (QUS) parameters measured simultaneously at the calcaneal and phalangeal bone in 174 patients with and without vertebral fractures. The aim of this study was to compare the ability of DXA and QUS measurements to discriminate patients with and without osteoporotic vertebral fractures and to evaluate whether QUS measurements in addition to the DXA measurements improve the clinical discrimination between patients with and without osteoporotic vertebral fractures. T-scores determined by DXA measurements at the spine and hip and QUS measurements at the calcaneus provide similar information regarding the discrimination of women with and without vertebral fractures. Phalangeal QUS measurements did not discriminate between patients with and without vertebral fractures. The discriminative power of the combined use of DXA and calcaneal QUS measurements to discern between patients with and without vertebral fractures increases in women. In contrast, the combined use of DXA and phalangeal QUS measurements resulted in decreased discriminative power as compared to DXA measurements alone. The number of fractures was higher in the quartiles with lower T-scores of the DXA and calcaneal QUS measurements whereas no difference was seen in the T-score quartiles of the phalangeal QUS device. These findings suggest that DXA and QUS measurements at weight-bearing skeletal sites provide useful information for assessing women with an anamnestic risk of osteoporotic bone loss. For DXA and calcaneal QUS measurements in men as well as for phalangeal QUS, however, a clinical algorithm remains to be established to understand the diagnostic implications and related therapeutic consequences of the obtained measurements.

Absorptiometry, Photon↗

Serum cholesterol predictive equations in product development.

The aim of the study was to incorporate trans fatty acids into predictive equations for serum cholesterol and compare their effects with the effects of the individual saturated fatty acids 12:0, 14:0 and 16:0. We have introduced trans fatty acids from partially hydrogenated soybean oil (TransV) and fish oil (TransF) into previously published equations by constrained regression analysis. Prior knowledge about the signs and ordering of existing regression coefficients were incorporated into the regression modelling by adding lower and upper bounds to the coefficients. Oleic acid (18:1) and polyunsaturated fatty acids (18:2, 18:3) were not sufficiently varied in the studies and the respective regression coefficients therefore set equal to those found by Yu et al. (Am J Clin Nutr 1995;61:1129-39). Stearic acid (18:0) considered to be neutral was not included in the equations. The regression analyses were based on results from four controlled dietary studies with a total of 95 participants and including 10 diets differing in fatty acid composition. The analyses resulted in the following equations where the change in cholesterol is expressed in mmol/L and the change in intake of fatty acids is expressed in E%: Delta Total cholesterol = 0.01 delta(12:0) + 0.12 Delta(14:0) + 0.057 delta(16:0) + 0.039 delta(TransF) + 0.031 delta(TransV)- 0.0044 delta(18:1) - 0.017 delta(18:2, 18:3) and deltaLDL cholesterol = 0.01 delta(12:0) + 0.071 delta(14:0) + 0.047 delta(16:0) + 0.043 delta(TransF) + 0.025 delta(TransV) - 0.0044 delta(18:1) - 0.017 delta(18:2, 18:3). The test set used for validation consisted of 22 data points from seven recently published dietary studies. The equation for total cholesterol showed good prediction ability with a correlation coefficient of 0.981 between observed and predicted values. The equation has been used to reformulate margarines into "trans free" products all with more favourable effects on serum cholesterol than previous products. Also a cholesterol reducing margarine has been produced. When tested against butter in an open clinical trial among subjects with mild hypercholesterolemia the observed cholesterol-lowering effect of this margarine corresponded reasonably well with the predicted (0.77 vs. 0.64 mmol/L). We conclude that the equation has practical applicability and can be used to formulate and nutritionally optimise fat products as well as to evaluate already existing products on the market.

Adult↗

[Treatment of phantom pain with botulinum-toxin A. A pilot study].

BACKGROUND: Therapy of phantom pain following amputation is still difficult, since pathophysiological mechanisms are not clarified. Botulinum-toxin A never has been used for this issue. We report four successfully treated cases with chronic phantom pain longer than 3 years. METHODS: We injected 100 IU botulinum-toxin A (4x25 IU in 0,5 ml preservative-free saline 0.9%) in four muscle-triggerpoints of the amputation stump of each patient. All triggerpoints were painful to compression before injection, all patients reported referred sensations in the phantom-foot from at least one of them. Controls were performed by questioning and pain-diaries after 1,2 and 5 weeks. RESULTS: In all cases phantom pain was reduced about 60-80%. The three patients, who had pain attacks, reported a dramatically reduction of the number of attacks (about 90%). In two of them duration of attacks shortened from 120 to 5-10 min and a reduction of pain intensity from VAS 9 to VAS 1 and VAS 9 to VAS 2 was reported. Disorder of sleep disappeared in both affected patients within 2-3 weeks. Three patients,who could move the phantom foot (mental), had a subjective weakness a few days after botulinum-toxin A injection; in one case although injection was performed in the muscles of the femur! CONCLUSIONS: This is the first report of the use of botulinum-toxin A in the treatment of phantom pain. The contribution of the muscles in the cause of phantom pain is unclear and may be local, as a trigger of spinal reflexes or by modulation of "cortical reorganisation" after amputation. Botulinum-toxin A could work analgesic by the relaxation of the stump muscles or by modulation of neuronal transmitters, for example substance P, with an indirect influence of the CNS.

Adult↗

Data assimilation in the decision support system rodos.

Model predictions for a rapid assessment and prognosis of possible radiological consequences after an accidental release of radionuclides play an important role in nuclear emergency management. Radiological observations, e.g. dose rate measurements, can be used to improve such model predictions. The process of combining model predictions and observations, usually referred to as data assimilation, is described in this article within the framework of the real time on-line decision support system (RODOS) for off-site nuclear emergency management in Europe. Data assimilation capabilities, based on Kalman filters, are under development for several modules of the RODOS system, including the atmospheric dispersion, deposition, food chain and hydrological models. The use of such a generic data assimilation methodology enables the propagation of uncertainties throughout the various modules of the system. This would in turn provide decision makers with uncertainty estimates taking into account both model and observation errors. This paper describes the methodology employed as well as results of some preliminary studies based on simulated data.

Algorithms↗

Mixed chimerism of erythro- and megakaryopoiesis following allogeneic bone marrow transplantation.

Until now, studies on mixed chimerism (MCh) after allogeneic bone marrow transplantation (BMT) have predominantly focused on the B- and T-lymphocyte population, but not on distinct myeloid cell lineages like nucleated erythroid precursors and megakaryocytes. To evaluate the lineage-restricted MCh more explicitly in 10 patients with chronic myelogenous leukemia (CML), a quantitative analysis was performed on bone marrow biopsies following a sex-mismatched host/donor constellation. Techniques included immunophenotyping (antiglycophorin C, CD61) for the identification of erythro- and megakaryopoiesis and a simultaneously conducted genotyping with x- and y-chromosome-specific DNA probes. Normal bone marrow and specimens taken before BMT served as controls. Contrasting a total gender-dependent sex-typing in the latter samples in the early and late posttransplant period (up to 586 days), 3-9% erythroid precursors and about 16% megakaryocytes revealed a host-type origin. This significantly higher number of host megakaryocytes is explained by their polyploidy generating an increased probability to detect positive signals at a certain section level of the corresponding biopsies. A striking conversion of MCh to a recipient cell type was found in leukemic relapse with a more than 90% host-derived erythroid and megakaryocytic cell population in 4 patients approximately 643 days after BMT.

Adult↗

Herpesviral, but no papovaviral sequences, are detected in cloacal papillomas of parrots.

Internal papillomatosis of parrots (IPP) is a tumour disease with unknown etiology, characterised by progressive development of papillomas in the oral and cloacal mucosa. Based on epidemiologic data, infectious agents, particularly DNA tumour viruses, are considered to be involved. In this study, cloacal papillomas were investigated by PCR for the presence of herpesvirus, papillomavirus and avian polyomavirus genomes, respectively. Using consensus and specific primers, 5 out of 12 papillomas were tested positive for herpesvirus; all papillomas were tested negative for papillomavirus and avian polyomavirus. The DNA sequence of one of the PCR products showed 86.5% homology to the corresponding region of the psittacine herpesvirus 1 DNA polymerase gene. Using a PCR with primers based on this sequence, additional 4 papillomas were tested positive. By in situ hybridisation, herpesviral sequences were detected in epithelial cells of the papilloma, but not in surrounding tissues. As 75% of the tumours proved to be positive, these data suggest an involvement of a herpesvirus in the etiology of IPP; the distinct role, however, needs to be investigated.

Animals↗