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Biomedical subjects

P Müller

Publications and source records attributed to P Müller.

At least 37 records · Page 2Linked to original sources
PubMed2003

A new conditioning regimen involving total marrow irradiation, busulfan and cyclophosphamide followed by autologous PBSCT in patients with advanced multiple myeloma.

The overall survival of patients with advanced multiple myeloma (MM) undergoing high-dose chemotherapy and autologous stem cell transplantation (SCT) depends mainly on the quality of response. Thus, to improve the response rate, a new intensified high-dose chemoradiotherapy was evaluated in a phase I/II study. After induction chemotherapy, 89 patients (median age 51 years, range 32-60 years) with MM stage II/III received a conditioning regimen with total marrow irradiation (9 Gy), busulfan (12 mg/kg) and cyclophosphamide (120 mg/kg) followed by SCT. Regimen-related toxicity according to WHO criteria and response rates defined by EBMT/IBMTR were analyzed. The main toxicity was mucositis grade III/IV in 76%, and fever grade >I in 75% of patients. Three patients developed reversible veno-occlusive disease. Transplant-related mortality was 2%. Among patients with de novo and pretreated MM, a CR rate of 48 and 41%, respectively, was documented. With a median follow-up of 45 months, the actuarial median durations of event-free survival (EFS) and overall survival (OS) after transplant were 29 and 61 months for the whole group, 36 and 85 months for patients with de novo MM, respectively. Thus, administration of this intensified conditioning regimen was associated with tolerable toxicity, a high response rate and long EFS and OS.

Adult↗
PubMed2003

Diffusion of gelation clusters in the Zimm model.

Starting from a Zimm model, we study self-diffusion in a solution of crosslinked monomers. We focus on the effects of the hydrodynamic interaction on the dynamics and the critical behaviour at the sol-gel point. Hydrodynamic interactions cause the clusters' diffusion constant to depend not only on the cluster's size but also on the cluster's shape --in contrast to the Rouse model. This gives rise to a non-trivial scaling of the Kirkwood diffusion constant averaged over all clusters of fixed size n, Dn approximately equal to n(-b) with b = 1/d(s) - 1/2 given in terms of the spectral dimension d(s) of critical percolation clusters. The long-time decay of the incoherent scattering function is determined by the diffusive motion of the largest clusters. This implies the critical vanishing D(eff) approximately equal to epsilon(a) of the cluster-averaged effective diffusion constant at the gel point with exponent a = (3/2 - tau + 1/d(s))/sigma.

Journal Article↗
PubMed2003

Fructose breath hydrogen test--is it really a harmless diagnostic procedure?

Usage of hydrogen breath tests has become one of the standard procedures in diagnosing chronic unspecific abdominal pain. These tests are said to be of sufficient specificity and sensitivity, are easily done, non-invasive and are more often practiced in outpatients. A 13-year-old boy is reported with chronic unspecific abdominal pain and growth retardation and so far misdiagnosed hereditary fructose intolerance (HFI), who developed life-threatening adverse effects during the fructose breath hydrogen test. It is concluded that the possibility of HFI should be excluded first by a carefully explored dietary history before the fructose breath test is performed under medical supervision. If there is any suspicion of HFI, a molecular genetic analysis should be preferred.

Abdominal Pain↗
PubMed2002

Butterfly hysteresis loop at nonzero bias field in antiferromagnetic molecular rings: cooling by adiabatic magnetization.

At low temperatures, the magnetization of the molecular ferric wheel NaFe6 exhibits a step at a critical field B(c) due to a field-induced level crossing. By means of high-field torque magnetometry we observed a hysteretic behavior at the level crossing with a characteristic butterfly shape which is analyzed in terms of a dissipative two-level model. Several unusual features were found. The nonzero bias field of the level crossing suggests the possibility of cooling by adiabatic magnetization.

Journal Article↗
PubMed2002

Trace determination of gadolinium in biomedical samples by diode laser-based multi-step resonance ionization mass spectrometry.

The application of high-resolution multi-step resonance ionization mass spectrometry (RIMS) to the trace determination of the rare earth element gadolinium is described. Utilizing three-step resonant excitation into an autoionizing level, both isobaric and isotopic selectivity of >10(7) were attained. An overall detection efficiency of approximately 10(-7) and an isotope specific detection limit of 1.5 x 10(9) atoms have been demonstrated. When targeting the major isotope (158)Gd, this corresponds to a total Gd detection limit of 1.6 pg. Additionally, linear response has been demonstrated over a dynamic range of six orders of magnitude. The method has been used to determine the Gd content in various normal and tumor tissue samples, taken from a laboratory mouse shortly after injection of gadolinium diethylenetriaminepentaacetic acid dimeglumine (Gd-DTPA), which is used as a contrast agent for magnetic resonance imaging (MRI). The RIMS results show Gd concentrations that vary by more than two orders of magnitude (0.07-11.5 microg mL(-1)) depending on the tissue type. This variability is similar to that observed in MRI scans that depict Gd-DTPA content in the mouse prior to dissection, and illustrates the potential for quantitative trace analysis in microsamples of biomedical materials.

Animals↗
PubMed2002

Glutaric aciduria type III: a distinctive non-disease?

Glutaric aciduria type III is a rare metabolic abnormality leading to persistent isolated glutaric acid excretion. We report the clinical and biochemical phenotypes of three affected children. The first patient is a boy with dysmorphic features and a chromosomal deletion (monosomy 6q26-qter) in whom a persistent glutaric aciduria (500 mmol/mol creatinine, normal <10) was detected during a routine metabolic investigation. The second boy suffered from acute gastroenteritis and hyperthyroidism, when an excessively high urinary glutaric acid excretion was identified (1460 mmol/mol creatinine). The third patient is a girl with constantly elevated glutaric acid in her urine (290 mmol/mol creatinine) but no symptoms of significant disease. In all our patients, glutaric aciduria type I (glutaryl-CoA dehydrogenase deficiency), glutaric aciduria type II (multiple acyl-CoA dehydrogenation defect), and secondary forms of glutaric aciduria (for example due to intestinal infections or mitochondrial dysfunction) could be excluded. Loading with the precursor amino acid lysine in all patients as well as with pipecolic acid in the third case led to an increase in urinary glutaric acid excretion, proving the endogenous origin of glutarate. Glutaric aciduria type III (a defect reported to be caused by peroxisomal glutaryl-CoA oxidase deficiency) is our presumptive diagnosis. However, peroxisomal glutaryl-CoA oxidase is not well characterized and no reliable approach for the direct determination of this enzyme is available to us. To our knowledge, in the English language literature only a single patient with glutaric aciduria type III has been described. Our cases reported here confirm the earlier assumption that glutaric aciduria type III is not related to a distinctive phenotype. Glutaric aciduria type III appears to be a rare metabolic abnormality, presumably of peroxisomal metabolism. However, its pathophysiological impact still needs further investigation.

Amino Acid Metabolism, Inborn Errors↗
PubMed2002

[Cardiac hemangiosarcoma in a dog].

The case of a 11 year-old mix breed dog is being described. It initially presented for watery diarrhea and inappetence. During the diagnostic workup, the dog developed a sustained ventricular tachycardia. Echocardiography showed a mass extending from the wall of the right ventricle which filled up the ventricle almost completely. Histopathologic examination of the mass after euthanasia of the dog revealed a hemangiosarcoma.

Animals↗
PubMed2002

Unusual case of a large midoesophageal diverticulum mimicking unstable angina pectoris.

We describe a 77-year-old lady who presented with progressive retrosternal pain radiating to the left arm and the back. After exclusion of cardiac causes a large midoesophageal diverticulum was found on oesophago-gastro-duodenoscopy. Importantly, the retrosternal pain completely disappeared after endoscopic removal of impacted food from the diverticulum. After the surgical resection the patient became fully asymptomatic. This is the first example of angina-like chest pain which definitively resulted from a midoesophageal diverticulum. Therefore, midoesophageal diverticula should be considered as a rare differential diagnosis of exercise-induced retrosternal pain.

Aged↗
PubMed2002

[Determinants of patient satisfaction: treatment and clinical factors, subjective concept of the illness and quality of life].

The aim of this study was to examine the associations between treatment factors, clinical factors and treatment satisfaction of psychiatric in-patients. Especially, the authors were interested in the question, whether treatment satisfaction in general and patient experiences in detail are equally affected by the factors mentioned above. Data were obtained from 91 in-patients of the Psychiatric Department of the Ludwig-Maximilians-University of Munich (85 % of all patients who had been in hospital since at least 3 weeks) by questionnaires on a fixed day. Global satisfaction and patients experiences with special aspects of the services were correlated to sociodemographic variables, diagnosis, psychopathological syndromes, actual mood state, patient's concept of the illness and quality of life. Global satisfaction and the rating of special treatment components are differently affected by the patients actual mood state and prior hospitalizations. Effects of gender, diagnosis and psychopathology are low; there is no correlation between education and satisfaction on both levels. In contrast, both rating levels correlate significantly with general trust in medication and physician. There are only weak correlations between global satisfaction and quality of life. Data indicate that global and specific satisfaction ratings are different in regard to some determinants but at the same time they are both affected by attitudinal factors.

Adult↗
PubMed2001

Self-deleting suicide vectors (SDSV): selective killing of p53-deficient cancer cells.

A self-deleting retrovirus vector carrying a herpes simplex virus (HSV)-thymidine kinase suicide gene has been developed to selectively kill cancer cells expressing a dysfunctional p53 tumor suppressor protein. When cells containing functional p53 are infected with the virus, the integrated provirus and the HSV-thymidine kinase gene are deleted from the genome by site-specific recombination (Cre/loxP). In contrast, cells without p53 or cells expressing a DNA-binding mutant of p53 retain the provirus and become susceptible to killing by ganciclovir. This strategy provides a new concept for the selective killing of cancer cells that can be adapted to any other dysfunctional transcription factor expressed by different tumors.

Animals↗
PubMed2001

Influence of the bovine seminal plasma protein PDC-109 on the physical state of membranes.

PDC-109 is the main component of bovine seminal plasma and has been suggested to play an important role in the genesis of bovine sperm cells. Here, the effect of binding of PDC-109 to membranes on the structure and physical properties of the lipid phase was investigated. For that, ESR measurements were undertaken on model membranes (lipid vesicles) and on biological membranes (epididymal spermatozoa) by employing various spin-labeled phospholipids. We found that PDC-109 alters the membrane structure of lipid vesicles as well as of bovine epididymal spermatozoa in that the mobility of spin-labeled phospholipids was reduced in the presence of the protein. This immobilizing effect of the protein was not restricted to analogues of phosphatidylcholine but was also detected with spin-labeled phosphatidylethanolamine. However, the extent of immobilization was lower for phosphatidylethanolamine compared with phosphatidylcholine, supporting the lipid headgroup specificity of the protein. Besides phospholipid headgroups, the physical state of membrane lipids is also important for the interaction of PDC-109 with membranes, in that, e.g., the immobilizing effect of the protein on labeled lipids was larger in membranes above the phase transition temperature compared with the effect below this temperature. The results are of relevance for understanding the physiological role of PDC-109 in the genesis of sperm cells.

Animals↗
PubMed2001

Halogenodisilanes: precursors for new disilane derivatives.

Starting from hexachloro- or hexabromodisilane a wide variety of 1,2-disubstituted tetrachlorodisilanes (RSiCl2SiCl2R) [R = Cp (2a), 4-iPrC6H4(SiMe3)N (2b), 2,6-iPr2C6H3(SiMe3)N (2c), (Me3Si)2CH (2d) (Me3Si)3C (2e), (Me3Si)3Si (2f)], tetrabromodisilanes (RSiBr2SiBr2R) [R = Cp (3a), 4-iPrC6H4(SiMe3)N (3b), (Me3Si)3Si (3f)] and the monosubstituted pentahalogenodisilanes CpSiX2SiX3 [X = Cl (4), Br (5)] were prepared. The tetrachlorodisilanes 2a-e are converted to various functionalized disilanes. Ammonolysis of 2a-e leads to the tetraaminodisilanes [RSi(NH2)2Si(NH2)2R] 6a-e. A reduction of 2d with LiAlH4 resulted in the formation of the disilane RSiH2SiH2R [R = (Me3Si)2CH] 7 and the metathesis with Me3SnF yielded the tetrafluorodisilane RSiF2SiF2R [R = (Me3Si)2CH] 8. Treatment of 6d with reagents containing H acidic protons (HX) [X = Br, I and OH] leads under elimination of NH3 to the tetrabromo- R2SiBr2SiBr2R (3d) tetraiodo- RSiI2SiI2R (9) and the tetrahydroxodisilane RSi(OH)2Si(OH)2R (10) [R = (Me3Si)2CH]. Single-crystal X-ray structural analysis of 2d, 6a, 6d, and 9 are reported.

Journal Article↗
PubMed2001

Magnetic anisotropy of a cyclic octanuclear Fe(III) cluster and magneto-structural correlations in molecular ferric wheels.

The magnetic anisotropy of the cyclic octanuclear Fe(III) cluster [Cs subsetFe(8)[N(CH(2)CH(2)O)(3)](8)]Cl was investigated. Based on a spin Hamiltonian formalism and the consequent use of all symmetries, the magnetic anisotropy could be calculated exactly to first order, i.e., in the strong exchange limit. Experimentally, the magnetic anisotropy was investigated by magnetic susceptibility and high-field torque magnetometry of single crystals. The field and angle dependence of the torque at 1.7 K could be accurately reproduced by the calculations with one single parameter set, providing accurate results for the coupling constant and single-ion zero-field-splitting. These magnetic parameters are compared to those of several related hexanuclear ferric wheels and are discussed with respect to magneto-structural correlations for both coupling constant and single-ion anisotropy.

Journal Article↗
PubMed2001

Microencapsulated cell-mediated treatment of inoperable pancreatic carcinoma.

Pancreatic cancer can seldom be resected, and chemotherapy has only a limited effect on survival or tumour load. We did a phase I/II trial in 14 patients with pancreatic cancer to assess the safety of local activation of low-dose ifosfamide. We encapsulated genetically modified allogeneic cells, which expressed a cytochrome P450 enzyme, in cellulose sulphate and delivered them by supraselective angiography to the tumour vasculature. These cells locally activated systemically administered ifosfamide. The tumours of four patients regressed after treatment, and those of the other ten individuals who completed the study remained stable. Median survival was doubled in the treatment group by comparison with historic controls, and 1-year survival rate was three times better. Further studies of this cell-therapy-based treatment combined with chemotherapy for inoperable pancreatic cancer are warranted.

Adenocarcinoma↗
PubMed2001

Transforming growth factor-beta1 induces desmoplasia in an experimental model of human pancreatic carcinoma.

Proliferation of fibrotic tissue (desmoplasia) is one of the hallmarks of several epithelial tumors including pancreatic adenocarcinoma. This tissue reaction may be deleterious or advantageous to the host or tumor. In a systematic analysis, we identified two growth factors expressed by human pancreatic carcinoma cells that are positively correlated with the ability to induce fibroblast proliferation both in vitro and in vivo, i.e., transforming growth factor (TGF)-beta1 and fibroblast growth factor-2. Here we demonstrate that the overexpression of TGF-beta1 induced up-regulation of matrix proteins and growth factors in the TGFbeta1-transfected pancreatic tumor cells. Furthermore, transfection of PANC-1 cells induces the same change in fibroblasts in either cocultivation experiments or when they are grown in conditioned medium from TGF-beta1-transfected PANC-1 cells. TGF-beta1-transfected pancreatic tumor cells induced a rich stroma after orthotopical transplantation in the nude mouse pancreas. The transfer of a single growth factor, TGF-beta1, conveys the ability to induce a fibroblast response similar to that seen in desmoplasia in human pancreatic adenocarcinoma. This effect cannot only be attributed to direct effects of TGF-beta1 but also results from the up-regulation of several other factors including collagen type I, connective tissue growth factor, and platelet-derived growth factor.

Animals↗
PubMed2001

Integrin and talin in the jellyfish Podocoryne carnea.

We have isolated an integrin-beta and -alpha subunit from Podocoryne carnea (Cnidaria, Hydrozoa) and studied their expression in the life-cycle and during cell migration, in vitro transdifferentiation and regeneration. Comparison of the integrin expression pattern with a Podocoryne talin homologue by RT-PCR demonstrates that all three genes are maternal messages and continuously expressed in the life-cycle, in medusa development and in all medusae tissues. In situ hybridisation experiments confirm co-expression of both integrin subunits in the different life-stages. Integrin expression was furthermore studied in isolated striated muscle induced to transdifferentiate to new cell types, or grafted on ECM where the muscle adheres and migrates. Integrin expression was maintained continuously throughout both processes. These results suggest that in Podocoryne carnea processes such as cell migration and differentiation are not controlled by up- or downregulation of alternative integrin subunits, but by a single integrin heterodimer which activates different downstream signalling cascades.

Amino Acid Sequence↗
PubMed2001

Clozapine-associated elevation of plasma cholinesterase.

OBJECTIVE: The goal of this study was to identify adverse effects of the atypical neuroleptic clozapine on liver function and lipid metabolism. METHODS: Data which included serum levels of clozapine and its hepatic metabolite N-desmethyl clozapine were collected from medical records of patients treated with clozapine and controls. RESULTS: We identified a clozapine-associated marked elevation of plasma cholinesterase (ChE) with unchanged levels of AST, ALT or g-GT. ChE was correlated to the serum level of clozapine and even closer to N-desmethyl clozapine. For the total patient group we observed significant correlations of ChE with the body-mass index and body weight. However, clozapine-treated patients and controls did not differ with regard to body-mass index, triglycerides, and cholesterol. CONCLUSION: We report for the first time a clozapine-associated and dose-dependent elevation of plasma ChE, which may be related to clozapine-associated effects on hepatic lipid metabolism or ChE enzyme induction.

Adult↗