Biomedical subjects

M Müller

Publications and source records attributed to M Müller.

At least 127 records · Page 7Linked to original sources

PubMed2004

Progressive dementia caused by Hashimoto's encephalopathy -- report of two cases.

Dementia induced by Hashimoto's encephalopathy (HE) seems to be a rare condition. We report on two patients, who revealed a syndrome consisting of a rapid progressive dementia with myocloni. In both patients, the detection of antithyroid antibodies enabled the diagnosis of HE. The symptoms receded completely during a high-dose glucocorticoid therapy. In patients with rapidly progressive dementia or with dementia of unknown origin, HE should be considered.

Adult↗

PubMed2004

Molecular characterization of the porcine TYK2 gene on SSC 2q1.3-->q2.1.

TYK2 is a member of the janus protein kinase family and plays an important role in the signal transduction of various cytokines including interferon alpha/beta. Cloning and characterization of the porcine TYK2 gene revealed a conserved organization with respect to other mammalian TYK2 orthologs. The porcine gene consists of 25 exons spanning approximately 26 kb and encoding a 5.3-kb mRNA. It is located in a GC-rich and gene-rich chromosome region and contains several CpG islands. The predicted 132-kDa TYK2 protein consists of 1,184 amino acids and shows 85% identity to the human TYK2 protein. The porcine TYK2 gene was localized by FISH and RH-mapping on SSC 2q1.3-->q2.1, which is in good agreement with established human-mouse-pig comparative maps.

Animals↗

PubMed2004

Polymorphic microsatellite markers in the outbred CFW and ICR stocks for the generation of speed congenic mice on C57BL/6 background.

Reliable definition of the phenotype of particular alleles is carried out in the genetic background of inbred strains. Appearance of mutations in outbred mice therefore requires the generation of congenic mice. The aim of this study was the establishment of a list of polymorphic microsatellite markers which can be used in a polymerase chain reaction (PCR)-based marker-assisted selection protocol (MASP) to allow the use of the two common outbred stocks, CFW and ICR, as donor animals for the fast generation of congenic C57BL/6 mice. The selection of informative microsatellite markers was carried out to provide a simple evaluation of the PCR products by conventional agarose gel electrophoresis. Outbred mice from three suppliers were examined. In total, 153 microsatellite loci were analysed. Here we present 76 and 70 microsatellite markers polymorphic for the outbred ICR and CFW stocks compared to C57BL/6. At least three microsatellite loci per chromosome were chosen as informative markers for the autosomal genome, giving rise to a maximum marker distance of 58 cM. Thus, additional individual markers have to be selected for the respective outbred mouse which is chosen as a donor animal.

Animals↗

PubMed2004

Detection of germ-cell-tumor-specific gene products in peripheral blood by immunomagnetic tumor cell enrichment followed by RT-PCR.

Therapeutic procedures in patients with testicular germ cell tumors (GCT) are determined by the histopathology of the primary tumor and the tumor extension. The aim of our study was to determine whether conventional staging could be supplemented by combining enrichment of disseminated testicular GCT cells from peripheral blood with subsequent detection of germ-cell-specific gene products. Blood samples from 46 patients with GCT of different clinical stages (CS) were examined by RT-PCR before therapy and >/=8 weeks thereafter for alpha-fetoprotein, beta-human chorionic gonadotropin and germ-cell-specific alkaline phosphatase mRNA. In addition, we performed titration experiments to evaluate whether the sensitivity can be improved by previous immunomagnetic tumor cell enrichment with anti-epithelial HEA-125 microbeads. No positive results were found in controls (n=15; specificity 100%). The overall ratio of positive PCR results in the group of patients with GCTs was 28.26%. The ratio was 35.7% for CS >IIb (n=5/14 patients), 20.0% for CS IIa-b (n=4/20) and 33.3% for CS I (n=4/12). FACS analysis in titration experiments with GCT cell lines showed that previous immunomagnetic tumor cell enrichment achieved a significant increase ranging up to 185.6 times the initial ratio and thus improved the measuring conditions for detection of tumor-specific transcripts. The sole qualitative RT-PCR of tumor-specific gene products in peripheral blood is not sensitive enough to improve staging in GCT patients. Immunomagnetic enrichment of GCT cells in peripheral blood seems a promising approach for increasing the sensitivity of RT-PCR.

Calcium-Binding Proteins↗

PubMed2004

Topical skin penetration of diclofenac after single- and multiple-dose application.

OBJECTIVE: Transdermal penetration of nonsteroidal anti-inflammatory drugs (NSAIDs) has been shown to be highly variable. The present study was performed to gain insight into the transdermal penetration process of topically applied diclofenac and to test whether transdermal absorption leads to pharmacologically effective concentrations in dermal tissue layers beneath the application site. MATERIAL AND METHOD: Six healthy male volunteers participated in this 2-way crossover study and were assigned to 2 treatment groups. In the first group, diclofenac was applied at a therapeutic dose of 60 mg/100 cm2 3 times daily for 4 days with subsequent occlusion with a plastic foil for 4 hours to enhance transdermal drug absorption. After a 1-week wash-out, diclofenac was applied at a single dose of 300 mg/100 cm2 without occlusion. Diclofenac in both groups was applied on a previously shaven area of the thigh. Transdermal penetration was assessed employing in vivo microdialysis. RESULTS: After multiple-dose administration mean diclofenac concentrations of 0.48 +/- 0.35 ng x ml(-1) were observed in subcutaneous tissue (mean +/- SEM). The mean AUC(subcutis/plasma) ratio of 0.08 +/- 0.02 indicates redistribution of diclofenac from the systemic circulation to the tissue. After single-dose treatment, mean tissue concentrations were 24.26 +/- 46.43 ng x ml(-1) with a mean AUC(subcutis/plasma) ratio of 60.85 +/- 57.59, which suggests direct tissue penetration of diclofenac. CONCLUSIONS: Transdermal penetration of diclofenac after multiple as well as after single application of the present formulation is highly variable. In addition to other factors influencing the transdermal penetration process, dose and mode of administration are important factors determining whether pharmacologically effective local tissue concentrations are attained.

Administration, Cutaneous↗

PubMed2004

[Endoscopic, pathologic-anatomic and histologic findings in the bovine teat. 1. Changes in the area of the teat cistern in slaughtered cows].

In the present study 795 teats of slaughtered cows were examined endoscopically. Teats which showed lesions were examined histologically. Abnormalities were detected endoscopically in 37 teats. In five cases red discolorations were observed. Histologically these alterations proved to be fresh bleedings within the fibromuscular layer of the teat cistern. Thirteen teats showed yellowish discolorations of the cistern surface. Three of these cases could not be cleared up histologically. In the other cases moderate or severe blood pigment deposition (n = 10) or severe fibrosis (n = 3) of the fibromuscular layer were found. Neither fresh bleeding nor severe blood pigment deposition was found in teats with normal coloured epithelium of the cistern. Cistern surface was smooth in 18 cases, whereas in 19 cases nodules were found. Histologically all nodules consisted of fibrovascular tissue ("granulation tissue") covered with cisternal epithelium. Detailed histological examinations, however, revealed considerable morphological variations regarding the overlying epithelium, the extent and kind of cellular infiltration, the extent of angioplasia and fibroplasia as well as fresh bleedings or deposition of blood pigment in the underlying fibrovascular tissue in some cases. It was concluded, that teat endoscopy enables a differentiation between fresh and old bleedings according to the coloration of the cisternal surface. Nodular proliferations of the cistern surface generally consists of fibrovascular ("granulation") tissue. Further histological details, however, and thus possible information about the pathogenesis of the lesions cannot be assessed endoscopically.

Animals↗

PubMed2004

[Endoscopic, pathologic-anatomic and histologic findings in the bovine teat. 2. Changes in the area of Fürstenberg's rosette].

In the present study endoscopically diagnosed changes of the Fürstenberg's rosette were examined histologically. For this purpose the teats of 200 slaughtered cows were inspected. In 19 cases proliferations in the region of the Fürstenberg's rosette were found. Additionally, tissue samples were taken from the Fürstenberg's rosette of 26 cows which showed milk flow disorders due to stenoses of this part of the teat. Teats of slaughtered cows as well as biopsy specimens were fixed in 5% formaldehyde and embedded in paraffin and in plastic. All specimens were stained according to H.E., Giemsa and Turnbull, respectively. Histologically, the proliferations of the Fürstenberg's rosette consisted of fibrovascular tissue (granulation tissue) covered by keratinized squamous epithelium (teat canal epithelium) in eleven cases. In the other cases double-layered cuboid epithelium (cisternal epithelium) was found additionally. The formation of granulation tissue and deposition of blood pigment was observed exclusively in areas covered by stratified epithelium. Therefore a traumatic lesion of the teat canal was supposed to be the cause of the histological findings. In contrast to several reports in the literature, however, no indications of an inversion of the teat canal epithelium were found. On the basis of these findings, the hitherto assumed idea of pathogenesis of proliferations of the Fürstenberg's rosette was modified and a new pathogenesis pattern was developed.

Animals↗

PubMed2004

Duodenum preserving pancreatic head resection in the treatment of chronic pancreatitis.

Chronic pancreatitis is an inflammatory disease which is characterized by a progressive conversion of pancreatic parenchyma into fibrous tissue. Most frequent causes are alcohol over-consumption, beside anatomic variants such as pancreas divisum, cholelithiasis or individual genetic predisposition. The process of fibrotic transformation with consecutive loss of pancreatic parenchyma leads to exocrine insufficiency and maldigestion, and in advanced stage of the disease to diabetes mellitus. In addition to exocrine and endocrine malfunction, mechanical complications such as formation of pancreatic pseudocysts, duodenal and common bile duct obstruction occur. About 50% of the patients with chronic pancreatitis will need surgical intervention due to intractable chronic pain. Recent investigations suggest that the head of the pancreas triggers the chronic inflammatory process. Therefore, resection of this inflammatory mass must be regarded as the pivotal part of any surgical intervention. Radical techniques such as Whipple-procedure are undoubtedly successful regarding pain reduction. However, even in its pylorus preserving variant this technique is associated with a high postoperative morbidity due to large loss of pancreatic parenchyma and the loss of the duodenal passage. 30 years ago, H. G. Beger described for the first time the technique of duodenum preserving pancreatic head resection that better combines resection of the pancreatic head with low morbidity. Over the years different variations of the original Beger technique (Frey, Izbicky, Berne modification) have been developed, and the excellent results obtained with these techniques underline, that organ sparing procedures should be preferred in the surgical treatment of chronic pancreatitis.

Chronic Disease↗

PubMed2003

Wedge filling and interface delocalization in finite Ising lattices with antisymmetric surface fields.

Theoretical predictions by Parry et al. for wetting phenomena in a wedge geometry are tested by Monte Carlo simulations. Simple cubic LxLxL(y) Ising lattices with nearest neighbor ferromagnetic exchange and four free LxL(y) surfaces, at which antisymmetric surface fields +/-H(s) act, are studied for a wide range of linear dimensions (4</=L</=320, 30</=L(y)</=1000), in an attempt to clarify finite size effects on the wedge filling transition in this "double-wedge" geometry. Interpreting the Ising model as a lattice gas, the problem is equivalent to a liquid-gas transition in a pore with quadratic cross section, where two walls favor the liquid and the other two walls favor the gas. For temperatures T below the bulk critical temperature T(c) this boundary condition (where periodic boundary conditions are used in the y direction along the wedges) leads to the formation of two domains with oppositely oriented magnetization and separated by an interface. For L,L(y)--> infinity and T larger than the filling transition temperature T(f)(H(s)), this interface runs from the one wedge where the surface planes with a different sign of the surface field meet (on average) straight to the opposite wedge, so that the average magnetization of the system is zero. For T T(f)(H(s)) from below, as is the corresponding behavior of the magnetization and its moments. We consider the variation of l(0) for T>T(f)(H(s)) as a function of a bulk field and find that the associated exponents agree with theoretical predictions. The correlation length xi(y) in the y direction along the wedges is also studied, and we find no transition for finite L and L(y)--> infinity. For L--> infinity the prediction l(0) proportional, variant (H(sc)-H(s))(-1/4) is verified, where H(sc)(T) is the inverse function of T(f)(H(s)) and xi(y) proportional, variant (H(sc)-H(s))(-3/4), respectively. We also find that m vanishes discontinuously at the filling transition. When the corresponding wetting transition is first order we also obtain a first-order filling transition.

Journal Article↗

PubMed2003

Surface modification of PLGA microspheres.

Microspheres made of poly(lactic-co-glycolic acid) (PLGA) are biocompatible and biodegradable, rendering them a promising tool in the context of drug delivery. However, nonspecific adsorption of plasma proteins on PLGA micro- and nanospheres is a main limitation of drug targeting. Poly(L-lysine)-g-poly(ethylene glycol) (PLL-g-PEG), physisorbed on flat metal oxide surfaces, has previously been shown to suppress protein adsorption drastically. The goal of our work was to characterize the efficiency of the protein repellent character of PLL-g-PEG on PLGA microspheres and to show the feasibility of introducing functional groups on the PLGA microspheres via functionalized PLL-g-PEG. To quantify the adsorbed amount of protein, a semiquantitative method that uses confocal laser scanning microscopy (CLSM) was applied. The first part of the experiment confirms the feasibility of introducing specific functional groups on PLL-g-PEG-coated PLGA microspheres. In the second part of the experiment, PLL-g-PEG-coated PLGA microspheres show a drastic decrease of adsorbed proteins by two orders of magnitude in comparison to uncoated PLGA microspheres. Low protein-binding, functionalizable microspheres provide a fundamental basis for the design of drug delivery and biosensor systems.

Biosensing Techniques↗

PubMed2003

[Vitreous body floaters and vitrectomy with full visual acuity].

PURPOSE: To evaluate the role of vitrectomy in patients with visually disturbing vitreous body floaters and full visual acuity (VA). METHODS: A total of 9 eyes from 8 patients (2 female, 7 male, median age 57 years) with a preoperative VA of 1.0 were analysed retrospectively. The median duration of symptoms was 12 months. In all eyes a pars plana vitrectomy was performed. The median follow-up period was 13 months. RESULTS: No intraoperative or postoperative complications were observed. In all patients vision improved subjectively and objective VA remained unchanged. In 2 out of 5 phacic patients a cataract extraction was performed during the follow-up period. CONCLUSIONS: In a selected group of patients vitrectomy can improve subjective vision even in eyes with full objective VA. A critical patient selection with respect to psychological criteria and the individual risk of vitrectomy is extremely important.

Adult↗

PubMed2003

Avoiding boundary effects in Wang-Landau sampling.

A simple modification of the "Wang-Landau sampling" algorithm removes the systematic error that occurs at the boundary of the range of energy over which the random walk takes place in the original algorithm.

Journal Article↗

PubMed2003

Gastrointestinal transit and release of 5-aminosalicylic acid from 153Sm-labelled mesalazine pellets vs. tablets in male healthy volunteers.

BACKGROUND: Mesalazine (5-aminosalicylic acid)-containing formulations, designed to optimize drug delivery to the ileo-caecal region, represent a cornerstone in the treatment of inflammatory bowel diseases. AIM: : To test, by means of pharmaco-scintigraphy, whether novel mesalazine-containing pellets release 5-aminosalicylic acid in the same target region as mesalazine tablets (Salofalk). METHODS: Fourteen healthy male volunteers received a single dose of either pellets or tablets containing 500 mg of mesalazine and 2 mg of 152Sm2O3 with a 1-week washout period. The gastrointestinal transit of 153Sm, incorporated into the formulations, was followed by gamma-scintigraphy. Mesalazine release was verified by assessing 5-aminosalicylic acid plasma pharmacokinetics. RESULTS: The formulations reached the ileo-caecal target region almost at the same time (3.3 +/- 1 and 3.8 +/- 1 h for pellets and tablets, respectively). Plasma 5-aminosalicylic acid tmax values were comparable and corresponded to the time during which the formulations were located in the target region. Plasma AUC values were significantly lower for pellets, which might be explained by a more prolonged release of 5-aminosalicylic acid. CONCLUSIONS: Novel mesalazine pellets and Salofalk tablets release active 5-aminosalicylic acid in the same target region and pass through the gastrointestinal tract under fasting conditions in healthy volunteers in a comparable time. From a comparison of in vitro dissolution and plasma concentration data, a slower and more prolonged release of 5-aminosalicylic acid from pellets is suggested.

Adult↗

PubMed2003

Platinum determination by inductively coupled plasma-sector field mass spectrometry (ICP-SFMS) in different matrices relevant to human biomonitoring.

The analytical challenges of Pt determination by ICP-SFMS posed by different human tissues and fluids have been critically assessed. Investigated samples were (1) urine, (2) serum of cancer patients sampled during chemotherapy with carboplatin, (3) microdialysates (20 micro L sample volume) collected from tumor and non-tumor tissue, and, finally-for the first time-(4) human lung tissue to study background concentrations of inhaled platinum. Sample preparation involved microwave digestion and open vessel treatment or simple dilution (microdialysates). Depending on the sample preparation and introduction systems used (microconcentric nebulization, ultrasonic nebulization with and without membrane desolvation) excellent procedural detection limits (3s criterion) of 0.35 pg g(-1) for urine, 420 pg g(-1) for serum, 400 pg g(-1) for lung tissue and 13 pg g(-1) for microdialysates could be obtained. Ultratrace concentrations of 1-40 pg g(-1), and 1000-3000 pg g(-1) were measured in urine and human lung tissue, respectively, as typical for samples in environmental studies. Quantification was carried out by IDMS and standard addition in the case of urine samples. Internal standardization could not correct for non-spectral interferences in external calibration. In the serum and microdialysates of patients during chemotherapy with carboplatin, elevated Pt levels ranging between 0.01 and 10 micro g g(-1) were determined by external calibration ((195)Pt isotope). For all investigated samples spectral interferences could be excluded by following different strategies. High-resolution control measurements ((194)Pt, (195)Pt) were performed in the case of elevated Pt levels, i.e. for microdialysates and serum samples. An Hf/Pt ratio of 0.4 was determined in human lung samples. An HfO formation ratio of 0.2% was assessed for standard solutions at the present experimental conditions, revealing that the contribution of (179)Hf(16)O, (178)Hf(17)O, (177)Hf(18)O to the (195)Pt isotope signal used for quantification was not significant.

Blood Chemical Analysis↗

PubMed2003

[Molecular diagnostics in urologic oncology. Detection of nucleic acids in urine samples].

The goal of molecular diagnostics in oncology is the early diagnosis of malignant disease processes during initial work-up or as part of follow-up. Body fluids serve as the primary material for non-invasive diagnostic methods. Besides actual tumor cells, the examination of urine can yield evidence of secreted proteins or even free nucleic acids. In principle, all of the methods available for the detection of tumor markers in tissue or blood samples can be successfully applied to the examination of urine samples. However, molecular biological examination of urine samples is associated with important problems because the cells in such samples are exposed to significant degradation and regression effects and because certain components of the urine act to inhibit the polymerase chain reaction. The present overview discusses the respective strengths and weakness of the available technology as applied to the diagnosis of urologic malignancies. Experimental studies conducted to date have reported high sensitivities and specificities for molecular diagnostics using urine samples. It is important to note that not only carcinomas of the urinary bladder can be diagnosed from material obtained in urine samples: in fact, the method can be used to diagnose entities such as renal cell and prostate carcinomas and, due to renal filtration of DNA, even non-urologic malignancies. The diagnostic application of these methods, however, remains in an experimental stage and must still clear several hurdles before becoming available for routine clinical use.

Biomarkers, Tumor↗

PubMed2003

Interface localization-delocalization in a double wedge: a new universality class with strong fluctuations and anisotropic scaling.

Using Monte Carlo simulations and finite-size scaling methods we study "wetting" in Ising systems in a LxLxL(y) pore with quadratic cross section. Antisymmetric surface fields H(s) act on the free LxL(y) surfaces of the opposing wedges, and periodic boundary conditions are applied along the y direction. In the limit L--> infinity, L(y)/L(3)=const, the system exhibits a new type of phase transition, which is the analog of the "filling transition" that occurs in a single wedge. It is characterized by critical exponents alpha=3/4, beta=0, and gamma=5/4 for the specific heat, order parameter, and susceptibility, respectively.

Journal Article↗

PubMed2003

Changes in linear dynamics of cerebrovascular system after severe traumatic brain injury.

BACKGROUND AND PURPOSE: We sought to describe the dynamic changes in the cerebrovascular system after traumatic brain injury by transfer function estimation and coherence. METHODS: In 42 healthy volunteers (mean+/-SD age, 37+/-17 years; range, 17 to 65 years), spontaneous fluctuations of middle cerebral artery blood flow velocity and of finger blood pressure (BP) were simultaneously recorded over a period of 10 minutes under normocapnic and hypocapnic conditions to generate normative spectra of coherence, phase shift, and gain over the frequency range of 0 to 0.25 Hz. Similar recordings were performed in 24 patients with severe traumatic brain injury (Glasgow Coma Scale score 70 mm Hg. Each blood flow velocity/BP recording was related to the presence or absence of middle cerebral artery territory brain parenchyma lesions on cranial CT performed within a close time frame. RESULTS: In controls, hypocapnia decreased coherence (0.0 to 0.20 Hz), increased phase shift (0.0 to 0.17 Hz), and decreased gain in the frequency range of 0.0 to 0.11 Hz but increased gain at frequencies of 0.20 to 0.25 Hz (P<0.01 for all frequency ranges reported). In patients with traumatic brain injury, 102 investigations were possible. Compared with controls, coherence was increased in the frequency range <0.03 Hz and between 0.13 and 0.25 Hz in both normocapnia and hypocapnia, irrespective of the CT findings. Gain was unchanged in normocapnia and in the absence of a CT lesion. Gain was decreased in hypocapnia at frequencies >0.12 Hz irrespective of the presence/absence of a CT lesion. Phase shift decreased rapidly between 0.06 and 0.13 Hz under hypocapnic conditions and under normocapnic conditions in the presence of a CT lesion (P< 0.01). CONCLUSIONS: Use of spontaneous fluctuations of blood flow velocity and BP to assess the cerebrovascular system dynamically requires consideration of the Paco2 level. In different conditions, including severe traumatic brain injury, the cerebrovascular system behaves linearly only in parts of the investigated frequency range.

Adolescent↗

PubMed2003

Fusion, leakage and surface hydrophobicity of vesicles containing phosphoinositides: influence of steric and electrostatic effects.

Calcium and lanthanum ion-induced fusion of lipid vesicles containing phosphatidylinositol (PI), phosphatidylinositol-4-monophosphate (PIP), phosphatidylinositol-4,5-bisphosphate (PIP2) or phosphatidylinositol-3,4,5-trisphosphate (PIP3) and its associated membrane properties, e.g., surface dielectric constant and vesicle leakage, were studied by fluorescence methods. The presence of poly-phosphorylated phosphoinositides (PPI) in lipid vesicles enhanced fusion, depending on the PPI phosphorylation level and the PPI concentration, as determined by the lipid mixing assay. This correlation held even at physiologically relevant small concentrations of PPI in vesicle membranes. However, the presence of nonphosphorylated PI inhibited fusion due to the steric effect of the inositol ring. The cation threshold concentration for the lipid mixing of vesicles made of mixtures of phosphatidylserine (PS) with PI increased with increasing PI contents. For all vesicle systems studied, a decrease in vesicle surface dielectric constant and an increase in vesicle leakage accompanied fusion. The presence of the nonphosphorylated inositol ring in PI did not interfere with the changes in the surface dielectric constant caused by fusogenic cations. Therefore, we deduce that the reduction of the surface dielectric constant is a necessary condition for membrane fusion to occur but it does not correlate with membrane fusion when interacting membranes are blocked for close approach as by the nonphosphorylated inositol ring.

Calcium↗