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Biomedical subjects

U Müller

Publications and source records attributed to U Müller.

At least 55 records · Page 3Linked to original sources
PubMed2003

[Clinical usefulness and diagnostic value of percutaneous liver biopsy in patients with chronically elevated liver enzymes of non-viral origin].

BACKGROUND: In the context of increasing non-invasive diagnostic techniques the purpose of the present study was to determine the clinical usefulness and the diagnostic value of percutaneous liver biopsy in patients with chronically elevated liver enzymes of non-viral origin. PATIENTS AND METHODS: 100 patients from the outpatient clinic of the department of gastroenterology and hepatology who had a liver biopsy in the years 1996 to 1998 because of chronically elevated alanine-aminotransferase (ALT) and/or gamma-glutamyltransferase (gamma-GT) levels were included. Exclusion criteria were as follows: chronic hepatitis B or C infection, focal liver disease and clinical signs of hepatic decompensation. Retrospectively gained clinical data were independently evaluated by two experienced hepatologists. Initially, both examiners made a preliminary clinical diagnosis prior to knowing results from liver histology. With the results from liver histology both examiners were asked to make a final diagnosis. For each patient, the preliminary clinical diagnoses of both examiners were then correlated with the corresponding final diagnoses. RESULTS: Liver histology led in 71 % respectively 74 % of the patients to confirmation or specification of the clinical diagnosis. Liver biopsy was particularly helpful in differentiating non-decompensated liver cirrhosis, cryptogenic hepatitis, auto-immune hepatitis and biliary diseases. CONCLUSION: Despite improved non-invasive diagnostic tools including a broad spectrum of serologic tests liver biopsy is often indispensable for differentiating primary liver from biliary diseases and for the early detection of patients with liver cirrhosis.

Adult↗
PubMed2003

[A systematic comparison of national and international dementia guidelines].

Several guidelines for the evidence-based diagnosis and treatment of dementing disorders have been published in Germany and worldwide during the last years. This review analyses the content and methodological quality of 13 recently published dementia guidelines. There are some unequivocal recommendations for diagnostic procedures (e. g. clinical evaluation, neuropsychological screening, structural brain imaging) and treatment (e. g. cholinesterase inhibitors). There is a broad range of opinions on other procedures (e. g. routine EEG, FDG PET, cognitive training). A discussion of the prevalent guideline pluralism and a pleading for regionally adapted international guidelines conclude this article.

Dementia↗
PubMed2003

The relationship between cup design and the radiological signs of aseptic loosening in total hip arthroplasty.

We assessed differences in the incidence and appearance of the radiological signs of loosening of the cup for various types of design. This was an observational study based on hip registry data of 15,340 patients with 17,951 total hip arthroplasties collected over a period of 33 years in 49 hospitals in Central Europe. The threaded and the press-fit titanium cups showed significantly less aseptic loosening than the other systems. The direction of migration and the frequency of the radiological signs of loosening differed between the cup systems and were time-dependent. Our findings indicate the superiority of uncemented threaded cups and press-fit titanium cups over other designs of cup.

Acetabulum↗
PubMed2002

Is the unitarity of the quark-mixing CKM matrix violated in neutron beta-decay?

We report on a new measurement of neutron beta-decay asymmetry. From the result A(0) = -0.1189(7), we derive the ratio of the axial vector to the vector coupling constant lambda = g(A)/g(V) = -1.2739(19). When included in the world average for the neutron lifetime tau = 885.7(7) s, this gives the first element of the Cabibbo-Kobayashi-Maskawa (CKM) matrix V(ud). With this value and the Particle Data Group values for V(us) and V(ub), we find a deviation from the unitarity condition for the first row of the CKM matrix of Delta = 0.0083(28), which is 3.0 times the stated error.

Journal Article↗
PubMed2002

Measurement of the beam-helicity asymmetry in the p((-->)e,e'p)pi(0) reaction at the energy of the Delta(1232) resonance.

In a p((-->)e,e'p)pi(0) out-of-plane coincidence experiment at the three-spectrometer setup of the Mainz Microtron MAMI, the beam-helicity asymmetry has been precisely measured around the energy of the Delta(1232) resonance and Q(2) = 0.2(GeV/c)(2). The results are in disagreement with three up-to-date model calculations. This is interpreted as a lack of understanding of the nonresonant background, which in dynamical models is related to the pion cloud.

Journal Article↗
PubMed2002

Effects of pallidal deep brain stimulation and levodopa treatment on reaction-time performance in Parkinson's disease.

Basal ganglia-thalamocortical circuits play an important role in movement preparation and execution. Tracer, single-cell, and lesion studies in monkeys suggest the existence of topologically segregated motor and nonmotor basal ganglia cortical circuits. In this study we used deep brain stimulation (DBS) of the posteroventrolateral globus pallidus internus (GPi) in patients with Parkinson's disease to elucidate the function of the GPi in human sensorimotor behavior. This question was investigated by comparing the influence of DBS on patients' performance in various reaction-time tasks that differed with respect to cognitive but not motor requirements. As a main result, DBS improved performance on the different tasks independently of the complexity of the involved cognitive processing functions. Furthermore, the observed effects did not depend on the modality of the processed information. These results suggest that the functional state of the posteroventrolateral GPi selectively affects the motor stage in simple sensorimotor acts, because this stage was the only stage involved in all investigated tasks. In addition to DBS, we manipulated the levodopa medication state of the PD patients. In contrast to DBS, levodopa effects on reaction times were less consistent. Levodopa improved reaction times in choice reaction tasks significantly, while affecting reaction times in a simple reaction task to a lesser extent. Error analysis revealed that the medication-dependent reaction-time improvement in the choice reaction tasks was accompanied by an increase in errors, suggesting a shift of the speed-accuracy criteria of the patients. A similar pattern of results was not observed for the DBS effects. Taken together, our data are in agreement with recent findings in monkeys that indicate a topological organization of the GPi in which motor functions are localized in posterolateral regions apart from cognitive regions. Furthermore, our data show a way to uncover the subcortical-cortical circuitry serving human sensorimotor behavior.

Acoustic Stimulation↗
PubMed2002

[Levodopa dependency in Parkinson's disease: case report and review].

Only a few patients with Parkinson's disease and levodopa dependency or abuse have been reported. We present a 35-year-old patient with young-onset Parkinson's disease who developed motor complications, levodopa dependency, and drug-induced psychosis after primary treatment with levodopa. Diagnostic criteria and treatment guidelines for this neuropsychiatric disorder are presented as well as a tentative neurobiological answer to the question of why levodopa dependency is observed only in a minority of patients with Parkinson's disease.

Adult↗
PubMed2002

Mutations of GCH1 in Dopa-responsive dystonia.

Dopa responsive dystonia (DRD) is an autosomal dominant dystonia caused by mutations in the gene GCH1 in about 50% of cases. GCH1 codes for GTP cyclohydrolase I, a rate limiting enzyme in the synthesis of tetrahydrobiobterin (BH(4)) from GTP. There is reduced penetrance and pronounced variation in expressivity of GCH1 mutations in families with DRD. Correlations between given mutations in GCH1 and phenotypes cannot be established. Mutations in GCH1 appear to function as dominant-negatives but the exact mechanism remains unclear. Additional open questions in DRD include the molecular mechanisms resulting in highly variable expressivity of symptoms and the more likely occurrence of symptoms in a female than in a male carrier of a GCH1 mutation.

Biopterins↗
PubMed2002

Comparison of four variants of a major allergen in hazelnut (Corylus avellana) Cor a 1.04 with the major hazel pollen allergen Cor a 1.01.

The aim of this study was to produce the Bet v 1-related major hazelnut allergen Cor a 1.0401 and variants thereof as recombinant allergens, and to compare their immuno-reactivity with the major hazel pollen allergen using sera of patients whose hazelnut allergy recently was confirmed by double-blind placebo-controlled food challenges (DBPCFC) in a multicenter study. Total RNA was isolated from immature hazelnuts and transcribed into cDNA. Full length coding DNA obtained by PCR-strategy was subcloned into pTYB11 vector and expressed in E. coli ER2566 cells. Native non-fusion target proteins were purified by DTT-induced self-cleavage of the intein-tagged N-terminal fusion proteins. IgE reactivity of the recombinant allergens was tested by enzyme allergosorbent test (EAST), EAST-inhibition, immunoblot-inhibition and histamine release assays. Four recombinant allergens were produced showing deduced amino acid sequence identities among each other of 97-99%, and were considered as variants Cor a 1.0401 (GenBank Accession no.: AF136945), Cor a 1.0402 (AF323973), Cor a 1.0403 (AF323974) and Cor a 1.0404 (AF323975). Cor a 1.0402 and 03 only differed in a C4S exchange. Cor a 1.0404 had a unique proline residue in position 99. Surprisingly, only 63% identity was revealed with hazel pollen Cor a 1. EAST with 43 sera of patients with positive DBPCFC to hazelnut indicated IgE reactivity to Cor a 1.0401 in 95% of the sera, to Cor a 1.0402 in 93%, to Cor a 1.0403 in 91%, and in only 74% of the sera to the proline variant Cor a 1.0404. The allergenic activity of the four variants was confirmed by histamine release assays in 15 hazelnut-allergic patients stimulated with the four variants and controls. Eleven sera were positive with extract from native hazelnut, 13 with rCor a 1.0401, 12 with rCor a 1.0402, 11 with rCor a 1.0403, and only two with rCor a 1.0404 containing the proline exchange. The high IgE binding variant Cor a 1.0401 showed only partial IgE cross-reactivity with pollen Cor a 1. IgE-binding and histamine release capacity led to a concordant ranking of the allergenic activity of the recombinant variants: Cor a 1.0401>Cor a 1.0402 and 03>Cor a 1.0404 (the proline variant). Similar results for Cor a 1.0402 and 03 suggest a minor influence in IgE binding of cysteine in position 4, whereas proline in position 99 appears to be responsible for the decrease in IgE reactivity in Cor a 1.0404. It appears that the epitopes of hazelnut Cor a 1.04 are less related to pollen Cor a 1 than to Bet v 1 from birch pollen. Low IgE binding variants or mutants of Cor a 1.04 are candidate compounds for developing a novel and safe approach of specific immunotherapy of hazelnut allergy.

Allergens↗
PubMed2002

Tests of biocompatibility of alpha-tocopherol with respect to the use as a stabilizer in ultrahigh molecular weight polyethylene for articulating surfaces in joint endoprostheses.

To inhibit the oxidation in vivo of hip-cups made of ultrahigh molecular weight polyethylene (UHMW-PE), the natural antioxidant alpha-tocopherol was added to the polymer. The added alpha-tocopherol may however undergo chemical transformations during manufacturing and sterilization by gamma-irradiation of hip-cups which may differ from human metabolism. Therefore, the question of the biocompatibility of the respective transformation products was investigated on test samples, which were prepared under the same conditions as applied for the production and sterilization of hip-cups. Thin plates (25 x 18 x 2 mm(3)) were fabricated out of test samples to investigate the cytotoxic activity according to EN 30993-5. In cytotoxicity testing, proliferation, mitochondrial activity and membrane integrity were not influenced by the material. In contrast, cell adhesion and cell spreading were diminished as shown with hemalum staining. In order to investigate the genotoxicity, the alpha-tocopherol and its transformation products were extracted from test specimens by n-heptane at 185 degrees C under nitrogen atmosphere. Then the n-heptane was evaporated in vacuo and the remaining alpha-tocopherol and its transformation products were dissolved in DMSO. The genotoxicity of this extract was then tested by the Ames-test according to DIN UA 12 (1995), which showed no indication for genotoxic activity.

Journal Article↗
PubMed2002

Enriched early experiences of mice underexpressing the beta-amyloid precursor protein restore spatial learning capabilities but not normal openfield behavior of adult animals.

We have previously reported severely impaired spatial learning in mutant mice underexpressing a shortened variant of the beta-amyloid precursor protein (beta-APPtheta/theta). This targeted mutation is functionally equivalent to a null mutation. It also disturbs behavioral and neurological maturation with deficits emerging mainly between postnatal day (pd) 11 and 19. Such early tested mice exhibited almost no genotype-related difference in Morris water maze learning, raising the possibility that early handling might have compensated for genetic deficits. To verify this effect, we compared watermaze learning and open field behavior of 66 adult mutant and wildtype mice having been handled during pd 3-27 with that of 70 non-handled mutant and wildtype mice. Neurological testing during pd 3-27 markedly reduced time near wall and improved spatial retention of adult mutants, restoring their learning capabilities to wildtype levels. Early handling did not cure the mutation associated activity deficit in the open field, but mainly increased center field exploration in both mutants and wildtypes. In a follow-up experiment we analyzed whether an early (pd 3-10, n = 22) or middle (pd 11-19, n = 24) period of handling in form of neurological testing had differential effects on adult behavior. Mice handled during pd 11-19 had slightly shorter escape times than mice handled during pd 3-10 but were not significantly different in other behavioral measures. There were no sex related differences. Correlational and factor analysis showed that both the mutation and early handling had pleiotropic behavioral effects, resulting in differentially impaired mutants depending on the test situation. Likewise, early handling affected not only thigmotactic tendencies but also, more subtly, other behavioral components underlying water maze learning. We conclude that early postnatal stimulation can prevent mutation induced learning deficits in adult mice, but probably through other developmental mechanisms than those affected by the mutation. This implies that some behavioral impairments related to beta-APP malfunction may be corrected through simple treatments.

Amyloid beta-Protein Precursor↗
PubMed2002

Manipulation of working memory information is impaired in Parkinson's disease and related to working memory capacity.

It has been suggested that in patients with Parkinson's disease (PD), difficulties in the manipulation of information, which result in problems in executive tasks, are related to a reduction of working memory capacity (J. D. E. Gabrieli, J. Singh, G. T. Stebbins, & C. G. Goetz, 1996). The present study selectively varied the manipulation demand irrespective of the maintenance requirement. In a group of 14 PD patients, performance declined overproportionally with the increasing task demand and was significantly correlated with a measure of working memory capacity. These results suggest that the complexity of working memory processing may decisively contribute to the exhaustion of resources in PD patients. Increasing complexity may either affect their manipulation ability directly or impede the management of inhibitory control requirements inherent to the task.

Adult↗
PubMed2002

A polymorphism of the brain-derived neurotrophic factor (BDNF) is associated with Alzheimer's disease in patients lacking the Apolipoprotein E epsilon4 allele.

Because of its implication in neuroprotection, formation of long lasting memories and a disturbed function in Alzheimer's disease (AD), brain-derived neurotrophic factor (BDNF) may represent an appropriate candidate gene conferring risk to AD. Recently, a single nucleotide polymorphism (C-270T) within the BDNF gene has been associated with late onset AD in a Japanese population giving an odds ratio (OR) of 3.8. Because of the importance of this finding we analysed the BDNF polymorphism in a German sample consisting of 210 patients with AD and 188 cognitively healthy controls. The T-allele frequency was higher in patients with AD (11.9%) compared to controls (6.9%) (P = 0.035; OR = 2.26; 95% CI: 1.04-4.48). The risk conferred by the T-allele was stronger in patients who lack the ApoE epsilon4 allele giving an OR of 2.61 (1.21-5.64) P = 0.015, particularly in patients with early onset of the disease; OR 3.13 (1.32-7.43); P= 0.01. Due to the small number of patients showing both, lack of the ApoE epsilon4 allele and the BDNF T allele (n = 18), the result needs to be confirmed in a larger sample. The results suggest that the BDNF C-270T polymorphism is a relevant risk factor for AD particularly in patients lacking the ApoE epsilon4 allele in this German sample.

Age of Onset↗
PubMed2002

Laser-induced weal and flare reactions: clinical aspects and pharmacological modulation.

BACKGROUND: Among the adverse effects of cutaneous laser therapy, weal and flare reactions immediately after treatment have received little attention, and the pathomechanisms are unclear. OBJECTIVES: To study clinical features and possible mechanisms of laser-induced weal and flare reactions in order to identify means of possible therapeutic intervention. METHODS: Normal skin from the inner arm of 20 volunteers was treated with an argon laser, and the size of weal and flare reactions was measured over a 60-min period. Skin biopsies were taken from four volunteers before and up to 24 h after laser treatment and examined histologically and immunohistologically. Possible underlying mechanisms were also explored using various topical or systemic pharmacological agents. RESULTS: Wealing was noted in 19 of 20, and flare reactions in all volunteers, with peak values at 15 min. Skin biopsies showed central coagulation of the tissue, cleft formation between epidermis and dermis, normal numbers of morphologically intact mast cells on toluidine blue staining close to the lesion, and only minor upregulation of endothelial and leucocyte adhesion molecules. In agreement with these findings, pretreatment with acetylsalicylic acid, the H1-blocker loratadine and triamcinolone cream was ineffective or resulted in a non-significant reduction of weal and flare reactions. In contrast, local anaesthetics as well as neuropeptide depletion of skin with capsaicin abolished the reactions almost completely. CONCLUSIONS: Transient weal and flare reactions in response to laser treatment occur in almost all persons and are based primarily on a neurogenic rather than a histamine- or mast cell-dependent mechanism.

Adult↗
PubMed2002

Diffuse neonatal hemangiomatosis associated with Simpson-Golabi-Behmel syndrome: a case report.

Diffuse neonatal hemangiomatosis (DNH) is a rare disorder characterized by multiple cutaneous and visceral hemangiomas that usually presents in newborns and has a high mortality rate. While previously reported cases of DNH describe multiple cutaneous hemangiomas, we present a patient with a single hemangioma of the ear, who also had DNH of the central nervous system and visceral organs. Furthermore, in this report we present a new constellation of findings, namely, a Simpson-Golabi-Behmel syndrome (SGBS). The practical implication on the basis of the experience with our patient is the need to ensure adequate diagnostics for patients with large hemangiomas as well as for patients with multiple cutaneous hemangiomas, because DNH also can occur in single hemangiomas in rare cases.

Central Nervous System Neoplasms↗
PubMed2002

Apolipoprotein E polymorphism in German patients with frontotemporal degeneration.

OBJECTIVES: The apolipoprotein E (apoE) polymorphism, designated as epsilon2, epsilon3, epsilon4, is a genetic risk factor associated with several forms of dementia. Inconclusive results have been reported in patients with frontotemporal degeneration which prompted this study of the apoE polymorphism in a German sample with frontotemporal degeneration. METHODS: the frequencies of the epsilon2 and epsilon4 alleles and the effect of these alleles on the age at onset in 52 patients with frontotemporal degeneration who underwent a thorough diagnostic examination and in 182 cognitively healthy age matched controls were assessed. Genotype comparisons between the groups were performed using multiple logistic regression analysis. Ages at onset according to the apoE genotype were compared by linear regression analysis. RESULTS: In patients with frontotemporal degeneration apoE epsilon2 and epsilon4 allele frequencies were 9.6% each, whereas the corresponding frequencies in controls were 9.6% and 9.9%, respectively. There was no significant difference in either epsilon2 or epsilon4 allele frequency between the groups. Age at onset was highest in patients with the epsilon2/epsilon3 genotype (61.3 years) followed by patients with the epsilon3/epsilon3 (58.3 years) and was lowest in patients with the epsilon3/epsilon4 genotype (56.4 years) but the differences failed to reach statistical significance. CONCLUSION: Allelic variants of the apoE gene do not modulate occurrence or age at onset in this sample of German patients with frontotemporal degeneration.

Age of Onset↗