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Thomas Müller

Publications and source records attributed to Thomas Müller.

At least 73 records · Page 4Linked to original sources
PubMed2004

Quantitative analysis of sinistrin in serum with high-performance liquid chromatography for renal function testing.

Sinistrin, as inulin, is widely used as a marker for renal function testing. A reliable and accurate method with a simple sample preparation for the quantitative determination of sinistrin would be of advantage. We developed a high-performance liquid chromatography (HPLC)-based method with electrochemical detection for the quantitative measurement of sinistrin in serum and plasma. Sample preparation is easy and includes enzymatic removal of glucose, deproteinization, acid hydrolysis of sinistrin, and HPLC separation of fructose. The recovery of sinistrin from serum is the same as that from water and is near 100%. The method presented has a linear range up to 500 mg/L. The results from our method are in agreement with a fully enzymatic quantification (regression coefficient 1.01, coefficient of variation 0.97). Sinistrin concentrations in aqueous solutions can be measured down to 2mg/L with a coefficient of variation of 5.7%. Quantification in serum is primarily limited by its physiological fructose content. The sensitivity of the described method is sufficient for its use in renal function testing. We describe a method for quantification of sinistrin which allows accurate measurements especially at low concentrations and low sample volumes. This laboratory method may be used for obtaining sinistrin pharmacokinetics in renal function testing.

Catalase↗
PubMed2004

Recovery of glucocorticoid-related loss of synaptic density in the fetal sheep brain at 0.75 of gestation.

Antenatal glucocorticoids routinely used to accelerate fetal lung maturation in human pregnancy at risk of preterm delivery decrease synaptic density and complex electrocortical activity in the fetal sheep brain at 0.87 gestation. We examined whether the effects of betamethasone on synaptic density depend on maturation of hypothalamo-pituitary-adrenal (HPA) axis and whether these effects are reversible. Betamethasone infusion to fetal sheep comparable to the dose used clinically (3.3 microg kg(-1) h(-1) over 48 h) at 0.75 gestation and, thus, before the prepartum increase of cortisol, reduced synaptophysin immunoreactivity (SY-IR) in the frontal neocortex, caudate putamen and hippocampus (P < 0.05). Loss of SY-IR exceeded that shown previously at 0.87 gestation (P < 0.05). It was not accompanied by neuronal damage and was reversible within 24h. In conclusion, fetal betamethasone exposure induces a gestational age-dependent decrease of synaptic density that is transient and more severe in younger fetuses.

Animals↗
PubMed2004

Chronic levodopa intake increases levodopa plasma bioavailability in patients with Parkinson's disease.

Previous pharmacokinetic trials with standard levodopa formulations showed a different behavior of levodopa degradation in plasma of patients with Parkinson's disease (PD) in various advanced stages. The objective of this trial was to compare levodopa plasma metabolism in PD patients with and without previous long-term levodopa intake after oral intake of a dispensable levodopa/benserazide formulation (DLB). The over a 150 min interval computed area under the curve values of levodopa plasma levels after DLB administration were significantly (ANCOVA: F(1,19) = 7.88, P = 0.01) higher in PD patients with chronic levodopa treatment compared to patients without prior levodopa treatment. The maximum plasma levodopa concentration did not differ (ANCOVA: F(1.19) = 1.17, P = 0.29). Long-term levodopa administration results in an increased levodopa plasma bioavailability in PD patients.

Adult↗
PubMed2004

Assessing anti-rabies baiting--what happens on the ground?

BACKGROUND: Rabies is one of the most hazardous zoonoses in the world. Oral mass vaccination has developed into the most effective management method to control fox rabies. The future need to control the disease in large countries (i.e. Eastern Europe and the Americas) forces cost-benefit discussions. The 'Increase bait density' option refers to the usual management assumption that more baits per km2 could compensate for high fox abundance and override the imperfect supply of bait pieces to the individual fox. METHODS: We use a spatial simulation, which combines explicitly fox space use (tessellation polygons) and aeroplane flight lines (straight lines). The number of baits actually falling into each polygon is measured. The manager's strategic options are converted into changes of the resulting bait distribution on the ground. The comparison enables the rating of the options with respect to the management aim (i.e. accessibility of baits). RESULTS: Above 5% (approx. 10%) of all fox groups without any bait (at most 5 baits) relate to the baiting strategy applied in the field (1 km spaced parallel flight lines, 20 baits per km2 distributed) under habitat conditions comparable to middle and western Europe (fox group home-range 1 km2, 2.5 adults; reference strategy). Increasing the bait density on the same flight-line pattern neither reduces the number of under-baited fox group home-ranges, nor improves the management outcome and hence wastes resources. However, reducing the flight line distance provides a more even bait distribution and thus compensates for missed fox groups or extra high fox density.The reference strategy's bait density can be reduced when accounting for the missed fox groups. The management result with the proper strategy is likely the same but with reduced costs. CONCLUSION: There is no overall optimal strategy for the bait distribution in large areas. For major parts of the landscape, the reference strategy will be more competitive. In situations where set backs are attributed to non-homogeneous bait accessibility the distribution scheme has to be refined zone-based (i.e. increase of the flight line length per unit area). However, increase in bait density above the reference strategy appears inappropriate at least for non-urban abundance conditions of the red fox.

Administration, Oral↗
PubMed2004

Few-cycle terahertz generation and spectroscopy of nanostructures.

We report on new schemes for terahertz (THz) generation. The THz efficiency of photoconducting antennas can be increased by using a cavity effect for the near-infrared pump beam. The cavity is formed by a molecular beam epitaxy grown semiconductor Bragg mirror below the photoconducting layer. The optical confinement is accompanied by an electrical confinement suppressing undesired leakage currents and providing a constant electric field in the active layers. The performance of this cavity-enhanced emitter is further improved by using a mobility optimized low-temperature GaAs layer. This emitter is successfully used in a femtosecond Ti:sapphire laser cavity for highly efficient intracavity THz generation, where the photoconductive layer serves also as a saturable absorber. The broadband THz pulses generated are used for time-resolved spectroscopy of nanostructures. We study the dynamics of intersubband transitions in semiconductor quantum wells. The relaxation of carriers excited by a near-infrared pump pulse is investigated by measuring the THz absorption between the different subbands with our THz pulses. For transition energies below the optical phonon energy we find relatively long relaxation times with a strong dependence on the excited carrier density.

Arsenicals↗
PubMed2004

Levodopa-associated increase of homocysteine levels and sural axonal neurodegeneration.

BACKGROUND: Levodopa metabolism via catechol O-methyltransferase increases levels of the neurotoxin homocysteine, which induces an axonal-accentuated degeneration in sensory peripheral nerves in vitro. OBJECTIVES: To demonstrate associations among daily levodopa/dopa decarboxylase inhibitor intake, total homocysteine plasma (tHcy) levels, and electrophysiologic sural nerve conduction findings. DESIGN: We performed bilateral assessment of sensory nerve conduction velocity and sensory nerve action potentials and determined tHcy levels. PATIENTS: Thirty-one levodopa-treated patients with Parkinson disease (PD) and 27 control subjects. RESULTS: Sensory nerve action potentials significantly (P<.001) differed between PD patients and controls. No differences between sensory nerve conduction velocities of PD patients and controls appeared. We found significant differences in sensory nerve action potentials be-tween PD patients with significantly elevated tHcy levels and controls (P<.001), PD patients with tHcy levels within the reference range and those with elevated levels (P =.001), and PD patients with tHcy levels levels within the reference range and and controls (P =.04). Our sensory nerve conduction velocity results showed no significant differences. There were significant associations between tHcy levels and sensory nerve action potentials (R = -0.52; P =.002) and and sensory nerve conduction velocity (R = -0.47; P =.008). Daily levodopa/dopa decarboxylase inhibitor intake was significantly related to tHcy levels (R = 0.43; P =.02). CONCLUSIONS: This electrophysiological sign of peripheral neuronal dysfunction may be circumstantial evidence suggesting that, to a certain extent, sensory nerve action potentials are a surrogate marker for the levodopa metabolism-induced elevation of homocysteine levels and the aggravation of the ongoing central neurodegenerative process.

Action Potentials↗
PubMed2004

Immunohistochemical analysis of Mallory bodies in Wilsonian and non-Wilsonian hepatic copper toxicosis.

Patients with Wilson's disease (WD), Indian childhood cirrhosis (ICC), and idiopathic copper toxicosis (ICT) develop severe liver disease morphologically characterized by ballooning of hepatocytes, inflammation, cytoskeletal alterations, and Mallory body (MB) formation, finally leading to mostly micronodular cirrhosis. The pathogenesis of MBs in copper toxicosis is still unresolved. Immunohistochemical analysis of MBs in different types of copper intoxication revealed that keratin, p62, and ubiquitin are integral components. Thus MBs associated with copper intoxication resemble those present in alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH). p62 is a multifunctional immediate early gene product that, on the one hand, is involved in stress-induced cell signaling (particularly that of oxidative stress) by acting as an adapter protein linking receptor-interacting protein (RIP) with the atypical protein kinase C. On the other hand, p62 binds with high affinity to polyubiquitin and ubiquitinated proteins. In conclusion, p62 accumulation in WD, ICC, and ICT and deposition in MBs indicates a central role of protein misfolding induced by oxidative stress in copper-induced liver toxicity. By sequestering potentially harmful misfolded ubiquitinated proteins as inert cytoplasmic inclusion bodies (e.g., as MBs), p62 may be a major player in an important cellular rescue mechanism in oxidative hepatocyte injury.

Adolescent↗
PubMed2004

Novel homozygous p.E64D mutation in DJ1 in early onset Parkinson disease (PARK7).

Mutations in the parkin gene have been identified as a common cause of autosomal recessive inherited Parkinson disease (PD) associated with early disease manifestation. However, based on linkage data, mutations in other genes contribute to the genetic heterogeneity of early-onset PD (EOPD). Recently, two mutations in the DJ1 gene were described as a second cause of autosomal recessive EOPD (PARK7). Analyzing the PARK7/DJ1 gene in 104 EOPD patients, we identified a third mutation, c.192G>C (p.E64D), associated with EOPD in a patient of Turkish ancestry and characterized the functional significance of this amino acid substitution. In the patient, a substantial reduction of dopamine uptake transporter (DAT) binding was found in the striatum using [(18)F]FP-CIT and PET, indicating a serious loss of presynaptic dopaminergic afferents. His sister, homozygous for E64D, was clinically unaffected but showed reduced dopamine uptake when compared with a clinically unaffected brother, who is heterozygous for E64D. We demonstrate by crystallography that the E64D mutation does not alter the structure of the DJ1 protein, however we observe a tendency towards decreased levels of the mutant protein when overexpressed in HEK293 or COS7 cells. Using immunocytochemistry in contrast to the homogenous nuclear and cytoplasmic staining in HEK293 cells overexpressing wild-type DJ1, about 5% of the cells expressing E64D and up to 80% of the cells expressing the recently described L166P mutation displayed a predominant nuclear localization of the mutant DJ1 protein.

Adult↗
PubMed2004

On psychotic transference and countertransference.

Following a brief discussion of the primary types of psychotic transferences, viewed from a theoretical position combining ego psychology with an object relations approach, the author presents detailed clinical material illustrating these transferences. The analyst's countertransference in work with such patients is also discussed in depth, including its use as a unique window into the patient's inner world.

Adult↗
PubMed2004

Hyperhomocysteinaemia in treated patients with Huntington's disease homocysteine in HD.

Significantly increased plasma total homocysteine levels (t-Hcys) appeared in treated Huntington disease (HD) patients compared to controls and untreated HD subjects. Because the protein Huntingtin interacts with the homocysteine metabolism modulating enzyme cystathionine beta-synthase, we hypothesize that homocysteine promotes neurodegeneration in HD.

Adult↗
PubMed2004

(M)VOC and composting facilities. Part 2: (M)VOC dispersal in the environment.

BACKGROUND, AIMS AND SCOPE: Composting facilities are known to release odorous volatiles due to biodegradation of municipal waste and plant residues. Although odour perception and its grading is influenced by experience, attitude and adaptation, these emissions have created a lack of acceptance for residents in the vicinity of composting facilities. Enclosure of compost pile halls, ventilation systems and biofilters are often insufficient to minimise the burden of compost-derived compounds in the air. Moreover, economic considerations forced smaller communities to establish less sophisticated facilities with open storage areas and other relevant sources for wind-borne dispersal of bioaerosols. Aim of the present study was to characterise the immission and dispersal of microbial volatiles (MVOC) and, besides, to find coincidences between MVOC and compost odour. METHODS: In the course of this study, the surroundings of two composting facilities, differing in their type of process engineering, were investigated for emission of volatiles in the environment. Both microbially and plant-derived substances were assessed, several of which have low odour thresholds. Air samples were taken in distances ranging from 50 to 800 m in a downwind direction from each facility. RESULTS AND DISCUSSION: Compost-derived and microbial volatile organic compounds (MVOC) were found at distances of up to 800 m from the composting facilities. Terpenes like alpha-pinene, camphene and camphor were the dominant compounds and coincided with typical compost odour, whereas several typical MVOC were not found at greater distances. The terpenes in combination with certain MVOC may play an important role in the perception of compost odour. Exposure concentrations were not of toxicological relevance, but sensory irritation and psychohygienic effects due to an annoyance potential of such compounds should not be dismissed. RECOMMENDATIONS AND OUTLOOK: Although terpenes are generally associated with pleasant odour characteristics, they seemed to contribute to malodours in a mixture with other VOC, in this context of volatile waste from compost facilities. Malodorous emissions from biowaste have to be considered as sources of health complaints and the investigation of mixtures of compost-derived volatiles is still inevitable. Exposure levels have to be discussed taking VOC mixtures into account. Within composting facilities, technical devices have to be improved to minimise dispersal of volatiles to prevent residents from immissions eventually causing health complaints.

Aerosols↗
PubMed2004

(M)VOC and composting facilities. Part 1: (M)VOC emissions from municipal biowaste and plant refuse.

GOAL, SCOPE AND BACKGROUND: Malodorous volatiles derived from the decomposition of biowaste within the process of composting might pose a risk to human health. Different techniques of process engineering have been developed to minimise the burden of malodorous compounds in air possibly affecting compost workers and residents in the vicinity. METHODS: In the present study, three different composting facilities were examined for the emission of volatiles to estimate the impact of process engineering on the dispersal of odorous compounds and to discuss its relevance for human health. RESULTS AND DISCUSSION: Concentrations of single compounds belonging to alcohols, ketones, furanes, sulfur-containing compounds and especially terpenes ranged from 10(2) up to nearly 10(6) ng/m3 depending on the sampling sites and the process engineering. The ratio of MVOC and total VOC measured changed throughout the process of biodegradation. A certain combination of volatile compounds coincided with the occurrence of typical compost odour. CONCLUSION: The type of process engineering seemed to have a major impact on the emission of volatiles, as amounts of (microbial) volatiles emitted were characteristic for the different techniques used. Thus, the MVOC emission basically depends on the degree of biodegradation. It is likely that the concentrations workers are exposed to can have an impact on human health. RECOMMENDATIONS AND OUTLOOK: It is obvious that less sophisticated types of process engineering give rise to greater amounts of bioaerosols and volatiles and, therefore, technical devices have to be improved and controlled regularly to minimise adverse health effects on workers.

Bioreactors↗
PubMed2004

Is levodopa toxic?

The objective of this workshop was to review and discuss the debate on neurotoxicity of levodopa in the treatment of Parkinson's disease (PD) with consideration of preclinical and clinical findings. We concluded that in particular preclinical outcomes of in vitro models of neurodegeneration describe neurotoxic effects of levodopa, whereas trials in animal models provided controversial results. To date, clinical trials in PD patients showed no convincing proof of direct neurotoxic effects of levodopa on progression of neurodegeneration with various applied functional imaging techniques particularly with specific radiotracers for nigral dopaminergic neurotransmission. However, the controversy on neurotoxicity of levodopa only partially considered indirect mechanisms, i. e. levodopa-associated homocysteine elevation. But there is accumulating evidence that this long-term side effect of chronic levodopa administration dose dependently individually contributes to progression of neurodegeneration due to increased release of neurotoxins, induction of oxidative stress and mitochondrial dysfunction according to results of in vitro and animal trials and to at least peripheral neuronal degeneration and increased risk for onset of atherosclerosis-related disorders according to clinical trials in PD patients. From this point of view we demand that future research on the efficacy and putative neurotoxicity of antiparkinsonian compounds should also consider putative toxic long-term effects of drug administration and should look for putative peripheral biomarkers and individual, environmental or nutritative risk factors in order to establish a preventive therapy, i. e. folic acid administration in the case of levodopa-associated homocysteine elevation.

Animals↗
PubMed2004

Changes of blood pressure and left ventricular mass in pediatric renal transplantation.

Cardiovascular events are among the most frequent causes for long-term morbidity and mortality in children after renal transplantation. The aim of this study was to analyze the effects of post-transplant changes in arterial hypertension, as assessed by 24-h ambulatory blood pressure measurement (ABPM), on myocardial architecture, as assessed by echocardiography. In a retrospective chart review analysis, 39 children were identified in whom 24-h ABPM and echocardiography had been assessed within a 3-month interval after a mean of 4 years post transplantation; 20 repeated pairs of measurements after a mean of 2 years of follow-up were available to analyze the longitudinal effects of post-transplant changes of blood pressure control on left ventricular mass index (LVMI). Arterial hypertension (59%) and left ventricular hypertrophy (50%) were highly prevalent in children after renal transplantation. Renal allograft function and number of antihypertensive medications, but not ABPM variables, were correlated with LVMI at the initial observation. However, at repeat assessment, a significant correlation between ABPM and LVMI was found. In the longitudinal assessment, left ventricular remodeling was dependent on change of dosage of cyclosporine and interval changes of blood pressure levels. Hence, control of blood pressure correlates with changes of LVMI in children with renal allografts. These results clearly underline the importance of blood pressure control for the maintenance of the myocardial architecture.

Adolescent↗
PubMed2004

Joubert-like syndrome unlinked to known candidate loci.

We observed the Joubert syndrome (JS) associated with bilateral morning glory disk anomaly and cystic dysplastic kidneys in three patients from a consanguineous kindred. Homozygosity mapping excluded three JS candidate loci as sites harboring the disease gene. We thus delineate an autosomal recessive disorder, distinct from JS and related conditions.

Adult↗
PubMed2004

Treatment benefit and daily drug costs associated with treating Parkinson's disease in a Parkinson's disease clinic.

OBJECTIVE: In some countries, such as Germany, there has been a move towards the treatment of patients with Parkinson's disease in specialised inpatient units. However, data on patient outcome and the daily costs of antiparkinsonian drugs in these settings are rare. This study was conducted to determine the effect of an inpatient setting (a specialised Parkinson's disease clinic) on drug therapy costs and patient symptoms. PATIENTS AND METHODS: This study involved 63 consecutively referred inpatients of a Parkinson's disease clinic. On entry to the clinic, the patients' antiparkinsonian drug regimen was titrated in order to improve their motor function. The daily costs of drug therapy per patient (in 2002 values) were calculated, and the severity of Parkinson's disease symptoms scored via scores on the Unified Parkinson's Disease Rating Scale (UPDRS) and standardised instrumental procedures (peg insertion and tapping), both initially and at the end of the patients' stay in the clinic. The variables between the two evaluation timepoints were compared. RESULTS: The titration of antiparkinsonian drugs was associated with a significant decrease in the symptoms of Parkinson's disease at discharge from the clinic compared with admission (as measured by UPDRS total and subscale scores [all p < 0.001], and, to a lesser extent, by peg insertion and tapping [both p < 0.05]). A significant increase in daily drug costs (an increase of euro14.11 per patient for all drugs and euro12.36 per patient for antiparkinsonian drugs [both p <0.001]) was also observed. CONCLUSION: The results demonstrate that the symptoms experienced by patients with Parkinson's disease improve after performance of antiparkinsonian drug titration within the setting of a specialised Parkinson's disease clinic. The effect on symptoms was seen most clearly with the UPDRS, although both peg insertion and tapping reflected this improvement to a certain extent. Drug titration resulted in, on average, a doubling of daily drug costs. Future trials are needed to investigate the long-term effects of such a hospital stay on indirect costs associated with treating Parkinson's disease, and on caregiver burden, and also to compare the efficacy of a Parkinson's disease clinic with an outpatient setting.

Adult↗