Search PubMed⌕ Search

Biomedical subjects

T Müller

Publications and source records attributed to T Müller.

At least 91 records · Page 5Linked to original sources

Typical medication errors in oncology: analysis and prevention strategies.

Pharmacotherapy in oncology is complex. It has a small therapeutic range, and is susceptible to errors. Medication errors--especially overdosage--often have serious effects while underdosage entails unnoticed impairment of the therapeutic success. Typical medications and procedures susceptible to errors are described: unintentional intrathecal injections, the application of platinum compounds and anthracyclines, confusion of total and single dose, errors of calculation and preparation, or in operation of infusion pumps. Suitable prevention strategies are standardisation, separation of intrathecal and intravenous chemotherapy, and use of specialized software for planning and calculating chemotherapy, as well as non-punitive notification and recording systems for errors and near-errors in treatment.

Antineoplastic Agents↗

Effects of various hormones on the sexual maturity of European eel (Anguilla anguilla L.) females from farm and lakes.

Previously described and alternative methods of the induction of sexual maturation in the European eel were investigated. Weekly administrations of a gonadoliberin agonist (nnRH-A=D-Phe6-GnRH-Ea) did not induce statistically significant effect on the gonads of treated eels in none of the dosages used (0.1 microg and 10 microg/fish). Carp pituitary extract and carp pituitary extract together with a dopamine antagonist caused considerable external changes (increase in eye size) and significant gonadal development in two treatment groups: wild and cultivated stocks. The induction of the ovulation by double amount of CP and gonadoliberin agonist with dopamine antagonist mixture was not successful in a wild stock. Fertilisation of stripped eggs of farm eel was attempted unsuccessfully in, due to low egg quality. An advanced phase of the sexual maturation process could be induced in specimen infected by Anguillicola crassus indicating, that nematode infection is not a limiting factor in the artificial propagation of the European eel.

Air Sacs↗

Reflectivity and energy balance in pulsed-laser deposition experiments from mono- and bi-atomic targets.

Reflectivity and complete energy balance from the planar targets of aluminum, copper, nickel, and molybdenum have been measured using a Nd: glass laser (lambda=1060 nm,tau=5 ns) in the low intensity regime of laser plasma interaction as a function of focal spot size. The magnitude of partition of total incident laser energy into different channels is observed to decrease as the focal spot size increases. It is further observed that the magnitude of partition of the incident energy into these channels, in general, decreases as the atomic number increases for any given focal spot size, although, the reflectivity component of the partitioned energy increases with focal spot size for any given element. The reflectivities of copper and tungsten and their alloy were measured separately. The reflectivity from the alloy plasma was reduced by a factor of 6 compared to either element separately. This observation confirms the recent theory that in the multiion plasma the ion acoustic waves are additionally damped due to additional Joule, thermal diffusion, and viscous terms in the modified ion-fluid theory of the ion acoustic waves in a multiion species plasma.

Journal Article↗

Ultrafast coherent electron transport in semiconductor quantum cascade structures.

Coherent electron transport is studied in an electrically driven quantum cascade structure. Ultrafast quantum transport from the injector into the upper laser state is investigated by midinfrared pump-probe experiments directly monitoring the femtosecond saturation and subsequent recovery of electrically induced optical gain. We demonstrate for the first time pronounced gain oscillations giving evidence for a coherent electron motion. The coexistence of a long dephasing time of quantum coherence and high Coulomb scattering rates in the injector points to the occurrence of scattering-induced coherence in electron transport.

Journal Article↗

Practical importance of neuroprotection in Parkinson's disease.

Consensus could be reached that there is overwhelming evidence of preclinical neuroprotection. However, the evidence of neuroprotection/neurorescue under clinical conditions is limited. Lessons from clinical trials designed to show neuroprotection (selegiline, amantadine, dopamine agonists) demonstrate that with the drugs available neuroprotection/neurorescue has to start as early as possible. A PET-controlled clinical trial with ropinirole shows that there seems to be a good chance for neuroprotection in the early phase of Parkinson's disease in patients treated from the very beginning of the disease while there is no such benefit in patients with a late start of a neuroprotective therapeutic strategy. Also long-term clinical neuroprotection cannot be reached. Complicating factors to demonstrate clinical neuroprotection are discussed.

Amantadine↗

Gemcitabine, vinorelbine and cisplatin combination chemotherapy in advanced non-small cell lung cancer: a phase II trial.

The purpose of this phase II trial was to investigate the efficacy and safety of a combination chemotherapy with gemcitabine, vinorelbine and cisplatin in the first-line treatment of advanced non-small cell lung cancer (NSCLC). Patients with NSCLC stage IIIB or IV disease received 1000 mg/m(2) gemcitabine and 25 mg/m(2) vinorelbine on days 1 and 8 and 75 mg/m(2) cisplatin on day 2, every 3 weeks. From December 1998 to May 1999, 31 patients (21 stage IV and 10 stage IIIB disease), with a median age of 59 years (range 40-72 years) were enrolled. The overall intent-to-treat response rate was 45% (95% confidence interval (CI): 27-64%) with 2 complete responders (CR) and 12 partial responders (PR), 7 patients had stable disease and 10 progressed. Median survival was 12.8 months (95% CI: 6.5-12.8+ months), median time to progression was 5.1 months (95% CI: 3.5-7.7 months), and the 1-year survival rate was 52.9% (95% CI: 36.7-76.2%). Patients with stage IIIB disease had a significantly longer overall survival than patients with stage IV disease (P=0.05). Transient World Health Organization (WHO) grade IV leucopenia, anaemia and thrombocytopenia occurred in 3 (10%), 2 (6%) and 3 (10%) patients, respectively. The predominant non-haematological toxicities were alopecia and nausea/vomiting. 15 patients (48%) had WHO grade II and III alopecia and 14 patients (45%) nausea/vomiting. The combination of gemcitabine, vinorelbine and cisplatin has demonstrated major antitumour efficacy in advanced NSCLC with a manageable toxicity profile.

Adult↗

Quantification of the dopaminergic response in Parkinson's disease.

BACKGROUND: Various investigators have developed complex quantitative procedures for objective assessment of parkinsonian motor impairment, since drawbacks of rating scales are interrater variability, subjective impression, insensitivity to subtle modifications. OBJECTIVES: To determine whether standardized performance of inserting pegs (i) differentiates between parkinsonian subjects and healthy controls and (ii) reflects quantification of the dopaminergic response with rating scales within a levodopa challenge test design. SUBJECTS AND METHODS: We used an easy-to-operate Purdue Pegboard-like apparatus, which measures the total time taken to insert 25 pegs from a rack into a series of appropriate holes by a computer to 100 ms accuracy, and simultaneous rating with part III of the Unified Parkinson's Disease Rating Scale for assessment of motor impairment in 28 idiopathic parkinsonian patients before and during a levodopa challenge test. Additionally we compared data of the instrumental task to age- and sex-matched healthy controls. RESULTS: We found significant differences between parkinsonian subjects and controls and significant correlations to the rated severity of Parkinson's disease. Within-subject comparisons and correlation analysis demonstrated the ability of this tool to reflect scored motor improvement after intake of levodopa. CONCLUSION: Inserting pegs provides an objective quantitative estimation of changes in motor impairment within a typical levodopa challenge test design.

Adult↗

Progress of visual dysfunction in Parkinson's disease.

Studies on progression of Parkinson's disease (PD) mainly focus on the nigrostriatal dopaminergic decline, but not on the visual system. We determined progression of (i) disturbed color vision, assessed with the Farnsworth-Munsell 100 Hue test (FMT) and (ii) intensity of PD in 18 patients. Significant differences occurred between (i) initial FMT error scores and follow-up results 3 years later (P=0.002) and analogously (ii) scored intensity of PD (P=0.002). A relation between computed differences of FMT error scores and rated activities of daily living appeared. Deterioration of color vision progresses in PD.

Color Perception↗

Improving diagnostic procedure and treatment in patients with non-epileptic seizures (NES).

The purpose of this study was to examine the incidence of patients with NES vs. NES and concomitant epilepsy in an epilepsy centre and to present a diagnostic algorithm. We collected and reviewed the data of 322 patients consecutively referred to the adult ward of our epilepsy centre in 1 year. The results of our study reveal that 44 (14%) of all patients referred had NES. Of these, nine proved to have concomitant epilepsy. Of 44 patients with NES, 20 were treated with AED on admission. In 14 cases this unnecessary antiepileptic drug treatment was stopped. In six remaining patients with NES and concomitant epilepsy, the total number of AEDs could be reduced until discharge. The maximum duration of AED treatment among patients with NES only, had been longer than 360 months (median 72 months). Much has been written about whether the diagnosis of psychogenic non-epileptic events is overused. According to our experience however, the fact that many patients with so-called 'pharmacoresistant epilepsy', suspected NES or other diagnoses are referred to a centre of excellence much too late, proves to be the key problem in diagnosis and treatment of NES. We conclude that early admission of so-called 'pharmacoresistant epilepsy' to an epilepsy centre, establishing a standard work-up and clarifying the medical terminology will improve diagnosis and lead to adequate therapy of NES as well as prevent unnecessary drug treatment.

Adolescent↗

Effects of oral creatine supplementation in a patient with MELAS phenotype and associated nephropathy.

An 18-year-old male patient with MELAS phenotype and 2 previous episodes of cerebral stroke, recurrent seizures and nephropathy, was treated with creatine monohydrate after the acute onset of psychomental regression and changing states of somnolence and aggressive and agitated behaviour. These symptoms disappeared completely after 4 weeks of treatment with creatine after which the patient regained all his previous mental abilites. Brain (white matter) proton magnetic resonance spectroscopy (chemical shift imaging) performed at 6 and 12 months of treatment showed lactic acid (Lac) accumulation and high creatine (Cr) levels in relation to choline-containing compounds (Cho). Urinary creatinine excretion as an indicator of the muscle and brain creatine pool increased upon short-term (12 days) high-dosage creatine supplementation (20 g per day) while plasma creatinine concentrations as possible indicators both of increasing creatine pool and of renal insufficiency increased during the course (28 months) of low-dosage creatine supplementation (5 g per day). Deterioration of renal function was finally indicated by urea retention and by impairment of renal creatinine clearance. These observations suggest that creatine supplementation may have a neuroprotective effect in patients with MELAS and episodes of acute mental deterioration. Adverse effects of creatine supplementation on renal function must be considered especially in patients with preexisting nephropathy.

Administration, Oral↗

[Experiences with follow-up investigations of oral vaccination campaigns against rabies in foxes in Saxony with special emphasis on a standardised serology].

An 8-year experience with organisation and standardisation of follow-up investigations within oral vaccination campaigns against rabies in foxes (OVF) in Saxony is summarised. With respect to OVF, the number of diagnostic tests performed during the years 1992-2000 on foxes amounts to a total of 52,226 Fluorescence antibody-(FAT), 7,551 marker-(TC) and 11,645 serological tests. The mean bait-uptake and the mean immunisation rate in foxes ranged between 78-86% and 60-89%, respectively. Based on the seroconversion rates of the years 1997-2000 observed in vaccination areas and in areas where vaccination was already finished, experience with a standardised serology under routine conditions is presented and discussed. Furthermore, recommendations concerning organisation and logistics of sampling are given.

Administration, Oral↗

Cost-efficient vaccination of foxes (Vulpes vulpes) against rabies and the need for a new baiting strategy.

In this study, ecological models, optimisation algorithms and threshold analysis were linked to develop oral-vaccination strategies against rabies in fox populations. It is important that such strategies are cost-efficient and resistant to environmental conditions which would lessen their success. The model validation shows that the ecological models used are suited to predict the proportion of tetracycline- (TC) marked foxes in the course of time. This figure indicates the proportion of foxes which had at least one contact to vaccine baits, and is based on the design of the vaccination strategy (i.e. the number and timing of vaccination campaigns and the number of baits used per square kilometre and campaign). The design of a vaccination strategy also determines the costs. It is the combination of ecological models and optimisation algorithms that helped us to design a vaccination strategy which is capable of achieving a continuous rate of >70% of TC-marked foxes within an analytical horizon of 3 years at low costs. Compared to the standard strategy (baseline comparator), the improved strategy incurs just over half of the cost while almost doubling the number of weeks during which the proportion of TC-marked foxes is >70%. In the improved strategy, June is recommended as the time for bait distribution. The standard strategy, however, avoids summer months (because high temperatures reduce the durability of the baits) which again leads to a reduction of the bait intake by the foxes. Using threshold analysis, we examined the effect of a reduced durability of the baits on the design of the improved vaccination strategy. We concluded that distribution of baits in June was optimal given that the durability of baits is above a threshold of 7 days.

Administration, Oral↗

Evaluation of the gamma-synuclein gene in German Parkinson's disease patients.

Mutations in the alpha-synuclein gene are responsible for an autosomal-dominantly inherited form of Parkinson's disease (PD) and alpha-synuclein was found to be the major component of Lewy bodies in PD. Because of the high homology to alpha-synuclein and the abundance in neuronal tissues, we investigated the gamma-synuclein gene in PD. We analyzed 262 German PD patients and 179 healthy German controls via two polymorphisms in the gamma-synuclein gene. No significant differences in the allelic or genotypic distributions of the investigated polymorphisms were observed between patients and controls. In addition no evidence for an increased risk of combined genotypes of polymorphisms in the gamma-synuclein and the alpha-synuclein gene was found. Therefore, our results do not support a major role of the gamma-synuclein gene in PD.

Aged↗

Efficient preparation of monoadducts of [60] fullerene and anthracenes by solution chemistry and their thermolytic decomposition in the solid state.

The efficient preparation of monoadducts of [60]fullerene and seven anthracenes (anthracene, 1-methylanthracene, 2-methylanthracene, 9-methylanthracene, 9,10-dimethylanthracene, 2,3,6,7-tetramethylanthracene, and 2,6-di-tert-butylanthracene) by cycloaddition in solution is described. The seven mono-adducts of [60]fullerene and the anthracenes were characterized spectroscopically and were obtained in good yields as crystalline solids. The monoadducts of [60]fullerene and anthracene, 1-methylanthracene, 2-methylanthracene and 9,10-dimethylanthracene crystallized directly from the reaction mixture. The thermolytic decomposition at 180 degrees C of the crystalline monoadducts of [60]fullerene and anthracene, 1-methylanthracene, 9-methylanthracene and 9,10-dimethylanthracene all gave rise to the specific formation of a roughly 1:1 mixture of [60]fullerene and the corresponding antipodal bisadducts ("trans-1"-bisadducts) of [60]fullerene and the anthracenes. In contrast, the crystalline monoadducts of [60]fullerene and the anthracene derivatives 2-methylanthracene, 2,3,6,7-tetramethylanthracene and 2,6-di-tert-butylanthracene all decomposed to [60]fullerene and anthracenes (without detectable formation of bisadducts) upon heating in the solid state to temperatures of 180 to 240 degrees C. The formation of the antipodal bisadducts from thermolytic decomposition of crystalline samples of the monoadducts was rationalized by topochemical control.

Journal Article↗

Decrease of methionine and S-adenosylmethionine and increase of homocysteine in treated patients with Parkinson's disease.

Levodopa is administered with dopa decarboxylase inhibitors (DDI) to prevent its peripheral degradation. This increases conversion of levodopa to 3-O-methyldopa (3-OMD) by catechol-O-methyltransferase (COMT). S-adenosylmethionine (SAM), which is synthesized from adenosine triphosphate and methionine (MET), serves as methyl donor for this O-metabolisation of levodopa with resulting conversion of SAM to total homocysteine (tHcy) via S-adenosylhomocysteine (SAH). Previous studies showed augmented plasma levels of tHcy in long-term levodopa/DDI-treated patients with Parkinson's disease (PP). Objective of this study was to compare MET, SAM, levodopa, 3-OMD, tHcy and SAH in plasma of 20 levodopa/DDI treated PP and corresponding controls. A significant decrease of MET respectively SAM and an increase of tHcy appeared in PP. SAH with its short half-life did not differ. Levodopa/DDI long-term treatment contributes to altered levels of substrates of the O-methylation cycle in PP.

Aged↗

Familial parkinsonism with synuclein pathology: clinical and PET studies of A30P mutation carriers.

BACKGROUND: The authors identified the second known mutation in the alpha-synuclein(SNCA) gene, an alanine-to-proline exchange in amino acid position 30 (A30P), that cosegregates with the disease in one German family with autosomal dominantly inherited parkinsonism (ADP). The authors studied carriers of the A30P mutation to compare the phenotype of this mutation with idiopathic PD (IPD) and to assess nigrostriatal dopaminergic function in symptomatic and preclinical mutation carriers. METHODS: The pedigree of the A30P family spans five generations with five affected individuals. The authors performed detailed neurologic examinations followed by mutation analysis in 11 living individuals. In three mutation carriers, two individuals with definite PD and one person at risk for PD, they used L-[18]F-fluoro-3,4-dihydroxyphenylalanine (F-DOPA), [11]C-raclopride (RAC), and [18]F-fluorodeoxyglucose (FDG) PET to investigate presynaptic dopaminergic function, dopamine D2 receptors, and cerebral energy metabolism. The authors studied the cognitive functions of carriers of the A30P mutation using neuropsychological screening. RESULTS: PET studies revealed striatal presynaptic dopaminergic alterations consistent with sporadic IPD in two affected family members and no evidence for nigrostriatal dopaminergic dysfunction in one presymptomatic mutation carrier. Neuropsychological testing in four mutation carriers provided evidence for cognitive impairment as a frequent and early symptom of the A30P mutation; this is also supported by regional cerebral energy metabolism alterations in the clinically presymptomatic subject. CONCLUSIONS: The phenotype of the A30P mutation in the SNCA gene is similar to that of sporadic IPD, including a high variability of the age at disease onset, ranging from 54 to 76 years. The follow-up of presymptomatic carriers of the A30P mutation may give insight into preclinical disease stages and early manifestations of PD.

Aged↗

Radon exposure and lung cancer risk--Czech cohort study on residential radon.

Epidemiological evidence of lung cancer risk from radon is based mainly on studies of men employed underground in mines where exposures are relatively high in comparison to indoor exposure. Nevertheless, direct evidence of risk from residential radon is desirable. In 1990, a study was started comprising 12,000 inhabitants of an area with elevated radon concentrations. The mean level in the houses was higher than general mean of the country by a factor of five. In the period 1961-1995, a total of 173 lung cancers were observed. Comparing to nationally expected numbers (E), the observed number (O) of cases is elevated (O/E = 1.11), in contrast to generally low figures for cancers other than lung (O/E = 0.85). Lung cancer risk related to cumulative exposures experienced in the past 5-24 or 5-35 years were both significant. In relation to standard radon progeny concentration 100 Bq/m3, the excess relative risk coefficient was 0.103 (95% CI, 0.039-0.168), the value somewhat lower than findings in other indoor studies.

Air Pollutants, Radioactive↗