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Biomedical subjects

Thomas Müller

Publications and source records attributed to Thomas Müller.

At least 145 records · Page 8Linked to original sources
PubMed2002

Dopaminergic substitution in Parkinson's disease.

Motor complications associated with long-term levodopa application, which follow the so-called honeymoon period of well-tolerated levodopa administration and are looked upon as one clinical marker for progression of Parkinson's disease (PD), initiated a long and controversial debate on the putative neurotoxicity of levodopa. Since dopamine agonists (DA) delay onset of motor complications, they support the neuroprotective treatment strategy in PD. Efficacy and tolerability of DA differs in particular due to their affinity to various dopamine receptor subtypes. The accumulating evidence for levodopa-associated homocysteinaemia, which represents a risk factor for increased incidence of vascular disease in PD, supports the strategy of initial DA application and the use of levodopa as an add-on compound in as low a dose as possible in young PD patients.

Animals↗
PubMed2002

Drug treatment of non-motor symptoms in Parkinson's disease.

Non-motor symptoms may considerably reduce parkinsonian quality of life, particularly in advanced stages of the disease. Autonomic features, such as seborrhoea, hyperhidrosis, orthostatic hypotension, excessive salivation, bladder dysfunction and GI disturbances, and neuropsychiatric symptoms, such as depression, sleep disorders, psychosis and dementia, appear in the course of Parkinson's disease. Pharmacotherapy of these non-motor symptoms complicates long-term antiparkinsonian combination drug therapy due to possible drug interactions, side effects and changes in metabolism. Moreover, antiparkinsonian compounds themselves contribute to the onset of these non-motor symptoms to a considerable extent. This complicates differentiation between the disease process itself and drug-related effects, thus influencing therapeutic options, which are often limited because of comorbidity and polypharmacy. Therefore, standardised recommendations are questionable, since drug tolerability and response differ between patients. Nevertheless, this review tries to provide a survey of possible therapeutic options for the treatment of the symptoms of Parkinson's disease other the dopamine-sensitive motor features.

Animals↗
PubMed2002

Termination of third-trimester pregnancy before term with gemeprost vaginal pessaries.

OBJECTIVE: Determination of the efficacy and side-effects of the synthetic prostaglandin analog gemeprost for termination of pregnancy in the third trimester. PATIENTS: Retrospective record study of 40 women who had undergone third trimester termination of pregnancy before term by serial administration of gemeprost because of intrauterine fetal death or hopeless fetal prognosis. Patients with multiple pregnancy, a Bishop score > 5, contractions or contraindications to prostaglandins were excluded. METHODS: Gemeprost vaginal pessaries (1-mg) were given at 6-hourly intervals until labor intervened. The main parameter studied was the induction-delivery interval, the length of time between administration of the first dose and delivery. Statistical analysis was performed with the chi-square and the Mann-Whitney U-test. RESULTS: The median induction-delivery interval was 14.4 h (range 3-48 h). Delivery occurred within 12 h in 17 women (42.5%), within 24 h in 27 women (67.5%) and within 36 h in 37 women (92.5%). An average of 2.6 doses were given per patient. Multigravidae had a significantly shorter induction-delivery interval than primigravidae (p < 0.01). A total of 87.5% women required analgesia. Side-effects were infrequent. CONCLUSIONS: The administration of gemeprost vaginal pessaries represents an efficient method with few side-effects for the induction of labor in the third trimester, provided patients are chosen carefully and monitored closely.

Abortifacient Agents, Nonsteroidal↗
PubMed2002

CPI-1189. Centaur.

The efficacy of the proapoptotic cytokine tumor necrosis factor (TNF) alpha-inhibiting compound CPI-1189 has been demonstrated in various cell culture and animal models of chronic neurodegenerative and inflammatory diseases. CPI-1189 intracellularly inhibits the p38 mitogen-activated protein kinase phosphoactivation, thereby protecting against TNF alpha-induced neurodegeneration. Clinical proof-of-concept phase IIa trials in patients with Parkinson's disease and AIDS dementia complex were successful. These studies demonstrated clinical relevance for treatment with CPI-1189 (50 to 100 mg/day), which attenuated the deterioration in cognitive and/or motor function without any relevant side effects. Since the importance of neuroprotection is emerging, in particular in neurodegenerative diseases with concomitant observed immunological pro-apoptotic alterations in the central nervous system, long-term application of CPI-1189 could represent a promising future therapeutic alternative, in addition to neuroprotective compounds such as selegiline.

Animals↗
PubMed2001

Immunogenicity of an E1-deleted recombinant human adenovirus against rabies by different routes of administration.

The immunogenic properties of an E1-deleted, human adenovirus type 5 (Ad5) vaccine virus with activity against rabies were examined in mice, foxes and dogs using different routes of administration. NMRI mice received 10(5.8), 10(5.3), 10(4.3), 10(3.3) and 10(2.3) TCID(50) by peroral or intramuscular (i.m.) administration. Furthermore, six mice received 10(5.8) TCID(50) intracerebrally (i.c.). The construct elicited marked seroconversion in mice after oral administration. Immunoreactivity in mice was even more pronounced i.m. and i.c. After direct oral administration (10(8.0) TCID(50)) in foxes, six of eight animals developed rabies virus-neutralizing antibodies (VNA). All foxes immunized by direct injection (10(7.7) TCID(50)) in the membrane of the jejunum were shown to seroconvert. Pre-existing immunity against canine adenovirus did not hinder the development of rabies VNA after oral application of the construct (10(8.0) TCID(50)). Fox cubs (24-29 days old) born from rabies-immune vixens were shown to develop very high levels of rabies VNA after i.m. administration (10(8.0) TCID(50)), indicating that the immunogenicity of the construct could surpass maternally transferred immunity. In dogs, the construct (10(8.0) TCID(50)) induced a very strong immune response after i.m. administration. However, no immune response was detectable in dogs after direct oral administration (10(8.3) TCID(50)) or after endoscopic deposition in the smaller intestine (10(8.0) TCID(50)). Hence, it must be concluded that the construct is not suitable for oral vaccination of dogs against rabies.

Adenoviridae↗
PubMed1997

Apically Linked Small Metallacarborane Clusters. Directed Synthesis and Structural Characterization of 7,7'-[CpCo(2,3-Et(2)C(2)B(4)H(3)](2) and [CpCo(2,3-Et(2)C(2)B(4)H(3)-7)](2)X Complexes (X = MeCH, HC=CH, C&tbd1;C)(,)(1).

A series of novel bis(cobaltacarboranyl) (CoC(2)B(4))(2)X dicluster complexes whose B(7) (apex) atoms are linked by organic moieties involving sp-, sp(2)-, or sp(3)-hybridized carbon, or by a direct B(7)-B(7') bond, has been prepared by extension of the recently described "recapitation" method (Curtis, M. A.; et al. Inorg. Chem. 1996, 35, 6703) that entails treatment of 6-vertex nido-CoC(2)B(3) dianions with monoboron reagents. Reactions of Li(2)[nido-CpCo(Et(2)C(2)B(3)H(3))] in toluene with MeCH(BCl(2))(2) and with cis-(BCl(2))C(2)H(2) gave, respectively, [CpCo(2,3-Et(2)C(2)B(4)H(3)-7-)](2)MeCH (5) and cis-[CpCo(2,3-Et(2)C(2)B(4)H(3)-7-)](2)C(2)H(2) (6a) following chromatographic separation. Ultraviolet irradiation of 6a induced partial conversion to the trans isomer 6b, affording a 46:54 trans/cis equilibrium mixture in 84 h. Reactions of the same cobaltacarborane dianion with bis(catecholboryl)acetylene and with bis(catecholdiboryl) gave [CpCo(2,3-Et(2)C(2)B(4)H(3)-7-)](2)C(2) (7) and [CpCo(2,3-Et(2)C(2)B(4)H(3)-7-)](2) (8), respectively. The new complexes were isolated as air-stable, crystalline orange solids and were characterized from their (1)H, (11)B, and (13)C NMR, IR, UV-visible, and mass spectra, supported by X-ray crystallographic studies of 5, 6a, 7, and 8. Crystal data for 5: space group P2(1)ca (orthorhombic); a = 14.220(10) Å, b = 15.690(10) Å, c = 16.860(10) Å, Z = 4; R = 0.041 for 7485 independent reflections. Crystal data for 6a: space group C2/c (monoclinic); a = 12.849(6) Å, b = 11.435(6) Å, c = 25.619(13) Å, beta = 96.230(10) degrees; Z = 4; R = 0.036 for 5440 independent reflections. Crystal data for 7: space group P2(1)/n (monoclinic); a = 17.298(12) Å, b = 13.932(10) Å, c = 30.82(2) Å, beta = 96.34(5) degrees; Z = 8; R = 0.070 for 9632 independent reflections. Crystal data for 8: space group P&onemacr; (triclinic); a = 9.150(10) Å, b = 10.270(10) Å, c = 10.340(10) Å, alpha = 84.52(5) degrees, beta = 78.05(5) degrees, gamma = 68.6(5) degrees; Z = 1; R = 0.056 for 5154 independent reflections.

Journal Article↗
PubMed1990

[Alternatives to Animal Experimentation in University Education: Principles of Neurophysiology Exemplified by the Computer]

The basic physiology courses for students in biology and medicine include experiments on live animals or animal tissue. This article describes alternatives by replacing such experiments with simulation programs on personal computers. Programs for a neurophysiological experiment were developed at the Department of Neurobiology, University of Heidelberg, within the last years and have served to replace animal experiments in the basic training of biologists.

Journal Article↗
PubMedDate not supplied

Impact of gastric emptying on levodopa pharmacokinetics in Parkinson disease patients.

Adjunction of the catechol-O-methyltransferase (COMT) inhibitor entacapone (EN) to levodopa/carbidopa (LD/CD) improves motor symptoms in patients with Parkinson disease (PD) by a prolonged elimination of LD. But it is not known whether EN addition influences gastric emptying and thus LD pharmacokinetics and pharmacodynamics. Objectives were to simultaneously determine plasma LD elimination, gastric emptying, and clinical response after a single intake of the same LD dosage as LD/CD--or as (LD/CD/EN) formulation on 2 consecutive days. In both groups, PD patients with delayed gastric emptying had significant lower LD plasma concentrations. Addition of EN did not influence gastric emptying but significantly improved motor response, which was not different for patients with delayed gastric emptying. However, with and without EN adjunction gastric emptying distinctly contributes to the variability of plasma LD bioavailability. This may impact LD delivery to the brain and thus motor response in PD patients. Therefore, fine tuning of LD application, which considers gastric emptying, becomes more and more essential in advanced PD stages with a reduced striatal neuronal dopamine capacity, which is responsible for maintenance of motor response in early PD patients.

Adult↗
PubMedDate not supplied

Treatment of somatoform disorders with St. John's wort: a randomized, double-blind and placebo-controlled trial.

OBJECTIVE: To investigate efficacy and safety of St. John's wort (SJW) LI 160 in somatoform disorders. METHODS: In a prospective, randomized, placebo-controlled, and double-blind parallel group study, 184 outpatients with somatization disorder (ICD-10 F45.0), undifferentiated somatoform disorder (F45.1), and somatoform autonomic dysfunction (F45.3), but not major depression, received either 300 mg of SJW extract LI 160 twice daily or matching placebo for 6 weeks. Six outcome measures were evaluated as a combined measure by means of the Wei Lachin test: Somatoform Disorders Screening Instrument--7 days (SOMS-7), somatic subscore of the HAMA, somatic subscore of the SCL-90-R, subscores "improvement" and "efficacy" of the CGI, and the global judgment of efficacy by the patient. RESULTS: In the intention to treat population (N=173), for each of the six primary efficacy measures as well as for the combined test, statistically significant medium to large-sized superiority of SJW treatment over placebo was demonstrated (p <.0001). Of the SJW patients, 45.4% were classified as responders compared with 20.9% with placebo (p =.0006). Tolerability of SJW treatment was equivalent to placebo. CONCLUSIONS: Administration of 600 mg of SJW extract LI 160 daily is effective and safe in the treatment of somatoform disorders, thereby confirming results from a previous study.

Adolescent↗
PubMedDate not supplied

Impact of levodopa on reduced nerve growth factor levels in patients with Parkinson disease.

The author s found 6.5-fold reduced nerve growth factor (NGF) levels in the plasma of treated patients with Parkinson disease (PD) compared with healthy control subjects (P = 0.03). A significant positive correlation between levodopa and NGF plasma levels appeared after acute levodopa/benserazide administration. The data suggest that acute levodopa administration may contribute to an increase of NGF plasma concentrations, which are reduced in treated PD patients due to the ongoing disease process itself or chronic antiparkinsonian drug treatment.

Adult↗
PubMedDate not supplied

Levodopa intake increases plasma levels of S-adenosylmethionine in treated patients with Parkinson disease.

Metabolism of levodopa via the enzyme catechol-O-methyltransferase requires S-adenosylmethionine (SAM) as a methyl donor. SAM caused Parkinson disease (PD)-like symptoms in rodents. Therefore, SAM could contribute to a decreased efficacy of levodopa in the long term. SAM levels were significantly reduced in levodopa-treated PD patients, but they showed increased enzyme methionine adenosyl transferase (MAT) activity, which induces SAM synthesis from methionine (MET). This may result from a rebound increase of SAM production. The objective of the study was to demonstrate an effect of acute levodopa intake on SAM synthesis in the plasma of treated PD patients. The authors measured SAM, MET, and levodopa plasma concentrations in 13 levodopa-treated PD patients before and after application of 125 mg levodopa/benserazide. Plasma levels of SAM and levodopa significantly increased, but MET concentrations did not significantly decrease. The SAM increase after levodopa intake may exert both a certain antidepressant and cognitive function improving effect. This is often observed in untreated PD patients who receive levodopa for the first time, or in more advanced, fluctuating PD patients, when they turn from the OFF to the ON phase. Because SAM in higher dosages may also counteract the antiparkinsonian efficacy of levodopa according to animal trials, this SAM increase may hypothetically contribute to the onset of wearing-off phenomena and other clinical signs of limited efficacy of levodopa during long-term treatment with levodopa in PD patients.

Administration, Oral↗
PubMedDate not supplied

Efficacy of mitoxantrone and intrathecal triamcinolone acetonide treatment in chronic progressive multiple sclerosis patients.

Treatment approaches are rare for chronic progressive patients with multiple sclerosis (MS). Objective was to evaluate the clinical benefit of repeated intrathecal application of the sustained release steroid triamcinolone acetonide or the administration of mitoxantrone (MIX) in 2 similar cohorts of chronic progressive patients with MS in an open-label fashion. Expanded Disability Status Scale scores significantly decreased after the first 6 intraspinal triamcinolone acetonide injections, which were performed every third day, and then remained stable. Walking distance significantly increased and did not reduce until the end of the 1-year-long trial period. Mitoxantrone treatment did not improve the Expanded Disability Status Scale score; however, no further significant deterioration appeared. Walking distance did not significantly decrease. Both treatment regimens were safe; the patients experienced nearly no adverse effects. Triamcinolone acetonide application provided a clinical benefit, whereas MIX administration prevented further worsening of MS symptoms. We stress that only specialists with a broad experience in intraspinal triamcinolone acetonide application and MIX administration should perform both kinds of therapy only after a careful information and risk-benefit evaluation in cooperation with the patient. Future trials will show the efficacy of combination of both treatment approaches in chronic progressive patients with MS.

Adult↗
PubMedDate not supplied

Patient evaluation of a home diary to assess duration and severity of dyskinesia in Parkinson disease.

OBJECTIVE: To evaluate patient perceptions of a new home diary designed to assess the duration and severity of dyskinesia in patients with Parkinson disease (PD) and to investigate whether the use of a training video and pictograms aids patient understanding of PD terminology. METHODS: Fifty advanced PD patients (Hoehn and Yahr stage 2.5-4.0; dyskinesia for >25% of the waking day) from the United States (n = 18), France (n = 12), and Germany (n = 20) were allocated alternately to 1 of 2 groups and shown a training video either with pictograms or without pictograms. The video explained the functional states "asleep," "OFF," "ON without dyskinesia," and "ON with dyskinesia," and how to complete the diary. Patients were given the corresponding version of the diary with or without pictograms to complete over a 24-hour period. Patients then participated in a second interview in which they were shown the alternate version of the video and diary for discussion only. RESULTS: Almost 95% of patients (47/50) reported that the video helped them to understand and clarify terms. Most patients [39/50 (78%)] preferred the diary with pictograms, but there was no evidence that pictograms improved the accuracy of diary completion. Overall, 80% of patients (40/50) completed the diaries correctly. Incorrect diary completion was usually because of confusion about the different functional states. CONCLUSIONS: Patients perceive diaries with pictograms as more helpful than those with words alone. Videos, in the patients' primary language, are considered valuable training aids that help patients complete daily diaries.

Activities of Daily Living↗
PubMedDate not supplied

Explanatory and illustrative visualization of special and general relativity.

This paper describes methods for explanatory and illustrative visualizations used to communicate aspects of Einstein's theories of special and general relativity, their geometric structure, and of the related fields of cosmology and astrophysics. Our illustrations target a general audience of laypersons interested in relativity. We discuss visualization strategies, motivated by physics education and the didactics of mathematics, and describe what kind of visualization methods have proven to be useful for different types of media, such as still images in popular science magazines, film contributions to TV shows, oral presentations, or interactive museum installations. Our primary approach is to adopt an egocentric point of view: The recipients of a visualization participate in a visually enriched thought experiment that allows them to experience or explore a relativistic scenario. In addition, we often combine egocentric visualizations with more abstract illustrations based on an outside view in order to provide several presentations of the same phenomenon. Although our visualization tools often build upon existing methods and implementations, the underlying techniques have been improved by several novel technical contributions like image-based special relativistic rendering on GPUs, special relativistic 4D ray tracing for accelerating scene objects, an extension of general relativistic ray tracing to manifolds described by multiple charts, GPU-based interactive visualization of gravitational light deflection, as well as planetary terrain rendering. The usefulness and effectiveness of our visualizations are demonstrated by reporting on experiences with, and feedback from, recipients of visualizations and collaborators.

Computer Graphics↗