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Biomedical subjects

T Müller

Publications and source records attributed to T Müller.

At least 55 records · Page 3Linked to original sources
PubMed2004

Effect of carotid endarterectomy or stenting on impairment of dynamic cerebral autoregulation.

BACKGROUND AND PURPOSE: Analysis of dynamic cerebral autoregulation (DCA) from spontaneous blood pressure fluctuations might contribute to prognosis of severe internal carotid artery stenosis, but its response to carotid recanalization has not been investigated so far. This study investigates the effect of carotid endarterectomy or stenting on various DCA parameters. METHODS: In 58 patients with severe unilateral stenosis undergoing carotid endarterectomy (n=41) or stenting (n=17), cerebral blood flow velocity (CBFV, transcranial Doppler) and arterial blood pressure (ABP, Finapres method) were recorded over 10 minutes before and on average 3 days after carotid recanalization. Nineteen patients were additionally examined after 7 months. Correlations between diastolic and mean ABP and CBFV fluctuations were averaged to form the correlation coefficient indices (diastolic [Dx] and mean values [Mx]). Transfer function parameters (low-frequency phase and high-frequency gain between ABP and CBFV oscillations) were calculated over the same 10 minutes. CO2 reactivity was assessed via inhalation of 7% CO2. RESULTS: Before recanalization, all DCA parameters were clearly impaired ipsilaterally compared with contralateral sides. Phase, Dx, and Mx indicated early normalization of DCA after both endarterectomy and stenting. By multiple regression, the degree of DCA improvement was highly significantly related to the extent of impairment before recanalization. No significant change in DCA was found at follow-up. Ipsilateral gain and CO2 reactivity increased significantly less after endarterectomy than after stenting (P<0.05). CONCLUSIONS: Dynamic cerebral dysautoregulation in patients with severe carotid obstruction is readily and completely remedied by carotid recanalization.

Blood Flow Velocity↗
PubMed2004

Comparative study of X-ray computerised tomography and conventional X-ray methods in diagnosis of swimbladder infection in eels caused by Anguillicola crassus.

To date, swimbladder lesions due to Anguillicola crassus infection of the European eel Anguilla anguilla have so far been studied only by conventional X-ray methods. This is the first study to report the use of computerised tomography (CT) for studying lesions induced by anguillicolosis. Of 50 eels caught by electrofishery from Lake Balaton, Hungary, in autumn 2002 and pre-selected by a conventional X-ray method, 22 specimens were examined with a Siemens Somatom Plus S40 spiral CT scanner. Tomograms, radiographs and photographs of 5 of these, showing anguillicolosis-induced swimbladder lesions of varying severity, are presented. Computerised tomograms provide information on the inner structure, air content and wall thickness of the swimbladder as well as on the number of worms it contains. When the swimbladder is not severely affected or not completely filled with worms, computerised tomography provides adequate data on the shape of the swimbladder, thickness of the swimbladder wall and the location of worms in the lumen. However, in more severe cases, i.e. when the swimbladder is tightly packed with worms or contains no air as a result of wall-thickening, this method fails to determine the number and location of helminths or the thickness of the swimbladder wall.

Air Sacs↗
PubMed2004

The Helmholtz Network for Bioinformatics: an integrative web portal for bioinformatics resources.

SUMMARY: The Helmholtz Network for Bioinformatics (HNB) is a joint venture of eleven German bioinformatics research groups that offers convenient access to numerous bioinformatics resources through a single web portal. The 'Guided Solution Finder' which is available through the HNB portal helps users to locate the appropriate resources to answer their queries by employing a detailed, tree-like questionnaire. Furthermore, automated complex tool cascades ('tasks'), involving resources located on different servers, have been implemented, allowing users to perform comprehensive data analyses without the requirement of further manual intervention for data transfer and re-formatting. Currently, automated cascades for the analysis of regulatory DNA segments as well as for the prediction of protein functional properties are provided. AVAILABILITY: The HNB portal is available at http://www.hnbioinfo.de

Algorithms↗
PubMed2004

Transdermal lisuride delivery in the treatment of Parkinson's disease.

Transdermal delivery of dopamine agonists (DA) is a promising therapeutic concept, which aims to ameliorate frequency and intensity of motor fluctuations in patients with Parkinson's disease (PD). We treated 8 PD patients with unpredictable on-off phenomena with lisuride patches (release: 2-5 microg lisuride base/cm2/hour in mice) in addition to their preexisting antiparkinsonian drug regime up to a period of 8 days. In order to quantify the intensity and frequency of motor fluctuations, we determined the motor changing rate (MCR), which corresponds to the patient's self rating of motor function, performed every thirty minutes, divided through the number of scored intervals minus 1. Additional lisuride patch application significantly (p = 0.023) improved the MCR compared to baseline. Relevant side effects were transient skin irritations in four patients. Our observational study demonstrates the safety, tolerability and efficacy of transdermal lisuride delivery in the treatment of motor complications.

Administration, Cutaneous↗
PubMed2004

MTHFR C677T polymorphism, folic acid and hyperhomocysteinemia in levodopa treated patients with Parkinson's disease.

Certain mutations (TT homozygous; CT heterozygous; CC wild-type) of the methylenetetrahydrofolate (MTHFR) gene and long-term levodopa application in patients with Parkinson's disease (PD) support onset of hyperhomocysteinemia. Total plasma homocysteine (t-hcys) depends on B6, B12, folic acid, all of which support remyelination from t-hcys to methionine. Objective of this trial were to compare B6, B12, folic acid and t-hcys levels in plasma of 83 levodopa treated PD patients and 44 controls. PD patients with the CT or TT genotype had significant higher t-hcys levels than controls or PD patients with the CC allele. Concentrations of B6 or B12 did not differ, but folic acid was significant higher in PD patients with the CT mutation. We recommend MTHFR genotyping, t-hcys monitoring and early vitamin supplementation in PD patients. The folic acid increase in PD patients with the CT allele is hypothetically due to an endogenous upregulation of folic acid absorption to decrease t-hcys.

Adult↗
PubMed2004

[Pumpless extracorporeal lung assist using arterio-venous shunt in severe ARDS. Experience with 30 cases].

BACKGROUND: Extracorporeal lung assist has been proposed as an invasive measure in patients with acute respiratory distress syndrome (ARDS) when oxygenation is critically impaired. However, this technique generally requires high personnel and technical resources. We report on a new system, which is characterised by a short circuit arterio-venous shunt using arterio-venous pressure gradient as driving force (pumpless extracorporeal lung assist [pECLA]). PATIENTS AND METHODS: In 30 patients with ARDS due to multitrauma, pneumonia or after surgery (p(a)O(2)/F(I)O(2)-ratio 67+/-23 mmHg) pECLA was established by insertion of cannulae to the femoral artery and vein followed by connection with a membrane gas exchanger. For this system, only "low dose" continuous heparin infusion is required. RESULTS: Arterial oxygenation was acutely and significantly increased by pECLA (p(a)O(2)/F(I)O(2)=103+/-56 mmHg 2 h after begin) and carbon dioxide removal was markedly enhanced in 25 out of 30 patients (87%) allowing a lung protective ventilation strategy. The mean duration of pECLA therapy was 6.5 days, 15 patients (50%) died due to ARDS or non-ARDS related reasons. CONCLUSION: pECLA represents a feasable and effective treatment in patients with severe ARDS. Compared with pump-driven systems pECLA is characterised by low costs and reduced personnel requirements. However, mortality remains high in patients suffering from severe ARDS despite newer treatment modalities.

Adult↗
PubMed2004

[Zoonoses in working- and wild animals and their significance in Germany. An overview].

The control of infectious diseases transmitted from animals to humans (zoonoses) was recently put on a new basis in the European Union when a new Zoonoses Directive entered into force. Brucellosis, campylobacteriosis, echinococcosis, listeriosis, salmonellosis, trichinosis, and the respective causative agents, tuberculosis due to Mycobacterium bovis, and verotoxigenic Escherichia coli must be included in monitoring. Additional zoonoses and zoonotic agents are to be monitored according to the epidemiological situation. Against this background, the current knowledge on important zoonoses transmitted from livestock and some wildlife animals to humans as well as the epidemiological situation in Germany with regard to these diseases is summarized.

Animals↗
PubMed2004

Copper-induced hepatotoxicosis with hepatic stellate cell activation and severe fibrosis in North Ronaldsay lambs: a model for non-Wilsonian hepatic copper toxicosis of infants.

Copper-sensitive North Ronaldsay sheep represent a possible model for certain hepatic-overload syndromes of infancy and childhood that are clinically, pathologically and genetically distinct from Wilson's disease. The purpose of this study was to simulate in artificially reared lambs the syndrome produced by copper exposure in susceptible human infants. Twenty four North Ronaldsay lambs were assigned to three groups of eight animals, namely, an unsupplemented control group and two trial groups given milk replacer to which copper (CuSO4) had been added at the rate of 5 mg/litre and 10 mg/litre. Four lambs from each group were killed at 40 or 69 days. Livers were fixed in 10% formalin and analysed for copper by mass spectrometry. Paraffin wax-embedded sections were stained with rhodanine for copper and labelled immunohistochemically for alpha smooth muscle actin (ASMA). At 40 days the maximum amounts of copper in the livers of both copper-supplemented groups was 1466-1605 microg/g dry weight (control group 172-201 microg/g Cu dry weight). Histochemically, copper was demonstrated within hepatocytes, together with marked apoptosis. At 69 days there was a florid pericellular fibrosis complemented by strong ASMA immunolabelling, confirming phenotypic modulation of hepatic stellate cells. Such primary copper-induced fibrogenesis confirms the unique status of this animal model in respect of childhood copper toxicosis.

Animals↗
PubMed2004

Differential response in choice reaction time following apomorphine based on prior dopaminergic treatment.

Choice reaction time (CRT) paradigms demonstrated deficits in the preparation and execution of movements in patients with Parkinson's Disease (PD). Predominantly these trials did not consider an influence of acute and long-term dopaminergic substitution. Objective was to determine the acute effect of apomorphine on the response to a repeatedly performed CRT task. We repeatedly executed the CRT paradigm before and after subcutaneous apomorphine injection in previously treated, untreated and long-term dopamine substituted PD patients, who took placebo. No significant change of CRT and movement time (MT) appeared in PD patients with chronic dopaminergic drug intake after apomorphine injection. CRT and MT both significantly worsened in untreated PD patients. Placebo application induced no significant alteration. Binding of apomorphine to presynaptic autoreceptors with subsequent sedation or inhibition of locomotor activity hypothetically explain our results in before untreated PD patients. Previous long-term dopaminergic substitution may cause a certain tolerance to this phenomenon.

Adult↗
PubMed2004

The carboxyterminal peptide of chorionic gonadotropin facilitates activation of the marmoset LH receptor.

Luteinizing hormone (LH) and chorionic gonadotropin (CG) are heterodimeric glycoprotein hormones acting on the luteinizing hormone receptor (LHR). In the LHR, which is genomically encoded by eleven exons, exon 10 encodes for the hinge region and its elimination impairs LH action, while CG maintains normal activity. The two gonadotropins differ in the carboxyterminal peptide (CTP) present in CG but absent in LH. Since the marmoset monkey (Callithrix jacchus) LHR naturally lacks exon 10 (LHR type II), we generated two recombinant marmoset gonadotropin preparations, one consisting of the wild type CG and one of truncated CG lacking the CTP (CG (-CTP)). After calibration in a mouse Leydig cell bioassay against the WHO LH80/522 standard, the ED (50) of the CG preparation on a COS7 cell line permanently expressing the marmoset LHR was 4.25 +/- 0.21 IU/L (n = 3). Stimulation of the COS7 cell line with equipotent concentrations of CG and CG (-CTP) resulted in significantly different formation of cAMP (two-way ANOVA, p < 0.001). In particular, cAMP production stimulated by CG (-CTP) was 3 - 4 times lower compared to CG at the saturating CG concentration (8 IU/L). We conclude, supplementing one current model of LHR activation, that exon 10 might play a permissive role in releasing the constraint of the receptor upon hormone binding, resulting in receptor activation. We speculate that, when exon 10 is lacking, the CTP can overcome its absence and facilitates the opening of the receptor, resulting in normal activation.

Amino Acid Sequence↗
PubMed2004

Spill-over of European bat lyssavirus type 1 into a stone marten (Martes foina) in Germany.

European bat lyssavirus type 1 (EBLV-1, genotype 5) is known to endemically circulate in insectivorous bat populations in Germany. In August 2001, a rabies suspect stone marten (Martes foina) was found in the city of Burg (Saxony-Anhalt, Germany) and was sent to the regional veterinary laboratory for routine rabies diagnosis. Whereas brain samples repeatedly tested negative in the fluorescent antibody test for classical rabies virus (genotype 1), the mouse inoculation test and the rabies tissue culture inoculation test yielded positive results. Rabies viral RNA was also detected in the stone marten brain sample both by nested and heminested RT-PCR specific for the nucleoprotein gene and for the nucleoprotein phosphoprotein junction of rabies virus. The amplification products were sequenced to genotype the isolate. Sequence data obtained from the first-round RT-PCR products were analysed and the suspect stone marten isolate was confirmed as a rabies related virus (EBLV-1a). Phylogenetic comparison with sequences from recent genotype five isolates from Germany and Denmark showed that it was closely related to a previous isolate of EBLV-1 from a serotine bat in Saxony-Anhalt obtained in the same year in an area adjacent to the place where the EBLV-1 infected stone marten was found. Both EBLV-1 isolates share a 99.5% identity. This is the first report of an EBLV-1a spill-over from an insectivorous bat into wildlife in Europe.

Animals↗
PubMed2004

Susceptibility of ferrets (Mustela putorius furo) to experimentally induced rabies with European Bat Lyssaviruses (EBLV).

Twenty ferrets (Mustela putorius furo) were inoculated by intramuscular (i.m.) injection with European Bat Lyssaviruses (EBLV) type-1 and 2 using 10(4.0) foci-forming units (FFU) EBLV-2 (n = 6), 10(4.0) FFU EBLV-1 (n = 7) and 10(6.0) FFU EBLV-1 (n = 7). Furthermore, 15 mice received 10(2.5) FFU EBLV-2 (n = 5), 10(2.5) FFU EBLV-1 (n = 5) and 10(4.5) FFU EBLV-1 (n = 5) by i.m. inoculation. All ferrets and mice receiving the higher dose of EBLV-1 succumbed to infection. In contrast, only three of seven ferrets and two of five mice inoculated experimentally with the lower EBLV-1 dose died. By comparison, all of the EBLV-2 infected ferrets and four of five mice survived infection. All 20 infected ferrets seroconverted. Using sensitive molecular tools, the virus was detected in different tissues, but it could not be found in any saliva samples taken during the 84-day observation period.

Animals↗
PubMed2004

Rabies in red foxes (Vulpes vulpes) experimentally infected with European bat lyssavirus type 1.

The susceptibility of red foxes (Vulpes vulpes) to European bat lyssavirus type 1 (EBLV-1) infection was examined. Eight foxes were inoculated intramuscularly (i.m.) with 10(4.9) foci-forming units (FFU) (n = 4) and 10(5.1) FFU (n = 4) and observed for up to 90 days. All foxes showed manifestations of a neurologic disorder (e.g. seizures, myoclonus, agitation), starting as early as 5 days post-infection (p.i.). Subsequently, all animals showed improvement followed by one or more relapses. One fox was killed 3 days after it recovered, 26 days post-infection. Two other foxes were also killed 38 and 54 days post-infection after severe neurologic signs returned. All foxes developed a humoral immune response against EBLV-1 as determined in serum and brain tissues. However, no rabies virus antigen was detected in the brain, other tissues and secretions examined (e.g. salivary gland, saliva, tonsils, lungs) by using different standard diagnostic techniques [fluorescent antibody test, reverse transcription polymerase chain reaction (RT-PCR), rabies tissue culture inoculation test], with the exception of one fox in which EBLV-1 RNA was detected by RT-PCR in only the spinal cord. Brain tissues showed moderate to severe multifocal, mononuclear encephalomyelitis in the three foxes that were killed during the observation period, although no EBLV-1 virus was detectable in these tissues.

Animals↗
PubMed2004

Tracking of the hormonally induced maturation of female eels by computed tomography.

Female European eels were kept in artificial seawater for a trial period of 14 weeks. Three fish were injected intra-abdominally with carp pituitary suspension (twice a week) and human chorionic gonadotropin (every 2nd week), with the aim to induce artificial maturation. Three further fish were not treated (control). Fish were not fed during the trial. The treated fish were scanned by computed tomography (CT) every second week (the controls only at the start and at the end of the trial) to follow changes in body composition. Notable decreases were shown in total body pixel number (body volume), total body fat content, total fillet volume and fillet fat content during the experiment. Changes were more pronounced in the treated group than in the control. The abdominal volume strongly increased in the responding fish throughout the trial. The ovary volume increased measurably, while its fat content increased only until the 8th week, after which a decrease was measured. Tissue volumetric estimations of the ovary were also supported by histological results. A so-called volumetric gonadosomatic index (gonad volume/total body volume x 100) was developed for the quantitative characterisation of eel maturation.

Abdomen↗
PubMed2004

Chorionic gonadotrophin beta subunit mRNA but not luteinising hormone beta subunit mRNA is expressed in the pituitary of the common marmoset (Callithrix jacchus).

The pituitary gonadotrophins LH and FSH are responsible for regulation of gametogenesis in the testis and ovary. Chorionic gonadotrophin (CG), a third closely related glycoprotein hormone derived by gene duplication of the LHbeta gene and secreted by the placenta in primates, is essential for the rescue of the corpus luteum and maintenance of pregnancy. We have recently shown that marmoset (m) CGbeta mRNA is highly expressed in the pituitary of the common marmoset (Callithrix jacchus) and that LH is less active than human CG in activating the human LH receptor lacking exon 10. To investigate further which gonadotrophin is the actual ligand of the LH receptor (LHR) of the marmoset monkey that naturally lacks exon 10, we identified and characterised the genomic organisation of the mLHbeta gene and its expression. Intergenic PCR amplification of the region encompassing the mLHbeta and the mCGbeta genes revealed that, surprisingly, mCGbeta is located 20 kbp upstream of the LHbeta gene, whereas in other species the intergenic distance is approximately 2-3 kbp. Sequence analysis of the mLHbeta coding region showed 70% identity to mCGbeta and 90% identity to human LHbeta at the amino acid level. Both gonadotrophin beta subunits are present at the genomic level, but RT-PCR of pituitary and placental total RNA using specific oligonucleotides for mCGbeta and mLHbeta showed high expression of mCGbeta mRNA in both tissues, whereas LHbeta was expressed neither in the pituitary nor in the placenta. Thus mLHbeta mRNA is lacking in the marmoset pituitary. Immunohistochemistry of marmoset pituitaries showed that mCG was confined to the gonadotrophes, and partly co-localised in cells stained positively for FSH. Western blot analysis confirmed the presence of mCG in the pituitary. Northern blot analysis using mCGbeta as a probe displayed one transcript of 0.7 kb in the pituitary and detected two transcripts of 1.1 kb and 2 kb in the marmoset placenta. Our results suggest that, in the common marmoset, CG is the only gonadotrophin with luteinising function that is present in the pituitary. We postulate that, owing to an unknown mutational event in evolution, expression of mLH was completely abolished, and CG - which, unlike LH, acts normally even when exon 10 is missing from the LHR - took over its function.

Amino Acid Sequence↗