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Biomedical subjects

T Müller

Publications and source records attributed to T Müller.

At least 271 records · Page 15Linked to original sources

Serological survey of viral pathogens in bean and white-fronted geese from Germany.

Sera from wild geese were tested for antibodies to selected viral pathogens at a resting site for wild waterfowl in Germany. Serum samples from both bean geese (Anser fabalis) and white-fronted geese (Anser albifrons) collected in October 1991 were examined using serological methods licensed for routine diagnosis in domestic poultry. Of 130 sera tested, antibodies to several infectious agents were found including Newcastle disease virus (45%), goose parvovirus (48%), avian reovirus (29%), and avian adenovirus or egg drop syndrome 76 virus (6%). Antibodies against duck hepatitis virus were not detected. Differences in seroprevalences were not detected between the two geese species. While role and significance of wild geese in the epidemiology of avian diseases remains to be determined, it is possible that they could be of some importance as reservoirs and carriers of certain viral diseases of domestic poultry.

Animals↗

Recurrence of renal disease after kidney transplantation in children: 24 years of experience in a single center.

The aim of this study was to assess the frequency and clinical implications of a recurrence of the original renal disease in children after kidney transplantation. Thus, the records of patients with immunological and metabolic diseases transplanted between 1970 and 1994 were retrospectively analyzed. There were 113 renal transplantations in 99 patients, who had the following original diseases: focal segmental glomerulosclerosis (FSGS), membrano-proliferative glomerulonephritis type I and type II (MPGN I, II), Henoch-Schoenlein nephritis, IgA-nephropathy, hemolytic uremic syndrome (HUS) and hyperoxaluria type I (PH I) and other rare diseases. Recurrences were observed in FSGS, MPGN II, HUS and PH I but not in the other diseases. In FSGS, the recurrence rate was 20% with graft failure in 5 of 6 grafts. No specific risk factors for recurrent FSGS could be determined. In MPGN II, the recurrence was 60% but the loss of grafts occurred at the same rate as in the non-recurrence group. In HUS, recurrence was seen in 4 out of 24 renal grafts (16.6%) with subsequent graft loss in all cases. All cases had suffered from an atypical HUS. PH I recurred in 4 of 5 allografts with graft loss in all patients. The remaining graft was transplanted after a liver transplantation and graft function was well preserved for 4 years. We confirm that the risk of recurrence with loss of the graft is high in a certain group of renal diseases. In these the indication for transplantation, particularly with living related donor kidneys, needs special evaluation. A better understanding of the pathomechanism of the diseases should lead to prevention of recurrence, as in PH I in which a liver transplant is now the primary option.

Adolescent↗

[Boar semen--a possible risk factor in infection occurrence of porcine reproductive and respiratory syndrome].

Based on an experimental study using two and six PRRS-negative young boars and gilts, respectively, it was proven wether boar semen could be a risk factor in the transmission of the disease. The two boars were inoculated intranasally with the PRRS-virus strain I10 (Intervet) containing 107 TCID50/ml. Using ovulation synchronization six gilts were prepared as bioindicators to be inseminated, two of them with semen of the two boars at day 4, 8 and 12 after infection. Following inoculation of the boars, PRRS virus was shown to be present in blood from the 2nd until the 35th and 40th day p.i., respectively. PRRS virus could also be isolated from nasal swabs at day 6, 9, 12 and 19 and from preputial swabs at day 4, 12 and 27 after infection. PRRS virus could only be detected at day 19 p.i. in semen of one boar. Drastic changes in quality and volume of the ejaculate were observed about day 25 p.i. in both animals. Insemination of the gilts with semen collected at day 4, 8 and 12 p.i., however, did not lead to an infection of the females, because neither clinical signs typical for PRRS nor seroconversion could be observed. Reproductive parameters as well as birth and growing traits of the gilts were in accordance with norm values.

Animals↗

[Chronic peritoneal dialysis as home therapy in childhood--risks and complications].

BACKGROUND: The aim of our study was to ascertain the complications of chronic peritoneal home dialysis in childhood. PATIENTS: 17 children were treated by ambulatory peritoneal home dialysis between 1984 and 1994 at the paediatric dialysis unit of the University Children's Hospital in Vienna, Austria. Their average age was 6.5 years (1 week to 12 years); 7 (41.2%) children were below school age (< 6 years). RESULTS: In our observation period of 369 dialysis months (DM), the average duration of dialysis was 21.7 months (4.0-74.3). In relation to total DM the incidence of peritonitis was 1:23.1 of exit site infection 1:14.8 and of catheter related complications 1:41.0. 5 children developed hernias. 5 children were switched to haemodialysis and 8 children received kidney transplants. 2 children died from non-dialysis-associated causes. CONCLUSION: Peritoneal dialysis, in contrast to haemodialysis, is a home treatment modality applicable even to infants. The most common complication is infection. Our data and the European and North American literature show that by close ambulatory monitoring and special hygenic procedures peritonitis frequency can be markedly reduced.

Austria↗

Cellular redistribution of protein tyrosine phosphatases LAR and PTPsigma by inducible proteolytic processing.

Most receptor-like protein tyrosine phosphatases (PTPases) display a high degree of homology with cell adhesion molecules in their extracellular domains. We studied the functional significance of processing for the receptor-like PTPases LAR and PTPsigma. PTPsigma biosynthesis and intracellular processing resembled that of the related PTPase LAR and was expressed on the cell surface as a two-subunit complex. Both LAR and PTPsigma underwent further proteolytical processing upon treatment of cells with either calcium ionophore A23187 or phorbol ester TPA. Induction of LAR processing by TPA in 293 cells did require overexpression of PKCalpha. Induced proteolysis resulted in shedding of the extracellular domains of both PTPases. This was in agreement with the identification of a specific PTPsigma cleavage site between amino acids Pro821 and Ile822. Confocal microscopy studies identified adherens junctions and desmosomes as the preferential subcellular localization for both PTPases matching that of plakoglobin. Consistent with this observation, we found direct association of plakoglobin and beta-catenin with the intracellular domain of LAR in vitro. Taken together, these data suggested an involvement of LAR and PTPsigma in the regulation of cell contacts in concert with cell adhesion molecules of the cadherin/catenin family. After processing and shedding of the extracellular domain, the catalytically active intracellular portions of both PTPases were internalized and redistributed away from the sites of cell-cell contact, suggesting a mechanism that regulates the activity and target specificity of these PTPases. Calcium withdrawal, which led to cell contact disruption, also resulted in internalization but was not associated with prior proteolytic cleavage and shedding of the extracellular domain. We conclude that the subcellular localization of LAR and PTPsigma is regulated by at least two independent mechanisms, one of which requires the presence of their extracellular domains and one of which involves the presence of intact cell-cell contacts.

Amino Acid Sequence↗

[Non-motor symptoms of Parkinson disease. Significant impact on quality of life--using possible treatments].

In patients with idiopathic Parkinson's disease, not only the motor disorders, but also disturbances of the autonomic nervous system and the psyche need to be treated. With respect to the autonomic nervous system, such symptoms as hypersalivation, seborrhea, dysregulation of the cardiovascular system, disturbances of the gastrointestinal tract and bladder motility, as also sleep disorders predominate. Also seen in Parkinson's disease are such psychiatric complaints as depression, dementia and psychoses, which latter in particular may also be a consequence of dopaminergic replacement therapy. A number of therapeutic concepts are available for the treatment of these disorders, which are often extremely stressful for the patient and therefore require early treatment.

Autonomic Nervous System Diseases↗

[Current therapy of idiopathic Parkinson disease. 1: Diagnosis, therapeutic guidelines, standard pharmacotherapy and physical therapy].

The necessary prerequisite for adequate medical and physical treatment are early diagnosis and differential diagnosis. The gold standard for medical treatment of Parkinsonism continues to be the administration of L-dopa. However, in view of the complications associated with the long-term use of L-dopa, combination treatment with dopamine agonists and substances presumed to have a neuroprotective effect, for example selegiline, administered at the onset of the disease is currently gaining importance and finding increased interest.

Antiparkinson Agents↗

[Current therapy of idiopathic Parkinson disease. 2: Recent and alternative therapies].

New possibilities in the medical treatment of Parkinson's disease are offered by the MAO-B inhibitor, selegiline, and L-dopa preparations with strongly accelerated or retarded kinetics. Possible new approaches to drug treatment might be, firstly, inhibition of the enzyme catechol-o-methyl-transferase, which influences the breakdown of dopamine, and secondly, administration of NADH with the aim of stimulating the body's own synthesis of dopamine. A third approach might be the reintroduction of stereotactic surgery with coagulation or stimulation of certain areas of the brain, that has now been made possible by the development of new and more subtle techniques. Neuroprotective and/or neuro-regenerative approaches, such as, for example, the administration or stimulation of growth factors and/or transplantation of neuronal dopaminergic cells might lead the treatment of Parkinson's disease from the palliative symptomatic approach it is today, to a future curative approach.

Antiparkinson Agents↗

Immunohistochemically detected HER-2/neu-expression and prognosis in endometrial carcinoma.

Expression of the HER-2/neu proto-oncogene product was looked for immunohistochemically in 222 endometrial carcinomas in a retrospective follow-up study. The intensity of protein expression was correlated with patient survival. Median follow-up time was 4.8 years. In 109 (49%) of 222 endometrial carcinomas there was aberrant expression of HER-2/neu. HER-2/neu-expression did not correlate with p53-expression and proliferation rate, as determined immunohistochemically by the monoclonal antibody Ki-S1. In univariate statistical analysis aberrant HER-2/neu expression was not predictive of adjusted survival (p = 0.18) and of disease-free survival (p = 0.42). In multivariate analysis HER-2/neu-expression was not found to be an independent prognosticator (p = 0.099) as compared to FIGO-stage (p = 0.0001), histologic grade (p = 0.00099) and proliferation rate (p = 0.0013). Therefore immunohistochemically detected expression of HER-2/neu seems not to be a clinical prognosticator in endometrial cancer.

Adult↗

Effect of the 21-aminosteroid tirilazad mesylate on leukocyte adhesion and macromolecular leakage during endotoxemia.

BACKGROUND: Interstitial accumulation of leukocytes has been related to the development of multiple organ failure after sepsis. Oxygen radicals are involved in the process of leukocyte adherence to the microvascular wall. This study investigates the effects of the oxygen radical scavenger tirilazad mesylate on leukocyte-endothelial interactions, macromolecular leakage, and microhemodynamics in mesenteric venules during endotoxemia. METHODS: Male Wistar rats were randomly allocated to receive tirilazad mesylate (group A, n = 10), its vehicle (group B, n = 10), or saline 0.9% (group C, n = 10) before a 120-minute infusion of endotoxin (2 mg/kg/hr). Furthermore, a control group without receiving endotoxin (group D, n = 10) was investigated. Leukocyte adherence, emigration of leukocytes, and macromolecular leakage were determined in postcapillary venules of the mesentery by using intravital videomicroscopy. RESULTS: During the administration of endotoxin the number of adherent leukocytes per square millimeter of vessel surface progressively increased in group B (baseline, 431 +/- 35 cells/mm2; 120 minutes, 1121 +/- 71 cells/mm2) and group C (baseline, 398 +/- 44 cells/mm2; 120 minutes, 1290 +/- 116 cells/mm2). In group A no increase in leukocyte adherence was observed after 120 minutes (baseline, 415 +/- 81 cells/mm2; 120 minutes, 638 +/- 87 cells/mm2). In control animals the leukocyte adherence remained unchanged (baseline, 347 +/- 41 cells/mm2; 120 minutes, 507 +/- 75 cells/mm2). After 120 minutes, tirilazad mesylate prevented the increase in leukocyte emigration observed in group B and C. Increased macromolecular leakage during endotoxemia (groups B and C) was not influenced by pretreatment with tirilazad. Tirilazad did not affect the decrease in red cell velocity, volumetric blood flow, and venular shear rate observed during endotoxemia. CONCLUSIONS: This study demonstrates inhibitory effects of tirilazad on endotoxin-induced leukocyte adherence and emigration, suggesting a potential therapeutic role for this substance in the prevention of sepsis-induced multiple organ failure.

Animals↗

GABA(A) receptor activation triggers a Cl- conductance increase and a K+ channel blockade in cerebellar granule cells.

GABA(A) receptor activation in cerebellar granule cells induced a complex physiological response, namely the activation of a Cl- conductance in concert with a blockade of the resting K+ outward conductance (by 71% as compared to controls). Both responses were mediated by the activation of GABA(A) receptors, since they were both mimicked by the GABA(A) receptor agonist muscimol and antagonized by picrotoxin and bicuculline. A substantial decrease of the mean open time of single, outwardly rectifying K+ channels was triggered by GABA as revealed from cell-attached recordings; this finding implies that an intracellular pathway links GABA(A) receptors and K+ channels. Furthermore, this action of GABA is mediated through the cytoplasm, as experiments with the cell-attached patch-clamp technique show. GABA induced a prominent membrane depolarization ranging from 10 to 25 mV as revealed by current-clamp recordings of gramicidin (or nystatin) permeabilized patches, thus selecting conditions not to perturb the physiological Cl- gradient across the cell. Our findings imply that the GABA-activated Cl- current depolarized the membrane as described for immature neurons. The blockade of the resting K+ channel conductance acts in concert and both mechanisms lead to this substantial depolarizing event.

Animals↗

[Therapy of Parkinson disease. 1: Standard therapy of motor and non-motor symptoms].

Early diagnosis is important for satisfactory pharmacotherapy of idiopathic Parkinson's disease (PD). L-Dopa therapy is still the gold standard in the treatment of PD, but due to complications of long term L-Dopa application, a combination therapy of levodopa with various dopamine agonists and putative neuroprotective drugs, like e.g. selegiline, is becoming increasingly important and attracts more and more attention, especially in the early phases of PD. Moreover, disturbances of the autonomic nervous system and the mind have to be considered and treated besides pharmacotherapy of motor symptoms in idiopathic Parkinson's disease (PD). Hypersalivation, seborrhoea, dysregulation of the cardiovascular system and disturbances of gastrointestinal and bladder motility and sleep are common mainly in the context of autonomic failure in PD. Moreover, Parkinsonian patients often complain of psychopathological features like depression, dementia and psychosis, which may also be due to dopaminergic Parkinsonian therapy. This review surveys possible therapeutic approaches of these disturbances of the psyche and the autonomic nervous system in PD.

Antiparkinson Agents↗

[Therapy of Parkinson disease. 2: New therapy concepts for treating motor symptoms].

New approaches in Parkinsonian pharmacotherapy may be (1) inhibition of catechol-O-methyl-transferase influencing the metabolism of dopamine, (2) the use of budipine, which is assumed to be neuroprotective, with an effect especially on tremor, (3) the application of NADH with the postulated stimulation of the endogenous dopamine synthesis and (4) the revival of stereotaxic surgery with the lesion or the stimulation of certain brain areas, enabled by the development of new and more sensitive methods. Neuroprotective, and/or neuroregenerative therapeutic approaches, like e.g. application or stimulation of growth factors and/or transplantation of neuronal dopaminergic cells, may redirect Parkinsonian therapy from present palliative, symptomatic therapeutic principles to acurative therapy in the future.

Antiparkinson Agents↗

Episodic variations of prolactin, thyroid-stimulating hormone, luteinizing hormone, melatonin and cortisol in infertile women with subclinical hypothyroidism.

Preliminary data have suggested that female infertility due to corpus luteum insufficiency may be caused by subclinical hypothyroidism [exaggerated thyroid-stimulating hormone (TSH) response to thyrotrophin-releasing hormone (TRH) stimulation]. L-Thyroxine supplementation has been recommended to achieve pregnancies in subclinical hypothyroid women. This controlled study was carried out in order to investigate the biochemical diagnosis of subclinical hypothyroidism as a possible infertility factor. Five infertile patients (aged 25-36 years) with subclinical hypothyroidism (n = 4, stimulated TSH >20 microU/ml) or primary hypothyroidism (n = 1) and five healthy controls (aged 22-39 years) with normal thyroid function (stimulated TSH <15 microU/ml), regular cycles and no history of infertility were studied in the early follicular phase. In the pre-study evaluation, eight of 23 volunteers (34.8%) had to be excluded because of subclinical hypothyroidism with stimulated TSH values (TSHs) >15 microU/ml. Cycle function of patients and controls was compared by the method of LH pulse pattern analysis. Therefore blood samples were drawn every 10 min during a 24 h period. Sleep was recorded from midnight to 7 a.m. Repetition of the TRH tests at the end of the 24 h blood sampling period confirmed the difference in stimulated TSH values of the two study groups. Pulse analysis for luteinizing hormone (LH), TSH and prolactin showed no differences between patients and controls for pulse frequency, amplitude, height, length, area under curve (AUC) and the 24 h mean. Even the hypothyroid patient had a normal LH pulse pattern. Additional measurement of melatonin in pooled sera every 30 min gave the well-documented diurnal profiles during day and night for both groups. Patients had significantly higher melatonin values at seven time points during the night. Peaks for LH, TSH, prolactin and cortisol were correlated with the sleep stages wake, rapid eye movement, 1 + 2 and 3 + 4. We concluded that corpus luteum insufficiency in female infertility cannot be explained by subclinical hypothyroidism and thus should not be treated with L-thyroxine for fertility reasons.

Adult↗

N-acetylcysteine attenuates endotoxin-induced leukocyte-endothelial cell adhesion and macromolecular leakage in vivo.

OBJECTIVE: To determine the influence of N-acetylcysteine on endotoxin-induced leukocyte-endothelial cell adhesion, vascular leakage, and venular microhemodynamics. DESIGN: Randomized, blinded, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Thirty male Wistar rats. INTERVENTIONS: After pretreatment with N-acetylcysteine (150 mg/kg; n = 40; group A) or 0.9% saline solution (n = 10; group B) animals were given an intravenous infusion of endotoxin (Escherichia coli lipopolysaccharide 026:B6; 2 mg/kg/hr) over 120 mins. Animals in the control group (n = 10; group C) received a volume-equivalent infusion of 0.9% saline solution. MEASUREMENTS AND MAIN RESULTS: Leukocyte adherence, red cell velocity (VRBC), vessel diameters, venular wall shear rate, and macromolecular leakage were determined in mesenteric postcapillary venules using in vivo videomicroscopy at baseline and at 30, 50, 90, and 120 mins after the start of the endotoxin challenge. Endotoxin exposure induced a marked increase in adherent leukocytes (group B: baseline, 391 +/- 24 cells/mm2; 120 mins, 1268 +/- 131 cells/mm2; p < .01). N-acetylcysteine pretreatment attenuated the adherence of leukocytes during endotoxemia (baseline, 366 +/- 28 cells/mm2; 120 mins, 636 +/- 49 cells/mm2; p < .01 vs. baseline; p < .01 vs. group B). Leukocyte adherence in control animals (group C) did not increase significantly. Administration of N-acetylcysteine did not influence the decrease in VRBC observed during endotoxemia. In group B1 VRBC decreased during the infusion of endotoxin from 2.0 +/- 0.2 mm/sec at baseline to 1.1 +/- 0.2 mm/ sec after 120 mins (p < .01 vs. baseline; p < .05 vs. group C), and in group A from 2.2 +/- 0.2 mm/sec to 1.1 +/- 0.1 mm/sec after 120 mins (p < .01 vs. baseline; p < .05 vs. group C). In group C, VRBC remained unchanged (baseline, 1.7 +/- 0.2 mm/sec; at 120 mins, 1.5 +/- 0.2 mm/sec). The venular diameters remained unchanged in all groups during the entire study period. After 120 mins, the venular wall shear rate decreased from 502 +/- 62 secs-1 at baseline to 272 +/- 46 sec-1 in group B (p < .01), and from 563 +/- 45 secs-1 at baseline to 283 +/- 31 secs-1 in group A (p < .01). No differences in venular wall shear rate were observed between these groups. In group C, the venular wall shear rate remained unchanged (baseline, 457 +/- 54 secs-1; at 120 mins, 409 +/- 51 secs-1). Macromolecular leakage, expressed as perivenular/intravenular fluorescence intensity after injection of fluorescence-labeled albumin, increased from 0.29 +/- 0.03 to 0.58 +/- 0.03 (p < .01) during the infusion of endotoxin in group B. In contrast, pretreatment with N-acetylcysteine diminished the extravasation of albumin (baseline, 0.27 +/- 0.01; at 120 mins, 0.37 +/- 0.02; p < .01 vs. baseline; p < .01 vs. group B). CONCLUSION: These results demonstrate that N-acetylcysteine attenuates endotoxin-induced alterations in leukocyte-endothelial cell adhesion and macromolecular leakage, suggesting N-acetylcysteine might be therapeutic in the prevention of endothelial damage in sepsis.

Acetylcysteine↗

2-[123I]-iodolisuride SPET visualizes dopaminergic loss in de-novo parkinsonian patients: is it a marker of striatal pre-synaptic degeneration?

The aim of this study was to assess the correlation between the functional integrity and density of striatal dopaminergic receptors and clinical data in 15 de-novo patients with idiopathic Parkinson's disease by single photon emission tomography (SPET) using 2-[123I]-iodolisuride (ILIS), a tracer based on the D2-dopamine receptor agonist lisuride. Deficient striatal uptake of ILIS correlated with the severity of the disorder, scored by the Unified Parkinson's Disease Rating Scale (UPDRS) (n = 15; ratio of ILIS uptake: basal ganglia/cerebellum [B/C] & UPDRS I-III, Spearman R = -0.562, P = 0.013), Beck's Depression Inventory (BDI) (n = 12; B/C & BDI, Spearman R = -0.825, P = 0.0009) and the ZUNG Depression Scale (ZDS) (n = 11; B/C & ZDS, Spearman R = -0.7425, P = 0.008). Experimental data indicate that lisuride shows a higher affinity for pre-synaptic dopaminergic autoreceptors than for post-synaptic D2-dopamine receptors under conditions of low applied ILIS concentrations as in this study. From the results of this study and these experimental data, we speculate that ILIS-SPET can visualize pre-synaptic striatal dopaminergic degeneration in Parkinson's disease.

Aged↗

Distorted colour discrimination in Parkinson's disease is related to severity of the disease.

The Farnsworth-Munsell 100-hue test (FMT) may be used for measurement of colour discrimination and error scores of the FMT provide an unspecific biological marker for the distinction between parkinsonian patients (PP) and healthy controls. The aim of this study was to examine the possible association between distorted colour discrimination and disease severity in untreated "de novo" PP Error scores of the FMT were significantly (P<0.0001) elevated in PP compared to age- and sex-matched controls and correlated to severity of the disease. We conclude that impaired colour discrimination is related to pathophysiology of Parkinson's disease. But it remains unclear whether these alterations of colour vision reflect striatal dopamine deficiency or changes of retinal dopaminergic pathways in PP.

Adult↗