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Biomedical subjects

A Richter

Publications and source records attributed to A Richter.

At least 181 records · Page 10Linked to original sources

[Effects of various antibiotic treatments of lactating cows with subclinical mastitis].

101 cows with 197 udder quarters with subclinical mastitis from 23 dairy farms were selected for different antibiotic treatments under field conditions. Group 1 consisting of 27 animals and 50 infected udder quarters was treated twice intramammaryly with 250 mg Cefacetril. Group 2 (26 animals/50 quarters) was treated twice intramuscular with 10 Mio IU Penethamathydrojodid and with 5 Mio IU respectively. Group 3 was treated twice with the combination of the intramammary and the intramuscular therapies in the above mentioned groups. Group 4 served as control. 23 animals with 36 subclinical infected udder quarters were treated twice intramuscular with 2.0 ml of sterile isotonic sodium-solution. Therapeutic success was controlled with bacteriological and cytological examinations of quarter milk probes one week, two weeks and four weeks after the end of treatments. Concerning bacteriological healing both the intramammary and the combined therapy had an even success with a 72.9% elimination rate of pathogenic bacteria whereas the intramuscular therapy led to bacteriological healing in 36.7%. In comparison cytological healing rates (< 100 x 10(3) cell counts per ml milk) with 29.8% in group 1, 32.3% in group 3 and 8.2% in group 2 were not satisfying. S. aureus was the predominating isolated bacteria. With respect to bacterial species found in the subclinically infected milk probes, elimination rates in Streptococcaceae and in Enterococcaceae was evident higher than in Staphylococcaceae. The results are discussed.

Animals↗

Analysis and sorting of T cells according to cytokine expression.

Functional distinct populations of T helper cells can be defined according to the expression of cytokines. A remarkable diversity of cytokine expression has been demonstrated in single T cells even from clonal populations and up to now no stable surface markers have been described which on the single-cell level directly correlate with the secretion of a certain cytokine. Since cytokines are the major parameters of T cell effector function we have developed strategies which now allow to separate cells according to the specific cytokines they secrete. The "affinity matrix technology"--secreted molecules are relocated to the cell surface by an artificially created antibody matrix--allows to isolate cells according to a distinct secreted product. In addition to this universal, but laborious technology, we could demonstrate by high-sensitivity immunofluorescence that IFN-gamma and IL-10 but not IL-2 and IL-4 are specifically expressed in low copy number on the surface of cells secreting these cytokines. Surface IFN-gamma and IL-10 are the first unambiguous surface markers for pro-inflammatory IFN-gamma-secreting Th 0/1 cells and IL-10-producing anti-inflammatory Th2/3 cells. We have used purified cytokine-secreting T cells to study in individual T cells the sequential production of IL-2, IFN-gamma, and IL-10, the stability of IFN-gamma expression and the selective homing of IFN-gamma-producing cells into inflamed tissues.

Animals↗

[Pancreatic carcinoma--conclusions and prospects].

Whereas no progress has been made in the diagnosis of early tumors, the staging of pancreatic cancer has improved, mainly through the introduction of ultrafast MRI, resulting in a higher resection rate. The early results of standard pancreatectomy are now excellent (operative mortality < 2.5%). The late results after R0 resections are improving (> 30% 5-year survival), but they are poor overall. So far, extended surgical techniques have not brought any improvement here. Unfortunately, so far adjuvant radiochemotherapy has not proved effective in a recent randomized controlled trial. Molecular and genetic research has deepened our understanding of the cancerogenesis of pancreatic cancer without leading to clinical consequences so far.

Aged↗

[Magnetic resonance tomography in diagnosis of vascular infiltration in malignant pancreas tumors].

This study was undertaken to evaluate the accuracy of magnetic resonance angiography (MRA) in assessing venous or arterial infiltration in pancreatic cancer. In 90 patients MRA showed a sensitivity of 81.1%, a specificity of 90.2% and an accuracy of 85.9% in predicting venous infiltration and a sensitivity of 81.8%, a specificity of 90.7% and an accuracy of 88.1% in predicting arterial infiltration. From these data we conclude that MRA is an accurate method for detecting vascular infiltration in pancreatic cancer.

Arteries↗

MK-801 potentiates antidystonic effects of clozapine but not of haloperidol in mutant dystonic hamsters.

The interaction of nigrostriatal dopamine and corticostriatal glutamate plays a critical role in motor output. Recent studies in mutant dystonic hamsters (dt[sz]), an animal model of idiopathic generalized dystonia, revealed antidystonic effects of both N-methyl-D-aspartate (NMDA) receptor antagonists, such as dizocilpine (MK-801), and of neuroleptics, such as haloperidol and clozapine. Whereas the neuroleptics reduced spontaneous locomotion at antidystonic effective doses, MK-801 caused hyperactivity in mutant hamsters. Therefore, the combination of neuroleptics and MK-801 may exhibit synergistic antidystonic effects, while the side effects may be counteracted. In order to prove this assumption, the neuroleptics haloperidol and clozapine were coadministered with MK-801 in dt(sz) hamsters in the present study. The antidystonic effects were potentiated by coadministration of MK-801 and clozapine, but not by the combination of MK-801 and haloperidol. The coadministration of MK-801 and clozapine did not cause severe side effects, such as catalepsy in dystonic hamsters. In contrast to the well-documented reverse of haloperidol-induced catalepsy by MK-801 in rats, in mutant hamsters, catalepsy was increased by coadministration of haloperidol and MK-801. This unexpected finding could be due to pathophysiological brain alterations in dt(sz) hamsters, because in non-dystonic control hamsters, combined treatment with MK-801 and haloperidol did not cause cataleptogenic effects.

Animals↗

Prodystonic effects of riluzole in an animal model of idiopathic dystonia related to decreased total power in the red nucleus?

The effects of riluzole (2-amino-6-trifluoromethoxy benzothiazole) on the severity of dystonia were examined in mutant hamsters (dtsz), an animal model of idiopathic dystonia in which dystonic attacks can be age dependently induced by mild stress. Previous studies in hamsters have shown antidystonic activity of various glutamate receptor antagonists whereas lamotrigine, considered as an inhibitor of glutamate release, exerted prodystonic effects. The latter, unexpected, finding prompted us to investigate riluzole which is thought to possess antiglutamatergic properties with mechanisms similar to those of lamotrigine. Riluzole (2, 5, 10 or 20 mg/kg i.p.) dose dependently decreased the latency to onset of dystonic attacks. A dose of 10 or 20 mg/kg significantly increased the severity of dystonia. Even in dtsz hamsters older than 70 days, i.e., after spontaneous remission of age-dependent dystonia, riluzole (10 or 20 mg/kg) provoked severe long-lasting (> 4 h) dystonic attacks. At a dose of 20 mg/kg, riluzole provoked short-lasting (< 1 h) dystonic disturbances also in non-dystonic control hamsters. Electroencephalographic recordings from depth electrodes in the red nucleus, where recent studies have shown abnormal neural activity before and during dystonic attacks in dtsz hamsters, revealed that riluzole (10 mg/kg) tended to cause a further decrease of the total power in dtsz hamsters and significantly reduced the total power in control animals. This finding may indicate that the prodystonic effects of riluzole are related to alterations of rubrospinal activity. With regard to antidystonic effects of glutamate receptor antagonists demonstrated in previous studies, the prodystonic effects of riluzole and, as shown by recent experiments, of lamotrigine also, may be due to the lack of selectivity of these drugs to inhibit glutamate release.

Animals↗

High-molecular-mass complexes of human minichromosome-maintenance proteins in mitotic cells.

Minichromosome-maintenance (Mcm) proteins perform essential functions regulating the replication of eukaryotic genomes. In interphase cells they are either bound to a nuclear structure, most probably chromatin, or occur as free multiprotein complexes in the nucleoplasm. Mcm proteins are displaced from their chromatin sites during S phase, and several become highly phosphorylated during mitosis. We investigated whether phosphorylation affects the ability of mitotic Mcm proteins to form multiprotein complexes. Our results clearly show that phosphorylated mitotic Mcm proteins form a 14-15-S complex, probably consisting of one molecule each of the six known human Mcm proteins.

Amino Acid Sequence↗

The electrical activity is impaired in the red nucleus of dt(sz) mutant hamsters with paroxysmal dystonia: an EEG power spectrum analysis of depth electrode recordings.

The genetically dystonic (dt(sz)) hamster is an animal model of paroxysmal dystonia that displays attacks of sustained abnormal movements and postures in response to mild stress. Dysfunctions within the basal ganglia may be critically involved in the pathophysiology of dystonia in mutant hamsters. Furthermore, previous observations from autoradiographic studies pointed to an altered neural activity in the red nucleus (RN). In the present study, computerized EEG spectral analysis of depth electrode recordings from the RN was performed before and after dystonic attacks in freely moving dt(sz) hamsters and compared to age-matched non-dystonic controls. No epileptic activity was seen in any of the recordings, substantiating previous notions that paroxysmal dystonia in these mutants has no epileptogenic basis. The predominant EEG changes in RN of dystonic hamsters were a decrease in total power over the range of 1.25-42.00 Hz, a decrease in maximum power and a shift of frequency at maximum power to lower frequencies. With regard to selected frequency bands, there was a decrease in the alpha, beta and gamma band. Although the observed changes of neural activity in the RN are probably based on a primary dysfunction in related structures, the present data demonstrate its importance in the expression of dystonic movements.

Animals↗

Increased levels of lipid oxidation products in low density lipoproteins of patients suffering from rheumatoid arthritis.

9-Hydroxy-10,12-octadecadienoic acid (9-HODE) and 13-hydroxy-9,11-octadecadienoic acid (13-HODE) are accumulated in the low density lipoproteins of patients suffering from rheumatoid arthritis for a factor of 20-50 compared to healthy individuals of the same age. Both acids, derived by lipid peroxidation of linoleic acid, induce the release of interleukin 1 beta. The latter induces bone degression. The genesis of 9- and 13-HODE seems therefore to be an important factor in the development and progression of rheuma; in addition 9-HODE was reported to be a stimulus of inflammation, comparable to leukotrienes.

Adult↗

Dextrorphan, but not dextromethorphan, exerts weak antidystonic effects in mutant dystonic hamsters.

The effects of dextromethorphan and its metabolite dextrorphan on severity of dystonia were examined in mutant dystonic hamsters, an animal model of idiopathic paroxysmal dystonia, in which recent examinations have shown antidystonic effects of selective N-methyl-D-aspartate (NMDA) receptor antagonists. Dextromethorphan and dextrorphan are non-competitive NMDA receptor antagonists which additionally exhibit affinity for sigma receptors. Dextrorphan (20 and 40 mg/kg i.p.) significantly retarded the progression of dystonia at the higher dose, whereas dextromethorphan (20, 40, 60 mg/kg i.p.) failed to exert any antidystonic effects even at high doses which caused severe effects. The lack of antidystonic efficacy of dextromethorphan may be related to its higher affinity to sigma receptors compared with dextrorphan.

Animals↗

Alterations in N-methyl-D-aspartate receptor binding in dystonic hamster brains.

The genetically dystonic hamster is an animal model of idiopathic dystonia that displays sustained abnormal movements and postures either spontaneously or in response to mild environmental stimuli. Previous pharmacological studies have shown that competitive and non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists exert potent antidystonic activity in this model, indicating that abnormal NMDA receptor function may be involved in the pathophysiology of this movement disorder. Autoradiographic analysis of NMDA receptor density in 67 brain regions, using the ligand [3H] N-(1-[2-thienyl]cyclohexyl)3,4-piperidine, which binds to the phencyclidine (PCP) site in the ion channel of the NMDA receptor channel complex, revealed that NMDA receptor binding is not substantially altered in dystonic hamster brains compared to age-matched controls. Nevertheless, there was a tendency towards enhanced binding during a dystonic attack in several regions, including a 25% increase in the ventrolateral thalamic nucleus (P < 0.05), which may be associated with altered basal ganglia output. While the data do not indicate widespread abnormalities in the PCP site of the NMDA complex, they do not exclude the possibility of more pronounced changes at other regulatory binding sites of the NMDA complex or other types of glutamate receptors in dystonia.

Animals↗

Phenotypic variability in Friedreich ataxia: role of the associated GAA triplet repeat expansion.

We studied genotype-phenotype correlations in a group of 100 patients with typical Friedreich ataxia (FRDA), and in three groups of patients with atypical clinical presentations, including 44 Acadian FRDA, 8 late-onset FRDA (LOFA), and 6 FRDA with retained reflexes (FARR). All patients, except 3 with typical FRDA, carried two copies of the FRDA-associated GAA triplet repeat expansion. Overall, the phenotypic spectrum of FRDA appeared to be wider than defined by the currently used diagnostic criteria. Our study indicated the existence of several sources of variability in FRDA. Patients with larger GAA expansions tended to have earlier onset and were more likely to show additional manifestations of the disease. Mitotic instability of the expanded GAA repeats may partially account for the limited degree of correlation between expansion sizes as determined in lymphocytes and clinical parameters. Some clinical variants associated with specific FRDA haplotypes, such as Acadian FRDA and FARR, turned out to be unrelated to expansion sizes. No polymorphism in the frataxin coding sequence could be associated with these clinical variants.

Adolescent↗

A new tremor mutant in the Pietrain pig: an animal model of orthostatic tremor? Clinical and neurophysiological observations.

A new tremor mutant, the "Campus syndrome" was studied in a breed of Pietrain pigs. Affected pigs showed a coarse tremor of the extremities when standing and walking, so they tended to remain recumbent, during which the tremor was suppressed. Needle electromyographic recordings of the semitendinosus muscle plus accelerometry revealed a high-amplitude 14- to 15-Hz tremor pattern activated specifically upon standing but maintained during walking. The observed syndrome thus bears similarities to the human condition of orthostatic tremor and might serve as an animal model for this as yet poorly understood disorder.

Animals↗

[In vivo imaging of corneal innervation in the human using confocal microscopy].

To date, descriptions of the structure of corneal innervation have only been possible on the basis of histological techniques. Confocal microscopy represents a new method for the structural examination of the cornea in vivo. Through our examinations we first defined the control group and then proceeded to record the reinnervation of donor tissue after perforating keratoplasty. We used the confocal slit-scanning video-microscope Microphthal to examine 40 corneas from 20 normal volunteers, 15 donor corneas and 5 eyes after enucleation for ocular tumors. These results were compared to our findings from postoperative checks on 14 patients after perforating keratoplasty (from 1 month to 2 years). With this system we were able to see nerves in the middle and in the superficial stroma. The course of these nerves can be followed, as well as their branching in the subepithelial plexus. Nerve fibers from superficial stromal nerves penetrate Bowman's membrane and create the basal epithelial plexus in the region of the basal epithelium. Seven months after perforating keratoplasty the first stromal nerves could be seen in the central corneal area. The first central reinnervation in the region of Bowman's membrane as well as in the basal epithelium was not detected until 15 months after operation. With confocal microscopy we have the potential to study the morphology of corneal innervation in vivo and in fresh donor tissue. For the first time it is possible to perform non-invasive morphological studies of reinnervation of the human cornea after surgical treatment.

Adolescent↗

[Detection of morphological corneal changes caused by chloroquine therapy using confocal in vivo microscopy].

BACKGROUND: Chloroquine keratopathy is known as a disease with epithelial deposits in the cornea. The appearance of corneal changes does not seem to be related to dose and duration of treatment. Chloroquine accumulates in lysosomes. The purpose of this study was to investigate microscopic changes of corneal morphology in patients treated with chloroquine in vivo. PATIENTS AND METHODS: Using the confocal slit scanning microscope, we examined 16 patients during chloroquine treatment and 4 patients after treatment. The patients' age was between 33 and 75 years. They were treated with chloroquine over a minimum period of 2 months up to a maximum period of 10 years. RESULTS: In 12 of 20 patients, corneal changes were visible. An atypical inverse reflectivity of basal cells in comparison to healthy volunteers was found. There were also deposits in the wing cell layer. We saw a higher density in the anterior stroma before the appearance of epithelial opacities, as well as in cases of keratopathy on slit-lamp examination and also after the cessation of chloroquine treatment. In one patient with long-term therapy, there were atypically shaped and branched nerves in the anterior stroma. CONCLUSIONS: Using confocal microscopy, it was in some cases possible to detect changes in the corneal morphology before these changes could be detected by slit-lamp examination. As a result of this study we found that chloroquine keratopathy is not limited to the epithelium but can affect the anterior stroma and possibly neural structures.

Adult↗

[Improving anal continence by selective stimulation of the external anal sphincter muscle].

Using the pig as a model, it was shown that stimulation of the distal nerve ending of the pudendal nerve leads to the isolated stimulation of the external anal sphincter muscle. No difference in pressure response was noted after application of between 0.5 and 1.5 mA unilateral or bilateral stimulation. Major advantages observed using between 1.5 and 2.5 mA bilateral stimulation; with a stimulation between 2.0 and 2.5 mA the pressure response was twice as high compared to unilateral stimulation. Continuous stimulation of the striated anal sphincter muscle leads to fatigue, reaching 50% fatigue after a median time between 40-90 s. In cyclic stimulation (alternation every 15 s, duration 20 min) a fatigue reaction was also seen. The peak pressure decreased after 20 min for a median of 11%, the final pressure was lowered in 15% following a logarithmic curve pattern. The experimental application of variable impulse ranges also caused pressure differences. Increasing the impulse range from 200 to 450 microseconds (peak pressure) vs. 400 microseconds (final pressure) resulted in a statistically significant pressure increase. Therefore, it was proven that selective stimulation of the external anal sphincter muscle can lead to a transient pressure increase, which possibly improves fecal continence.

Anal Canal↗

[Procalcitonin. A new marker for acute phase reaction in acute pancreatitis].

Procalcitonin is a protein which is found in elevated concentrations in the blood circulation during systemic bacterial, fungal or protozoal infection. In contrast to classical acute-phase proteins like C-reactive protein or interleukin-6, it is not elevated after operative trauma. In this paper we present current opinions on the assumed induction mechanisms of the protein by cytokines and endotoxin. Furthermore, the clinical value for early detection of systemic infections in abdominal and transplantation surgery is demonstrated by examples from the literature. Our investigation shows that eight patients with necrotizing pancreatitis had a PCT mean value of 6.9 ng/ml on the day of admission. Seven patients with edematous pancreatitis had only a PCT mean value of 0.69 ng/ml. Despite these differences in the mean values, a significant difference between the normal value and the mean value of the group with necrotizing pancreatitis or edematous pancreatitis was not observed due to the wide range of PCT levels in the group of patients with necrotizing pancreatitis. The fact that only a few of the patients had a superinfected necrosis with systemic evasion of bacterias or their toxins may be the reason for this wide range. We suggest that a discrimination between superinfected necrotizing or sterile pancreatitis and edematous pancreatitis by PCT could be possible but more extensive studies with microbiological examination of the necrotic material are required to recognize the subgroups and to establish the real diagnostic efficiency of PCT in clinical practice, especially in the prediction of the outcome of acute pancreatitis.

Acute-Phase Reaction↗

The Friedreich ataxia GAA triplet repeat: premutation and normal alleles.

The most common mutation causing Friedreich ataxia (FRDA), an autosomal recessive neurodegenerative disease, is the hyperexpansion of a polymorphic GAA triplet repeat localized within an Alu sequence (GAA-Alu) in the first intron of the frataxin (X25) gene. GAA-Alu belongs to the AluSx subfamily and contains several polymorphisms in strong linkage disequilibrium either with a subgroup of normal alleles, or with hyperexpanded FRDA-associated alleles. GAA repeat sizes in 300 normal chromosomes (97 from carriers and 203 from controls) were distributed in two separate groups: 83% of them contained between six and 10 triplets (small normal alleles), while the remaining 17% had more than 12 triplets, up to 36 (large normal alleles). Sequence analysis showed that no normal, stable allele contained more than 27 uninterrupted GAA triplets. All longer normal alleles were interrupted by a hexanucleotide repeat (GAGGAA). An allele containing an uninterrupted run of 34 GAA triplets was stably transmitted in four instances, but in one case underwent hyperexpansion to 650 triplets. Overall, our results suggest that the FRDA-associated expanded GAA repeats originate from normal alleles by recurrent expansions of alleles at risk.

Alleles↗