[Anatomy and physiology of the auditory tube. Therapeutic possibilities in chronic disorders of tubal function].
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Chronic Disease↗
Biomedical subjects
U Koch
Publications and source records attributed to U Koch.
HLA-DR/DQ interaction in patients with erosive rheumatoid arthritis presenting articular and extraarticular disease manifestations.
In the present study we have analysed the effect of HLA-DRB1 and -DQB1 alleles on disease progression and genetic predisposition among 201 RA patients. We clearly confirm the association of RA with HLA class II alleles sharing the (Q)R/KRAA amino acid (AA) cassette in the third hypervariable region (HVR3) of the DR beta-chain. The HVR3 (Q)R/KRAA motif was significantly overrepresented among RA patients (79% vs. 40%, P < 0.001), with one third of the patients homozygous (28% vs. 6.7%, P < 10(-9)) and the number of rheumatoid factor positive (RF+) patients was significantly increased among HVR3 (Q)R/KRAA homozygous in comparison to HVR3 (Q)R/KRAA negative individuals. Erosive disease defined by the Larsen Score and personal disability determined using the Health Assessment Questionnaire (HAQ) was significantly increased among patients positive for the HVR3 motif with the worst outcome among HVR3 (Q)R/KRAA homozygous patients. In contrast, there was no association of the shared HVR3 AA cassette and disease severity in the majority of patients presenting systemic (extraarticular) disease. Homozygosity for the shared HVR3 motif was only marginally increased among patients presenting 'severe' extraarticular disease in comparison to patients with articular disease (33% vs. 43%, P = ns). Similarly, patients with nodular disease were not more often homozygous for the HVR3 (Q)R/KRAA motif. Furthermore, we observed no HLA-DR independent association of DQB1 alleles among HVR3 (Q)R/KRAA positive patients and controls. Our analysis supports the predominant role of HLA-DR for genetic susceptibility to RA. In the clinical setting, however, HLA-DR typing may be limited to assess the individual risk of patients for disease progression.
Adult↗
Association of (Q)R/KRAA positive HLA-DRB1 alleles with disease progression in early active and severe rheumatoid arthritis.
OBJECTIVE: We have shown that HLA-DRB1 alleles influence inflammatory activity in patients with early active and severe rheumatoid arthritis (RA). Therefore, we analyzed the effect of HLA-DRB1 alleles on disease progression in patients with early RA during a clinical followup period of 18 months. METHODS: Disease progression was defined by the Larsen Score, the Ritchie Index (RI), and the Health Assessment Questionnaire (HAQ) score. RESULTS: Patients carrying arthritogenic HLA-DRB1 alleles on one or both haplotypes are characterized by increased radiological joint destruction (Larsen Score). Further, (Q)R/KRAA homozygous patients were characterized by worse overall disease course (higher RI and HAQ). However, analysis of changes in joint effects (delta-RI) and personal disability (delta-HAQ) did not reveal significant differences between patients with or without disease associated HLA-DRB1 alleles. CONCLUSION: The predisposing genetic pattern with disease associated HLA-DRB1 alleles did not profoundly influence the therapeutic outcome. Our data support the role of the HLA-DRB1 gene locus in disease modulation of RA. The genetic predisposition due to HLA-DRB1, however, may have only a limited influence on the therapeutic outcome in clinically severe cases of RA.
Adult↗
[How great is the need for ambulatory rehabilitation in the orthopedics field?--Results of a multi-perspective approach].
Despite the necessity to expand the outpatient rehabilitation system in Germany the development up to now must be described as quite reluctant. As yet there is a considerable lack of information about the demand for such care in Germany. On the basis of a complex study design insurants, applicants for medical rehabilitation, physicians in a rehabilitation hospital and general practitioners were asked how they estimated the demand for outpatient orthopedic rehabilitation care. Resulting data unanimously show a substantial demand in roughly one third of insurants who desire rehabilitation, clearly exceeding the already realized outpatient care. The investigation also illustrated that physicians often are uncertain as to their decisions and that depending on the respective point of view (insurants or different groups of physicians) there are different preferences as to the kind of rehabilitative care for the benefit of one specific patient. The results stress not only the fact that there is a demand for information of insurants and their referring physicians regarding the new outpatient rehabilitation offer, but also reveal the demand for a development of differential indication criteria for outpatient and inpatient rehabilitation, as well as for definite procedural regulations which should be harmonized among all insurers.
Adult↗
[Differential indications for ambulatory and inpatient medical rehabilitation--results of an expert survey].
Medical rehabilitation in the Federal Republic of Germany has been provided in an almost exclusively inpatient setting up to now. However, in view of an intensified development of outpatient rehabilitation programs there are new challenges to confront. As to indication criteria, new preconditions and handling directives have to be defined in order to refer patients to those rehabilitation programs from which they can profit the most. Up to now, there has been a considerable lack of knowledge as to what kind of criteria must be considered in the transfer process. The present study represents results of expert interviews (Delphi method) regarding this topic. 50 experts from inpatient and outpatient rehabilitation facilities, from the Medical Services of health insurance funds and the pension insurance system, from rehabilitation agencies as well as rehabilitation research, have been questioned since they take important stands on these questions and since their assessment has a guiding quality. An additional study had been directed at the factors which determine present decision-making in terms of inpatient vs. outpatient rehabilitation. The results show that the experts stress the importance of a multitude of different aspects; however, there still is but little consensus concerning the criteria that should invariably be considered in making these rehabilitation decisions.
Adult↗
[Need for rehabilitation and utilization].
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Germany↗
[Treatment dropout as failed utilization--development of a predictive model for inpatient psychosomatic rehabilitation].
Premature discontinuance of rehabilitative measures can be considered a revised decision by the patient concerning participation or a revised decision by the clinic concerning admittance. Such termination of therapy suggests that the individual need for rehabilitation (defined as the fit between the patient's need for rehabilitation and the treatment offered by the rehabilitation facility) is not (or no longer) present, at least at this point in time. Assuming that the individual need for rehabilitation actually existed when treatment was requested or approval for rehabilitative measures was granted, the question arises as to when and how the need changed in such a way that would prevent the treatment from continuing as planned and being concluded in a regular fashion. This question will be taken into focus in the present article by developing a model for the prediction and explanation of prematurely discontinued treatment. This model will give central significance to the intention to co-operate, which is considered a dependent variable by reference to individual symptoms and treatment related expectations. Furthermore, various factors of influence during the stay in the clinic are formulated, which, firstly, have a presumed effect on the intention to cooperate and, secondly, have an influence on whether the intention to prematurely terminate treatment develops from a specific intention to cooperate and whether this is then realized. The model is discussed with regard to its practicability and possibilities for operationalization.
Germany↗
A synthetic CD4-CDR3 peptide analog enhances skin allograft survival across a MHC class II barrier.
The efficacy of a synthetic peptide analogue (rD-mPGPtide), mimicking the CDR3 region in the first domain of the CD4 surface molecule, was investigated in a murine model for CD4+ T cell-mediated skin allograft rejection. A single injection of rD-mPGPtide shortly before transplantation exhibited significantly prolonged graft survival in the B6 anti-B6.C-H2bm12 MHC class II-disparate strain combination. Long-term graft survival (>100 days) was achieved when thymectomized adult recipient mice were transplanted along with rD-mPGPtide treatment. The peptide also affected secondary rechallenge responses with MHC class II allografts. In addition, the inhibitory effect of the rD-mPGPtide in this transplantation model was directed against CD4+ T cells and was exclusively specific toward donor alloantigen. In vitro analysis of CD4+ T cells isolated from the draining lymph nodes of rD-mPGPtide-treated recipients indicated a 450-fold decrease in precursor frequency in response to donor allostimulation compared with the untreated control group. There was also significant down-regulation of the frequency of IL-2-, IFN-gamma-, and IL-4-producing CD4+ T cells upon in vitro allogeneic restimulation of host cells 4 days posttransplantation. However, these same CD4+ T cells maintained the capacity to produce normal cytokine levels upon third-party allostimulation. Thus, these studies demonstrate that a CD4-CDR3 peptide analogue can specifically and effectively prolong skin graft survival across MHC class II barriers.
Animals↗
Product inhibition of the hepatitis C virus NS3 protease.
The nonstructural protein NS3 of the hepatitis C virus (HCV) harbors a serine protease domain that is responsible for most of the processing events of the nonstructural region of the polyprotein. Its inhibition is presently regarded as a promising strategy for coping with the disease caused by HCV. In this work, we show that the NS3 protease undergoes inhibition by the N-terminal cleavage products of substrate peptides corresponding to the NS4A-NS4B, NS4B-NS5A, and NS5A-NS5B cleavage sites, whereas no inhibition is observed with a cleavage product of the intramolecular NS3-NS4A junction. The Ki values of the hexamer inhibitory products [Ki(NS4A) = 0.6 microM, Ki(NS5A) = 1.4 microM, and Ki(NS4B) = 180 microM] are lower than the Km values of the respective substrate peptides [Km(NS4A-NS4B) = 10 microM, Km(NS5A-NS5B) = 3.8 microM, and Km(NS4B-NS5A) > 1000 microM]. Mutagenesis experiments have identified Lys136 as an important determinant for product binding. The phenomenon of product inhibition can be exploited to optimize peptide inhibitors of NS3 protease activity that may be useful in drug development.
Amino Acid Sequence↗
Afferent regulation of glycine receptor distribution in the gerbil LSO.
Synaptic activity plays an important role in many aspects ofneuronal development, particularly the expression of proteins. In this study, the influence of inhibitory and excitatory afferents on the development of glycine receptor density in the lateral superior olive (LSO) of Mongolian gerbils was investigated. Afferent activity was manipulated by removing one or both cochleas at postnatal day 7, prior to the onset of sound-evoked responses. Due to the anatomy of the LSO, these manipulations result in either excitatory denervation, inhibitory denervation, or both. The density of glycine receptors in the LSO was determined at 21 days postnatal. Glycine receptors were either labeled with tritiated strychnine (3H-SN) or with an antibody directed against gephyrin, a protein closely associated with the receptor complex. Antibody binding was used to quantify the differential glycine receptor density between the medial limb (high frequency area) and the lateral limb (low frequency area) of the LSO. 3H-SN was used to quantify the amount of glycine receptors in each part of the LSO in control and experimental animals. In addition, changes in neuron density and neuron cross-sectional area were quantified following cochlear ablations. In control animals, the amount of glycine receptors is about 2- to 3-fold higher in the high-frequency than in the low-frequency region. In bilaterally ablated animals, the same density of glycine receptors was measured in the high- and low-frequency region. Unilateral ablations had no significant effect on glycine receptor distribution, either ipsi- or contralateral to the ablation. The neuron cross-sectional area decreased about 30% in the ipsilateral LSO of unilaterally ablated animals and in bilaterally ablated animals. However, alterations of soma density and cross-sectional area were similar in the high- and low-frequency projection region. These results suggest that the distribution of glycine receptors is only changed when excitatory and inhibitory afferents have been denervated.
Afferent Pathways↗
Chronic gastrointestinal symptoms in hemodialysis patients.
INTRODUCTION: Gastrointestinal disorders occur frequently in dialysis patients. Few data are available on the prevalence of symptoms originating from the gastrointestinal tract in this group of patients. Our aim was to obtain data on the prevalence of chronic gastrointestinal symptoms in patients undergoing hemodialysis. METHODS: All 109 patients of our dialysis unit were given a questionnaire to complete which was previously validated and designed to measure the occurrence of gastrointestinal, and some general symptoms during the preceding year. 105 subjects responded (96% response rate). RESULTS: 79% of dialysis patients had at least one of the following chronic gastrointestinal symptoms: Esophageal symptoms were reported in 21% abdominal pain in 28% and dyspeptic symptoms in 48%. The irritable bowel syndrome was diagnosed in 12 patients (11%), 40% had chronic constipation and 24% had chronic diarrhoea. Colonic pain was described in 20% of patients. Frequent general symptoms (such as weakness, headaches, insomnia and fatigue) were described in up to 51%, and patients were severely bothered by symptoms in up to 33% of cases. CONCLUSION: Although patients on hemodialysis generally report a good quality of life, the prevalence of gastrointestinal symptoms and of general symptoms is high and many dialysis patients consider these symptoms to cause major impairment of daily life.
Adult↗
[Rehabilitation of the chronically ill and handicapped. Survey and perspectives].
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Chronic Disease↗
The quality of life in end stage renal disease care.
The improved prognosis and survival statistics of both renal transplantation and dialysis have focused attention on the quality of life offered by these treatments. Using a standardized questionnaire, we assessed the quality of life of 612 patients undergoing renal replacement therapy at our center. Of these patients, 359 had been transplanted and 253 patients were on dialysis. Concerning the sociodemographic data, only the time on specific treatment was longer in dialysis patients than in transplanted patients (49.2 versus 55.6 months, P < 0.05). Most complaints were more common in dialysis patients than in transplanted patients. Only the side effects of medication were seen more in transplanted patients (P < 0.005). Life satisfaction was higher in transplanted patients than in dialysis patients. Dialysis patients were more anxious (P < 0.05) and more depressed (P < 0.001) than transplanted patients. Transplanted patients also felt that they had more social support than did dialysis patients. Overall life quality was almost equal between patients on hemodialysis and patients on peritoneal dialysis, and between patients on the waiting list for transplantation and those not on the waiting list. Despite a significantly better quality of life after renal transplantation, the percentage of patients working remained unchanged. (57.5% versus 57.8%, P = n.s.). We conclude that despite an improved quality of life after renal transplantation, these patients are economically not more productive than patients on dialysis.
Female↗
GABAergic and glycinergic inhibition sharpens tuning for frequency modulations in the inferior colliculus of the big brown bat.
Discrimination of amplitude and frequency modulated sounds is an important task of auditory processing. Experiments have shown that tuning of neurons to sinusoidally frequency- and amplitude-modulated (SFM and SAM, respectively) sounds becomes successively narrower going from lower to higher auditory brain stem nuclei. In the inferior colliculus (IC), many neurons are sharply tuned to the modulation frequency of SFM sounds. The purpose of this study was to determine whether GABAergic or glycinergic inhibition is involved in shaping the tuning for the modulation frequency of SFM sounds in IC neurons of the big brown bat (Eptesicus fuscus). We recorded the response of 56 single units in the central nucleus of the IC to SFM stimuli before and during the application of the gamma-aminobutyric acid-A (GABAA) receptor antagonist bicuculline or the glycine receptor antagonist strychnine. To evaluate tuning to the modulation frequency, the normalized spike count (normalized according to the maximal response for each condition tested) was plotted versus the modulation frequency and the upper and lower 50% cutoff points were determined. Bicuculline increased the upper cutoff in 46% of the neurons by >/=25%. The lower cutoff decreased in 48% of the neurons tested. In some neurons (approximately 30%), a sharpening of the tuning by bicuculline was observed. Strychnine induced an increase of the upper cutoff in almost half of the neurons. Compared with bicuculline these changes were smaller. The lower cutoff decreased in 50% of the neurons with strychnine. The synchronization coefficient (SC) was calculated and compared for three modulation frequencies (50, 100, and 200 Hz) between predrug and drug condition. For all neurons, synchronization decreased (n = 36) or did not change (n = 26) during drug application. This was mainly an effect of the prolonged discharge in response to each cycle. Under predrug conditions, many neurons exhibited selectivity to the direction of the FM, hence they only responded once to each cycle. In a minority of neurons, direction selectivity was abolished by drug application. The main finding was that neuronal inhibition sharpens tuning to the modulation frequency in the majority of neurons. In general, changes induced by bicuculline or strychnine were comparable.
Acoustic Stimulation↗
[Current status and progress in scientific rehabilitation research].
When compared to the entire field of health research, to the significance and role of rehabilitation in the health care system, to future developments in demand and to international developments, the field of rehabilitation in Germany has formerly suffered from a considerable deficit in research regarding both structure and content. The German Federal Ministry of Research and the German Statutory Pension Insurance have now established a common focus in research. This decision reflects not only a new political attitude toward the promotion of research but also represents the initiation of attempts to overcome existing research deficits permanently by means of an extensive programme for the promotion of research. In addition to the construction of a scientific infrastructure, the funders most importantly expect results that will contribute to the further optimisation of effectiveness and efficiency in rehabilitation services. An improved scientific foundation of rehabilitative practice will also assist the field of rehabilitation in finding greater socio-political recognition as an interdisciplinary field. In order to achieve the demanding goals of this promotion of research, the promoters will accompany the programme with efficient scientific management and quality assurance. The statutory pension insurance institutes will systematically analyse the expected research results and offer recommendations and suggestions for realisation in dialogue with scientific experts and specialist practitioners.
Forecasting↗
[Strategies for classification of rehabilitation clinics based on structural equality].
Comparison between clinics is a basic part of most quality assurance programmes. The classification of structurally similar clinics is a prerequisite for enabling comparisons between clinics according to quality criteria. As a part of the programme point 1 "structural quality" of the Pension insurance quality assurance programme in medical rehabilitation, a procedure was developed to classify clinics into structurally similar groups. For this purpose the data of the structure survey of the quality assurance programme was used. The first step was to check whether existing classification systems could be used, which made the need for a new classification procedure apparent. The 942 participating clinics were clustered according to a successive differentiation system employing only quality-neutral criteria, e.g., the indication group, the number of different indications, the part of AHB, number of beds, and the therapeutic focus. Further differentiation beyond indication group was necessary for the indications orthopaedics, cardiology, psychosomatics, addiction and neurology. The procedure is demonstrated using the indications orthopaedics and cardiology as examples.
Germany↗
[Concept definition in medical rehabilitation: an instrument for quality assurance].
A survey of organizational aspects of rehabilitation clinics was part of the Pension Insurance quality assurance programme in medical rehabilitation. The goal of this survey was to strengthen the awareness for these organizational dimensions and to initiate discussion with the goal of optimizing the efficiency of the clinical working process. For the structured description of various conceptual aspects a questionnaire "Dokumentationsbogen-Konzepte" was developed and its appropriateness for the indication groups orthopaedics, cardiology and psychosomatics was examined. The focus of this examination was development of different possibilities to give feedback to the clinics. The questionnaire was appropriate for the description of conceptual aspects. Differences both between and within the indication groups were discovered. The instrument can be used in the quality assurance process.
Documentation↗
Bioactive peptide design based on protein surface epitopes. A cyclic heptapeptide mimics CD4 domain 1 CC' loop and inhibits CD4 biological function.
The interaction between CD4 and major histocompatibility complex class II proteins provides a critical co-receptor function for the activation of CD4(+) T cells implicated in the pathogenesis of a number of autoimmune diseases and transplantation responses. A small synthetic cyclic heptapeptide was designed and shown by high resolution NMR spectroscopy to closely mimic the CD4 domain 1 CC' surface loop. This peptide effectively blocked stable CD4-major histocompatibility complex class II interaction, possessed significant immunosuppressive activity in vitro and in vivo, and strongly resisted proteolytic degradation. These results demonstrate the therapeutic potential of this peptide as a novel immunosuppressive agent and suggest a general strategy of drug design by using small conformationally constrained peptide mimics of protein surface epitopes to inhibit protein interactions and biological functions.
Amino Acid Sequence↗