[Bilateral corneal ulcers with hypopyon in a patient with lethal outcome].
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Biomedical subjects
Publications and source records attributed to F Merkel.
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Management of critically ill patients regularly involves the treatment of water and electrolyte disturbances. Moreover, critical care itself may contribute to volume overload and electrolyte abnormalities. Initial therapy should be followed by consequent diagnostic evaluation. The shift of volume and potassium in severe pancreatitis, for example, may lead to a life-threatening situation. In brain-dead patients, successful organ donation is facilitated by careful maintenance of water and electrolyte homeostasis.
Functionally relevant damage caused by chronic systemic inflammatory disorders of autoimmune and/or unknown origin can be reduced or sometimes avoided by early initiation of treatment. This requires a correct diagnosis which makes treatment as early as possible. Due to the often uncharacteristic symptoms at the onset of disease, early diagnosis in systemic inflammatory disorders represents a diagnostic challenge. This review outlines current standards and limitations in the early diagnosis of rheumatoid arthritis, collagen vascular diseases and primary systemic vasculitides. Recent advances especially in serology and imaging techniques have improved early diagnosis of systemic inflammatory disorders.
The preparation for colonoscopy is essential for the results of the examination. The effectiveness of 3 commercially available Golytely solutions for colonoscopy (Original-Golytely-salt, Oralav and Delcoprep) were compared in a randomized prospective study. 310 outpatients were randomized into 3 groups. One of the above-mentioned solutions were used in these patients. Before the examination the patients were asked to drink 3 l of the given solution within 2 h. The colonoscopy was realized within 3-5 h after the end of preparation. Outcome criteria were the subjective acceptability of the solution for the patient, cleanness of the bowel and the formation of foam. In all 3 groups sufficient up to very good results could be achieved. There were no significant differences in the 3 groups. We conclude that the used procedure is absolutely sufficient to prepare for colonoscopy and that administration of liquids of more than 3 l or the use of enema or laxans on the previous day, are unnecessary. The suggested procedure can be used for children, too.
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Systemic lupus erythematosus is a chronic disease with many clinical features, while Goodpasture's syndrome usually becomes manifest with progressive glomerulonephritis and pulmonary hemorrhage. Rapidly declining renal function and even pulmonary hemorrhage may be the common feature. Early and precise diagnosis is most important as it may provide general prognostic information and serve as a guideline for initial therapy. Immunosuppression with oral cyclophosphamide and high dose corticosteroids together with plasmapheresis is used in Goodpasture's syndrome. Progressive lupus nephritis requires high dose corticosteroids together with i.v. pulses of cyclophosphamide for at least six months, followed by maintenance immunosuppression. The benefits of therapy must always be weighed against the risks. Nevertheless, current therapy remains less than optimal. A better understanding of the pathogenesis of systemic lupus erythrematosis (SLE) and Goodpasture's syndrome may provide more specific information about the nature and the role of the immune response and thus lead to new treatment strategies.
Goodpasture's syndrome is mediated by immunopathogenic autoantibodies to the alpha 3 NC1 domain of type IV collagen. It is not known whether collaborating T-cells participate in this autoreactive response. Here we describe the first T-cell clone isolated from a Goodpasture patient autoreactive to alpha 3 type IV collagen of glomerular basement membrane. To investigate cellular autoreactivity, T-cells from Goodpasture patients or controls were isolated and stimulated by purified native or recombinant type IV collagen proteins and synthetic oligopeptides. Cell surface markers, the T-cell receptor repertoire, and MHC-restriction were analyzed. T-cell clones specific for the alpha 3 (IV) NC1 domain were established in two Goodpasture patients, but not in controls. One of the three CD8+ T-cell clones was characterized further. It was MHC class I restricted (HLA-A11) and expressed the T-cell receptor V beta 5.1. chain. This clone specifically recognized a motif at the N-terminal area of the alpha 3 (IV) NC1 domain (AA 51 to 59: GSPATWTTR). We conclude that autoreactive T-cells exists in Goodpasture patients and may play a crucial role in the inflammatory process. T-cell clones are autoreactive to the alpha 3 (IV) NC1 domain. At least for one of the clones, the T-cell epitope is different from the putative antibody-binding site.
The mechanisms of glomerular injury are multiple: one aspect is cell-mediated immunity in inflammatory kidney disease. Its fundamental role has been established within the last decade. T cells seem to play a regulatory role in the course of inflammation not only in the proliferative and crescentic disease, but also in nonproliferative glomerulonephritis. T cells become increasingly important in the pathogenesis of both glomerular and interstitial kidney diseases and seem to determine course and prognosis. The recent advances in understanding the mechanisms of T cell-mediated inflammation in kidney disease offer new approaches in therapy.
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Anti-basement membrane antibody (anti-BM Ab) mediated disease is reported to be a rare disorder frequently leading to severe deterioration of renal function. It was our purpose to work out parameters necessary to predict the outcome reliably and to examine, who will benefit most from therapy. Data from 35 patients were evaluated retrospectively. Diagnosis was based on the detection of linear IgG staining (n = 28) along the glomerular basement membrane (GBM) in renal biopsies and/or on the demonstration of anti-BM Ab both by ELISA and immunoblotting (n = 35). Patients were followed up for at least 6 months. Several variables were analysed as to whether they are appropriate prognostic factors. Twenty patients (57%) presented with Goodpasture's syndrome, 13 (37%) had anti-GBM glomerulonephritis alone, whereas two patients suffered solely from pulmonary haemosiderosis. Frequent initial symptoms were haemoptysis (n = 18), haematuria (n = 26), proteinuria (n = 26) and elevated serum creatinine (n = 27). Among all, 10 patients improved, having stable renal function. Twenty-one patients developed end-stage renal failure and four died. Parameters indicating a poor prognosis were a serum(s)-creatinine greater than 600 mumol/l and crescent formation in more than 50% of the glomeruli on renal biopsy. By combining these two parameters the outcome could be reliably predicted. The initial antibody titre and cigarette smoking were without predictive value. In conclusion, the earlier therapy starts, the better will be the result. Patients presenting early with a serum creatinine < 200 mumol/l and without severe glomerular alterations gained the most benefit from therapy, indicating that outcome may be improved by early diagnosis.
We examined whether expectancy, one of several factors influencing attention, is similarly affected in rats and humans by manipulation of relative stimulus frequency. A two-choice reaction time (RT) task was developed for rats, and an analogous task was used for humans. Errors, RTs, discriminability, and response bias were measured. Both rats and humans shifted their response bias to the more frequent stimulus, with no change in overall discriminability. As stimulus probability or stimulus repetition increased, RTs and errors decreased. These results illustrate the similarity of expectancy in rats and humans. This two-choice RT task for rats can be used in future studies to examine the neuronal mechanisms of expectancy and attention.
The purpose of this study was to investigate possible additive effects of calcium antagonists on the cyclosporin A (CsA)-induced inhibition of cellular immunity. Human T-cells were isolated using standard methods and stimulated with phytohaemagglutinin (PHA, n = 8), the monoclonal antibody OKT3 (n = 6), or mixed lymphocyte reaction (MLR, n = 5). Verapamil, nifedipine, nimodipine or diltiazem were added (5 x 10(-7) - 5 x 10(-5) M) to the cultures, either alone, or in combination with CsA (62.5, 125, and 250 ng/ml). 3H-thymidine uptake was measured to estimate the proliferative responses and dose response curves were constructed for the Ca antagonists and their combinations with CsA. A 50% inhibition of T-cell proliferation in the different stimulation assays was achieved with 3.2 x 10(-5) - 5.3 x 10(-5) M verapamil, 2.5 x 10(-5) -4.3 x 10(-5) M nifedipine, 3.7 x 10(-6) - 5 x 10(-6) M nimodipine, and greater than 5 x 10(-5) M diltiazem. In combination with CsA a dose-dependent additive inhibitory effect of the Ca antagonists on T-cell proliferation was observed. This effect was less pronounced in the OKT3 assay, intermediate after PHA stimulation and most pronounced in MLR. Even in low concentrations, which correspond to therapeutic serum concentrations, Ca antagonists have an additive inhibitory effect in MLR. We conclude that Ca antagonists exert a dose-dependent inhibitory effect on T-cell proliferation. A combination of CsA with verapamil, nifedipine, nimodipine, or diltiazem is more effective than each drug given alone. This additive effect of Ca antagonists and CsA may possibly contribute to a better graft survival in clinical transplantation.
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