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S. BISCHOFF, G. KAHALY, S. MOHR-KAHALY, J. BEYER, and K. v. OLSHAUSEN

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S. MOHR-KAHALY, G. KAHALY, U. KRAUSE, R. ERBEL, and J. BEYER

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G Kahaly, C Stover, J Beyer, and E Otto

The effects of humoral and cell-mediated immunity on the glycosaminoglycan synthesis of retrobulbar fibroblasts was evaluated in patients with endocrine ophthalmopathy. After incubation with IgG and sera, secreted glycosaminoglycans, radiolabeled with D-6-3H-glucosamine and 35sulfate, were precipitated with cetylpyridinium chloride and ethanol. Hyaluronic acid synthesis of human retrobulbar fibroblasts after incubation with sera and IgG and after co-culture with lymphocytes was assessed by means of a radiometric test. Patients' IgG, compared to controls', accounted for a higher secretory stimulation of porcine retrobulbar fibroblasts (as measured by cetylpyridinium chloride precipitation) after 24 and 48 h. Contrasting with 24 h incubation time, glycosaminoglycan values after 48 h were increased two to threefold. Patients' and controls' sera caused earlier and stronger, yet indistinguishable glycosaminoglycan production. Non-sulfated hyaluronic acid was the preponderant glycosaminoglycan secreted into the media by retrobulbar fibroblasts. As assessed with the radiometric test, incubation with patients' and controls' sera and IgG did not reveal a significant difference in stimulating the hyaluronic synthesis of patients' and controls' retrobulbar fibroblasts. When measuring the hyaluronic acid synthesis of controls' and patients' retrobulbar fibroblasts after co-cultivation of lymphocytes, however, patients' lymphocytes had a marked ability to increase the hyaluronic acid concentration compared to controls' lymphocytes. The hyaluronic acid concentration after incubation of a patient's retrobulbar fibroblasts with autologous lymphocytes was markedly more elevated than the intrinsic hyaluronic acid production of retrobulbar fibroblasts. In conclusion, though a significant in vitro influence of patients' IgG and sera on the glycosaminoglycan release of both porcine and human (patients' as well as controls') retrobulbar fibroblasts could not be observed in this study, the indications of a marked stimulatory influence of lymphocytes on the hyaluronic acid secretion of retrobulbar fibroblasts demand further investigation.

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C Stover, E Otto, J Beyer, and G Kahaly

The exact role of retrobulbar fibroblasts in the immunopathogenesis of endocrine ophthalmopathy still remains to be elucidated. To evaluate the in vitro influence of humoral immunity on retrobulbar fibroblasts, the effects of immunoglobulin G as well as of the sera of 50 euthyroid patients with endocrine ophthalmopathy and 30 controls on both porcine and human (patients' and controls') retrobulbar fibroblasts were measured by means of several assays: a colorimetric test involving a heterocyclic chemical, a tetrazolium bromide, was applied to quantify the activity of mitochondrial dehydrogenases; the incorporation of 3H-thymidine was determined as a sensitive parameter for cell proliferation, and an enzyme-linked immunosorbent assay was to reveal specific binding of antibodies to the cells. There was consistently no significant difference between patients' (untreated or treated) and controls' IgG to bind to, to activate or to stimulate the proliferation of porcine and human (patients and controls) retrobulbar fibroblasts. The effects of patients' heat-inactivated and non-inactivated sera were indistinguishable from those of the controls. Incubation of autologous sera, however, led to an activation of retrobulbar fibroblasts which was both higher than the median caused by the patients' group and that engendered by incubation of autologous IgG. Yet, a significant role that humoral immunity might play directly on retrobulbar fibroblasts could not be detected in the experiments conducted in this study.

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G. KAHALY, R. MONCAYO, U. BEMETZ, U. KRAUSE, and J. BEYER

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G. KAHALY, H. BÖCKMANN, U. CORDES, and J. BEYER

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GJ Kahaly, HP Dienes, J Beyer, and G Hommel

OBJECTIVE: Iodine is essential for normal thyroid function and the majority of individuals tolerate a wide range of dietary levels. However, a subset of individuals, on exposure to iodine, develop thyroid dysfunction. In this double-blind trial, we evaluated the efficacy and tolerability of low-dose iodine compared with those of levo-thyroxine (T4) in patients with endemic goitre. METHODS: Sixty-two patients were assigned randomly to groups to receive iodine (0.5 mg/day) or T4 (0.125 mg/day) for 6 months. Subsequently, both groups were subject to placebo for another 6 months. Thyroid sonography, determination of thyroid-related hormones and antibodies, and urinary excretion of iodine were carried out at baseline and at 1, 6 and 12 months. RESULTS: At 6 months, markedly increased urinary values of iodine were found in patients receiving iodine (36 microg/24 h at baseline, 415 microg/24 h at 6 months) compared with those receiving T4 (47 microg/ 24 h at baseline, 165 microg/24 h at 6 months; P < 0.0001 compared with iodine group). T4 administration engendered a greater (P < 0.01) decrease in thyroid volume (from 32 ml to 17 ml, P < 0.0001) than did intake of iodine (3 3 ml to 21 ml. P < 0.005). High microsomal and thyroglobulin autoantibody titres were present in six of 31 patients (19%) receiving iodine, and iodine-induced hypo- and hyperthyroidism developed in four and two of them, respectively. Fine-needle biopsy revealed marked lymphocyte infiltration in all six. After withdrawal of iodine thyroid dysfunction remitted spontaneously and antibody titres and lymphocyte infiltration decreased markedly. Follow-up of these six patients for an additional 3 years showed normalisation of antibody titres in four of them. CONCLUSION: Although nearly comparable results were obtained with both treatment regimens regarding thyroid size, partly reversible iodine-induced thyroid dysfunction and autoimmunity were observed among patients with endemic goitre.

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M. SCHULER, G. KAHALY, A. C. SEWELL, H. SCHMIDT, G. BERNHARD, J. BEYER, and U. KRAUSE

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J.P. YUAN, G. KAHALY, K. HÜLBÜSCH, U. KRAUSE, and J. BEYER

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G. Kahaly, W. Lieb, W. Müller-Forell, M. Mainberger, J. Beyer, J. Vollmar, and Ch. Staiger

Abstract

The influence of ciamexone on the activity and course of endocrine orbitopathy was investigated. Fifty-one patients with active orbitopathy classes II-VI were allocated randomly to two groups: over a period of six months, 26 patients received 300 mg/day ciamexone and 25 patients received placebo tablets. In both groups, prednisolone was administered in addition in the first four weeks. Ophthalmological investigations and clinical tests as well as orbit sonography were carried out before as well as one, three and six months after the beginning of therapy. Before and after treatment, computer tomography of the orbit was performed. Symptoms and signs did not show any significant improvement one and six months after therapy. No differences between the two therapy groups were observed. Detailed examination did not reveal any preferential action of the product on individual parameters. Sonography and computer tomography showed no significant alterations of the thickness of the oculomotor muscles. Thus administration of 300 mg ciamexone once a day as compared with placebo did not show any effect on the course and activity of endocrine orbitopathy.