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Biomedical subjects

G Kahaly

Publications and source records attributed to G Kahaly.

At least 19 recordsLinked to original sources
PubMed1992

Relation of endocrine and cardiac findings in acromegalics.

Cardiac involvement in 32 acromegalics was related to endocrine parameters, clinical score and duration of the disease as well as compared to that of 50 controls free of cardiac disease. Stress ECG, 24h Holter monitoring and echocardiography revealed that supraventricular premature complexes did not occur more often in acromegalics than in controls, both prevalence and severity of ventricular arrhythmia, however, were higher in patients compared to controls: 15/32 (48%) acromegalics had complex ventricular arrhythmia as compared with 6/50 (12%) normal subjects (p less than 0.01). Repetitive ventricular arrhythmia was manifest in 10/32 (31%) patients but only in 4/50 (8%) controls (p less than 0.01). Furthermore, frequency of ventricular premature complexes increased with duration of acromegaly (p less than 0.01), the severity of the former being correlated with left ventricular mass and with clinical activity score (p less than 0.01). No correlation, however, was found between the degree of ventricular arrhythmia and hormone levels. Left ventricular muscle mass was increased (p less than 0.02) due to concentric hypertrophy. Thus, compared to controls, acromegalics show more frequent and complex ventricular arrhythmia and left ventricular hypertrophy. Duration of the disease rather than hormone levels seems to be relevant for these pathological changes.

Acromegaly↗
PubMed1992

Arrhythmia profile in acromegaly.

In a controlled study, the cardiac involvement and arrhythmia profile of 32 patients with acromegaly were correlated with endocrine parameters (somatomedine C, growth hormone), clinical score and duration of the disease. Data were compared with those of 50 controls free of cardiac disease. Stress ECG, 24 h Holter monitoring and echocardiography were performed. Supraventricular premature complexes occurred no more often in acromegalics than in controls. Both prevalence and severity of ventricular arrhythmia, however, were significantly higher in patients compared to controls (P less than 0.01). 15/32 (48%) acromegalic patients had complex ventricular arrhythmias (Lown III-IV) as compared with 6/50 (12%) normal subjects (P less than 0.01). Repetitive ventricular arrhythmias (Lown IV a/b) occurred in 10/32 (31%) patients, but only in 4/50 (8%) controls (P less than 0.01). Furthermore, the frequency of ventricular premature complexes increased with duration of acromegaly (P less than 0.01). No correlation was found between the severity of ventricular arrhythmia and hormone levels. Left ventricular muscle mass was significantly increased (285 +/- 139 g, P less than 0.02) due to concentric hypertrophy. Severity of ventricular arrhythmias correlated with left ventricular mass and with clinical activity score (P less than 0.01). Thus, compared to controls, acromegalic patients show more frequent and complex ventricular arrhythmias and left ventricular hypertrophy. Duration of the disease rather than hormone levels seems to be relevant for these pathological changes.

Acromegaly↗
PubMed1992

Humoral immunity and retrobulbar fibroblasts in endocrine ophthalmopathy.

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.

Adult↗
PubMed1992

In vitro synthesis of glycosaminoglycans in endocrine ophthalmopathy.

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Glycosaminoglycans in thyroid-associated ophthalmopathy.

Glycosaminoglycan (GAG) accumulation in the retrobulbar space of patients with thyroid-associated ophthalmopathy (TAO) has been documented in a number of immunohistochemical studies. In order to gain further insight into possible immunopathogenic mechanisms, the influence of humoral immunity on retrobulbar fibroblasts (RF) as GAG producing cells as well as on GAGs themselves was investigated. The effect of lymphocytes on hyaluronic acid (HA) synthesis of RF as well as in turn the influence of RF on lymphocytes were evaluated. In search of methods which would facilitate management of patients with TAO and allow assessment of disease activity, GAGs were determined in both urine and plasma. Immunoglobulin G (IgG) of patients with TAO were found to markedly stimulate the 3H-GAG secretion of RF. Patients with TAO exhibited significantly greater antibody values directed against HA than controls. Preliminary results concerning the influence of lymphocytes on RF indicate a tendency for patients' lymphocytes to increase the synthesis of HA. Furthermore, these lymphocytes in turn were stimulated more by irradiated autologous RF than by irradiated heterologous RF. Urine and plasma GAG determination proved to be suitable for the routine assessment of disease activity and outcome of therapy. In conclusion, GAGs seem to play an important role in the pathogenesis of the disease and their measurement may provide aid to the endocrinological evaluation of patients with TAO.

Antibody Formation↗
PubMed1991

Relationship of eye muscle antibodies with HLA phenotypes and thyroid-stimulating immunoglobulins in endocrine orbitopathy.

The relationship between endocrine orbitopathy and Graves' hyperthyroidism is still not clarified. The purpose of this study was to elucidate the incidence of eye muscle antibodies and the relationship with HLA phenotypes and thyroid antibodies in 65 patients with endocrine orbitopathy classes 1-5. Both bovine and abdominal muscles were used as antigens in ELISA systems in which IgG and IgM antibodies were assayed. Before starting the immunosuppressant therapy, 46/65 patients (71%) showed a positive result for eye muscle antibodies. Those patients with an active disease had such antibodies more frequently. Where the ophthalmopathy was of recent onset IgM antibodies were found, whereas patients with chronic disease were mostly IgG-Ab positive. No association was found either with HLA phenotypes (B8, DR3) or with antibodies directed against thyroglobulin, thyroid microsomes, and the TSH receptor measured as thyroid-stimulating immunoglobulins. Furthermore, there was no correlation between ophthalmopathy class and optic muscle antibody-binding activity. There was no relation between the degree of exophthalmos and eye muscle, thyroid-stimulating, antithyroglobulin, or antithyroid microsomal antibodies. These results suggest that, although very closely related, endocrine orbitopathy and Graves' hyperthyroidism are separate, organ-specific autoimmune diseases.

Adolescent↗
PubMed1991

Graves ophthalmopathy: role of MR imaging in radiation therapy.

Twenty-three patients with Graves ophthalmopathy who underwent radiation therapy were monitored by means of magnetic resonance (MR) imaging. T2 relaxation times of extraocular muscles and orbital fat, areas of extraocular muscles, and degree of exophthalmos were measured by means of MR imaging at the beginning, at the end, and 3 months after completion of radiation therapy. As a result, patients with primarily elevated T2 times of extraocular muscles showed a better therapy response regarding muscle thickening than patients with primarily normal T2 times. Elevated T2 times, which probably represent acute inflammatory changes, were markedly decreased at the end of therapy. Therefore, quantitative MR imaging favors the choice of anti-inflammatory therapy regimens in patients with elevated T2 times of extraocular muscles. However, the clinical response (activity scores) to the low-dose treatment protocol that was used did not correlate well with primarily elevated T2 times. Furthermore, T2 times increased again after cessation of therapy. Whether a higher radiation dose or a different fractionation scheme leads to better results must be clarified by means of further study.

Adult↗
PubMed1990

Long-term observation of endocrine ophthalmopathy and retrospective appraisal of therapeutic measures.

The course of endocrine ophthalmopathy was investigated on the basis of clinical and biochemical parameters and in relation to different therapeutic strategies. A retrospective appraisal was made of 297 patients (44 +/- 14 yr, 249 women) with inclusion of anamnestic and clinical data as well as the results of computer tomography. At the beginning of therapy, 253 patients were hyperthyroid, 36 were euthyroid and eight were hypothyroid. The HLA typing carried out in 89 patients showed the phenotypes B8 and DR3 in 32% and 42% of the cases, respectively. Raised microsomal antibodies were present in 56% of the patients and there were raised thyroglobulin antibodies in 19%. Sixty-three % of the patients received immunosuppressants in the course of therapy: glucocorticoids in all cases, nonsteroid immunosuppressants in 15%. Eight % of the patients were irradiated retrobulbarly. The inflammatory parameters could be favorably affected, whereas eye muscle involvement and bulbar protrusion proved to be more resistant to therapy. In patients with combined immunosuppressant therapy or steroids + retrobulbar radiation, there were unequivocal successes with regard to the proptosis, vision and intraocular pressure. None of the strategies applied constitutes an optimal treatment with regard to the long-term course. Following therapy, there is an improvement of endocrine ophthalmopathy, but not complete healing.

Adolescent↗
PubMed1990

Urinary glycosaminoglycans in Graves' ophthalmopathy.

An increased accumulation of glycosaminoglycans (GAG) in retrobulbar tissues has been reported in patients with thyroid eye disease. We examined the quantitative urinary GAG excretion in 101 patients with Graves' ophthalmopathy of different classes, 36 patients with Graves' hyperthyroidism without ophthalmopathy, 14 patients with toxic nodular goitre and 103 control subjects. Glycosaminoglycans were isolated from 24-h urine collections by precipitation with cetylpyridinium chloride and ethanol followed by photometrical quantification of hexuronic acids after reaction with carbazole. In comparison with the control group (15.8, 10.4, 21.6 mg/24 h; median, 25th, 75th percentile) a significant (P less than 0.005) elevation of urinary GAG excretion was found in patients with ophthalmopathy (19.2, 12.2, 28.7 mg/24 h), whereas patients with Graves' hyperthyroidism and no ophthalmopathy (16.2, 11.9, 21.7 mg/24 h) and patients with toxic nodular goitre (15.8, 11.5, 21.2 mg/24 h) exhibited no markedly increased values. Especially, patients with active, untreated ophthalmopathy showed on average a twofold increase (36.7, 28.1, 48.4 mg/24 h) in urinary GAG excretion. In contrast, high values were not found in patients with inactive ophthalmopathy and elevated values decreased under treatment, which correlated with clinical findings. Further, relapses were also accompanied by high GAG excretion. Thus, using a simple laboratory method, quantitative determination of urinary GAG excretion appears to present an effective parameter for the activity of Graves' ophthalmopathy.

Adolescent↗
PubMed1990

Ciamexone in endocrine orbitopathy. A randomized double-blind, placebo-controlled study.

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.

Adjuvants, Immunologic↗
PubMed1990

[Effect of hyperlipidemia and hypothyroidism on auditory evoked brain stem responses].

Temporary changes in audiometry have been reported in hypercholesterolaemia and in hypo- and hyperthyroidism. The purpose of the present prospective and controlled study was to record changes in conduction time of auditory brain-stem response (ABR) in patients with hyperlipidaemia and hypothyroidism before and after therapy over a period of 6 months. The acoustic evoked brain-stem response Jewett waves I-V were delayed in patients with hypercholesterolaemia, hypertrigliceridaemia and hypothyroidism in comparison with an age-matched control group. The changes in pure-tone threshold and brain-stem responses correlated with the degree of hyperlipidaemia or hypothyroidism. After treatment the brain-stem responses of hypothyroid patients tended to return to normal, and in a few cases normal pure-tone thresholds were achieved. Of the patients with hypercholesterolaemia and hypertrigliceridaemia, 28% had improvements in pure-tone thresholds, whereas no significant changes were found in the ABR following therapy.

Auditory Threshold↗
PubMed1989

[Petit mal status in hyperthyroidism].

A 68-year-old woman who, for the first time, had a generalized tonic-clonic seizure and persisting confusional state was found to have nodular enlargement of the thyroid and a tachycardic arrhythmia. Electroencephalography (EEG) demonstrated a continuous irregular polyspike wave pattern. Total T4 concentration was elevated to 23 micrograms/dl. Consecutive Administration of 250 mg phenytoin, 4 mg clonazepam and 7.5 mg midazolam changed neither the clinical nor the EEG findings. But after general intensive care measures and high-dose thyrostatic treatment (40 mg thiamazole intravenously every four hours) the clinical and neurological status became normal. Serial EEGs over the subsequent weeks and months showed gradual disappearance of the abnormal changes with increasingly prolonged periods of normal activity.

Aged↗
PubMed1989

Cardiac arrhythmias and heart rate in hyperthyroidism.

The arrhythmia profile and heart rate (HR) were analyzed by 24-hour Holter monitoring in 37 hyperthyroid patients before (triiodothyronine [T3] hormone level = 331 +/- 108 ng/dl), during (T3 level = 202 +/- 98 ng/dl) and after an antihyperthyroid therapy of 8 to 89 weeks' duration (T3 level = 149 +/- 41 ng/dl). The data were compared with those of 50 control subjects free from cardiac disease. Only 12 hyperthyroid patients (32%) had complex ventricular arrhythmias (Lown grade 3 or 4) as compared with 6 normal subjects (12%, p greater than 0.05). Three patients (8%) had repetitive ventricular arrhythmias (Lown grade 4A/B) as compared with 4 normal subjects (8%, p greater than 0.05). Supraventricular premature complexes occurred more often in hyperthyroid patients than in normal subjects before and after therapy (p less than 0.001). The prevalence of supraventricular tachycardia decreased from 8 patients to 1 during therapy (p less than 0.002). The HR decreased from 95 +/- 13 to 79 +/- 9 beats/min after therapy, but was still increased as compared with the normal subjects (72 +/- 8 beats/min, p less than 0.001). A day/night difference in HR greater than 10% was found in 32 patients (86%) and was more pronounced than in the normal group (p less than 0.001). Compared with the normal HR profile, the HR curve of hyperthyroid patients was shifted to a higher level (about 20 beats/min). Serum T3 level correlated best with HR at night in hyperthyroid patients (r = 0.74, p less than 0.001). Thus, hyperthyroid patients show frequent supraventricular arrhythmias that might be reversible during therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1989

[Long-term study of endocrine ophthalmopathy and retrospective assessment of therapeutic measures].

The follow-up of Graves' ophthalmopathy was analysed regarding to clinical and chemical data on the one hand and to dependence on different therapeutic alternatives on the other. 297 patients (44 +/- 14 years, 249 female, 48 men) were observed with inclusion of data from the history and clinical data as well (computer tomography and orbital sonography). At the onset of therapy 253 patients were hyperthyroid, 36 euthyroid and eight showed hypothyroidism. The staging was: I 13, II 54, III 113, IV 95, V five, VI eight patients. The HLA-typing in 89 patients showed the following results: B8 in 32%, DR3 in 42%, B8 as well as DR3 in 24% of the patients. In about 50% of the cases there were raised microsomal and in about 18% there were raised thyroglobuline antibodies. 63% of the patients received immunosuppressive medication: corticosteroids in 100% (more than one time in 43%), cyclosporine A in 11%, ciamexone in 10%, other non-steroid immunosuppressants in 5% of the cases. The retrobulbar irradiation was performed in 9%, and total thyroidectomy in 7%. During therapy the inflammatory process was clearly ameliorated, however exophthalmos and diplopia were more resistant to treatment. In the group of patients with combined cyclosporine and prednisone therapy and in the group of patients with total thyroidectomy and partly retrobulbar radiotherapy, significant differences were observed regarding to visual acuity and Hertel values. None of the therapies applied constitutes an optimal treatment with the regard to the long-term course. Under therapy an improvement can be reached, but no complete healing.

Adolescent↗