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Biomedical subjects

R Paschke

Publications and source records attributed to R Paschke.

At least 163 records · Page 9Linked to original sources

Regional stimulation of thyroid epithelial cells in Graves' disease by lymphocytic aggregates and plasma cells.

The significance of intrathyroidal lymphocytic infiltration is not known. However, several indirect lines of evidence suggest that interstitial or intraepithelial lymphocytes are the effector or thyroid autoantibody-producing lymphocytes in Graves' disease. This has not been investigated in vivo. Changes of nuclear volume of endocrine cells have previously been shown to be a reliable parameter of functional stimulation of endocrine glands. Therefore we investigated this parameter near and off lymphocytic aggregates, loosely distributed plasma cells and memory T cells in paraffin sections of Graves' disease thyroid glands. In 21 Graves' disease thyroid glands we found significant increases of thyroid epithelial cell nuclear volume near plasma cells (198.4 micron3) as well as near lymphocytic aggregates (219.1 micron3) compared with thyroid epithelial cell nuclear volume one microscopic field away (160.1 and 137.7 micron3 respectively). Similar nuclear volume differences were observed after propanolol and thiourelene antithyroid drug treatment. These nuclear volume differences could not be observed in 10 control thyroid glands and around CD45R0-positive memory T cells in Graves' disease thyroid glands. These direct in vivo investigations of regional functional stimulation of thyroid epithelial cells in Graves' disease show local stimulation near lymphocytic aggregates and diffusely distributed plasma cells. Therefore our in vivo data do not permit to identify stimulatory lymphocytes only interstitially or intraepithelially as previously suggested.

Adolescent↗

Thyrotoxic crisis in Graves' disease: indication for immediate surgery.

Thyrotoxic crisis (thyroid storm) is a rare complication of hyperthyroidism. It can be observed not only in thyroid autonomy with latent hyperfunction after exposure to iodine, but also in Graves' disease with overt hyperfunction. Adequate management of thyrotoxic crisis is still controversial. We report about four patients (four women, mean age 75 years) with Graves' disease who developed thyrotoxic crisis during therapy with antithyroid drugs so that surgical intervention became necessary. The patients had been admitted to the hospital for nonspecific symptoms such as headache, cachexy, and psychosis. Thyroid hormone levels had reached twice the normal range prior to surgery. All patients showed severe neurological deficits leading to coma. In three cases euthyroidism was achieved within two days after surgery. The neurological symptoms disappeared after an average of four days. The postoperative course did not show severe complications and all patients recovered completely. Especially in the elderly a monosymptomatic or nonspecific course of thyroid storm with neurological symptoms may represent a severe and life-threatening situation. In these cases surgery can become necessary even if euthyroidism has not been achieved preoperatively.

Aged↗

Sequential psychological testing during the course of autoimmune hyperthyroidism.

Although the psychological disturbances accompanying Graves' disease are well known, the time required for normalisation of these disturbances during antithyroid drug treatment is not known. Therefore sequential psychological testing during the course of Graves' disease was done. There are also contradictory results concerning the possible correlation of neurophysiological and psychological test results during the course of Graves' disease with thyroid hormone values. Finally, psychological disturbances have been proposed as possible etiologic factors in Graves' disease. In our study, a significant decrease in anxiety and irritability could be observed at the time euthyroidism was achieved. Self-evaluations of depressivity, activity, exhaustion, well-being, extraversion, introversion, and the ability to concentrate changed 1 or 2 months after euthyroidism was induced. Similar test results could be observed after induction of euthyroidism by antithyroid drugs and subtotal thyroid resection. Therefore the mode of therapy does not seem to influence the course of normalisation of psychological parameters. In contrast to other investigations there was hardly any correlation between thyroid hormone values and psychological test results or the ability to concentrate. Nontheless, patients with Graves' disease showing high scores for depression and anxiety exhibit abnormal peripheral helper/suppressor T-lymphocyte relations. Furthermore, patients suffering from Graves' disease tend to be more anxious than controls. It remains to be determined whether an increased susceptibility to psychological disturbances has led to these alterations of lymphocyte subsets in Graves' disease patients with severe depression and anxiety.

Adult↗

Evidence for a role of anti-idiotypic antibodies in the induction of remission in Graves' disease.

Serum and Ig samples obtained from a patient with Graves' disease during exacerbation and remission were evaluated in the nu/nu bioassay. Blocking of the exacerbation serum's biological activity was demonstrated by several biological assay parameters after it was mixed with the remission serum. Since this blocking effect can be ascribed to immunoglobulins, anti-idiotypic antibodies in the remission serum and immunoglobulin samples are the most likely cause of this blocking effect. Therefore a role of anti-idiotypic antibodies in the induction of remission in Graves' disease is postulated.

Animals↗

Significance of latent hyperthyroidism.

In euthyroidism the circadian rhythm and pulsatility of TSH is well known. With regard to hyperthyroidism only very preliminary data were described. In this study we investigated the secretion pattern of the pituitary-thyroid axis hormones during 24 h in latent and overt hyperthyroidism and in euthyroidism with regard to common and different properties. Blood was obtained for 24 h at 10-min intervals. In euthyroidism we found intraindividually three overlapping patterns of TSH, which are different in amplitude and frequency and can be found interindividually, too. These patterns are equal to the circadian rhythm, pulsatile secretion and lastly to the methodic rustle. The circadian rhythm in latent hyperthyroidism is distinctly suppressed and in overt hyperthyroidism totally. Whereas in latent hyperthyroidism pulsatile secretion is extant, in overt hyperthyroidism the TSH pulses are absent. To record the patients' TSH circadian rhythm with only three blood samples, we defined the TSH-Triplex. In young as well as in elderly healthy volunteers it demonstrated significantly higher TSH levels at midnight (at 24:00 h) than it did at 4 p.m. and 8 a.m. The present study shows a significantly different TSH pattern in latent hyperthyroidism compared to euthyroidism. It should be discussed whether latent hyperthyroidism could be defined as hyperthyroidism stage I. On the other hand, latent hyperthyroidism could be an illness with its own cause, different from hyperthyroidism. Our data suggest that the laboratory findings of latent hyperthyroidism in each age are non-physiological. However, the cause for this disorder is unclear until now; hence further investigations are necessary.

Adult↗

[Results of clinical trials with the gluconeogenesis inhibitor 2-(3-methylcinnamylhydrazono)-propionate (MCHP)].

Many compounds which directly or indirectly inhibit gluconeogenesis have been described. Some of them showed hypoglycemic action in animal experiments. 2-(3-Methylcinnamylhydrazono)-Propionat (MCHP) a derivative of hydrazine demonstrated marked hypoglycemic action in animal experiments. Nontheless the administration of MCHP to type II diabetic patients showed no hypoglycemic action. Clinical or biochemical sideeffects could not be observed.

Aged↗

[Hepatotoxicity with etoposide-ifosfamide combination therapy].

Combination chemotherapy with etoposide and ifosfamide in 2 patients with advanced bronchial carcinomas caused hepatotoxic side effects. Hepatotoxicity was observed during and immediately after the 5-day therapy and was characterised by a massive rise in direct bilirubin, drop in cholinesterase, as well as a rise in the alkaline phosphatase and to a lesser extent in gGT and GOT. Hepatotoxicity was lethal in one case and reversed to normal in the other. Hepatotoxicity was most likely caused by ifosfamide, since this drug was applied for the first time in both cases. Nonetheless, a contribution of etoposide in this regard can not be excluded since there were liver enzyme alterations in one case after a previous course of chemotherapy using etoposide and cis-platinum.

Aged↗

Is remission of Graves' disease regulated by anti-idiotypic antibodies?

Our results show evidence for regulation of Graves' disease remission by anti-idiotypic antibodies in a biologic assay. The polyclonality and functional heterogeneity of thyroid receptor antibodies is most likely the reason why evidence for idiotypic-anti-idiotypic regulation can be demonstrated in the autologous but not consistently in the homologous system.

Animals↗

Extrathyroidal synthesis and biologic action of thyroid receptor antibody (TRAb) in Graves' disease.

In a patient with Graves' disease who underwent thyroidectomy with subsequent radioiodine therapy thyroid receptor antibody could be detected by radioligand assay. No thyroid tissue could be detected by 131I-scintiscanning. Thyroglobulin was repeatedly negative. Biologic activity of this patients serum could be demonstrated in the nude mice bio assay. 131I-incorporation and secretion of human thyroglobulin could be stimulated by injecting thymusdysplastic nude mice with transplants of thyroid tissue from a patient with Graves' disease with the athyroid patients serum. These results demonstrate evidence for extrathyroidal production and biological activity of TRAb in vivo.

Adult↗

Transplantation of human endocrine tissues to nude mice: a suitable in vivo model for the study of pathomechanisms involved in autoimmune thyroid diseases.

After transplantation of human tissue to nu/nu mice the human lymphocytes disappear. In this context, interestingly, the DR-expression is not detectable anymore after transplantation of the tissues from patients with autoimmune thyrotoxicosis and cancer. Neopterin release was only demonstrable when T-lymphocytes from patients with autoimmune thyrotoxicosis or PHA-stimulated lymphocytes were added, independently of the presence of DR-expression in the used culture tissues. These results seem to exclude a functional role of DR-expression as a trigger mechanism of autoimmunity. It is supposed that DR-priming on epithelial cells is mediated by kinine production of activated T-lymphocytes or macrophages.

Animals↗

Clinical effect of dopamine on incidence of peptic ulceration.

Dopamine and its agonists diminish gastric acid secretion and exert a protective effect on experimentally induced peptic ulcers in rats. For treatment of peptic ulcer disease in man, dopamine and dopamine antagonists have been recommended, but clear evidence is not yet available. To answer the question of whether dopamine has any protective effect regarding peptic ulcer formation in man, autopsy reports were evaluated for the incidence of acute peptic ulcerations before and after the introduction of dopamine as a common drug in intensive care units. The analysis showed no change in ulcer incidence, i.e., our retrospective study demonstrated no ulceroprotective action of dopamine in critically ill patients.

Dopamine↗

Pathophysiological aspects of dacarbazine-induced human liver damage.

Hepatic Veno-occlusive Disease (VOD) and Budd Chiari syndrome (BCS) have been reported as fatal complications of Dacarbazine therapy. Peripheral eosinophilia and eosinophilic infiltrates after repeated Dacarbazine therapy in some cases were interpreted as evidence of an allergic drug reaction. Since no mention of an allergic drug reaction is to be found in other reports on veno-occlusive disease or Budd Chiari syndrome due to Dacarbazine, the pathophysiological mechanism of these fatal complications of Dacarbazine remain to be elucidated. We describe a case of VOD due to Dacarbazine which showed peripheral eosinophilia after the first cycle of Dacarbazine treatment with no prior possibility of sensibilization, along with signs of a toxic drug reaction. This observation suggests that peripheral eosinophilia, so far interpreted as a sign of an allergic reaction induced by Dacarbazine, can be observed together with obvious signs of toxic drug reaction, thus providing further evidence of a toxic mechanism of Dacarbazine-induced VOD or BCS.

Adult↗

Effect of pentobarbital anesthesia and bile acids on cysteamine-induced duodenal and gastric ulcers in rats.

Cysteamine given three times within 8 h produced severe duodenal and gastric ulcers in female SIV rats. A pentobarbital anesthesia during the first 10 h prevented gastric ulcer formation without affecting duodenal ulcer. An additional 10 h lasting intragastric infusion with 0.6 ml/h Ringer containing 5 mmol/l of a mixture 3: 1 pure taurocholic and glycocholic acid or 20 and 50 mmol/l pure taurocholic acid in 0.2 N HCl did not reverse the protective effect of pentobarbital, e.g. incidence and intensity of gastric ulcer did not change. Treatment with somatostatin significantly reduced the intensity of duodenal ulcer. The inhibition of cysteamine-induced gastric ulcer formation by pentobarbital does not seem to be due to a possible inhibition of duodenogastric reflux but more likely to an inhibition of central nervous stress reactions by anesthesia.

Anesthesia, General↗