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Biomedical subjects

K H Usadel

Publications and source records attributed to K H Usadel.

At least 163 records · Page 9Linked to original sources
PubMed1992

In vivo effects of TSH receptor antibodies in xenotransplanted human thyroid tissue.

From the data presented it can be concluded that the xenotransplantation model is well suited for studies concerning pathogenesis, diagnosis and therapy of AITD. Human thyroid transplants of Graves' disease tissue, depending upon extrinsic stimulators, lose all signs of hyperfunction after transplantation into athymic nude mice, but hyperfunction can again be induced in the transplants by injections of sera or immunoglobulin fractions from patients with active Graves' disease, containing stimulating TSH receptor antibodies. Our data demonstrate that thyroid function and growth are independent phenomena and can be differentiated by means of the xenotransplantation model. Furthermore the presented results indicate that TSH receptor antibodies are able to alter the expression of gene products in human thyroid transplants of Graves' disease, emphasising their important role in inducing/perpetuating immune phenomena related to AITD.

Animals↗
PubMed1992

Relapse of Graves' disease following development of a pheochromocytoma.

Catecholamines stimulate thyroid hormone synthesis as well as release of thyroid hormone and cause immunologic disturbances that possibly contribute to the manifestations of Graves' disease. This has led to repeated speculations about the possible role of catecholamines in the initiation and maintenance of hyperthyroidism. We describe a patient with Graves' disease who was treated with antithyroid drugs for 2 years. After withdrawal of antithyroid drugs, the patient was in remission for 5 years. After the antithyroid drug treatment and the long remission, the probability of relapse of Graves' disease was very low. Nonetheless, a relapse did occur. Two years after subtotal thyroid resection, further investigation because of persistent hypertension revealed a pheochromocytoma. Retrospective anamnestic data suggest that this pheochromocytoma had been present 2 years before the patient's relapse of Graves' disease. This sequence of diseases has not been described previously. The low probability for a Graves' disease relapse in this patient and the association of this patient's relapse with the manifestation of a pheochromocytoma suggest a possible etiologic role of excess catecholamine production in the relapse of Graves' disease.

Adrenal Gland Neoplasms↗
PubMed1992

Increased plasma levels of endothelin in diabetic patients with hypertension.

In order to gain insight into the potential role of endothelin, a 21 amino acid peptide produced by endothelial cells, in the development of complications of diabetes mellitus, basal plasma endothelin levels were measured in 152 patients with diabetes mellitus (83 patients with type 1 diabetes mellitus, 69 patients with type 2 diabetes mellitus) and compared to those in 50 healthy controls. Blood was drawn at 8:00 AM under resting conditions and endothelin was measured after prior extraction by a sensitive radioimmunoassay specific for both endothelin 1 and 2. Endothelin levels were increased in patients with diabetes mellitus in comparison to controls. In type 1 diabetes mellitus a positive correlation between endothelin levels and age was found. We found that 60% of patients with type 1 diabetes mellitus and elevated endothelin levels higher than 2.5 pg/mL (highest value in a control person) had had diabetes for more than 20 years (P less than .05 v patients with normal endothelin levels). In type 2 diabetes mellitus the relation between elevated endothelin levels and diabetes duration was reversed. Glycosylated hemoglobin (HbA1) concentrations above 10% of total hemoglobin were measured in 62% of the patients. Arterial hypertension was present in 60% of the patients with type 1 diabetes mellitus and increased endothelin levels greater than 2.5 pg/mL (both P less than .05 v patients with normal endothelin levels).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Tumor necrosis factor beta gene polymorphisms in Graves' disease.

The physical mapping of tumor necrosis factor alpha (TNF alpha) and lymphotoxin (TNF beta) genes to the short arm of chromosome 6 in man between the loci for histocompatibility leucocyte antigens (HLA)-B and the complement system focused attention to this genetic region that controls immune responses in many ways. It also holds susceptibility genes for a variety of autoimmune disorders that are linked to specific alleles of loci in the HLA D subregion. We have recently identified a TNF restriction fragment length polymorphism with the enzyme NcoI (K. Badenhoop, G. Schwarz, J. Trowsdale, et al. Diabetologia. 1989;32:445-8). The less frequent fragment of 5.5 kilobase (kb) is in strong linkage disequilibrium with the HLA haplotype A1B8DR3. Since Graves' disease is linked to A1B8DR3, we analyzed TNF gene polymorphisms in a large group of Graves' disease patients and normal controls derived from four Centers. We show here a significant association of TNF beta polymorphisms with Graves' disease. The patients have less homozygotes for the 10.5 kb band (60 of 174, 34%) and more heterozygotes 10.5/5.5 kb (96 of 174, 55%), than 173 controls (49% homozygotes 10.5 kb and 42% heterozygotes; chi 2 = 7.45, P less than 0.03). When DR3+ patients and controls were analyzed separately, heterozygotes were still significantly increased in DR3+ Graves' disease patients (54 of 77, 70%) compared to DR3+ controls (21 of 45, 47%; chi 2 = 6.6, P less than 0.04). Furthermore, TNF fragment heterozygotes were found predominantly in patients, who had TSH-receptor antibodies (29/45, 64%, P less than 0.007), implying that these patients might represent an immunogenetic subset of the disease. Although TNF beta polymorphisms are linked to A1B8DR3, these results suggest that they represent an additional susceptibility marker in Graves' disease.

Autoantibodies↗
PubMed1992

Bromocriptine treatment over 12 years in acromegaly: effect on growth hormone and prolactin secretion.

It is not known whether bromocriptine treatment in acromegaly can be implemented for a life-long period. To elucidate this problem, the secretory GH and PRL states of 12 patients with acromegaly were determined, before bromocriptine treatment, under therapy (15.0 +/- 6.8 mg/day for 12 +/- 3 years; mean +/- SD) and during two-weeks long drug withdrawal after long-term treatment, respectively. Before therapy, all patients showed a non-sufficient GH suppression after oral glucose load (greater than 2 micrograms/l), whereas under dopaminergic treatment the post-glucose GH levels of three patients fell below 2 micrograms/l; normal IGF-I concentrations were found in five patients. However, under bromocriptine, only two patients showed GH suppressions below 2 micrograms/l following glucose, accompanied with normal IGF-I levels. During bromocriptine withdrawal, GH secretion at 60 min in the oral glucose tolerance test increased significantly (17.0 +/- 15.5 vs 5.7 +/- 5.2 micrograms/l; p less than 0.01); the mean IGF-I level rose from 2.1 +/- 0.8 to 4.9 +/- 2.2 kU/l (p less than 0.01). IGF-I was normal during bromocriptine cessation in only one patient; none of the 12 patients showed a GH suppression below 2 micrograms/l after oral glucose load. Under dopaminergic treatment hyperprolactinemia could not be detected. In conclusion, bromocriptine led to a stable suppression of both GH hypersecretion and--if present--concomitantly elevated PRL levels. Severe side effects or a further tumor growth could not be observed. Thus, the data of the longest follow-up investigation that has so far been published indicate that effective life-long bromocriptine therapy seems to be possible in selected patients with acromegaly.

Acromegaly↗
PubMed1992

Somatostatin in acute bleeding oesophageal varices. Pharmacology and rationale for use.

Somatostatin was originally isolated from the hypothalamus, but has subsequently been found throughout the whole gastrointestinal tract. It exerts an inhibitory effect upon numerous functions of the body, and, therefore, increasing attention has been focused on its potential as a therapeutic agent with cytoprotective properties and a potent inhibitory action on a wide variety of functions in endocrine diseases, cancer and gastrointestinal haemorrhage, including bleeding from oesophageal varices. As somatostatin has a very short plasma half-life and requires administration by continuous infusion to maintain therapeutic levels, stable long-acting analogues have been developed. The analogue octreotide has been shown to have a plasma half-life of 113 minutes and to produce a profound selective inhibition of growth hormone. Hepatic excretion of octreotide has been estimated to be between 30 and 40% in healthy volunteers; no data are available in cirrhotic patients. A review of published data assessing systemic and hepatic haemodynamics in animals and humans over varying dosage regimens of somatostatin and octreotide reveals that cardiac output, arterial pressure and peripheral resistance are modified more in animals than in humans. Hepatic haemodynamics are significantly altered in animals as well as in humans in most of the studies. Circumstantial evidence is provided indicating that the mechanisms of action of somatostatin and octreotide in the therapy of bleeding oesophageal varices are mainly mediated by a splanchnic vasoconstrictive effect. Furthermore, gastric acid suppression and potential enhancement of platelet aggregation may contribute to the beneficial outcome after treatment of oesophageal varices with somatostatin.

Acute Disease↗
PubMed1992

HLA-DR/DQ gene variation in nongoitrous autoimmune thyroiditis at the serological and molecular level.

The etiology of autoimmune diseases is multifactorial with genetic factors being an important prerequisite. There are two clinical manifestations of autoimmune thyroiditis: the goitrous form (Hashimoto's thyroiditis) and the atrophic variant, which is characterized by hypothyroidism (primary myxoedema). Different genetic markers were assumed to be predisposing factors for the distinct clinical presentation. In the present study, we determined HLA A,B,C,DR,DQ alloantigens serologically and HLA-DQ by gene analysis in patients with nongoitrous autoimmune thyroiditis and randomly chosen controls. To verify the exact classifications, thyroid volume (median 5.85 ml) was measured by ultrasonography. HLA-DR5 was found in 16 of 36 (44%) patients with nongoitrous autoimmune thyroiditis and in only 26 of 175 controls (15%) (Pc = 0.0018). There was a tendency towards a lower frequency of HLA-DR7 with 6% positivity in patients vs. 29% in controls (Pc = 0.052). Regarding HLA-DQ, DQ7 was found in 17 of 35 patients (48%) vs. 21 of 98 controls (21%) (Pc = 0.028) (relative risk 3.5). No other association was found with HLA-A,B,C and HLA-DR and -DQ. Our data indicate that the genetic susceptibility to autoimmune nongoitrous thyroiditis is closely associated to HLA-DR5 and DQ7 and not distinct from goitrous disease. We conclude that factors other than genetic ones explain the different immunological and clinical manifestation of chronic lymphocytic thyroiditis.

Autoimmune Diseases↗
PubMed1992

The effect of somatostatin, gabexate mesilate and dextran 40 on the microcirculation in sodium taurocholate-induced pancreatitis.

In vivo microscopy was performed to assess the effect of dextran 40, gabexate mesilate and somatostatin on the microcirculation in sodium taurocholate-induced pancreatitis in rats. Intraductal infusion of 0.4 ml of a 4% solution of sodium taurocholate decreased capillary blood flow, induced capillary stasis and increased vascular permeability in the head of the pancreas. Dextran 40, gabexate mesilate and somatostatin improved capillary blood flow in the initial phase of acute pancreatitis significantly and prevented stasis in 5 of 9, 3 of 8 and 7 of 10 (p < 0.05) cases. Only dextran 40 reduced the increase of vascular permeability. Decrease of capillary blood flow, capillary stasis and vascular permeability changes are important factors contributing to the pathogenesis of sodium taurocholate-induced pancreatitis. Dextran 40, gabexate mesilate and somatostatin exert a beneficial effect on the microcirculatory changes in this model of acute pancreatitis.

Animals↗
PubMed1992

[Polyneuropathy in hyperthyroidism--a clinical neurophysiologic study].

In this prospective study, 27 patients with hyperthyroidism were evaluated neurophysiologically. There were 24 women and 3 men: the mean age was 56.4 years (range 21 to 84 years). Neurologic complaints of the patients were muscle weakness (59.3%), muscle cramps (18.5%) and sensory symptoms (11.1%). Tendon reflexes were increased in 18.5% and decreased in 14.8%, respectively. While the motor nerve conduction velocities (NCV) of the tibial and the peroneal nerve revealed normal results in the majority of patients, there were pathological findings of the sensory NCV of the sural nerve in 29.6% of patients. In another 22.2%, borderline findings were obtained. Six patients presented myopathic changings in electromyography of the m.vastus lateralis. Neither neuropathic nor myopathic findings correlated with the serum levels of TT3, TT4 or the T4/TBG-quotient. A polyneuropathy in hyperthyroidism seems not to be uncommon and is probably caused by hypermetabolism in thyroid hyperfunction.

Adult↗
PubMed1992

[Multi-visceral upper abdominal resection and orthotopic liver transplantation--a surgical treatment concept for regionally metastatic tumors of the endocrine pancreas].

Islet cell carcinoma is rare. Even in advanced metastasizing tumors, relatively long survival times were reported. Aim of surgical treatment is complete removal of the tumor mass, if possible. When not, palliative procedures were described to be efficient in some of the cases. In the literature, among the first patients with regional metastasizing intraabdominal malignancies and upper abdominal exenteration, some cases with neuroendocrine tumors were reported. Aim of the following study is to describe the results in 4 patients with metastasizing islet cell carcinomas, which were treated by multi-visceral upper abdominal exenteration and combined orthotopic liver transplantation.

Adenoma, Islet Cell↗
PubMed1992

The possible etiological role of psychological disturbances in Graves' disease.

In the discussion of possible factors in the etiology of Graves' disease, stress has always played a major role. We investigated the possible influence of present depression (depressivity scale DS) and anxiety (State Trait Angstinventar STAI X1) on peripheral lymphocyte subpopulations in 10 patients with Graves' disease. The tests were done in hyperthyroidism and after 2-4 months in stable euthyroidism. Parallel to the psychometric testing, peripheral lymphocyte subpopulations were investigated. Elevated anxiety as a constant personality trait was investigated with the State Trait Angstinventar STAI X2 in 19 hyperthyroid patients with Graves' disease. 5 of the 10 patients had a pathological T4:T8 ratio and very high raw values for present anxiety (mean = 53,8; STAI X1), as well as a a high percentile for depression (median 93,1; DS). The other 5 patients with a normal T4:T8 ratio had much lower values for anxiety (mean = 37,8; STAI X1) and depression (median 78,4; DS). In those patients, the T4:T8 ratio remained normal in stable euthyroidism, while the values for anxiety and depression decreased. This also happened in the patients with a formerly pathologic T4:T8 ratio. However, the pathologic T4:T8 ratio persisted in those patients. The STAI X2 percentage ranking for the 19 hyperthyroid patients was 76,5. The value for healthy people is 55,5. Therefore a significantly elevated anxiety--representing a constantly elevated internal psychological stress--seems to be present in patients with Graves' disease. Since psychological stress is known to influence the immune system, such a constant personality trait could be a predisposing factor for Graves' disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Immunologic findings in tissue of thyroid carcinoma.

We studied the occurrence of DR-antigen (DR-Ag) positive thyroid epithelial cells (TEC), lymphocyte (Ly)-subsets, and antigen-presenting cells (APC) in thyroid carcinoma and the influence of thyroid-stimulating hormone (TSH) on immunologic behavior. Tissue slices from various thyroid carcinomas (n = 14) and endemic goiters (n = 12) were investigated by immunohistochemical methods (PAP/APAAP/FITC) using monoclonal antibodies (MoAbs) against DR-Ag, dendritic cells (APC), endothelial cells, CD-3 Ly, CD-4 Ly, and CD-8 Ly. Monolayers of TEC were cultured in the presence or absence of TSH (0.01 mU/ml) and/or PHA (0.1 mg/ml) over 24 h and screened for DR-Ag expression. Various ranges of DR-Ag expression were detectable in 13 thyroid carcinomas. One thyroid carcinoma and all endemic goiters were DR-Ag-. The amount of APC and local infiltrating Ly correlated very well with the presence and intensity of DR-Ag+ TEC. The lymphocytic CD-4/CD-8 ratio varied in a wide range. No prevalence of Ly-distribution for any type of carcinoma was found. PHA induced DR-Ag expression in all thyroid carcinomas and endemic goiters. This effect was enhanced significantly by TSH. DR-Ag expression on thyroid carcinoma cells may be considered as an immune activating factor. These "neoantigens" may be induced by lymphokines released by the local immune competent cells. The distribution of Ly and DR-Ag+ TEC in thyroid carcinoma seems to represent the individual immunologic response against the tumor. Whether TSH acts as an immune modulator directly or indirectly, as described elsewhere, cannot be concluded from these results.

Antigens, Neoplasm↗
PubMed1991

Prevalence of HLA-DQ beta chain non-Asp alleles in type I (insulin-dependent) diabetics with young and older ages of onset.

Particular HLA-DQ beta chain alleles were reported as immunogenetic markers of type I diabetes mellitus with young onset of the disease. In a homogeneous German population, we studied HLA-DR specificities and HLA-DQ beta chain alleles in young-onset (less than 21 years of age; n = 185) and adult-onset (greater than 40 years of age; n = 48) insulin-dependent diabetics. In both cohorts of type I diabetics, the HLA-DR3 and -DR4 specificities were significantly increased. The presence of an HLA haplotype with an amino acid other than aspartic acid at position 57 of the DQ beta chain was significantly associated with type I diabetes in both cohorts (etiologic fraction: 93% and 73%). We conclude that the presence of DNA sequences coding for an amino acid other than aspartic acid at the 57th position of the DQ beta chain provides a molecular risk marker for type I diabetes of both and adult onset.

Adolescent↗
PubMed1991

Characterization of a rat pancreatic secretory protein associated with pancreatitis.

A new protein was purified from the pancreatic juice of rats with acute pancreatitis. That protein, not detectable in control animals, was called "pancreatitis-associated protein." It was first observed 6 hours after induction of experimental pancreatitis with taurocholate or cerulein, reached maximal levels of 45 micrograms/mg protein in zymogen granules and 1.8 micrograms/mg protein in pancreatic tissue during the acute phase (48 hours), and disappeared during recovery (day 5). It was never detected in spleen, liver, kidney, heart, or lung. The detection limit of the assay system was 12 ng/mg protein, so that pancreatitis-associated protein levels increased at least 100-fold in pancreatic tissue during the acute phase. The molecular weight (12,000) and isoelectric point (8.2) were determined by two-dimensional gel electrophoresis. Subcellular fractionation and immunoelectron microscopy showed that the protein was synthesized on the rough endoplasmic reticulum and stored in zymogen granules before being secreted, similar to other pancreatic secretory proteins. Immunoblotting and two-dimensional gel electrophoresis revealed that the same protein was synthesized upon induction of pancreatitis by cerulein infusion, by retrograde injection of bile acids, or pancreatitis induced by pancreatic surgery. The pancreatitis-associated protein is therefore an acute-phase protein that differs from other proteins of that family because of its exocrine nature.

Acute Disease↗