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Biomedical subjects

D Lohmann

Publications and source records attributed to D Lohmann.

At least 55 records · Page 3Linked to original sources
PubMed1987

Electron microscopical investigations on lymphocyte cytotoxicity against beta-cells in recent onset IDDM.

The effect of lymphocytes from patients with newly diagnosed insulin dependent diabetes on isolated rat or human islets during a 20 h in vitro incubation was investigated by morphological and biochemical methods. All stages of target cell reaction of lymphocytes against beta-cells were observed. Cytoplasmic projections towards and contacts with beta-cells, circumscribed lysis of the outer cell membrane at the contact side and complete lysis of beta-cells were seen. Such findings could not be registered with alpha- or other non beta-cells and in control experiments using lymphocytes from healthy persons. In some cases the lymphocytes were phenotyped using monoclonal antibodies by the indirect immuno-gold technique. It could be demonstrated that lymphocytes in contact with necrotic beta-cells were of the CD8+ve subset. In addition the morphological investigations were supplemented by quantitative biochemical studies measuring the non-secretory insulin release ("cytotoxic" release) from islets into the culture medium and their ability to respond to a consecutive stimulation by arginin with insulin and glucagon secretion. The mean cytotoxic insulin release was 11.3 +/- 1.5 ng/islet/20 h (n = 25) in the diabetic group versus 0.56 +/- 0.15 ng/islet/20 h (n = 15) in the control subjects (alpha less than 0.001). Functional testing of the islets following incubation with lymphocytes from diabetic patients showed diminished insulin (58.6 +/- 5.1%, n = 18, alpha less than 0.001) and unchanged glucagon response (103.0 +/- 3.4%, n = 10, n.s.) when compared with untreated islets (= 100%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

[Diabetes mellitus as a primary and secondary metabolic disease].

Already in the preface of his book "Alimentary and Metabolic Diseases" Max Bürger writes: "I see a difficulty in the definition in the field of metabolic diseases. Since all life processes are finally based on a change of the substances, the accentuation of individual diseases as metabolic diseases is more or less arbitrary." The diabetes mellitus belongs to the classical metabolic diseases. But here only the symptoms are taken into consideration which phenotypically are standing in the foreground. The further clarification of the etiopathogenesis shows that the diabetes mellitus has heterogeneous causes and an existing insulin deficiency is etiologically to be classified as a primary immunological or endocrinological disease and thus one should speak of a secondary metabolic disease, while in normal insulin secretion it should be regarded as a primary metabolic disease.

Autoantibodies↗
PubMed1986

Cell-mediated immune reactions against B cells and defect of suppressor cell activity in type 1 (insulin-dependent) diabetes mellitus.

A cytotoxic effect of peripheral blood mononuclear cells from 22 out of 23 newly diagnosed Type 1 (insulin-dependent) diabetic patients against B cells of isolated rat islets was demonstrated. The addition of peripheral blood mononuclear cells from healthy subjects reduced the cytotoxic effect in 9 out of 10 patients. The addition of peripheral blood mononuclear cells from other diabetic patients was without significant effect in 14 out of 16 cases. The results indicate functional abnormalities of peripheral blood mononuclear cells in newly diagnosed Type 1 diabetes. Beside cytotoxic effects against B cells, a defect in the suppressor function seems to exist. The activation of T-lymphocytes might be a consequence of such a defect.

Adolescent↗
PubMed1986

Specific immunotherapy in insulin-dependent diabetes mellitus (preliminary report).

In 7 patients with newly diagnosed insulin-dependent diabetes mellitus a cytotoxic effect of blood lymphocytes against B-cells could be demonstrated by incubation of isolated rat islets with the lymphocytes. The addition of lymphocytes from healthy persons significantly reduced this effect in vitro. The transfusion of 1.9 X 10(9) - 1.5 X 10(10) lymphocytes from the parents to the patients produced a significant decrease of the cytotoxic effect of the lymphocytes from the patients. This effect could be demonstrated during the preliminary control period up to 12 weeks.

Adolescent↗
PubMed1986

[Clinical value of the determination of TSH-binding inhibitory immunoglobulins (TBII) by a radioreceptor assay].

The aim of the present study was to evaluate the clinical value of a commercial kit for determination of TBII. The study consisted of 50 patients with untreated Graves' disease, 21 patients with Graves' disease before und during medical therapy, 18 patients after finishing medical therapy and 10 patients after surgical treatment. Besides these, 41 patients with other thyroid diseases and 36 patients without any thyroid disorder were included. In 47 (94%) of 50 patients with untreated Graves' disease TBII were detectable in serum using a TSH-standard-curve. Binding activities exceeding 10 U/l TSH equivalents were regarded as positive. In other thyroid diseases TBII were negative with the exception of 3 of 22 patient with autonomously functioning thyroid nodules. After 12 months of antithyroid drug treatment of 19 patients the incidence of positive antibody findings was 26%. During follow-up after medical therapy (1-9 years) 7 of 18 patients had increased TBII in correlation with clinical and functional findings. The determination of TBII by TRAK-Assay proved to be a sensitive and specific method. The assay can be used to differentiate between hyperthyroidism of autoimmune or non-immunogenic origin. Even so this method seems to be helpful for the follow-up under medical treatment of patients with Graves' disease.

Autoimmune Diseases↗
PubMed1986

[The synthesis of 3-amino-5-(4-pyridinyl)-1,2-dihydropyrid-2-one (Cordemcura) from a technical mixture of pyridines].

For preclinical and clinical research the headline compound 6 has been synthesized from pyrid-4-yl-malondialdehyde (3) and its bis-N,N-dimethyl)-aldimin-derivative 1 by cyclization with cyanoacetamide giving 4, partial hydrolysis to the amide 5, and degradation by sodiumhypochlorite to the amine 6, concerning to the way described in patent literature. Starting product was a mixture of alkyl pyridines from which 4-picoline reacted selectively with the Vilsmeyer-complex of phosgene/DMF to give cristalline 1. Optimization in all steps resulted in a procedure that gives us the intermediates in good yields and qualities and the final product 6 with high purity, suitable for pharmaceutical use.

Aminopyridines↗
PubMed1985

[Bromocriptine treatment of hyperprolactinemia].

In 36 female patients with microprolactinoma was carried out a primary therapy and in 19 patients (10 males, 9 females) with a postoperatively persisting hyperprolactinaemia a secondary therapy with bromocriptine. In close correlation between the PRL-levels and the bromocriptine dose we achieved a normalisation of the hormone levels in the microprolactinomas. A normalisation of the cycle was observed in 80%, a persisting of the galactorrhoea in about 90% and a conception in nearly two thirds of the women. Also in those patients who underwent a secondary therapy in nearly 80% a decrease of the PRL-levels into the normal region developed. In a longterm therapy with bromocriptine a reduction of the dose may become possible, so that controls of the hormone levels are necessary in larger intervals. Most side effects of a bromocriptine treatment are transitory.

Adenoma↗
PubMed1985

[Effect of sodium salicylate on insulin secretion and blood glucose behavior in metabolically healthy and type II diabetic patients].

The influence of Sodium-salicylate on insulin secretion and blood glucose behaviour was examined in 6 metabolic healthy persons and 9 type II-diabetics. Insulin secretion and blood glucose were twice examined under a combined stimulation with 100 g glucose (orally), 0.33 g glucose (Bolus injection) and 1.0 mg glucagon (i. v.) with and without a simultaneous infusion of Sodium salicylate during the whole period of examination (40 mg over 120 min). Sodium salicylate effected in type II-diabetics and metabolic healthy persons higher insulin levels. Qualitative differences of the insulin secretion pattern were not to be seen. In spite of higher insulin levels blood glucose was not influenced by Sodium salicylate. It is discussed if the results could be explained by a direct effect of Sodium salicylate on the cells ore on the metabolism of insulin and the gluconeogenesis.

Blood Glucose↗
PubMed1985

[New derivatives of 10,11-dihydro-5H-dibenz[b,f]azepine with antiarrhythmic action].

After an introduction about the importance of the 10, 11-Dihydro-5H-dibenz[b,f]azepine system for the drug research and according to experiences about the change of pharmacodynamic effects in the field of the phenothiazine bases by dialkylaminoacyl substitution in the following report some new 3-carbalkoxyamino-5-omega-aminoacyl-10,11-dihydro-5H-dibenz[b,f]++ +azepines and their intermediates for synthesis are described. In result of pharmacological investigations which showed antiarrhythmic activities the substance 3-carbethoxyamino-5-dimethylaminoacetyl-10,11-Dihydro-5H-dib enz[b, f]azepine X HCl (GS 015, AWD 19-166, Bonnecor) was selected for clinical tests. For studying the biotransformation of this substance the expected main metabolites were prepared by chemical synthesis.

Animals↗
PubMed1984

[The thyrotropic function of the hypophysis and peripheral thyroid hormones after removal of bland and autonomous nodular goiters].

Bilateral subtotal resection or enucleation or unilateral resection was performed in 60 patients (36 with bland nodular goitre, 24 with autonomic adenoma). The thyrotropic pituitary activity and the peripheral thyroid function were examined in all patients preoperatively and followed up for 12 months postoperatively. The results show that all patients with bilaterally resected bland nodular goitre require postoperative administration of thyroid hormone, since enhanced thyrotropic activity is seen not later than three months after surgery. Since thyrotropic function remains normal in unilaterally operated nodular goitre, thyroid hormone administration does not appear generally necessary. In patients with autonomic adenoma there is postoperatively variability of function, independent of the surgical method employed. In view of possible functional recompensation, final decision on the administration of thyroid hormones should not be made before the end of the sixth postoperative month. These results can be considered as guidelines for a differentiated postoperative management.

Goiter, Nodular↗
PubMed1984

[Operative findings and therapeutic results in patients with primary hyperparathyroidism].

In the period from 1976 to September 1982 39 patients with the clinical diagnosis of primary hyperparathyroidism were operated on. Among then were 24 women and 14 men. The most frequent manifestation form is the renal one (n = 26). The proportion of patients with hypercalcaemic crisis was very large (n = 4). Topographically and anatomically the adenomas were most frequently found in the region of the right lower pole of the thyroid gland. 23 patients had a singular adenoma, 11 patients showed multiple adenomas and only 2 had a diffuse hyperplasia. In patients with persisting hyperparathyroidism before a repeated intervention an attempt of localization should be performed by a selective phlebography with taking of blood samples for the determination of PTH. The success of the operation is to be read off most clearly at the behaviour of the post-operative values of serum calcium. In 29 patients a normocalcaemia was achieved. 6 patients showed at first a hypocalcaemia, which however, was only temporary in 4 patients. 3 patients had a persisting hyperparathyroidism. In accordance with the literary data the formation of renal calculi clearly decreased after a successful operation.

Adenoma↗
PubMed1984

Simultaneous biochemical and morphological investigations on the effect of leukocytes from type I diabetics on isolated rat islets.

The first morphological and biochemical findings on the effect of leukocytes from a newly diagnosed type I diabetic patient on isolated rat islets are presented. Leukocytes from venous blood were co-incubated with isolated neonatal rat islets for 22 h. According to the biochemical and electron-microscopical findings, beta cells localized in the periphery of the islets and a few single beta cells show lytic alterations (single cell necroses). The electron micrographs suggest that the beta cells were lysed after contact with lymphocytes or lymphoid cells from the diabetic patient (target cell reaction). The simultaneous biochemical and morphological investigations reveal that after beta cell lysis, insulin released in a granular state can be phagocytosed by granulocytes and thus escape the estimation of insulin concentration in the medium.

Animals↗
PubMed1984

[Glucose tolerance and insulin secretion in relation to age in type-II diabetes--a contribution to the pathogenesis of type-II diabetes mellitus].

It is reported on investigations carried through between age at manifestation of a type II diabetes and stimulated insulin secretion. In a group of 130 recently manifested diabetics and non selected diabetics no differences between insulin secretion, stimulated by glucose (orally given) and glucagon could be found when we compared the resulted in dependence on the age. Patients were grouped in four classes of age: less than 50, 51 less than or equal to 60, 61 less than or equal to 70, greater than 70. Similar results of insulin secretion were to be seen as well in a group of diabetics, selected at random, when glucose-, tolbutamide- and glucagon stimulation of insulin secretion were evaluated as in patients first examined after longer diabetes duration (about 6,5 years, n = 51). The entire insulin secretion after all three stimuli was nearly identical with those of probands, who were examined immediately after the manifestation and 5 years later (n = 34). In diabetics both in investigations at the manifestation of the disease and after prolonged diabetes and in follow-up studies wee found no hints, that with progressing age and disease a reduction of insulin secretion in the type II develops. These findings contradict the assumption that a permanent hyperglycemic stimulus provokes a gradual loss of the B-cell function. With the manifestation of the disease already a change of the B-cell function seems to exist which remains constant in nearly the same degree. A possibly concomitant physiological process of aging evidently does not significantly influence the remaining function of the B-cells. The disturbed insulin secretion and the insulin resistance in type II diabetes seem to processes developing in parallel, which are being on the same pathogenetic principle.

Aged↗
PubMed1984

[Long-term course of type I-simulating type II-diabetes mellitus].

In only few cases of primarily non- insulin-dependent diabetes mellitus after many years an absolute insulin dependency can develop. Within 5000 patients of a diabetic outpatient clinic in 2 years this happened in 21 patients. These patients offered a C-peptide-secretion after stimulation which was typical for an insulin dependent diabetes. The investigation of HLA-frequencies showed a marked increase of the DR 3 und DR 4 loci. These results demonstrate that obviously the genetically as type I characterized diabetes may appear clinically in the picture of type II-diabetes for many years. This must be taken in consideration in therapeutic or epidemiologic questions.

Blood Glucose↗
PubMed1984

[Electron microscopic findings in A-cells of the islands of Langerhans in diabetes mellitus].

A description is given of the electron microscopic-morphometric findings obtained for the islets of Langerhans of the pancreas and for the glucagon-producing A cells of one patient suffering from longstanding insulin-dependent diabetes mellitus (IDDM, type I diabetes), two patients with longstanding insulin-independent diabetes mellitus (NIDDM, type II diabetes), and one non-diabetic. A morphometric determination of the volume densities of the vascular connective tissue and the various endocrine cells per islet tissue and organelles/ultrastructures per A cell was made, and the diameters of the A-granules were measured. So far, no such studies have been made for human diabetes mellitus, and only a few are available for humans with sound metabolism. In general, the qualitative and, particularly, the quantitative electron microscopic results found for the IDDM patient show greater and clearer deviation from the control with normal metabolism than the findings obtained for the NIDDM patients. As regards the cellular composition of the pancreatic islets and changes caused by diabetes mellitus, the morphometric values obtained from electron micrographs are in essential agreement with comparable findings reported in the literature for light microscopic-histochemical and -immunohistochemical morphometry. The patient with insulin-dependent diabetes has a higher proportion of vascular connective tissue in the pancreatic islets than the non-diabetic. This increase is both relative and absolute and is primarily connected with the loss of B cells in this type of diabetes. In the IDDM patient, A cells were found in the islets but also scattered as single cells in the exocrine tissue and in the walls of pancreatic ductules. The ultrastructural composition of the A cells varies within wide limits even in persons with sound metabolism. Diabetes mellitus does not cause major qualitative alterations in the A cells. The A cells of the IDDM patient contained a remarkable number of nuclei and rarely showed A-granule crinophagia. The casuistic electron microscopic findings, most of which have been obtained for the first time, are discussed. Nothing can be said at this stage about the general applicability of the findings. The morphometric results obtained for the A cells can be interpreted as indicating increased metabolism with heightened glucagon synthesis and secretion in the case of the insulin-dependent diabetic and, to a lesser extent, in the NIDDM patients. This interpretation would support the assumption of a normally existing mutual local paracrine regulation of the A and B cells which stems from close topographical relations (contact, gap junctions).

Adolescent↗
PubMed1983

[Thyrostatic therapy of hyperthyroidism with special reference to drug side effects].

In discussing undesirable therapy effects by thyrostatics one must issue from the fact that the possible side effects have a different genesis and appear in different frequency. While pharmacodynamically caused therapy effects are generally to be avoided, when considering the pathophysiology of the regulation of the thyroid gland, this is not the case as to allergic side effects and only to a limited extent with regard to toxic side effects. Allergic side effects abruptly and suddenly appear and do not show any dependence on dosage. But for the greater part these side effects are harmless. Severe side effects are nearly without exception of toxic genesis. The decrease of the initial dose and the early transition to a still effective maintenance dose reduce the possibility of toxic complications. In case that side effects lead to a discontinuation of the corresponding thyrostatic, a change to a thyrostatic of another chemical group is possible and necessary.

Antithyroid Agents↗