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Biomedical subjects

G Leb

Publications and source records attributed to G Leb.

At least 55 records · Page 3Linked to original sources

Enhancing in vivo effect of propranolol on human lymphocyte function is not due to stereospecific beta-adrenergic blockade.

Immunoenhancing in vivo effects of beta-adrenergic blockers have been previously ascribed to a reduced beta-receptor-mediated immunosuppression. In the present study using a whole blood stimulation assay, the effects of a five-day treatment with the purified (R)- or (S)-isomer of propranolol (3 x 40 mg/day) on the polyclonal in vitro responsiveness of peripheral blood lymphocytes (PBL) of normothyroid and hyperthyroid persons were assessed. It is shown that both isomers likewise exhibit a significant enhancing effect on the proliferative response of PBL to T and B cell mitogens, which strongly argues for nonspecific effects of propranolol to be responsible rather than a specific beta-adrenergic receptor blockade.

Adult↗

Expression of various MHC class II molecules and of intracellular adhesion molecule-1 (ICAM-1) on focal clusters of dendritic cells in iodine deficiency goitres.

Thyroid sections from 18 consecutive euthyroid patients undergoing surgery for iodine deficiency goitre were investigated by means of immunohistochemistry and immunofluorescence, evaluating the expression of MHC class II antigens (HLA-DR, -DP, -DQ, and RFD1) and intercellular adhesion molecule-1 on the formerly described clusters of dendritic cells, as well as on thyrocytes. Eleven of 18 iodine deficiency goitres contained clusters of dendritic cells. These clusters appeared to express only HLA-DR in two cases; in nine of 12 cases they showed a differential expression of class II molecules in the following frequency: HLA-DR > DQ and/or -DP > RFD1. These dendritic cells also were ICAM-1+. In four of 18 iodine deficiency goitres, thyroid epithelial cells showed MHC class II expression in several combinations, but were ICAM-1-. In normal thyroids and in nodular goitres from inhabitants of the endemic area not having an actual iodine deficiency, only sparse clusters of dendritic cells were found; these cells were only HLA-DR+. Follicle lining cells were negative for the MHC class II molecules. In normal thyroids from an area with sufficient iodine supply, no clusters of dendritic cells were seen. The few dendritic cells observed were lying isolated in the interstitium and only positive for HLA-DR and ICAM-1; epithelial cells were negative for the studied markers. These data show clusters of dendritic cells in thyroids of inhabitants of an endemic area. When goitre is accompanied by iodine deficiency at the moment of operation, there appears to be activation of these dendritic cells and of thyroid epithelial cells.

Adult↗

The effect of treatment with levothyroxine or iodine on thyroid size and thyroid growth stimulating immunoglobulins in endemic goitre patients.

OBJECTIVE: We assessed the effect of levothyroxine or iodine on thyroid size and on thyroid growth stimulating immunoglobulins in endemic goitre patients. DESIGN: Levothyroxine or iodine was given orally in an open randomized prospective study (100 and 200 micrograms respectively). PATIENTS: Thirty-seven euthyroid patients with diffuse iodine deficiency goitres and thyroid growth stimulating immunoglobulins were studied. MEASUREMENTS: Thyroid size, thyroid growth stimulating immunoglobulins (mitosis arrest assay), basal TSH, free T3, free T4, thyroid anti-microsomal antibodies, antithyroglobulin antibodies, anti-TSH receptor antibodies and urinary iodine excretion were measured. RESULTS: Thyroid size decreased significantly in both groups, in the levothyroxine group more than in the iodine treated group. Thyroid growth stimulating immunoglobulins levels also decreased significantly in both groups. Between groups there was no statistically significant difference. A statistically significant correlation between thyroid growth stimulating immunoglobulins reduction profiles and goitre size reduction could not be established. TSH levels became suppressed in the levothyroxine group while the T4 values rose; in the iodine treated group TSH levels stayed constant as did T4. None of the patients developed thyroid microsomal or thyroglobulin auto-antibodies and/or hyperthyroidism during the treatment. CONCLUSIONS: Levothyroxine as well as iodine was effective in reducing thyroid size as well as thyroid growth stimulating immunoglobulins levels in endemic goitre patients. Since in both groups TSH levels were not related to thyroid size reduction, other factors than TSH suppression must be responsible for the observed thyroid size reduction. Iodine itself by virtue of its antiproliferative action on thyrocytes may have had a direct action on the goitre reduction during iodine treatment; however, the levothyroxine dose, containing less iodine, had a similar effect. A complicated picture hence emerges with regard to factors involved in the shrinkage of iodine deficiency goitre during thyroxine or iodine therapy. These findings indicate that TSH and thyroid growth promoting immunoglobulins are not the only influences on the size of endemic goitres, although it cannot be excluded that these two factors contribute to influence the pathogenetic process.

Antibodies↗

[Clinical value of the various methods of ACTH determination].

We determined 293 plasma-ACTH levels out of 49 patients. In 12 patients with various pituitary diseases 168 samples were collected during a standardized pituitary stimulation test. For this purpose we used the following kits: the DYNOtest ACTH and LUMItest ACTH and Allegro HS-ACTH test. Additionally, morning ACTH levels were analyzed from 49 patients using Allegro HS ACTH test and DYNOtest ACTH. Regarding ACTH concentrations during pituitary stimulation the clinical usefulness of the 3 named tests were comparable. Pair differences of morning ACTH levels were not statistically significant. In a setting of a wide range of ACTH levels all 3 trials proved appropriate for making a diagnosis. Practicability of all 3 tests was similar. For all 3 methods incubation can be done overnight which saves time. Reagents can be reused when frozen immediately after reconstitution.

Adrenocorticotropic Hormone↗

[Primary and follow-up studies of patients with carcinoid metastases using indium 111 octreotide--rational use of Sandostatin].

Carcinoids may express Somatostatin receptors. Therefore, a Somatostatin-analogue, In-111 Octreotide (OctreoScan), was used for their demonstration. A total of 6 patients who presented with radiologically verified carcinoid-metastases was examined. In order to control tumor progress, 4 of these patients were reexamined within a period of 3 to 11 months. All of the radiological findings were confirmed scintigraphically, except some small retroperitoneally located lymph nodes. The follow-up examinations of 2 patients revealed additional metastases by scintigraphy only. There were no false positive results. The results of OctreoScan scintigraphy may be used for predicting the success of receptor-specific therapies and therefore, permit the rational and efficient application of Sandostatin.

Aged↗

Successful treatment of primary adrenal insufficiency due to malignant non-Hodgkin's lymphoma.

Although the adrenal glands are frequently the site of tumor metastases, adrenal insufficiency is exceedingly rare. We report on a patient with high-grade B-cell centroblastic lymphoma who initially presented with right axillary lymphadenopathy and bilateral adrenal masses. Four months after axillary lymphadenectomy the patient developed overt signs of Addison's disease. He recovered promptly after initiation of hormone replacement therapy and bilateral adrenalectomy. At present, 16 months after additional chemo- and radiation therapy the patient is considered free of tumor. To our knowledge this is the first report on a patient who presented with adrenal insufficiency in the course of non-Hodgkin's lymphoma and who was successfully treated. Demonstrating this case, we would also like to stress that the development of adrenal insufficiency does not necessarily indicate widespread tumor manifestation in patients with non-Hodgkin's lymphoma.

Adrenal Cortex Hormones↗

Involvement of the immune system in iodine deficient goiter.

Iodine deficient goiters were studied by immunohistochemistry and showed extensive presence and typical arrangement of dendritic cells, known to have excellent antigen presenting capacity. These cells were positive for all MHC-class II epitopes and for ICAM-1. Epithelial follicle lining cells were also seen to be class II positive but lacked ICAM-1. Thyroglobulin seemed not to be iodinated at the C-terminal hormogenic site, as shown by reactions with monoclonal antibodies. Iodine therapy, as well as thyroxine therapy were effective in reducing thyroid size. Both forms of therapy were found to decrease the pretreatment levels of circulating thyroid growth stimulating immunoglobulins (TGI).

Antibodies, Monoclonal↗

Skin lesions in carbon monoxide intoxication.

A 25-year-old man who survived carbon monoxide intoxication presented erythematous cutaneous lesions with blister formation in pressure areas. Histologic examination revealed subepidermal vesicles with extensive sweat gland necrosis. We discuss the clinicopathological findings of carbon monoxide poisoning. Similar cutaneous features have been observed in patients with various kinds of drug-induced coma.

Adult↗

Chromatographically purified immunoglobulin G of endemic and sporadic goiter patients stimulates FRTL5 cell growth in a mitotic arrest assay.

A strain of differentiated rat thyroid cells (FRTL5) in continuous culture was used to study the presence of thyroid growth-promoting immunoglobulins (TGI) in the serum of patients with endemic and sporadic euthyroid goiters. To identify true in vitro cell proliferation a microscopic mitotic arrest assay was used. Immunoglobulins G (IgGs) were prepared with QAE-Sephadex A-50 or protein-A-Sepharose. A positive growth stimulation index was found in IgG preparations of 65 of 71 patients with endemic goiter and in 9 of 14 IgG preparations of patients with sporadic goiter. IgG preparations of 15 control subjects from an area where endemic goiter due to iodine deficiency does not occur and of 18 subjects without iodine deficiency and without thyroid enlargement living in the endemic area did not stimulate FRTL5 cell growth. FRTL5 cell growth stimulation with IgGs of these euthyroid goiter patients could only be detected when IgG was tested in combination with a small dose of TSH. Immunoprecipitation with polyclonal and monoclonal antihuman IgG was able to abolish the growth-promoting effects. In 32 blinded samples the Feulgen cytobiochemical assay, formerly used to detect TGI, was compared with the FRTL5 mitotic arrest assay. The two methods showed similar results. Our observations of chromatographically purified IgG promoting thyroid cell proliferation in vitro provide good evidence that IgG was responsible for thyroid cell growth in vitro and suggest that autoimmune growth mechanisms may be involved in the pathogenesis of both endemic and sporadic goiters.

Adult↗

Thyroid growth promoting serum-IgG in endemic goiter.

In this study a strain of differentiated rat thyroid cells in continuous culture was used to detect the presence of thyroid growth promoting immunoglobulins (TGI) in IgG preparations of serum of patients with endemic and sporadic euthyroid goiters. TGI was detected when FRTL5 cells were used in a mitotic arrest assay by costimulating the cells with IgG and a suboptimal dose of TSH. TGI was present in 65 of 71 endemic goter cases and in 9 of 14 sporadic goiter cases.

Autoantibodies↗

Thyroid infiltrating dendritic cells, epitheloid cells and giant cells in iodine deficiency.

This study describes dendritic cells in thyroid sections of iodine deficient goiters. Cells were characterized by monoclonal markers and detected by immunohistochemistry and double labelling immunofluorescence. We observed dendritic cells located in focal aggregates in the interstitium and epitheloid cells as well as multinucleated giant cells filling thyroid follicles. All these cells showed strong positivity for the MHC class II molecules HLA-DR, -DQ, -DP and RFD1, a monoclonal marker for active antigen presenting cells.

Antigen-Presenting Cells↗

[Sonography and cytology of cold thyroid nodules].

270 patients with a scintigraphically cold thyroid nodule of sonographically increased (n = 34), diminished (n = 72) or neutral (n = 86) echogenity or cystic criteria (n = 78) were subjected to fine needle aspiration biopsy. This revealed unequivocal malignancy in 8 and follicular neoplasia in another 30 patients, 10 of whom proved to have malignomas on further evaluation. A total of 12 papillary and 2 follicular carcinomas, 2 non-Hodgkin lymphomas, 1 sarcoma and the metastasis of a breast carcinoma were diagnosed. The most sensitive criteria for malignancy were diminished echogenity, an inhomogeneous echo pattern and the occurrence of a solitary nodule. The incidence of malignancy was increased among males but not among especially young persons. There was no sonographic feature that would permit omission of fine needle aspiration.

Adenocarcinoma↗

Intrathyroidal dendritic cells, epitheloid cells, and giant cells in iodine deficient goiter.

Immunohistochemistry and immunofluorescence were performed on thyroid sections of 44 consecutive patients undergoing thyroid surgery for goiter due to iodine deficiency. Sections were compared with specimens from ten individuals without goiters from the same endemic area, with specimens from ten sporadic nontoxic goiter patients, and with specimens from an area with sufficient iodine supply from nine healthy subjects. Cells were characterized using monoclonal antibodies to the CR3 receptor (CD11b) and the p150/95 antigen (CD11c) present on macrophages, to HLA-DR, to antigen presenting cells (RFD1), to T helper (CD4) and to T suppressor/cytotoxic cells (CD8), and with a polyclonal antibody to human cytokeratin. In iodine deficient goiters, focal aggregates were found of RFD1-positive dendritic cells. Furthermore, RFD1-positive epitheloid cells were seen. In 27% of cases, these epitheloid cells completely filled the thyroid follicles. Within the epitheloid cell clusters, multinucleated giant cells could be detected that carried the macrophage markers. Dendritic cells, epitheloid cells, and giant cells were strongly HLA-DR positive. In nongoitrous thyroids from the endemic area such aggregates could also be seen but they were more sparse and were RFD1 negative. Giant cells were absent there. In normal thyroids with sufficient iodine supply, only a few isolated dendritic cells were seen. All except RFD1, which was negative, showed the same marker pattern. In sporadic nontoxic goiters from an area with sufficient iodine supply, dendritic cells occurred in much higher numbers than in the normal thyroids from that area, and they were RFD1 positive. They never aggregated as in iodine deficiency, and giant cells were not observed. These observations on iodine deficient goiter strongly suggest involvement of active antigen-presenting cells in this disorder. However, the immunohistologic difference between this disease and sporadic goiter suggests different underlying mechanisms.

Adult↗

Aclarubicin in advanced thyroid cancer: a phase II study.

Twenty-four patients with metastatic thyroid cancer were treated with aclarubicin intravenously at a dose of 25-30 mg/m2 daily for 4 days and treatment was repeated every 3 weeks. None of the patients had previously received chemotherapy. Twenty-three patients received two or more treatment cycles and were evaluated for their response. One complete remission and four partial remissions were noted (objective remission rate 22%). Mean survival time was 57 weeks. Side-effects were evaluated in 24 patients with 18 patients receiving prophylactic antiemetic therapy. Nausea was observed in 18 (75%) and vomiting occurred in three patients (13%). In 15 patients (63%) there was mild myelosuppression. We conclude that aclarubicin alone represents an effective therapy in patients with metastatic thyroid cancer and that side-effects are minor.

Aclarubicin↗

[Relation of neopterin and beta 2 microglobulin to disease activity in chronic polyarthritis].

The correlations of the serum levels of neopterin and beta-2-microglobulin with the disease activity-measured by a clinical index-were investigated in 41 patients suffering from rheumatoid arthritis. Both parameters correlated significantly with the sum of the used disease activity index. There was a closer correlation between the serum levels of beta-2-microglobulin and the sum of the index and most of the particular parameters of the index than it was seen for the neopterin serum levels.

Adult↗