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H Dralle

Publications and source records attributed to H Dralle.

At least 163 records · Page 9Linked to original sources
PubMed1995

Clinical significance of E-cadherin as a prognostic marker in thyroid carcinomas.

The aim of this study was to evaluate the expression of E-cadherin as a potential marker for the prognosis of thyroid carcinomas. In normal thyroid (n = 8), the expression of E-cadherin messenger ribonucleic acid levels was uniformly high and seemed to be restricted to thyrocytes. Steady-state messenger ribonucleic acid levels and immunostaining were both completely lost in undifferentiated thyroid carcinomas (n = 7) and were variably reduced in differentiated thyroid carcinomas (n = 44). In a follow-up study during a mean of 4.5 +/- 1.4 yr, E-cadherin messenger ribonucleic acid and immunohistochemical expression were compared with the initial clinicopathological parameters and with locoregional recurrence and the development of nodal or distant metastases in differentiated thyroid carcinomas. Immunohistochemical expression of E-cadherin was greatly reduced with the progression to primary tumor stage 4 (pT4) tumors. In parallel, patients with pT4 tumors had a higher rate of locoregional tumor recurrence and distant metastasis than did the group of patients with pT1-3 tumors. In 5 of 29 patients with pT4 tumors, positive E-cadherin staining of more than 30% of the cells was detected. None of these patients showed signs of a regional recurrence or distant metastases during an observation period of 4.3 +/- 1.1 yr. In 13 patients with E-cadherin-positive tumors, none developed new distant metastases which was in contrast to 7 of the group of 31 patients with less than 30% E-cadherin-positive cells. Thus, E-cadherin expression seems to be associated with the dedifferentiation, progression, and metastatic spread of thyroid carcinomas and may be a useful marker for the prognosis of these tumors.

Adenocarcinoma, Follicular↗
PubMed1995

Functional and morphological changes of the thyroid gland following 5 days of pulsatile TRH stimulation in male rats.

The aim of the present study was to evaluate in vivo the selective effects of a small increase in plasma TSH levels on thyroid function, proliferation and morphology. Chronically catheterized male Sprague-Dawley rats were stimulated i.v. over 5 days either with TRH (2 micrograms TRH in 100 microliters 0.9% (w/v) NaCl (TRH-P) or the NaCl carrier alone (P), both given as pulses every 2 h. Control groups were cotreated i.v. with 10 micrograms thyroxine (T4)/100 g body weight per day (TRH-P + T4) starting 2 days before pulsatile stimulation. TSH plasma levels were approximately doubled by TRH-P (P < or = 0.001), T4 plasma levels significantly increased (P < or = 0.001) but tri-iodothyronine plasma levels did not change compared with treatment with P. No significant changes between groups were found in thyroid weight and in intrathyroidal iodine content, but the percentage of 5-bromo-2'-desoxyuridine-labelled thyrocytes as a marker of proliferation in TRH-P-treated animals was significantly increased over P or TRH-P + T4 (P < or = 0.001). Ultrastructural analysis of the thyroid evaluated by electron microscopy revealed a significant increase in the number of lysosomes (P < or = 0.001). The size of the endoplasmic reticulum (ER) in relation to the cytoplasm was significantly increased when treated with TRH-P compared with P or TRH-P + T4 (P < or = 0.001). Post-embedding immunogold staining revealed Tg as a major product within ER cisternae. Immunogold labelling was moderate in controls and higher densities of gold particles were obtained in TRH-P-treated animals (P < or = 0.001). In conclusion, short-term pulsatile TRH stimulation increasing the plasma levels of immunoreactive TSH only twofold is capable of inducing hypertrophy of the thyrocytes by gross ultrastructural changes which are paralleled by an increase in circulating T4. These data underscore the dominant role of TSH on thyroid ultrastructure within the narrow boundaries of normal physiological regulation.

Animals↗
PubMed1995

[Diagnostic measures before laparoscopic cholecystectomy].

Successful use of laparoscopic cholecystectomy requires good cooperation between surgeon and gastroenterologist. Standard preoperative workup includes detailed history of the patient, blood chemistry of serum bilirubin and liver enzymes as well as sonography for the detection of common bile duct stones. Intravenous cholangiography can be performed to diagnose anatomic variations of the bile ducts. In case of common bile duct stones "therapeutic splitting" by endoscopic retrograde cholangiography with sphincterotomy and gallstone extraction preoperatively may help to avoid unnecessary conventional open cholecystectomy.

Cholangiography↗
PubMed1995

Metabolism of the immunosuppressant tacrolimus in the small intestine: cytochrome P450, drug interactions, and interindividual variability.

The small intestinal metabolism of tacrolimus, which is used as an immunosuppressant in transplantation medicine, was investigated in this study. Tacrolimus was metabolized in vitro by isolated human, pig, and rat small intestinal microsomes. The metabolites generated were identified by HPLC/MS. Tacrolimus and its metabolites were quantified using HPLC or HPLC/MS. The cytochrome P450 (CYP) enzymes responsible for tacrolimus metabolism in small intestine were identified using specific CYP antibodies and inhibitors. For characterization of the interindividual variability, microsomes were isolated from small intestinal samples of patients who had undergone resection for various reasons. In an in vitro model using pig small intestinal microsomes, 32 drugs were analyzed for their interactions with tacrolimus metabolism. After incubation with human, rat, and pig small intestinal microsomes, the metabolites 13-O-demethyl and 13,15-O-demethyl tacrolimus were identified. The metabolism of tacrolimus by human small intestine was inhibited by anti-CYP3A, troleandomycin, and erythromycin, indicating that, as in the liver, CYP3A enzymes are the major enzymes for tacrolimus metabolism in the human small intestine. Metabolism of tacrolimus by small intestinal microsomes isolated from 14 different patients varied between 24 and 110 pmol/13-O-demethyl tacrolimus/min/mg microsomal protein, with a mean +/- SD of 54.2 +/- 29.2 pmol/min/mg. Of 32 drugs tested, 15 were found to inhibit small intestinal tacrolimus metabolism: bromocryptine, corticosterone, cyclosporine, dexamethasone, ergotamine, erythromycin, ethinyl estradiol, josamycin, ketoconazole, nifedipine, omeprazole, progesterone, rapamycin, troleandomycin, and verapamil. All of these drugs inhibited tacrolimus metabolism by human liver microsomes as well. It is concluded that tacrolimus is metabolized by cytochrome CYP3A enzymes in the small intestine. The rate of the CYP3A enzymatic activities varies about 5 times from patient to patient, and drugs that interfere with the in vitro metabolism of tacrolimus in the liver also inhibit its small intestinal metabolism.

Animals↗
PubMed1994

[Symptoms and endocrinologic features of catecholamine-secreting tumors. Results in 106 consecutive patients].

The clinical and endocrinological features in 106 patients (40 men, 66 women, mean age 48 +/- 14.3 years) treated between 1973 and 1993 for proven catecholamine-secreting tumours (phaeochromocytoma: n = 88, paraganglioma: n = 10, adrenal medullary hyperplasia: n = 8) were analysed. The most frequent symptoms were palpitations (68%), severe sweating (53%) and headache (42%). 10% of patients were symptom-free. 58% of patients had consistently raised blood pressure, and 20% of patients suffered paroxysmal blood pressure crises. However, 22% of patients did not have hypertension. Raised urinary catecholamines were found in more than 95% of cases; MIBG (metaiodobenzylguanidine) scintigrams were abnormal in more than 85% of cases. Patients with catecholamine-secreting tumours do not always have "classical" features. The high sensitivity of properly performed catecholamine measurement on plasma and urine has made dangerous stimulation and suppression tests obsolete.

Adolescent↗
PubMed1994

Western blot analysis of thyrotropin receptor expression in human thyroid tumours and correlation with TSH-binding.

Expression of thyrotropin receptor (TSHr) was analyzed in normal human thyroids and differentiated thyroid tumours by Northern blotting of total RNA and by Western blotting of detergent-solubilized membrane proteins with an antibody specific for the extracellular domain of TSHr. Under nonreducing conditions TSHr stained as a 90-kDa protein in normal thyroid tissue. Expression varied in differentiated carcinomas from normal to not detectable in parallel to steady state TSHr mRNA levels and TSH binding in a TSH binding assay. The negative expression of TSHr in some patients with differentiated carcinomas may have consequences for the TSH suppressive treatments of these patients.

Binding Sites↗
PubMed1994

MHC class I molecule-restricted presentation of viral antigen in beta 2-microglobulin-deficient mice.

Normally, Ag is presented to CD8+ T lymphocytes as a tripartite complex consisting of peptide epitope, MHC-encoded class I heavy (alpha) chain, and beta 2-microglobulin (beta 2-m) light chain. Although there is agreement about the function of both peptide and alpha-chain, the role of beta 2-m has remained uncertain. In particular, can Ag be presented without its participation? We have sought to obtain an answer by using mice in which the gene for beta 2-m had been disrupted by homologous recombination. As a consequence, no light chains are synthesized and, furthermore, few if any CD8+ T lymphocytes are formed. Elimination of lymphocytic choriomeningitis (LCM) virus from the tissues of acutely infected mice is mediated solely by CD8+ T lymphocytes; hence, in the beta 2-m-lacking mutants the infection cannot be terminated. Here it is shown that infusion of immune spleen cells from syngeneic beta 2-m+/+ mice and from mice compatible in K or D of the MHC resulted in virus clearance. Approximately five times more cells were required to achieve antiviral effects in beta 2-m-deficient than in wild-type mice but attempts to improve elimination by treatment of the former with IFN-gamma or beta 2-m have failed. Depleting the immune splenocytes of CD8+ T lymphocytes but not of CD4+ T lymphocytes abolished the antiviral potential. We conclude that LCM virus-infected murine cells can present viral Ag to CD8+ effector T lymphocytes together with class I MHC molecules K and D, despite the total absence of beta 2-m.

Animals↗
PubMed1994

Compartment-oriented microdissection of regional lymph nodes in medullary thyroid carcinoma.

Lymph node metastases have been proven to be the main prognostic factor in medullary thyroid carcinoma (MTC). This retrospective study was undertaken to evaluate the efficiency of two surgical techniques of regional lymph node dissection with regard to the normalization of pentagastrin-stimulated serum calcitonin level and patient survival: selective lymphadenectomy, i.e., the excision of macroscopically or microscopically involved lymph nodes, versus a systematic lymphadenectomy performed by the new technique of a compartment-oriented microdissection. From 1970 to 1990, 82 patients with sporadic (n = 57) and hereditary (n = 25) MTC underwent a total of 142 operations including 63 selective lymphadenectomies and, since 1986, 35 systematic lymphadenectomies. The study revealed that in node-positive MTC the rate of interventions with a postoperative normalization of pentagastrin-stimulated serum calcitonin was higher after systematic lymphadenectomy (29.2%) than after selective lymphadenectomy (8.5%) (P < 0.01). The rate of patients undergoing repeat surgery due to a recurrence of MTC was 48% after selective lymphadenectomy and 10% after systematic lymphadenectomy. Survival was significantly better for patients after systematic versus selective lymphadenectomy (P < 0.005). This study thus emphasizes that systematic lymphadenectomy, using the technique of a compartment-oriented microdissection of cervicomediastinal lymph nodes, represents the preferred surgical treatment as well as the optimum technique in primary as well as secondary node-positive MTC.

Adolescent↗
PubMed1994

[Mediastinal tumor and airway obstruction in general anesthesia. Case report and review of the literature].

Case report of an acute airway obstruction during general anaesthesia by compression of the left main bronchus in an asymptomatic patient with unknown mediastinal mass. The patient was scheduled for a relief of a thyroid gland cyst. The compression occurred after uneventful induction of anaesthesia during the patient's positioning with flexed neck and elevated upper thorax on a pad. Increasing FiO2 from 0.5 to 1.0, repeated fiberoptic bronchoscopic examination and changing of the position of the endotracheal tube facilitated the operation. After reversal of the flexed neck position ventilation was normal. The intraoperatively suspected mediastinal tumour was confirmed by postoperative computerised tomography of thorax and neck. The teratoma was removed in toto in a second operation. In a review of the literature pathophysiological changes, preoperative assessment and anaesthetic management of patients with mediastinal tumour are discussed.

Adult↗
PubMed1994

Thyrotropin receptor and leukocyte adhesion molecules in autoimmune thyroid disease: a study of their gene expression by northern blot analysis and in situ hybridization.

In order to characterize the role of leukocyte-activating antigens and other immunological parameters in autoimmune thyroid disease, mRNA levels of intercellular adhesion molecule 1 (ICAM-1), endothelial leukocyte adhesion molecule 1 (ELAM-1, E-selectin), invariant chain (Ii) and the thymic hormone thymosin beta (T beta 4) were investigated in 18 human thyroid glands, including eight Graves' thyroids, two Hashimoto's thyroids, two endemic goiters and six healthy controls. Northern blot analysis showed that in autoimmune thyroid disease, expression of ICAM-1 and T beta 4 was correlated to transcript levels of Ii, whereas in the healthy controls, expression of T beta 4, ICAM-1 and ELAM-1 was low or nearly absent. ELAM-1 and TSH receptor (TSH-R) expression, the latter serving as a thyroid specific marker, was increased in some diseased gland but showed no relation to the immunological parameters mentioned above. Localization of the specific mRNAs by in situ hybridization demonstrated a cell-specific expression of TSH-R (thyrocytes), ELAM-1 (vascular endothelial cells) and T beta 4 (cells of hematopoietic origin). In contrast, transcripts of Ii and ICAM-1 were found in thyrocytes, leukocytes and endothelial cells. Our results implicate a coordinate expression of ICAM-1, T beta 4 and Ii in autoimmune thyroid disease, yielding distinct cellular expression patterns. Differential expression of ICAM-1, Ii and the TSH-R in thyroid epithelial cells indicates active regulatory events within the thyrocyte.

Autoimmune Diseases↗
PubMed1993

E-cadherin: a differentiation marker in thyroid malignancies.

Loss of E-cadherin (uvomorulin), a Ca(2+)-dependent cell adhesion molecule required for normal epithelial function, has been attributed a pathogenetic role in tumor invasion. The expression of E-cadherin was studied in normal and neoplastic follicular epithelium of the human thyroid by Northern blot analysis and immunofluorescence on frozen tissue sections. In the normal thyroid (n = 10) and in benign thyroid disorders (n = 21; toxic diffuse goitre; multinodular goitre; follicular adenomas), E-cadherin mRNA levels were equally high and the follicles were generally stained, mainly along the lateral surface of the epithelial cells, by the anti-E-cadherin monoclonal antibody. In anaplastic thyroid carcinomas (n = 6) E-cadherin expression was very low or lacking. In papillary carcinomas (n = 23), E-cadherin mRNA levels varied from nearly normal to highly reduced, which roughly correlated with the overall immunofluorescence intensity. However, the immunostaining also revealed a heterogeneous "all-or-nothing" expression of E-cadherin among adjacent cells in the same tumor. In the follicular carcinomas (n = 9), E-cadherin mRNA levels were in general rather high but the immunostaining varied considerably. A few papillary and follicular tumors lacked immunoreactive E-cadherin in spite of high mRNA levels. In oxyphilic (Hürthle) cell tumors, comprising both adenomas (n = 4) and carcinomas (n = 2), E-cadherin immunoreactivity was reduced and distributed intracellularly rather than at the cell surface. The expression of E-cadherin in relapsing thyroid carcinomas and in tumors with metastatic spreading was, irrespective of the histiotype, low or lacking. Sequential Northern analysis revealed a close correlation between the expression levels of E-cadherin and the thyrotropin receptor. Together, the data suggest that in human thyroid malignancies both gene expression and posttranscriptional control of E-cadherin may be impaired.

Adenoma↗
PubMed1993

Expression levels of the thyrotropin receptor gene in autoimmune thyroid disease: coregulation with parameters of thyroid function and inverse relation to major histocompatibility complex classes I and II.

Using a human TSH receptor (TSH-R) cDNA probe, we investigated TSH-R transcript levels in 13 human thyroid fragments by Northern blot analysis; 7 Graves' disease, 2 Hashimoto's disease, 3 endemic goiter, and 1 healthy thyroid gland were studied. TSH-R expression levels were variable, but displayed a close correlation to the expression of thyroid peroxidase (r = 0.703; P < 0.05), thyroglobulin (r = 0.817; P < 0.01), and the nuclear oncogene c-fos (r = 0.935; P < 0.001), but not c-myc. Overall, TSH-R transcript levels were low or absent in those thyroids in which expression of the major histocompatibility complex class I or II (MHC I or II) was high, thus establishing an inverse relation (MHC I, r = -0.791; P < 0.01; MHC II, r = -0.784; P < 0.01). In situ hybridization showed that apart from lymphocytes, thyroid cells themselves were the source of MHC II transcripts. gamma-Interferon expression was only detectable in 1 Hashimoto's goiter. Our findings suggest that next to lymphocyte infiltration, active regulatory events in the thyrocyte are responsible for the inverse relation between functional parameters (TSH-R, thyroid peroxidase, thyroglobulin, and c-fos) and immunological markers (MHC I and II).

Adolescent↗
PubMed1993

[Diagnosis and surgical treatment of extra-adrenal pheochromocytoma].

From 1980 until 1991 10 patients were operated upon a paraganglioma: 5 patients with an encapsulated solitary tumor, two with infiltrating tumors and 3 with metastatic disease. The diagnosis of a catecholamine-producing tumor was most reliably made by norepinephrine analysis in urine and serum. The localization of the tumor was diagnosed in 9 of 10 cases by sonography and CT-scan. In 9 patients the tumor was excised completely, 4 times by extended resections. Whereas 4 out of 5 patients with an encapsulated solitary paraganglioma live to date without recurrence, all 3 patients suffering from metastatic disease had recurrent disease within one year postoperatively. A differentiated operative therapy of paragangliomas based on a clinical characterization is proposed: Encapsulated paragangliomas should always be excised. For solitary infiltrating tumors an extended resection may be necessary. This seems not to be justified for multiple infiltrating or metastasizing paragangliomas. Thus, only a reduction in size may be adequate for these tumors.

Abdominal Neoplasms↗
PubMed1992

[Trans-sternal cervico-mediastinal primary tumor resection and lymphadenectomy in thyroid gland cancer].

Thyroid carcinoma may invade the mediastinum by direct extension of the primary tumor or metastases to the paratracheal or retroclavicular-parajugular lymph nodes. From 1975 to 1991 in 47 out of 622 thyroid cancer patients (7.6%) [14 papillary (PTC), 5 follicular (FTC), 16 medullary (MTC) and 12 undifferentiated carcinoma (UTC)] transsternal tumor resection has been performed. Four patients (UTC three, MTC one) deceased 7, 8, 35, and 41 days after resection of the primary tumor due to cardiac or tumor disease, and in one patient because of acute arteriotracheal haemorrhage after external irradiation; no patient deceased after transsternal resection as a result of cervicomediastinal lymphadenectomy. At the time of primary operation 80% of patients showed an advanced tumor stage (greater than pT3). In 34% of patients (PTC 64%, FTC 40%, MTC 13%, UTC 25%) no tumor recurrence was observed neither by imaging nor by biochemical methods. In 18 patients a transsternal microdissection of all four cervicomediastinal lymph node compartments has been performed. Histological analyses of excised and tumor involved lymph nodes revealed in 9 patients unilateral cervical and mediastinal and in 9 patients bilateral cervical and mediastinal lymph node metastases. In the case of unilateral cervicomediastinal lymph node metastases 2 out of 2 patients with papillary and 2 out of 6 patients with medullary thyroid carcinoma could be cured surgically. In the case of bilateral cervicomediastinal lymph node metastases 3 out of 4 patients with papillary thyroid carcinoma, but no other thyroid cancer patient were free of disease. In conclusion, main indications for transsternal cervicomediastinal resection in thyroid carcinoma are (1) primary tumors extending to the upper mediastinum, but without lymph node metastases, and (2) thyroid carcinomas with unilateral cervicomediastinal lymph node metastases. In the case of bilateral cervicomediastinal lymph node metastases probable only papillary thyroid carcinomas are supposed to be curable by transsternal multicompartmentectomy.

Adenocarcinoma↗
PubMed1992

Immunocytochemistry in adrenocortical tumours: a clinicomorphological study of 72 neoplasms.

Surgical specimens of 72 adrenocortical tumours (ACTs) were investigated. Histologically, 57 tumours were classified as adenomas and 15 as carcinomas. In 9 of the latter cases, distant metastases and/or lethal outcome of disease was recorded. Immunocyto-chemistry showed only 2 ACTs to be positive for cytokeratin and 6 for vimentin. None of the 72 tumours showed argyrophilia or immunoreactivity for epithelial membrane antigen (EMA), S-100 protein, chromogranin A, Leu 7 or Leu-M1, while 31 cases exhibited positivity on immunostaining with a polyclonal antiserum against synaptophysin. All 72 ACTs were immunoreactive with the recently described antibody D11. Thus the panel of antibodies described here could not discriminate between adenomas and carcinomas or between carcinomas with aggressive and indolent behaviour. Immunostaining with D11 and for EMA and Leu-M1 may help to distinguish ACTs from phenotypically similar lesions of different histogenesis.

Adrenal Cortex Neoplasms↗