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Biomedical subjects

B Niederle

Publications and source records attributed to B Niederle.

At least 19 recordsLinked to original sources

Relationship of CD15 immunoreactivity and prognosis in sporadic medullary thyroid carcinoma.

Immunoreactivity with monoclonal antibody CD15 (Leu-M1) was investigated in the primary tumours, the metastases and local recurrences of 47 cases of sporadic medullary carcinoma of the thyroid (MTC). Of these tumours, 36.5% showed a varying degree of CD15 immunostaining; in 7 carcinomas the CD15 immunoreactivity was found to be significant (greater than 15% tumour cells positively stained). Staining of the amyloid stroma was observed in 3 tumours. Significantly higher epithelial CD15 positivity was seen more frequently in the group with larger tumours (greater than 4 cm) and was found exclusively in the presence of lymph node metastases. No substantial difference in the percentage of immunostained cells was seen between primary tumours and metastatic or recurrent lesions, except for two cases that revealed a significant increase in the number of CD15-immunostained cells in metastatic and recurrent lesions. Five of 7 patients with recurrences showing significant CD15 immunostaining died of cancer, while in the absence of significant CD15 staining all patients with recurrences were still alive at the conclusion of the study. The prognostic value of CD15 immunoreactivity, found by univariate analysis, becomes weaker after adjustment for the size and stage of tumour. Particularly in patients with tumour recurrences CD15 immunostaining may be of clinical relevance for the selection of patients in whom a more radical surgical approach would be justified.

Adult

The prognosis of rectal carcinoid tumours.

Carcinoid tumours of the rectum are very rare, and they may present special therapeutic problems for the surgeon. Tumour size and muscle layer invasion are the two most important factors predicting their malignant potential. A series of 20 patients with carcinoid tumours of the rectum were reviewed. 16 tumours less than 2 cm in diameter had neither muscle layer invasion nor lymph node metastases, with the exception of one tumour. Four patients with tumours larger than 2 cm died from metastatic carcinoid. In order to plan operative management endoluminal ultrasound should be performed preoperatively. Rectal carcinoid tumours should be treated like carcinomas of the rectum if they are 2 cm or more in diameter or if they demonstrate muscularis propria invasion independent of tumour size.

Adult

[Color-coded Doppler sonography of the thyroid: an advance in carcinoma diagnosis?].

There are several papers suggesting that colour-coded Doppler sonography is a useful diagnostic tool for the differentiation of malignant and benign lesions of the thyroid gland. This hypothesis (hypervascularization of malignant nodules) is reconsidered by preoperative examination of 65 patients by using colour-coded Doppler sonography and scintigraphy. Among these patients 21 carcinomas and 2 malignant lymphomas of the thyroid gland were found histologically. Colour-coded Doppler sonography was true positive in 10 cases, true negative in 28 cases, false positive in 14 cases and false negative in 13 cases. Our conclusion is that colour-coded Doppler sonography cannot be used unconditionally for the detection of carcinoma of the thyroid gland.

Adult

Insulin secretion, insulin sensitivity and hepatic insulin extraction in primary hyperparathyroidism before and after surgery.

OBJECTIVE: Primary hyperparathyroidism (pHPT) is associated with hypertension, hyperinsulinaemia, and insulin resistance. The present study investigated the causes of these metabolic disturbances by quantifying insulin sensitivity and glucose effectiveness, and by assessing the time course of beta-cell insulin secretion and hepatic insulin extraction, during a dynamic condition such as after an intravenous glucose load. In addition, we evaluated the possible link between metabolic disorders and high blood pressure. SUBJECTS: We studied 16 patients with pHPT, before and 12 weeks after parathyroidectomy; eight of these patients were re-evaluated one year after surgery. The control group consisted of 18 healthy volunteers. DESIGN AND MEASUREMENTS: All subjects underwent an oral and a frequently sampled intravenous glucose tolerance test. The data from the intravenous glucose tolerance test were analysed by means of the minimal model technique which yields relevant parameters to comprehend the metabolic status of the single individual. RESULTS: The glucose intolerance condition was characterized by a severely impaired insulin sensitivity in pHPT (3.2 +/- 0.5 vs 9.5 +/- 1.5 x 10(4)/min/(microU/ml) of control subjects; P < 0.001), as well as by a reduced glucose effectiveness, (0.02 +/- 0.002 vs 0.03 +/- 0.003/min of control subjects; P < 0.04). Total insulin secretion during the 4 hours of the test was almost twofold elevated in comparison to the control subjects (32795 +/- 4769 vs 16864 +/- 1850 pM, P < 0.004) and its basal component significantly correlated with the high blood pressure. Hepatic extraction of insulin was significantly increased in pHPT (85 +/- 2 vs 76 +/- 2%, P < 0.03), possibly as a compensatory mechanism of hypersecretion, which however did not prevent peripheral hyperinsulinaemia in pHPT. Patients with pHPT were divided into two subgroups with normal and impaired glucose tolerance. The patients with impaired glucose tolerance had a significant reduction of first phase insulin response, although their basal and stimulated insulin levels were higher. Tissue insulin sensitivity and glucose effectiveness did not significantly differ between the two subgroups. After surgery, all the biochemical parameters (former hypercalcaemia, hypophosphataemia, elevated parathormone levels) were normalized, insulin sensitivity significantly improved (6 +/- 1 x 10(4)/min/(microU/ml), P < 0.001), whereas glucose effectiveness remained completely unchanged. Basal and stimulated insulin responses were insignificantly lowered after surgery, and hepatic extraction did not change either. CONCLUSIONS: Patients with pHPT exhibited decreased insulin sensitivity and insulin hypersecretion. The latter is only partially ameliorated by increased hepatic insulin extraction. After surgery, although the biochemical abnormalities were fully reversible, the metabolic changes improved only partially.

C-Peptide

Suramin affects differentiated and undifferentiated human thyroid epithelial cells in vitro.

In the last decade, suramin has become known for its antiproliferative, differentiation-inducing effects on cells and has been successfully used in the therapy of cancer patients. The present study was undertaken to investigate the effects of suramin on normal human thyroid cells in primary monolayer culture and to analyse whether it also affected cells from thyroid carcinomas. The results show that suramin, at concentrations similar to serum levels obtainable during therapy, inhibited the proliferation of thyroid cells as well as the secretion of thyroglobulin. It suppressed the activation of adenylyl cyclase in thyroid membranes and decreased the immunogenicity of the cells by reducing their surface expression of HLA-DR and ICAM-1. Although the morphology of differentiated thyroid cells remained unaffected by suramin, morphological changes compatible with differentiation were observed in cells from undifferentiated thyroid carcinomas when suramin was added to the culture medium. In conclusion, the data demonstrate that suramin has pronounced in-vitro effects on normal and neoplastic thyroid cells. It may, therefore, also be effective in patients with thyroid cancer, for whom no other form of treatment is available.

Adenylyl Cyclases

Biologic and cytogenetic characterization of three human medullary thyroid carcinomas in culture.

Neuroendocrine features and cytogenetic abnormalities of one continuous cell line (MTC-SK) and two long-term cultures (GER, STAH) derived from three sporadic cases of human medullary thyroid carcinomas (MTCs) were studied. Specific neuroendocrine markers (NSE, chromogranins, calcitonin, calcitonin gene-related peptide) were identified by electron microscopy and immunocytochemistry. In situ hybridochemistry and Northern blot analysis confirmed endocrine activity. Cytogenetic studies of the cell line MTC-SK revealed three consistent marker chromosomes, t(3;10), 11p+, and 22p+. Cells of long-term cultures GER and STAH exhibited a consistent translocation t(2;18), a trisomy 7, and two consistent marker chromosomes der3 and 5p+, respectively. Recently, we have isolated 12 stable clones of this MTC-SK cell line, which showed two different growth patterns. Quantitative measurement of mitotic activity flow cytometry and semiquantitative analysis of AgNOR-, Ki67-, and Cyclin/PCNA-(immuno)reactivity showed different DNA composition and duplication rates, indicating at least two subpopulations. Some of our clones developed a new consistent marker (i.e., an unbalanced translocation between mar11p+ and 1q). However, no correlations between chromosome findings, growth rate, and neuroendocrine markers were observed.

Carcinoma

[Multivisceral and extended resection in tumor surgery--esophageal cancer].

Extended resections are strategies in the surgical treatment of cancer which provide large oncological safety margins: these are of particular relevance in the neck in view of the close anatomical relation of the major cervical organs. In the region of the distal esophagus, extended resections may be a reasonable alternative to conservative approaches even when only intended as a palliative treatment. The removal of metastases does not influence the outcome in patients with esophageal carcinoma, in contrast to simultaneous surgery of other malignancies.

Esophageal Neoplasms

Serum osteocalcin levels in primary hyperparathyroidism.

The serum levels of osteocalcin, a 49-amino-acid bone-matrix protein, have been found to be a specific biochemical parameter of bone formation. The aim of our study was to compare the sensitivity of serum osteocalcin levels with that of alkaline phosphatase in the evaluation of patients with primary hyperparathyroidism. In 40 patients with biochemically and histologically confirmed primary hyperparathyroidism, the serum levels of osteocalcin, intact parathyroid hormone, alkaline phosphatase, calcium, phosphorus, and creatinine were determined preoperatively. The serum levels of osteocalcin were elevated in 22 patients (55%), whereas the serum levels of alkaline phosphatase were increased in 18 patients (45%). In 10 patients (25%) the serum levels of osteocalcin, but not those of alkaline phosphatase, were increased, whereas in six patients the activity of alkaline phosphatase was high, but the serum osteocalcin levels were normal. When the biochemical data of the patients with increased serum osteocalcin levels were compared with those of the patients with serum osteocalcin levels within the normal range, the serum levels of intact parathyroid hormone and alkaline phosphatase were significantly increased in the group of patients with elevated serum osteocalcin levels. Our data indicate that serum osteocalcin levels might be a clinically useful additional parameter in the evaluation of patients with primary hyperparathyroidism.

Adult

The effects of suramin on human adrenocortical cells in vitro: suramin inhibits cortisol secretion and adrenocortical cell growth.

Suramin, a polycyclic and polyanionic drug, has been successfully used in the therapy of inoperable adrenocortical cancer. The present study was undertaken to investigate the effects of suramin on normal human adrenocortical cells in primary monolayer cultures. The proliferation and the basal, as well as the adrenocorticotropin (ACTH)-stimulated, cortisol secretion of these cells were studied. The data show that suramin decreases basal, as well as ACTH-stimulated, cortisol secretion in a dose-dependent manner (P less than .05 from 300 mumol/L upward). At a suramin concentration of 3 mmol/L, cortisol secretion was inhibited by 70% +/- 4% in ACTH-stimulated cells and by 42% +/- 6% in unstimulated cells. The proliferation of adrenocortical cells in response to fetal calf serum was also inhibited by suramin at concentrations from 300 mumol/L upward, maximal suppression (71% +/- 6%, P less than .01) being observed at a concentration of 10 mmol/L. Both inhibition of cortisol secretion and inhibition of adrenocortical cell proliferation were not due to toxicity of the compound, as could be shown by restimulation of cortisol secretion in suramin-treated cells with ACTH. Our results indicate that suramin exerts an inhibitory influence on the cortisol secretion and on the proliferation of normal human adrenocortical cells. Suramin may not only be useful in the treatment of adrenocortical cancer, but may also have an ameliorative effect on other malignant conditions with augmented steroid hormone production, resistant to conventional forms of therapy.

Adrenal Cortex

The immunoregulatory influence of transforming growth factor beta in thyroid autoimmunity: TGF beta inhibits autoreactivity in Graves' disease.

The immunoregulatory influence of transforming growth factor beta (TGF beta) was studied in patients with Graves' disease and in normal controls. Special attention was given to determine how TGF beta affects the interaction between thyroid epithelial cells and T lymphocytes. Human recombinant TGF beta 1 (rTGF beta 1) was immunosuppressive in patients with Graves' disease and in controls. In both groups it inhibited the proliferation of peripheral blood mononuclear cells and of peripheral and thyroid derived T cell lines and clones in response to non-specific stimuli. It also decreased the number of serine esterases expressing cytotoxic T cells and suppressed the recognition of thyroid epithelial cells by thyroid autoantigen specific T cell clones. Inhibition of autoantigen recognition was not only observed when rTGF beta 1 was added to the thyroid epithelial cell/lymphocyte co-culture, but was also found when thyroid epithelial cells were preincubated with rTGF beta 1, which was then removed before the initiation of co-culture. This was probably as a result of a decrease in the antigenicity of the target cells, as rTGF beta 1 also suppressed thyroid peroxidase as well as HLA class II autoantigen expression, in cultured thyroid epithelial cells. These results demonstrate that TGF beta may exert a variety of down-regulatory influences in Graves' disease. It may be of importance for the suppression of autoaggression in persons predisposed to autoimmunity; may be quantitatively overrun by immunostimulatory influences in the acute phase of the disease; and may be important for the induction of remission in patients with Graves' disease.

Adolescent

Extra-anatomic femoro-femoral crossover bypass (FF) vs. unilateral orthotopic ilio-femoral bypass (IF): an attempt to compare results based on data matching.

Some surgeons feel that femoro-femoral suprapubic crossover bypass (FF) is the treatment of choice in unilateral artery disease, whereas others reserve this procedure for the rare high risk patient. Results and their evaluation seem to differ depending upon the indications and the patients elected for comparison. We analysed 57 consecutive patients, who received a FF-PTFE graft between 1977 and 1989 (age 48-95 years; male/female 47/10; preoperative clinical status [Fontaine Classification] St. II: 19%, St. III: 58%, St. IV: 23%; diabetics: 14; smokers: 40). The estimated cumulative primary and secondary patency according to the Kaplan-Meier method were 52 +/- 10% (three grafts at risk) and 63 +/- 10% (six grafts at risk), respectively at 5 years. There was no statistical difference in the secondary patency comparing patients with a good and bad run-off (Breslow, Mantel-Cox). The cumulative 5-year survival was 35 +/- 7% (nine patients at risk). The results were compared with those obtained in a group of 150 patients, in whom an unilateral ilio-femoral (IF) retroperitoneal orthotopic graft had been implanted for the same indication and within the same period. Comparing the primary patency of FF and IF patients (55 +/- 6%; 24 grafts at risk) no significant difference could be seen at 5 years. But there was a significant difference in the 5-year survival rates, being in favour of the IF-group (43 +/- 5%; 43 patients at risk) suggesting that both groups were not comparable.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

[Balloon dilatation of benign esophageal stenoses].

Benign stenoses of the oesophagus have been conventionally treated by endoscopic bougienage and were operated on in case of failure. Now that balloon catheters with large balloon diameters are available, interventional radiological dilatation of enteric strictures can be easily performed. In case of eccentric high-grade stenosis with or without blind loop, stenosis is often easier to manage and associated with less risk with an angiographic guide wire and catheter than by endoscopy. 53.3% of the patients were referred to balloon dilatation after failed endoscopic bougienage. The indications for balloon dilatation were anastomotic stenosis (66.2%), peptic stenosis (16.9%), achalasia (7%), pylorospasm (5.6%) and stenosis due to pemphigus vulgaris, acid ingestion and (in one case) a Schatzki ring. The complication rate was low at 1%. The experience collected with 297 dilatations in 71 patients with benign oesophageal stenosis, is reported.

Adult

Suramin and the human adrenocortex: results of experimental and clinical studies.

Suramin, a sulfonated drug, has been used successfully in the treatment of inoperable adrenocortical cancer. This study was undertaken to investigate the effects of suramin on the basal and the adrenocorticotropin-stimulated cortisol and pregnenolone secretion and on the proliferation of primary monolayer cultures of normal human adrenocortical cells. Suramin decreases basal and adrenocorticotropin-stimulated cortisol secretion in a dose-dependent manner (p less than 0.05 from 0.3 mmol/L upward). At a suramin concentration of 3 mmol/L cortisol, secretion was inhibited by 70% +/- 4% in adrenocorticotropin-stimulated cells and by 42% +/- 6% in unstimulated cells. The proliferation of adrenocortical cells in response to fetal calf serum was inhibited by suramin at concentrations from 0.3 mmol/L upward, maximal suppression (71% +/- 6%; p less than 0.05) being observed at a concentration of 10 mmol/L. Neither down-regulation of cortisol secretion nor inhibition of adrenocortical cell proliferation was caused by toxicity of the compound, as could be shown by adrenocorticotropin-restimulating cortisol secretion in suramin-treated cells. The results indicate that suramin exerts an inhibitory influence on the cortisol secretion and the proliferation of normal human adrenocortical cells and may be useful in treating adrenocortical cancer.

Adrenal Cortex

Evaluation of glucose tolerance, insulin secretion, and insulin action in patients with primary hyperparathyroidism before and after surgery.

Glucose tolerance, insulin secretion, and insulin sensitivity were evaluated in 8 asymptomatic patients with primary hyperparathyroidism (PHPT) before and at least 8 weeks after surgical correction of PHPT by means of the hyperglycemic clamp technique. In addition, 15 sex- and age-matched control subjects were investigated for comparative reasons by the same technique. Glucose metabolized (M) during the hyperglycemic clamp was not significantly (NS) different between patients with PHPT and controls (7.9 +/- 2.3 vs. 6.3 +/- 1.9 mg/kg/min). However, insulin secretion (I) was significantly elevated in patients with PHPT compared to controls (87 +/- 17 vs. 45 +/- 12 microU/ml, P less than 0.05). The calculated insulin sensitivity index (M/I) was significantly reduced in PHPT compared to controls (11.0 +/- 2.1 vs. 15.2 +/- 1.4 mg/kg/min per microU/ml x 100, P less than 0.05). Comparing patients with PHPT before and after surgery, the M value, which is a measure of glucose tolerance, was not significantly different (7.9 +/- 2.3 vs. 7.8 +/- 1.5 mg/kg/min). However, insulin secretion was significantly lower after surgical correction of PHPT compared to the preoperative situation (48 +/- 9 microU/ml vs. 87 +/- 17 microU/7 ml, P less than 0.01). The calculated M/I rose significantly after surgery compared to the preoperative value (11 +/- 2.1 vs. 17.6 +/- 2.7 mg/kg/min per microU/ml x 100, P less than 0.001). We conclude that disturbed carbohydrate metabolism, such as insulin hypersecretion and insulin resistance, in patients with PHPT is an early finding in this disease and that these early disturbances in glucose metabolism are, however, fully reversible.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Endoscopic tube implantation for the palliation of malignant esophageal stenosis.

One hundred endoscopic tube implantations were carried out on 95 patients with malignant esophageal stenosis. Palliative treatment was performed in 43% of cases because of the advanced stage of the tumor, and in 57% of cases because of risk factors which made resection inadvisable. Clinical mortality was 16%, with six deaths caused by technical complications (perforation, arrosion bleeding), and ten by cardiopulmonary problems. Dislodgement or obstruction of the prostheses was observed in 20% of cases, but could readily be corrected. The median survival time was two months, with 17% of the patients still alive after six months. Poor general health, advanced age and the presence of distant metastases were established as unfavorable prognostic indications with a significant influence on postoperative mortality. Functional results were good: 87% of patients were able to eat solid or pulpy food post-operatively.

Adult