Acute effect of 1,25-dihydroxy-vitamin D3 on calcitonin secretion in rats.
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Biomedical subjects
Publications and source records attributed to F Raue.
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The influence of selective calcitonin blood level measurements and the radical surgical approach in the treatment of C-cell carcinoma of the thyroid is demonstrated using the case of an 11-year-old girl.
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An interlaboratory study for the radioimmunological determination of calcitonin was performed within the European PTH Study Group (ESPG), to improve comparability using external quality control. Twelve laboratories determined calcitonin in 21 deep frozen samples using their respective calcitonin radioimmunoassay systems. The samples included a standard curves of human calcitonin (sequence 1-32) in serum as well as in assay buffer, several dilutions of a serum from a patient with medullary thyroid carcinoma, and additional sera containing calcitonin levels of clinical importance. For evaluation, the known concentrations were related to the measured values of each laboratory, and of all laboratories together. Except for one, the laboratories recognized the different dilutions used, although absolute values were scattered over a wide range. Satisfactory agreement was reached only when the data were calculated as the percentage of a given value. In future, a serum with a well defined and constant calcitonin concentration should be used as an international standard in all determination of calcitonin by radioimmunoassay.
Two batches of synthetic human calcitonin batch A = delivered until 1976, and batch B = distributed since 1977 from Ciba-Geigy, have been tested and compared biologically and radioimmunologically. In the biossay B is almost twice as active as A when compared ampoule content and exerts a biological activity of 188 IU per mg pure hCT. In the radioimmunoassay there is no difference from each other in radioiodination and purification, but using them as standard and again comparing them on declared ampoule content, B contains twice as much immunological activity as A. For those, who are using hCT for analytic or biological purposes it is of importance to consider the increased hormone content of batch B with a twofold biological and immunological activity, in comparison to the preparations delivered before 1977.
We describe a sequential saturation double-antibody radioimmunoassay for carboxyl-terminal fragments of human parathyrin (hPTH) in serum. Standards are prepared with synthetic hPTH (residues 53-84) in hPTH-free serum. Antisera are obtained by immunizing guinea pigs with partly purified hPTH extracted from adenomatous glands. Tracer is prepared by labeling hPTH (53-84), presumably at the histidine residue, with 125I by the Chloramine T method at pH 8.6. Dilution curves for hPTH extracted from adenomas are superimposable on dilution curves for the synthetic 53-84 fragment. Dilution of sera from hyperparathyroid patients showed linearity of response with concentration in the present assay, but non-linearity in the heterologous radioimmunoassay. In contrast to the heterologous system, which discriminated 28 of 32 patients with primary hyperparathyroidism from 32 normals (normal range: undetectable to 54 pmol/L, omitting the highest and lowest values from controls), the present assay separated these groups without overlap.
A RIA system for human PTH is presented using a goat antibody (Code name 017-spring-78) against C-terminal hPTH fragments, as well as a human PTH standard from hemodiafiltration of a hyperparathyroid patient. It proved to be useful for the differentiation not only between hyperparathyroid patients and normals, but even within the normal range and hypoparathyroid states.
As pheochromocytoma sometimes is accompanied by medullary thyroid carcinoma (in the sense of multiple endocrine adonomatosis type II = Sipple-Syndrome), serum calcitonin (CT) was measured by radioimmunoassay in 4 patients with pheochromocytoma. Before extirpation of the adreno-medullary tumor, serum CT was distinctly increased to 3 and 30 ng/ml in 2 of 4 patients, respectively. After removal of the tumor, serum CT was normal in the patients and pentagastrin stimulation produced no exaggerated CT response. In hydrochloric acid extracts from the two corresponding pheochromocytoma tissues, immunoreactive-Calcitonin (IR-CT) was detected, the concentrations amounting 1 and 4 ng/mg wet tissue. These findings suggest that hypercalcitonism in patients with pheochromocytoma cannot always be ascribed to the thyroid, i.e. increased calcitonin levels do not necessarily indicate a medullary carcinoma of this organ.
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The significance of measuring calcitonin by biological and radioimmunological methods for diagnostic and therapeutic purposes is demonstrated in 18 cases of medullary thyroid carcinoma (MTC). The radioimmunoassay used permits the differentiation between normals (up to 0.5 ng/ml) and patients with MTC (3 to 120 ng/ml). As clinical symptomatology is often unspecific (tumor of the neck, perhaps in combination with diarrhea), the determination of calcitonin proved to be a useful preoperative diagnostic tool which can be improved by calcitonin stimulation tests (pentagastrin i.v.). Calcitonin values provide information on the completeness of surgical procedures or the recurrence of the tumor before clinical symptoms are manifest.
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Using synthetic human parathormone 1-34, a radioimmunological method for measuring this hormone fragment was developed which, as the amino-terminal PTH assay, permits the measurement of the concentration gradient in the neighborhood of OTH-secreting tumors. The use of preoperative location diagnosis in primary hyperparathyroidism is demonstrated with some typical cases, especially in revision operations.
In three women intoxication with vitamin D or dihydrotachysterol occurred. Two patients died from complications despite successful lowering of the serum calcium, the third died after a pulmonary embolus during hypercalcaemia 5 months after cessation of vitamin D. Correct observation of the narrow therapeutic range of vitamin D preparations appears most important in the treatment of hypoparathyroidism and other indications. Particular attention should be given to the prophylaxis of over dosage. Apart from regular serum calcium estimations instruction of the patient and relatives as to the dangers and symptoms of intoxication is recommended. The issuing of a therapy identity card would meet these requirements.
The strain of Walker carcinosarcoma 256 described induces hypercalcaemia, hyperphosphataemia and hyperuraemia in tumour bearing rats. Changes in calcium and phosphorus excretion are observed as well as accompanying calcification of soft tissue organs and loss of bone calcium. These changes in calcium metabolism disappear after removal of the tumour, so that long-range action of the tumour can be stated. The results are discussed in comparison with three other animal models of tumour dependent hypercalcaemia.
We compared an optimized contrast-enhanced CT technique for the neck and upper mediastinum with a conventional technique and with nonenhanced images, using densitometric measurements. The optimized protocol included slice thickness, infusion rate, postural maneuvers, and manipulation of the gantry tilt. Densitometric evaluation showed significantly higher enhancement values in vessels and metastases with the optimized protocol than with conventional technique, without significant enhancement in muscle. Semiquantitative assessment demonstrated significantly better image quality with the optimized protocol. The optimized technique has been implemented into routine use.
The multiple endocrine neoplasia syndromes are divided into two categories: MEN type I and MEN type II. The MEN type II syndrome is further divided into MEN IIa and MEN IIb. The syndromes are characterized by benign and malignant changes in two or more endocrine organs, as well as incidental changes in nervous, muscular and connective tissue. Two main forms can be distinguished: the MEN-I syndrome with hyperplasia of the parathyroid gland, accompanied by islet cell tumor and pituitary adenoma; the MEN-II syndrome with medullary thyroid carcinoma in combination with bilateral pheochromocytoma and hyperplasia of the parathyroid gland (MEN IIa), while type IIb is characterized by the additional appearance of neurocutaneous manifestations without primary hyperparathyroidism. Characteristics shared by these syndromes include the involved cell type, most of the tumors are composed of one or more specific polypeptide- and biogenic amine-producing cell types (APUD--amine precursor uptake and decarboxylation). The second characteristic is the increased incidence in certain families. The hereditary component is autosomal dominant with variable expression but high penetrance. Mechanisms of tumorigenesis differ in these syndromes. While MEN I is caused by an inherited mutation of a tumor suppressor gene, menin, located on the long arm of chromosome 11, MEN II is caused by activation of the RET proto-oncogene. We have reported the case of a young man exhibiting bilateral pheochromocytoma. In addition, the patient showed mild primary hyperparathyroidism and marfanoid habitus, all these stigmata usually being part of the MEN-II syndrome. Although this described patient showed a phenotypic mixture of the MEN-IIa and MEN-IIb syndrome, the genetic analysis for MEN II and von-Hippel-Lindau gene did not reveal any pathologic mutations, the endocrine disorders described here are not related to multiple endocrine neoplasia syndromes.
In about 80% of the cases, primary hyperparathyroidism (pHPT) is caused by a single parathyroid adenoma. However, the disease may be complicated by involvement of more than one parathyroid gland or by the combination with other endocrine tumors (syndrome of multiple endocrine neoplasia = MEN). This presentation deals with our experience in such conditions. During 11 years, 98 cases of pHPT were seen (90 in Ulm from 1968 to 1979, 8 since then in Heidelberg). In 9 patients, 2 to 4 parathyroids were in hyperfunction. A recurrence of pHPT was diagnosed after symptomfree intervals of 2 - 13 years in 5 patients. Data are presented of 4 patients suffering from MEN type I (Wermer syndrome): 3 had Zollinger-Ellison syndrome and pHPT, and the 4th insulinoma and pHPT. Whereas pHPT is the most frequent endocrinopathy in MEN type I, it is rarely seen in MEN type II, the Sipple syndrome (combination of medullary thyroid carcinoma, MTC, and pheochromocytoma). Among 20 own cases with MTC and 10 others with pheochromocytoma, no pHPT was observed. The common basis for the development of MEN syndromes is Pearse's concept of the diffuse neuroendocrine system (DNES).