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Biomedical subjects

E D Williams

Publications and source records attributed to E D Williams.

At least 163 records · Page 9Linked to original sources

Chromogranin A and B and secretogranin II in medullary carcinomas of the thyroid.

We have studied the presence of chromogranins A and B and secretogranin II in medullary carcinomas of the thyroid using the methods of immunoblotting and immunohistochemistry. All three antigens were identified by immunoblotting. Chromogranin A and secretogranin II behaved identically to the adrenal antigens in electrophoresis, whereas the molecular size of chromogranin B in the thyroid tissue appeared slightly smaller, possibly due to a higher degree of proteolytic processing. In immunohistochemistry, positive staining was obtained with all three antigens throughout the tumor tissue. All three antigens, as well as the hormone calcitonin, were apparently present in the same cells. Our study suggests that in addition to chromogranin A, the other two antigens (chromogranin B and secretogranin II) may also be useful markers for tumors arising from endocrine tissues.

Carcinoma↗

Monitoring radiation dose to the hands in nuclear medicine: location of dosemeters.

The relatively high radiation dose which can be received by the hands of staff in nuclear medicine departments means that in many departments it is necessary to monitor such doses. A convenient method is to use a TLD sachet in a plastic strip around a finger. This study was done to determine whether a dosemeter worn at the base of the middle finger was adequate to monitor the dose to the surface of the whole hand. Dosemeters were worn at the finger tips, finger base and palm of both hands, on two people while preparing and dispensing radio-pharmaceuticals, and two others while giving injections using syringe shields. The pattern of distribution of radiation does to the hands was similar for all workers and for both types of work. A single, convenient site (base of middle finger) may therefore be used for monitoring radiation dose to the hand.

Fingers↗

Immunohistochemical study of calcitonin gene-related peptide in human medullary carcinoma and C cell hyperplasia.

The distribution of calcitonin and calcitonin gene-related peptide (CGRP) has been studied by immunohistochemistry in normal, hyperplastic and neoplastic C cells. Fewer normal C cells contained immunoreactive CGRP than calcitonin, though both peptides can be co-expressed by a single cell. In the hyperplastic C cells that accompany familial medullary carcinoma immunohistochemistry was strongly and diffusely positive for both CGRP and calcitonin. In contrast, in medullary carcinoma, whether sporadic or familial, little CGRP was identified; often only a few strongly positive cells were found in a negative background, while immunoreactive calcitonin was commonly present in large amounts. The findings suggest that CGRP immunohistochemistry may be of value in identifying hyperplastic C cells, and that CGRP levels should be studied in medullary carcinoma families.

Calcitonin↗

Struma ovarii: a case report.

A patient with struma ovarii and hyperthyroidism is described. She was treated for Graves' hyperthyroidism at age 22 and received thyroxine for post-operative hypothyroidism. Twenty years later she became thyrotoxic and was treated with antithyroid drugs and radioiodine. Diagnosis of struma ovarii was made by radioiodine profile scanning and an ovarian tumour was removed. This had the pathological features of struma ovarii and autoradiographic evidence of pre-operatively administered 125I was seen in the lesion. The patient had positive results for long acting thyroid stimulator (LATS) and LATS-protector (LATS-P) pre- and post-operatively. Bioassays for thyroid stimulators were positive post-operatively but radioreceptor assays for TsAb were consistently negative. It is suggested that profile scanning is an appropriate investigation for diagnosis. It is not clear whether the lesion was autonomous or being stimulated by circulating thyroid stimulators.

Female↗

Synchronous duodenal neuroendocrine tumours in von Recklinghausen's disease--a case report of co-existing gangliocytic paraganglioma and somatostatin-rich glandular carcinoid.

The co-existence of a gangliocytic paraganglioma and a glandular psammomatous carcinoid in the duodenum of a patient with von Recklinghausen's disease and bilateral phaeochromocytomas is reported. The two lesions were considered to be distinctive by light microscopy, electron microscopy and immunocytochemistry. The cells of the glandular carcinoid showed strong cytoplasmic immunoreactivity for somatostatin and contained only scanty intracytoplasmic microfilaments on electron microscopy. In contrast, the endocrine cells of the gangliocytic paraganglioma were positive for pancreatic polypeptide and serotonin, were negative for somatostatin, and contained conspicuous intracytoplasmic aggregates of filaments. The histogenic relationship between the two tumours is discussed. This case strengthens the known association of glandular duodenal somatostatinoma with von Recklinghausen's disease and phaeochromocytoma and, in the light of a previous case report, suggests that von Recklinghausen's disease and gangliocytic paraganglioma may co-exist more commonly than expected.

Carcinoid Tumor↗

Duodenal carcinoid tumours, phaeochromocytoma and neurofibromatosis: islet cell tumour, phaeochromocytoma and the von Hippel-Lindau complex: two distinctive neuroendocrine syndromes.

To clarify neuroendocrine syndromes we have reviewed the association of neurofibromatosis with carcinoid tumours and of neurofibromatosis, phaeochromocytoma or von Hippel-Lindau complex with either carcinoid or islet cell tumours. In nine cases of neurofibromatosis with a carcinoid tumour studied all carcinoid tumours were in the duodenum, were distinctive histologically and had widespread somatostatin immunoreactivity. The duodenum was the primary site in 18 of 20 further published cases of carcinoid tumour and neurofibromatosis. Phaeochromocytoma was also present in six of these 27 cases with neurofibromatosis and duodenal carcinoid tumour. Six patients have been reported with Von Hippel-Lindau complex, phaeochromocytoma and islet cell tumour. A further 11 patients showed phaeochromocytoma and islet cell tumour. No cases of Von Hippel-Lindau complex had a carcinoid tumour, and no cases of neurofibromatosis had an islet cell tumour. We conclude that the association of neurofibromatosis, duodenal carcinoid tumour and phaeochromocytoma forms a distinctive neuroendocrine syndrome, sharply separated from the association of Von Hippel-Lindau complex with islet cell tumour and phaeochromocytoma. This separation is important in pathogenesis, diagnosis and clinical management.

Adenoma, Islet Cell↗

The reproducibility of the natural head position in lateral cephalometric radiographs.

The reproducibility of radiographs taken in the natural head position was compared with and found similar to those taken in a standard cephalostat. Between three and six films were taken for each patient. The natural head position was found to be not as reproducible as has been suggested by others. Reasons for this finding have been examined, and some proposals made concerning a rational approach to cephalometric radiographs.

Adolescent↗

The use of radionuclide bone scintigraphy to determine local spread of oral squamous cell carcinoma to mandible.

In oral squamous cell carcinoma, conservative resection of mandible is not recommended if there is tumour invasion. The use of bone scintigraphy to obtain a more accurate assessment of tumour spread has been evaluated in comparison with radiographs and histology in 11 patients. Tumour invasion of bone was shown on scans and radiographs, but periosteal reaction to tumour was detected by scintigraphy only. Thus both scintigraphy and radiography are recommended for preoperative assessment of bony margins for radical resection.

Adult↗

Reparative growth in the rat thyroid: effect of TSH suppression.

Previous investigations have shown that thyroid incision leads to a dramatic burst of follicular cell mitotic activity in cells adjacent to the wound edge in both normal rats and rats made hypothyroid by chronic goitrogen administration. Wound-induced thyroid mitotic activity therefore, is seen in rats with either normal or supranormal levels of circulating thyrotropin (TSH). This study was designed to investigate the thyroid mitotic response to wounding in the absence of detectable levels of circulating TSH. Rats were injected with large doses of L-thyroxine twice daily to render circulating TSH undetectable. Thyroids were incised and follicular cell mitotic activity, in relation to distance from the incision, determined at 24, 48 and 72 hr after incision. A mitotic response to wounding was maintained in L-thyroxine treated rats, even though circulating TSH was undetectable. The peak of activity was at 48 hr, but was only 50% of that found in the incised normal rat thyroid. The spatial distribution of the response suggests that there are two components of the wound response in the normal thyroid, one dependent on the presence of circulating TSH, the other TSH-independent. The results are discussed in relation to current understanding of cellular growth control.

Animals↗

The preoperative and postoperative investigation of TSH and prolactin release in the management of patients with hyperprolactinaemia due to prolactinomas and nonfunctional pituitary tumours: relationship to adenoma size at surgery.

We report here our results of the pre- and post-operative assessment of prolactin and TSH status in 41 hyperprolactinaemic patients who underwent pituitary surgery over a 5 year period. Preoperatively in patients with prolactinomas (n = 33) the TSH response to domperidone decreased with increasing adenoma size. When the data are expressed on a group mean basis the exaggerated TSH response to domperidone in preoperative prolactinoma patients was reduced significantly in patients rendered normoprolactinaemic by surgery but persisted in those who remained hyperprolactinaemic. Similarly the reduced preoperative PRL responses to domperidone and TRH were significantly increased by successful surgery. In contrast patients with stalk-compression hyperprolactinaemia (n = 6) due to larger lesions which were not prolactinomas all showed reduced or absent TSH responses to domperidone. The PRL responses to domperidone and TRH were reduced or absent both in patients with prolactinomas and in those with stalk-compression hyperprolactinaemia. All patients with stalk-compression hyperprolactinaemia showed a delayed pattern of TSH response to TRH with 60 min values being greater than 20 min ones. In contrast a normal pattern of TSH response to TRH was observed in all patients with hyperprolactinaemia due to prolactinomas. Postoperatively TSH and PRL responses were largely unchanged in patients with stalk-compression hyperprolactinaemia regardless of whether normoprolactinaemia was restored by surgery. In conclusion a reduced or absent PRL response to TRH or domperidone is not diagnostic of the presence of a prolactinoma since it occurs in hyperprolactinaemic patients with prolactinomas or stalk-compression. In contrast, the TSH response to acute dopamine antagonism is exaggerated in most patients with small prolactinomas but not in those with stalk-compression hyperprolactinaemia and we have found this to be helpful diagnostically since the presence of an exaggerated TSH response to dopamine antagonism is evidence against the presence of stalk-compression hyperprolactinaemia. The observation of a delayed TSH response to TRH in a hyperprolactinaemic patient should alert the clinician to the possibility of stalk-compression hyperprolactinaemia due to a large lesion which may not be a prolactinoma.

Adenoma↗

Calcitonin gene-related peptide and calcitonin in medullary thyroid carcinoma.

We have investigated the levels of serum calcitonin and calcitonin-gene related peptide (CGRP) in 35 patients with well-documented medullary thyroid carcinoma (MTC). Immunohistochemical investigations for calcitonin and CGRP have been performed on tumour tissue from 9 patients to clarify the cellular pattern of production. In four patients with aggressive disease, serum calcitonin and CGRP values have been monitored in relation to progression of disease after surgery. All 35 patients with MTC have elevated calcitonin and 26 elevated CGRP levels. Generally calcitonin values were found to be higher than those of CGRP, although the ratio of the two peptides varied from patient to patient. The immunohistochemical investigations corresponded with these findings, generally showing diffuse staining for calcitonin in MTC tumour-cells and only a small number of CGRP positive cells. Calcitonin and CGRP are produced by alternative processing of the common precursor gene transcript. Our results suggest that absolute values of either calcitonin or CGRP in serum have no direct relationship to aggressiveness of disease. Thus whilst serum CGRP measurements appear to be a useful additional marker for the disease, they can be considered to be only a useful adjunct to serum calcitonin as a marker for tumour progression.

Adolescent↗

Growth factor control of rat thyroid follicular cell proliferation.

We have investigated the proliferative responses of rat thyroid follicular cells in serum-free culture to a range of growth factors including TSH, epidermal growth factor, and insulin, added singly or in combination. Follicles released from normal thyroids by collagenase/dispase digestion were cultured in suspension in agarose-coated microtiter plates to prevent monolayer formation. Growth responses were measured by [3H] thymidine incorporation and by autoradiography over successive 24- or 36-h periods. Insulin, even in the absence of other growth factors, stimulated [3H]thymidine incorporation in a concentration-dependent manner, rising from basal levels of 486 +/- (SE) 18 cpm to 4222 +/- 367 cpm/5 X 10(4) cells at 8 micrograms/ml. In contrast, TSH alone had no effect. In the presence of threshold levels (0.08 micrograms/ml) of insulin, however, there was a highly significant (P less than 0.001) response to TSH, [3H]thymidine incorporation rising from 1089 +/- 163 cpm in the absence of TSH to a maximum of 7548 +/- 585 with 1 mU/ml TSH. There was a synergistic interaction between insulin and TSH over the concentrations tested. Epidermal growth factor either alone or in combination with insulin failed to produce a significant response. Parallel autoradiographic studies were concordant with the [3H]thymidine incorporation data. We conclude that whereas in the absence of other growth factors TSH is unable to stimulate DNA synthesis in isolated rat thyroid follicles, the inclusion of just a single growth factor, insulin, permits a marked response. These observations emphasize the need for inclusion of appropriate permissive growth factor(s) when assessing the in vitro effect of a suspected tissue-specific mitogen.

Animals↗

Multiple-section radionuclide tomography of the kidney: a clinical evaluation.

The clinical utility of radionuclide emission tomography of the kidney in comparison with conventional gamma-camera imaging has been assessed from scans of 60 patients suspected of having space-occupying lesions of the kidney. Nineteen patients had renal tumour, 17 had cysts and seven had renal pseudotumours; the remainder had no lesion. Objective trials using four observers showed only a slight, statistically insignificant advantage from the addition of tomographic sections to conventional images. However, in several individual cases tomography had aided diagnosis, particularly in obese patients, when an alternative non-invasive investigation (ultrasonography) was inconclusive. In seven patients a positive diagnosis of renal pseudotumour was made possible by tomography; definite identification of ectopic functioning cortical tissue at the location of a mass suspected after urography was considered to be a distinct diagnostic advantage gained from emission tomography of the kidney.

Adenocarcinoma↗

The association of neurofibromatosis, pheochromocytoma, and somatostatin-rich duodenal carcinoid tumor.

The association of neurofibromatosis and pheochromocytoma is well recognized; more recently, attention has been drawn to links between neurofibromatosis, pheochromocytoma, and ampullary somatostatin-rich carcinoid. Because of this association, the duodenum was explored during a recent laparotomy for resection of bilateral pheochromocytoma in a patient with von Recklinghausen's disease. A clinically unsuspected ampullary tumor was discovered; this proved to be in part a ganglioneuroma and in part a somatostatin-rich carcinoid. This paper presents full details of this carefully investigated and documented case and reviews the recent advances in this field. These studies lead us to conclude that: the clinical association of neurofibromatosis, pheochromocytoma, and D cell carcinoids ("somatostatinomas") of the ampullary region is confirmed; this association may be more common than has been previously thought, and the duodenum should be carefully examined in any patient with neurofibromatosis who undergoes laparotomy for pheochromocytoma.

Adrenal Gland Neoplasms↗