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Biomedical subjects

I Doniach

Publications and source records attributed to I Doniach.

At least 37 records · Page 2Linked to original sources
PubMed1985

Pituitary ACTH dependent Cushing's syndrome due to ectopic production of a bombesin-like peptide by a medullary carcinoma of the thyroid.

A 41-year-old man presented with Cushing's syndrome and the biochemical features of ectopic ACTH production. Investigation revealed mediastinal metastases from a medullary carcinoma of the thyroid. The peripheral plasma contained grossly elevated levels of bombesin-like immunoreactivity (irBombesin) as well as calcitonin; blood sampling via a venous catheter confirmed a gradient of irBombesin, but not of ACTH, in the mediastinal vein draining the tumour. On extraction the tumour contained a bombesin-like peptide, but not vasopressin or corticotrophin releasing factor and only very low levels of ACTH; immunohistochemical studies showed positive immunostaining for bombesin and calcitonin but none for ACTH or CRF. No ACTH was released from dispersed tumour cells in vitro. However an extract of the tumour stimulated ACTH release in vitro from perifused dispersed rat anterior pituitary cells. This is the first reported case of Cushing's syndrome due to ectopic production of a bombesin-like peptide, causing excessive pituitary ACTH secretion.

Adrenocorticotropic Hormone↗
PubMed1985

The effect of dopamine agonist therapy on large functionless pituitary tumours.

Fifteen patients (12 male) with large pituitary tumours and serum prolactin levels below 1000 mU/l were given dopamine agonist therapy (bromocriptine, mesulergine or pergolide) for a mean of 9 months (range 3-36 months). Serum prolactin became undetectable in all. Despite this, significant suprasellar extensions and any associated neurological defect remained in 14 patients, who therefore were referred for surgery. In one patient there was evidence of spontaneous pituitary infarction unrelated to dopamine agonist therapy. At operation 12 patients had apparently functionless pituitary adenomas which failed to immunostain for prolactin, one had an epidermoid cyst and one a Rathke's pouch cyst. We conclude that patients with large pituitary tumours and only a mildly elevated serum prolactin are unlikely to have prolactinomas, and that such tumours are not likely to show significant tumour shrinkage with medical treatment with dopamine agonists.

Adenoma, Chromophobe↗
PubMed1985

Bombesin-like peptides in human endocrine tumors: quantitation, biochemical characterization, and secretion.

Bombesin-like immunoreactivity (BLI) in 20 human endocrine tumors was studied using an antiserum directed toward the C-terminal region of bombesin. Additionally, plasma BLI was assayed in normal subjects and patients with known BLI-containing tumors. In 7 tumors (medullary carcinoma of the thyroid, n = 2; carcinoid of the lung, n = 3; hepatic carcinoid, n = 1; pheochromocytoma, n = 1), the BLI content ranged from 6-2000 pg/mg wet wt of tissue. Sephadex G-50 gel chromatography of tumor extracts under acid-dissociating conditions revealed 2 peaks of BLI: 1 coeluting with porcine gastrin-releasing peptide (GRP) and 1 with bombesin. Reverse phase ODS silica HPLC analysis of the G-50 peaks using a methanol-trifluoroacetic acid gradient showed that human tumor BLI more closely resembled porcine GRP and its C-terminal fragment GRP-(14-27) than bombesin itself. Partial tryptic digestion of the tumor GRP-like peptide generated a product which, on HPLC, was similar to GRP-(14-27). Elevated plasma BLI was detected in the peripheral circulation of three subjects and in the vessels draining the tumor metastases of one of these patients. BLI was undetectable in normal subjects. These results indicate 1) that BLI is present in and may be secreted by various human endocrine tumors, and 2) that human tumor BLI closely resembles porcine GRP and its C-terminal fragment GRP-(14-27).

Animals↗
PubMed1984

Corticotrophin-releasing factor--mediated adrenocorticotrophin release from rat anterior pituitary cells is potentiated by C-terminal gastrin-releasing peptide.

The remission of Cushing's syndrome following surgical removal of a tumour containing bombesin-like immunoreactivity (BLI), but insignificant levels of ACTH, is described. However, an acid extract of the tumour tissue caused the release of ACTH from isolated rat anterior pituitary cells in vitro. These observations led to an investigation of the effects of synthetic C-terminal gastrin-releasing peptide (GRP(14-27] on ACTH release from isolated rat anterior pituitary cells. GRP(14-27) (10-1000 ng/ml) directly stimulated the release of ACTH in vitro, whereas lower doses (10-1000 pg/ml), ineffective themselves in eliciting ACTH release, potentiated the CRF-mediated in-vitro release of ACTH.

ACTH Syndrome, Ectopic↗
PubMed1982

Bromocriptine in management of large pituitary tumours.

Bromocriptine has an accepted place in the management of small pituitary tumours that secrete either prolactin or growth hormone. The treatment of large tumours with extrasellar extensions is more difficult, however: though surgery is the standard treatment, it is often unsuccessful in returning excessive hormone secretion to normal and may cause hypopituitarism. A prospective trial was undertaken to assess the frequency with which changes in pituitary function and size of large tumours occurs. Nineteen patients were studied before and during treatment with bromocriptine (7.5 to 60 ml/day) for three to 22 months, using contrast radiology and a detailed assessment of pituitary function. Eighteen patients had hyperprolactinaemia and two of these also had raised concentrations of growth hormones; one patient had an apparently non-functioning tumour. In 12 patients (63%) tumour size decreased with bromocriptine and no tumour enlarged. Nine patients had visual-field defects, which improved in seven, becoming normal in five. Pituitary function improved in nine patients (47%) becoming entirely normal in three. Bromocriptine should be the treatment of choice in patients with large pituitary tumours with extrasellar extensions, provided close supervision is maintained.

Adult↗
PubMed1982

Histology of the islets of Langerhans following administration of human lymphocytes into athymic mice.

Lymphocytes from seven newly diagnosed insulin-dependent (Type 1) diabetics, five islet cell antibody positive unaffected children and five normal subjects were injected i.p. into athymic nude mice. A further six mice were injected with medium and six control mice received no injection. Blood was taken from the tail vein before injection for glucose determination. After 10 days blood was again obtained from the tail vein; the pancreas was removed under deep ether anaesthesia and the mice sacrificed by exsanguination. Routine histological sections of the pancreas were prepared. There was no difference between groups in respect of the initial blood glucose. However, final blood glucose levels were raised in all mice that had received an injection including medium only, the rise being statistically significant both after injection of lymphocytes from normal subjects (P less than 0.05) and from newly diagnosed diabetics (P less than 0.001). Histology did not reveal any evidence of 'insulitis' or islet cell damage although enlarged, hyperplastic islets could be found in each group of treated mice. We conclude that passive transfer of diabetes was not achieved in this animal model. Elevation of blood glucose levels and islet hyperplasia may simply reflect a non-specific 'stress' reaction.

Animals↗
PubMed1977

Thyroid cancer in an iodide rich area: a histopathological study.

A comparison of the incidence of the different histological types of thyroid carcinoma in an area of high dietary iodide and an area of normal iodide intake has been made. The areas chosen were Iceland and the region of Northeast Scotland centred on Aberdeen; both areas have clearly defined populations served by a single pathology laboratory. All definite and dubious thyroid carcinomas from both regions were examined and classified by the same two pathologists. The age-specific incidence rates for papillary carcinoma in surgical specimens in both areas rose with age; they were five times higher in Iceland (high iodide area) than in Northeast Scotland. The numbers of follicular carcinomas were small, and this tumor was relatively less frequent in Iceland than Aberdeen. These findings, together with the known high relative frequency of follicular carcinoma and low frequency of papillary carcinoma in areas of endemic goitre, lead to the suggestion that the incidence of papillary carcinoma and follicular carcinoma are separately influenced by dietary iodide, papillary carcinoma being high in areas of high iodide intake and low in areas with low dietary iodide. No evidence to implicate lymphocytic thyroiditis, radiation or genetic factors in the genesis of thyroid carcinoma in Iceland or Northeast Scotland was found in this study. Undifferentiated carcinoma was about three times as common in Iceland as in Northeast Scotland. Malignant lymphoma of the thyroid was suprisingly common in Northeast Scotland, possibly related to the high frequency of thyroiditis found in this region. These studies suggest that the incidence of different histological types of thyroid malignancy is influenced by different etiological factors. They also provide support for the subdivision of thyroid malignancy into these different types, and for the general importance of accurate histological typing in cancer epidemiology.

Adenocarcinoma↗
PubMed1976

Primary malignant tumours of the thyroid: the relationship between histological classification and clinical behaviour.

One hundred and seventy-nine primary malignant tumours of the thyroid seen at The London Hospital between 1945 and 1972 were classified by the system of Woolner et al. (1961) and Hazard (1964). The distinct pathological and clinical features of the differentiated primary carcinomas and the similarities and differences between malignant lymphoma and anaplastic carcinoma were confirmed. This study showed the 'benign' behaviour of more than half the 'differentiated' papillary and follicular carcinomas when treated by thyroid lobectomy and the very malignant nature of anaplastic carcinomas and lymphomas whatever their treatment. The behaviour of medullary carcinoma was closer to that of the other differentiated tumours than to the undifferentiated varieties. Our patients were not thought to have been exposed to known goitrogens or previous thyroid irradiation.

Adolescent↗
PubMed1976

Biological effects of 131I and 125I isotopes of iodine in the rat.

From the differences in radiation profiles between 131I and 125I isotopes of iodine it would be expected that they would show different effects on thyroid function. The differences should lead to lower rates of thyroid gland destruction with 125I and hence less post-irradiation hypothyroidism. This difference in biological effect has been demonstrated in rats by indirect assessment of thyroid function. In this report the long-term effects of a range of similar doses of 131I and 125I were compared, in male and female rats, by direct assessment of thyroid function. Seventeen months after receiving 25 and 125 muCi of 131I, male and female rats showed significant elevation of serum TSH concentration and a reduction in 3 h radioiodine uptake. Rats receiving 1 and 5 muCi of 131I and all doses of 125I showed no significant changes in thyroid function. These findings confirm the previously reported differences in effect between the 131I and 125I isotopes of iodine in the rat.

Animals↗
PubMed1975

Prevalence of asbestos bodies in a necropsy series in East London: association with disease, occupation, and domiciliary address.

The prevalence of asbestos bodies was measured in lung sections in a necropsy series carried out at the London Hospital (1965-66) after exclusion of all known asbestos factory workers and cases of asbestosis and of mesothelioma. Associations were sought between the presence and number of asbestos bodies with the patients' sex, domiciliary address, occupation, industry, and diseases recorded at necropsy. Asbestos bodies were present in 42% of the 216 men in the series and in 30% of the 178 women. The number of bodies in the positive cases was small in comparison with the numbers seen typically in asbestosis; thus there were less than 6 asbestos bodies per 6-75 mm-3 lung tissue in 107 of the total 145 positive cases in contrast to 1 000 or more in asbestosis. In comparison with the overall series, an increased number of asbestos body positives was present in males with carcinoma of stomach and females with carcinoma of breast. In view of this finding lung sections were counted in further post-mortem examples of these carcinomas making a total of 50 males with carcinoma stomach and 82 females with carcinoma breast. Thirty-five positive cases were found in the carcinoma stomach group as against 22-7 expected and 38 in the carcinoma breast group against 26-35 expected. There was no excess of observed over expected asbestos body positives in 51 males with carcinoma of bronchus. There was an excess of asbestos body positives (60-9%) in heavy manual workers and in both heavy and light manual male workers in the shipping (61%), electrical and engineering (56%), and transport (54%) industries. The incidence in male clerical workers was 12-8%. The incidence of asbestos body positives according to home address was highest (53% in males, 45% in females) in patients living in the industrial and cockland area due east of the hospital. The incidence fell in the less industrial areas north-east of the hospital. Consideration of possible environmental sources of the inhaled asbestos suggests that in this survey occupation, industry, and comiciliary area all play a part. The comparatively minor intensity of asbestos pollution in our positive cases showed a positive association with carcinoma of stomach and breast, possibly playing a direct pathogenic role in carcinoma of stomach. No positive association was identified with any other neoplastic disease including carcinoma of bronchus.

Adolescent↗
PubMed1975

Correlation of diameters of secretory granules in clinically non-functioning chromophobe adenomas of the pituitary with those of normal thyrotrophs.

Diameters of secretory granules in thyrotrophs in gonadotrophs were measured in electron micrographs of operation specimens of 4 pituitary glands and of the secretory granules in operation specimens of 10 clinically non-functioning chromophobe adenomas. The mean diameter of the thyrotroph granules was 137 plus or minus 26 nm, of the gonadotrophs 204 plus or minus 38 nm, of 9 of the adenomas 141 plus or minus 20 nm and of the remaining adenoma 248 plus or minus 67 nm. The significance of the close correlation in granule size in most of the adenomas with that of thyrotrophin granules is discussed briefly.

Adenoma, Chromophobe↗
PubMed1974

Carcinogenic effect of 100, 250 and 500 rad X-rays on the rat thyroid gland.

Male rats were given 0, 100, 250 or 500 rad x-rays to the thyroid gland at 9-12 weeks of age and killed 18-20 months later. No thyroid tumours were found in the unirradiated animals, a few follicular adenomata developed after 100 and 250 rad and a follicular carcinoma after 500 rad. A similar group was set up and maintained on a diet with thyroxine added in a quantity to give a daily consumption of 5-6 μg/100 g body weight in order to suppress TSH secretion. Thyroid tumour production was considerably lowered. At the termination of the experiment the efficiency of the TSH suppression was tested by measurement in some rats of T/S (131)I concentration ratios and in others of the 24 h% (131)I thyroid uptake. In some rats TSH was totally suppressed, in others partially suppressed. A further group was set up and maintained on the goitrogen 0·1% aminotriazole in the drinking water to cause excessive TSH secretion. All its subgroups, including unirradiated animals, developed numerous follicular adenomata and carcinomata. Enhancement of carcinoma production was present in the 500 rad subgroup. It was concluded that the development of thyroid adenomata after the above doses of x-radiation may occur without an excessive rise in TSH secretion, that suppression of TSH lowers radiation tumour production and that therefore TSH may play a permissive role in the development of thyroid tumours following low dose x-radiation to the thyroid gland.

Adenocarcinoma↗