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Biomedical subjects

J G Ratcliffe

Publications and source records attributed to J G Ratcliffe.

At least 91 records · Page 5Linked to original sources
PubMed1980

Assessment of the secretin provocation test in the diagnosis of gastrinoma.

The effect of intravenous secretin on plasma immunoreactive gastrin is presumed to improve diagnostic accuracy in patients with a gastrinoma. To investigate this further, the secretin provocation test was performed in control patients (n = 10), patients with a primary duodenal ulcer (n = 10), patients who had previously had surgery for a duodenal ulcer (n = 20), patients with symptomatic recurrent peptic ulceration (n = 50) and 2 patients with a histologically proved gastrinoma. It was found that the secretin test gave a false positive result in 3 out of 10 symptomatic duodenal ulcer patients, 2 out of 20 patients who had had previous duodenal ulcer surgery and were now asymptomatic and 15 out of 50 patients with recurrent peptic ulceration. Both gastrinoma patients had positive secretin tests but there were no obvious criteria that separated the gastrin response of a gastrinoma patient from those with primary or recurrent peptic ulceration. It is concluded that the secretin test is probably of little value in both the screening and the diagnosis of a gastrinoma.

Adenoma, Islet Cell↗
PubMed1980

The effect of fenclofenac on thyroid function tests in vivo and in vitro.

Clinically euthyroid patients on long term maintenance therapy with the non-steroidal anti-inflammatory drug fenclofenac (Flenac) show an unusual and abnormal pattern of serum thyroid function tests. In all twelve patients studied, total T4 concentrations were grossly subnormal (mean 28.4 +/- 9.9 (SD) nmol/l and total T3 levels low-normal (mean 1.4 +/- 0.3 (SD) nmol/l), whereas rT3 (mean 0.36 +/- 0.06 (SD) nmol/l) and basal TSH levels (mean 1.9 +/- 0.5 (SD) mu/l) were within their respective normal ranges. Free T4 levels were low normal (mean 11.0 +/- 1.0 (SD) pmol/l) while TSH, T4 and T3 responses to intravenous TRH were similar to those found in euthyroid subjects. These effects appear to be due predominantly to in vivo inhibition of binding of thyroid hormones to carrier proteins in serum, rather than in vitro drug interference in the radioimmunoassays employed. Fenclofenac does, however, interfere in those laboratory methods employing serum proteins as binding agents. Thus the Thyopac 4 method for serum total T4 grossly over-estimates T4 levels, while thyroid hormone binding capacity (Thyopac 3) is low. Since fenclofenac is one of the most potent drugs interfering with routine indices of thyroid status, it is suggested that suspected thyroid dysfunction is excluded before commencing therapy with the drug.

Adult↗
PubMed1980

Clinical and laboratory evaluation of four methods of assessing free thyroxine status in thyroid clinic patients.

The clinical value of four laboratory methods of assessing free thyroxine status was compared in 82 consecutive patients newly referred to a thyroid clinic with suspected thyroid dysfunction. The methods of determining free thyroxine used were: (1) free thyroxine index using a thyroid hormone uptake test (FTI (THUT)); (2) a free thyroxine index using thyroxine binding globulin (FTI (TBG)); (3) a kinetic radioimmunoassay (Immophase); and (4) an equilibrium dialysis method. The definitive thyroid status was evaluated by a combination of clinical assessment (including Wayne index), routine tests of thyroid function (total T4, T3, TSH, and TRH tests where appropriate), and by therapeutic trial in one case. The diagnostic efficiency of the tests was markedly dependent upon the method of determining the reference range for euthyroid patients. Best efficiency for each test was achieved using an amended range after excluding outliners. Test efficiency was then 97.6% for FTI (THUT) and the kinetic RIA and 96.8% for FTI (TBG). Misclassification by one or more of these tests occurred in only four patients (mild hypothyroid, euthyroid on phenytoin, euthyroid on oral contraceptive and valium, T3 hyperthyroid). In contrast, free T4 by equilibrium dialysis was much less efficient (86.6%) and was technically the most complex. Overall the kinetic T4 RIA provided similar diagnostic information to the indirect indices. However, further studies of cost benefit in settings other than a thyroid clinic are required to assess whether this method might replace total T4 and/or FTI as a first-line test of thyroid function.

Adult↗
PubMed1980

Ectopic hormones--biochemical aspects.

Biochemical evidence suggests that ectopic hormone production is much more common than suspected clinically. The majority of lung carcinomas of oat cell or carcinoid type appear to synthesise ACTH and related peptides, calcitonin and less frequently, chorionic gonadotrophin and vasopressin. The primary amino acid sequences of ectopic hormones closely resemble their normal counterparts but ectopic hormone producing tumours contain greater proportions of high molecular weight, subunit and fragment forms than the normal gland of origin. Assays for ectopic hormones are clinically useful in diagnosis, tumour localisation, and monitoring patients with ectopic hormonal syndromes. Currently the clinical value of hormone assays in the routine management of common forms of malignancy in the absence of overt ectopic hormonal syndromes is unproven. However, better characterisation of hormonal forms relatively specific for neoplasia together with improved assay specificity and sensitivity may enhance the clinical value of ectopic hormones as tumour markers, particularly in malignancies which are commonly associated with ectopic hormone production (e.g. lung cancer).

Adrenocorticotropic Hormone↗
PubMed1980

Prolactin receptors in the rat kidney.

Specific binding of 125I-labelled ovine prolactin iodinated by a lactoperoxidase method was demonstrated in crude membrane preparations of kidneys and adrenals of male Sprague-Dawley rats and livers from female rats. Membrane preparations derived from the 100,000 g fractions of tissue homogenates contained most of the specific prolactin binding. Kinetic and affinity characteristics of prolactin binding to kidney membranes were examined in detail. Maximal specific binding occurred after incubation for 30 h at room temperature. Scatchard analysis indicated that prolactin binding to kidney membranes was of high affinity (dissociation constant = 1.4 x 10(-10) mol/l) and similar to that for liver membranes, although kidney membranes from male rats bound approximately sixfold less prolactin/mg membrane protein than did liver membranes from female rats. Specific prolactin binding was demonstrated in both renal medulla and cortex. Autoradiography showed maximal prolactin binding activity in the epithelial cells of the proximal tubule and faint activity in the tubular cells throughout the nephron. Specificity of uptake by proximal tubular cells was indicated by the gross reduction in prolactin activity when excess ovine prolactin was administered simultaneously. The demonstration of specific binding sites for prolactin localized primarily in the proximal tubules was consistent with renal action of prolactin, predominantly on sodium metabolism.

Adrenal Glands↗
PubMed1979

Tests of prolactin secretion in diagnosis of prolactinomas.

Prolactin-secreting tumours of the pituitary were identified and treated by transsphenoidal microsurgery in fourteen infertile females with hyperprolactinaemia. Resting prolactin levels were 590--9000 mU/1 (mean 3400). In seven patients, tomography of the pituitary fossa was normal and resting prolactin levels were 590-6000 mU/1 (mean 3400). In these patients the pre-operative diagnosis prolactinoma in these patients was made by demonstrating loss of the normal circadian prolactin profile and impaired prolactin response to intravenous thyrotrophin-releasing hormone (T.R.H.) and metoclopramide stimulation. Prolactin response to the acute oral administration of L-dopa and bromocriptine was of less diagnostic value. Preoperative assessment of anterior pituitary function identified abnormalities other than hyperprolactinaemia in four patients (28%). Post-operative assessment indicated that microsurgery was curative in twelve patients (86%), selective in all, and without significant side-effect. It is concluded that dynamic tests such as T.R.H. and metoclopramide stimulation have considerable value in identifying hyperprolactinaemic patients with prolactin-secreting adenomas, particularly those which are radiologically occult.

Adolescent↗
PubMed1979

Radioimmunoassay of serum myelin basic protein and its application to patients with cerebrovascular accident.

Myelin basic protein-like immunoactivity was measured in the serum of patients after cerebrovascular accident (CVA) using a double antibody radioimmunoassay for myelin basic protein with a detection limit of 3 ng/ml serum. For up to 6 days after ictus, serum myelin basic protein levels in patients with severe CVA and patients who died as a result of CVA were significantly greater than those in control patients, patients with moderate CVA and patients surviving CVA. All patients with serum myelin basic protein levels greater than the range found in control subjects subsequently died. Serial dilutions of positive sera suggested that the immunoactivity differs from authentic myelin basic protein and may represent breakdown products of the protein. Serum from some patients with a previous history of moderate CVA had myelin basic protein binding activity consistent with the presence of antibodies to the protein.

Cerebrovascular Disorders↗
PubMed1979

The effect of label affinity on the sensitivity and specificity of a hapten radioimmunoassay: a comparison of three [125I]diphenylhydantoin radioligands with the 14C-labelled drug.

The effect on the sensitivity and specificity of a radioimmunoassay for diphenylhydantoin (DPH)has been investigated using three 125I-labelled tyrosine ester derivatives of DPH having different bridge lengths between the tyrosine moiety and the DPH moiety and 14C-labelled DPH. The results demonstrate that for a hapten which does not completely fill the antibody-binding sites, greatest sensitivity is achieved when the bridge of the iodine label is most dissimilar to that present in the original immunogen, when the hapten and label affinities are nearly equivalent. Greatest specificity is achieved with the label which most resembles the original immunogen. These results illustrate the difficulty of designing satisfactory labels for assays of both high specificity and sensitivity since minimal changes in label structure may produce greatly amplified changes in the subsequent affinity of the label for the antiserum.

Affinity Labels↗
PubMed1979

Glial fibrillary acidic protein (GFAP): purification from human fibrillary astrocytoma, development and validation of a radioimmunoassay for GFAP-like immunoactivity.

The extraction and purification of glial fibrillary acidic protein (GFAP) from human fibrillary cerebellar astrocytoma is described. Using an immunoperoxidase method, antisera raised to the protein showed specific staining of astrocytes in normal spinal cord and in tumours of astrocytic origin. A double antibody radioimmunoassay for GFAP in tissue extract was developed, the detection limit of the assay being 360 pg. Extracts of tissues other than brain or spinal cord did not cross-react significantly in the assay, neither did purified preparations of myelin basic and S-100 proteins. Levels of GFAP in normal CNS tissue were higest in spinal cord (1370 microgram/g wet weight) but a level of 3050 microgram/g wet weight was detected in a fibrillary astrocytoma.

Astrocytes↗
PubMed1979

The short metyrapone test: comparison of the plasma ACTH response to metyrapone and insulin-induced hypoglycaemia.

Plasma ACTH levels in response to metyrapone and insulin hypoglycaemia were compared in subjects with normal pituitary-adrenal function. After a single dose of 2 g of metyrapone given with a snack at midnight, the ACTH level was 468 ng/l +/- 66 )SEM) at 07.30 h the next morning (mean increment approximately nine fold over normal morning values). After insulin-hypoglycaemia the peak ACTH level was 369 ng/l +/- 31 (SEM). Peak ACTH levels greater than 200 ng/l were achieved in twenty of twenty-one (95%) subjects after metyrapone and twenty of twenty-four (83%) after insulin. No major side effects were noted after metyrapone. It is concluded that the short single-dose metyrapone test produces at least as strong and consistent a stimulus to ACTH release as the standard insulin-hypoglycaemia test in normal subjects. A direct assay of ACTH avoids misinterpretations which are inherent in a judgement based on compound S increase only. The short test has significant practical advantages over the classical metyrapone test, and provides a convenient and sensitive method of assessing the negative feedback ACTH control mechanism. It may be particularly useful in detecting minor degrees of pituitary suppression. The value of this test in clinical practice for the investigation of patients with hypothalamic-pituitary diseases in comparison to the classical tests of ACTH stimulation has yet to be demonstrated.

Adolescent↗
PubMed1979

Grouping of streptococci by Streptex.

Streptex was compared to routine laboratory identification methods available. The results from Streptex sometimes required several attempts before final identification could be achieved. In the main, group D streptococci other than Strep. faecalis failed to group with the Streptex antisera, and this method cannot therefore be used exclusively as a means of identifying this group of streptococci.

Immune Sera↗
PubMed1979

Total and free thyroid hormone concentrations after elective surgery.

Changes in thyroid hormone concentration and distribution and plasma cortisol levels have been followed in 11 patients undergoing elective cholocystectomy. A significant rise in total and free thyroxine (T4) and fall in total and free triiodothyronine (T3) were noted after surgery. Reverse T3 concentrations rose substantially, suggesting that peripheral conversion of T4 to T3 is diminished and that there is preferential formation of reverse T3. Serum thyroid stimulating hormone concentrations did not change. There was no direct correlation between the change in cortisol and the change in thyroid hormone or reverse T3 concentrations.

Adult↗
PubMed1979

Laboratory assessment of prolactin status.

The laboratory assessment of prolactin status was evaluated by detailed study of 921 subjects (587 normal subjects and 334 patients with pathological conditions). The effect on serum prolactin levels of age, sex, circadian rhythm, pulsatility of secretion, stress, drug ingestion, and pregnancy was defined in normal subjects. The normal prolactin responses to stimulation (TRH metoclopramide) and suppression (L-dopa, bromocriptine) were also determined. Basal prolactin levels were measured in patients with defined pathological conditions including prolactinoma, idiopathic hyperprolactinaemia, acromegaly, Cushing's disease, chronic renal failure, primary hypothyroidism, pituitary ablation, Kallman's syndrome, Nelson's syndrome, growth hormone deficiency, gonadotrophin deficiency, craniopharyngioma, panhypopituitarism, and chronic progressive arthropathy. Based on these data, a strategy for the routine laboratory assessment of prolactin status is outlined.

Adolescent↗