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Biomedical subjects

J G Ratcliffe

Publications and source records attributed to J G Ratcliffe.

At least 127 records · Page 7Linked to original sources
PubMed1978

Hypothalamo-pituitary-thyroid axis function during cardiopulmonary bypass.

Marked alterations in levels of circulating thyroid hormone were found in patients undergoing cardiopulmonary bypass with a rise in the free thyroxine and a fall in the free triiodothyronine levels. Studies using thyrotropin-releasing hormone during bypass demonstrated a blunted response to this stimulus. This reduced response is related to changes in thyroid hormone levels and it is suggested that bypass surgery may have a direct inhibitory action on thyroid-stimulating hormone release at the hypothalamo-pituitary level. The potential significance of these hormonal changes is discussed.

Adult↗
PubMed1977

The evaluation of a radioimmunoassay for diphenylhydantoin using an iodinated tracer.

Radioimmunoassays (RIA) for diphenylhydantoin (DPH) are described using a rabbit antiserum to the immunogen, diphenylhydantoin-3-omega-valerate bovine serum albumin, and DPH labelled with carbon-14 (14C), tritium (3H) or iodine-125 (125I). The [125I]DPH label is prepared by iodination of DPH-3-N-ethyl-acetamido-tyrosine ethyl ester, and is stable for several months. The radioimmunoassays are rapid, precise, specific and sensitive requiring only 50 microliter serum for duplicate analyses. Serum DPH levels measured by the three RIA methods correlate well with each other (3H vs. 14C, r = 0.96 : 3H vs. 125I, r = 0.97) and with values obtained by a conventional gas chromatographic method (125I RIA vs. GC, r = 0.95). However, RIA employing the iodinated DPH tracer has significant practical advantages over the other methods and is well suited to large scale clinical application.

Carbon Radioisotopes↗
PubMed1977

Salivary phenytoin radioimmunoassay. A simple method of the assessment of non-protein bound drug concentrations.

A simple, specific and rapid radioimmunoassay (RIA) method for the assessment of non-protein bound ('free') phenytoin (DPH) concentrations in mixed saliva is described. Epileptic patients on maintenance phenytoin therapy have mixed saliva phenytoin concentrations similar to 'free' drug levels measured directly in serum or cerebrospinal fluid (CSF), Salivary phenytoin levels are approximately 10% of the total serum level in treated epileptic patients and in normal subjects after ingestion of a single oral dose. The half time of disappearance of phenytoin after 100 or 300 mg doses is 12.2 +/- 3.0 (SD) h in serum and 12.3 +/- 3.2 (SD) h in saliva. This method of assessing the biologically active fraction of the drug may be particularly valuable in situations where serum protein binding is abnormal or in drug interactions. It is also non-invasive and requires small sample volumes (20mul) and may therefore be valuable in paediatric practice and in pharmacokinetic studies in which multiple venepunctures would otherwise be required.

Adult↗
PubMed1977

Lung tumours and ACTH production.

ACTH levels measured by N- and C-terminal immunoassays and cytochemical bioassay, were measured in fourteen lung tumours not associated with the ectopic ACTH syndrome and in macroscopically normal lung tissue taken from the same patients at thoracotomy. Significant concentrations of immunocative (greater than 3 ng/g wet weight) and bioactive (greater than 0.2 ng/g wet weight) ACTH were found in all the carcinoid and oat cell tumours (n=9), a combined tumour (poorly differentiated adenocarcinoma with large cell carcinoid elements), and a poorly differentiated squamous cell tumour. All the carcinoid tumours contained more C- than N-terminal ACTH immunoactivity. The squamous cell tumours (n=2), anaplastic tumours (n=2) and adenocarcinoma contained insignificant ACTH levels. There was a good correlation between the ACTH levels and the presence of secretory granules in the tumours examined ultrastructually. All the macroscopically normal samples of lung tissue contained immuno and bioactive ACTH-like material, the levels of which correlated well with ACTH levels in the tumour tissue. It is suggested that all lung tumours of carcinoid or oat cell type synthesize ACTH-like materials although clinical evidence of the ectopic ACTH syndrome may be absent. The presence of ACTH-like materials in non-tumorous lung tissue in patients with lung cancer may indicate a low level of ACTH production throughout the lung or sequestration of ACTH containing granules secreted by the tumour.

Adenocarcinoma↗
PubMed1977

Thyroid function in adults with Down's syndrome.

The thyroid status of 82 institutionalized adults with Down's syndrome has been assessed. Compared to age and sex matched control subjects, these patients had significantly lower mean total serum thyroxine (T4) and triiodothyronine (T3) concentrations (T4; 69.1+/-22.2 nmol/1; (mean+/-SD) vs. 100.1+/-19.1, P less than 0.001; T13; 1.61+/-0.47 nmol/1 vs. 1.76+/-0.34, P less than 0.025), lower free thyroxine index (FTI), (FTI; 66.1+/-22.4 vs. 95.1+/-20.2, P less than 0.001), and higher basal serum thyrotrophin (TSH) concentrations (TSH; 7.6+/-10.7 mU/1 vs. 3.8+/-1.5, P less than 0.001). These changes were not related to age or sex. Abnormalities in one or more test of thyroid function were demonstrated in at least 38 (46%) of the 82 patients. Two main patterns of abnormality were defined: 1) subnormal T4, FTI and elevated basal TSH levels (primary hypothyroidism) in 13 (16%). All seven of the 13 patients in whom TRH tests were performed showed the expected exaggerated TSH response, and seven out of the 13 patients (54%) had positive thyroid antibodies, 2) Subnormal T4, subnormal or low normal FTI, and basal TSH levels within the normal range in 18 (22%). The mean basal TSH concentration was, however, significantly higher than in patients with normal T4 and FTI levels, suggesting a minor degree of thyroid failure. Only two of the 18 patients (11%) had positive thyroid antibodies. Of the 17 patients in the group tested, 13 showed a normal TSH response to TRH, three an exagerrated response (all females), and one had an impaired response. Other patterns of abnormal thyroid function were observed occasionally: one female patient had biochemical T3 toxicosis; another had the biochemical pattern of subclinical hypothyroidism, four patients with normal basal T4, FTI and TSH levels showed an exaggerated TSH response to TRH and one patient had an impaired response. These data indicate that htyroid dysfunction, in particular hypothyroidism, is common in adults with Down's syndrome, though specific tests are usually required to make the diagnosis. The general reduction in thyroid function in Down's syndrome may be due to impaired development of the thyroid gland. However, frank chemical hypothyroidism may occur only when thyroiditis is superimposed on preexisting diminished thyroid reserve.

Adult↗
PubMed1977

Developmental changes in the responses of the adrenal glands of foetal sheep to endogenous adrenocorticotrophin, as indicated by hormone responses to hypoxaemia.

The change in plasma ACTH and corticosteroid concentrations in response to a 60 min period of hypoxaemia were studied in foetal and adult sheep during the latter half of pregnancy. Hypoxaemia consistently caused large rises in the concentration of ACTH in foetal plasma, the magnitude of which did not change with gestational age but was related to the physiological state of the foetus. Before 139 days small and slow rises in corticosteroid (predominantly cortisol) concentration in foetal plasma were observed during hypoxaemia, and these may have been of maternal origin. After 139 days, hypoxaemia caused a rapid and large rise in the concentration of cortisol and corticosterone in foetal plasma, which was largely of foetal origin. Hypoxaemia caused no consistent change in maternal plasma ACTH concentration but was associated with progressive increases in plasma cortisol concentrations. The cortisol: corticosterone ratio in foetal plasma was 1-5 before 139 days and increased to 4-1 several days before term which was lower than the value of 9 in maternal plasma. Small concentrations of 11-deoxycortisol and cortisone were detected in maternal and foetal plasma, the changes of which were small during hypoxaemia. The results indicate that a maturational change in the sensitivity of the foetal adrenal to endogenous ACTH occurs several days before term.

Adrenal Glands↗
PubMed1977

Sporadic non-toxic goitre. A long-term follow-up of 36 patients.

Thirty-six patients with non-toxic goitre were reviewed after a mean period of 13 years. Initially 19 patients were iodine deficient (Group I) and 17 had normal plasma inorganic iodine (Group II). In general the iodine deficient patients had larger goitres, developed more complications (26% became hyperthyroid, hypothyroid or required partial thyroidectomy), and required more treatment. There were marked changes in thyroid function tests. In both groups thyroid uptake fell and PII rose though the final PII remained significantly lower in Group I patients. Thyroid and renal iodide clearance fell significantly in Group I patients only. In both groups the final mean total serum T3 levels were abnormally elevated whereas the mean PBI levels did not change significantly during the period of study and the final mean total T4 concentrations were noraml. All goitres became smaller and there were no complications in patients whose goitre became impalpable. No cases of malignancy and no postoperative recurrences of goitre were observed. It is suggested that the incidence of complications in those patients who persist with palpable goitres is sufficent to merit follow-up of this group.

Aged↗
PubMed1977

Radioimmunoassay of lysergic acid diethylamide (LSD) in serum and urine by using antisera of different specificities.

We raised high-titre antisera to two LSD-bovine serum albumin conjugates, one linked via the indole nitrogen, the other via the amide side-chain. The antisera were specific for different parts of the LSD molecule, as demonstrated by cross-reactivity studies with LSD, its metabolites, ergot alkoloids, and closely related compounds. The antisera were used to develop a double-antibody radioimmunoassay with a detection limit of about 0.4 mug of LSD per liter of unextracted urine or serum. We saw no nonspecific interference by urine, serum, or from a series of commonly used drugs. There was good correlation between immunoassay values obtained with the two antisera (r = 0.91). However, the antiserum linked via the indole nitrogen gave consistently higher results for samples from persons who had taken LSD, owing to greater cross-reactivity with LSD metabolites. Radioimmunoassay by use of two such antisera is a more specific screening procedure for LSD abuse than has been available previously. In addition, antisera cross-reacting with LSD metabolites allow measurement of these compounds, for which there is no satisfactory method at the concentrations found in biological fluids in man.

Antibody Specificity↗
PubMed1976

Production and characterisation of antisera to diphenylhydantoin suitable for radioimmunoassay.

The effect of carrier protein, nature of hapten-carrier bridge, and density of hapten substitution on the immunogenicity of diphenylhydantoin (DPH) derivatives in rabbits is described. DPH-3-valerate-bovine serum albumin (BSA) with a hapten: protein ratio of 27: 1 yields antisera of high titre and specificity for DPH. An antiserum to DPH-valerate-BSA was employed to develop a rapid, sensitive, one stage double antibody radioimmunoassay suitable for clinical application to serum, saliva, and urine samples. The assay, using 14C-DPH as tracer, is accurate and precise over the range 0.5--50 mug DPH per ml. Results by radioimmunoassay correlate closely with those obtained by gas-liquid chromatography (r = 0.97).

Animals↗
PubMed1976

The assessment of 125I treatment of thyrotoxicosis.

257 patients have been reviewed 1-5 years (mean 3 years 2 months) after receiving one of five dose regimes of 125I for thyrotoxicosis. The cumulative incidence of hypothyroidism was 34% and of persistent thyrotoxicosis 17%. The group receiving doses between 351 and 500 muCi/g had the highest proportion of euthyroid patients (65%) with the lowest requirement for repeat therapy (46%). In the euthyroid patients, increasing dose of 125I was associated with progressive decline in mean thyroxine (T4) level and free thyroxine index (FTI) within the respective normal ranges, and increase in mean thyroid stimulating hormone (TSH) level to above the normal range. Euthyroid patients with elevated TSH levels had significantly lower T4 and FTI values compared with those with normal TSH, and showed a 3-4-fold increased rate of development of hypothyroidism over 1 year. Euthyroid patients with elevated T3 levels remained euthyroid during the subsequent year and mean T3 levels declined significantly, suggesting that abnormally elevated T3 levels after 125I do not generally indicate impending relapse of thyrotoxicosis. It is concluded that the potential admantages of 125I therapy for thyrotoxicosis in reducing the incidence of hypothyroidism have not been realized in practice.

Adult↗