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Biomedical subjects

J G Ratcliffe

Publications and source records attributed to J G Ratcliffe.

At least 73 records · Page 4Linked to original sources
PubMed1982

Circulating ACTH and related peptides in lung cancer.

The prevalence of high levels of circulating ACTH-like immunoactivity was determined in 134 patients with lung cancer, using reference ranges from 52 age- and sex-matched patients with non-malignant lung disease. Two studies used ACTH radioimmunoassays with different specificities. Study A used an unextracted plasma or serum assay for total ACTH immunoactivity. High serum ACTH levels occurred in 24% of patients with small-cell carcinoma and 3% of patients with non-small-cell cancer. In patients with small-cell carcinoma, levels were high in 12% with limited disease and 32% with extensive disease. Study B used an ACTH assay after plasma extraction by porous glass, which measured mainly regular 1-39 ACTH. Here no lung-cancer patient had levels above the reference range, suggesting that the high levels in Study A may be due to plasma ACTH components which are poorly extracted by porous glass. It is concluded that high circulating ACTH immunoactivity occurs in a minority of patients with lung cancer, particularly those with extensive small-cell carcinoma. Indirect evidence suggests that the high ACTH levels detected with assays for total ACTH are due to molecular forms other than 1-39 ACTH, probably high-mol.-wt species.

Adrenocorticotropic Hormone↗
PubMed1982

Biochemical and clinical effects of fenclofenac in thyrotoxicosis.

Administration of the anti-inflammatory drug fenclofenac (600 mg bd) for 28 days to four females with thyrotoxicosis resulted in a rapid decline in thyroid hormone levels. The mean total thyroxine (T4) level of 173 +/- 8.6 (SEM) nmol/l before therapy was normalized to 70 +/- 6.4 nmol/l after administration of the drug for 7 days. Free T4 levels also decreased significantly but not to within the reference range in all subjects. Mean total triiodothyronine (T3) and reverse T3 levels declined from 6.2 +/- 0.9 nmol/l and 0.63 +/- 0.2 nmol/l respectively before therapy to 3.8 +/- 0.5 nmol/l and 0.52 +/- 0.1 nmol/l after 7 days' treatment but remained consistently elevated in all subjects. Clinical thyroid status remained unchanged despite these marked reductions in circulating thyroid hormone levels, suggesting that fenclofenac was of no therapeutic benefit.

Adult↗
PubMed1982

Precocious pseudopuberty due to a rare form of congenital adrenal hyperplasia. Biochemical investigation and pitfalls in interpretation of hormone assays.

The biochemical investigation is described of a boy who presented with precocious puberty at the age of 3 years 9 months due to a rare form of congenital adrenal hyperplasia (CAH), steroid 11 beta-hydroxylase deficiency. Serum androgen levels were grossly elevated (17 hydroxyandrogens 10 nmol/l, androstenedione 129 nmol/l), 17 hydroxyprogesterone was modestly elevated (21 nmol/l), while serum gonadotrophins were low and testes were prepubertal in size. The major differential diagnosis was between an androgen-producing tumour and CAH. Initial serum and urine corticosteroid concentrations and their responses to dexamethasone were diagnostically misleading, later found to be due to lack of specificity of the radioimmunoassays and fluorimetric methods employed. Elevated basal plasma ACTH levels and suppression of androgen and ACTH levels by dexamethasone strongly suggested CAH. Definitive diagnosis of an 11 beta-hydroxylase defect was established by capillary column gas liquid chromatography of urine which demonstrated excess androgen and 11-deoxycortisol metabolites but no cortisol metabolites. The diagnosis was confirmed by specific serum assays of 11-deoxycortisol, deoxycorticosterone, and cortisol. The contribution of hormone assays and a protocol for their use in the diagnosis and monitoring of precocious puberty is discussed.

Adrenal Hyperplasia, Congenital↗
PubMed1981

Autonomic neural control mechanisms of substrate and hormonal responses to acute hypoglycaemia in man.

The contributions of adrenergic and cholinergic mechanisms to recovery from acute hypoglycaemia induced by insulin (0.15 units/kg i.v.) were examined in eleven normal subjects, six subjects with a pre-ganglionic sympathectomy (adrenergic denervation) and six sympathectomized subjects given atropine (combined adrenergic denervation and cholinergic blockade). Blood glucose recovery was impaired only in the sympathectomized subjects given atropine. The blood lactate response was reduced and the rise in free fatty acids was delayed in both groups of sympathectomized subjects, in whom the normal rises of plasma cyclic AMP and noradrenaline were absent. The plasma pancreatic glucagon response was appropriate to the prevailing blood glucose concentrations in all three groups. The cortisol response was impaired and the pattern of ACTH secretion was abnormal in sympathectomized subjects given atropine. Growth hormone levels were higher in both sympathectomized groups. Blood glucose homeostasis was impaired during combined adrenergic denervation and cholinergic blockade. Glucagon secretion was activated independently of vagal control. In the sympathectomized group given atropine, the rise in plasma cortisol was blunted despite a greater degree of hypoglycaemia. A blockade of central cholinergic receptors producing impaired activation of ACTH secretion at hypothalamic level may explain, at least in part, this delayed restoration of normoglycaemia.

Adrenergic Fibers↗
PubMed1981

Patterns of plasma cortisol and ACTH concentrations in patients with Addison's disease treated with conventional corticosteroid replacement.

Plasma cortisol and adrenocorticotrophin hormone (ACTH) profiles were estimated in twelve patients with Addison's disease following randomized oral administration of either cortisone acetate (25 mg) or hydrocortisone (20 mg) alternately, at 0900 h on consecutive days. Normal corticosteroid replacement therapy was discontinued from 1200 h on the day prior to the study period. In four patients elevated basal plasma ACTH concentrations were not suppressed to the limit of detection following the administration of either drug, and in three of these no suppression was found following the prolonged administration of pharmacological doses of dexamethasone. Diminished sensitivity of pituitary ACTH secretion to cortisol inhibition may result from chronic loss of negative feedback before and/or after diagnosis and treatment. In three patients elevated basal plasma ACTH concentrations were suppressed adequately during the administration of either drug, but in five, low basal ACTH concentrations following corticosteroid withdrawal suggested chronic inhibition of anterior pituitary corticotrophs by over-replacement with glucocorticoid. However, further study is necessary to determine whether the estimation of ACTH profiles is a more accurate reflection of the adequacy of corticosteroid replacement than the estimation of cortisol profiles alone, and whether this estimation leads to an improvement in patient management. Hydrocortisone (20 mg) achieved higher mean cortisol levels and lower mean ACTH levels than cortisone acetate (25 mg), but either drug may be suitable for glucocorticoid replacement provided the dose is tailored to the individual needs.

Addison Disease↗
PubMed1981

The measurement of serum thyroglobulin in the presence of thyroglobulin antibodies.

In a significant proportion of patients with thyroid disorders, thyroglobulin antibodies (TgAb) invalidate double-antibody radioimmunoassays (RIA) for thyroglobulin (Tg). A modified RIA procedure for determining serum Tg in the presence of TgAb, is described. Two measurements are made on each sample. a Ratio of immunoglobulin (Ig)-bound thyroglobulin to free thyroglobulin (bound:free ratio). This is measured by the distribution of a trace quantity of 125I-Tg between bound and free fractions. b Concentration of free, i.e. unbound thyroglobulin. This is measured in the supernatant after precipitation of IgG-bound Tg. Then, bound Tg=B:F x (free Tg) and total Tg=(bound Tg)+(free Tg). Critical factors examined in the validation of the modified method were: (1) use of immunologically intact 125I-Tg (specific activity less than or equal to 5 mCi/mg); (2) equilibration of tracer Tg with endogenous serum Tg, and (3) clean separation of IgG-bound and free fractions of Tg with goat anti-human IgG. Recovery of added Tg in the presence of TgAb was 105% and interassay precision of total Tg assay was less than or equal to 9.3%. In euthyroid subjects without TgAb, the correlation between total Tg levels by the modified and standard double-antibody method was 0.931. The correlation was much poorer in the presence of TgAb (r=0.752) reflecting their interference in the standard method. Reference ranges for serum total Tg levels by the modified method in euthyroid, hyper- and hypothyroid subjects with and without TgAb are detailed.

Adolescent↗
PubMed1981

The short metyrapone test: comparison of the plasma ACTH response to metyrapone with the cortisol response to insulin-induced hypoglycaemia in patients with pituitary disease.

After a single dose of 2 g metyrapone given with a snack at 2300 h, blood was taken for estimation of plasma adrenocorticotrophin hormone (ACTH) concentrations at 0800 h the next morning from normal individuals and from patients with pituitary disease. Plasma ACTH concentrations following metyrapone were significantly lower in patients with pituitary disease with no evidence of anterior pituitary hormone deficiency (mean 90.0 +/- SD 63.9 ng/l) when compared with normal individuals (mean 182.5 +/- SD 14.1 ng/l, P leads than 0.01) but significantly greater than in patients with pituitary disease in whom a deficiency of one or more anterior pituitary hormones was demonstrated (mean 50.8 +/- SD 14.1 ng/l, P less than 0.01). It is concluded that the short metyrapone test is a sensitive method of detecting minor degrees of impairment of the negative feedback control of aCTH secretion that would be unrecognized by conventional assessment by insulin-induced hypoglycaemia. The clinical relevance of impaired ACTH release in response to a single dose of metyrapone in patients with pituitary tumours, in whom pituitary function is otherwise shown to be adequate, needs to be determined.

Adrenocorticotropic Hormone↗
PubMed1981

Diabetic ketoalkalosis due to ectopic ACTH production from an oat cell carcinoma.

A diabetic patient is described who presented with the bizarre biochemical association of hyperglycaemia, ketosis and severe alkalosis. Investigation revealed hypercortisolaemia due to ectopic adrenocorticotrophic hormone secretion from an oat cell carcinoma of the bronchus and post-mortem studies demonstrated clinically unsuspected resolving pancreatitis. a possible mechanism for the metabolic upset is discussed.

Acidosis↗
PubMed1981

Prolactin status in chronic nephropathy in the rat.

Decreased specific prolactin binding to kidney membrane preparations, and an upward trend in serum prolactin levels were observed concomitantly with the onset of chronic progressive nephropathy im male rats of the OFA Sandoz SPF strain. Females of the same strain developed a less severe form of the disease at a later age, but failed to show the changes in prolactin status seen in male rats. Nephropathy in both male and female animals was associated with morphological abnormalities of a predominantly tubular nature, but was not associated with development of renal failure as indicated by serum urea and creatinine levels. Possible mechanisms for the observed alterations in prolactin status are discussed.

Aging↗
PubMed1981

Prolactin status in experimentally induced acute renal failure in the rat.

Serum prolactin levels were elevated in male Sprague-Dawley rats with acute renal failure induced by glycerol administration. Specific prolactin binding to kidney membrane preparations was reduced in glycerol and antirat glomerular basement membrane serum-treated rats, after morphological and biochemical acute renal failure was evident. Extensive tubular damage after glycerol administration may account for loss of renal binding, since prolactin receptors are mainly tubular in localization. However, the predominant glomerulopathy, with less severe tubular lesions, after antirat glomerular basement membrane serum suggests that reduced renal prolactin binding in these animals is unlikely to be due to tubular destruction alone. Thus, alterations in prolactin status occur with development of experimentally induced acute renal failure and suggest altered renal responsiveness to prolactin in uraemia.

Acute Kidney Injury↗
PubMed1981

Neonatal screening for hypothyroidism in Scotland: results of a pilot study.

We have assessed the feasibility of screening for neonatal hypothyroidism based on thyroxine (T4) or thyrotrophin (TSH) assays on dried blood spots collected for the phenylketonuria (PKU) screening programme in Scotland. The TSH assay was both more sensitive and specific than T4 in detecting primary hypothyroidism and was sufficiently rugged and rapid for routine application. Using a labelled antibody assay for TSH, 99.7 per cent of the first 30,000 babies tested had values less than 25 mU/l, and 0.24 per cent had values between 25 and 50 mU/l. Of the 11 suspected positives (TSH greater than 50 mU/l), nine were confirmed on serum specimens as primary hypothyroidism (prevalence 1:3,300) and the two false positives (0.007% of total) were explicable by inappropriate time of sampling. No false negatives have so far been identified. The median time to detection by blood spot assay was 16 days (range 6 to 22 days). Five of the nine cases were not suspected clinically at the time of screening. It is concluded that TSH fulfils most of the criteria for an ideal screening test for primary hypothyroidism and a screening programme based on blood spot TSH will allow therapy to be commenced within one month of birth.

Congenital Hypothyroidism↗
PubMed1981

Syndrome of inappropriate ADH secretion concealed by hypokalaemia due to ectopic ACTH production.

A case is described of a patient with an oat cell carcinoma of the bronchus with moderately elevated levels of plasma corticotrophin (ACTH) and antidiuretic hormone (ADH). Ectopic secretion of ACTH induced severe hypokalaemia and concealed the effects of concomitant ADH secretion on renal function. Normal renal responsiveness was restored following correction of hypokalaemia. The hypokalaemia was associated with evidence of a marked increase in corticosteroid secretion but plasma ACTH concentrations did not show a proportionate elevation. Chromatographic studies on tumour extracts suggest that the presence of a large fraction of high molecular weight ACTH in plasma could explain this discrepancy.

Adrenocorticotropic Hormone↗
PubMed1981

Automated particle-counting immunoassay for alpha-fetoprotein.

PACIA, a homogeneous non-radioimmunoassay, has been adapted to the determination of serum alpha 1-fetoprotein. This technique is based on the agglutination of latex particles coated with antibodies to the antigen to be determined. The agglutination is measured by using an optical cell counter designed to count blood cells, to determine the reduction in the number of non-agglutinated particles. Interferences by serum constituents are avoided by coating the particles with the F(ab')2-fragments of th immunoglobulin G fraction of the antiserum. The system is automated, with a sampling rate of 50/h and an incubation time of 26 min. Concentrations used in preparing the standard curve ranged from 1 to 50 microgram/L; analytical recoveries were 93.5 to 98.4%; the correlation coefficient of PACIA with radioimmunoassay, calculated from results on 127 samples, was 0.98; maximum within- and between-assay CVs were 7.4% and 9.6%, respectively.

Agglutination Tests↗
PubMed1980

The clinical significance of the pattern of elevated serum carcinoembryonic antigen (CEA) levels in recurrent colorectal cancer.

Serial serum carcinoembryonic antigen (CEA) assays were performed in 148 patients after potentially curative surgery for colorectal cancer. Thirty-seven patients developed proved recurrent tumour in a follow-up period of 2-5 years. Elevated CEA levels were recorded in 36 of these patients and in 27 rising levels preceded clinical symptoms of recurrent tumour. Two distinct patterns of CEA rise were observed: a 'fast' rise in which serum concentrations reached 100 microgram/l within 6 months of the first elevation and a 'slow' rise in which concentrations remained less than 75 microgram/l for at least 12 months. The majority of patients with the 'fast' rise had metastatic spread, whereas most patients with a 'slow' rise had local recurrence alone. This differential pattern may help to predict the site of recurrent tumour.

Adenocarcinoma↗