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Biomedical subjects

D J Goldie

Publications and source records attributed to D J Goldie.

13 recordsLinked to original sources

Diurnal profiles of serum insulin, C-peptide and blood intermediary metabolites in insulin treated diabetics, their relationship to the control of diabetes and the role of endogenous insulin secretion.

The 24-hour profiles of blood metabolites, serum free and total insulin, and C-peptide were measured in 16 insulin dependent diabetics, and then analysed in order to compare the effects of the presence or absence of residual endogenous insulin secretion and the presence of good or bad diabetic control as judged by the levels of blood glucose or total ketone bodies. Retention of endogenous insulin secretion, responsive to meals, and changes in the level of blood glucose and serum free insulin, were detected in nine patients, its presence having important effects in maintaining metabolic regulation closer towards normal. Despite the fact that apparently well controlled diabetics were selected for the study, the diurnal changes of the levels of blood metabolites, serum free and total insulin and their interrelationships were all grossly abnormal. The levels of both the blood total ketone bodies and the blood glucose were found to be a poor guide to the presence or absence of other metabolic abnormalities of diabetes. High levels of blood total ketone bodies appeared to have a protein sparing effect.

Adult

Change of insulin dosage, circulating free and bound insulin and insulin antibodies on transferring diabetics from conventional to highly purified porcine insulin.

Fifty-eight patients on long term conventional mainly bovine insulins have been transferred to highly purified porcine insulin preparations. There was an overall reduction of 22% in daily insulin dosage and improved diabetic control as shown by decreased blood glucose concentration. Increased concentrations of serum free insulin and falls in serum bound insulin levels were also found. There were reductions in the serum binding capacities and affinity constants on changeover from conventional to highly purified insulin due to a combination of the effects of differential conventional/purified porcine binding and the substitution of a low antigenicity insulin. However, 12 of the patients receiving higher doses of insulin experienced marked hypoglycaemic reactions immediately on insulin changeover despite initial dosage reductions of 30% and prior to any changes in antibody characteristics.

Adolescent

A comparison between diabetics receiving a high or low daily insulin dosage.

Two groups of 8 diabetics, similar in many aspects, who required high (greater than or equal to 128 units) or low (less than or equal to 32 units) total daily insulin dosage were compared during a 24 hour period. C-peptide secretion was detected in all but one of the low dose group, but only in two of the high dose group. No significant differences in serum free and total insulin concentrations were detected and the patterns of blood metabolites were also similar, apart from higher blood glycerol concentrations in the low dose group. No significant differences in the binding characteristics of the antiinsulin antibodies were detected.

C-Peptide

Combined test of anterior pituitary function in children.

A combined test of anterior pituitary function was used on 21 normal children. It shows that a comprehensive evaluation can be made of growth hormone, thyroid stimulating hormone, adrenocorticotrophic hormone, and gonadotrophin reserve. Simultaneous assessment of those peripheral glands associated with the anterior pituitary is possible by the measurement of thyroid hormones, cortisol, and gonadal steroids. The procedure can be completed in 4 hours with minimum inconvenience and distress to the child.

Child

Measurement of serum ferritin by radioimmunoassay.

A direct radioimmunoassay for ferritin in serum is described in which Bolton and Hunter reagent is used to label ferritin. The detection limit of the assay is 150 pg; 95% reference ranges were found to be 12-200 microgram/l for men and 5-76 microgram/l for women. Ferritin concentrations in patients with iron deficiency anaemia were found to be uniformly low in subjects with uncomplicated iron deficiency but were normal or even raised in subjects with iron deficiency anaemia associated with malignant or inflammatory conditions.

Adolescent

The relationship between circulating free and bound insulin, insulin antibodies, insulin dosage and diabetic control in insulin treated diabetics.

Free and bound insulin concentrations, blood glucose and anti-insulin antibody binding characteristics have been determined in 100 insulin treated diabetics; medium serum free insulin was 11 mU/l when fasting and rose to 30 mU/l after the mid-day meal. Significant correlation between blood glucose and serum free (but not bound) insulin was found. No relationship between insulin antibodies and daily insulin dose or diabetic control were found, nor a relationship between free insulin and antibody characteristics.

Adolescent

The "Southmead System," a simple, fully-automated, continuous-flow system for immunoassays [Appendix: application to serum thyroxine radioimmunoassay].

A simple, fully-automated, continuous-flow system suitable for radioimmunoassay, enzyme immunoassay, and fluoro-immunoassay is described. The system is versatile, inexpensive, and requires only equipment and skills that already are available in most clinical chemistry laboratories. In this system, the antibody is covalently linked to solid-phase, porous particles of agarose (Sepharose, size 40-70 micrometer in the dry form). After sampling and mixing the assay reactants, the assay "cocktail" containing the solid-phase-bound antigen and the unbound fraction is directed to the separation block. Separation is achieved by use of a highly porous membrane (pore size, about 10 micrometer) and by controlling the volume of inflow and outflow a fixed and precise amount of fluid is filtered through the membrane containing only the free (unbound fraction), which can then be quantitated. The percentage of unbound fraction misclassified is negligible (less than 1.0%). Application of these principles to the assay of serum thyroxine is described in an appendix.

Autoanalysis

Thyroid function in patients with breast cancer.

Thyroid function has been assessed in 40 patients with breast cancer and compared with an age-matched control female population. The free thyroxine index was lower and the level of thyroid-stimulating hormone in the serum higher in the cancer group and these changes became more marked at 6 months. It is concluded that patients with breast cancer show more evidence of hypothyroidism as time progresses.

Breast Neoplasms

Alcohol-induced pseudo-Cushing's syndrome.

In 4 patients corticosteroid hypersecretion associated with excessive intake of alcohol led initially to an erroneous diagnosis of Cushing's syndrome. If diagnostic errors are to be avoided, a history of alcohol intake should always be sought in a patient in whom the diagnosis of Cushing's syndrome is entertained. The abnormalities of pseudo-Cushing's syndrome revert to normal on ethanol withdrawal.

Adrenal Cortex Function Tests

The measurement of serum free insulin by steady-state gel filtration.

A method for the separation of bound and free insulin in the serum of insulin treated diabetics by steady state gel filtration is described. The method meets the criteria which have been suggested for the validation of a method of separating bound from free ligand. The precision of the method is satisfactory, and the results compare well with those obtained by the methods of ethanol precipitation and polyethylene glycol precipitation.

Chromatography, Gel

Simultaneous radioimmunoassay of thyroid hormones in unextracted serum.

A combined radioimmunoassay for the two thyroid hormones is described which uses 125iodine labelled triiodothyronine and 131iodine labelled thyroxine. The assay employs a double antibody separation technique and is suitable for use with unextracted serum. The results from the simultaneous assay compare very well with the results obtained in the single assays, and the discriminating power and precision of the simultaneous assay is a least as good as in the single assays.

Humans

The significance of raised maternal serum alpha-fetoprotein levels.

A radioimmunoassay for alpha-fetoprotein (AFP) is described and normal ranges for both maternal serum and in amniotic fluid throughout pregnancy are defined. Maternal serum AFP levels in at risk pregnancies were found to be no different from those in normal pregnancies. AFP levels in pregnancies complicated by neural tube and other congenital defects, fetal death or maternal hypertension are documented. Eight patients with a fetus deformed by anencephaly or an open spina bifida were tested before 22 weeks; seven of them had raised serum AFP levels. Other causes of raised serum AFP levels are described and the significance of a raised serum AFP level is discussed with particular reference to screening programmes.

Amniotic Fluid