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Biomedical subjects

G T Warner

Publications and source records attributed to G T Warner.

At least 19 recordsLinked to original sources

Lymphocyte proliferation and cytotoxic assays using flat-bed scintillation counting.

Lymphocyte 51Cr release and [3H]thymidine uptake assays were evaluated with respect to measurement of sample radioactivity using the flat-bed scintillation counter. 51Cr lysates were spotted onto a glass fibre filter sheet while [3H]thymidine-labelled cells were filtered onto a similar sheet using a cell harvester. The 96 samples were rapidly processed for counting, without removal of individual sample areas. Either form of preparation showed good linearity of count rate with the quantity of material on the filter. Reproducibility was good; the coefficient of variation for 96 samples being within 5%. The low background and high efficiency of this counter results in increased assay sensitivity and allows considerable economies in materials to be made. A commercial version of the counter has six counting heads permitting a high rate of sample throughput.

Beta Particles

A new design for a liquid scintillation counter for micro samples using a flat-bed geometry.

A new design for a liquid scintillation counter based on a flat-bed geometry is described. Micro-samples are dried or filtered onto transfer membranes or glass fibre filters in a 6 X 16 matrix, compatible with 96-well micro-titration plate filtration assays of labelled cells. A prototype counter without lead shielding had low background countrates (2-3 cpm for 3H) giving a figure of merit of 1325 (and 1292 for 14C). Only 5-15 ml of scintillant/96 samples are required and thus the volume of radioactive waste is low.

DNA

Calcium metabolism in subjects living with a permanent ileostomy.

Several indices of calcium metabolism have been studied in 39 subjects living with a permanent ileostomy after proctocolectomy for ulcerative colitis, and in a control group of 39 healthy volunteers, matched for age and sex. No significant differences were found in plasma levels of calcium, phosphate, magnesium, parathyroid hormone, calcitonin and 25-hydroxy-vitamin D nor in the urinary excretion of calcium and phosphate, but the alkaline phosphatase was raised in the ileostomists. The bone density of the ileostomists was rather low, but the difference from the control subjects was not statistically significant. The absorption of calcium was measured by means of a total body counter. The ileostomists retained significantly more calcium than expected. It is suggested that this may represent the correction of a state of calcium deficiency at the time of proctocolectomy, due to the effects of the colitis and its medical treatment with corticosteroids.

Alkaline Phosphatase

Iron absorption and loading in beta-thalassaemia intermedia.

Iron absorption and rates of iron accumulation were analysed in a group of patients with beta-thalassaemia intermedia. Iron absorption was strikingly increased and there was a progressive iron loading with increasing age. Balance studies indicated that by the time many of these patients reach the third or fourth decades their total iron loads may be of a similar magnitude to those of transfusion-dependent beta-thalassaemia homozygotes. If these patients are to be protected from cardiac, hepatic, and endocrine complications of iron overload in middle life it will be necessary to reduce gastrontestinal iron absorption, starting from early childhood.

Adolescent

Is 24,25-dihydroxycholecalciferol a calcium-regulating hormone in man?

Small doses (1-10 microgram daily) of 24,25-dihydroxycholecalciferol (24,25-(OH)2D3), a renal metabolite of vitamin D of uncertain function, increased intestinal absorption of calcium in normal people and in patients with various disorders or mineral metabolism, including anephric subjects. In five of six patients studied, calcium balance increased, but, unlike 1,25-dihydroxycholecalciferol, 24,25-(OH)2D3 did not increase plasma or urinary calcium concentrations. These results suggest that 24,25-(OH)2D3 may be an important regulator of skeletal metabolism in man with potential value as a therapeutic agent.

Adult

Physiological and pharmacological aspects of 24,25-dihydroxycholecalciferol in man.

The present study describes the response to small oral doses (1--10 microgram/day) of 24,25-DHCC in man. Contrary to expectation, 24,25-DHCC was as potent as 1,25-DHCC in increasing intestinal absorption of calcium both in normal persons and in patients with a variety of disorders of calcium metabolism. Despite this increase in intestinal absorption, plasma and urine calcium did not increase after 24,25-DHCC as they did after 1,25-DHCC. Metabolic balance studies showed calcium balances to increase by 1.6 to 11.5 mmoles/day in 5 of the 6 patients studied. 24,25-DHCC increased intestinal absorption of calcium equally well in anephric patients, suggesting that conversion of 24,25-DHCC to 1,24,25-trihydroxycholecalciferol by the kidney cannot be the sole mechanism by which 24,25-DHCC expresses biological activity, even though in vitamin D deficient rats nephrectomy does abolish the ability of large doses of 24,25-DHCC to increase calcium absorption. It is concluded that 24,25-DHCC may be a calcium-regulating hormone in man. In view of the effects demonstrated here and its relatively high concentration in plasma and slow turnover rate, 24,25-DHCC has the properties that might be ideal for a long-acting stimulator of bone mineralisation. Further work is needed to explain why 24,25-DHCC has effects in man which are not readily seen in other species.

Bone Development

Absorption of inorganic and haemoglobin iron in coeliac disease.

Absorption from a 5 mg dose of iron as Fe++ or haemoglobin iron was studied using a Total Body Counter in control subjects and patients with coeliac disease. In both groups the majority of subjects were iron deficient. Thirteen control subjects, 13 patients with untreated coeliac disease and 14 on treatment with gluten-free diet had both absorption tests. Absorption of Fe++ iron was reduced in untreated coeliac disease. This was particularly significant in iron deficient patients. Absorption was improved on treatment with gluten-free diet; In contrast, the absorption of haemoglobin iron was not affected in coeliac disease, indicating that absorption of iron in this form is not dependent on the integrity of the mucosa of the proximal small bowel.

Adult

Factors influencing the early plasma disappearance rate and liver uptake of thyroxine.

The early disappearance from plasma (T 1/2) of i.v. administered thyroxine (T4) labelled with 131I was studied in order to find a simple biochemical parameter with which it could be correlated in health and disease. The radioactivity of the liver was also measured by surface counting to determine the time for the peak liver count rate. The T 1/2 for the 131I-T4 showed a correlation of borderline significance with T4 in plasma but a good correlation was found with T4-binding globulin (TBG) in plasma and an even better with the T3-test. The T3-test showed a significant correlation with TBG but when the T4-binding capacity of prealbumin (TBPA) was taken into account the correlation was even better indicating that the result of the T3-test was not only dependent on the TBG concentration in plasma but also on the TBPA. The T 1/2 correlated best with the time for the liver peak count rate. The study supports the hypothesis that in the early distribution phase of T4, the free binding sites extracellularly and the available intracellular binding locations compete for T4 until a state of equilibrium is reached.

Colitis, Ulcerative

Treatment of menorrhagia with tranexamic acid. A double-blind trial.

In a double-blind trial tranexamic acid (Cyclokapron) 1 g. four times a day for the first four days of menstruation, significantly decreased menstrual blood loss in women with menorrhagia for which no organic cause had been found. No difference in side-effects was noted between the active and placebo treatment.

Adult