Biomedical subjects
Publications and source records attributed to P J Howorth.
The two common forms of heat illness in the Services are heatstroke and heat exhaustion. Biochemical predisposing factors are considered for each. Susceptibility to malignant hyperthermia should be tested for in cases of heat stroke. The heterozygote status for cystic fibrosis should be established in cases of heat exhaustion.
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The role of intravenous salt solutions in resuscitation is reviewed historically. A brief account of the pathophysiology of shock is given. The particular use of hypertonic solutions in the resuscitation of severely shocked patients is reviewed and its mechanism of action discussed. It is considered that hypertonic solutions may find a role in any future major military conflict. Two hypertonic solutions that are suggested for consideration in this context are 12% sodium chloride (2 mmol/ml) and 8.4% sodium bicarbonate (1 mmol/ml).
Pure thyroxine-binding globulin (TBG) is required in radioimmunoassay to prepare monospecific antisera, [125I]TBG and as primary standard. Homogeneous TBG was prepared by a three-stage affinity chromatography procedure; it could not be dissociated into subunits and its molecular weight by SDS polyacrylamide gel electrophoresis was 59 000. The amino acid composition was in agreement with two earlier reports. The secondary structure determined by circular dichroism in the far U.V. showed it to contain 24% each of alpha-helix and beta-pleated sheet. Serum TBG was determined by a 24-h radioimmunoassay using polyethyleneglycol to separate bound and free TBG. Serum TBG (mg/l, mean +/- S.D.) was: normal men 15.3 +/- 2.11 (n = 34), normal women 18.4 +/- 2.72 (n = 32) (P less than 0.005), in women on oral oestrogens 24.0 +/- 5.0 (n = 23), in normal pregnancy 38.6 +/- 3.0 (n =37), in cord blood 21.7 +/- 3.5 (n = 25) (P less than 0.001) and in euthyroid subjects aged over 60 years 17.8 +/- 4.5 (P n.s.). In women with thyroid disease TBG was reduced in hyperthyroidism: 15.5 +/- 2.5 (n = 28) and elevated in hypothyroidism: 21.0 +/- 4.0 (n = 25). Wider use in TBG-assay of non-denatured TBG of proven composition and structure should decrease the scatter in reference ranges and improve its value as a routine thyroid function test as both a primary measurement and as the T4 : TBG ratio.
Three kits for measurement of serum thyroxine-binding globulin (TBG) were compared with a reference radioimmunoassay in forty-three normal euthyroid subjects. The Corning Immophase kit gave similar results to those with the reference method with satisfactory precision and accuracy. The Behringwerke AG RIA-gnost kit gave results with adequate but lower correlation with the reference method (r = 0.80) than that of the Corning kit trial (r = 0.92). The mean value was significantly greater than the reference method mean, indicating that the Behringwerke kit was inaccurately standardized. The CEA-Sorin TBG kit (Eurotope services) gave results with a poor correlation against the reference method (r = 0.59). The mean value was also significantly greater than the reference mean indicating that this kit is both inaccurately standardized and less precise than the other two. It is stressed that TBG-kits need to be periodically standardized against reference methods in the absence of properly validated primary standards in all batches.
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In view of promising, but uncontrolled, reports of the use of D-penicillamine in active chronic hepatitis, a randomised, prospective, controlled trial of this drug against prednisone was carried out. Of the 35 patients entered, 18 received D-penicillamine (increasing to 1-2 g daily) and 17 prednisone (15 mg daily). In all patients the disease had already been brought under biochemical control with corticosteroids. During the first year of the trial, the treatment of nine patients in the D-penicillamine group was discontinued (two because of lack of disease control and seven because of side-effects) compared with six patients in the prednisone group (four because of lack of disease control, one because of side-effects, and one because of the development of carcinomatosis. Detailed statistical analysis of the liver function tests in the patients remaining in the trial at the end of the year showed no significant differences. D-penicillamine is associated with a higher frequency of side-effects than is prednisone. However, in some patients it is as satisfactory as prednisone in keeping the disease under control.
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A rapid kit method for the determination of serum triiodothyronine levels is described. The method was satisfactory in cases of thyrotoxicosis, but its lower sensitivity in euthyroid patients gave higher levels (range 2.3-3.3 nM/liter) than normally found. The kit would be of value as a rapid method (little over 3 hr) to screen patients suspected of early or T3 thyrotoxicosis.
22 patients with Grave's disease were followed up for up to a year after antithyroid drug therapy was discontinued. Clinical assessment and serum T3, T4, and thyroid-stimulating-hormone (T.S.H.) estimations were done serially and simultaneously. Serum T3 or T4 concentrations may be elevated briefly in the first few weeks after antithyroid drugs are stopped, as a rebound effect not necessarily indicative of subsequent relapsf. Clinical relapse of hyperthyroidism with subsequent improvement on antithyroid drugs occurred in 13 patients. Of these 13, serum T3 concentrations became elevated before serum T4 concentrations in 5, thus predicting the subsequent development of clinical hyperthyroidism. In the remaining 8 patients who relapsed, serum T4 was elevated a month before the serum T3. Hyperthyroidism was diagnosed clinically after elevated serum T3 concentrations in 11 patients and at the same time in 2 patients. The mean period of "biochemical hyperthyroidism" in these 11 patients was 12 weeks, with a range of 1 to 56 weeks. During this period 9 of the 11 had minor clinical changes attributable to hyperthyroidism. It is concluded that serial estimations of serum T3 provide the most reliable method of monitoring relapse in hyperthyroidism.
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A rapid and precise radioimmunoassay (RIA) for serum total thyroxine (T4) on as little as 1-10 mul of unextracted serum is described. Results in hypothyroidism (overt and borderline), in euthyroid subjects in pregnant and oestrogen-medicated subjects, and in hyperthyroidism (overt and borderline) are compared with the results on the same sera by an established competitive protein binding technique (Ames' Tetralute) on unextracted serum from a different laboratory. The correlation between the two methods was excellent (r= 0.94) and no significant difference between overall appeared to measure total T4 Reliaby in sera containing only 1-3 or 2-6 nmol/1. Both methods predicted the clinical outcome in borderline hypothyroidism and borderline hyperthyroidism equally well and both gave normal results in T3-toxicosis. It is concluded that both techniques reliably measure total T4- RIA appears to have advantages of sensitivity and precision (especially in the hypothroid range), of simplicity, and of low cost.
A system has been developed for the analysis of 24-h urine collections for sodium, potassium, calcium, phosphate, urea, and creatinine, using a six channel AutoAnalyzer for the analysis,and a computer for calculating the results and producing cumulative reports.
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