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Biomedical subjects

P J Howorth

Publications and source records attributed to P J Howorth.

11 recordsLinked to original sources

SI units and acidity.

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Hydrogen-Ion Concentration

Controlled trial of synthetic D-penicillamine and prednisone in maintenance therapy for active chronic hepatitis.

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.

Adolescent

Rapid radioimmunoassay of triiodothyronine on Sephadex G-25 by the Ames kit.

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.

Contraceptives, Oral

Hormonal pattern of relapse in hyperthyroidism.

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.

Carbimazole

A comparative study of serum total thyroxine estimation on unextracted serum by radioimmunoassay and by competitive protein binding.

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.

Binding, Competitive

The physiological assessment of acid-base balance.

Acid-base terminology including the sue of SI units is reviewed. The historical reasons why nomograms have been particularly used in acid-base work are discussed. The theoretical basis of the Henderson-Hasselbalch equation is considered. It is emphasized that the solubility of CO2 in plasma and the apparent first dissociation constant of carbonic acid are not chemical constants when applied to media of uncertain and varying composition such as blood plasma. The use of the Henderson-Hasselbalch equation in making hypothermia corrections for PCO2 is discussed. The Astrup system for the in vitro determination of blood gases and derived parameters is described and the theoretical weakness of the base excess concept stressed. A more clinically-oriented approach to the assessment of acid-base problems is presented. Measurement of blood [H+] and PCO2 are considered to be primary data which should be recorded on a chart with in vivo CO2-titration lines (see below). Clinical information and results of other laboratory investigations such as plasma bicarbonate, PO2,P50 are then to be considered together with the primary data. In order to interpret this combined information it is essential to take into account the known ventilatory response to metabolic acidosis and alkalosis, and the renal response to respiratory acidosis and alkalosis. The use is recommended of a chart showing the whole-body CO2-titration points obtained when patients with different initial levels of non-respiratory [H+] are ventilated. A number of examples are given of the use of this [H+] and PCO2 in vivo chart in the interpretation of acid-base data. The aetiology, prognosis and treatment of metabolic alkalosis is briefly reviewed. Treatment with intravenous acid is recommended for established cases. Attention is drawn to the possibility of iatrogenic production of metabolic alkalosis. Caution is expressed over the use of intravenous alkali in all but the severest cases of metabolic acidosis. The role of 2,3-diphosphoglycerate on tissue oxygenation is stressed and use of intravenous sodium phosphate as an alternative to intravenous bicarbonate is mentioned.

Acid-Base Equilibrium