Search PubMedSearch

Biomedical subjects

K E McColl

Publications and source records attributed to K E McColl.

13 recordsLinked to original sources

The effect of H2-blockade on plasma gastrin concentration in patients with an achlorhydric stomach.

The mechanisms of hypergastrinaemia during H2-receptor antagonist therapy remain unclear. In addition, the effect of food stimulation in conditions of hypergastrinaemia is poorly understood. These effects may be important when considering long-term therapy with potent acid inhibitory agents. To investigate this we studied the effect of H2-receptor antagonist therapy on basal and meal-stimulated plasma gastrin concentrations in 9 patients with pentagastrin fast gastric achlorhydria associated with pernicious anaemia. The subjects received in double-blind randomized fashion 28-day courses of 300 mg ranitidine q.d.s. and placebo, with one-month wash-out between. The fasting and peptone meal-stimulated gastrin concentrations were studied on the final day of each course of treatment. The median fasting gastrin concentrations (ng/L) were similar following placebo (1100, range 25-2100), and 300 mg ranitidine q.d.s. (1075, range 15-2600) and both markedly elevated when compared with our laboratory's normal range of 0-100. Despite the elevated basal levels the pernicious anaemia patients still showed a further increase in response to the peptone meal. Their median peak percentage rise over basal in response to the meal was similar following placebo (96%, range 0-375) and 300 mg ranitidine q.d.s. (100%, range 25-425) (both P less than 0.02 c.f. basal). This study shows that: (a) in hypergastrinaemia in pernicious anaemia subjects, meal stimulation leads to a marked and prolonged increase in plasma gastrin concentrations; (b) H2-receptor antagonists have no effect on plasma gastrin in the neutral stomach and this is consistent with their gastrin effect being entirely secondary to acid inhibition.

Achlorhydria

Hypertension and renal impairment as complications of acute porphyria.

Chronic hypertension with renal failure is the most common cause of death in a large family (10 children, 40 grandchildren, 109 great-grandchildren) with acute porphyria. A prospective study of 26 porphyric (19 latent) and 26 nonporphyric subjects shows a significant difference between mean systolic (141 versus 123 mmHg, P < 0.05) and diastolic (88 versus 74 mmHg, P < 0.05) blood pressures and plasma creatinines (geometric mean 99 versus 79 mmol/l, P < 0.02). Five of the 19 porphyric grandchildren have died of the complications of chronic hypertension, with renal failure in three. When the results of the retrospective and prospective studies in these 19 subjects are combined, 10 of the 16 tested (62%) had hypertension and seven of the 14 tested (50%) had renal impairment. Neither hypertension nor renal failure are known to affect the 21 grandchildren who were either not porphyric or of unknown status. This family provides a unique opportunity to study these common but little reported sequelae of acute porphyria. These complications affect subjects with latent porphyria as well as those who have experienced clinical attacks.

Acute Disease

Haematin therapy and leucocyte delta-aminolevulinic-acid-synthase activity in prolonged attack of acute porphyria.

The activity of leucocyte delta-aminolaevulinic-acid (A.L.A.) synthase was monitored throughout a prolonged attack of acute intermittent porphyria in a 29-year-old women. Clinical severity was associated with a pronounced increase in activity of this enzyme and high urinary excretion of A.L.A. Haematin therapy resulted in clinical improvement associated with a reduction in the activity of A.L.A. synthase and reduction in urinary excretion of A.L.A.

5-Aminolevulinate Synthetase

Correlation of ethanol concentrations in blood and saliva.

1. The concentrations of ethanol in blood, mixed saliva obtained before and after rinsing and drying the mouth and parotid saliva have been monitored in 12 healthy subjects after the ingestion of alcohol. 2. A highly significant linear correlation was found between blood and the three types of saliva examined from 20 min after completion of drinking. 3. Blood and mixed saliva samples were obtained from 20 patients attending the Casualty Department with evidence of ethanol intoxication. A similar correlation was obtained. 4. These results show that salivary ethanol may be used as an index of blood ethanol concentrations, provided that the salivary sample is not obtained within 20 min of the ingestion of alcohol.

Adult

The porphyrias.

The heterogeneous group of diseases called the porphyrias may all be characterised by derangement of specific stages in the haem biosynthetic pathway. In the acute porphyrias; acute intermittent porphyria, urophorphyrinogen 1 synthase, hereditary coproporphyria, coproporphyrinogen oxidase and variegate porphyria, ferrochelatase or protoporphyrinogen oxidase, are the enzymes affected, whilst in the non acute porphyrias, cutaneous hepatic porphyria, uroporphyrinogen decarboxylase, congenital porphyria, uroporphyrinogen cosynthase; and erythropoietic protoporphyria; ferrochelatase are the enzymes affected. In each of the porphyrias, the activity of the initial and rate controlling enzyme of the pathway, delta-aminolaevulinic acid synthase is raised which constitutes the principal control point of the pathway. Secondary control in each of these diseases lies at the leve of uroporphyrinogen 1 synthase. As a consequence of this secondary control, there is excessive excretion of the porphyrin precursors delta-aminolaevulinic acid and porphobilinogen in the acute porphyrias and excessive excretion of porphyrins leading to solar photosensitivity in the non-acute porphyrias and in variegate and hereditary coproporphyria. There are a number of secondary metabolic aspects in the porphyrias, such as the role of steroid metabolism; the influence of drugs in the potentiation of attacks; and the potential for the pathway to branch at stages prior to porphyrin formation which result in the synthesis of various monopyrroles. The therapy of the two groups of porphyrias are quite different. Prophylaxis is important in both types but is particularly important in the avoidance of various drugs in the acute porphyrias. The acute attack may be specifically treated with carbohydrates, beta-blockers and haematin. Cutaneous hepatic porphyria may be treated by venesection, erythropoietic protoporphyria with beta caratene whilst congenital porphyria may be improved by splenectomy and chloroquine therapy.

5-Aminolevulinate Synthetase

Haem biosynthesis in cutaneous hepatic porphyria: comparison with alcoholism and liver disease.

The enzymes of haem biosynthesis have been measured in the peripheral blood of 13 patients with cutaneous hepatic porphyria. The activity of leucocyte delta-aminolaevulinic acid synthase was significantly elevated (p less than 0.001) as was that of erythrocyte porphobilinogen deaminase (p less than 0.05). Leucocyte ferrochelatase activity was depressed (p less than 0.001) and the activity of erythrocyte uroporphyrinogen decarboxylase did not significantly differ from control values. Similar enzyme activities were assayed in 12 chronic alcoholics and 8 patients with liver disease and the results differed markedly from those obtained from the porphyric patients. It is unlikely that the raised leucocyte delta-amino-laevulinic acid synthase activity can be attributed to alcohol ingestion or liver disease. A defect in the activity of uroporphyrinogen decarboxylase may exist in cutaneous hepatic porphyria but this could not be demonstrated in erythrocytes in this study.

5-Aminolevulinate Synthetase

Parotid salivary gland function in patients with exocrine pancreatic insufficiency.

Parotid function tests were performed on 12 patients with pancreatic insufficiency due to chronic pancreatitis. The concentrations of sodium and bicarbonate in stimulated parotid juice were reduced compared to controls (p less than 0.001). The secretion of 75Se-selenomethionine by the parotid salivary gland and exocrine pancreas following a Lundh test meal was measured in 12 patients with normal pancreatic function and 16 patients with exocrine pancreatic insufficiency. Eight of these patients had chronic pancreatitis both parotid and pancreatic secretion of the isotope were impaired. In pancreatic carcinoma the pancreatic excretion was impaired with no significant impairment of parotid secretion. The combined pancreatic/parotid radio-selenium test may be useful in differentiating between chronic pancreatitis and pancreatic carcinoma as the cause of pancreatic insufficiency.

Bicarbonates