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Biomedical subjects

K E McColl

Publications and source records attributed to K E McColl.

At least 145 records · Page 8Linked to original sources
PubMed1989

Therapy of the acute porphyrias.

In the management of acute porphyria it is essential to be aware of the potential for many drugs to induce porphyrin synthesis and thus precipitate the acute porphyric crisis. In this review, lists of drugs unsafe and safe for use in the porphyrias are presented. In addition, therapeutic regimens are described which are appropriate to the porphyric subject. These include the use of high carbohydrate intake and the intravenous infusion of haem arginate.

Dietary Carbohydrates↗
PubMed1989

Acute intermittent porphyria in two patients on anticonvulsant therapy and with normal erythrocyte porphobilinogen deaminase activity.

1. Acute intermittent porphyria (AIP) is sometimes termed a 'pharmacogenetic' disease. patients with genetic deficiency of the enzyme porphobilinogen deaminase are liable to develop acute attacks of porphyria if exposed to a variety of drugs. 2. Two patients are reported who had no evidence of deficiency of erythrocyte porphobilinogen deaminase yet developed typical attacks of AIP while on anticonvulsant therapy. 3. Normal activity of erythrocyte porphobilinogen deaminase does not completely exclude porphyria. 4. Acute porphyria should be suspected if clinical deterioration occurs during therapy with anticonvulsants, or other porphyrinogenic drugs, even in the absence of an underlying genetic defect in haem synthesis in peripheral blood cells.

Adolescent↗
PubMed1989

Inhibition of gastric secretion and motility by simulated upper gastrointestinal haemorrhage: a response to facilitate haemostasis?

As gastric acid and pepsin inhibit blood coagulation and platelet aggregation it is surprising that most upper GI haemorrhages stop spontaneously. To investigate this paradox we have studied acid and pepsin secretion, gastric motility and GI hormones after simulated upper GI haemorrhage. In seven healthy volunteers intraduodenal infusion of 160 ml autologous blood decreased pentagastrin stimulated submaximal acid secretion (mmol/h) from 30.0 (3.2) (mean (SE] in the hour preceding infusion to 21.4 (3.7) in the hour following infusion (p less than 0.02), representing a mean reduction in acid output of 30%. Pepsin output (mg/h) was also decreased from 207.5 (67.7) (mean (SE] in the hour preceding blood infusion to 135.7 (54.7) in the hour after infusion (p less than 0.02) representing a mean reduction in pepsin output of 43%. In six volunteers gastric emptying of a liquid meal was delayed after intraduodenal blood infusion compared with intubation alone with the emptying time (min) to half volume (t 1/2) being prolonged at 75.0 (8.2) (mean (SE] after blood infusion compared with 35.5 (6.6) after intubation alone (p less than 0.02). Plasma GIP concentrations (ng/l) increased to peak levels of 127.9 (62.7) (mean (SE] after intraduodenal blood infusion compared with the pre-infusion value of 58.3 (2.3) (p less than 0.02). These changes may represent protective physiological responses to facilitate haemostasis.

Adult↗
PubMed1989

Rebound nocturnal hypersecretion after four weeks treatment with an H2 receptor antagonist.

Daytime intragastric pH, fasting and meal stimulated serum gastrin and nocturnal acid output were studied in eight male duodenal ulcer patients before, during and two days after completing nizatidine 300 mg nocte (20:00 h) for four weeks. Median nocturnal acid output (mmol/10 h) decreased during treatment to 11.6 (range 0.4-26.7) compared with pretreatment value of 39.4 (9.8-91.2); median acid inhibition 77% (p less than 0.01) which was strongest between 24:00 and 04:00 h. Two days after discontinuing treatment, nocturnal acid output increased to 74.1 (11-181). Compared with the pretreatment value this represents median rebound hypersecretion of 77% (p less than 0.05), caused by increased H+ concentration and volume of secretion. Overall median daytime intragastric pH (09:00-21:00 h) was unchanged on the final day of treatment and two days after completing therapy, compared with the pretreatment values. Fasting serum gastrin measured between 09:30 and 10:00 h and the integrated gastrin response to an OXO breakfast taken out at 10:00 h were also similar during and after treatment, compared with pretreatment values. The rebound nocturnal hypersecretion may be relevant to the high ulcer relapse rates after stopping H2 receptor antagonists.

Adult↗
PubMed1989

Comparison of gastric body and antral pH: a 24 hour ambulatory study in healthy volunteers.

Simultaneous ambulatory records of gastric antral and body pH were made over 24 hours in nine healthy volunteers by means of endoscopically positioned and anchored glass electrodes. Intragastric pH was temporarily raised after the endoscopy with the median pH value 30 minutes after the procedure being 3.9 (range 1.5-7.0) for the antrum and 4.1 (range 1.5-7.0) for the body. Daytime pH (median pH value between 12 00 h and 23 00 h) was lower in the antrum (median = 1.9, range 1.6-2.6) than in the body (median = 2.7, range 1.8-4.5) (p less than 0.05) and this was because of the rise in pH on eating being less marked in the antrum than in the body. The median peak pH recorded during the evening meal was only 4.1 (range 2.4-6.2) in the antrum compared with 6.3 (range 4.4-6.7) in the body (p less than 0.01). Preprandial pH (median value over the hour prior to the evening meal) was similar in the antrum (median = 1.9, range 1.2-2.5) and body (median = 1.9, range 1.3-2.8). Night-time pH (median pH value between 23 00 h and 05 00 h) in six subjects remained low and was similar in the antrum (median = 1.4, range 1.2-1.7) and body (median = 1.3, range 1.1-1.7). In two subjects, however, there were episodes of raised night-time pH which were more marked in the antrum than in the body. Antral biopsies showed gastritis in four of the nine normal volunteers, which in three was associated with the presence of campylobacter-like organisms. This study shows the significant regional variations in day and night-time intragastric pH.

Adult↗
PubMed1988

A comparison of the effects of treatment with either famotidine 40 mg or cimetidine 800 mg nocte on gastric acid secretion and serum gastrin.

The effects on gastric acid secretion and serum gastrin of 4 weeks treatment with famotidine 40 mg nocte or cimetidine 800 mg nocte (at 2200 h) were studied in 16 patients with previous duodenal ulcer. Patients were studied before commencing therapy, on days 5, 12 and 26 of treatment, and on days 3, 10 and 24 after completion of therapy. In contrast to cimetidine, basal and pentagastrin-stimulated gastric acid secretion measured 12 h after dosing was significantly inhibited during treatment with famotidine. In addition, with famotidine there was inhibition of stimulated gastric acid secretion at 3 and 24 days after completion of treatment. Fasting serum gastrin measured 12 h after dosing was not significantly altered by either drug.

Adult↗
PubMed1988

Effect of low-dose omeprazole on gastric acid secretion in duodenal ulcer patients.

The effect of 7 days of oral dosing with 5 mg day-1 and 20 mg day-1 omeprazole on basal and pentagastrin-stimulated gastric acid output was studied in nine duodenal ulcer patients. Basal acid output measured 5-6 h post-dosing was decreased by a mean of 75% on 5 mg omeprazole and by 90% on 20 mg omeprazole (P less than 0.05 and P less than 0.01, respectively). Peak acid output measured 6-7 h post-dosing was decreased by a mean of 75% on 5 mg omeprazole and 97% on 20 mg omeprazole (P less than 0.01 for each). There was a wide interindividual variation in response to the 5 mg dose, with five of the nine patients having more than 90% inhibition of peak acid output, but two patients having less than 40% inhibition. This unpredictable response to daily low-dose omeprazole therapy makes it unsuitable for maintenance treatment.

Adult↗
PubMed1988

Hypertrophic gastritis associated with increased gastric mucosal prostaglandin E2 concentrations in a patient with the carcinoid syndrome.

A case of a 69 year old man in whom hypertrophic gastritis was associated with the carcinoid syndrome is reported. Concentrations of prostaglandin E2 were increased in plasma, gastric juice, gastric mucosa and urine. He had marked hypochlorhydria in response to pentagastrin stimulation (Peak acid output (PAO) pg:0.2 mmol/h). After successful hepatic arterial embolisation of the metastases (as indicated by an 85% decrease in 24 h urinary 5-HIAA) the concentrations of prostaglandin E2 decreased in the plasma, gastric juice and gastric mucosa. The gastric mucosal hypertrophy regressed and secretion of acid in response to pentagastrin returned (PAO pg:9.0 mmol/h). These findings suggest that the carcinoid tumour was producing a substance which stimulated increased local synthesis of prostaglandin E2 in the gastric mucosa, with concomitant gastric mucosal hypertrophy and inhibition of gastric acid secretion.

Dinoprostone↗
PubMed1987

Effect of haem arginate therapy on porphyrin metabolism and mixed function oxygenase activity in acute hepatic porphyria.

The effect of haem arginate on porphyrin metabolism and haemoprotein function was studied during seven attacks of acute hepatic porphyria in 5 patients. In each attack it greatly reduced the overproduction of porphyrin precursors and repressed the overactivity of the rate-controlling enzyme of haem synthesis delta-aminolaevulinic acid (ALA) synthase measured in leucocytes. Antipyrine clearance, an index of the oxidative function of cytochromes P-450, the major group of hepatic haemoproteins, was increased during haem therapy. Thus, haem arginate not only suppresses the overproduction of haem precursors but also improves hepatic oxidative metabolism in acute porphyria.

Acute Disease↗
PubMed1987

An endoscopic procedure for accurate localisation of intraluminal pH electrodes.

An endoscopic procedure has been developed which permits the accurate fixation of pH electrodes to the mucosa of the upper gastrointestinal tract. The electrode is carried to the desired position tethered to the endoscope. A clip-fixing device is passed through the biopsy channel of the endoscope and the electrode is anchored to the mucosa with stainless steel clips. Repeat endoscopy in 20 patients has confirmed that the electrode remains firmly secured to the mucosa for at least 24 h. The electrode can be safely removed at any time by traction on its cable. This procedure should allow, for the first time, accurate 24 h ambulatory pH monitoring of specific regions of the upper gastrointestinal tract.

Electrodes↗
PubMed1987

Antipyrine metabolism in acute hepatic porphyria in relapse and remission.

Antipyrine kinetics following a single oral dose were obtained in porphyric patients in attack and in remission and in controls. The clearance of antipyrine was significantly lower during an acute porphyric attack (median: 0.34 ml min-1 kg-1; range: 0.1-0.71, P less than 0.05) than in patients in remission (median: 0.53 ml min-1 kg-1; range: 0.28-0.87) or controls (median: 0.52 ml min-1 kg-1; range: 0.32-0.93). There was a significant negative correlation between weight-adjusted antipyrine clearance and the urinary excretion of the porphyrin precursors, delta-aminolaevulinic acid (r = 0.86, P less than 0.001) and porphobilinogen (r = 0.82, P less than 0.002). These data suggest that the more severe the porphyric attack, the greater the impairment of hepatic monooxygenase activity.

5-Aminolevulinate Synthetase↗
PubMed1987

Effect of rifampicin on haem and bilirubin metabolism in man.

Haem and bilirubin metabolism was studied in seven healthy volunteers during 4 weeks treatment with rifampicin 600 mg at night. The serum unconjugated bilirubin concentration increased 2-3 fold in the first 24 h of treatment (P less than 0.01) and subsequently fell to below pretreatment values (P less than 0.05) during the third and fourth weeks of rifampicin therapy. In each subject, the activity in leucocytes of delta-aminolaevulinic acid (ALA) synthase increased and that of protoporphyrinogen (proto) oxidase decreased during the first week of therapy. The mean ALA synthase activity was most markedly increased on day 4 being seven-fold its pretreatment value (P less than 0.01), and the mean proto oxidase activity most depressed on day 2 at 50% its pretreatment value (P less than 0.02). There was increased urinary excretion of porphobilinogen (PBG) during the first week of therapy and increased excretion of porphyrins and PBG during the third week of treatment. The increase in ALA synthase activity and haem precursor excretion can be explained by the combination of increased haem demand for haemoprotein induction and partial block in haem synthesis due to reduced proto oxidase activity.

Adult↗
PubMed1987

Studies in laboratory animals to assess the safety of anti-inflammatory agents in acute porphyria.

The safety of various anti-inflammatory drugs in acute porphyria was assessed by examining their effect on rat hepatic haem synthesis. Azapropazone, chloroquine, and gold increased delta-aminolaevulinic acid (ALA) synthase activity, indicating that they are liable to precipitate porphyric crises. Aspirin, ibuprofen, indomethacin, ketoprofen, flurbiprofen, phenylbutazone, naproxen, prednisolone, and penicillamine did not increase ALA synthase activity and should be safe in porphyria. Though these animal studies can be used as a guide to prescribing in patients with acute porphyria, some caution is still required as species may vary in their response to inducing agents.

5-Aminolevulinate Synthetase↗
PubMed1987

Porphyrin metabolism and haem biosynthesis in Gilbert's syndrome.

Studies in 14 patients with unconjugated hyperbilirubinaemia caused by Gilbert's syndrome have revealed abnormalities of the enzymes of haem biosynthesis measured in peripheral blood cells. The activity of the penultimate enzyme of haem biosynthesis protoporphyrinogen (PROTO) oxidase was reduced at 3.1 +/- 2.6 nmol PROTO/g protein/h (mean +/- ISD) compared with 8.2 +/- 5.1 in controls (p less than 0.005). This was associated with a compensatory increase in the activity of the initial and rate controlling enzyme of the pathway delta-aminolaevulinic acid (ALA) synthase at 866 +/- 636 nmol ALA/g/protein/h compared with 156 +/- 63 in controls (p less than 0.001). Unlike variegate porphyria in which there is a genetic deficiency of PROTO oxidase there was no increased excretion of porphyrins or their precursors in Gilbert's syndrome. Accentuation and subsequent correction of the unconjugated hyperbilirubinaemia with rifampicin produced reciprocal changes in PROTO oxidase activity indicating that bilirubin may be inhibiting the activity of this enzyme.

5-Aminolevulinate Synthetase↗
PubMed1987

Effects of nifedipine on gastric acid secretion and gastrin release in man.

As calcium is important in the regulation of gastric acid secretion and gastrin release, we have examined the effect of the calcium antagonist nifedipine on these processes in man. Nifedipine 30 mg orally inhibited basal acid output by 37% (p less than 0.025) and that stimulated by low infusion rates of pentagastrin--that is, 0.031 and 0.062 microgram/kg/h by 44% (p = 0.05) and 39% (p less than 0.02) respectively. On increasing the pentagastrin infusion rate the inhibition was surmounted suggesting it was competitive in type. Nifedipine did not affect basal or Oxo meal stimulated gastrin concentrations in normal volunteers nor did it affect resting serum gastrin or calcium stimulated increase in gastrin in a single patient with Zollinger-Ellison syndrome. These findings are consistent with the transmembrane flux of calcium ions being involved in basal and pentagastrin stimulated acid secretion in man.

Adult↗
PubMed1987

Electrodes for 24 hours pH monitoring--a comparative study.

Three pH electrodes in clinical use were examined--(1) antimony electrode with remote reference electrode (Synectics 0011), (2) glass electrode with remote reference electrode (Microelectrodes Inc. MI 506) and (3) combined glass electrode with integral reference electrode (Radiometer GK2801C). In vitro studies showed that both glass electrodes were similar and superior to the antimony electrode with respect to response time, drift, and sensitivity. The effect of the siting of the reference electrode on the recorded pH was examined in five human volunteers. The pH reading using a remote skin reference electrode was higher by a mean of 0.3 pH units (range 0.0-0.6) in the stomach, lower by 0.65 pH units (0.5-0.8) in the duodenum and lower by 0.3 pH units (0.0-0.6) in the oesophagus than that simultaneously obtained with an intraluminal reference electrode. Buccal reference electrodes gave similar readings to skin. Combined reference and glass pH electrodes are recommended for 24-hour ambulatory pH monitoring.

Antimony↗