PubMed Health⌕ Search

Biomedical subjects

K E McColl

Publications and source records attributed to K E McColl.

At least 127 records · Page 7Linked to original sources
PubMed1991

Erythroid 5-aminolaevulinate synthase activity during normal and iron deficient erythropoiesis.

Reduced erythroblast 5-aminolaevulinate (ALA) synthase activity was observed during iron/haem deficient erythropoiesis. Enzyme activity was reduced approximately threefold to levels similar to those previously detected during sideroblastic erythropoiesis. This response would appear to be erythroblast specific as haem deficiency is known to stimulate hepatic ALA synthase activity. It is, however, unclear as to whether this reduced enzyme activity relates to iron deficiency or to the consequent haem deficiency.

5-Aminolevulinate Synthetase↗
PubMed1991

Effect of increasing Helicobacter pylori ammonia production by urea infusion on plasma gastrin concentrations.

It has been proposed that the hypergastrinaemia in subjects with Helicobacter pylori infection is caused by the action of the ammonia produced by the organism's urease activity on the antral G cells. To investigate this hypothesis we examined the effect on plasma gastrin of increasing the bacterium's ammonia production by infusing urea intragastrically to eight H pylori positive duodenal ulcer patients. After a 60 minute control intragastric infusion of dextrose solution at 2 ml/minute, a similar infusion containing urea (50 mmol/l) was continued for four hours. During the urea infusion, the median gastric juice urea concentration rose from 1.1 mmol/l (range 0.3-1.6) to 15.5 mmol/l (range 7.9-21.3) and this resulted in an increase in the ammonium concentration from 2.3 mmol/l (range 1.3-5.9) to 6.1 mmol/l (range 4.2-11.9) (p less than 0.01). This appreciable rise in ammonia production did not result in any change in the plasma gastrin concentration. The experiment was repeated one month after eradication of H pylori, at which time the median basal gastrin was 20 ng/l (range 15-25), significantly less than the value before eradication (30 ng/l range 15-60) (p less than 0.05). On this occasion, the gastric juice ammonium concentration was considerably reduced at 0.4 mmol/l (range 0.1-0.9) and the urea infusion did not raise the ammonium concentration or change the plasma gastrin concentration. In conclusion, augmenting H pylori ammonia production does not cause any early change in plasma gastrin.

Adult↗
PubMed1991

Is Helicobacter pylori associated hypergastrinaemia due to the bacterium's urease activity or the antral gastritis?

Eradication of Helicobacter pylori is associated with a fall in serum gastrin but the way in which the infection raises the serum gastrin concentration is not clear. It may be related to the ammonia produced by the bacterium's urease stimulating gastrin release by the antral G cells. Alternatively, the antral gastritis induced by the infection may modify the regulation of gastrin release. We have examined serum gastrin in 10 patients before and 24 hours after starting triple anti-H pylori treatment consisting of tripotassium dicitrato bismuthate 120 mg four times daily, metronidazole 400 mg three times daily, and amoxycillin 500 mg three times daily. The urease activity, assessed by the 20 minute value of the 14C-urea breath test, fell from a median of 176 (range 116-504) kg% dose/mmol CO2 x 100 pretreatment to 5 (2-15) at 24 hours (p less than 0.005). The median antral gastritis score was 6 (4-6) pretreatment and fell to 3 (2-5) at 24 hours (p less than 0.02), and this was due to resolution of the polymorphonuclear component. Despite this complete suppression of bacterial urease activity and partial resolution of antral gastritis the median basal gastrin concentration remained unchanged, being 57 ng/l (45-77) pretreatment and 59 ng/l (45-80) at 24 hours and the median integrated gastrin response to a standardised meal was also unaltered, being 4265 ng/l/min (range 1975-8350) and 4272 ng/l/min (range 2075-6495) respectively. These findings do not support a causal association between H pylori urease activity and hypergastrinaemia and show rapid improvement of antral gastritis after starting anti-H pylori treatment.

Adult↗
PubMed1991

Enhanced gastric mucosal haemostasis after upper gastrointestinal haemorrhage.

An endoscopic technique for the measurement of gastric mucosal bleeding time has been developed to study gastric haemostasis in patients with acute upper gastrointestinal haemorrhage. The relation of gastric mucosal bleeding time to skin bleeding time and nonsterodial anti-inflammatory drug usage was examined in 61 control patients and in 47 patients presenting with bleeding peptic ulcers or erosions. Gastric mucosal bleeding time was shorter in patients with haemorrhage (median 2 minutes, range 0-5 minutes) than in the control group (median 4 minutes, range 2-8 minutes) (p less than 0.001). Skin bleeding times were similar in the two groups (medians 4 minutes in patients with haemorrhage and 4.5 minutes in controls). In 21 patients with haemorrhage who were taking non-steroidal anti-inflammatory drugs, the median gastric mucosal bleeding time (2.5 minutes, range 1.0-5.0 minutes) was similar to that in 26 patients with haemorrhage not associated with these drugs (2.0 minutes, range 0.0-5.0 minutes). These results show that gastric mucosal haemostasis is accelerated in response to haemorrhage in the upper gastrointestinal tract, even in patients taking nonsteroidal anti-inflammatory drugs. This enhanced gastric haemostasis probably reflects a local protective response to minimise blood loss from the bleeding lesion.

Acute Disease↗
PubMed1991

Effect of inhibition of Helicobacter pylori urease activity by acetohydroxamic acid on serum gastrin in duodenal ulcer subjects.

The mechanism of the hypergastrinaemia associated with Helicobacter pylori infection is unknown. It may be an effect of the ammonia produced by the bacterium near the antral epithelial surface. We have examined the effect on serum gastrin of inhibiting H pylori urease activity with acetohydroxamic acid in six duodenal ulcer patients. On day 1 the fasted patients received placebo tablets at 8 am, a peptide meal at 10 am, and a 14C urea breath test at 11.30 am. The next day 750 mg acetohydroxamic acid was administered orally in place of the placebo. The median (range) 30 minute breath test value (dose/mmol CO2 X kg body wt X 100) was 152 (111-335) on day 1, but only 22 (14-95) the next day (p less than 0.03). Further studies performed in one subject confirmed that acetohydroxamic acid lowered the ammonium concentration and raised the urea concentration in gastric juice. The inhibition of urease activity and ammonia production did not result in a fall in the basal gastrin concentration or in the median integrated gastrin response to the peptide meal, which was 78 ng/1.h (range 21-222) on day 1 and 79 ng/1.h (33-207) the next day. Ten days after acetohydroxamic acid, the urea breath test values were similar to those before treatment. This study shows that the raised gastrin concentration in patients with H pylori infection is not directly related to the organism's urease activity. It also shows that temporary suppression of H pylori urease activity does not clear the infection.

Adult↗
PubMed1991

Detection of Helicobacter pylori infection of the gastric mucosa by measurement of gastric aspirate ammonium and urea concentrations.

Helicobacter pylori possesses unusually high urease activity that lowers the urea concentration and raises the ammonium concentration of the gastric juice in infected people. The value of measuring urea and ammonium concentrations in gastric juice obtained during upper gastrointestinal endoscopy as a means of diagnosing the presence and eradication of the infection was assessed. Twenty four subjects with the infection and 14 in whom it had been eradicated were examined. Their H pylori status was confirmed by antral biopsy and 14C urea breath test. The median (range) gastric juice urea concentration in infected subjects was 0.8 mmol/l (0.5-2.9 mmol/l), which was lower than that in the uninfected subjects (2.1 mmol/l (1.0-3.7 mmol/l)) (p less than 0.001). The median gastric juice ammonium concentration in infected subjects was 3.4 mmol/l (1.0-13.0 mmol/l), which was higher than that in the uninfected subjects (0.64 mmol/l (0.02-1.4 mmol/l)) (p less than 0.001). Though the two groups overlapped in respect of their urea and ammonium concentrations, they were completely different when the urea: ammonium ratios were calculated--the ratios ranged from 0.04-0.7 (median 0.26) and from 1.1-113 (median 3.4) in infected and uninfected subjects respectively (p less than 0.001). Treatment with H2 antagonists did not change the concentrations of urea and ammonium or their ratio in gastric juice. Measurement of the urea: ammonium ratio in aspirated gastric juice obtained during routine upper gastrointestinal endoscopy may provide a rapid method of detecting H pylori infection and of confirming its eradication.

Adolescent↗
PubMed1991

Harnessing of urease activity of Helicobacter pylori to induce self-destruction of the bacterium.

Eradication of Helicobacter pylori with currently available antibacterial agents is unsatisfactory due to the risk of side-effects and the emergence of resistance. The organism rapidly dies in vitro in the presence of urea at pH 6. When incubated in citrate buffer (pH 6) plus urea (10 mM) the five minute survival was 26% compared with 96% without urea and the survival progressively decreased with increasing urea concentrations, being only 9% in 50 mM urea. The bactericidal effect depended on pH as the organism survived in citrate buffer (pH 7) plus urea (50 mM). The death of the organism at pH 6 in the presence of urea was prevented by the addition of the competitive urease inhibitor hydroxyurea. These findings indicate that destruction of the organism is mediated by its exceptionally high urease activity. Harnessing this enzyme to induce self-destruction could provide a new approach to eradicating this common infection.

Buffers↗
PubMed1991

Suicidal destruction of Helicobacter pylori: metabolic consequence of intracellular accumulation of ammonia.

The role of pH, citrate buffer, and urea were investigated in the suicidal destruction of Helicobacter pylori, with particular reference to the organism's urea and ammonia metabolism. The median five minute survival of H pylori in the presence of 50 mmol/l urea in 0.2 M citrate buffer at pH 6.0 was only 14%, compared with 53% in the same solution at pH 7.0. The median amount of ammonium released into the incubating solution over five minutes was lower at pH 6.0 (9 mumol) than at pH 7.0 (18 mumol) despite similar uptake of urea. The median five minute survival of H pylori in 0.2 M citrate buffer, pH 6.0, decreased from 89% to 14% when the urea concentration was increased from 1 mmol/l to 50 mmol/l. Likewise, the recovery in the incubating solution of ammonia resulting from the hydrolysis of urea fell from 27% to 3% when the initial urea concentration was increased from 1 mmol/l to 50 mmol/l. Survival of H pylori in the presence of 30 mmol/l urea at pH 6.0 was compared in 0.2 M citrate, acetate, and phosphate buffers. The median five minute survival was less in the citrate buffer, at 29%, than in either the acetate buffer 80% or the phosphate buffer 100%. The percentage recovery of ammonia was similar in the three buffers. These findings indicate that the suicidal destruction of the bacterium may be explained by intracellular accumulation of ammonia due to production in excess of the rate of excretion.

Ammonia↗
PubMed1991

Plasma gastrin, daytime intragastric pH, and nocturnal acid output before and at 1 and 7 months after eradication of Helicobacter pylori in duodenal ulcer subjects.

Nine patients with Helicobacter pylori-related antral gastritis and history of duodenal ulceration were studied before and at 1 and 7 months after eradication of the infection by a 4-week course of tripotassium dicitrato bismuthate, metronidazole, and amoxycillin. The median basal gastrin concentration before eradication was 30 ng/l (range, 20-60) and fell to 20 ng/l (5-20) at 1 month (p less than 0.02) and 15 ng/l (5-20) at 7 months (p less than 0.01) after eradication. The integrated gastrin response to a peptide meal was 3650 ng/l.min (range, 1875-6025) before treatment compared with 1800 ng/l.min (range, 1200-3075) at 1 month (p less than 0.01) and 1312 ng/l.min (875-2625) at 7 months (p less than 0.03). Daytime intragastric pH (0900-2100 h) was similar before treatment (median, 1.4; range, 1.1-2.1) and at 1 month (1.4; 1.1-2.3) and 7 months (1.4; 1-2.2) after eradication. In five of the patients nighttime acid output (2300-0900 h) was also studied and was similar before (median, 86 mmol/10 h; range, 52-114) and at 1 month (76 mmol/10 h; 50-143) and 7 months (94 mmol/10 h; 63-106) after eradication. In conclusion, eradication of H. pylori is accompanied by a sustained fall in serum gastrin concentrations but is not accompanied by an early or late reduction of daytime intragastric acidity or nighttime acid output.

Adult↗
PubMed1990

Elevation of blood lactate and pyruvate levels in acute intermittent porphyria--a reflection of haem deficiency?

Blood lactate concentrations after glucose loading were significantly higher in 6 patients with acute intermittent porphyria in clinical remission than in 6 control subjects and the percentage rise in glucose pyruvate and lactate concentrations were greater in the porphyric subjects than in the control group. It is postulated that the raised lactate levels in the porphyric patient group may reflect haem deficiency affecting the cytochromes of the terminal respiratory chain.

Adult↗
PubMed1990

Elevation of hormone-binding globulins in acute intermittent porphyria.

Sex hormone-binding globulin (SHBG), thyroxine-binding globulin (TBG) and cortisol-binding globulin (CBG) were measured in plasma of 26 patients with acute intermittent porphyria (AIP). Twelve patients had clinically manifest disease and all had elevated SHBG levels. All but one of 14 patients with latent porphyria had normal SHBG levels. TBG was elevated in 9 of the patients with clinically manifest porphyria and CBG elevated in three. Levels of TBG and CBG were either normal or only slightly elevated in those with latent porphyria. In a prospective study of 30 attacks of AIP in 7 patients, SHBG levels fell between admission and discharge, the fall being significant in the group of 21 attacks treated with haem arginate (p less than 0.001). Our findings suggest that a close correlation exists between elevated SHBG and clinical expression of AIP.

Adolescent↗
PubMed1990

The porphyrias.

The porphyrias are a group of metabolic disorders arising from defects in the haem biosynthetic pathway. Most forms are inherited as Mendelian autosomal dominant characters, but some are recessive and others acquired. There is a linked group of diseases, which are not porphyrias, but have in common alterations of haem biosynthesis. The haem biosynthetic pathway is now well understood and the molecular biology of its function and dysfunction in the porphyrias is currently an area of major investigation. The acute porphyrias are of most importance since attacks of these may be life-threatening. A variety of factors may precipitate these attacks including various drugs, alcohol, strict dieting or fasting and hormonal fluctuations. The non-acute porphyrias are largely dermatological conditions, which present clinically as cutaneous photosensitivity. The dermatological changes are brought about by the photosensitizing properties of circulating porphyrins. On the basis of this photoactivity, porphyrins are now being used, therapeutically, in the treatment of cancer.

Acute Disease↗
PubMed1990

Antinuclear antibodies and the diagnosis of systemic lupus erythematosus in patients with acute intermittent porphyria.

To investigate the previously postulated association of systemic lupus erythematosus (SLE) and porphyria 38 patients with various types of porphyria were investigated for clinical and laboratory evidence of a connective tissue disease. Antinuclear antibodies (ANAs) were found in 8/15 (53%) patients with acute intermittent porphyria. These patients were more likely to have had a recent acute attack of porphyria, but only one patient had clinical evidence of SLE. Antinuclear antibodies were not found in any patients with latent acute intermittent porphyria or appreciably in any of the other types of porphyria studied. This finding of ANAs in patients with acute intermittent porphyria may explain the previously described association with SLE. Strict diagnostic criteria need to be used in any one patient as these two disorders have many similar clinical manifestations.

Adult↗
PubMed1990

Effect of simulated intragastric haemorrhage on gastric acid secretion, gastric motility, and serum gastrin.

The majority of upper gastrointestinal bleeds stop spontaneously despite the low pH and proteolytic activity of gastric juice which inhibit coagulation and platelet aggregation. In order to investigate this paradox six healthy male volunteers received intragastric infusions of 160 ml autologous venous blood or 160 ml egg white acting as control in random order on separate days. Basal acid output was calculated before infusion, net acid secretion and gastric volume emptied were calculated after intragastric infusions. Serum gastrin concentrations were also measured before and after intragastric infusions and expressed as the integrated gastrin response. Basal acid output (mmol/h) was 4.7 (1.9) (mean (SEM)) before egg white infusion and 5.9 (2.6) before venous blood infusion. After egg white infusion net acid secretion (mmol/20 min) increased to 5.6 (3.1) compared with 2.3 (1.3) after venous blood infusion (p less than 0.05). The gastric volume emptied (ml/20 min) was less after venous blood infusion at 105 (28) compared with 321 (66) after egg white infusion (p less than 0.03). Integrated gastrin response was similar after venous blood and egg white infusion. When compared with an equivalent protein meal intragastric blood stimulates less acid secretion and delays gastric emptying. This effect may facilitate haemostasis after gastric bleeding.

Adult↗
PubMed1990

LHRH analogue treatment for the prevention of premenstrual attacks of acute porphyria.

We have assessed the value of suppressing ovulation with the luteinizing hormone releasing hormone (LHRH) analogue buserelin in seven patients experiencing crises of acute intermittent porphyria related to the menstrual cycle. Clinical course, plasma oestradiol and progesterone levels, and urinary porphyrin and precursor excretion were monitored over a baseline period of approximately one year, and then for a similar period on buserelin treatment. There was a trend towards clinical improvement on buserelin therapy. The median number of attacks fell from seven during the baseline period to three on treatment (p = 0.06). The response to buserelin varied considerably, with those patients in whom the association between baseline attacks and the menstrual cycle was strongest gaining the most benefit. All patients became amenorrhoeic with suppression of plasma oestradiol and progesterone levels. Urinary delta-aminolaevulinic acid and total porphyrin excretion fluctuated widely both before and during treatment. Our experience indicates that ovulation suppression may be of value in the management of young women in whom recurrent attacks of porphyria are related to the menstrual cycle.

Acute Disease↗
PubMed1989

Controlled trial of haem arginate in acute hepatic porphyria.

A double-blind study comparing placebo and haem arginate was conducted in 12 patients with acute intermittent porphyria. 2 days after admission in attack patients were randomised to receive intravenous haem arginate 3 mg/kg per 24 h for 4 days or placebo. 9 patients were readmitted with a further attack and were given the alternative treatment. Before randomisation the paired attacks were of similar severity with respect to urinary porphobilinogen (PBG) excretion and clinical manifestations. With haem arginate the median PBG excretion of the 9 patients with two attacks (normal range 0-16 mumol per 24 h) fell significantly from 332 mumol per 24 h (range 137-722) on admission to a median lowest level of 40 (range 22-105). On placebo, median PBG excretion was 382 (range 196-542) on admission, falling to 235 (range 128-427). Median duration of admission after the start of treatment was 11 days (range 2-28) for placebo and 8 days (3-26) for haem arginate. Median total analgesic requirement between the start of treatment and discharge was 8150 mg pethidine equivalents (range 0-17,650) with placebo versus 6425 (range 50-20,650) with haem arginate. Phlebitis occurred in 5 patients on haem arginate and in 2 on placebo. Haem arginate effectively reduces porphyrin precursor overproduction in the acute porphyric attack but this reduction is not accompanied by striking resolution of the clinical manifestations of the attack.

Acute Disease↗
PubMed1989

Haem biosynthesis in the unconjugated hyperbilirubinaemias: observations in the Gunn rat model.

Disturbances of the enzymes of haem biosynthesis have been reported in patients with unconjugated hyperbilirubinaemia. We have examined the excretion of haem precursors in the Gunn rat which suffers from severe unconjugated hyperbilirubinaemia. In urine, levels of aminolaevulinic acid and total porphyrin were significantly reduced when compared to controls. In feces both coproporphyrin and protoporphyrin levels were reduced in Gunn rats, the former being more affected. Blood porphyrin levels in control and Gunn rats were similar.

Aminolevulinic Acid↗