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K E McColl

Publications and source records attributed to K E McColl.

At least 91 records · Page 5Linked to original sources
PubMed1995

Review article: gastrin releasing peptide and its value in assessing gastric secretory function.

Gastrin releasing peptide (GRP) has proved to be a particularly valuable tool in detecting disturbances of gastric secretory function associated with duodenal ulcer disease and Helicobacter pylori infection, and it has furthered understanding of the pathophysiology of these conditions. Its attractiveness lies in the fact that it simultaneously activates many physiological control processes, both stimulatory and inhibitory. This facilitates the detection of a defect in any of the many controls involved in regulating biological function. Other gastrointestinal functions such as gall-bladder contraction, pancreatic secretion and gastrooesophageal motility are also subject to complex regulatory controls, and GRP may also be of value in investigating disturbances of these processes.

Duodenal Ulcer↗
PubMed1995

Effect of omeprazole and feeding on plasma gastrin in patients with achlorhydria.

BACKGROUND: The mechanism of hypergastrinaemia during omeprazole therapy is unclear, but is generally assumed to be entirely a consequence of acid suppression. However, direct stimulation of G cells by omeprazole could also be a factor. In order to further investigate the mechanism of omeprazole-induced hypergastrinaemia, we have studied the effects of the drug on plasma gastrin in patients with achlorhydria, in whom altered acid secretion cannot play a role. METHODS: We estimated fasting and peptone meal stimulated plasma gastrin in nine patients (seven female) with pernicious anaemia and achlorhydria, before and on the final day of 4 weeks' dosing with omeprazole 40 mg daily. RESULTS: Despite the high fasting gastrin concentrations, the peptone meal produced a further elevation in plasma gastrin concentrations, median gastrin concentrations rising from 1500 ng/L (range 225-10,875 ng/L) to 3750 ng/L (range 585-15,600 ng/L) post-prandially (P = 0.004). The median post-prandial rise in plasma gastrin at this initial visit was 44% (3-260%), and the median time interval until plasma gastrin concentrations returned to fasting levels was 120 min (range 10- > 150 min). There was a significant negative correlation between fasting plasma gastrin concentrations and the percentage increase in plasma gastrin levels in response to meal stimulation (Spearman correlation coefficient -0.79, P = 0.01). Fasting plasma gastrin concentrations were similar pre-omeprazole (median 1950 ng/L, range 240-16,500 ng/L) and post-omeprazole (median 1500 ng/L, range 315-7650 ng/L). Likewise, peak plasma gastrin concentrations were also similar pre-omeprazole (median 2700 ng/L, range 585-16,500 ng/L) and post omeprazole (median 3420 ng/L, range 720-11,250 ng/L). CONCLUSIONS: (i) The hyperplastic G cell mass in patients with pernicious anaemia can be further stimulated by a peptone meal, which causes a prolonged rise in plasma gastrin concentrations. (ii) There is a negative correlation between fasting plasma gastrin concentrations and the percentage increase in plasma gastrin levels in response to meal stimulation. (iii) Omeprazole has no effect on plasma gastrin in achlorhydric patients, which is consistent with its hypergastrinaemic effect being entirely secondary to acid inhibition.

Achlorhydria↗
PubMed1995

A substantial proportion of non-ulcer dyspepsia patients have the same abnormality of acid secretion as duodenal ulcer patients.

Acid secretion in response to gastrin releasing peptide (GRP) is increased six-fold in Helicobacter pylori positive duodenal ulcer (DU) patients and threefold in H pylori positive healthy volunteers, and this fully resolves after eradication of the infection. This study was undertaken to determine whether a proportion of H pylori positive patients with non-ulcer dyspepsia (NUD) have an acid secretion disturbance similar to DU patients. Basal and GRP stimulated gastrin concentrations and acid output were examined in 25 H pylori positive NUD patients and the results compared with those of 25 H pylori positive healthy volunteers, 25 H pylori negative healthy volunteers, and 25 H pylori positive DU patients. Compared with the H pylori negative healthy volunteers, GRP stimulated gastrin was increased approximately three fold in each of the three infected groups. GRP stimulated acid secretion (median, range) was higher in the H pylori positive NUD patients (29.6 mmol/h (5.2-46.5)) (p < 0.005) than in the H pylori positive healthy volunteers (19.0 (1.0-38.3)) (p < 0.001) or H pylori negative healthy volunteers (6.3 (2.8-20.9)) (p < 0.0001). The H pylori positive NUD patients, however, had lower acid output than the DU patients (39.1 (17.9-64)) (p < 0.005). These findings are consistent with approximately 50% of the NUD patients having a similar disturbance of GRP stimulated acid secretion to DU patients.

Adolescent↗
PubMed1994

Regulation of haem biosynthesis in normoblastic erythropoiesis: role of 5-aminolaevulinic acid synthase and ferrochelatase.

The development of haem biosynthetic enzyme activity during normoblastic human erythropoiesis was examined in seven patients. The first and last enzymes of the haem biosynthetic pathway, ALA synthase and ferrochelatase, were assayed by radiochemical/high performance liquid chromatographic (HPLC) methods. An assay for ferrochelatase activity in human bone marrow was developed. Enzyme substrates were protoporphyrin IX and 59Fe2+ ions. 59Fe-labelled haem was isolated by organic solvent extraction/sorbent extraction followed by reversed-phase HPLC. Optimal activity occurred at pH 7.3 in the presence of ascorbic acid, in darkness and under anaerobic conditions. Haem production was proportional to cell number and was linear with time to 30 min. The assay was sensitive to the picomolar range of haem production. ALA synthase and ferrochelatase activity was assayed in four highly purified age-matched erythroid cell populations. ALA synthase activity was maximal in the most immature erythroid cells and diminished as the cells matured with an overall five fold loss of activity from proerythroblast to late erythroblast development. Ferrochelatase activity was, however, more stable with less than a two fold change in activity observed during the same period of erythroid differentiation. Maximal activity occurred in erythroid fractions enriched with intermediate erythroblasts. These results support sequential rather than simultaneous appearance of these enzymes during normoblastic erythropoiesis. Quantitative analysis of relative enzyme activity however indicates that at all times during erythroid differentiation ferrochelatase activity is present in excess to that theoretically required relative to ALA synthase activity since ALA and haem are not produced in stoichiometric amounts. The lability of ALA synthase versus the stability and gross relative excess of ferrochelatase activity indicates a far greater role for ALA synthase in the regulation of erythroid haem biosynthesis than for ferrochelatase.

5-Aminolevulinate Synthetase↗
PubMed1994

Plasma gastrin concentrations are normal in patients with colorectal neoplasia and unaltered following tumor resection.

BACKGROUND/AIMS: Previous studies have found that colorectal cancer patients have hypergastrinemia, but most have been inadequately controlled. Preoperative fasting and meal-stimulated gastrin levels were measured in patients with colorectal tumors (n = 42) and in carefully matched controls (n = 34). Helicobacter pylori status was assessed because it causes significant hypergastrinemia. METHODS: Plasma gastrin levels were measured by radioimmunoassay. Helicobacter status was assessed using the [14C]urea breath test and serology (immunoglobulin G). RESULTS: Preoperatively, fasting plasma gastrin levels were similar in patients with tumors (median, 55 ng/L; interquartile range, 45-82.5) and controls (77.5 ng/L; 53.7-137.5; P = 0.10). Similarly, peak gastrin levels were not significantly different in tumor patients (200 ng/L; 137.5-312.5) and controls (247.5 ng/L; 147.5-375; P = 0.21). The prevalence of H. pylori infection in patients with tumors (60%) and controls (53%) was similar in both groups. Five (20%) tumor patients who were H. pylori-positive preoperatively were negative postoperatively, and their median peak plasma gastrin level decreased from 200 ng/L to 140 ng/L. After these patients were excluded, fasting and peak plasma gastrin concentrations were similar preoperatively and postoperatively. CONCLUSIONS: When confounding factors are controlled for, plasma gastrin levels are not increased in colorectal cancer and do not decrease after curative resection. Previously noted decreases in gastrin levels after tumor resection may be attributable to loss of H. pylori infection in some patients, as noted here.

Adult↗
PubMed1994

Urease-mediated destruction of bacteria is specific for Helicobacter urease and results in total cellular disruption.

The survival of Helicobacter mustelae, Proteus mirobilis, Escherichia coli and Campylobacter jejuni in the presence of urea and citrate at pH 6.0 was examined. H. mustelae, which has urease activity similar to H. pylori, had a markedly reduced survival, median 2.5% (0-78%) (P < 0.001) when incubated under these conditions. Only 7% of the ammonia produced by H. mustelae urease activity was recovered from the buffer, a similar percentage to that previously reported with H. pylori. None of the other organisms, all of which had lower urease activity, had impaired survival under these conditions. Electron microscopical studies demonstrated extensive structural damage to H. pylori following exposure to urea and citrate at pH 6.0. This structural damage to the organisms makes it unlikely that the low recovery of ammonia was due to retention of ammonia within the bacteria and suggests that the ammonia may have been incorporated into glutamate or other amino acids. Incorporation of ammonia into these compounds would deplete the cell of the key metabolic intermediate alpha-ketoglutarate and could thus explain the mechanism of the urease-dependent destruction of the organism.

Ammonia↗
PubMed1994

Acute intermittent porphyria and mental illness--a family study.

All cases of acute intermittent porphyria (AIP) are believed to be caused by a mutation in the gene encoding for porphobilinogen deaminase, a rate-limiting enzyme in the haem synthetic pathway. This gene has been mapped to the long arm of chromosome 11, a region of the genome that has recently attracted considerable attention as a possible location for genes implicated in major mental disorder. This study was designed to show whether major mental illness co-segregated with acute intermittent porphyria in families where the two conditions are found. The study also investigated the relation between clinical mental symptoms and biochemical parameters of acute intermittent porphyria. The case records of 344 consecutive patients admitted to the Porphyrias Research Group in the Western Infirmary in Glasgow between 1950 and 1988 with acute intermittent porphyria were examined for evidence of psychiatric contact. Of 16 individuals identified, 12 were available for the study. Forty relatives of these 12 probands, including 9 who were asymptomatic carriers of AIP, were interviewed for lifetime history of mental illness and current symptoms. Comparisons were made between 4 groups of patients based on urinary porphyrin levels and erythrocyte enzyme activity; 1) manifest acute intermittent porphyria, 2) latent acute intermittent porphyria, 3) normal relatives and 4) total acute intermittent porphyria (latent and manifest combined). No association was found between AIP and schizophrenia or manic-depressive illness. Only one patient with schizophrenia was found in the sample of 344 case notes, and in 2 families bipolar illness was found but did not segregate with acute intermittent porphyria. The commonest psychiatric diagnosis in patients was generalized anxiety.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Low prevalence of Helicobacter pylori in inflammatory bowel disease: association with sulphasalazine.

The prevalence of IgG antibodies to Helicobacter pylori was examined in 110 patients with inflammatory bowel disease (IBD) (63 ulcerative colitis, 47 Crohn's disease) and compared with 100 age and sex matched control patients. The overall prevalence of H pylori seropositivity in the IBD patients was 22%, which was significantly less than that of 52% in the controls (p < 0.002). There was no difference in prevalence between ulcerative colitis and Crohn's patients. The low seropositivity in the IBD patients resulted from a very low prevalence of 10% in those currently receiving sulphasalazine (n = 40) and similarly low prevalence of 7% in those previously receiving sulphasalazine (n = 30). In those receiving olsalazine or mesalazine and who had never had sulphasalazine, the prevalence of seropositivity was 45%. Further studies using 14C urea breath test and microscopy of antral biopsy specimens confirmed that the negative serology in patients receiving sulphasalazine resulted from absence of the infection rather than absence of humoral immune response to it. In six control patients with H pylori infection, a two week course of sulphasalazine (500 mg four times daily) only caused slight suppression of the 14C urea breath test. In vitro studies failed to show any direct antibacterial effect of sulphasalazine on H pylori. These findings indicate that longterm treatment with sulphasalazine leads to eradication of H pylori infection and that this does not result from a direct antibacterial effect. It may be caused by the drug treating the gastritis and thereby depriving the bacterium of essential nutrients exuded by the inflamed mucosa.

Adult↗
PubMed1994

Effect of Helicobacter pylori and its eradication on gastric juice ascorbic acid.

The presence of ascorbic acid in gastric juice may protect against gastric carcinoma and peptic ulceration. This study examined the effect of Helicobacter pylori (H pylori) on the secretion of ascorbic acid into gastric juice by measuring fasting plasma and gastric juice ascorbic acid concentrations in patients with and without the infection and also before and after its eradication. Gastric juice ascorbic acid concentrations in 19 H pylori positive patients were significantly lower (median 2.8, range 0-28.8 micrograms/ml) than those in 10 H pylori negative controls (median 17.8, range 5.6-155.4 micrograms/ml) (p < 0.0005) despite similar plasma ascorbic acid concentrations in both groups. The median gastric juice:plasma ascorbic acid ratio in the H pylori positive patients was only 1.16 (range 0.02-6.67), compared with a median ratio of 4.87 (range 0.76-21.33) in H pylori negative controls (p < 0.01). In the patients with H pylori infection there was a significant negative correlation between the severity of the antral polymorphonuclear infiltrate and gastric juice ascorbic acid concentrations (correlation coefficient -0.52, p = 0.02). After eradication of H pylori in 11 patients, gastric juice ascorbic acid concentrations rose from 2.4 (0-12.8 micrograms/ml) to 11.2 (0-50 micrograms/ml) (p = 0.01). The median gastric juice: plasma ascorbic acid ratio also increased from 1.33 (0.05-6.67) to 2.89 (0.01-166) (p = 0.01). In conclusion, the high gastric juice:plasma ascorbic acid ratio in H pylori negative subjects shows active secretion of ascorbic acid into gastric juice. Secondly, H pylori infection causes a reversible lowering of gastric juice ascorbic acid concentrations, which may predispose to gastric carcinoma and peptic ulceration.

Ascorbic Acid↗
PubMed1994

Safety of general anaesthesia and surgery in acute hepatic porphyria.

Patients with acute hepatic porphyria are denied essential operations because of concern that general anaesthesia and surgery will precipitate a life threatening porphyric crisis. This study assessed the safety of surgery under general anaesthesia in these patients. A combined prospective and retrospective case note study, with a biochemical study, was conducted in 25 patients with acute hepatic porphyria undergoing 38 surgical operations. Clinical outcome measures were survival and occurrence of porphyric crisis after surgery. The biochemical activity of porphyria was assessed by measurement of the perioperative 24 hour excretion of the haem precursors delta amino-laevulinic acid (ALA) and porphobilinogen (PBG). There were no deaths or crises after 29 operations in 19 patients who were known to have porphyria before their surgery, and therefore given only appropriate drugs. These operations include such major procedures as mitral valve replacement, hip replacement, coronary artery grafting, cholecystectomies, and renal transplantation. In eight of these patients the urinary excretion of ALA and PBG were studied, and showed no sustained postoperative increase. Nine operations were performed in eight patients before the diagnosis of porphyria was known and who thus received routine anaesthetic agents. Seven of these patients developed a postoperative porphyric crisis. Two of them died. It is concluded therefore that even the most major surgery can be undertaken safely in patients with porphyria. The risk is for undiagnosed cases.

Acute Disease↗
PubMed1993

Tin protoporphyrin prolongs the biochemical remission produced by heme arginate in acute hepatic porphyria.

BACKGROUND: In acute porphyria, repletion of intrahepatic heme, with exogenously administered heme, suppresses the overproduction of delta-aminolaevulinic acid (ALA) and porphobilinogen (PBG). The effect of reducing heme breakdown has been assessed by administering tin protoporphyrin, a competitive inhibitor of heme oxygenase. METHODS: The effect of tin protoporphyrin, 1 mumol/kg, and heme arginate, 3 mg/kg, individually and combined was compared with placebo in patients with an acute porphyric crisis. The treatments were given by intravenous infusion on three successive mornings. Thirty-four attacks were studied in 8 patients (9 placebo, 10 heme arginate alone, 4 tin protoporphyrin alone, and 11 combination treatments). RESULTS: Placebo and tin protoporphyrin alone had little effect on ALA and PBG excretion. Following heme arginate alone or combined with tin protoporphyrin, there was a marked and similar suppression of both ALA and PBG excretion (P < 0.005 for each, compared with pretreatment values). However, on the 5th day after discontinuing treatment, the excretion of ALA and PBG were both lower following combination therapy than following heme arginate alone (P < 0.005 and P < 0.01, respectively). CONCLUSIONS: These findings suggest that inhibition of heme oxygenase by tin protoporphyrin prolongs the biochemical remission induced by heme arginate in the porphyric crisis.

Acute Disease↗
PubMed1993

Acute perforated duodenal ulcer is not associated with Helicobacter pylori infection.

Most patients with chronic duodenal ulcer disease have Helicobacter pylori infection and eradicating it considerably reduces the relapse rate. The prevalence of H pylori in 80 patients (mean age = 52 years, range 17-85) presenting with acute perforated duodenal ulcer was examined and compared with age and sex matched hospital control patients. H pylori state was assessed by serum anti-H pylori IgG (Helico-G kit, Porton) using a titre of 18 or less as negative with a specificity of 89% and sensitivity of 88%. Only 47% of the perforated duodenal ulcer patients were positive for H pylori and this was similar to the value of 50% in the controls. In 51 of the perforated duodenal ulcer patients 14C-urea breath tests were also performed 4-10 weeks after surgery and this confirmed that only 49% were positive for H pylori. None of these patients had received perioperative drugs that might have eradicated the infection. The H pylori positive and H pylori negative perforated duodenal ulcer patients were similar with respect to age (53, 51), smoking (84%, 83%), and consumption of more than 15 units of alcohol per week (42%, 38%). Duodenal ulcer disease had been diagnosed before acute perforation in only 24% of those with H pylori and also 24% of those without the infection. Regular non-steroidal anti-inflammatory drug (NSAID) use was common in both those with (44%) and without (45%) H pylori. In conclusion, the lack of association of acute perforated duodenal ulcer and H pylori infection suggests that perforated duodenal ulcer has a different pathogenesis from chronic duodenal ulcer disease, and that the first should not be regarded simply as a complication of the second.

Acute Disease↗
PubMed1993

Omeprazole inhibits colorectal carcinogenesis induced by azoxymethane in rats.

Numerous clinical and experimental studies suggest that gastrin plays an important part in the development of colorectal cancer in humans. This study was done to assess the influence of omeprazole induced hypergastrinaemia on the development of colorectal tumours in an experimental animal model. Forty female Sprague-Dawley rats received either omeprazole (40 mumol/kg) or vehicle (0.25% methylcellulose) by once daily oral gavage throughout the experiment. All animals received 12 consecutive weekly subcutaneous injections of azoxymethane (10 mg/kg/week) beginning at week 6. Serum gastrin concentrations were measured during weeks 1 and 5 and at death (week 27). Chronic omeprazole treatment resulted in appreciable hypergastrinaemia during the study, mean gastrin concentrations in omeprazole treated rats being raised by up to nine to 10 fold, compared with vehicle treated control rats (p < 0.001). Despite this, tumour incidence in the omeprazole group was significantly lower at 63%, compared with 95% in the vehicle only group (p < 0.02). The median number of tumours in the omeprazole group (1) compared with the vehicle group (3) was also significantly lower (p = 0.02). Average tumour size, site distribution, and the comparative frequencies of adenomas and adenocarcinomas were similar in the two groups. This study shows that omeprazole protects against colorectal carcinogenesis in this model despite causing appreciable hypergastrinaemia. The mechanism by which this occurs is unclear and merits further investigation. Because of the compounding protective effects of omeprazole, this model is not a suitable one for studying the longterm trophic effects of gastrin on the colon.

Animals↗
PubMed1993

Helicobacter pylori related hypergastrinaemia is the result of a selective increase in gastrin 17.

Helicobacter pylori infection increases the serum concentration of gastrin, and this may be one of the mechanisms by which it predisposes to duodenal ulceration. Different forms of circulating gastrin were studied both basally and postprandially in 13 duodenal ulcer patients before and one month after eradication of H pylori. Three antisera that are specific for particular regions of the gastrin molecules were used. Gel chromatography indicated that > 90% of the circulating gastrin consisted of gastrin (G) 17 and G34 both before and after eradicating the infection. The basal median total immunoreactive gastrin concentration fell from 26 pmol/l (range 11-43) to 19 pmol/l (8-39) (p < 0.05), entirely because of a fall in G17 from 6 pmol/l (< 2.4-25) to < 2.4 pmol/l (< 2.4-23) (p < 0.001). The median (range) basal G34 values were similar before (15 pmol (2-36)) and after (10 pmol (2-30)) eradication. The median total immunoreactive gastrin concentration determined 20 minutes postprandially fell from 59 pmol/l (38-114) to 33 pmol/l (19-88) (p < 0.005), and again this was entirely the result of a fall in G17 from 43 pmol/l (9-95) to 17 pmol/l (< 2.4-52) (p < 0.001). The median postprandial G34 values were similar before (13 pmol/l, range 6-42) and after (15 pmol/l, range 6-30) eradication. Eating stimulated a noticeable rise in G17 but little change in G34, both in the presence and absence of H pylori. The finding that H pylori infection selectively increases G17 explains why the infection causes mainly postprandial hypergastrinaemia. G17 is increased selectively because H pylori predominantly affects the antral mucosa which is the main source of G17 whereas G34 is mainly duodenal in origin. This study also indicates that the increased concentration of gastrin in H pylori infection is the result of an increase in one of the main biologically active forms of the hormone.

Adult↗