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Biomedical subjects

K E McColl

Publications and source records attributed to K E McColl.

At least 55 records · Page 3Linked to original sources
PubMed1999

Molecular forms of gastrin in the circulation of patients with achlorhydria.

BACKGROUND/AIM: To study circulating gastrin profile, both fasting and postprandially, in patients with achlorhydria due to auto-immune atrophic gastritis, comparing these with normal healthy controls. METHODS: Circulating gastrins were measured using three region-specific radio-immunoassays: amidated gastrins (R98), N-terminal G34 (R526) and N-terminal G17 (GP168). Samples were analysed further using gel chromatography. RESULTS: Fasting gastrin concentrations were elevated in achlorhydria as measured using all three antisera: median 714 pmol/l (range 107-5176) in achlorhydria versus 12 pmol/l (2-33) in controls (R98), 343 pmol/l (45-4316) versus 10 pmol/l (5-41) (R526), and 720 pmol/l (14-6000) versus 2 pmol/l (1-10) (GP168). In patients, 47% of gastrin was amidated (95% in controls) and 30% was processed N-terminally only to G71 (4% in controls). Gastrin rose significantly postprandially: 1643 pmol/l (269-7142) in patients versus 24 pmol/l (5-142) in controls (R98), 432 pmol/l (113-4756) versus 15 pmol/l (7-45) (R526) and 2189 pmol/l (304-7150) versus 15 pmol/l (7-45) (GP168). Only 25% was amidated in the patient group (93.5% in controls) and 21% remained as component I (4% in controls). CONCLUSIONS: This abnormal gastrin profile associated with hypergastrinaemia secondary to achlorhydria is consistent with saturation of the enzymes involved in the processing of the pro-hormone, in particular amidation of the C-terminus.

Achlorhydria↗
PubMed1999

Does concern about missing malignancy justify endoscopy in uncomplicated dyspepsia in patients aged less than 55?

OBJECTIVE: There is increasing interest in using noninvasive H. pylori testing rather than endoscopy in determining the management of younger patients presenting with dyspepsia. However, there is concern that this approach may result in missing potentially curable malignancy. The aim of the study was therefore to assess whether concern over occult malignancy is valid in patients aged <55 yr presenting with uncomplicated dyspepsia. METHODS: A predetermined questionnaire was used to review the case notes of patients aged <55 yr who had presented with esophageal or gastric cancer between 1989 and 1993 within the Greater Glasgow Health Board population of 940,000. RESULTS: A total of 169 patients aged <55 yr were diagnosed to have gastroesophageal malignancy over the 5-yr period, representing an incidence of about 1 per 28,000 total population/yr. There were only five patients who were found to have upper GI malignancy when undergoing upper GI investigation in the absence of sinister symptoms. This represents an incidence of underlying malignancy in patients of <55 yr with uncomplicated dyspepsia of 1.06 per million total population/yr. Of these five patients, all had lymph node metastases at diagnosis and four had died between 2 months and 3 yr of follow-up. CONCLUSIONS: Upper GI malignancy is extremely rare in patients <55 yr presenting with uncomplicated dyspepsia and, when found, is usually incurable. Consequently, concern about missing underlying curable malignancy is not a valid indication for endoscoping patients <55 yr presenting with uncomplicated dyspepsia.

Adult↗
PubMed1999

Dyspepsia on withdrawal of ranitidine in previously asymptomatic volunteers.

OBJECTIVE: H2 receptor antagonist therapy has been shown to produce rebound acid hypersecretion. The clinical significance of this phenomenon is not known. We performed this study to determine whether withdrawal of H2 receptor antagonist therapy results in dyspepsia in previously asymptomatic volunteers. METHODS: Thirty-five Helicobacter pylori-positive asymptomatic volunteers were randomized in double-blind fashion to receive 2 months' treatment with either ranitidine 300 mg nocte or placebo. Dyspeptic symptoms were measured before starting treatment and over the course of 10 days after stopping treatment by means of a validated questionnaire. RESULTS: Thirty-one subjects completed the study; 17 were randomized to ranitidine. The pretreatment median aggregate dyspepsia score of the placebo group was 0 (0-4), as was that of the ranitidine group (0-8) (N.S.). During the 10 days after completion of ranitidine, the median aggregate dyspepsia score was 1.4 (0-30), compared with 0 (0-6.3) after placebo (p < 0.01). Of those given ranitidine, 59% experienced dyspepsia after treatment, compared with only 14% who took placebo. In the subgroup that developed dyspepsia after active therapy, the median duration of symptoms was 2 days, symptom severity being maximal on the second day after completion of the tablets. On the days when dyspepsia was experienced, the median daily dyspepsia score was 5 (range, 2-10), which was similar to that of a control group with active duodenal ulcer disease (5; range, 0-11). CONCLUSIONS: Withdrawal of a 2-month course of ranitidine 300 mg nocte results in the development of dyspeptic symptoms in a proportion of previously asymptomatic subjects. Patients receiving ranitidine should be warned about this rebound dyspepsia and advised not to immediately resume treatment, as rebound symptoms are likely to improve within a few days.

Adult↗
PubMed1999

Helicobacter pylori infection potentiates the inhibition of gastric acid secretion by omeprazole.

BACKGROUND: Omeprazole has a greater intragastric pH elevating effect in Helicobacter pylori positive than negative subjects. Ammonia production by H pylori has been suggested as a probable mechanism. AIMS: To assess the effect of H pylori status on gastric acid secretion during omeprazole treatment, and to examine the possible role of ammonia neutralisation of intragastric acid in increased omeprazole efficacy in infected subjects. METHODS: Twenty H pylori positive and 12 H pylori negative healthy volunteers were examined before and six to eight weeks after commencing omeprazole 40 mg/day. On both occasions plasma gastrin and acid output were measured basally and in response to increasing doses of gastrin 17 (G-17). Gastric juice ammonium concentrations were also measured. RESULTS: Prior to omeprazole, measurements were similar in the H pylori positive and negative subjects. During omeprazole, median basal intragastric pH was higher in the H pylori positive (7.95) versus negative (3.75) subjects (p<0.002). During omeprazole basal, submaximal (180 pmol/kg/h G-17), and maximal acid outputs (800 pmol/kg/h G-17) were lower in H pylori positive subjects (0.0, 3.6, 6.0 mmol/h respectively) versus negative subjects (0.3, 14.2, 18.6 mmol/h) (p<0.03 for each). This effect was not explained by neutralisation by ammonia. CONCLUSION: The presence of H pylori infection leads to a more profound suppression of acid secretion during omeprazole treatment. The effect cannot be explained by neutralisation of intragastric acid by bacterial ammonia production and its precise mechanism has to be explained.

Adult↗
PubMed1998

The acid response to gastrin distinguishes duodenal ulcer patients from Helicobacter pylori-infected healthy subjects.

BACKGROUND & AIMS: Helicobacter pylori-induced hypergastrinemia is accompanied by increased acid secretion in patients with duodenal ulcer (DU) but not in infected healthy volunteers. The aim of this study was to investigate the mechanism underlying this difference. METHODS: Thirty-four H. pylori-negative and 20 H. pylori-positive healthy volunteers and 15 H. pylori-positive patients with DU were studied. Maximal acid output and sensitivity to gastrin (gastrin concentration required to achieve 50% maximal acid output) were assessed by examining the dose response to gastrin 17. Inhibitory control was tested by comparing the maximal acid response to cholecystokinin octapeptide with that for gastrin 17. RESULTS: Sensitivity to gastrin was similar in patients with DU (median, 69.5 ng.L-1; range, 26.2-142) and H. pylori-negative healthy volunteers (median, 82.2 ng.L-1; range, 17.7-410); H. pylori-positive healthy volunteers were less sensitive than either (164.5 ng.L-1; range, 44.8 to > 3360 ng.L-1). Patients with DU had higher maximal acid output (51.2 mmol.h-1; range, 30.8-73.7 mmol.h-1) than either infected healthy volunteers (37.8 mmol.h-1; range, 0.0-65.0 mmol.h-1; P < 0.04) or uninfected healthy volunteers (35.3 mmol.h-1; range, 21.3-67.3 mmol.h-1; P < 0.002). The maximal acid output in both groups of healthy subjects was similar. The proportion of maximal acid output to gastrin 17 achieved by cholecystokinin was similar in patients with DU (36.6%; range, 21.5%-58.2%) and H. pylori-negative healthy volunteers (28.7%; range, 5.9%-85.8%). CONCLUSIONS: A combination of decreased sensitivity to gastrin in infected healthy volunteers and increased maximal acid secretory capacity in patients with DU underlies their different acid response to H. pylori-induced hypergastrinemia.

Diagnosis, Differential↗
PubMed1998

Role of gastric acid in the aetiology of dyspeptic disease and dyspepsia.

The main diseases associated with dyspepsia are peptic ulcer disease, gastro-oesophageal reflux disease and non-ulcer dyspepsia. Increased gastric acid secretion is a characteristic of most duodenal ulcer patients and of a small minority of non-ulcer dyspepsia and gastro-oesophageal reflux disease patients. Although acid secretion is normal in most gastro-oesophageal reflux disease patients, the condition is mainly the result of excess exposure of the distal oesophagus to acid refluxing from the stomach. Increased mucosal sensitivity to acid is involved in the aetiology of dyspeptic symptoms in the majority of patients with peptic ulcer disease and gastro-oesophageal reflux disease, and in a minority of non-ulcer dyspepsia subjects. Gastric acid, therefore, plays an important role in both the aetiology of dyspeptic diseases and in the aetiology of dyspeptic symptoms.

Duodenal Ulcer↗
PubMed1998

Association between antibodies to heat shock protein 65 and coronary atherosclerosis. Possible mechanism of action of Helicobacter pylori and other bacterial infections in increasing cardiovascular risk.

INTRODUCTION: There is growing evidence that the immune response is involved in atherosclerosis. Antibodies to heat shock protein 60/65 have been shown to be a risk factor for carotid atherosclerosis and been proposed as a diagnostic marker of atherosclerosis. In addition, it has been suggested that the immune response to heat shock protein 60/65 may be a link between exposure to microorganisms and increased cardiovascular risk. AIMS: (1) To investigate the association between anti-shock protein 65 titre and coronary atherosclerosis. (2) To assess whether anti-mhsp65 titre is a useful diagnostic marker of atherosclerosis; (3) To examine the influence of Helicobacter pylori infection on anti-heat shock protein 65 titre. METHODS AND RESULTS: In the first study we measured anti-heat shock protein 65 titres in 136 consecutive male subjects admitted for routine coronary angiography. Anti-heat shock protein 65 titres correlated with both the severity and extent of coronary atherosclerosis and the relationship remains statistically significant for the presence of atherosclerosis (P = 0.012) after adjustment for possible confounding influences. However the association had insufficient sensitivity to be a useful clinical test. In the second study we recruited 100 patients with confirmed active H. pylori infection and double blindly randomized them to eradication therapy or placebo. Successful eradication of H. pylori led to a significant fall in anti-heat shock protein 65 titres (from a mean of 256.4 AU.ml-1 to 137.5 AU. ml-1. P = 0.033). CONCLUSION: These results raise the possibility that exposure to H. pylori and other micro-organisms lead to an increased risk of clinically manifest coronary artery disease by an autoimmune process.

Adult↗
PubMed1998

Interactions between H. pylori infection, gastric acid secretion and anti-secretory therapy.

There is evidence of a two-way interaction between gastric acid secretion and H. pylori-associated gastritis. Gastric acid secretion influences the density of H. pylori colonisation, its distribution within the stomach and the severity of the mucosal inflammatory response to the infection. In addition, H. pylori gastritis alters gastric acid secretion. In subjects with a predominant antral gastritis, it increases acid secretion predisposing to duodenal ulcer, whereas in others with predominant body gastritis, acid secretion is impaired and the subjects have an increased risk of gastric cancer. The two-way interaction between acid secretion and H. pylori gastritis is observed when H. pylori-positive subjects are treated with proton pump inhibitor agents. The inhibition of acid secretion induces a body gastritis and this inflammation of the body mucosa inhibits acid secretion thus augmenting the anti-secretory effect of the drug. In this article, we discuss the interaction between gastric acid secretion and H. pylori gastritis and its importance in determining disease outcome.

Achlorhydria↗
PubMed1998

Gastrin and colorectal cancer: where now?

Gastrin exerts a trophic influence on various regions of the gastrointestinal (GI) tract and this has led to an interest in its potential role in the growth of GI tumours. There is little evidence that elevated circulating levels of gastrin predispose to colonic tumours. However, the hormone can be detected within some colonic tumour tissues and a possible paracrine or autocrine role has been proposed. At present, evidence for such a role is conflicting, as is the evidence that colonic tumour cells possess receptors for the mature hormone. Colonic tumours have been found to contain much higher concentrations of incompletely processed gastrin precursors such as glycine extended gastrin and recent studies indicate that they may exert trophic effects mediated by specific receptors. Further studies of this are required. Whether specific hormone receptor antagonists will have a role in the clinical management of colonic tumours remains unclear.

Animals↗
PubMed1998

Current or recent proton pump inhibitor therapy markedly impairs the accuracy of the [14C]urea breath test.

BACKGROUND: There are increasing indications for assessing Helicobacter pylori status by non-invasive means in dyspeptic patients. There is also increasing use of proton pump inhibitor therapy for dyspeptic disease. AIMS: To determine the effect of proton pump inhibitor therapy on the accuracy of the [14C]urea breath test. PATIENTS: [14C]Urea breath tests were performed in 20 H. pylori-positive and 13 H. pylori-negative dyspeptic patients before commencing omeprazole and after 4 weeks of treatment with 40 mg/day and then 6 months of treatment with 20 mg/day. Further studies were done in H. pylori-positive patients to examine the time course of the onset and resolution of the effect observed. RESULTS: False negative results occurred in 45% of the H. pylori-positive subjects after 4 weeks of omeprazole 40 mg/day and in 28% after 6 months of 20 mg/day. False positive results occurred in 15% of the H. pylori-negative subjects after 4 weeks of omeprazole 40 mg/day. In the H. pylori-positive subjects time course studies showed increasing suppression of the breath test result over the first 2-4 weeks of treatment. It took a similar time for the breath test result to recover after stopping treatment. There was no significant change in H. pylori IgG serology in the H. pylori-positive patients after 7 months of omeprazole treatment. CONCLUSIONS: Proton pump inhibitor therapy markedly impairs the accuracy of the [14C]urea breath test and, in particular, produces a high proportion of false negative results. The effect is dose related and may persist for 2-4 weeks after stopping therapy. Patients should be carefully questioned about recent proton pump inhibitor therapy before accepting a negative breath test result as reliable.

Anti-Ulcer Agents↗
PubMed1998

Comparison of helisal rapid blood test and 14C-urea breath test in determining Helicobacter pylori status and predicting ulcer disease in dyspeptic patients.

OBJECTIVE: Noninvasive tests for Helicobacter pylori are used increasingly. Our aim was to compare the Helisal Rapid Blood (HRB) test and 14C-urea breath test (UBT) for determining H. pylori status and predicting ulcer disease. METHODS: Three hundred fifty-one consecutive patients with dyspepsia (mean age 40 yr; range 16-77 yr) had an HRB test and UBT followed by endoscopy with biopsies of the antrum and body for histology and antral urease slide test (CLO test). Patients were excluded if they had previously confirmed ulcer disease, gastric surgery, or anti-H. pylori therapy or were taking nonsteroidal anti-inflammatory drugs. RESULTS: Sixty-three percent of the patients were "gold standard" H. pylori positive (positive CLO test, positive staining), 34% were gold standard negative (negative CLO test, negative staining), and 3% had conflicting CLO test and histology. The UBT was superior to HRB for determining H. pylori status (sensitivity 98% vs 92%, p = 0.04; specificity 100% vs 69%, p < 0.001). The specificity of the HRB decreased with increasing patient age (74% for age <46 yr; 57% for age > or =46 yr). A negative UBT was superior to a negative HRB test for predicting the absence of ulcer disease (47% vs 36 %; p < 0.01). A positive UBT was similar to a positive HRB in predicting the presence of ulcer disease (92% vs 84%; p = 0.23). CONCLUSIONS: The HRB test is inferior to the UBT for determining H. pylori status. The tests have a similar ability to predict the presence of ulcer disease when positive, but a negative UBT is a better predictor of the absence of ulcer disease.

Adolescent↗
PubMed1998

Eradicating Helicobacter pylori reduces hypergastrinaemia during long-term omeprazole treatment.

BACKGROUND: Both proton pump inhibitor drug treatment and Helicobacter pylori infection cause hypergastrinaemia in man. AIMS: To determine whether eradicating H pylori is a means of reducing hypergastrinaemia during subsequent proton pump inhibitor treatment. METHODS: Patients with H pylori were randomised to treatment with either anti-H pylori or symptomatic treatment. One month later, all received four weeks treatment with omeprazole 40 mg/day for one month followed by 20 mg/day for six months. Serum gastrin concentrations were measured before and following each treatment. RESULTS: In the patients randomised to anti-H pylori treatment, eradication of the infection lowered median fasting gastrin by 48% and meal stimulated gastrin by 46%. When gastrin concentrations one month following anti-H pylori/symptomatic treatment were used as baseline, omeprazole treatment produced a similar percentage increase in serum gastrin in the H pylori infected and H pylori eradicated patients. Consequently, in the patients in which H pylori was not eradicated, median fasting gastrin concentration was 38 ng/l (range 26-86) at initial presentation and increased to 64 ng/l (range 29-271) after seven months omeprazole, representing a median increase of 68% (p < 0.005). In contrast, in the patients randomised to H pylori eradication, median fasting gastrin at initial presentation was 54 ng/l (range 17-226) and was unchanged after seven months omeprazole at 38 ng/l (range 17-95). CONCLUSION: Eradicating H pylori is a means of reducing the rise in gastrin during subsequent long term omeprazole treatment. In view of the potential deleterious effects of hypergastrinaemia it may be appropriate to render patients H pylori negative prior to commencing long-term proton pump inhibitor treatment.

Adult↗
PubMed1998

Assessment of symptomatic response as predictor of Helicobacter pylori status following eradication therapy in patients with ulcer.

BACKGROUND: Helicobacter pylori eradication therapy is routinely used for treating patients with peptic ulcer disease. AIMS: To assess the value of symptomatic response to H pylori eradication therapy as a marker of post-treatment H pylori status. PATIENTS AND METHODS: One hundred and nine dyspeptic patients with active duodenal or gastric ulceration association with H pylori infection had their symptoms measured by a validated questionnaire before and three months following H pylori eradication therapy. The symptomatic response was compared with post-treatment H pylori status as determined by the 14C urea breath test. RESULTS: An eradication rate of 84% was achieved. Of the 92 patients eradicated of H pylori, 47% experienced complete or near complete resolution of dyspepsia. Of the 17 patients in whom the infection was not eradicated, only one (6%) experienced resolution of dyspepsia. Resolution of dyspepsia was therefore a powerful predictor of eradication of H pylori with a predictive value of 98%. In contrast, persistence of dyspepsia was a weak predictor of persisting infection with a predictive value of only 25%. Excluding patients with endoscopic evidence of coexisting oesophagitis and/or retrosternal discomfort or reflux at initial presentation did not increase the predictive value of persisting dyspepsia for persisting infection. CONCLUSIONS: Complete resolution of dyspeptic symptoms is a powerful predictor of eradication of H pylori infection in ulcer patients. Persistence of symptoms is a weak predictor of persisting infection and patients with persisting dyspepsia must have their H pylori status rechecked to guide future management.

Adult↗
PubMed1997

Helicobacter pylori infection and chronic gastric acid hyposecretion.

BACKGROUND & AIMS: We have identified a subgroup of Helicobacter pylori-infected subjects with low or absent gastric acid output. The aim of this study was to document the morphological and functional abnormalities in these subjects and to assess the effect of eradicating the infection. METHODS: The 16 hypochlorhydric subjects (6 men) had a mean age of 55 years (range, 36-79 years). They underwent a 14C-urea breath test, H. pylori serology, fasting gastrin, gastric autoantibodies, gastroscopy with antral and body biopsies, and measurement of peak acid output to pentagastrin (PAO(PG)). Their histology was compared with that of age- and sex-matched duodenal ulcer and nonulcer dyspepsia patients (16 each). H. pylori infection was eradicated in the hypochlorhydric subjects, and the investigations were repeated 6 months later. RESULTS: Compared with controls, the hypochlorhydric subjects had less dense H. pylori colonization, body-predominant colonization and gastritis, and increased prevalence of body atrophy and intestinal metaplasia. Median PAO(PG) before eradication in the hypochlorhydric subjects was 1.1 mmol/h and increased to 12.6 mmol/h after eradication (P < 0.001), with no significant change in body atrophy or intestinal metaplasia. CONCLUSIONS: In some subjects, chronic H. pylori infection produces a body-predominant gastritis and profound suppression of gastric acid secretion that is partially reversible with eradication therapy.

Achlorhydria↗
PubMed1997

What remaining questions regarding Helicobacter pylori and associated diseases should be addressed by future research? View from Europe.

A variety of questions regarding Helicobacter pylori need to be addressed by future research. Further investigations are needed on the relationship between H. pylori and gastric cancer. In particular, the mechanism of the interaction between H. pylori infection and host genetic factors and dietary factors that lead to the cancer need to be unraveled. Also, the reversibility of cancer-associated abnormalities (e.g., hypochlorhydria, atrophy, and intestinal metaplasia) by eradication of H. pylori needs to be determined. Noninvasive means of identifying H. pylori-positive subjects at high risk of developing gastric cancer are required for such subjects to be targeted for eradication therapy. Further studies are also required on the interactions between H. pylori and proton pump inhibitor therapy that might predispose to cancer. There is considerable interest in the possibility of noninvasive H. pylori testing replacing endoscopy in determining management of nonelderly patients with uncomplicated dyspepsia unassociated with nonsteroidal anti-inflammatory drugs (NSAIDs). Randomized studies comparing endoscopy vs. noninvasive H. pylori testing in this situation are required with comprehensive outcome measures. Improvement in eradication therapy is required and will depend on the development of more effective and specific antibiotics and therapeutic vaccines. Wide-scale elimination of the infection will depend on preventing its spread from person to person. Achieving this will require further knowledge of its mode of transmission, particularly in childhood, and the development of prophylactic vaccines. Further studies are required to define the role of H. pylori infection in other diseases, including predisposition to enteric infection in the developing world as a result of H. pylori-induced chronic hypochlorhydria, nonulcer dyspepsia, pernicious anemia, atherosclerosis, and NSAID-related ulcer disease. Finally, we need to know whether H. pylori infection may be beneficial in certain circumstances and whether eradicating the infection may be disadvantageous to some subjects.

Anti-Bacterial Agents↗