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Biomedical subjects

Kenneth E L McColl

Publications and source records attributed to Kenneth E L McColl.

16 recordsLinked to original sources
PubMed2006

Cancer of the gastric cardia.

Current evidence indicates that cardia cancers are of at least two distinct and disparate aetiologies. One type resembles cancer of the more distal stomach (Type A), being a consequence of atrophic gastritis due to Helicobacter pylori infection or more rarely autoimmune atrophic gastritis. Another type (Type B) resembles oesophageal adenocarcinoma and is likely to be a consequence of short-segment gastro-oesophageal reflux disease. The two cancers are themselves indistinguishable but examination of the gastric phenotype indicates the aetiology: Type A occurring in patients with evidence of atrophic gastritis whereas Type B occurs in subjects with healthy acid secreting stomachs. In subjects with healthy acid secreting stomachs the cardia has a specific luminal chemistry remaining highly acidic and unbuffered following a meal and having very active nitrosative chemistry due to the acidification of nitrite in saliva. This luminal chemistry may contribute to the high incidence of metaplasia and neoplasia at this anatomical site.

Adenocarcinoma↗
PubMed2006

Endoscopy has minimal impact on mortality from upper gastrointestinal cancer in patients older than 55 years with uncomplicated dyspepsia.

INTRODUCTION: The objective of the study was to determine the effectiveness of endoscopy to detect curable upper gastrointestinal malignancy in patients older than 55 years presenting with uncomplicated dyspepsia. METHODS: A cohort study was performed in North Glasgow Health Trust. One hundred and thirty-one patients older than 55 years of age, diagnosed to have upper gastrointestinal cancer within the North Glasgow Trust between January 1995 and December 1997, identified by the West of Scotland Cancer Registry were included. The main outcome measures were the proportion of upper gastrointestinal cancers that present in patients older than 55 years with uncomplicated dyspepsia, and the proportion of patients that presented with uncomplicated dyspepsia who have curable upper gastrointestinal cancer. RESULTS: Of the 131 cancer cases identified, only 30 (23%) had dyspepsia (complicated or uncomplicated) as their predominant symptom and only eight (6%) patients presented with uncomplicated dyspepsia. Of those eight patients presenting with uncomplicated dyspepsia and found to have upper gastrointestinal cancer, six were found to have lymph node metastases and/or extensive metastases at the time of diagnosis. Each of these six patients died from their cancer within 39 months of diagnosis. Of the two patients presenting with uncomplicated dyspepsia without evidence of lymph node spread, one died 55 days after diagnosis. Only one patient presenting with uncomplicated dyspepsia and found to have cancer remains alive at 5-year follow-up. CONCLUSIONS: Of the 131 patients diagnosed with upper gastrointestinal cancer, only eight presented with uncomplicated dyspepsia and only one of these was cured. Consequently a policy of endoscoping patients older than 55 years with uncomplicated dyspepsia will reduce death from upper gastrointestinal cancers by less than 1% in our population.

Aged↗
PubMed2005

Acute intermittent porphyria.

Acute intermittent porphyria (AIP) is characterised by neurovisceral crises the most common clinical presentation of which is abdominal pain. It is an autosomal dominant condition with incomplete penetrance and is potentially life-threatening. The key point in management is to suspect and confirm the diagnosis as early as possible in order to treat the attack and to avoid inappropriate treatments which may exacerbate the crisis. In this chapter we briefly outline the haem biosynthetic pathway and how deficiencies in individual enzymes give rise to the different porphyrias. We then describe the clinical features and diagnosis of AIP, followed by a discussion of pathogenesis, highlighting advances in the molecular biology of AIP and introducing the debate as to whether neurovisceral crises might result from porphyrin precursor neurotoxicity or from haem deficiency. Finally we discuss management, including family screening, avoidance of triggering factors, analgesia, maintenance of a high calorie intake, and administration of haem derivatives.

Abdominal Pain↗
PubMed2005

Gastroduodenal disease, Helicobacter pylori, and genetic polymorphisms.

Over the past 20 years, there has been marked progress in our understanding of the role of genetic and environmental factors in the etiology of gastroduodenal disease. Helicobacter pylori infection now is recognized to be the most important environmental factor for both noncardia gastric cancer and peptic ulcer disease. The likelihood of the infection resulting in significant disease depends on genetic polymorphisms influencing the virulence of the organism. However, the specific pattern of disease induced by the infection is determined to a great extent by genetic polymorphisms in the host that govern the local gastric immune response elicited. Genetic factors also are important in the treatment of gastroduodenal diseases. Polymorphisms of host CYP2C19 influence the pharmacokinetics and clinical efficacy of proton pump inhibitor therapy.

Duodenal Diseases↗
PubMed2005

Helicobacter pylori "test and treat" or endoscopy for managing dyspepsia: an individual patient data meta-analysis.

BACKGROUND & AIMS: Helicobacter pylori "test and treat" has been recommended for the management of young dyspeptic patients without alarm symptoms, and trials have suggested that it is as effective as endoscopy. However, none of these trials have had sufficient sample size to confirm that "test and treat" costs less or to detect small differences in effect. A collaborative group has prospectively registered trials comparing prompt endoscopy with a "test and treat" approach, with the aim of performing an individual patient data meta-analysis of both effect and resource utilization data. METHODS: Researchers provided data for meta-analysis, pooling effects of interventions on individual dyspepsia symptoms. Standardized unit costs were applied to resource utilization, and net benefit was calculated at patient level. Effects, costs, and net benefit were then pooled at study level. RESULTS: Five trials were identified, containing 1924 patients (946 endoscopy [mean age, 40 years], 978 "test and treat" [mean age, 41 years]). The relative risk (RR) of remaining symptomatic after 1 year was reduced with endoscopy compared with "test and treat" (RR = 0.95; 95% confidence interval [CI]: 0.92-0.99). "Test and treat" cost 389 dollars less per patient (95% CI: 275-502 dollars). Using the net benefit approach, at no realistic level of willingness to pay per patient symptom-free did prompt endoscopy become cost-effective. CONCLUSIONS: Prompt endoscopy confers a small benefit in terms of cure of dyspepsia but costs more than "test and treat" and is not a cost-effective strategy for the initial management of dyspepsia.

Cost-Benefit Analysis↗
PubMed2005

Prediction of malignant potential in reflux disease.

There is interest in noninvasive means of identifying reflux patients at increased risk of developing Barrett's esophagus and adenocarcinoma. In this issue, Gough et al. studied the prevalence of polymorphisms of cytokine genes in patients with uncomplicated esophagitis versus Barrett's/esophageal adenocarcinoma. They reported a difference between the groups with respect to the interleukin-1 receptor antagonist and interleukin-10 genes. However, the number of comparisons carried out mean that the association is not statistically significant and further studies will be required to confirm/refute the association. The genetic markers reported would unfortunately be of little value in predicting individual risk of esophageal adenocarcinoma as they are weak predictors and relatively rare within the esophagitis population. The findings of this study demonstrate the general principle that polymorphisms of individual genes are of limited value in identifying patients at risk of sporadic-types of cancer such as most cases of esophageal adenocarcinoma.

Adenocarcinoma↗
PubMed2004

Helicobacter pylori eradication releases prolonged increased acid secretion following omeprazole treatment.

BACKGROUND & AIMS: Rebound increased acid secretion has been observed at 2 weeks after discontinuing omeprazole treatment in Helicobacter pylori -negative, but not H. pylori -positive, subjects. It is unknown whether this is a prolonged phenomenon or whether a similar phenomenon appears later in H. pylori positives or is released by eradication therapy. The aims of this study were to answer these 3 questions. METHODS: Twelve H. pylori -negative and 20 H. pylori -positive subjects were studied. Each had a basal, submaximal, and maximal pentagastrin-stimulated acid secretion study before, during, and at 7, 14, 28, 42, and 56 days after a 56-day course of omeprazole 40 mg/day. Ten of the H. pylori -positive subjects had their infection eradicated during the last week of treatment. RESULTS: In the H. pylori -negative subjects, there was rebound secretion of submaximal (P < 0.003) and maximal (P < 0.003) acid output, which persisted until at least 56 days after discontinuing omeprazole. The H. pylori -uneradicated subjects had no rebound increased secretion other than in maximal acid output at 28 (P < 0.01) and at 42 days after treatment (P < 0.02). In those eradicated of H. pylori close to the end of omeprazole, there was rebound increased secretion of submaximal acid output (P < 0.04) lasting until 56 days and of maximal acid output (P < 0.01) lasting until 28 days after treatment. CONCLUSIONS: Rebound increased acid secretion following omeprazole is a prolonged phenomenon in H. pylori -negative subjects. There is little evidence of it in H. pylori -infected subjects, but eradicating the infection releases the phenomenon. The accentuated H. pylori -related oxyntic gastritis induced by omeprazole is likely to protect against the rebound phenomenon.

Adult↗
PubMed2003

Novel mechanism of nitrosative stress from dietary nitrate with relevance to gastro-oesophageal junction cancers.

High luminal concentrations of nitric oxide are generated at the human gastro-oesophaegal junction and within Barrett's oesophagus due to the reduction of salivary nitrite to nitric oxide by acidic gastric juice. Salivary nitrite is derived from the entero-salivary recirculation of dietary nitrate. Our aim was to determine whether nitric oxide generated within the lumen will exert nitrosative stress on the adjacent epithelium. A benchtop model was constructed reproducing the nitrite chemistry occurring within the lumen of the upper gastrointestinal tract where saliva encounters acidic gastric juice. It incorporated an epithelial compartment maintained at pH 7.4 and separated from the lumen by a hydrophobic barrier with the properties of the epithelial lipid cell membrane. The secondary amine morpholine was used to measure N-nitroso compound formation in both the lumen and epithelial compartment. Adding 100 micro M nitrite to the acidic (pH 1.5) luminal compartment depleted of ascorbic acid generated 6.2 +/- 2.0 micro M (mean +/- SE) N-nitrosomorpholine in that compartment and 2.2 +/- 0.1 micro M nitrosomorpholine in the epithelial compartment at 30 min. When 100 micro M nitrite was added to the acidic luminal compartment containing physiological concentrations of ascorbic acid, all the nitrite was immediately converted to nitric oxide and no N-nitrosomorpholine was formed within that compartment. However, the nitric oxide rapidly diffused from the luminal compartment into the epithelial compartment and there generated very high concentrations of N-nitrosomorpholine (137 +/- 5.6 micro M at 30 min). The addition of ascorbic acid or glutathione to the epithelial compartment could only reduce nitric oxide-induced nitrosation within that compartment by 40%. The nitrate-derived nitric oxide generated within the lumen where saliva encounters gastric acid is likely to exert substantial nitrosative stress on the adjacent epithelium. This may contribute to the high prevalence of mutagenesis at this anatomical site.

Ascorbic Acid↗
PubMed2003

Barrett's esophagus evokes a quantitatively and qualitatively altered response to both acid and hypertonic solutions.

OBJECTIVE: The stomach contents become hypertonic after a meal and provide esophageal refluxate that is both acidic and hypertonic. This study examined the symptomatic response to esophageal exposure to hypertonic and acidic solutions in patients with gastroesophageal reflux disease (GERD) and Barrett's esophagus. METHODS: Symptom intensity and character were measured in double-blind fashion during esophageal instillation of water, hypertonic saline (osmolality 1030 mOsm/kg), hydrochloric acid (pH 1 and 2.5), and acidified hypertonic saline (pH 1 and 2.5). The studies were performed in healthy controls and GERD patients with and without Barrett's esophagus. RESULTS: The GERD patients with Barrett's differed from the non-Barrett's GERD patients in being less sensitive to acid (mean intensity score, 2.3 vs 4.8, p < 0.05), more sensitive to hypertonic saline (1.3 vs 0.4, p < 0.05) and by showing an additive effect when the acid and hypertonic solutions were combined, resulting in similar scores in the two patient groups to the combination (4.4 vs 4.3). The frequency of nausea was higher in the Barrett's group compared to the other GERD patients after hypertonic saline (21% vs 0%, p < 0.05), acid (50% vs 21%, p < 0.05) and the acid hypertonic combination (71% vs 29%, p < 0.05). CONCLUSIONS: Barrett's mucosa is associated with reduced symptomatic response to acid, increased response to hypertonic solutions, and a higher incidence of nausea in response to either stimulus.

Adult↗
PubMed2003

The role of interleukin-1beta and other potential genetic markers as indicators of gastric cancer risk.

Helicobacter pylori infects half of the world's population, and is associated with asymptomatic gastritis and also with more serious conditions such as peptic ulcer disease and gastric carcinoma. The clinical outcome is largely dependent on the severity and distribution of the H pylori-induced gastritis, but the pathogenesis remains poorly understood. Bacterial virulence factors and environmental influences contribute to the pathogenesis, but do not explain the divergent outcomes. There is emerging evidence that host genetic factors play a key role in determining the clinical outcome of H pylori infection. In particular, proinflammatory genotypes of the interleukin-1 beta (IL-1b) gene are associated with an increased risk of gastric cancer and its precursors. The effects are most likely mediated through the induction of hypochlorhydria and severe corpus gastritis with the subsequent development of gastric atrophy. The roles of IL-1b and other host genetic factors in the pathogenesis of H pylori related cancer are discussed in this article.

Diet↗
PubMed2002

Motion--Helicobacter pylori causes or worsens GERD: arguments against the motion.

Data from large epidemiological studies show that Helicobacter pylori is less prevalent in patients with gastroesophageal reflux disease (GERD) than in control subjects. The more virulent cagA-positive strains of the organism are also less commonly seen in patients with erosive esophagitis and in those with Barrett's esophagus than in those with less severe forms of GERD. Although the relationship between H pylori and gastric physiology is complex, the organism has little effect on acid secretion in most North American or Western European subjects, and has a net suppressive effect, especially in elderly subjects, in other parts of the world. Thus, the organism has a potential protective effect against GERD, which is exacerbated by gastric acidity. H pylori has no proven effect on other gastric factors that might provoke reflux, including delayed gastric emptying or inappropriate relaxation of the gastric fundus. Two well-designed interventional studies have found that eradication of H pylori either provoked GERD or had no effect. A third smaller study, which seemed to demonstrate that persistent infection was associated with GERD, was flawed, in that the two treatment groups were not comparable. The evidence thus does not support the idea that H pylori infection provokes or aggravates GERD.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2002

How does H. pylori infection cause gastric cancer?

H. pylori is now recognised to be an important co-factor in the aetiology of non-cardia gastric cancer of both the diffuse and intestinal histological type. The latter type develops via a complex multistage and multifactorial process. The fist stage involves progression from superficial gastritis to atrophic pangastritis with intestinal metaplasia and associated hypochlorhydria. This gastric phenotype may then progress to dysplasia and cancer. Many co-factors are involved in this progression including the strain of H. pylori, host genetic factors, such as interleukin-1 polymorphisms and gender, plus environmental factors such as smoking and diet. Intestinal colonisation with helminthic infection may retard the progression by altering the immune and inflammatory response to H. pylori and colonisation of the achlorhydric stomach with nitrosating bacteria may promote progression to cancer. H. pylori appears to be an obligatory co-factor in the aetiology of most gastric cancers. Consequently, prevention of the infection or its eradication in early life should reduce the incidence of this common and usually fatal tumour.

Genotype↗