PubMed Health⌕ Search

Biomedical subjects

K G Wormsley

Publications and source records attributed to K G Wormsley.

At least 19 recordsLinked to original sources
PubMed1992

[Effectiveness and safety of long-term H2-receptor antagonist maintenance therapy].

The long-term maintenance therapy with an H2 receptor antagonist is currently the best treatment for ulcer disease. The treatment is effective in keeping most ulcers in remission, and is safe both by preventing ulcer complications and because the treatment itself is innocuous. Maintenance therapy achieves the objective of all treatment--it restores patients to normal health. Treatment of ulcer disease with an H2 receptor antagonist can be considered one of the triumphs of modern therapy.

Dose-Response Relationship, Drug↗
PubMed1992

Flow cytometry of oesophageal mucosal biopsies; epidermal growth factor receptor, and CD15.

Flow cytometry may be used to examine the properties of single or isolated cells. We have shown that it is possible to disaggregate and label oesophageal epithelial cells for two surface markers, CD15 and epidermal growth factor receptor. We have previously demonstrated these markers in oesophageal squamous cells using immunoperoxidase techniques. These labelled disaggregated cells could then be measured by flow cytometry.

Adult↗
PubMed1992

Complications associated with ulcer recurrence following gastric surgery for ulcer disease.

The present study is an attempt to assess the risks of the complications associated with recurrent ulcers in patients who have undergone gastric surgery and to determine whether these risks differ from those observed in patients receiving long term maintenance treatment with H2-receptor antagonists for ulcer disease. One hundred and thirty studies reported in the literature during the past three decades have been analysed to determine both the approximate rate of ulcer recurrence and the proportion of patients with recurrent ulcers who have presented with either haemorrhage or perforation following the various types of gastric surgery for ulcer disease. From these data, estimates of the risks of haemorrhage and of perforation during the years following gastric surgery have been calculated. Vagotomy and antrectomy is associated with a low risk of ulcer recurrence (less than 1%) and the risk of complications in later years is accordingly very small (less than 0.5%). Partial gastrectomy, although associated with low recurrence rates, has a higher risk of complications (1.3% for haemorrhage, 0.3% for perforation) because the proportion of recurrent ulcers that present with haemorrhage or perforation is high (33% and 8%, respectively). Truncal vagotomy plus drainage (TV + D) and highly selective vagotomy (HSV) are associated with recurrence rates of 9% and 12%, respectively, but ulcer recurrences following these operations are less frequently accompanied by complications then recurrences after gastric resection and, as a result, the risks of haemorrhage (1.7% for TV + D; 1.3% for HSV) are similar to the risks after gastric resection. During long term (five years or more) maintenance treatment with H2-receptor antagonists, the risks of haemorrhage and perforation are less than 2% and less than 0.5%, respectively. It appears, therefore, that the likelihood of developing haemorrhage or perforation following gastric surgery is of the same order as that during maintenance treatment with H2-receptor antagonists, at least during the first decade of follow-up.

Histamine H2 Antagonists↗
PubMed1992

Growth regulatory peptides in gastric mucosa.

1. Epidermal growth factor and the related peptide transforming growth factor alpha have been implicated in the stimulation of gastric mucosal proliferation. We assessed the immunohistochemical distribution of these peptides and their receptor, epidermal growth factor receptor, in mucosa from the antrum and body of the stomach from 28 patients. Twenty-three of the 56 biopsies were histologically normal (12 antrum and 11 body), whereas the other 33 showed varying degrees of inflammation. 2. Epidermal growth factor, transforming growth factor alpha and epidermal growth factor receptor had maximal density of distribution on the apical surfaces of the superficial epithelial cells, but were also expressed to a lesser extent on neck and body cells of the glandular tissue (P less than 0.05). We also demonstrated that epidermal growth factor expression was greater in the epithelial cells of inflamed mucosa than in those of normal mucosa (P less than 0.05). 3. We assessed mucosal proliferation by the Ki-67 labelling index. Ki-67-positive cells were found predominantly in the neck area of the glands and were more frequent in glandular antral tissue than in body glandular tissue (P less than 0.05). Expression of epidermal growth factor receptor in the neck and isthmus cells had a significant correlation with the Ki-67 labelling index (P less than 0.05). 4. We conclude that epidermal growth factor and epidermal growth factor receptor may be important in the adaptation of gastric mucosa to inflammation.

Epidermal Growth Factor↗
PubMed1992

Mallory-Weiss tears occurring during endoscopy: a report of seven cases.

Mallory-Weiss tears occurring during the course of upper gastrointestinal endoscopy are apparently rare. The present report describes seven cases of iatrogenic gastro-oesophageal tears encountered during 10,000 endoscopic examinations over a period of six years. Five of the seven patients were female and six patients were aged 75 years or older. Six patients had hiatal hernias. The site of the mucosal tear was similar in all patients, extending from a V-shaped breach at the gastro-oesophageal junction inferiorly along the lesser curve for a variable distance of up to 8 cm. Neither retching nor struggling during the procedure contributed to the development of the lesion in any of the patients. One patient suffered from a haematemesis which required transfusion, and in a further patient the tear resulted in a haematemesis and gastric perforation necessitating laparotomy. The study indicates that Mallory-Weiss tears complicating endoscopy occur especially in elderly, female patients with hiatal hernias. The importance of admitting patients with this complication to hospital for overnight observation is recommended in view of the possible development of haemorrhage or perforation.

Age Factors↗
PubMed1992

Review article: maintenance treatment with H2-receptor antagonists for peptic ulcer disease.

In recent years a number of different strategies for managing patients with peptic ulcer disease have become available. The present review discusses the relative merits of each form of treatment. Intermittent treatment (whether given in response to symptoms or as a prophylactic regimen prescribed seasonally or at weekends) fails to prevent ulcer recurrence and leaves patients at risk of haemorrhage and perforation. Anti-Helicobacter pylori therapy, although useful in certain circumstances, cannot be recommended for all patients with ulcer disease because of side effects and, in any case, requires further assessment of efficacy. Gastric surgery reduces ulcer recurrence and complications, but operations which have a low incidence of side effects are associated with higher rates of ulcer recurrence, particularly when patients are followed up for more than 10 years. Long-term continuous maintenance treatment with H2-receptor antagonists for 5 or more years effectively prevents ulcer recurrence in the majority of patients and significantly reduces the risk of ulcer complications. In addition, maintenance treatment has proved to be safe and is well tolerated by patients. Maintenance treatment with H2-receptor antagonists is the preferred option for the management of patients with peptic ulcer disease.

Antacids↗
PubMed1992

Nine years of maintenance treatment with ranitidine for patients with duodenal ulcer disease.

Four hundred and sixty-four patients with duodenal ulcer disease received continuous maintenance treatment with ranitidine for up to 9 years. Treatment failure was defined as either the first symptomatic recurrence of ulcer or the first ulcer recurrence accompanied by haemorrhage. Life tables were constructed using the Kaplan-Meier product-limit method; comparisons of survival curves were performed using the log-rank test; and multivariate analysis was carried out using the Cox proportional hazards model. Results. The proportion of patients remaining free from symptomatic recurrence of ulcer during maintenance treatment with either 150 mg/day or 300 mg/day ranitidine was: 95% at 1 year; 88% at 3 years; 86% at 5 years; and 81% at 7 and 9 years (95% C.I. 76-86%). Young age and the absence of exposure to non-steroidal anti-inflammatory drugs (NSAIDs) at the time of diagnosis of ulcer were shown to increase the likelihood of developing ulcer recurrence. The rate of ulcer recurrence after 9 years of maintenance treatment (17%) was significantly less than that after 5 years without active anti-ulcer therapy (80%), P = 0.0001. The proportion of patients who remained free from ulcer haemorrhage during maintenance treatment was: 99.1% at 1 year and 98.1% at 5 and 9 years (95% C.I. 96.7-99.6%). The risk of haemorrhage was significantly greater in patients who were not receiving active treatment (12.4% at 5 years) than in patients receiving maintenance treatment (less than 2% at 9 years), P = 0.0001 (log-rank test). Patients who had originally presented with haemorrhage had an increased risk of further ulcer bleeding compared with patients who presented with pain (P = 0.0013). A significantly greater proportion of patients with NSAID-associated duodenal ulcers remained free from ulcer recurrence during maintenance treatment compared with patients suffering from 'idiopathic' ulcers (P = 0.0238), although there was no difference between the two groups in respect of haemorrhage during maintenance treatment. Conclusions. (a) Continuous maintenance treatment with ranitidine for up to nine years successfully prevents ulcer recurrence in more than 80% of patients with duodenal ulcer disease. (b) Young age increases the risk of ulcer recurrence during maintenance treatment with ranitidine. Ulcers associated with NSAID-intake at the time of diagnosis have a lesser risk of recurrence during maintenance treatment. (c) The risk of haemorrhage in patients with ulcer disease receiving maintenance treatment with ranitidine for nine years was less than 2% compared with greater than 12% in untreated patients observed for 5 years.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

Maintenance therapy in duodenal and gastric ulcer disease: survey of practice amongst British gastroenterologists.

We have used a postal questionnaire to obtain data on the practice of maintenance therapy for peptic ulcer disease by members of the British Society of Gastroenterology. Completed questionnaires were returned by 434 members. Ninety-six per cent used maintenance therapy for patients with duodenal ulcer and 81% for gastric ulcer. Maintenance therapy was considered to be safe (duodenal ulcer 91%; gastric ulcer 78%), acceptable to patients (duodenal ulcer gastric ulcer 89%; gastric ulcer 80%) and to reduce the incidence of ulcer complications (duodenal ulcer 81%; gastric ulcer 68%). There was consensus that increasing age of patient, current use of non-steroidal anti-inflammatory drugs, previous ulcer complications, and ulcer relapse after surgery were relatively strong indications for maintenance therapy. However, the proportion of patients who received maintenance therapy varied widely amongst respondents (from < 10% to > 50%). There was no agreement on the optimal duration of therapy, nor on management of patients who relapsed during maintenance therapy. It appears that the criteria for use of maintenance therapy need to be better defined, and that established knowledge about the practice of maintenance therapy should be better disseminated and acted upon.

Age Factors↗
PubMed1992

Epidermal growth factor in the oesophagus.

Epidermal growth factor (EGF) has been implicated in mitogenesis and oncogenesis in the gastrointestinal tract. To determine the role of EGF in oesophageal disease, its quantity and distribution in the oesophageal mucosa of control subjects and patients with oesophageal disease were studied. Oesophageal biopsy specimens, taken 20-40 cm from the incisors in 72 patients, were graded histologically and adjacent specimens were taken for immunohistochemical analysis of the distribution of EGF. In patients with Barrett's columnar lined oesophagus, specimens were also taken from the gastric cardia for comparison. Twenty two biopsy specimens showed oesophagitis, 20 Barrett's mucosa, and 30 were histologically normal. EGF was found in the capillary endothelium of the normal oesophageal papillae and basal mucosa. Significantly more EGF positive papillae were found in the normal mucosa (81%) than in the inflamed mucosa (42%) (p < 0.001). The 20 patients with Barrett's mucosa showed abnormal expression of EGF in 25% of the isthmus and superficial epithelial cells. This study has shown that EGF is found only in the endothelial cells of the capillaries of the normal oesophageal mucosa and that the peptide is detectable significantly less frequently than normal in the inflamed oesophageal mucosa. EGF is also abnormally present, in large quantities, in the cytoplasm of the epithelial cells of Barrett's mucosa compared with gastric mucosa.

Adult↗
PubMed1992

Epidermal growth factor receptors in the oesophagus.

The quantity and distribution of epidermal growth factor receptors (EGF-R) in oesophageal mucosa was studied in the oesophagus in order to determine its role in oesophageal disease. Fifty five biopsies were taken from different levels of the oesophagus in 25 consecutive patients undergoing endoscopy. Another group of eight patients with histologically proven Barrett's oesophagitis had a biopsy taken from the area of columnar lined oesophagus. A peripheral, membranous pattern was seen predominantly confined to the basal and immediately suprabasal cells in all of the first group of patients. In the superficial cells a few granular cytoplasmic structures were positive. All patients with Barrett's oesophagitis showed EGF-R staining of the surface epithelium. A computerised planimeter was used to determine the proportion of stained areas of squamous cells which were expressed as a percentage of the total area of squamous cells. The difference in the area of cells stained for EGF-R between normal and inflamed oesophageal mucosa (29.5% and 43.1% respectively) was significant (p less than 0.001).

Adult↗
PubMed1992

Proliferating cell nuclear antigen in oesophageal diseases; correlation with transforming growth factor alpha expression.

This study was designed to correlate mucosal proliferation in Barrett's oesophagus with expression of a growth promoting peptide, transforming growth factor alpha (TGF alpha). Oesophageal mucosa was studied from 50 patients with oesophageal disease who had been treated by oesophagectomy. Histological analysis showed a range of oesophageal pathology - 18 patients had gastric type Barrett's mucosa, 18 had intestinal type Barrett's mucosa, and 14 had oesophageal adenocarcinomas. Sections were stained immunohistochemically for proliferating cell nuclear antigen (PCNA) (an index of cellular proliferation) and TGF alpha. PCNA immunostaining was seen mainly in the basal cells of the neck/foveolar epithelial compartment of the glands in Barrett's oesophagus. However, in mucosa with high grade dysplasia, the proliferative compartment extended upwards into the superficial layers of the glands. At least 2000 cells were counted in each patient to determine the proportion with PCNA immunoreactivity (PCNA labelling index). The labelling index was highest in adenocarcinoma (25%) and in Barrett's intestinal type mucosa with high grade dysplasia (26%) compared with intestinal type mucosa with no significant dysplasia (20%) and Barrett's gastric type mucosa (12%). There was a significant positive correlation between PCNA labelling indices and TGF alpha expression in Barrett's mucosa (p less than 0.01). In glands showing high grade dysplasia, TGF alpha immunoreactivity was seen in the same regions of the glands as PCNA immunoreactivity, indicating the possibility of involvement of TGF alpha in (pre) neoplastic proliferation in Barrett's oesophagus.

Adenocarcinoma↗
PubMed1992

Oncogenes and onco-suppressor gene in adenocarcinoma of the oesophagus.

While the activation of the proto-oncogenes has been implicated in the development and progression of cancer of many tissues, the role of oncogenes in the development of oesophageal adenocarcinoma has not been defined. Fifteen patients who had undergone resection for oesophageal adenocarcinoma and 15 who had undergone oesophagectomy or biopsy for Barrett's oesophagus were studied. The latter patients also had adjacent normal gastric mucosa biopsied for comparison with the metaplastic oesophageal mucosa. The mucosal samples were snap frozen and subsequently stained with monoclonal antibodies to the following oncogene associated proteins; c-erbB2 (neu and CE-1) (external domain), c-erbB2 (NCL-CB11) (internal domain), c-src, c-ras, c-myc, c-fos, c-jun, and the onco-suppressor gene--p53. All tumours were well or moderately differentiated adenocarcinomas arising from the lower third of the oesophagus. Eleven specimens showed strong membraneous staining with both c-erbB2 (neu) and c-erbB2 (CBL-CB11). Seven specimens showed strong nuclear staining with p53 onco-suppressor gene. Three specimens were positive for c-ras and c-src, and two were positive for c-jun. In Barrett's epithelium, nine specimens were positive for c-erbB2 (neu and CB11), three were positive for c-src, two were positive for c-ras and c-jun, and one was positive for c-fos. Two of the gastric mucosal biopsy specimens expressed c-erbB2 weakly but no other oncogenes were found. The frequency of positive staining for c-erbB2 is very high, compared with the expression of these genes in other tumours. It is also concluded that errors in the onco-suppressor gene p53, and especially in the external and internal domains of c-erbB2, which is also often expressed in Barrett's mucosa, may be implicated in the development of adenocarcinoma of the oesophagus.

Adenocarcinoma↗
PubMed1992

Nocturnal gastric secretion in duodenal ulcer patients and healthy controls. Ranges and reproducibility.

The nocturnal gastric acid secretion of 22 male duodenal ulcer patients was compared with that of 47 healthy male volunteers. Median nocturnal acid output was greater in duodenal ulcer patients (55 mmol versus 33 mmol 10 h-1; p = 0.013), but there was almost complete overlap of the ranges. Five duodenal ulcer patients and three volunteers had nocturnal outputs of acid previously considered to be pathognomonic of the Zollinger-Ellison syndrome in the absence of other evidence of a gastrinoma. Nineteen healthy volunteers underwent a repeat study to assess the reproducibility of nocturnal gastric acid output. Median intraindividual variability (+/- distribution-free 95% confidence limits) was 23% (-34% to +72%). Studies of nocturnal gastric secretion are of no diagnostic value, and their variability should be taken into consideration when evaluating gastric antisecretory drugs.

Circadian Rhythm↗
PubMed1992

Adaptive mutagenesis--cause of alimentary cancer?

The tissues of the alimentary tract react to abnormal functional demands or to injury from environmental chemicals by reactions which involve change in morphology, functional characteristics and cellular proliferation. The work hyperplasia, wound repair or response to xenobiotics may become distorted by inherent, or induced, genomic abnormalities of the affected cells. It seems that some of the reactions are 'programmed' or 'planned' and depend on predetermined changes in gene expression. Although the reactions permit survival in the face of environmental hazards, the necessary alterations in gene expression may predispose to malignant change in the affected cells.

Adaptation, Physiological↗
PubMed1992

Flow-cytometric analysis of growth-regulatory peptides and their receptors in Barrett's oesophagus and oesophageal adenocarcinoma.

The conventional assessment of the premalignant potential of Barrett's oesophagus is unsatisfactory. However, it has recently been shown that abnormalities of growth-regulatory peptides and their receptors may be important in the pathogenesis of this condition. In an attempt to improve the diagnostic and prognostic criteria we have studied 21 consecutive patients with Barrett's oesophagus and 7 others with adenocarcinoma of the oesophagus. In each patient biopsy specimens were taken from the columnarlined oesophagus or the adenocarcinoma and from the gastric cardiac mucosa for routine histologic evaluation. Immediately adjacent specimens were taken from both the Barrett's mucosa or adenocarcinoma and from the gastric mucosa for flow-cytometric study. The latter samples were disaggregated and labelled with antibodies to epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and epidermal growth factor receptor (EGF-R). The flow cytometer selected cells labelled with each antibody and expressed them as a percentage of the total number of disaggregated cells (average, 5500 cells). Epidermal growth factor receptors were expressed in a greater number of cells from Barrett's mucosa, with the intestinal type or those with dysplasia, than in gastric cardiac mucosa (p less than 0.05). All seven adenocarcinoma had many more cells expressing EGF, TGF-alpha, and EGF-R than normal gastric mucosa (p less than 0.01). We conclude that flow-cytometric evaluation of EGF-R can help in the understanding of the pathogenesis of Barrett's oesophagus.

Adenocarcinoma↗
PubMed1991

Uptake of horseradish peroxidase by human oesophageal explants over 24 h.

Human oesophageal biopsies, endoscopically and histologically normal, were incubated in Ham's F10 for periods up to 24 hours in the presence of horseradish peroxidase. The fluid phase marker was taken up most avidly by the prickle cells but to a lesser extent in the functional layers and by basal cells. Endocytosed markers proceeded to multivesicular bodies (segrosomes). Horseradish peroxidase was later deposited in lysosome-like structures and also in the Golgi apparatus. The lesser uptake by the functional cells may represent reduced access of the marker to the cells due to the intercellular barrier.

Cell Membrane↗