PubMed Health⌕ Search

Biomedical subjects

S E Patchett

Publications and source records attributed to S E Patchett.

18 recordsLinked to original sources
PubMed1998

Helicobacter pylori eradication cost-benefit: the case against.

Helicobacter pylori is an important human pathogen, implicated in the pathogenesis of peptic ulcer disease, gastric cancer, and perhaps also in other non-gastrointestinal disease. There is little doubt that in peptic ulcer disease at least, there is a strong argument for its eradication on both clinical and economic terms. The majority of subjects infected with Helicobacter pylori never develop clinically overt disease, and it is this group that the clinical and financial benefit of eradication needs to be closely examined.

Cost-Benefit Analysis↗
PubMed1998

Does CagA contribute to ulcer pathogenesis in a developing country, such as Sudan?

BACKGROUND AND OBJECTIVE: In Western populations, peptic ulcer disease is closely associated with Helicobacter pylori (H. pylori) strains expressing the CagA antigen. In Africa the prevalence of H. pylori infection and peptic ulcer disease is high, although information regarding potential virulence factors is lacking. This study examines the prevalence of antibodies to CagA both in African patients with dyspepsia who are undergoing gastroscopy, and in asymptomatic healthy African volunteers. METHODS: Eighty two consecutive patients (median age 34 years, range 15-73 years), attending for gastroscopy were studied, of whom 78 (95.1%) were subsequently found to be Helicobacter positive. Three antral biopsies were obtained from each patient and 5 ml of blood was taken for determination of CagA seropositivity using western blot analysis. CagA seropositivity was also determined in 65 H. pylori positive healthy volunteers (median age 30 years, range 18-70 years), with no symptoms or previous history of gastroduodenal disease. RESULTS: Of the 78 H. pylori positive patients, CagA seropositivity was present in all 22 patients with active peptic ulcer disease (100%), in eight of nine patients with duodenitis (89%), in 15 of 19 patients with macroscopic gastritis (78.9%), and in 24 of 28 patients with a normal endoscopy (85.7%). On histological assessment, 46 patients had chronic active gastritis, 29 patients had gastritis with atrophy and three patients had intestinal metaplasia. CagA seropositivity rates were 84.7%, 93% and 100%, respectively, for these groups. In the 89 healthy volunteers studied, 57 of the 65 H. pylori positive subjects (87.7%) were seropositive for the CagA protein. CONCLUSIONS: As in Western countries, CagA seropositivity in this African population was closely related to endoscopic gastroduodenal disease, and to the presence of more advanced histological lesions in the antrum. However, there was also a high prevalence of CagA seropositivity in asymptomatic healthy individuals, suggesting that factors other than CagA predominate in ulcer pathogenesis in this population.

Adolescent↗
PubMed1998

The relation between gastric vitamin C concentrations, mucosal histology, and CagA seropositivity in the human stomach.

BACKGROUND: Vitamin C may be protective against gastric cancer though infection with Helicobacter pylori is associated with a reduction in intragastric concentrations of vitamin C. AIMS: To examine the effects of H pylori infection, gastric juice pH, the severity and extent of gastric inflammation, and CagA antibody status of the individual on gastric juice and mucosal vitamin C concentrations. PATIENTS: One hundred and fifteen patients undergoing routine gastroscopy for investigation of dyspepsia. METHODS: High performance liquid chromatography was used to determine vitamin C concentrations. CagA antibody was detected by western blot analysis. RESULTS: Gastric juice ascorbic acid concentration was significantly lower in patients infected with H pylori compared with those uninfected (19.3 mumol/l (interquartile range (IQR) 10.7-44.5) versus 66.9 mumol/l (IQR 24.4-94.2), p = 0.003). The reduction in gastric juice ascorbic acid concentration was inversely related to the severity of gastritis (p = 0.01). CagA positive patients had significantly lower gastric juice ascorbic acid concentrations than CagA negative ones (14.8 mumol/1 (IQR 7.9-52.2) versus 39 mumol/l (IQR 19.9-142.2), p = 0.05). Decreased gastric juice dehydroascorbic acid concentrations were observed in patients with gastric atrophy and intestinal metaplasia. Mucosal ascorbic acid concentrations were also significantly lower in infected patients than uninfected patients (p = 0.04). CONCLUSIONS: The reduction in gastric vitamin C concentrations is related to gastric juice pH, the severity and extent of gastritis, the presence of H pylori, and the CagA antibody status of the individual. These findings may have implications in H pylori associated carcinogenesis.

Adult↗
PubMed1997

Identifying stage B colorectal cancer patients at high risk of tumor recurrence and death.

PURPOSE: This study was designed to determine clinical and pathologic variables associated with poor outcome following resection of Stage B colorectal cancer. METHODS: This was a retrospective study of 117 patients with Stage B cancer who underwent curative surgery and survived the postoperative period. Fourteen clinical and pathologic features were studied. Clinical data were extracted from a prospective colorectal cancer database, and histologic slides were retreived and examined by a pathologist blinded as to clinical details and outcome. RESULTS: After a median follow-up period of 8.2 years, bowel obstruction was significantly related to a poor prognosis (log-rank test; P = 0.03). Extensive necrosis (P = 0.01) and perineural invasion (P = 0.03) were also associated with decreased survival. Vascular invasion was associated with poor long-term outcome in the subgroup of patients with rectal (P = 0.07) but not colonic (P = 0.57) cancer. Multivariate regression analysis identified both tumor necrosis (P = 0.01) and perineural invasion (P = 0.03) as independently related to outcome. CONCLUSION: Further study of prognostic indicators might result in an algorithm to distinguish Stage B cases at high risk of tumor recurrence and death. Such patients could be included in future trials of adjuvant therapies.

Adult↗
PubMed1997

Regional proliferative patterns in the colon of patients at risk for hereditary nonpolyposis colorectal cancer.

UNLABELLED: Patients from a hereditary nonpolyposis colorectal cancer (HNPCC) kindred (Lynch Type 1 and Type 2) have an increased risk of developing large-bowel cancer. Tumors occur at a young age and are characteristically right-sided. Colonic mucosal proliferation is known to be increased in several groups of patients at risk of colorectal cancer. PURPOSE: This study was performed to assess the pattern of mucosal proliferation at different sites in the colon of patients at risk of HNPCC and to determine whether this pattern differs from normal patients. METHODS: Mucosal biopsies were obtained at colonoscopy from 21 patients at risk for HNPCC (16 females; mean age, 42 years) and from 7 normal patients (4 females; mean age, 38 years), and mucosal proliferation was quantified using the whole crypt mitotic count (WCMC) technique. RESULTS: In patients from HNPCC families, WCMC and crypt area were significantly greater in the cecum than in the transverse colon and left colon (P < 0.001). Compared with normal patients, WCMC in HNPCC patients was significantly greater in the cecum only (P < 0.05). A significant right-to-left shift was also observed in normal patients, but the percentage increase from right to left was two-fold greater in HNPCC patients. CONCLUSIONS: These results confirm a proximal-to-distal proliferative gradient in the human colon and suggest that this may be exaggerated in HNPCC. This increased proximal proliferative rate may be a factor in the development of right-sided cancer in these patients.

Adult↗
PubMed1996

A double-blind randomized trial of low-dose versus high-dose topical anaesthesia in unsedated upper gastrointestinal endoscopy.

BACKGROUND: Upper gastrointestinal endoscopy is frequently performed on unsedated subjects. Pharyngeal anaesthesia is thought to improve patient tolerance to the procedure but the optimum dose of anaesthesia is not known. The aim of this study was to assess the benefits of low-dose vs. high-dose topical anaesthesia in unsedated gastroscopy. METHODS: One hundred and fourteen subjects attending for diagnostic gastroscopy were studied. Patients were randomized to receive either 30 mg or 100 mg of topical pharyngeal lidocaine spray prior to endoscopy in a double-blind fashion. Subjects completed a questionnaire before and after endoscopy. RESULTS: A similar proportion of patients in each group required intravenous sedation because of discomfort or anxiety during the procedure (P = 0.48). The high-dose group experienced less discomfort during endoscope insertion (P = 0.002) and throughout the examination (P = 0.01). Overall satisfaction was almost identical in the two groups (P = 0.85) and a similar percentage of the high-dose and low-dose groups stated that they would request sedation prior to future endoscopy (37 vs. 44%; P = 0.48). Further analysis showed that apprehensive patients and younger patients reported relatively high levels of discomfort, and that female subjects were more likely to express a preference for sedation at any future gastroscopy. CONCLUSION: High-dose pharyngeal anaesthesia reduces patient discomfort during unsedated upper gastrointestinal endoscopy. However, patient tolerance is also influenced by clinical features, which might be useful in deciding which patients are suitable for this procedure.

Administration, Topical↗
PubMed1996

Ornithine decarboxylase activity is a marker of premalignancy in longstanding Helicobacter pylori infection.

BACKGROUND: Longstanding Helicobacter pylori infection may increase the risk of developing gastric adenocarcinoma. The sequence of chronic active gastritis leading to gastritis with atrophy and subsequent intestinal metaplasia is thought to be a key step in gastric carcinogenesis. Ornithine decarboxylase (ODC) activity is increased in some pre-malignant gastrointestinal conditions and is essential for malignant transformation in vitro. AIMS: To measure ODC activity in the antrum of H pylori infected and non-infected subjects and to relate this to histological abnormalities associated with recent and longstanding H pylori infection. METHODS: Six antral mucosal biopsy specimens were obtained from 75 patients for detailed histological assessment and measurement of ODC activity. Samples were measured in duplicate and results expressed as median, interquartile range in pmol/mg protein/h. RESULTS: ODC activity was significantly higher in H pylori positive (164, 88-259 pmol/mg/h) than H pylori negative subjects (99.8, 55-158 pmol/mg/h, p = 0.003). However the presence of gastritis, irrespective of the severity of inflammation or activity had no influence on ODC activity. Gastritis with atrophy was associated with increased ODC activity, which was closely related to the severity of the atrophy (p = 0.01). Similarly, ODC activity was significantly increased in subjects with intestinal metaplasia (196, 83-25) compared with those without intestinal metaplasia (111.7, 65-175, p < 0.04). CONCLUSIONS: These results indicate that the histological changes associated with longstanding H pylori infection rather than inflammation alone are associated with increased polyamine biosynthetic activity. This may be relevant to H pylori associated gastric carcinogenesis.

Adolescent↗
PubMed1995

A randomized prospective comparison of clarithromycin versus amoxycillin in combination with omeprazole for eradication of Helicobacter pylori.

AIM: To compare H. pylori eradication rates using omeprazole in conjunction with either amoxycillin or clarithromycin. BACKGROUND: Omeprazole with amoxycillin is the most widely used dual therapy regimen for eradication of H. pylori. A recent open study suggested a high eradication rate combining omeprazole with the newer macrolide, clarithromycin. METHODS: A randomized prospective trial in 54 patients was conducted to compare 2 weeks of treatment with omeprazole 40 mg once daily and either amoxycillin 500 mg three times daily or clarithromycin 500 mg three times daily. H. pylori eradication was assessed using the 13C urea breath test. RESULTS: Eradication was achieved in 18/26 (69.2%) of subjects treated with omeprazole and amoxycillin and 18/25 (72.0%) of those treated with omeprazole and clarithromycin (P = N.S.). Minor side effects, most commonly altered taste, were reported by 16% of patients and were more frequent in those randomized to clarithromycin (P = 0.01). CONCLUSIONS: These regimens are similarly effective. However, clarithromycin is more expensive, associated with a greater frequency of side effects and, unlike amoxycillin, resistance by H. pylori has been reported. This suggests that clarithromycin may be a useful alternative when there is penicillin allergy or previous treatment failure, but it should not replace amoxycillin as first choice in omeprazole-based dual therapy.

Adolescent↗
PubMed1995

Pharmacological manipulation of gastric juice: thrombelastographic assessment and implications for treatment of gastrointestinal haemorrhage.

The impairment of formation and maintenance of a formed fibrin clot contributes to the prolonged bleeding and high incidence of rebleeding in upper gastrointestinal haemorrhage. To investigate the basis for the use of drug therapy in gastric bleeding, this study used thrombelastography to determine the effects of pharmacological manipulation of gastric juice on coagulation and fibrinolysis. The thrombelastograph is a mechanical device that provides a visual assessment of all stages of coagulation and fibrinolysis. The effects of fresh and pharmacologically changed gastric juice was assessed after its addition to fresh whole blood in the thrombelastograph cuvette. Pharmacological manipulation was achieved through alkalisation or through addition of tranexamic acid, aprotinin, or sucralfate. Fresh gastric juice delayed clot formation, decreased maximum clot amplitude, and stimulated clot lysis. Alkalisation inhibited the lytic effects of fresh gastric juice and improved the induced abnormalities in coagulation. Tranexamic acid partially inhibited gastric juice induced clot lysis but did not exhibit a beneficial effect on coagulation. Sucralfate, and to a lesser extent aprotinin significantly inhibited fibrinolysis but exacerbated the detrimental effect of gastric juice on the parameters of coagulation. Alkalisation of gastric juice reduces the adverse effect on coagulation and fibrinolysis. Tranexamic acid, aprotinin, and sucralfate can all reduce or inhibit clot lysis, but the adverse effects on clot formation may outweigh any potential benefit in the treatment of gastrointestinal bleeding.

Aprotinin↗
PubMed1995

Ornithine decarboxylase as a marker for premalignancy in the stomach.

Assessment of mucosal ornithine decarboxylase (ODC) activity in the human large bowel may be of value as a marker of potential malignant risk. Its value as a marker of premalignancy in the upper gastrointestinal tract is less clear. Using a [14C]-ornithine bioassay, gastric mucosal ODC activity was measured in 32 normal subjects and 22 patients with confirmed gastric cancer. These results were compared with 47 patients at increased risk of upper gastrointestinal malignancy, (32 patients with partial gastric resection, 15 patients with familial adenomatous polyposis). Median ODC activity in normal subjects was 371 pmol/mg protein/h, (interquartile range (IQR), 230-617). There was no variation with age or sex and no relation to Helicobacter pylori status. Normal subjects had significantly lower ODC activity than patients with a gastric resection or confirmed gastric cancer, but similar to patients with familial adenomatous polyposis. Furthermore, no difference in activity was identified between patients with a gastric resection and established gastric cancer. ODC activity was, however, significantly increased in areas of gastric atrophy or intestinal metaplasia, regardless of the clinical group from which the samples were obtained. It is concluded that measurement of mucosal ODC activity does not provide additional predictive information of malignant risk in the stomach and investigation of other potential biomarkers of malignancy is warranted.

Adenomatous Polyposis Coli↗
PubMed1994

Prognosis of elderly patients with large bowel cancer.

The effect of age on the presentation, diagnosis, management and survival of patients with colorectal cancer was studied prospectively in 512 patients admitted to a single institution. In all, 225 patients were aged 70 years or more and 287 less than 70 years. Older patients had a significant excess of emergency presentations (18 versus 11 per cent). Methods of diagnosis, proportion of curative operations performed, stage and histological grade were similar in the two age groups. The postoperative mortality rate was 6 per cent in the elderly group and 3 per cent in younger patients. The postoperative mortality rate rose to 15 and 12 per cent respectively in those undergoing emergency surgery. The relative 5-year survival rate standardized for age and sex was 52 per cent for older patients and 45 per cent for younger patients; for those undergoing curative surgery it was 68 and 59 per cent respectively. The behaviour of colorectal carcinoma changes little with age and, allowing for population mortality, age has no effect on the long-term survival of elderly patients with large bowel cancer.

Adult↗
PubMed1994

Rectal mucosal ornithine decarboxylase activity in familial adenomatous polyposis after ileorectal anastomosis.

Resection of the colon in patients with familial adenomatous polyposis frequently results in the regression of polyps in the remaining rectum, suggesting a reduction of cellular proliferation. These patients remain at risk of developing rectal cancer but whether this risk increases with time is uncertain. Since ornithine decarboxylase activity is associated with cellular proliferation, mucosal ornithine decarboxylase was measured in rectal biopsy specimens from patients with familial adenomatous polyposis after ileorectal anastomosis (n = 36) and from normal controls (n = 30). The relationship between ornithine decarboxylase activity, age, and time from surgery was also examined. Median ornithine decarboxylase activity in familial adenomatous polyposis patients after ileorectal anastomosis (186, interquartile range (IQR) 107-534 pmol/mg protein/h) was not different from that in control subjects (227, IQR 123-374, p = 0.6). When patients were divided into three equal groups according to age, however, younger patients (< 25 years) had significantly higher activity than both older age groups (p < 0.02). Similarly, when patients were stratified according to the time elapsed since surgery, those who had had surgery less than six years previously had a significantly higher ornithine decarboxylase activity than those in whom a longer time interval had elapsed since surgery (p = 0.02). These results indicate that after colon resection, ornithine decarboxylase activity in patients with familial adenomatous polyposis is similar to that in normal controls but seems to fall over time. This may explain the regression of rectal polyps after colonic resection in this disorder.

Adenomatous Polyposis Coli↗
PubMed1993

Colonoscopic surveillance after curative resection for colorectal cancer.

Colonoscopic surveillance after resection for colorectal cancer has been advocated to improve detection of anastomotic recurrence, and of synchronous and metachronous tumours. The benefit provided by colonoscopy remains unproven, and the best timing of examination is unclear. To determine the value of colonoscopy after curative resection for large bowel cancer, the efficacy of an endoscopic surveillance programme in the early detection of intraluminal bowel recurrence in a series of patients admitted with colorectal cancer was examined. Between April 1983 and December 1988, 132 patients underwent colonoscopy. Eight (6.1 per cent) were found to have intraluminal recurrence without evidence of extraluminal spread. Six of these recurrences were at the site of anastomosis and two represented metachronous tumour development. All of these patients were symptomatic at the time of diagnosis. In 15 patients (11.4 per cent), adenomatous polyps were discovered during the initial endoscopic examination. These results indicate that colonoscopic surveillance will rarely allow early detection of asymptomatic intraluminal bowel recurrence, but is valuable in the detection of synchronous lesions. Frequent surveillance is not justified in the early postoperative years and colonoscopy should probably be confined to a single procedure to exclude synchronous lesions.

Adenomatous Polyps↗
PubMed1989

Clot lysis by gastric juice: an in vitro study.

Gastric juice from patients with peptic ulcer disease and from patients with no upper gastrointestinal abnormality was studied in order to assess its effect on a formed fibrin clot. In both groups of patients gastric juice caused a marked increase in fibrinolysis as evidenced by a shortening of the euglobulin clot lysis time. This plasmin mediated fibrinolytic activity was found to be heat labile and only present in an acid environment. Addition of tranexamic acid or sucralfate to gastric juice almost completely reversed this effect, whereas pepstatin was only partially effective. It is probable that acid dependent proteases other than pepsin are responsible for the marked fibrinolysis. The ulcer healing agent sucralfate might be useful in those patients at risk of bleeding or rebleeding from active peptic ulcer disease.

Fibrinolysis↗