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Biomedical subjects

S E Patchett

Publications and source records attributed to S E Patchett.

At least 19 recordsLinked to original sources

Direct-vision stenting: the way forward for malignant oesophageal obstruction.

BACKGROUND AND STUDY AIMS: Self-expanding metallic stents now form the mainstay of treatment for palliation of dysphagia in oesophageal cancer. These stents are generally inserted under fluoroscopic guidance. However, both the internal and external marking of the tumour can be inaccurate and time-consuming, and access to fluoroscopic facilities is sometimes limited. We prospectively assessed the use of a method of stent insertion under direct vision without the aid of fluoroscopy. PATIENTS AND METHODS: A total of 50 consecutive patients presenting with obstructive symptoms secondary to inoperable oesophageal cancers were included in the study. We used either the 7-cm or the 11-cm covered Choo stent (MI-Tech Ltd., Seoul, South Korea). RESULTS: A total of 52 stents were inserted under direct vision. The procedure generally took less than 15 minutes and good palliation was achieved without complications. Fluoroscopic assistance was required in only one patient. CONCLUSIONS: Direct-vision stent insertion is simple, safe, effective, and only rarely requires fluoroscopic assistance. The technique may be of particular use in centres with limited access to fluoroscopy.

Adenocarcinoma↗

Combined terminal ileoscopy and biopsy is superior to small bowel follow-through in detecting terminal ileal pathology.

BACKGROUND: Several studies have compared small bowel barium examination with ileoscopy in assessment of terminal ileal disease. Some suggest that ileoscopy is superior in detection of terminal ileal disease whereas others suggest similar disease detection rates for both techniques. AIMS: The aim of this retrospective study was to determine if small bowel follow-through and ileoscopy with terminal ileum biopsy compare favourably at detecting pathology in the terminal ileum. PATIENTS AND METHODS: All colonoscopies with terminal ileoscopy performed over a 16-month period were reviewed. We determined which of these patients had also had small bowel follow-through studies within 2 weeks of colonoscopy. We compared the diagnoses of terminal ileum pathology using ileoscopy with terminal ileal biopsy versus small bowel follow-through. RESULTS: Forty-six patients had both terminal ileoscopy with biopsy and small bowel follow-through. In 19 patients, the terminal ileum was abnormal at ileoscopy and/or biopsy but normal at small bowel follow-through. In 27 patients, terminal ileum findings at small bowel follow-through and at ileoscopy and/or biopsy were compatible. CONCLUSIONS: This study suggests that examination of the terminal ileum by combined ileoscopy and biopsy may be superior to small bowel follow-through at detecting terminal ileal pathology. In our series, many patients received effective treatment that otherwise would not have been offered based on the small bowel follow-through results alone. Using combined ileoscopy and biopsy, microscopic inflammatory changes, otherwise missed without biopsy, can be detected. Retrograde ileoscopy is recommended in patients with a clinical history of organic diarrhoea and/or abdominal pain even in the presence of a normal small bowel follow-through.

Adolescent↗

A prospective analysis of inpatient consultations to a gastroenterology service.

The provision of a formal consultation service for inpatients between subspecialists is little studied. We prospectively surveyed the pattern of inpatient consultations from hospital-based generalists and surgeons to the gastroenterology (GI) service for inpatients in a large urban teaching hospital over a 5 month period. There are two GI consultants/attendings and five GI registrars/fellows on the service. A formal consultation is made by the requesting team to the GI service using the hospital computer network. All referrals over a 5 month period were prospectively analysed. 242 consecutive inpatient referrals were sent to the GI service over 5 months. Average age was 56 years, 48.8% males. 32 consultants/attendings from other disciplines sent referrals. Most patients were seen within one working day. Urgent referrals were seen without delay. The commonest reasons for referral were abdominal pain (15.8%), percutaneous endoscopic gastrostomy (PEG) tube insertion (13.6%), diarrhoea (12.8%), abnormal liver blood tests (10%), nausea and vomiting (8.2%), anaemia (6.2%), and melaena (4.9%). Iatrogenic diseases accounted for 6.2% of consultations. Ongoing patient care was assumed by the GI team in 9.5% of referrals. 15.3% required a second consultation visit before discharge. 22.7% of referrals were followed in the GI outpatients' clinic after discharge. 51.2% underwent an endoscopic procedure. 13.6% of referrals were for PEG tube insertion. A quarter of these were considered unsuitable for immediate PEG tube insertion. Subspecialty consultation provides an expert opinion, encourages discussion and learning, and improves patient care. In our experience, the provision of specialist advice and reassurance often speeded up a patient's work-up and expedited discharge. However, evaluating referral patients and subsequently providing ongoing inpatient and outpatient care and provision of endoscopy for these referrals contributes significantly to the workload of the GI service.

Adolescent↗

Changing patterns of sedation use for routine out-patient diagnostic gastroscopy between 1989 and 1998.

BACKGROUND: Knowledge of sedation trends for upper gastrointestinal endoscopy is important for health service planning, particularly in view of rapidly increasing demands on endoscopy services. However, no data are available on sedation trends in Britain over the past 10 years. AIM: To determine sedation use for routine gastroscopy in a single endoscopy unit between 1989 and 1998. METHODS: This was a retrospective study of 9795 consecutive adults (mean age 56 years, range 18-100 years; 4512 females) who had undergone a gastroscopy between 1989 and 1998. Clinical, pharmacological and endoscopic data were retrieved from a computerized database. RESULTS: Over the 10-year study period, the sedation rate remained constant for patients undergoing therapeutic endoscopy (P=0.99) and those undergoing in-patient diagnostic examinations (P=0.63). In contrast, the sedation rate for out-patient diagnostic endoscopy decreased by 54%, from a high of 70% in 1990 to 32% in 1998 (P < 0.0001). Logistic regression analysis showed that the decline in sedation use was greater in females (P < 0.0001) than males and in procedures performed by non-consultant compared to consultant staff (P=0.01). CONCLUSIONS: If our results form part of a national trend, they will have important implications for cardiopulmonary monitoring strategies, recovery room practices and for complication rates due to the use of sedation for upper gastrointestinal endoscopy.

Adolescent↗

p27(Kip1) loss does not predict survival in patients with advanced gastric carcinoma.

BACKGROUND: p27(Kip1) is a cyclin-dependent kinase inhibitor whose loss is associated with disease progression and an unfavorable outcome in several malignancies. The authors studied its expression in a consecutive series of resected gastric carcinomas. METHODS: Expression of p27(Kip1) in 71 advanced gastric carcinomas and 10 lymph nodes containing metastases was determined using an avidin-biotin-peroxidase immunohistochemical method. The relations between p27(Kip1) expression and pathologic features, patient characteristics, and survival were analyzed. RESULTS: p27(Kip1) levels in gastric carcinomas ranged from 0.63-82.97% (median, 23. 10%; mean, 27.99%). There was no association found between p27(Kip1) expression and patient gender (P = 0.21), patient age (P = 0.13), tumor stage (P = 0.17), tumor grade (P = 0.22), or histologic type (P = 0.72). Univariate analysis showed that long term survival was related to stage (P < 0.0001) and grade (P = 0.03). However, tumors with p27(Kip1) levels above and below the median value were associated with a similar outcome, regardless of whether all cases (P = 0.19) or those without metastatic disease (P = 0.50) or those with residual or metastatic disease (P = 0.92) were included. When entered into a multivariate analysis, stage (P < 0.0001) and grade (P = 0.05), but not p27(Kip1) levels (P = 0.16), were found to be related to patient outcome. In lymph node metastases, p27(Kip1) expression (median, 16.5%) was similar to that found in the corresponding primary lesion (median, 30.9%). CONCLUSIONS: p27(Kip1) may play a role in the pathogenesis and progression of gastric carcinoma, but its expression is unlikely to be useful as a prognostic indicator, at least in European patients with advanced disease.

Adult↗

Topoisomerase I inhibitor (camptothecin)-induced apoptosis in human gastric cancer cells and the role of wild-type p53 in the enhancement of its cytotoxicity.

Camptothecin (CPT), a human topoisomerase I inhibitor, blocks DNA replication in human cancer cells. It represents a promising new class of chemotherapeutic agents with broad anti-tumor activity. However, its effect on gastric cancer cells remains unknown. We examined cell growth, apoptosis and cell cycle phase distribution in gastric cancer cells by exposing these cells to CPT for up to 72 h. Cell viability was determined by the Trypan blue exclusion assay. Cell cycle phase distribution and apoptosis were measured using flow cytometry, fluorescence microscopy and DNA ladder assay. Exposure of exponentially growing gastric AGS cancer cells to CPT induced time-dependent apoptosis and growth inhibition. Serum starvation-synchronized AGS cells (about 60% cells in G0/G1 phase) showed similar cellular responses. Analysis of cell cycle phase distribution of AGS cells treated with CPT for up to 72 h showed no obvious differences compared to untreated control cells. Although the induction of apoptosis was noticed in gastric cancer cell lines both with and without p53, cells lacking p53 showed less apoptosis compared to those cell lines possessing p53. Our data show that CPT is capable of inducing gastric cancer cell growth inhibition and apoptosis. Wild-type p53 may enhance the cytotoxicity of CPT against gastric carcinoma.

Antineoplastic Agents, Phytogenic↗

Gastric alpha-tocopherol and beta-carotene concentrations in association with Helicobacter pylori infection.

OBJECTIVE: The effects of Helicobacter pylori infection and its associated gastric histology on alpha-tocopherol and beta-carotene concentrations in serum, gastric juice and antral mucosa were investigated in patients undergoing routine gastroscopy for investigation of dyspepsia. METHOD: Eighty-six patients were studied. High-performance liquid chromatography was used to measure alpha-tocopherol and beta-carotene concentrations. H. pylori infection was assessed by histology, bacterial culture, rapid urease test and serology. RESULTS: No obvious association was found between age, sex, smoking or endoscopic diagnosis and alpha-tocopherol or beta-carotene concentrations in serum, gastric juice and antral mucosa. However, alcohol drinkers had significantly lower antral mucosal and gastric juice beta-carotene concentrations compared to non-drinkers. Gastric juice beta-carotene concentration was markedly lower in patients infected with H. pylori than uninfected controls (2.9 nmol/l (interquartile range 0.3-4.3) versus 4.6 nmol/l (interquartile range 3.5-7.6), P = 0.01), but there was no significant difference in serum or gastric mucosal beta-carotene concentrations between the two patient groups. The presence of gastric atrophy and intestinal metaplasia was significantly associated with reduced mucosal alpha-tocopherol and beta-carotene concentrations. Furthermore, antral mucosal alpha-tocopherol concentrations decreased progressively as antral mucosal histology changed from normal to chronic gastritis alone and finally to atrophy and intestinal metaplasia. CONCLUSION: Gastric alpha-tocopherol and beta-carotene concentrations are affected by H. pylori-associated gastric histological changes, and these findings suggest that H. pylori infection may not only impair the protective role of vitamin C, but also of alpha-tocopherol and beta-carotene in the stomach.

Adult↗

Early experience with intrasphincteric botulinum toxin in the treatment of achalasia.

BACKGROUND: Recent reports have suggested that intrasphincteric injection of botulinum toxin is effective and long-lasting in the treatment of achalasia. AIM: To report our experience of botulinum toxin injection in a prospective series of consecutive patients with achalasia. METHODS: Eleven consecutive patients with achalasia (eight male, mean age 55 years, range 20-87) were treated with 60 units of botulinum toxin (Dysport; Speywood Pharmaceuticals Ltd, UK) into each of four quadrants at the lower oesophageal sphincter. Patients were assessed pre-treatment and 1 month after treatment using a symptom score and oesophageal manometry. Median follow-up was 12 months (range 6-28). RESULTS: The injection procedure was simple to perform and free of adverse effects. Although treatment had a beneficial effect on dysphagia (median pre-treatment score 3 [interquartile range 3-3]; post-treatment score 2 [0-3]: P=0.03) 1 month following therapy, there was no significant improvement in chest pain or regurgitation scores. Similarly, no significant reduction in median lower oesophageal sphincter pressure was observed (29.5 mmHg [21-42] pre-treatment, 28.5 [17.5-55.5] post-treatment P=0.67). Four patients (36%) required further therapy within 3 months and the overall relapse rate was 73% (eight of 11) within 2 years. CONCLUSION: Although botulinum toxin injection was well tolerated, these results using Dysport at a dose of 240 mouse units question its efficacy as a treatment for achalasia.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗