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Biomedical subjects

R C Stuart

Publications and source records attributed to R C Stuart.

At least 19 recordsLinked to original sources

An elevated C-reactive protein concentration, prior to surgery, predicts poor cancer-specific survival in patients undergoing resection for gastro-oesophageal cancer.

There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor outcome in patients undergoing resection for a variety of tumours. The aim of the present study was to examine the relationship between clinico-pathological status, preoperative C-reactive protein concentration and cancer-specific survival in patients undergoing resection for gastro-oesophageal cancer. One hundred and twenty patients attending the upper gastrointestinal surgical unit in the Royal Infirmary, Glasgow, who were selected for potentially curative surgery, were included in the study. Laboratory measurements of haemoglobin, white cell, lymphocyte and platelet counts, albumin and C-reactive protein were carried out at the time of diagnosis. All patients underwent en-bloc resection with lymphadenectomy and survived at least 30 days following surgery. On multivariate analysis, only the positive to total lymph node ratio (hazard ratio (HR) 2.02, 95% confidence interval (CI) 1.44-2.84, P<0.001) and preoperative C-reactive protein concentration (HR 3.53, 95% CI 1.88-6.64, P<0.001) were independent predictors of cancer-specific survival. The patient group with no evidence of a preoperative systemic inflammatory response (C-reactive protein < or =10 mg l(-1)) had a median survival of 79 months compared with 19 months in the elevated systemic inflammatory response group (P<0.001). The results of the present study indicate that in patients selected to undergo potentially curative resection for gastro-oesophageal cancer, the presence of an elevated preoperative C-reactive protein concentration is an independent predictor of poor cancer-specific survival.

Aged↗

Effects of genetically modified herbicide-tolerant cropping systems on weed seedbanks in two years of following crops.

The Farm Scale Evaluations (FSEs) showed that genetically modified herbicide-tolerant (GMHT) cropping systems could influence farmland biodiversity because of their effects on weed biomass and seed production. Recently published results for winter oilseed rape showed that a switch to GMHT crops significantly affected weed seedbanks for at least 2 years after the crops were sown, potentially causing longer-term effects on other taxa. Here, we seek evidence for similar medium-term effects on weed seedbanks following spring-sown GMHT crops, using newly available data from the FSEs. Weed seedbanks following GMHT maize were significantly higher than following conventional varieties for both the first and second years, while by contrast, seedbanks following GMHT spring oilseed rape were significantly lower over this period. Seedbanks following GMHT beet were smaller than following conventional crops in the first year after the crops had been sown, but this difference was much reduced by the second year for reasons that are not clear. These new data provide important empirical evidence for longer-term effects of GMHT cropping on farmland biodiversity.

Agriculture↗

Evaluation of an inflammation-based prognostic score in patients with inoperable gastro-oesophageal cancer.

There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor outcome in patients with advanced cancer. The aim of the present study was to examine whether an inflammation-based prognostic score (Glasgow Prognostic score, GPS) was associated with survival, in patients with inoperable gastro-oesophageal cancer. Patients diagnosed with inoperable gastro-oesophageal carcinoma and who had measurement of albumin and C-reactive protein concentrations, at the time of diagnosis, were studied (n=258). Clinical information was obtained from a gastro-oesophageal cancer database and analysis of the case notes. Patients with both an elevated C-reactive protein (>10 mg l(-1)) and hypoalbuminaemia (<35 g l(-1)) were allocated a GPS score of 2. Patients in whom only one of these biochemical abnormalities was present were allocated a GPS score of 1, and patients with a normal C-reactive protein and albumin were allocated a score of 0. On multivariate survival analysis, age (hazard ratio (HR) 1.22, 95% CI 1.02-1.46, P<0.05), stage (HR 1.55, 95% CI 1.30-1.83, P<0.001), the GPS (HR 1.51, 95% CI 1.22-1.86, P<0.001) and treatment (HR 2.53, 95% CI 1.80-3.56, P<0.001) were significant independent predictors of cancer survival. A 12-month cancer-specific survival in patients with stage I/II disease receiving active treatment was 67 and 60% for a GPS of 0 and 1, respectively. For stage III/IV disease, 12 months cancer-specific survival was 57, 25 and 12% for a GPS of 0, 1 and 2, respectively. In the present study, the GPS predicted cancer-specific survival, independent of stage and treatment received, in patients with inoperable gastro-oesophageal cancer. Moreover, the GPS may be used in combination with conventional staging techniques to improve the prediction of survival in patients with inoperable gastro-oesophageal cancer.

Aged↗

Benefits of organic farming to biodiversity vary among taxa.

Habitat and biodiversity differences between matched pairs of organic and non-organic farms containing cereal crops in lowland England were assessed by a large-scale study of plants, invertebrates, birds and bats. Habitat extent, composition and management on organic farms was likely to favour higher levels of biodiversity and indeed organic farms tended to support higher numbers of species and overall abundance across most taxa. However, the magnitude of the response varied; plants showed larger and more consistent responses than other taxa. Variation in response across taxa may be partly a consequence of the small size and isolated context of many organic farms. Extension of organic farming could contribute to the restoration of biodiversity in agricultural landscapes.

Agriculture↗

Cytokeratin 7 and 20 expression in intestinal metaplasia of the distal oesophagus: relationship to gastro-oesophageal reflux disease.

AIMS: Intestinal metaplasia and gastro-oesophageal reflux disease typify classical Barrett's oesophagus. Cytokeratin (CK) 7 and 20 phenotypes differentiate intestinal metaplasia in long segment Barrett's oesophagus from gastric intestinal metaplasia. This study examines the relationship between CK7/20 phenotypes and reflux disease in intestinal metaplasia of the distal oesophagus. METHODS AND RESULTS: Eighty patients with oesophageal pH studies included 30 with long segment Barrett's, 16 with short segment Barrett's and 34 with intestinal meatplasia of the gastro-oesophageal junction. Representative biopsy specimens were immunostained for CK7 and CK20. All 30 long segment patients demonstrated a Barrett's CK7/20 phenotype. All nine short segment patients with gastro-oesophageal reflux had a Barrett's CK7/20 phenotype, while four of seven short segment patients without reflux had a gastric CK7/20 phenotype (P = 0.019). Of 14 patients with intestinal metaplasia of the gastro-oesophageal junction and reflux, 10 (71%) had a Barrett's CK7/20 phenotype, compared with 11 (55%) of the 20 non-reflux patients. CONCLUSIONS: CK7/20 immunoreactivity for patients with intestinal metaplasia of the distal oesophagus without long segment Barrett's oesophagus suggests a heterogeneous group, with an association between Barrett's CK7/20 pattern and gastro-oesophageal reflux disease in both short segment Barrett's and intestinal metaplasia of the gastro-oesophageal junction.

Barrett Esophagus↗

Effect of physical exercise on esophageal motility in patients with esophageal disease.

The most common type of esophageal dysfunction associated with chest pain is gastroesophageal reflux, which may be induced by exercise. The effect of exercise on esophageal function has mainly been investigated in normal subjects or trained athletes. Few studies have investigated exercise and esophageal motility disorders. One hundred and thirty-five patients underwent ambulatory esophageal manometry and pH monitoring, before, during and immediately after moderate exercise. Patients were divided into four groups: Normal, nutcracker, diffuse spasm and gastroesophageal reflux disease (GERD). Ambulatory manometry and pH were monitored while exercising on a treadmill during which standardized boluses of water were administered. Nutcracker and diffuse spasm patients demonstrated a significant fall in esophageal wave amplitude during exercise compared to controls, which returned rapidly to pre exercise values after resting. There was no evidence of acid reflux in the non-reflux groups during exercise. Reflux was noted in 13 patients with GERD during exercise, none of whom had evidence of reflux at the onset of exercise. When these patients were classified by reflux type, the majority, 11 patients, were found to come from the combined or supine reflux group. Esophageal amplitude in nutcracker esophagus does not increase during moderate exercise. Moderate exercise provokes reflux in GERD patients with combined or supine reflux.

Esophageal Motility Disorders↗

Field boundaries in Great Britain: stock and change between 1984, 1990 and 1998.

Field boundaries are man-made features found worldwide and their multiple functions in agricultural landscapes are now widely recognised. These landscape features have declined drastically in many developed countries as a result of agricultural intensification. In Great Britain, field boundaries are regarded as elements of particular significance in the countryside, both in term of extent and value, whether ecological, cultural, or aesthetic. The Countryside Surveys of Great Britain, a national ecological, surveillance programme initiated in the late 1970s, provides information about the change in extent and ecological condition of field boundaries. In this paper, we present the main results on field boundaries derived from the latest survey, Countryside Survey 2000. These include stock and change of boundaries for the 1990-1998 period as well as an update of the previously published 1984-1990 data. Special attention is given to the evolution of the length of hedges. Applicability of the Countryside Survey methodology to other monitoring programmes and further use of the data is discussed together with the potential ecological consequences of the changes described in the paper.

Agriculture↗

Marimastat as maintenance therapy for patients with advanced gastric cancer: a randomised trial.

This randomised, double-blind, placebo-controlled study was designed to evaluate the ability of the orally administered matrix metalloproteinase inhibitor, marimastat, to prolong survival in patients with non-resectable gastric and gastro-oesophageal adenocarcinoma. Three hundred and sixty-nine patients with histological proof of adenocarcinoma, who had received no more than a single regimen of 5-fluorouracil-based chemotherapy, were randomised to receive either marimastat (10 mg b.d.) or placebo. Patients were treated for as long as was tolerable. The primary endpoint was overall survival with secondary endpoints of time to disease progression and quality of life. At the point of protocol-defined study completion (85% mortality in the placebo arm) there was a modest difference in survival in the intention-to-treat population in favour of marimastat (P=0.07 log-rank test, hazard ratio=1.23 (95% confidence interval 0.98-1.55)). This survival benefit was maintained over a further 2 years of follow-up (P=0.024, hazard ratio=1.27 (1.03-1.57)). The median survival was 138 days for placebo and 160 days for marimastat, with 2-year survival of 3% and 9% respectively. A significant survival benefit was identified at study completion in the pre-defined sub-group of 123 patients who had received prior chemotherapy (P=0.045, hazard ratio=1.53 (1.00-2.34)). This benefit increased with 2 years additional follow-up (P=0.006, hazard ratio=1.68 (1.16-2.44)), with 2-year survival of 5% and 18% respectively. Progression-free survival was also significantly longer for patients receiving marimastat compared to placebo (P=0.009, hazard ratio=1.32 (1.07-1.63)). Marimastat treatment was associated with the development of musculoskeletal pain and inflammation. Events of anaemia, abdominal pain, jaundice and weight loss were more common in the placebo arm. This is one of the first demonstrations of a therapeutic benefit for a matrix metalloproteinase inhibitor in cancer patients. The greatest benefit was observed in patients who had previously received chemotherapy. A further randomised study of marimastat in these patients is warranted.

Adenocarcinoma↗

Aberrant expression of minichromosome maintenance proteins 2 and 5, and Ki-67 in dysplastic squamous oesophageal epithelium and Barrett's mucosa.

BACKGROUND: Minichromosome maintenance (Mcm) proteins are essential for eukaryotic DNA replication, and their expression implies potential for cell proliferation. Expression is dysregulated in dysplastic states but data for oesophageal squamous mucosa and Barrett's mucosa have not been published. AIM: To test the hypothesis that Mcm proteins are downregulated together with the proliferation marker Ki-67 in differentiating epithelial compartments of non-dysplastic squamous and Barrett's epithelium, and that this process does not occur in dysplastic mucosae. METHODS AND CASES: Forty five patients with Barrett's oesophagus included 20 with glandular dysplasia (10 low grade, eight high grade, two both, and four with invasive adenocarcinoma). Twenty five other patients included 12 with oesophageal squamous dysplasia (three low grade, six high grade, three both, and four with invasive squamous carcinoma). Formalin fixed paraffin embedded tissue sections from biopsy series and resections were immunostained using antibodies to Mcm2, Mcm5, and Ki-67. Percentage of nuclei positive for Mcm2, Mcm5, and Ki-67 was estimated and scored from 0 to 6 as: 0, none +; 1, <10%+; 2, 10-30%+; 3, 30-70%+; 4, 70-90%+; 5, >90%+; 6, all+. Four separate epithelial strata were scored: in squamous epithelium the basal layer and thirds to the surface, in Barrett's mucosa the luminal surface, upper and lower crypt, and deep glands. RESULTS: In non-dysplastic squamous epithelium and Barrett's mucosa, high level expression of Mcm2, Mcm5, and Ki-67 proteins was largely confined to the proliferative compartments and downregulated in differentiated compartments. Expression persisted up to the mucosal surface in dysplastic squamous epithelium and Barrett's mucosa. CONCLUSIONS: Persistent expression of Mcm2, Mcm5, and Ki-67 proteins in luminal compartments of dysplastic oesophageal squamous epithelium and dysplastic Barrett's mucosa may be diagnostic markers and imply disruption of cell cycle control and differentiation in these dysplastic epithelia.

Barrett Esophagus↗

Helicobacter pylori eradication for peptic ulceration: an observational study in a Scottish primary care setting.

Despite being established for the treatment of peptic ulcer (PU) disease, few studies have assessed the long-term effectiveness and economic benefits of Helicobacter pylori (Hp) eradication in primary care. Our aim was to investigate the effect of community based Hp eradication for patients with chronic peptic ulcer disease requiring maintenance acid suppression. The endpoints used were the patients dyspeptic symptoms and the requirement for the prescription of maintenance acid suppression therapy. The study area covered seven general practices in the Glasgow area. Patients with previously diagnosed peptic ulcer disease receiving prescribed acid suppression therapy were invited to a dyspepsia clinic. Hp status was assessed by Helisal rapid blood test (HRBT). Positive patients received Hp eradication therapy and were reviewed six weeks later. At six months a review of practice records was carried out, and two years after eradication a postal questionnaire was sent to participating patients. A total of 243 patients attended the initial clinic of which 81.9% were HRBT positive. 156 of 196 patients offered Hp eradication re-attended at six weeks. The per protocol eradication rate was 91.7%. After six months patients who had received eradication therapy were less likely to require maintenance acid suppression therapy compared with those to whom eradication was not given. Two years after treatment 76.5% of patients felt their symptoms were improved, but 42.2% were still receiving maintenance therapy. The estimated cost of treatment per month per patient had fallen from 20.23 Pounds to 9.39 Pounds after eradication. In conclusion we felt that community based Hp eradication for patients with chronic PU disease is effective, however it does not completely alleviate dyspepsia. Predictors of symptomatic response or of no longer requiring acid suppression therapy after two years were younger age of onset of PU disease and absence of pre-documented gastro-oesophageal reflux disease or hiatus hernia. Hp eradication improves patients symptoms, reduces the requirement for maintenance acid suppression and is cost-effective after two years follow-up in this targeted group.

Female↗

Expression of telomerase RNA in oesophageal and oral cancer.

BACKGROUND: Telomerase is detectable in 85% of cancers, but is largely repressed in normal tissues. Human telomerase RNA (hTR) inhibition is a promising anti-cancer strategy, but requires differential expression between malignant and normal tissue. METHOD: Archival paraffin sections from 48 oral squamous cell carcinomas (SCC) (23 floor of mouth, 25 tongue) and 56 oesophageal carcinomas (41 SCC, 15 adenocarcinomas) were evaluated for hTR expression using a radiolabelled riboprobe. Results were compared with expression in controls and adjacent histologically normal tissue. Statistical analysis was by the chi2 test. RESULTS: hTR was detectable in 76% of oral SCC overall (floor of mouth 65%, tongue 88%, P=0.61), and in 54% of oesophageal cancers (SCC 51%, adenocarcinoma 60%, P=0.56). Detectable hTR expression was significantly more frequent in oral SCC than oesophageal SCC (P=0.01). hTR expression was only detected in normal tissue at low levels in basal squamous epithelium. There was agreement of hTR expression between 8/9 surgically excised carcinomas and their initial diagnostic biopsies. CONCLUSION: Tumour-specific hTR expression confirms hTR inhibition as a possible therapeutic strategy in some if not all oesophageal and oral cancers. Generally concordant hTR status between biopsy and resection suggest that biopsy may have a role in selecting candidates for telomerase inhibition therapy.

Adenocarcinoma↗

A pilot study of the safety and effects of the matrix metalloproteinase inhibitor marimastat in gastric cancer.

The aim of this study was to evaluate the safety and tolerability of 4 weeks administration of marimastat, and to seek evidence of biological activity as observed by changes in the endoscopic appearance of the gastric tumours. 35 patients with advanced, inoperable gastric or gastro-oesophageal tumours were recruited. The dose of marimastat was reduced from the starting dose of 50 mg twice daily (6 patients) to 25 mg once daily (29 patients). 31 completed the 28 day study period. Marimastat was generally well tolerated, with the principal treatment-related toxicity being pain and stiffness of the musculoskeletal system. These symptoms occurred more frequently at the higher-dose, and increased to involve a total of 13 patients (37%) with longer-term treatment. The events were usually rapidly reversible on drug discontinuation. 3 patients receiving prolonged treatment experienced more severe symptoms, with the development of skin thickening and contractures in the hands. At endoscopy, 10 patients showed an increased fibrotic cover of the tumour, 8 had decreased haemorrhagic appearance, and in at least 2 cases where comparative tumour histology was assessable, there was evidence of increased stromal fibrotic tissue.

Adult↗

Barrett's esophagus and the presence of Helicobacter pylori.

OBJECTIVE: Although the role of Helicobacter pylori in the pathogenesis of peptic ulcer disease and antral gastritis has been well documented, the role of H. pylori in esophageal disease has not been clearly defined. To clarify this issue, we analyzed 141 patients with histologically confirmed esophageal disease. METHODS: The study group consisted of 82 patients with Barrett's esophagus, 19 with adenocarcinoma of the esophagus arising in columnar epithelium and 40 patients with reflux esophagitis without columnar metaplasia of the esophagus. In each of these cases the presence or absence of H. pylori was assessed histologically. RESULTS: H. pylori was present in 19 of 82 patients (23%) with Barrett's esophagus, but was absent in all patients with adenocarcinoma of the esophagus and in patients with reflux esophagitis without Barrett's metaplasia. H. pylori was found only in areas of gastric type metaplasia in the patients with Barrett's esophagus. All of the 19 Barrett's esophagus group with H. pylori had chronic inflammation, and in 16 the inflammation was severe. H. pylori was significantly associated with severity of inflammation in patients with Barrett's esophagus (p < 0.001). Members of the Barrett's group with evidence of moderate to severe dysplasia were negative for H. pylori. CONCLUSION: These data confirm that the presence of gastric type mucosa within the esophagus is a prerequisite for H. pylori colonization, and that H. pylori may contribute to the severity of inflammation in Barrett's epithelium.

Adenocarcinoma↗

Gastroesophageal reflux, motility disorders, and psychological profiles in the etiology of globus pharyngis.

The aim of this study was to investigate the origin of globus pharyngis with particular reference to esophageal disorders such as gastroesophageal reflux disease (GERD), motility disorders, structural abnormalities, other gastrointestinal tract diseases, and psychological profile. Previous studies on this subject using 24-hour pH monitoring give conflicting results and are hampered by the high background prevalence of asymptomatic GERD in the normal Western population. The local Chinese population is known to have a very low background level of GERD and therefore is an ideal study population. Twenty-six patients with globus pharyngis underwent 24-hour ambulatory pH monitoring, esophageal manometry, and esophagogastroduodenoscopy with lower esophageal biopsy. A control group of 20 patients presenting with non-ulcer dyspepsia was similarly investigated. Personality profiles of the globus pharyngis subjects and an appropriate control group were assessed. Eight of the globus pharyngis group (30.7%) had evidence of GERD, whereas only one of the controls (5%) demonstrated GERD on 24-hour esophageal pH monitoring (P < 0.05). The manometric and personality profile studies did not show significant differences between study and control groups. We concluded that the finding of GERD in patients with globus pharyngis is not a coincidental finding but that there is a true association between GERD and globus pharyngis.

Adult↗

Laparoscopic truncal vagotomy and gastroenterostomy for pyloric stenosis.

BACKGROUND: Gastric outlet obstruction secondary to chronic duodenal ulceration is an indication for surgery as conservative management with balloon dilatation frequently fails. The standard operation is truncal vagotomy and a drainage procedure. However, development of minimally invasive surgery has revolutionized the surgical approach to this clinical problem. METHODS: Twelve male patients with pyloric stenosis secondary to duodenal ulceration underwent laparoscopic truncal vagotomy and gastrojejunostomy. The perioperative and long term outcome of this group of patients were analyzed. RESULTS: The median operating time was 210 (range 180 to 240) minutes. Median postoperative stay was 6 (range 4 to 41) days. Conversion to laparotomy was necessary in one patient. Delayed gastric emptying occurred in two patients but resolved on conservative measures. At a median postoperative followup of 6 (range 1 to 12) months all patients had a good symptomatic outcome (Visick grades I or II). CONCLUSIONS: Laparoscopic truncal vagotomy and gastrojejunostomy is a feasible technique. Intermediate followup shows good symptomatic results when used for pyloric stenosis.

Adult↗

Urban to urban migration: Soviet patterns and post-Soviet implications.

"In spite of extensive literature on migration in the Soviet Union, we know little about household-level decisions. This study specifies and estimates those variables important to understanding the migration decision. Using data from the Soviet Interview Project (SIP), we examine the forces influencing the decision to migrate or not to migrate, and in addition, for those who did migrate, the forces influencing the locational choices made. The results indicate that, while some of the traditional factors influencing migration are important, others are not, suggesting that in the post-Soviet era, differentiating the persistence of Soviet-type forces from emerging market-type forces will be important for an understanding of urban to urban migration."

Behavior↗

Thoracoscopic resection of oesophageal diverticulum: a case report.

The introduction of video-assisted surgery has revolutionized thoracic surgery. The main attraction is the avoidance of a large thoracotomy incision and its associated morbidity. We present the case of a 55-year-old woman with an oesophageal diverticulum presenting with troublesome dysphagia. A thoracoscopic assisted oesophageal diverticulectomy was performed. Post-operative recovery was uneventful, and only two doses of intramuscular opiate analgesic were required. The patient remained asymptomatic at a follow-up of 3 months.

Diverticulum, Esophageal↗