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Biomedical subjects

J V Reynolds

Publications and source records attributed to J V Reynolds.

At least 37 records · Page 2Linked to original sources
PubMed2003

Impaired visceral sensitivity to acid reflux in patients with Barrett's esophagus. The role of esophageal motility*.

Patients with Barrett's esophagus have been reported to have impaired visceral sensitivity to acid perfusion and distension compared with non-Barrett's refluxers, but the mechanism is poorly understood. Esophageal motility and clearance mechanisms may be important, and this study explored the relationship of motility with symptoms. Seventy-four patients with Barrett's esophagus were compared with 216 patients with gastro-esophageal reflux disease (GERD) with abnormal acid reflux scores, and 50 symptomatic patients who had normal acid exposure. All patients had esophageal manometry and 24-h pH monitoring. Thirty-six Barrett's patients also had 24-h bile reflux monitoring. Symptoms were assessed by Symptom Index (SI) during 24-h pH monitoring. Barrett's patients with normal motility had a significantly lower SI than GERD patients for similar acid exposure (P < 0.001). Barrett's patients with abnormal motility had higher acid exposure than those with normal motility (P < 0.05), but the SI values for this group was not significantly different from the GERD patients. SI and Bile reflux in Barrett's esophagus was not significantly different in patients with normal or abnormal motility. Barrett's patients had less sensitivity than GERD patients for similar acid exposure. Normal motility in Barrett's esophagus is associated with the poorest sensitivity and the presence of increased acid exposure is required in order to achieve sensitivity levels comparable with GERD patients.

Adolescent↗
PubMed2003

Endocinch therapy for gastro-oesophageal reflux disease: a one year prospective follow up.

BACKGROUND: Gastro-oesophageal reflux disease (GORD) is, in the main, treated with either proton pump inhibitor (PPI) drugs or a Nissen fundoplication operation. Recently, BARD developed Endocinch, a device used to place sutures just below the oesophagogastric junction (OGJ) to treat GORD. AIM: To evaluate the long term benefit of the Endocinch technique in patients seen up to 12 months post procedure. PATIENTS: Twenty six patients with symptoms of GORD were recruited and had the procedure performed. Four patients were lost to follow up. METHODS: Twenty two patients completed their one year follow up. Pre procedure and post procedure (up to 12 months) assessments included symptom scoring (DeMeester), upper intestinal endoscopy, oesophageal manometry and 24 hour oesophageal pH, and completion of quality of life (QOL) questionnaires. RESULTS: Mean age was 39 years (range 22-62). Heartburn symptom score was reduced from a mean value of 19.22 at baseline to 7.5 at 12 months (n=22) (p<0.0001). Regurgitation score reduced from a mean of 2.27 at baseline to 0.86 at 12 months (n=22) (p<0.001). Mean (SEM) pH DeMeester acid score was reduced from 44.1 (4.3) to 33.32 (4.73) (p=0.028) at three month post procedure. Percentage upright acid exposure and number of reflux episodes were also reduced significantly. Use of PPIs was reduced by 64% at 12 months post procedure. All QOL assessments showed significant improvement (p=0.01). All transient post procedure complaints resolved within 72 hours. CONCLUSION: The Endocinch procedure is an effective and safe outpatient procedure that offers GORD patients significant improvement in symptomatology, QOL, and reduced requirements for PPIs over at least a one year period.

Adult↗
PubMed2002

Endovascular approach to abdominal aortic aneurysms limits the postoperative systemic immune response.

OBJECTIVES: endovascular repair of abdominal aortic aneurysms (E-AAA) has in recent years developed as an alternative to the conventional open repair (C-AAA). Adverse outcomes following the open approach may relate to immune cell activation and the systemic inflammatory response syndrome (SIRS) and organ failure but the benefits in this respect of the endovascular approach are unclear. This study evaluated this question and focused on T-cell activation and function. DESIGN: prospective clinical study. MATERIALS: twenty patients undergoing abdominal aortic aneurysm repair (12 C-AAA and 8 E-AAA). METHODS: peripheral T-cell expression of surface markers CD69, CD62L and CD25 in vivo and Interleukin 2 (IL-2) and Interleukin-10 (IL-10) responses to the superantigen staphylococcal enterotoxin B (SEB) in vitro were measured preoperatively, 24 h and 1 week postoperatively. RESULTS: there was no significant increase (p=0.23) in the incidence of SIRS in the open compared with the endovascular group. Enhanced T cell activation occurred following C-AAA and this was associated with significantly greater IL-2 production in response to SEB, with no change in IL-10 production. CONCLUSIONS: E-AAA attenuates proinflammatory T-cell changes compared with C-AAA repair. A reduction in T-cell activation and impaired responsiveness to superantigen suggests that the immunological sequelae of the endovascular approach to aneurysm repair is more favourable than after the open approach with potentially less risk of adverse outcomes. Proof of this thesis will require a larger prospective study.

Aged↗
PubMed2001

Spontaneous and inducible apoptosis in oesophageal adenocarcinoma.

The use of neoadjuvant chemoradiotherapy prior to surgery in the treatment of oesophageal adenocarcinoma has increased in recent years, and up to 25% of patients will have a complete pathological response to the neoadjuvant therapy. Many patients will not respond, however, and the knowledge of molecular factors predicting response or resistance to chemoradiotherapy is required to enhance treatment results. An understanding of apoptosis and cell proliferation may be relevant and this study focused on apoptotic indices and cell-cycle related (Ki-67, p53 and bcl-2) protein expression in a cohort of 42 patients with primary oesophageal adenocarcinoma. We documented that apoptosis occurs among viable (proliferating) tumour cells in all adenocarcinoma cases examined in this study. Pre-operative chemoradiotherapy significantly increased apoptosis and significantly decreased cell proliferation (estimated by Ki-67 expression). Immunohistochemically detected p53 and bcl-2 gene products had no regulatory role in the apoptotic process. The cumulative expression of p53 protein is significantly associated with increasing proliferation activity. Evaluation of apoptosis in pre-treatment specimens may have potential utility in predicting the efficacy of treatment. Assessment of the tumours proliferation activity by Ki-67 expression might identify patients who are at risk of developing metastatic disease.

Adenocarcinoma↗
PubMed2001

A common p73 polymorphism is associated with a reduced incidence of oesophageal carcinoma.

The incidence of oesophageal adenocarcinoma is rising; to date, no susceptibility genes have been identified. p73, a novel p53 homologue, maps to chromosome 1p36, a region commonly deleted in oesophageal cancers. p73 shares some p53-like activity, but in addition, may also play a role in gastrointestinal epithelial inflammatory responses. A non-coding p73 polymorphism (denoted AT or GC) may be functionally significant. We investigated whether this polymorphism might play a role in the aetiopathogenesis of oesophageal cancer. This was a case-control, retrospective study. 84 cases of oesophageal cancer (25 squamous and 59 adenocarcinoma) and 152 normal population controls were genotyped for this polymorphism. Informative cases were examined for p73 LOH within the tumour. AT/AT homozygotes were significantly less prevalent in the oesophageal cancer population (1/84 = 1.2%) compared to controls (15/152 = 9.9%) (P < 0.02), corresponding to an odds ratio of 0.11 (95% C.I. 0.02-0.6, P < 0.02), or 9-fold reduced risk. Moreover, AT/AT homozygotes were significantly less frequent in the cancer population than would be expected under the Hardy-Weinberg hypothesis (P = 0.0099). LOH at the p73 locus was observed in 37.8% (14/37) of the AT/GC heterozygotes studied; in all cases there was loss of the AT allele. Our findings indicate that p73 AT/AT homozygotes appear to be protected against the development of oesophageal cancer. Clinically, this observation could have implications in aiding identification of high-risk Barrett's oesophagus patients.

Adenocarcinoma↗
PubMed2001

A pathological study of tumour regression in oesophageal adenocarcinoma treated with preoperative chemoradiotherapy.

AIMS: To measure residual tumour in oesophageal adenocarcinoma treated with preoperative chemoradiotherapy, to correlate specific pathological variables with survival, and to describe morphological changes in tumour and non-neoplastic tissue resulting from preoperative treatment. METHODS: Resection specimens from 47 cases of oesophageal adenocarcinoma treated with preoperative 5-fluorouracil/cisplatin and radiotherapy were reviewed. Residual tumour was assessed in terms of tumour regression grade (TRG), pTNM stage, lymphovascular space invasion, and resection margin involvement. Survival analysis was performed using the Kaplan-Meier method and log rank test. Cox's proportional hazard model was used for multivariate analysis. RESULTS: A complete pathological response (TRG1) was present in eight cases. The absence of residual tumour was confirmed by negative immunohistochemical staining for MNF116. Tumour corresponding to TRG2 was present in five cases, to TRG3 in nine, to TRG4 in 22, and to TRG5 in three. By multivariate analysis, pN0 status (n = 35) had a positive effect on survival (p = 0.04) and TRG had no significant effect on survival (p = 0.06). Patients with pN0 tumours had a median survival of 48 months versus eight months for those with pN1 tumours (log rank test, p < 0.0001). We found that giant fibroblasts were discernible from single large residual tumour cells on haematoxylin and eosin alone. CONCLUSION: Response to preoperative chemoradiotherapy in oesophageal adenocarcinoma is variable. Although there are as yet no reliable predictors of response to treatment, patients who are identified at diagnosis as having negative loco-regional lymph nodes should benefit considerably from this treatment approach.

Adenocarcinoma↗
PubMed2001

Expandable metal stents in the palliation of malignant dysphagia and oesophageal-respiratory fistulae.

The use of self expandable metal stents in the palliation of malignant dysphagia and oesophago-respiratory fistulae has increased in recent years. The aim of this study was to report a comprehensive 4 year audit of a Specialist Unit's experience with the expandable stent. 200 expandable metal stents were deployed for palliation of non operable malignant dysphagia or fistulae. Per-operative, early (<30 days) and late (>30 days) complications specific to the stent were documented. Stents were successfully positioned in all patients. There was no mortality associated with the insertion and no perforation. Dysphagia was palliated initially in 93 per cent of cases. The mean dysphagia score improved significantly from 3.2 to 1.5 (p<0.01). This significant benefit persisted at 3 months and 6 months of follow-up. The commonest complication was stent migration (5.5%) and 23 patients (11%) required a second stent insertion. Oesophago-respiratory fistulae were successfully palliated in all cases. This study demonstrates the effectiveness of self expandable metallic stents in the palliation of non operable malignant dysphagia and oesophago-respiratory fistulae. The minimal risk of significant complications and low incidence of reintervention should establish this approach as first line palliation in these patients.

Aged↗
PubMed2000

Specialized intestinal metaplasia in patients with gastro-oesophageal reflux disease.

BACKGROUND: There is an increasing awareness that short (less than 3 cm) segments of Barrett's epithelium and macroscopically normal cardia epithelium may harbour specialized intestinal metaplasia (SIM), a premalignant phenotype. The prevalence of SIM was studied prospectively in an unselected population of patients attending for endoscopy, and the association of SIM with symptoms, lifestyle, medication, endoscopic oesophagitis and carditis was investigated. METHODS: Two hundred consecutive patients underwent endoscopy. Biopsies taken from just below the squamocolumnar junction were stained for SIM, and were analysed for carditis and Helicobacter pylori infection. A detailed questionnaire of symptoms, tobacco consumption and the use of proton pump inhibitors was completed. RESULTS: Forty-two patients (21 per cent) had SIM: 19 (15 per cent) of 126 in an endoscopically normal oesophagus, 15 (24 per cent) of 63 in a short segment of Barrett's epithelium and eight of 11 in classical Barrett's oesophagus. There was a significant association between SIM and carditis (P < 0.0001) and endoscopic oesophagitis (P = 0.03). CONCLUSION: SIM is prevalent in patients undergoing endoscopy, does not correlate with symptoms or H. pylori infection, but is significantly associated with endoscopic and pathological markers of gastro-oesophageal reflux.

Adolescent↗
PubMed2000

Lack of correlation between failure of gut barrier function and septic complications after major upper gastrointestinal surgery.

OBJECTIVE: To determine the influence of abnormal gut barrier function on the risk of septic complications in patients undergoing major resectional surgery for upper gastrointestinal cancer. SUMMARY BACKGROUND DATA: A failure of the gut mucosal barrier to exclude bacteria and endotoxin from the portal and systemic circulation is incriminated in the development of sepsis and multiple organ failure. Although the experimental data is compelling, corroborative evidence from studies in humans is sparse. This study attempted to correlate both preoperative gut barrier dysfunction and the pattern of change after surgery with septic outcome. METHODS: Sixty-eight patients undergoing curative resectional surgery for upper gastrointestinal cancer were monitored for 30-day septic morbidity (intraabdominal abscesses/empyema and pneumonia). Intestinal permeability, serum IgM and IgG anti-endotoxin antibodies (EndoCAb), and serum C-reactive protein were measured before surgery and on postoperative days 1 and 7. RESULTS: Increased intestinal permeability before surgery did not predict septic outcome. Major surgery was associated with increased intestinal permeability and evidence of endotoxin exposure. Comparing sepsis and nonsepsis groups, however, there was no significant difference in intestinal permeability, endotoxin exposure, and the acute phase response after surgery. CONCLUSIONS: This study demonstrates that gut barrier dysfunction occurs after surgery, but the magnitude of change does not differentiate patients in whom sepsis develops and those in whom it does not. Preoperative increased intestinal permeability had no predictive value for sepsis. This study failed to support the thesis that gut barrier dysfunction is directly linked to sepsis.

Acute-Phase Reaction↗
PubMed2000

The isolated hypertensive lower oesophageal sphincter: audit in a specialist unit.

The hypertensive lower oesophageal sphincter (HLOS) is a distinct clinical entity defined by a lower oesophageal sphincter (LOS) pressure > or = 30mmHg and normal LOS relaxation and oesophageal peristalsis. The clinical, physiological, and radiological details of 27 patients with HLOS diagnosed in a 3-year period were reviewed. The reasons for referral included: gastro-oesophageal reflux disease (GORD) (33%), dysphagia (18.5%), epigastric discomfort (11%), non-cardiac chest pain (15%), globus (7.5%) and other (15%). All patients had manometric evidence of HLOS (Median LOS pressure 30 mmHg, range 25-50 mmHg) and 6 patients (20.7%) had abnormal pH studies. Less than 22% of contrast studies demonstrated an abnormality. There was no change in manometric findings following pharmacological treatment. Two patients underwent oesophagomyotomy and had normal manometry on follow up. We conclude that HLOS mimics a variety of upper gastrointestinal disorders and oesophageal manometry is the gold standard of diagnosis. There was an unexpectedly high incidence of GORD (22%) in this group. The significance and treatment of HLOS is discussed.

Adult↗
PubMed1998

Increased intestinal permeability and altered mucosal immunity in cholestatic jaundice.

OBJECTIVE: To examine the effects of cholestatic jaundice on gut barrier function. SUMMARY BACKGROUND DATA: Gut barrier failure occurs in animal models of jaundice. In humans, the presence of endotoxemia indirectly implicates failure of this host defense, but this has not previously been investigated in jaundiced patients. METHODS: Twenty-seven patients with extrahepatic obstructive jaundice and 27 nonicteric subjects were studied. Intestinal permeability was measured using the lactulose-mannitol test. Small intestinal morphology and the presence of mucosal immunologic activation were examined in endoscopic biopsies of the second part of the duodenum. Systemic antiendotoxin core IgG antibodies and serum interleukin-6 and C-reactive protein were also quantified. Intestinal permeability was remeasured in 9 patients 5 weeks after internal biliary drainage. RESULTS: The median lactulose-mannitol ratio was significantly increased in the jaundiced patients. This was accompanied by upregulation of HLA-DR expression on enterocytes and gut-associated lymphoid tissue, suggesting immune activation. A significant increase in the acute phase response and circulating antiendotoxin core antibodies was also observed in the jaundiced patients. After internal biliary drainage, intestinal permeability returned toward normal levels. CONCLUSIONS: A reversible impairment in gut barrier function occurs in patients with cholestatic jaundice. Increased intestinal permeability is associated with local immune cell and enterocyte activation. In view of the role of gut defenses in the modern paradigm of sepsis, these data may directly identify an important underlying mechanism contributing to the high risk of sepsis in jaundiced patients.

Acute-Phase Reaction↗
PubMed1998

Gut barrier function in malnourished patients.

BACKGROUND: The integrity of the gastrointestinal mucosa is a key element in preventing systemic absorption of enteric toxins and bacteria. In the critically ill, breakdown of gut barrier function may fuel sepsis. Malnourished patients have an increased risk of postoperative sepsis; however, the effects of malnutrition on intestinal barrier function in man are unknown. AIMS: To quantify intestinal barrier function, endotoxin exposure, and the acute phase cytokine response in malnourished patients. PATIENTS: Malnourished and well nourished hospitalised patients. METHODS: Gastrointestinal permeability was measured in malnourished patients and well nourished controls using the lactulose:mannitol test. Endoscopic biopsy specimens were stained and morphological and immunohistochemical features graded. The polymerase chain reaction was used to determine mucosal cytokine expression. The immunoglobulin G antibody response to endotoxin and serum interleukin 6 were measured by enzyme linked immunosorbent assay. RESULTS: There was a significant increase in intestinal permeability in the malnourished patients in association with phenotypic and molecular evidence of activation of lamina propria mononuclear cells and enterocytes, and a heightened acute phase response. CONCLUSIONS: Intestinal barrier function is significantly compromised in malnourished patients, but the clinical significance is unclear.

Aged↗
PubMed1998

Compared with parenteral nutrition, enteral feeding attenuates the acute phase response and improves disease severity in acute pancreatitis.

BACKGROUND: In patients with major trauma and burns, total enteral nutrition (TEN) significantly decreases the acute phase response and incidence of septic complications when compared with total parenteral nutrition (TPN). Poor outcome in acute pancreatitis is associated with a high incidence of systemic inflammatory response syndrome (SIRS) and sepsis. AIMS: To determine whether TEN can attenuate the acute phase response and improve clinical disease severity in patients with acute pancreatitis. METHODS: Glasgow score, Apache II, computed tomography (CT) scan score, C reactive protein (CRP), serum IgM antiendotoxin antibodies (EndoCAb), and total antioxidant capacity (TAC) were determined on admission in 34 patients with acute pancreatitis. Patients were stratified according to disease severity and randomised to receive either TPN or TEN for seven days and then re-evaluated. RESULTS: SIRS, sepsis, organ failure, and ITU stay, were globally improved in the enterally fed patients. The acute phase response and disease severity scores were significantly improved following enteral nutrition (CRP: 156 (117-222) to 84 (50-141), p < 0.005; APACHE II scores 8 (6-10) to 6 (4-8), p < 0.0001) without change in the CT scan scores. In parenterally fed patients these parameters did not change but there was an increase in EndoCAb antibody levels and a fall in TAC. Enterally fed patients showed no change in the level of EndoCAb antibodies and an increase in TAC. CONCLUSION: TEN moderates the acute phase response, and improves disease severity and clinical outcome despite unchanged pancreatic injury on CT scan. Reduced systemic exposure to endotoxin and reduced oxidant stress also occurred in the TEN group. Enteral feeding modulates the inflammatory and sepsis response in acute pancreatitis and is clinically beneficial.

APACHE↗
PubMed1997

Interleukin-10. A role in the development of postoperative immunosuppression.

BACKGROUND: The cause of diminished monocyte major histocompatibility complex class II antigen expression after surgery or trauma is unclear. Interleukin-10 (IL-10) regulates inflammatory cytokine production and major histocompatibility complex class II (HLA-DR) expression in vitro. OBJECTIVES: To quantify in vivo IL-10 messenger RNA (mRNA) and protein and monocyte HLA-DR expression after major surgery and to investigate the effects of IL-10 neutralizing blockade on monocyte HLA-DR expression in vitro. DESIGN: Inception cohort study of 48 surgical patients from preoperative status to postoperative day 7 and 9 healthy volunteers (controls). SETTING: Large teaching hospital, Northern England. PATIENTS: Monocyte HLA-DR and cytokine mRNA expression was determined in 32 of 48 consecutive patients undergoing elective major resectional surgery. Mononuclear cells for in vitro studies and serum samples for IL-10 measurement were obtained from the remaining 16 patients. MAIN OUTCOME MEASURES: Monocyte HLA-DR expression determined by flow cytometry, IL-10, and tumor necrosis factor mRNA in peripheral blood mononuclear cells assayed by multiplex reverse transcriptase polymerase chain reaction, and serum IL-10 determined by enzyme-linked immunosorbent assay. RESULTS: Monocyte HLA-DR expression (in mean channel fluorescence units [MCF]) was significantly reduced 24 hours after surgery (MCF [+/- SEM], 32.6 +/- 2.3 vs 16.3 +/- 1.2; P < .001) and remained low during the first postoperative week. A relative increase in IL-10 to G3PDH mRNA ratio (mean [+/- SEM], 0.95 +/- 0.08 vs 0.59 +/- 0.06; P < .01) and serum IL-10 (mean [+/- SEM], 18.1 +/- 4.1 vs 5.4 +/- 0.8 pg/mL; P < .01) was noted on the first postoperative day. A significant correlation existed between HLA-DR antigen expression and the presence of IL-10 mRNA transcript on the first postoperative day (P < .01). Lipopolysaccharide-induced up-regulation of monocyte HLA-DR expression was significantly impaired on the first postoperative day (mean [+/- SEM], 151% +/- 24.4% vs 60% +/- 10.1%; P < .01), but this was partially reversed by IL-10 neutralizing antibody (mean [+/- SEM], 60% +/- 10.1% vs 115% +/- 11.6%; P < .01). CONCLUSIONS: Interleukin-10 gene expression correlates with the fall in monocyte HLA-DR antigen expression in patients undergoing major abdominal surgery and may account for the immunosuppression associated with surgical injury.

Gene Expression↗
PubMed1997

Pseudolipoma of inverted Meckel's diverticulum: clinical, radiological and pathological correlation.

Three cases of isolated inverted Meckel's diverticulum are described. In two cases an initial pathological diagnosis of small bowel lipoma was suggested. In a third case central fat was demonstrated on CT and peristalsis of the intraluminal polypoid mass was observed during US examination. In all three cases small bowel enema examination demonstrated the lesion. Correlation of the clinical, radiological and pathological features is emphasised, as this will allow the correct diagnosis.

Adult↗
PubMed1997

Monocyte activation after open and laparoscopic surgery.

BACKGROUND: The level of expression of major histocompatibility complex class II antigens, human leucocyte antigen (HLA)-DR, on monocytes correlates with the development of sepsis after surgery or trauma. Normally interferon (IFN) gamma can increase monocyte HLA-DR expression and thus may be a potential biological prophylactic antisepsis agent in patients suffering from accidental or surgical trauma. The purpose of this study was to determine the capacity of monocytes to respond to IFN-gamma after conventional open surgery and laparoscopic surgery of similar magnitude. METHODS: A whole blood flow cytometric assay was used to measure monocyte HLA-DR antigen expression before and after monocyte activation with either IFN-gamma or bacterial lipopolysaccharide (LPS). Blood was obtained before operation and on postoperative day 1 from 43 patients undergoing conventional open surgery and from 15 undergoing laparoscopic surgery of similar magnitude. RESULTS: Whole blood monocyte HLA-DR expression fell significantly after both conventional open and laparoscopic surgery. IFN-gamma caused monocyte HLA-DR expression to rise by a median (interquartile range) of 43 (26-60) per cent and 63 (10-124) per cent before operation in the open and laparoscopic groups respectively. However, after operation the corresponding values were 20 (6-41) per cent and 26 (9-74) per cent (P < 0.003 in all cases). Identical findings but of greater magnitude were observed with LPS stimulation before and after operation in the two surgical groups. CONCLUSION: Monocyte HLA-DR expression is diminished by surgical operations and is relatively refractory to further stimulation by IFN-gamma or LPS after surgery. Laparoscopic surgery is as suppressive as conventional surgery in this regard. The resistance of postoperative monocytes to further activation by IFN-gamma suggests that this agent may be ineffective as a biological response modifier after major surgery or trauma.

Adult↗
PubMed1996

Pathological evidence in support of total mesorectal excision in the management of rectal cancer.

Some 50 total mesorectal excision specimens were examined following rectal excision for cancer. Circumferential margin involvement was rare, but mesorectal tumour deposits were present in 17 of 44 patients with pT3 tumours, and 23 of 44 had mesorectal nodal involvement. No patient with a pT2 tumour had mesorectal involvement. Failure to excise the mesorectum completely has the potential to leave gross or microscopic residual disease that may in theory predispose to local failure. Total mesorectal excision is necessary to avoid incomplete pathological evaluation of the mesorectum and understaging of rectal cancer.

Adenocarcinoma↗