Biomedical subjects

K D Bardhan

Publications and source records attributed to K D Bardhan.

At least 19 recordsLinked to original sources

PubMed2006

Characterisation of the haemodynamics of the superior mesenteric artery.

In contrast to its prevalence in the surrounding vasculature, occurrence of primary atherosclerotic disease in the superior mesenteric artery (SMA) is rare (Glagov et al., 1988. Hemodynamics and atherosclerosis, Insights and perspectives gained from studies of human arteries. Archives of Pathology and Laboratory Medicine 112(10), 1018-1031; Hansen et al., 2004. Mesenteric artery disease in the elderly. Journal of Vascular Surgery 40(1), 45-52). We hypothesise that this sparing might be attributed to more favourable haemodynamic characteristics in the SMA than in other vessels locally. Dynamic magnetic resonance imaging (MRI) images established that the SMA is highly mobile (Jeays, 2006. Investigation of blood flow in the superior mesenteric artery and its potential influence on atheroma and gut ischaemia. Ph.D. Thesis, University of Sheffield), and thus that an analysis based on rigid geometry might be inappropriate. This paper describes an efficient methodology for the construction of a patient-specific, time-dependent model of an arterial segment and reports the results of a haemodynamic characterisation of the SMA for one individual. A transient computational fluid dynamic (CFD) model was constructed by morphing a parametric mesh constructed from simple geometric primitives. This process has the merit that it is easy to control the element size distribution mapped onto the original geometric primitives. It is robust in operation, and is ideally suited to the generation of dynamic CFD meshes of arterial systems that are free from major pathology. Flow boundary conditions were determined based on phase contrast MRI velocity measurements. Comparative studies with rigid walls and with moving walls, based on the transient data, indicated that, despite the significant motion of the SMA (radial dilation of the order of 10% and translation of the order of the radius), the maximum (spatially and temporally-resolved) wall shear stresses changed by no more than 21.6% of a global norm, and the average change was less than 2.1%.

Hemorheology↗

PubMed2006

Recent trends in hospital admissions and mortality rates for peptic ulcer in Scotland 1982-2002.

BACKGROUND: While overall hospital admission rates for peptic ulcer declined in England in the 1990 s, they increased among the elderly, especially for complicated ulcer. However, peptic ulcer admissions fell for all age groups in the United States. AIM: To examine time trends in the incidence of hospital admissions, mortality and operations because of peptic ulcer in Scotland from 1982 to 2002, and the use of various drugs relevant to the aetiology and treatment of peptic ulcer from 1992 to 2002. RESULTS: There was a general decrease in admission rates, especially for younger individuals. For individuals aged above 74 years, admission rates actually increased for gastric ulcer with haemorrhage among men, and for duodenal ulcer haemorrhage between both sexes. The number of operations fell dramatically, especially for younger patients. Mortality rates generally declined. Case fatality rates were greater for women than men, and declined over the study period for gastric ulcer, but increased for duodenal ulcer. The use of low-dose aspirin, oral anticoagulants, selective serotonin reuptake inhibitors and proton-pump inhibitors increased while those of non-steroidal anti-inflammatory drugs and histamine-2 antagonists declined. CONCLUSIONS: Admission rates for peptic ulcer generally fell for younger individuals, but increased for older people with haemorrhage.

Adult↗

PubMed2005

Reflux rising! An essay on witnessing a disease in evolution.

BACKGROUND AND AIM: The prevalence of gastro-oesophageal reflux disease is thought to be rising but supporting evidence is sparse. We assessed trends from data prospectively collected over 25 years at our centre which serves Rotherham's 250000 population. PATIENTS AND METHODS: Detailed computerised records have been kept of all patients investigated for upper gastrointestinal symptoms. DEFINITION: Erosive oesophagitis=endoscopy-verified erosive changes. Non-erosive reflux=heartburn+/-regurgitation but normal endoscopy. Gastro-oesophageal reflux disease=erosive oesophagitis+non-erosive reflux, i.e. total. RESULTS: The data, presented in 5-year time periods spanning 1977-2001, showed four major changing trends. (1) The numbers with newly diagnosed gastro-oesophageal reflux disease rose markedly, affecting both erosive oesophagitis and non-erosive reflux. Gastro-oesophageal reflux disease: n=714; 1587; 2381; 3812; 3880. (2) The proportion of women affected rose from 0.36 to 0.82. (3) Gastro-oesophageal reflux disease patients were older than the general population; the mean age at presentation rose from 48.0 to 53.5 years. (4) Presentation with haemorrhage (percentage of erosive oesophagitis) rose from 5.2% to 10.9% but, as with stricture (around 4%), remained uncommon. Throughout, few (4.4%) changed from non-erosive reflux to erosive oesophagitis. CONCLUSION: The marked increase in gastro-oesophageal reflux disease cannot be accounted for by greater awareness alone for the demographic profile has changed, or by misclassification as erosive oesophagitis was diagnosed on endoscopic appearances. The dramatic five-fold increase in gastro-oesophageal reflux disease is a new phenomenon, perhaps an example of a disease in evolution.

Aged↗

PubMed2005

Electrical bioimpedance readings increase with higher pressure applied to the measuring probe.

Electrical bioimpedance spectroscopy (EBIS) is a technique that uses a probe to calculate the transfer impedance from tissues. This transfer impedance can give information about the normal or pathological condition of the tissue. To take readings, pressure has to be applied to the probe in order to get a good contact between the electrodes and the tissue. We have been using EBIS to investigate the early diagnosis of dysplasia and cancer in the human cervix, oesophagus and bladder. We have found that, with increasing pressure (range used here was approximately 1 kPa to approximately 50 kPa), the resistivity readings increase in a consistent way up to 80%. In this paper, we show how this is a case in three different tissue types (oesophageal, gastric and vesical samples). These increases can be higher than those associated with the pathological changes that we are investigating (non-inflamed columnar tissue, for instance, shows values 50% higher than dysplastic columnar tissue). Finite-element modelling was also used to investigate the effect of volume reduction in the connective tissue or stroma. This simulation suggests no strong correlation between reduction of this structure and increase in resistivity. We hypothesize therefore that these changes may be mainly associated with the squeezing of water from the extracellular space. Finally, as pressure is difficult to control by hand, we raise the issue of the necessity of considering this variable when making EIS measurements.

Animals↗

PubMed2005

Pantoprazole in severe acid-peptic disease: the effectiveness and safety of 5 years' continuous treatment.

OBJECTIVE: This is our final report on the clinical effectiveness and safety of long-term pantoprazole in patients with severe peptic ulcer or reflux disease during continuous treatment for up to 5 years. METHODS: Patients (n= 150) with peptic ulcer or reflux erosive oesophagitis running an aggressive course or with complications, and refractory to H2-receptor antagonists, were entered into this 5-year programme. Assessment was by serial endoscopy, clinical examination, serum gastrin estimation, gastric mucosal histology and mucosal endocrine cell quantification. RESULTS: Healing results were presented earlier. The estimated rates of remission on maintenance treatment with pantoprazole (n = 115) were 82% at 1 year, 75% at 2 years, 72% at 3 years, 70% at 4 years and 68% at 5 years. Helicobacter pylori infection appeared not to influence the outcome in reflux patients, with roughly two-thirds continuing in remission irrespective of infection. Only four patients had adverse events considered to be definitely related to pantoprazole. Median gastrin levels rose by 1.5-2-fold and were higher in those with H. pylori infection; 13 patients had levels >500 ng/L on at least one occasion, but these high levels were not sustained. Histological changes were more marked in patients infected with H. pylori: chronic gastritis decreased in the antrum and increased in the corpus, which also showed atrophic changes. The total number of endocrine cells in the antrum showed little variation over 60 months but fell by around one-third in the corpus. CONCLUSION: Long-term treatment with pantoprazole is effective and safe.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2004

International validation of ReQuest in patients with endoscopy-negative gastro-oesophageal reflux disease.

BACKGROUND: Reflux Questionnaire (ReQuest), a newly developed gastro-oesophageal reflux disease-sensitive scale, can be used to reliably evaluate the effect of treatment on gastro-oesophageal reflux disease symptoms. AIM: International validation of this scale, in patients suffering from endoscopy-negative gastro-oesophageal reflux disease. METHODS: In this open, multicentre and multinational clinical trial 840 endoscopy-negative gastro-oesophageal reflux disease patients received pantoprazole 20 mg daily for 28 days. The long and short versions of ReQuest were completed both in the pre-treatment and treatment phases. For scale development an item reduction analysis was performed. Internal consistency, test-retest reliability and responsiveness were calculated for psychometric analysis. Construct validity was evaluated by comparison with the Gastrointestinal Symptom Rating Scale and the Psychological General Well-being questionnaire by means of correlation coefficients. RESULTS: Factor analyses confirmed the content validity of both long and short version of ReQuest. Psychometric calculations proved high internal consistency (Cronbach's alpha: 0.9), test-retest reliability [Intraclass Correlation Coefficient: 0.9 (long vs. long) and 0.8 (short vs. short)], and responsiveness (Responsiveness Index 320.3) of the scale, for which also good construct validity was achieved (correlation coefficient: Gastrointestinal Symptom Rating Scale -0.6; Psychological General Well-being -0.4). CONCLUSION: ReQuest proved valid, reliable, and responsive in this multinational clinical trial to evaluate treatment response in endoscopy-negative gastro-oesophageal reflux disease patients.

Adult↗

PubMed2004

The effects of withdrawing tegaserod treatment in comparison with continuous treatment in irritable bowel syndrome patients with abdominal pain/discomfort, bloating and constipation: a clinical study.

BACKGROUND: The post-withdrawal characteristics of tegaserod treatment in patients with irritable bowel syndrome with constipation remain undefined. AIM: To evaluate the effects of continuous tegaserod treatment, versus intermittent or withdrawal of treatment in patients with irritable bowel syndrome with constipation. METHODS: In a randomized, open-label trial, all patients initially received tegaserod 6 mg b.d. Responders were randomized to continue or withdraw from treatment for 8 weeks and symptom recurrence was assessed. Tegaserod was re-introduced in withdrawal patients who experienced symptom recurrence, allowing an assessment of intermittent treatment. Two separate analyses assessed the effects of intermittent and withdrawal of treatment on symptom recurrence. RESULTS: Five hundred irritable bowel syndrome with constipation patients initially received tegaserod; 410 completed treatment. Time to symptom recurrence was shorter in withdrawal patients than those maintained on tegaserod. Significantly more patients maintained on tegaserod had not experienced symptom recurrence by week 8, compared with intermittent (86.5% vs. 58.1%, respectively) or withdrawal of treatment (69.2% vs. 11.3%, respectively) (P < 0.0001 for both). Significant treatment effects were observed for bloating (P < 0.01) and abdominal pain/discomfort (P < 0.02). Most adverse events were mild to moderate. CONCLUSIONS: Irritable bowel syndrome with constipation patients who receive continuous or intermittent tegaserod are less likely to experience symptom recurrence than patients withdrawn from treatment.

Abdominal Pain↗

PubMed2004

Evaluation of GERD symptoms during therapy. Part II. Psychometric evaluation and validation of the new questionnaire ReQuest in erosive GERD.

BACKGROUND/AIMS: Evaluation of the response of gastroesophageal reflux disease (GERD) symptoms to treatment would be facilitated by a brief, valid, reliable and responsive, self-assessed GERD-sensitive scale. We therefore developed the Reflux Questionnaire (ReQuest). This publication describes the psychometric evaluation and validation of ReQuest. METHODS: This second phase of development was based on data from a clinical trial of patients with erosive GERD who received pantoprazole 20 or 40 mg daily for 28 days and completed weekly the long, and daily the short version of ReQuest. The psychometric analyses of ReQuest included internal consistency, test-retest reliability and responsiveness. Construct validity was evaluated by comparison with the Gastrointestinal Symptom Rating Scale (GSRS) and the Psychological General Well-Being (PGWB) scale. RESULTS: Validation of ReQuest indicated very high internal consistency (Cronbach's alpha = 0.90) and test-retest reliability (intraclass correlation coefficient 0.94 (long-long) and 0.86 (short-short)). This was also the case for the two subscales ReQuest-GI and ReQuest-WSO with Cronbach's alpha coefficients of 0.84 and 0.81. Responsiveness was high with a responsiveness index of >0.8 at day 28. Construct validity was good. CONCLUSION: ReQuest is a highly reliable, valid and responsive self-assessment tool for evaluating treatment response in patients with erosive GERD, and can be applied daily.

Endpoint Determination↗

PubMed2004

Evaluation of GERD symptoms during therapy. Part I. Development of the new GERD questionnaire ReQuest.

BACKGROUND/AIMS: The changes in gastroesophageal reflux disease (GERD)-related symptoms on treatment are variously described, but currently available questionnaires have shortcomings. We therefore developed a self-assessment reflux questionnaire (ReQuest). This article describes the process of development and testing. MATERIALS AND METHODS: For the first version of ReQuest the symptom spectrum of GERD and the various symptom descriptions were investigated. The 67 identified symptom descriptions were condensed empirically into 6 dimensions, to which a 7th dimension on general well-being was added. The symptom burden of the dimensions was measured by frequency and/or intensity. ReQuest was translated into different languages and then tested in focus groups. The initial validation was based on data from a clinical trial of patients with erosive GERD, treated with pantoprazole 20 or 40 mg daily for 28 days. Factor analyses determined the contribution of each symptom to the different dimensions. Additionally, correlation analyses between the identified factors and the dimensions were performed. RESULTS: On the basis of factor analyses, ReQuest was reduced to a 60-item scale. The factors generated correlated strongly with the dimensions and confirmed the empirical process mathematically. CONCLUSION: ReQuest provides a valuable, self-assessment tool for evaluating the daily treatment response in patients with erosive GERD.

Adult↗

PubMed2004

Systematic review: do we need a new gastro-oesophageal reflux disease questionnaire?

BACKGROUND: Gastro-oesophageal reflux disease (GERD) is highly prevalent in Western countries. Because the majority of patients do not present with endoscopic abnormalities, the assessment of the symptom severity and quality of life, and their response to treatment, has become increasingly important. Self-assessed symptom questionnaires are now key instruments in clinical trials. AIM: To evaluate the validity of available GERD measurement tools. METHODS: An ideal GERD symptom assessment instrument, suitable as a primary end-point for clinical trials, should possess the following characteristics: (i) be sensitive in patients with GERD; (ii) cover the frequency and intensity of typical and atypical GERD symptoms; (iii) be multidimensional (cover all symptom dimensions); (iv) have proven psychometric properties (validity, reliability and responsiveness); (v) be practical and economical; (vi) be self-assessed; (vii) use 'word pictures' which are easy to understand for patients; (viii) respond rapidly to changes (responsiveness over short time intervals); (ix) be used daily to assess changes during and after therapy; and (x) be valid in different languages for international use. RESULTS: A literature review revealed five scales that met some of the above characteristics, but did not fulfil all criteria. CONCLUSION: There is a need for a new evaluative tool for the assessment of GERD symptoms and their response to therapy.

Dyspepsia↗

PubMed2004

Admission rates for peptic ulcer in the trent region, UK, 1972--2000. changing pattern, a changing disease?

BACKGROUND AND AIM: Peptic ulcer disease is believed to be less common and less severe as a result of modern medical treatment. We therefore examined changes in the admission rates for patients with duodenal ulcer and gastric ulcer, both emergency (for haemorrhage, perforation or severe pain) and for elective surgery, before and since the introduction of the new advances in therapy. These admission indices reflect disease prevalence and severity. PATIENTS AND METHODS: We identified admission rates during 1972--2000 within the Trent Regional Health Authority, UK (population 4.7 million), from computerised patient information using diagnostic search codes ICD8-10 and expressed as rates per million resident population. Drug expenditure details were obtained from the Department of Health. RESULTS: Emergency admission rates as a whole changed little, a decline in the young being offset by an increase in the elderly. Haemorrhage was the most common reason (approximately 115 per million for duodenal ulcer and 87 for gastric ulcer) throughout [compared with perforation (80 and 21) and pain (90 and 68)]. In contrast, elective surgery has almost disappeared; this reduction began before the introduction of modern treatment. CONCLUSION: Emergency admission rates for duodenal and gastric ulcer for complications or severe pain have fluctuated over the last three decades but with little overall change. In contrast, elective surgery has declined dramatically, as a result of advances in treatment but also from changes in the natural history.

Adult↗

PubMed2003

Oesophageal acid-peptic strictures in the histamine H2 receptor antagonist and proton pump inhibitor era.

BACKGROUND AND AIM: We present a survey on the incidence, demography and natural history (re-dilatation rates) of patients with oesophageal acid-peptic stricture seen between 1977 and 1995. PATIENTS AND METHODS: Prospective, cohort observational study. Stricture severity was graded mild, moderate or severe (needing forcible dilatation with bougies). Most were treated with histamine H2 receptor antagonists or proton pump inhibitors, and were followed up by serial check endoscopy. RESULTS: A total of 156 of 7429 (2%) reflux patients had stricture: mild, n=56; moderate, n=25; severe, n=75. The prevalence of reflux disease is rising, paralleled by an increase in the number of patients with stricture; hence the incidence of stricture is unchanged: 1977-1982, 1.8% (18/986); 1983-1989, 2.4% (61/2595); 1990-1995, 2% (77/3848). Demography: mean age 68 years; mean length of reflux history 6.4 years; 15% on non-steroidal anti-inflammatory drugs/aspirin; 18% with Barrett's metaplasia. Mean follow-up: 5.6 years. OUTCOME: of the 75 with severe stricture, 36 (48%) needed forcible dilatation only once, and 39 more often (13 twice, nine three times), most within 2 years. Only six of these patients need > or = 6 re-dilatations. CONCLUSION: The incidence of stricture is low and remains unchanged, despite the increased prevalence of reflux disease. Most patients have a good prognosis, only half needing further forcible dilatation, mainly within the first 2 years.

Adult↗

PubMed2003

History in our lifetime: the changing nature of refractory duodenal ulcer in the era of histamine H2 receptor antagonists.

BACKGROUND AND AIM: This prospective cohort observational study, set in a district hospital, presents our experience (1976-1993) of duodenal ulcer refractory to histamine H2 receptor antagonists (defined as not healed after 3 months' treatment) and comments on onset, outcome and spontaneous decline. METHODS: Patients were treated mainly with cimetidine, the dose being titrated (up to 3.2 g daily) according to response, and followed by serial check endoscopy and clinical assessment. RESULTS: A total of 782 of the 4032 duodenal ulcer patients seen (19%) were refractory; the incidence declined over time: 1976-1978: 124/379 (33%); 1979-1983: 390/1240 (31%); 1984-1988: 190/1295 (15%); 1989-1993: 78/1118 (7%). A total of 344 were refractory for the first time on their first healing course and 174 on their second. Healing was achieved in two-thirds after a mean of 7 months' treatment with cimetidine 1 g; treatment for 12-18 months with higher doses was needed in the remainder. Relapse occurred in up to three-quarters of patients despite maintenance cimetidine up to 3 g daily. Eventually 47 patients were operated upon but good results (i.e., no ulcer, no symptoms) were achieved in only 11. CONCLUSION: Refractoriness was common until recently. Its incidence has declined dramatically, the fall preceding the newer more powerful treatment with proton pump inhibitors and with Helicobacter pylori eradication. We suggest this phenomenon is a modern example of a spontaneous change in the natural history of the disease.

Adult↗

PubMed2003

A randomized, double-blind trial of the efficacy and safety of 10 or 20 mg rabeprazole compared with 20 mg omeprazole in the maintenance of gastro-oesophageal reflux disease over 5 years.

BACKGROUND: Gastro-oesophageal reflux disease has a chronic course, and often requires long-term treatment. Proton pump inhibitors are the treatment of choice for both acute and maintenance treatment, but little is known from randomized controlled trials of their effects beyond 1 year. AIM: To compare the efficacy and safety of two doses of rabeprazole with 20 mg omeprazole in the maintenance treatment of erosive gastro-oesophageal reflux disease over 5 years. METHODS: Two hundred and forty-three patients who had previously responded to acute treatment for erosive gastro-oesophageal reflux disease were prospectively randomized to receive 5 years of treatment with rabeprazole (10 or 20 mg daily) or omeprazole (20 mg daily). The primary outcome measure was endoscopically confirmed relapse of erosive gastro-oesophageal reflux disease. RESULTS: One hundred and twenty-three patients (51%) completed all 5 years of the study, with similar completion rates in the three groups. Relapses occurred in nine of 78 (11.5%), eight of 82 (9.8%) and 11 of 83 (13.3%) patients in the rabeprazole 20 mg, rabeprazole 10 mg and omeprazole 20 mg groups, respectively. Gastric biopsy showed no evidence of any harmful effects. All treatments were well tolerated. CONCLUSIONS: Rabeprazole 10 mg, rabeprazole 20 mg and omeprazole 20 mg all had similar efficacy in the maintenance treatment of gastro-oesophageal reflux disease. All three were safe and well tolerated during 5 years of treatment.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2003

Effects of aspirin and indomethacin on endothelial cell proliferation in vitro.

BACKGROUND AND AIM: Non-steroidal anti-inflammatory drugs (NSAID) are associated with delayed peptic ulcer healing. Ulcer healing is dependent on angiogenesis, which requires endothelial cell (EC) proliferation. The present study aimed to determine whether NSAID and prostaglandin E2 (PGE2) inhibited EC proliferation in vitro. METHODS: Effects of 50 micro L aspirin (10 micro M-1 mM), indomethacin (10 micro M-1 mM) and PGE2 (1 micro M-0.1 mM) on the proliferation, viability and cell cycle of human dermal microvascular (HuDMEC) and human umbilical vein (HUVEC) EC were assessed using dual staining cell viability, 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide and flow cytometry assays. RESULTS: Proliferation of HuDMEC and HUVEC was significantly inhibited by 0.1 mM/1 mM indomethacin, 1 mM aspirin and 100 micro M PGE2, with a significant (P < 0.05) increase in EC necrosis with 1 mM indomethacin and 100 micro M PGE2. No effects on cell cycle were demonstrated. CONCLUSIONS: High concentrations of NSAID inhibit both HuDMEC and HUVEC proliferation in vitro by cytotoxic (indomethacin) or cytostatic (aspirin and indomethacin) mechanisms. Interestingly, PGE2 was also antiproliferative. Inhibition of EC proliferation may prevent angiogenesis at the ulcer site, which may in part explain the delayed ulcer healing associated with NSAID.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2003

Low frequency electrical bioimpedance for the detection of inflammation and dysplasia in Barrett's oesophagus.

Biological tissues undergoing inflammation and dysplasia seem to exhibit changes in the intercellular space that can be sensed using low frequency electrical impedance methods. Basically, low frequency electric current flows through this space and its widening as well as the disruption of the tight junction decrease the resistance, facilitating current flow. The electrical changes accompanying structural changes from columnar tissue to adenocarcinoma in Barrett's metaplastic mucosa and gastric tissue are illustrated using resected tissue from 32 patients. Two hundred and fifty-eight biopsies were analysed, correlating their electrical resistivity (R) at 9.6 kHz and their histopathological interpretation. Compared to non-inflamed non-dysplastic columnar tissue (R = 4.9 ohms m), the results suggest a small but statistically significant decrease of electrical impedance in columnar tissue showing inflammation (R = 4.2 ohms m, p = 0.016) and a larger decrease when dysplasia is present (R = 3.4 ohms m, p = 0.040). If this method is validated further, this technique could be used to obtain guided biopsies from patients undergoing surveillance programmes for Barrett's oesophagus. We aim to refine this technique using a new system with lower frequencies and, possibly, in vitro (cultured cells) and in vivo (rats) models of Barrett's oesophagus.

Adenocarcinoma↗

PubMed2002

Percutaneous endoscopic gastrostomy: a prospective audit of the impact of guidelines in two district general hospitals in the United Kingdom.

OBJECTIVE: Percutaneous endoscopic gastrostomy (PEG) is the accepted method for long-term enteral nutrition. Recent studies have suggested a higher mortality than was initially reported. The demands for gastrostomy insertion have risen, encompassing indications where the long-term outcomes are uncertain. We, therefore, constructed guidelines to try and improve the appropriateness of patient selection. Our aim was to prospectively assess the impact of guidelines for PEG insertion over a 1-yr period in a single center, Rotherham District General Hospital (hospital A) and compare against an adjacent center serving a similar population, Doncaster Royal Infirmary (hospital B) where guidelines had not been instituted. METHODS: Data were collected from June, 1998 to May, 1999. Indication for PEG was documented and survival analysis performed using the Kaplan-Meier survival method. RESULTS: The number of PEG insertions had been rising each year in both centers. After guidelines were introduced in hospital A, the number of procedures fell by 20, whereas in hospital B, the PEG insertion rate continued to rise (p = 0.02). There was a lower mortality observed in hospital A (at 1 month, 16%; at 3 months, 26%; at 6 months, 39%; and at 1 yr, 46%) than in hospital B (at 1 month, 26%; at 3 months, 44%; at 6 months, 58%; and at I yr, 68%), although this did not achieve statistical significance (log rank test, p = 0.1). CONCLUSIONS: This is the first study to prospectively assess the impact of guidelines and a proactive role in the decision for PEG insertion. Fewer procedures were performed, and there was a trend toward a reduction in mortality.

Adult↗

PubMed2002

Toxigenic Helicobacter pylori induces changes in the gastric mucosal microcirculation in rats.

BACKGROUND AND AIMS: One of the key components of inflammation is changes in vascular structure and function. This suggests that the microcirculation may be a key target of Helicobacter pylori released factors. It has previously been shown in vivo that pooled H pylori extracts from duodenal ulcer/gastritis patients induce platelet aggregation but no leucocyte activation within rat gastric mucosal microcirculation (GMMC). However, infection with strains associated with ulcer disease as compared with gastritis may exert greater effects on the microcirculation. This study used fluorescent in vivo microscopy to determine the acute effects of extracts of genotypically different H pylori strains on the GMMC. METHODS: Three H pylori extracts, with different cagA and VacA toxigenic status, were individually administered to the gastric mucosa of anaesthetised Wistar rats. The mucosal surface was visualised via an incision made in the exteriorised stomach. Fluoroscein isothiocyanate conjugated to bovine serum albumin (FITC-BSA) or acridine orange was used to quantify macromolecular leak (MML) and leucocyte/platelet activity respectively for 120 minutes. Changes in capillary and post-capillary venule (PCV) diameters were also monitored. RESULTS: The cagA(+) VacA toxigenic strain 60190 induced significant and sustained MML by five minutes (p<0.01). Transient and less leakage was observed with its isogenic VacA(-) mutant and other non-toxigenic strains regardless of cagA status. Significant increases in leucocyte adhesion (p<0.05), platelet aggregation (p<0.05), and PCV vasoconstriction (p<0.05) were only observed with the cag A(+) and toxigenic strain. CONCLUSION: Extracts of H pylori are capable of inducing marked disturbances within the rat GMMC. These disturbances seem to be dependent on the production of an active vacuolating cytotoxin. Varying effects on the GMMC may explain the clinically diverse outcomes associated with genotypically different strains.

Animals↗