Biomedical subjects
J C Mansfield
Publications and source records attributed to J C Mansfield.
Management of irritable bowel syndrome.
The diagnosis of irritable bowel syndrome (IBS) is made on clinical grounds with appropriate limited investigations to exclude organic disease. IBS is common and may have a significant impact on a patient's quality of life. Psychological symptoms are common. IBS may benefit from pharmacological and non-pharmacological management. Specific measures should be directed towards the dominant symptoms of constipation or diarrhoea. Several new drugs are currently under evaluation and may prove valuable for subgroups of patients with IBS. Successful management requires a combination of reassurance and explanation about the natural history of the condition.
A double-blind comparison of balsalazide, 6.75 g daily, and sulfasalazine, 3 g daily, in patients with newly diagnosed or relapsed active ulcerative colitis.
BACKGROUND: Sulfasalazine is well established in the treatment of active ulcerative colitis. Intolerance to sulfasalazine, however, is a common problem. Balsalazide has been designed to deliver 5-aminosalicylic acid to the colon without the poor tolerability of sulfasalazine. AIM: To compare the safety and efficacy of balsalazide, 6.75 g daily, with sulfasalazine, 3 g daily, in the treatment of active ulcerative colitis of all grades of severity. METHODS: Balsalazide and sulfasalazine were compared in a multicentre, double-blind, parallel group study over 12 weeks. Patients were stratified for disease severity and topical and/or oral steroids were co-administered where clinically necessary. RESULTS: Fifty-seven patients were randomized: 28 to receive balsalazide and 29 to receive sulfasalazine. Significantly fewer patients withdrew from the balsalazide group due to adverse events (2/28 vs. 9/29, P=0.041). These data confirm that balsalazide is better tolerated than sulfasalazine. In patients able to tolerate the treatment, similar improvements were recorded in clinical, sigmoidoscopic and histological assessments in both treatment groups. CONCLUSIONS: This study confirms the better tolerability of balsalazide compared to sulfasalazine, and supports the use of balsalazide in ulcerative colitis of all grades of severity.
A double-blind comparison of balsalazide, 6.75 g, and sulfasalazine, 3 g, as sole therapy in the management of ulcerative colitis.
BACKGROUND: Sulfasalazine is accepted therapy for active ulcerative colitis, but side-effects and intolerance are common. Balsalazide is an azo-bonded pro-drug which also releases 5-aminosalicylic acid into the colon, but uses an inert carrier molecule. AIM: To compare the safety and efficacy of sul- fasalazine, 3 g, with balsalazide, 6.75 g, in the initial daily treatment of mild to moderate ulcerative colitis. METHODS: A randomized, multicentre, double-blind, parallel group study was performed, with a treatment duration of 8 weeks. Patients on previous maintenance treatment were excluded. The trial medication was the sole treatment for the colitis. Efficacy was assessed by patient diaries, symptom assessment, sigmoidoscopic appearance and histology. RESULTS: Fifty patients were recruited: 26 allocated to the balsalazide group and 24 to the sulfasalazine group. More patients withdrew due to adverse events in the sulfasalazine group (nine patients vs. one patient in the balsalazide group, P=0.004). Improvement occurred in both groups, with a tendency to a faster response with balsalazide. Of the patients taking balsalazide, 61% achieved clinical and sigmoidoscopic remission. CONCLUSIONS: Balsalazide, 6.75 g, is effective as the sole treatment for patients with mild to moderately active ulcerative colitis, with significantly fewer withdrawals due to side-effects than in a similar group of patients taking sulfasalazine, 3 g.
Role of polymorphisms in the interleukin-10 gene in determining disease susceptibility and phenotype in inflamatory bowel disease.
Interleukin-10 (IL-10) has a key role in regulating mucosal inflammation. The role of functional polymorphisms at positions -627 and -1117 in the IL-10 gene as candidate susceptibility loci in inflammatory bowel disease and their importance in determining disease extent were evaluated in 159 patients with ulcerative colitis (83 left-sided; 76 extensive), 90 patients with Crohn's disease (22 small bowel; 29 large bowel; 39 both), and 227 controls. Genotyping was performed either by PCR-RFLP assays (-627 site) or SSCP analysis (-1117 site). An excess of -627A allele was observed in patients with left-sided colitis (52%) compared with controls (33%; P = 0.004) suggesting that IL-10 may influence the extent of the disease. These results were not replicated in a newly recruited group (N = 100) of patients with UC. We conclude that polymorphisms at -627 and -1117 sites in the IL-10 gene do not contribute to the susceptibility to IBD or determining the extent of the disease in our population.
The CC chemokine receptor 5 delta32 mutation is not associated with inflammatory bowel disease (IBD) in NE England.
Inflammatory bowel disease (IBD) is a group of chronic inflammatory diseases of the gastrointestinal tract of unknown aetiology. Evidence of abnormalities in immune regulation and cytokine production in patients with IBD has led to investigations of various immuno-regulatory genes as potential candidate susceptibility loci. Studies using whole genome scanning have highlighted chromosomes 3, 7, 12 and 16. A 32 base-pair deletion in the CC-chemokine receptor-5 gene (CCR5-A32, chromosome 3p21.3) has been associated with susceptibility to IBD. We have investigated CCR5 as a candidate susceptibility gene in 350 patients (251 with ulcerative colitis and 99 with Crohn's disease) and 103 controls using polymerase chain reaction. There were no significant differences in the distribution of CCR5 genotypes or frequencies comparing patients and controls, or associations with extent of colitis. In contrast to preliminary data, these findings suggest no evidence for involvement of this mutation in susceptibility/resistance or disease progression in IBD.
Review article: the risk of lymphoma associated with inflammatory bowel disease and immunosuppressive treatment.
Lymphoma complicating inflammatory bowel disease is well described. Whether the risk of lymphoma is increased by immunosuppressive treatment with azathioprine, 6-mercaptopurine or infliximab is a common concern among patients and physicians considering using these agents. This review aims to quantify the lymphoma risk in inflammatory bowel disease and the added risk attributable to these treatments. The evidence from published cases is that lymphomas occur at sites of active inflammatory bowel disease more often than expected for this to be a chance association. Studies on inflammatory bowel disease populations are conflicting, with some follow-up studies from large inflammatory bowel disease clinics showing an increase in lymphoma incidence, while other population-based studies show little or no increase in risk of lymphoma. A small increase in lymphoma risk in inflammatory bowel disease, perhaps 2-3-fold, may be compatible with both sets of data. Studies of the risks associated with immuno- suppression are less satisfactory, with smaller numbers of patients and relatively short follow-up. The available evidence would support a further increase in lymphoma risk associated with immunosuppressive treatment in inflammatory bowel disease of around fivefold compared to no immunosuppressive use, and tenfold compared to the general population. The risks appear to be less than that associated with renal and hepatic transplant-related immunosuppression. Infliximab treatment is still too new to make a full assessment of its long-term safety, but post-marketing surveillance currently suggests that lymphoma risk may not be any greater than that associated with azathioprine and 6-mercaptopurine. Population-wide surveillance for lymphoma in inflammatory bowel disease would be required to narrow the confidence intervals on these estimates of lymphoma risk in inflammatory bowel disease and immunosuppressive treatment.
Difficulties in diagnosis and treatment of spinal tuberculosis.
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A prospective evaluation of cytology from biliary strictures.
BACKGROUND: Bile duct strictures may be benign or malignant. A definite diagnosis is desirable to advise patients of their prognosis and to identify any amenable to curative surgery. AIMS: To compare different methods of cytology sampling from biliary strictures and evaluate the use of cytology in this context. PATIENTS AND METHODS: In a prospective study 54 patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) had cytology samples obtained as follows: (1) biliary stricture brushings, (2) from the screw thread of a "Soehendra stent retriever" inserted through the stricture, (3) from the proximal end of a blocked biliary stent, and (4) cellular material spun down from a 20 ml specimen of bile. Examination of slides and rinsings was performed by an expert cytologist who graded them for the adequacy of the sample and for evidence of malignancy. RESULTS: Prolonged follow up disclosed malignancy in 52 of the 54 cases, the other two being chronic pancreatitis. Bile samples provided adequate cytology samples in 44%, the Soehendra stent retriever in 70%, retrieved stents in 84%, and cytology brush sampling in 96%. Overall, 28 malignancies were detected by cytology, including 14 of 28 pancreatic carcinomas and 12 of 16 cholangiocarcinomas. Twenty two of the malignancies were detected by brush sampling and the other methods added a total of another six cases. CONCLUSIONS: Cytology sampling is best done by brushing the biliary stricture. Cytology sampling can confirm the diagnosis in 75% of cholangiocarcinomas and 50% of pancreatic carcinomas. The techniques involved are simple to perform and should be routine clinical practice whenever potentially malignant biliary strictures are encountered at ERCP.
Open access gastroscopy findings are unrelated to the use of aspirin and non-steroidal anti-inflammatory drugs.
This study aims to determine whether priority should be given to patients taking non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin when selecting which dyspeptic patients to refer for open access gastroscopy. A total of 8156 patients underwent gastroscopy, all of whom had upper gastrointestinal symptoms. Patients taking NSAIDs or aspirin showed no significant differences in the frequency of ulcer disease when age-matched groups were compared. Although NSAIDs and aspirin are frequently implicated in gastrointestinal bleeding in the elderly, patients referred for investigation of dyspepsia show no increase in major endoscopic pathology.
Percutaneous endoscopic trigonoplasty: a minimally invasive approach to correct vesicoureteral reflux.
PURPOSE: A procedure was designed to correct vesicoureteral reflux with minimally invasive technology. MATERIALS AND METHODS: A total of 22 children 14 months to 18 years old underwent percutaneous endoscopic trigonoplasty between January and June 1995. Followup ranges from 4 to 11 months. In 32 ureters reflux was grade 2 in 13, grade 3 in 13, grade 4 in 5 and grade 5 in 1. RESULTS: All patients had normal sonography of the kidneys after surgery. On followup voiding cystourethrography at 2 or 6 months there was resolution of reflux in 20 of the 32 ureters (62.5%). The probability of resolution was unrelated to patient age, laterality of reflux, initial grade, operative sequence or preoperative bladder instability. The 3 major complications were vesicovaginal fistula, hyponatremia and perivesical fluid collection. CONCLUSIONS: Percutaneous endoscopic trigonoplasty is technically feasible but it involves a distinct learning curve. It offers significant advantages related to more rapid recovery with less discomfort. The success rate is modest at present. If it were to be improved with technical modifications, percutaneous endoscopic trigonoplasty may change the basic approach to treating children with vesicoureteral reflux.
Controlled trial of oligopeptide versus amino acid diet in treatment of active Crohn's disease.
Elemental diets are effective in inducing remission in active Crohn's disease, but how they exert this therapeutic effect is unclear. In a previous study a whole protein containing diet proved less effective than one in which food antigens were excluded, suggesting that exclusion of food antigens from the gut was a possible mechanism. This study was designed to test whether an oligopeptide diet of hydrolysed proteins was as effective as an amino acid based diet. These diets were equally antigen free but with different nitrogen sources. Forty four patients with active Crohn's disease were randomised in a controlled trial of amino acid versus oligopeptide diet. The feeds were given by nasogastric tube in equicaloric quantities and were the sole form of nutrition. Treatment was continued for four weeks although failure to improve by day 10 resulted in withdrawal. Quantitative leucocyte scintigraphy was used to investigate the effect of diet treatment on gut inflammation. Clinical and nutritional responses to treatment were also measured. Sixteen patients entered remission (including withdrawal of corticosteroids), six patients could not tolerate the nasogastric tube, and 22 patients failed to respond. The two diets were equally effective. Patients who responded had a rapid drop in clinical index of disease activity and a major reduction in the bowel uptake of leucocytes on scintigraphy. The oligopeptide and amino acid based enteral feeds were equally effective at inducing remission in active Crohn's disease. With both diets clinical improvement was accompanied by a reduction in intestinal inflammation.
Quantitative assessment of overall inflammatory bowel disease activity using labelled leucocytes: a direct comparison between indium-111 and technetium-99m HMPAO methods.
The ideal imaging method in inflammatory bowel disease would reliably detect inflammation, identify the correct intestinal location, and assess the severity of the disease. The aim of this study was to compare scintigraphic methods of quantifying overall disease activity using both indium-111 (111In) and technetium-99M (99mTc) HMPAO labelled leucocyte scans. The four day faecal excretion of 111In was measured after 111In scintigraphy in 24 patients known to have inflammatory bowel disease. The same patients also underwent 99mTc HMPAO scanning. The scans were performed 10 days or less apart with no changes in treatment between scans. Bowel activity on the 99mTc HMPAO scans was assessed using a computer based method (scan score) and a visual grading method in a further 54 99mTc HMPAO. The results showed a close correlation between inflammatory activity defined by faecal 111In excretion and the scan score generated from the computer analysis of the 99mTc HMPAO image (Spearman rank correlation: rs = 0.78; p < 0.001). Accurate information to localise inflammatory activity could be obtained by simple visual assessment of both types of scan images, although image quality was superior with 99mTc HMPAO. Qualification of disease activity from 99mTc HMPAO images by visual grading was associated with a large variability, only 69% of scans had similar scores when graded by three observers. Computer generated image analysis was more reproducible. In conclusion, in inflammatory bowel disease 99mTc HMPAO scintigraphy and faecal 111In excretion correlated well. Either method can quantify and localise the inflammation. As 99mTc HMPAO scanning provides a quicker result, with a lower radiation dose, and avoids faecal collection, it may be the preferred method.
Novel genetic association between ulcerative colitis and the anti-inflammatory cytokine interleukin-1 receptor antagonist.
BACKGROUND/AIMS: Ulcerative colitis and Crohn's disease have well-recognized familial tendencies, but the genetic basis of this clinical observation remains unknown. The cytokine interleukin-1 receptor antagonist is a potent anti-inflammatory protein that can prevent immune-mediated bowel inflammation in animals. We have previously characterized a polymorphism within the gene for this cytokine and others in the genes for the proinflammatory cytokines interleukin 1 alpha, interleukin 1 beta, and tumor necrosis factor alpha. The aim of this study was to determine whether inflammatory bowel disease was associated with particular alleles of these polymorphic cytokine genes. METHODS: The allelic frequencies of these polymorphic cytokine genes were determined in patients with ulcerative colitis (n = 113), Crohn's disease (n = 78), and healthy controls (n = 261). RESULTS: Allele 2 of interleukin-1 receptor antagonist was significantly over-represented in the ulcerative colitis patients: 35% versus 24% in controls (P = 0.007). Carriage of at least one copy of this allele gave an odds ratio of 2.0 for ulcerative colitis compared with controls. This association with allele 2 of interleukin 1 receptor antagonist was greatest in patients with total colitis and was not seen in Crohn's disease. There were no associations between UC and any of the other cytokine genes examined. CONCLUSIONS: This observation provides evidence that interleukin-1 receptor antagonist may have a role in determining the genetic susceptibility to and pathogenesis of ulcerative colitis.
Combined percutaneous and endoscopic procedures for bile duct obstruction: simultaneous and delayed techniques compared.
BACKGROUND/AIMS: In patients with obstructive jaundice, when the endoscopic approach fails to achieve biliary drainage, percutaneous cannulation and combined endoscopic/percutaneous endoprosthesis insertion can be performed simultaneously or in stages. This study compared these two approaches. METHODOLOGY: Over a three-year period 41 patients were studied. All had obstructive jaundice for which endoscopic drainage had failed. In 22 patients (group 1) percutaneous transhepatic drainage was followed a few days later by combined endoscopic and percutaneous procedure. In 19 patients (group 2) the percutaneous transhepatic drainage and combined drainage were performed at the same session. In the multiple stage group the mean interval between the first endoscopic retrograde cholangiopancreatography and final combined procedure was 9 days (SD 5.2). The groups were similar for sex, underlying pathology and reasons for failure of endoscopic approach. Group 1 patients were older 73 vs. 65 years (p < 0.05). RESULTS: Patients in group 2 had a more rapid recovery and discharge home: mean 6 days, compared to mean 18 days from the initial procedure for group 1 (p < 0.001). Five patients died of their disease without leaving hospital (4 in group 1, 1 in group 2). In each group drainage failed in 1 patient. Complications were more common in group 1: 73% vs. 37% (p < 0.05). Pancreatitis (3 vs. 2) and septicemia (4 in group 1, 3 in group 2) were similar but group 1 had complications from the external drain: cholangitis and pyrexia in 4 patients, 3 bile leaks, and 1 catheter displacement. CONCLUSIONS: When endoscopic drainage alone fails, a combined percutaneous/endoscopic procedure should only be performed if it can be carried out simultaneously.
Information for patients about inflammatory bowel disease.
In inflammatory bowel disease it is important that patients understand their condition since this helps to improve long-term management of the disease. The aim of this study was to assess the information given to patients with inflammatory bowel disease about their condition, its treatment and the National Association for Colitis and Crohn's disease. Two surveys were performed, using anonymous questionnaires. One was of all association members in north-east England, the other was a sample of patients attending medical outpatients. The surveys showed that more patients heard of the National Association for Colitis and Crohn's disease from the media than from medical sources. Of patients seen in medical clinics, 75% would welcome more information about their disease. In four of the six participating centres less than half the patients had been told about the existence of a patients' association. There was considerable variation in the instructions on what action to take in the event of a relapse. These findings suggest that the opportunity offered by out-patient clinics to educate and inform patients is often wasted. Clinicians often neglect to mention the National Association for Colitis and Crohn's disease, especially to patients with long-standing disease. A higher priority should be given to providing patients with appropriate information on inflammatory bowel disease. Three simple audit standards for the organisation of outpatient clinic information are proposed.