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Biomedical subjects

M R Welfare

Publications and source records attributed to M R Welfare.

16 recordsLinked to original sources

Postinfectious irritable bowel syndrome may occur after non-gastrointestinal and intestinal infection.

Postinfectious functional gastrointestinal disorders (FGIDs) may not be specific to gastroenteritis. This pilot study aimed to ascertain the 3- and 6-month incidence of functional gut disorders in people with non-gastrointestinal (GI) infection, gastroenteritis and healthy controls. This was a prospective study of three cohorts recruited from hospital (non-GI infections) and the community (others). FGIDs were diagnosed using self-completed Rome II modular questionnaires administered at baseline, 3 and 6 months. Thirty-six subjects with non-GI infection, 219 healthy subjects and 108 with bacterial gastroenteritis participated. No difference in incidence of FGID was detected between the GI and non-GI infection cohorts. Any FGID was more frequent in people who had a non-GI infection than in controls at both 3 [odds ratio: 4.34 (95% CI: 3.60-16.45)] and 6 months [4.76 (4.42-27.92)]. Irritable bowel syndrome (IBS) alone was more frequent in people with non-GI infections than in controls at 3 months (6.12 [1.30-29.12]) but did not quite reach statistical significance at 6 months (4.58 [0.79-26.46]). Our findings were unexpected. Postinfectious FGIDs may be related to non-GI and GI infection, although not all potential biases were controlled in study design. Further studies need to explore these preliminary findings and, if confirmed, the underlying mechanisms.

Adolescent↗

A comparison of the discriminatory power of the Inflammatory Bowel Disease Questionnaire and the SF-36 in people with ulcerative colitis.

The aim of this study was to compare the discriminatory power of a generic and a condition-specific quality of life measure (the Medical Outcomes Study Short-Form 36 (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ)) with respect to sub-groups defined by disease-related and other factors, in a sample of patients with ulcerative colitis. Disease activity was generally more highly correlated with IBDQ scores than with SF-36 scores. The only significant differences with respect to disease extent were in the SF-36 energy/vitality and social function domains. Age was negatively and weakly to moderately correlated with the physical domains of the SF-36 but positively though weakly correlated with scores on the IBDQ emotional domain and those domains of the SF-36 related to mental well-being. Co-existing chronic illness, even on controlling for age, was associated with significantly poorer scores on the generic measure, but had little influence on IBDQ scores. In conclusion, generic and disease-specific measures of quality of life appear to be complementary rather than interchangeable. We recommend the use of both types of measure in parallel.

Adult↗

Influence of dietary factors on the clinical course of ulcerative colitis: a prospective cohort study.

BACKGROUND AND AIMS: The causes of relapses of ulcerative colitis (UC) are unknown. Dietary factors have been implicated in the pathogenesis of UC. The aim of this study was to determine which dietary factors are associated with an increased risk of relapse of UC. METHODS: A prospective cohort study was performed with UC patients in remission, recruited from two district general hospitals, who were followed for one year to determine the effect of habitual diet on relapse. Relapse was defined using a validated disease activity index. Nutrient intake was assessed using a food frequency questionnaire and categorised into tertiles. Adjusted odds ratios for relapse were determined using multivariate logistic regression, controlling for non-dietary factors. RESULTS: A total of 191 patients were recruited and 96% completed the study. Fifty two per cent of patients relapsed. Consumption of meat (odds ratio (OR) 3.2 (95% confidence intervals (CI) 1.3-7.8)), particularly red and processed meat (OR 5.19 (95% CI 2.1-12.9)), protein (OR 3.00 (95% CI 1.25-7.19)), and alcohol (OR 2.71 (95% CI 1.1-6.67)) in the top tertile of intake increased the likelihood of relapse compared with the bottom tertile of intake. High sulphur (OR 2.76 (95% CI 1.19-6.4)) or sulphate (OR 2.6 (95% CI 1.08-6.3)) intakes were also associated with relapse and may offer an explanation for the observed increased likelihood of relapse. CONCLUSIONS: Potentially modifiable dietary factors, such as a high meat or alcoholic beverage intake, have been identified that are associated with an increased likelihood of relapse for UC patients. Further studies are needed to determine if it is the sulphur compounds within these foods that mediates the likelihood of relapse and if reducing their intake would reduce relapse frequency.

Adult↗

Defining relapse of ulcerative colitis using a symptom-based activity index.

BACKGROUND: Several tools exist to assess disease activity in patients with ulcerative colitis (UC), but a definition of relapse does not exist. The aim of the study was to determine the score in the Simple Clinical Colitis Activity Index (SCCAI) that defined relapse. The reliability and validity of the SCCAI when self-administered was also examined. METHODS: Patients with UC routinely attending hospital completed the SCCAI questionnaire, which was later administered by their clinician blinded to the scoring process. In the absence of a gold standard definition of relapse, a subjective global assessment of disease status was made by the clinician. The SCCAI was evaluated in a separate cohort of patients. RESULTS: Seventy-one presentations were analysed; mean age 48 years, 49% male, 37% relapse rate. The mean patient score was 4.2 (range 0-14) and mean physician score 3.8 (0-14). A score of 5 or more defined relapse with 92% sensitivity, 93% specificity, 88% positive predictive value and 95% negative predictive value. The difference between the scores obtained by the patient and clinician (0.35, 95% CI 0.09-0.62) was small. Correlation with a more complex symptom and laboratory-based activity index was very high (r = 0.79, P < 0.01). The index was quick to use and comparative results for sensitivity and specificity were recorded in the second cohort of patients. CONCLUSIONS: The SCCAI is a simple tool that can be accurately and quickly self-administered, correlates well with a more complex disease activity index, and can be used to define relapse of UC with high specificity and sensitivity.

Colitis, Ulcerative↗

Esophageal mucin: an adherent mucus gel barrier is absent in the normal esophagus but present in columnar-lined Barrett's esophagus.

OBJECTIVES: The presence of a protective adherent mucus gel barrier against gastric reflux in the healthy esophagus is uncertain. The aim was to characterize the surface mucin composition and determine the extent of any adherent mucus gel layer on the normal esophagus, and compare this with that in Barrett's esophagus. METHODS: Isolated surface mucins were characterized by density centrifugation, gel filtration chromatography, and chemical composition. Adherent surface mucus was visualized in situ on unfixed and cryostat sections of mucosa and biopsies using a method that preserves mucus layer thickness. RESULTS: There was a complete absence of adherent mucus gel layers on normal human, pig, and rat esophagi. This was in contrast to the thick adherent mucous layer (median thickness = 100-200 microm) seen on the corresponding gastric mucosa. Small quantities of glycoprotein with a composition characteristic of a secretory mucin were isolated from the pig esophagus surface. The mucin, density range between 1.44 and 1.48 g x ml(-1), contained 80% carbohydrate and was rich in serine, threonine, and proline. The mucin fragmented into smaller glycoprotein units on proteolysis and partially on reduction. Cryostat sections from columnar-lined esophageal biopsies had a substantial adherent surface mucous layer (median thickness = 90 microm, interquartile range = 84-94 microm) staining for neutral mucins (gastric-type epithelium) and acidic mucins (intestinal metaplasia). CONCLUSIONS: A secretory mucin, with an analysis distinct from that of gastric or salivary mucin, is present in very small quantities on the esophageal mucosa and in amounts insufficient to form an adherent gel layer. It is unlikely that mucus has a role in protecting the normal esophagus against reflux. However, an adherent mucous layer was observed over columnar-lined esophagus, and this may protect against reflux.

Animals↗

The short inflammatory bowel disease questionnaire is reliable and responsive to clinically important change in ulcerative colitis.

OBJECTIVE: The Short Inflammatory Bowel Disease Questionnaire (SIBDQ) is a health-related quality of life (HRQoL) tool measuring physical, social, and emotional status (score 10-70, poor to good HRQoL). The SIBDQ has been predominantly used in trials for Crohn's disease, and further validation of the SIBDQ is desirable in ulcerative colitis (UC) patients. The primary objective was to further validate the SIBDQ by examining discriminant ability against measures of disease activity. The secondary objectives were to examine reliability and responsiveness to change. METHODS: UC patients attending hospital completed the SIBDQ and two activity indices. Patients' disease status (remission, mild, moderate, or severe relapse) was determined subjectively by the patients and their physician. RESULTS: Scores were obtained for 69 events in 61 patients. mean age 47.8 yr (range 16-79). All classes of disease extent were represented. The mean SIBDQ score was 48.4 (13-70). The difference between mean score in patients in remission and relapse was -20.1 (95% CI = -25.1 to -15.1). The difference for remission and mild relapse was -14.6 (95% CI = -8.9 to -20.2). The correlation between SIBDQ and the activity indices were good, r = -0.83 and r = -0.61. Eight patients presented twice. Those with unchanged disease status showed no significant difference in the mean SIBDQ score. Patients whose disease status had deteriorated from remission to mild relapse, or from mild to moderate relapse demonstrated a mean reduction of 11.8 points (95% CI = 20.1-3.4). CONCLUSIONS: This study contributes to the validation of the SIBDQ as a HRQoL tool in UC. It is reproducible and responsive to changes in disease activity.

Adolescent↗

The effect of NAT2 genotype and gender on the metabolism of caffeine in nonsmoking subjects.

AIMS: To establish whether gender or N-acetyltransferase 2 (NAT2) genotype influence the urinary 17 U+17X/137X ratio after dosing with caffeine. METHODS: Ninety-two nonsmoking individuals underwent caffeine phenotyping. NAT2 genotype was determined by the polymerase chain reaction followed by a restriction digest (PCR-RFLP). RESULTS: The median ratio for urinary 17 U+17X/137X was 6.7 (range 1.45-18. 65). 55% of subjects were slow acetylators. Gender did not affect the metabolic ratio or NAT2 genotype. Mean 17 U+17X/137X ratio differed between fast (6.75) and slow (8.69) acetylators (95% CI for the difference, 0.32-3.56). CONCLUSIONS: The findings are further evidence that the 17 U+17X/137X urinary ratio is not a robust measure of CYP1A2 activity. A possible mechanism by which the ratio might be influenced by NAT2 genotype is suggested.

Adolescent↗

Experiences of volunteer patients during undergraduate examinations: printed information can lead to greater satisfaction.

BACKGROUND: Whilst most patients are happy to participate in medical examinations, previous studies have shown that some are dissatisfied with the information that they receive beforehand. OBJECTIVES: To demonstrate that patient satisfaction can be improved by the provision of written information. METHODS: Thirty-seven patients attending the final MBBS examination were sent written information about what to expect. The patients' experiences were assessed by means of an anonymous postal questionnaire 1 week after the examination. Their satisfaction with the level of information received beforehand was compared with that of an historical cohort who had received no written information. RESULTS: The patients had few complaints about their experience of participating in examinations and many enjoyed it. Only 5% of patients registered dissatisfaction with the level of information that was provided, compared with 18% in the previous study (P = 0.077). CONCLUSIONS: Written information led to a (near significant) improvement in patients satisfaction when compared to a previous cohort. We recommend that all patients attending for medical examinations should be provided with written information.

Education, Medical, Undergraduate↗

Detailed modelling of caffeine metabolism and examination of the CYP1A2 gene: lack of a polymorphism in CYP1A2 in Caucasians.

The cytochrome P450 CYP1A2 is important in the metabolism of both drugs and procarcinogens such as heterocyclic amines. We aimed to clarify the existence of a phenotypic polymorphism and explore the molecular basis of such a polymorphism. Ninety-two non-smoking individuals underwent caffeine phenotyping. The distribution of the 1,7-dimethylxanthine + 1,7-dimethyluracil/caffeine (17U + 17X/137X) ratio and log-transformed data were determined. Probit plots were constructed and the distribution fitted using maximum likelihood method. The CYP1A2 gene, including upstream regulatory regions, was examined for sequence polymorphisms using the single-strand conformation polymorphism technique in 19 individuals and by complete DNA sequencing in two individuals from the extremes of the distribution. We found a similar range (1.45-18.65) and median (6.7) for the 17U + 17X/137X ratio to that found in previous studies of non-smoking Caucasians and no effect of sex. The 17U + 17X/137X ratio gave a normal distribution when log-transformed. Maximum likelihood analysis showed that the log-normal and bimodal distributions had similar deviances but the log-normal distribution was favoured because it has fewer parameters. There was no evidence for significant DNA sequence differences between fast and slow metabolizers, although some differences from published sequences including a silent polymorhpism in exon 7 which were unlikely to be of functional significance were found. We therefore conclude that CYP1A2 does not show functionally significant polymorphism but that the wide interindividual variation in activity may be due to environmental factors.

Adolescent↗

The inflammatory bowel disease questionnaire: a valid and reliable measure in ulcerative colitis patients in the North East of England.

BACKGROUND: The validity and reliability of the Inflammatory Bowel Disease Questionnaire (IBDQ) needed to be confirmed before its use in the UK. METHODS: The IBDQ was administered to 28 subjects with ulcerative colitis (UC) on 3 separate occasions over a period of 4 weeks, twice by an interviewer and once by self-completion. Convergent and concurrent validity was assessed by using the Colitis Activity Index (CAI) and the Short Form 36 Health Survey (SF-36). Test-retest reliability and internal consistency were also tested. RESULTS: There were moderately high Pearson correlations between related IBDQ domains and SF-36 dimensions and also between the CAI score and the IBDQ Bowel domain and the SF-36 Pain dimension. Cronbach's alpha, corrected item-total correlations, and intra-class correlation coefficients were high. CONCLUSIONS: The IBDQ is a valid and reliable health-related quality of life scale for use in patients with UC and is suitable for use in the UK.

Age Factors↗

Relationship between acetylator status, smoking, and diet and colorectal cancer risk in the north-east of England.

Some previous studies have suggested that the fast phenotype of the N-acetyltransferase NAT2 may confer susceptibility to colorectal cancer because of greater activation of dietary heterocyclic amines, particularly in individuals who also consume well-done red meat, but other studies have not supported this. We describe a large case-control study examining the interaction between dietary, smoking and drinking habits, and acetylation genotype in relation to susceptibility to colorectal cancer. One-hundred-and-seventy-four incident cases and 174 matched controls were recruited. Genotyping for polymorphisms in NAT2 was performed using a method that detects >95% of slow alleles and data on personal habits were collected using a standardized questionnaire. We found no difference in the frequency of the fast acetylator genotype between cases and controls [odds ratio = 0.95 (95% CI 0.61-1.49)], and analysis by sex, age and site also revealed no difference in acetylator genotype. There was, however, considerable heterogeneity in dietary risk factors between fast and slow acetylators. Analysis by acetylator type shows that recent smoking was more frequent in slow acetylator cases than matched controls [OR = 2.31 (1.16-4.6)] and that heavy alcohol consumption was also more frequent in the slow acetylator cases than controls [OR = 2.5 (1.02-7.29)]. In contrast, frequent fried meat intake was seen more frequently in fast acetylator cases than matched controls [OR = 6.0 (1.34-55)]. The odds ratio for the combination of fast acetylator status and frequent fried meat consumption in cases was 6.04 (1.6-26). Our study suggests that there may be different risk factors for colorectal cancer in slow and fast acetylators, and reveals a new observation that slow acetylators may be at risk of colon cancer from smoking. In our community, the overall effect of acetylator status on colorectal cancer risk is neutral.

Acetylation↗

The Angelchik antireflux device: a 5-year experience.

A total of 44 patients had an Angelchik antireflux prosthesis inserted over a 5-year period. Of these, 41 were available for review and were assessed by interview using a modified Visick grading. Of the 23 patients followed up for a minimum of 3 years 74% had an excellent or satisfactory outcome; 92% of patients with symptoms of reflux obtained relief, but less than 50% of those patients presenting with dysphagia had a satisfactory outcome. The incidence of mild postoperative dysphagia increased the longer the period of follow-up. The main cause of a Visick 3 or 4 result was prosthesis migration. We have modified our technique of insertion to reduce these complications, and in a more recent series have achieved a Visick Grade 1 or 2 in up to 92% of patients. We conclude that dysphagia is a relative contraindication to the insertion of the Angelchik prosthesis. Our recent results encourage the use of the prosthesis provided steps are taken to reduce the incidence of migration and pericapsular fibrous tissue formation.

Adult↗

The MRCP (UK) examination from the patient's point of view.

Each year approximately 3,200 volunteer patients attend the examinations of the Royal College of Physicians in England and Wales. A confidential postal questionnaire concerning patients' experiences and satisfaction was administered to those attending North Tees General Hospital in June 1992 with a 90% response rate. The majority of patients derive some enjoyment from the experience and do not mind being repeatedly examined, some even up to eight times per session; but they do feel neglected if examined only once per session. Twenty-two per cent of first time attenders would have liked to have had more information about the proceedings beforehand.

Clinical Competence↗