Assessment of patient pain at colonoscopy: are nurses better than endoscopists?

The pain that patients recollect having experienced at colonoscopy is likely to influence uptake of the procedure. We used visual analogue scales to assess recollected pain shortly before discharge, and compared these scores with assessments by the endoscopist and the attending nurse. Data were complete for 426 procedures (90%). The mean perceived pain score for patients was 3.2, for endoscopists 2.8 and for nurses 3.1. On multivariate analysis, the endoscopists' assessments of pain had little predictive value over and above those of nurses, whereas nurses' assessments remained significant when adjusted for endoscopists' assessments. Nurses were more accurate than endoscopists in gauging the pain of colonoscopy. This may be because endoscopists are focused on the video monitor while nurses are focused on the patient. More active use of nurses' assessments might help keep pain to a minimum.

Coeliac disease and Down syndrome: associations not due to genetic linkage on chromosome 21.

BACKGROUND: Individuals with Down syndrome have an increased prevalence of coeliac disease (CD). The HLA region accounts for only 30% of the heritability of CD, and segregation analyses have suggested the involvement of at least one other non-HLA gene. Distribution of known HLA susceptibility types in Down syndrome and normal populations are similar and do not explain the difference in disease frequency. This study tests the hypothesis that the association between these disorders is due to a susceptibility gene for coeliac disease being present on chromosome 21. METHODS: We studied 21 families multiply affected with CD, none of whom had Down syndrome. The typing information of six microsatellite markers across chromosome 21 was used to test linkage. RESULTS: Negative results from lod score and model-free linkage analysis were obtained, providing no support for genetic linkage of coeliac disease to chromosome 21 in this population. CONCLUSIONS: The high prevalence of coeliac disease in Down syndrome is not due to an increased copy number of a polymorphic susceptibility gene on chromosome 21.

A genome-wide family-based linkage study of coeliac disease.

The susceptibility to develop coeliac disease (CD) has a strong genetic component, which is not entirely explained by HLA associations. Two previous genome wide linkage studies have been performed to identify additional loci outside this region. These studies both used a sib-pair design and produced conflicting results. Our aim is to identify non-MHC genetic loci contributing to coeliac disease using a family based linkage study. We performed a genome wide search in 16 highly informative multiply affected pedigrees using 400 microsatellite markers with an average spacing of 10 cM. Linkage analysis was performed using lod score and model free methods. We identified two new potential susceptibility loci with lod scores of 1.9, at 10q23.1, and 16q23.3. Significant, but lower lod scores were found for 6q14 (1.2), 11p11 (1.5), and 19q13.4 (0.9), areas implicated in a previous genome wide study. Lod scores of 0.9 were obtained for both D78507, which lies 1 cM from the gammaT-cell receptor gene, and for D2S364, which lies 12 cM from the CTLA4 gene.

Tissue transglutaminase antibodies in celiac disease.

OBJECTIVE: Tissue transglutaminase is the antigen for antiendomysial antibodies, whose power in screening for celiac disease is well known. Our aim was to assess the efficacy of an ELISA assay for tissue transglutaminase antibodies. METHODS: Tissue transglutaminase antibodies were analyzed in serum from 39 untreated celiac disease patients and 61 controls. Tissue transglutaminase was used as antigen, and test sera analyzed by ELISA. Results higher than 0.6 optical density were considered positive, lower than 0.4 negative, and between 0.4 and 0.6 borderline. RESULTS: Optical density of the serum from the patients with untreated celiac disease (median: 1.41; range: 0.33-1.47) were significantly higher than the controls (median: 0.32; range: 0.17-0.68; p < 0.0001; 95% confidence interval 0.87-1.08). Thirty-three patients with untreated celiac disease were positive, 4 borderline, and 2 negative. Fifty-five controls were negative, 4 borderline, and 2 positive. If we consider borderline results to be positive, sensitivity is 94.8% and specificity 90.1%. None of the controls gave results higher than 0.7 optical density. Apart from the 2 negative patients with untreated celiac disease, the two groups overlapped only between 0.4 and 0.7 optical density. CONCLUSIONS: Because of the high sensitivity (approximately 95%) and technical simplicity, tissue transglutaminase antibodies may prove useful for the screening of celiac disease in population at low or medium risk of celiac disease. To avoid duodenal biopsies in patients without celiac disease, the specificity of the screening procedure may be increased by confirming with antiendomysial antibodies by immunofluorescence on human umbilical cord in individuals with results between 0.4 and 0.7 optical density.

Family linkage study of the T-cell receptor genes in coeliac disease.

BACKGROUND: The susceptibility to coeliac disease is genetically determined by possession of certain HLA DQ alleles, together with a one or more non-HLA genes. The central role of the T-cell receptor in disease pathogenesis makes the T-cell receptor genes strong candidates as disease susceptibility genes, and previous studies had provided equivocal ambiguous results. METHODS: A pedigree based genetic linkage study was used to determine if any of the T-cell receptor genes have a role in the genetic aetiology of coeliac disease. Intragenic microsatellite markers were used to study T-cell receptor alpha, beta, and delta, while gamma was studied using two flanking microsatellites D7S484 and D7S629. RESULTS: Conventional linkage analysis was performed using the MLINK computer package. Model-free linkage analysis was performed using MFLINK. No evidence of linkage between coeliac disease and the T-cell receptor genes was found in these pedigrees. CONCLUSIONS: Mutations in the T-cell receptor genes are not implicated in the genetic aetiology of coeliac disease.

Common HLA alleles, rather than rare mutants, confer susceptibility to coeliac disease.

Coeliac Disease (CD) is a gluten sensitive enteropathy characterised by villous atrophy and crypt cell hyperplasia. It has a very strong HLA class II association to the DQ locus. The nature of the involvement of the DQ locus in the susceptibility to CD has been examined by tissue culture experiments, association and peptide binding studies. We examined the role of the DQ molecules in the pathogenesis from the perspective of a genetic family study. Using flanking microsatellite markers to the class II region of the MHC to establish the parental origin of the susceptibility DQ alleles, we have evidence suggesting that the HLA association is probably due to the necessity to have these DQ alleles in order to express CD and there is no support for the presence of a rare mutation within the DQ alleles nor any rare HLA-linked gene nearby in linkage disequilibrium with the DQ locus. This approach is applicable to other diseases demonstrating strong association with common alleles, and can be used to predict whether screening the region for rare mutations is likely to be worthwhile.

A pedigree-based linkage study of coeliac disease: failure to replicate previous positive findings.

Coeliac Disease (CD) is a gluten sensitive enteropathy characterised by villous atrophy and crypt cell hyperplasia. There is a tight HLA association between CD and the HLA DQ alleles DQA1*0501, DQB1*0201 (DQ2), arranged in either cis- or trans- configuration, are found in 98.9% of cases in Northern European populations and 80% in Greeks and Ashkenazi Jews resident in Israel. We have previously shown that the HLA alleles and CD do not co-segregate in families multiply affected with CD, suggesting that the HLA association is entirely due to the necessity to have these normal DQ alleles for CD to manifest, and that the main genetic predisposition lies at a locus other than the MHC. It is therefore possible to conduct genetic linkage studies in order to isolate the non HLA genes which predispose to CD. Recently a group conducted a genome screen for the non HLA genes in an affected sib-pair analysis and identified four non HLA loci with positive lod scores. We examined these loci using a pedigree based linkage study. Our pedigree sample consisted of a cohort of 21 families with 60 affected individuals and 125 unaffected family members. We used 11 microsatellite markers at the loci implicated and analysed the genotype data using both MLINK and MFLINK to detect linkage. The MLINK and MFLINK analyses did not provide any evidence to support the earlier findings, although the difficulties involved in analysing complex diseases mean that one cannot be certain that these regions do not harbour susceptibility loci, at least in some families.

Characterization of the humoral immune response to Klebsiella species in inflammatory bowel disease and ankylosing spondylitis.

This study was carried out to characterize the antibody class response by ELISA to seven Klebsiella pneumoniae serotypes (K2, K3, K17, K21, K26, K36, K50) in five different groups, 40 HLA-B27-positive ankylosing spondylitis (AS) patients, 46 patients with Crohn's disease (CD), 38 patients with ulcerative colitis (UC), 50 patients with active anti-endomysial antibody-positive coeliac disease and 40 healthy controls, using whole bacteria and capsular polysaccharide. IgG antibody levels were significantly elevated in AS patients to K17, K36, K50; IgA to K2, K3, K21, K26, K36 and K50; and IgM to serotype K21 when compared to normal controls. Furthermore, IgG antibody levels were significantly elevated in CD patients to K2, K17, K21, K26, K36 and K50; IgA to K2, K3, K21, K26, K36 and K50; and IgM to K2, K3, K17, K21 and K50. Increased IgG antibody levels in the UC group were limited only to K17, K36 and K50. No antibody class was increased to any of the K. pneumoniae serotypes in the coeliac disease group. The immune responses in AS patients also involve Klebsiella bacteria having capsular serotypes other than K26, K36 and K50. The similarity in the immune responses between CD and AS groups suggests that many AS patients may have occult bowel inflammation.

Prospective study of CAM 17.1/WGA mucin assay for serological diagnosis of pancreatic cancer.

BACKGROUND: Serological tests for pancreatic cancer are little used, partly because such assays have proved insufficiently specific for screening. However, retrospective studies have reported results that compare well with commonly used scanning techniques. In this prospective study we assessed a new type of combined lectin/antibody enzyme-linked mucin assay, CAM 17.1, in a routine clinical setting. METHODS: Clinicians at a 1200-bed teaching hospital were encouraged to request the CAM 17.1 assay for any patient whose differential diagnosis included pancreatic cancer. Serum samples from 250 patients were tested during an 18-month period. Patients were followed up for at least 8 months. 75 patients who did not have symptoms of pancreatic cancer and had alternative diagnoses were also studied as a control group. FINDINGS: Of the 250 patients, 36 had pancreatic cancer, as defined by histological and imaging criteria, and eight of these patients had a resectable tumour. The sensitivity and specificity of the CAM 17.1 assay were 86% and 91%, respectively, in all patients, 85% and 81% in those who presented with jaundice, and 89% and 94% in patients who did not have jaundice. The sensitivity of the assay compared well with that of ultrasound scanning (59%) and computed tomography (83%) in these patients. Use of the CAM 17.1 assay in combination with ultrasonography allowed identification of 94% of patients with pancreatic tumours and all of those with resectable tumours. CAM 17.1 binding activity did not correlate with tumour size. INTERPRETATION: Our study confirms the usefulness of the CAM 17.1 tumour-marker assay for the diagnosis of pancreatic cancer. Serological mucin assays should be used more widely in combination with ultrasonography in the investigation of non-jaundiced patients with unexplained abdominal pain or weight loss.

Detection and characterisation of anti-endomysial antibody in coeliac disease using human umbilical cord.

OBJECTIVES: To verify the effectiveness of human umbilical cord (HUC) in the detection of anti-endomysial antibodies (AEA) in coeliac disease and to characterize further these antibodies by studying tissue adsorption characteristics and antibody inhibition studies. METHODS: AEA were detected on HUC and primate oesophagus in a blind study, using sera from 46 patients with untreated coeliac disease and 108 controls. Tissue adsorption studies were performed using homogenized tissue from rodent liver, HUC, primate oesophagus and human liver. Sera were adsorbed with each of these homogenates and antibody was detected using HUC, primate oesophagus and rat kidney. In the inhibition experiments AEA was detected on HUC, and inhibition of binding was attempted by pre-incubating the sections with antibodies against collagen types I, III and IV. RESULTS: The sensitivity of AEA was 91% when detected on HUC, 89% when detected on primate oesophagus (93% and 91%, respectively, after exclusion of 1 patient with IgA deficiency). Specificity was 100% for both assays. Tissue adsorption studies showed identical results for AEA detected on both HUC or primate oesophagus, whereas antireticulin antibody was adsorbed only by rodent tissue. Blocking of the HUC with anticollagen antibodies did not prevent binding of AEA. CONCLUSIONS: HUC is an effective substrate for the detection of AEA and may be superior to primate oesophagus. The antibody detected by HUC shows identical tissue adsorption specificities to that detected on primate oesophagus.

Genetic and immunological markers in pouchitis.

OBJECTIVES: Previous studies of the interleukin-1 receptor antagonist (IL-1RN) have found an increased frequency of the associated variable number tandem repeat (VNTR) allele 2 for ulcerative colitis (UC) and further evidence has been reported that this allele is associated with increased severity of several other inflammatory conditions. The HLA type of UC patients has also been implicated in the extent of disease as has the presence of perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA). We therefore decided to test the hypothesis that the p-ANCA, HLA type or the presence of the IL-1RN allele 2 in patients who received a restorative proctocolectomy for UC had an effect on the risk of developing pouchitis. PATIENTS: We determined the genotypes of the IL-1RN and HLA DR beta and DQ beta loci for 28 subjects with previous UC and a pouch with no evidence of pouchitis for a minimum of 2 years after formation of an ileo-anal reservoir (mean 6.3 years; range 2-17 years) and 25 subjects with previous UC and pouchitis confirmed by strict histological examination of pouch mucosal biopsy. The IL-1RN genotypes were also determined for 86 healthy controls and 61 unrelated patients with familial adenomatous polyposis (FAP). The p-ANCA status was determined for all 25 pouchitis subjects but only 23/28 non-pouchitis subjects, with 15 unaffected subjects as a negative control. METHODS: The HLA haplotypes of the UC groups were determined by polymerase chain reaction sequence-specific primer (PCR-SSP) typing and the IL-1RN genotypes were determined by PCR and agarose gel electrophoresis. The p-ANCA status was determined by indirect immunofluorescence. RESULTS: A chi 2 of 5.686 with 1 degree of freedom and a P value of 0.0171 using Yates' correction was obtained by comparing the IL-1RN allele frequencies of the combined UC groups to the FAP controls, and a chi 2 of 6.801 with 1 degree of freedom and a P value of 0.0091 comparing the pouchitis group to the FAP controls. The HLA haplotype frequencies did not vary significantly between groups nor did they correlate with p-ANCA status. There were also no significant associations of the p-ANCA status and pouchitis. CONCLUSION: There is an increased frequency of IL-1RN allele 2 in UC, with the majority of the association arising from the pouchitis group, suggesting that the presence of allele 2 in patients with UC affects the disease outcome. However, the HLA frequencies and p-ANCA status do not have any significant associations.