The sensitivities and specificities of the IgA and IgG antigliadin antibody and the IgA antireticulin antibody have been compared with the recently described endomysial antibody directed against the basement membrane of smooth muscle in monkey oesophagus. One hundred and seventeen patients with adult coeliac disease (21 untreated), 84 patients with inflammatory bowel disease, systemic lupus erythematosus and rheumatoid arthritis (comprising the disease control group), 47 normal controls and a miscellaneous group of 29 patients, who were selected because of a positive reticulin staining pattern, were investigated. These results were correlated with the degree of abnormality of the intestinal mucosa in patients with adult coeliac disease. Endomysial antibodies were found in all patients with untreated coeliac disease and subtotal villous atrophy and in 47% of patients on a non-strict gluten free diet. One patient on a strict gluten free diet was positive and had partial villous atrophy while all patients in disease control groups were negative. Results were variable with the antireticulin and antigliadin antibodies. Sensitivity and correlation with subtotal villous atrophy in the untreated patients was 100%. It is concluded that the endomysial antibody is superior to other current antibody tests and should be used in preference for the diagnosis of coeliac disease.
Because cytomegalovirus (CMV) is an important opportunistic infection after liver transplant, we conducted a prospective study to see if the same applied to human herpesviruses (HHV)-6 and -7. We used polymerase chain reaction (PCR) methods optimised to detect active, not latent, infection and studied patients not receiving antiviral prophylaxis for CMV. Post-transplant, 536 blood samples were tested by PCR (median 7; range 4-50). Active infection with CMV was detected in 28/60 (47%), HHV-6 in 19/60 (32%), and HHV-7 in 29/60 (48%) of patients. The PCR-positive samples were tested by quantitative-competitive PCR to measure the virus load of each betaherpesvirus. The median peak virus load for CMV was significantly greater than that for HHV-6 or HHV-7. Detailed clinicopathological analyses for the whole population showed that CMV and HHV-6 were each significantly associated with biopsy-proven graft rejection. Individual case histories suggested that HHV-6 and HHV-7 may be the cause of some episodes of hepatitis and pyrexia. It is concluded that HHV-6 is a previously unrecognized contributor to the morbidity of liver transplantation, that HHV-7 may also be important and that both viruses should be included in the differential diagnosis of graft dysfunction.
Background: The breakdown of glycosaminoglycans is an important consequence of inflammation at mucosal surfaces, and inhibition of metalloprotease activity may be effective in treating chronic inflammation. Aim: To report an alternative approach, using the nutriceutical agent N‐acetyl glucosamine (GlcNAc), an amino‐sugar directly incorporated into glycosaminoglycans and glycoproteins, as a substrate for tissue repair mechanisms. Methods: GlcNAc (total daily dose 3–6 g) was administered orally as adjunct therapy to 12 children with severe treatment‐resistant inflammatory bowel disease (10 Crohn’s disease, 2 ulcerative colitis). Seven of these children suffered from symptomatic strictures. In addition, similar doses were administered rectally as sole therapy in nine children with distal ulcerative colitis or proctitis resistant to steroids and antibiotics. Where pre‐ and post‐treatment biopsies were available (nine cases), histochemical assessment of epithelial and matrix glycosaminoglycans and GlcNAc residues was made. Findings: Eight of the children given oral GlcNAc showed clear improvement, while four required resection. Of the children with symptomatic Crohn’s stricture, only 3 of 7 have required surgery over a mean follow‐up of > 2.5 years, and endoscopic or radiological improvement was detected in the others. Rectal administration induced remission in two cases, clear improvement in three and no effect in two. In all cases biopsied there was evidence of histological improvement, and a significant increase in epithelial and lamina propria glycosaminoglycans and intracellular GlcNAc. Conclusions: GlcNAc shows promise as an inexpensive and nontoxic treatment in chronic inflammatory bowel disease, with a mode of action which is distinct from conventional treatments. It may have the potential to be helpful in stricturing disease. However, controlled trials and an assessment of enteric‐release preparations are required to confirm its efficacy and establish indications for use.
Summary Background : Crohn's disease is a chronic debilitating disorder affecting a child's physical and emotional well‐being. Recent emphasis on ‘quality of life’ (QOL) has led to re‐evaluation of available medical treatments. Aim : To assess prospectively change in QOL, clinical disease activity and intestinal mucosal inflammation in active paediatric Crohn's disease after treatment with exclusive enteral nutrition. In addition, we evaluated whether change in QOL could predict changes in paediatric Crohn's disease activity index (PCDAI) and mucosal inflammation (endoscopic and histologic). Methods : The IMPACT II questionnaire was used prospectively and longitudinally in 26 consecutively recruited children [16 males (67%), median 14 years, s.d. = 1.7 years] with active Crohn's disease (PCDAI > 20). They were treated with a new polymeric enteral feed (ACD004, Nestle) for a period of 8 weeks. All had PCDAI, QOL and endoscopic assessment at the time of diagnosis and after 8 weeks of treatment. Results : Twenty‐three of 26 children achieved a clinical remission at 8 weeks, with improvement in the QOL scores (P < 0.05). The change in QOL score after treatment was predictive of achieving a clinical remission, but not of histological improvement. Conclusions : Although children may find dietary restrictions difficult, this study confirms a clear improvement in QOL after treatment with exclusive enteral nutrition. However, improvement in QOL scores is not reflected by improvement in mucosal inflammation. Whilst improving QOL remains a core principal in patient management, the long‐term consequences of ongoing mucosal inflammation must be better understood before relying only on short‐term QOL measures to dictate treatment choices.
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