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  1. Robin Spiller,
  2. Alastair Watson, Editor and Assistant Editor

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NEW EVIDENCE CONCERNING THE CAUSE OF OESOPHAGEAL SMOOTH MUSCLE ATROPHY IN SCLERODERMA

Dysphagia and reflux are common features of scleroderma that, in the past, have been attributed to ischaemia and secondary fibrosis. However, this substantial study of an archival database containing 74 patients suggests otherwise. There was marked atrophy of circular smooth muscle (see fig), most obvious distally in 93% of patients compared with 5% of controls. However, there was no evidence of fibrosis. Although vascular intimal hyperplasia was noted in 38% of patients compared with 5% of controls, this did not correlate with smooth muscle atrophy. Furthermore, there was atrophy of circular smooth muscle even when it was interdigitated with skeletal muscle, a feature incompatible with an ischemic basis. They found no significant increase of inflammatory cells in the myenteric plexus but did find reduced staining for the interstitial cells of Cajal (ICCs), although these data are preliminary as there were only three patients with tissue available for this stain. The authors speculate that the smooth muscle atrophy may be secondary to damage to ICCs, a novel hypothesis which is worthy of further exploration.
See p 1697


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Central atrophy (a) of circular smooth muscle from the distal oesophagus in scleroderma. Peripheral smooth muscle (m) is normal.

USE OF TISSUE-ENGINEERED CELL SHEET GRAFTS TO PREVENT STRICTURE FORMATION AFTER ENDOSCOPIC MUCOSAL RESECTION

Endoscopic mucosal resection (EMR) is now the treatment of choice for M1 and M2 oesophageal cancer. Although EMR is far less destructive than oesophageal resection, stricturing at the site of EMR is a major problem, which limits the size of resection to tumours with a diameter of <20 mm. Ohki and colleagues describe a new technique for grafting the EMR wound, enabling complete healing without scarring. Epithelial cells are harvested from the buccal mucosa of dogs and cultured using a new technique that enables the cultured cells to be harvested as a single 1 cm square sheet. This epithelium sheet is then laid onto the EMR wound directly. Four weeks later EMR wounds in dogs are healing completely with no stricturing. If this technique can be transferred to humans it will be possible to treat much larger tumours than possible hitherto without stricturing.
See p 1704


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An EMR wound treated with a autologous transplanted epithelial sheet shown by arrowheads.

ANTIBIOTIC RESISTANCE OF HELICOBACTER PYLORI IN CHILDREN LIVING IN EUROPE

Infection with H pylori is a major public health problem, with up to 15% of infected individuals developing peptic ulcer disease or gastric cancer. Little is known about the patterns of antibiotic resistance in children living in Europe. Koletzko and colleagues have carried out a multicentre prospective study of 1233 children infected with H pylori and tested its antibiotic susceptibility. The resistance rate to clarithromycin was 24%. This rate is higher than that in adults and suggests that the resistance is acquired during childhood, possibly because of the high use of clarithromycin for upper respiratory tract infection; particularly the case in Southern Europe. The resistance rate to metronidazole was 25% and was particularly common in children born in Africa or Asia. Resistance to both antibiotics was less common, at 5%, while the incidence of resistance to amoxicillin was rare at 0.6%.
See p 1711

FEATURES OF ENDOMYSIAL-NEGATIVE COELIAC DISEASE

Endomysial autoantibodies (EmA) have proved an excellent screening tool for the diagnosis of coeliac disease; however, 10–20% of patients with coeliac disease have a negative serum EmA. This report compares 151 EmA-positive patients with 26 EmA-negative patients, four of these being IgA deficient. EmA-negative patients were on average 15 years older and were more likely to be male and to have abdominal symptoms and associated features such as mouth ulceration, neurological symptoms, osteoporosis and other autoimmune disorders, with three of them having an enteropathy-associated T cell lymphoma (EATL). EmA status did not alter the crypt:villus ratio or intraepithelial lymphocyte (IEL) counts. Both patient groups responded to a gluten-free diet and showed IgA deposits in the small bowel mucosa, which colocalised with extracellular tissue transglutaminase 2 (TG2). The authors conclude that examining biopsies for TG2-specific IgA could be a useful way of diagnosing EmA-negative coeliac disease, which avoids the need for gluten challenge to confirm the diagnosis.
See p 1746


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Transglutaminase-2 (TG2)–specific IgA deposits in the small bowel mucosa showing similar resolution on a gluten free diet in both EmA negative and EmA positive coeliacs. No such deposits were found in controls.

LOW BIRTH WEIGHT AS A RISK FACTOR FOR IBS

Several studies have suggested that impaired intrauterine growth can be a risk factor for developing cardiovascular and renal disease. This study used the Norwegian twin registry to examine the impact of birth weight on the risk of developing irritable bowel syndrome (IBS) while controlling for genetic factors. The study involved 3199 twin pairs who were asked whether they had ever had IBS. Twenty two per cent of the monozygotic twins with IBS had a twin who also had IBS but this was only true for 9% of dizygotic twins. Modelling indicated that heritability of IBS among females was 48%, confirming earlier studies. IBS twin pairs had significantly lower birth weights (see fig). After adjusting for gestational age, weighing <1500 g at birth increased the odds of having IBS 2.5 fold. Whether the more solicitous parental behaviour naturally associated with low birth weight encouraged IBS symptoms to develop remains to be determined.
See p 1754


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Birth weight in IBS twins is significantly lower compared with non IBS twins, p = 0.01.

PIT PATTERNS OF RECTAL MUCOSA PREDICT RELAPSE OF ULCERATIVE COLITIS

Relapse of ulcerative is difficult to predict clinically. If this were feasible it might be possible to reduce the severity of relapse by pre-emptive treatment. Nishio and colleagues classified pit patterns within the rectum into four grades on the basis of size, shape and distribution. They performed magnifying colonoscopy with methylene blue staining on 113 patients with colitis in remission and classified their rectal pit patterns. The interval until relapse was then determined over the following 12 months. They found that the grade of pit pattern correlated with histological grade and mucosal interleukin 8 activity. Multivariate analysis showed that the grade of pit pattern was a significant predictor of relapse, with grade 1 having no relapse whereas grade 4 predicted relapse in 60% of cases.
See p 1768


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Proportion of patients who had a relapse according to grade of pit pattern.

Clarithromycin resistance among patients not previously treated for H pylori.

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