Antonio Salas

mtDNA analysis of the Galician population: a genetic edge of European variation

Analysis of mitochondrial DNA (mtDNA) variation has become a useful tool for human population studies. We analysed the first hypervariable region of mitochondrial DNA control region (position 16024–16383) in 92 unrelated individuals from Galicia (Spain), a relatively isolated European population at the westernmost continental edge. Fifty different sequences defined by 56 variable positions were found. The frequency of the reference sequence reaches in Galicians its maximum value in Europe. Moreover, several genetic indexes confirm the low variability of our sample in comparison to data from 11 European and Middle Eastern populations. A parsimony tree of the sequences reveals a high simplicity of the tree, with few and small well defined clusters. These results place Galicians on the genetic edge of the European variation, bringing together all the traits of a cul-de-sac population with a striking similarity to the Basque population. The present results are fully compatible with a population expansion model in Europe during the Upper Paleolithic age. The genetic evidence revealed by the analysis of mtDNA shows the Galician population at the edge of a demographic expansion towards Europe from the Middle East.

Evolution of the incidence of collagenous colitis and lymphocytic colitis in Terrassa, Spain: A population-based study†

Background: Previous studies suggest an increase in the incidence rate of microscopic colitis in recent decades. The aim was to evaluate changes in the population‐based incidence rate of microscopic colitis and its subtypes over time in Terrassa, Spain. Methods: This was a prospective study during the period 2004–2008, with a comparison of data from the period 1993–1997. The catchment area was a mixed rural‐urban type, with nearly 290,000 inhabitants. All patients with nonbloody chronic diarrhea referred for a diagnostic colonoscopy were included. Multiple biopsy specimen samples were obtained when the macroscopic appearance of the colonic mucosa was normal to rule out microscopic colitis. Crude and adjusted incidence rates based on either the year of diagnosis or the date of onset of symptoms were calculated. Results: Forty patients with collagenous colitis (CC) and 32 with lymphocytic colitis (LC) were identified. The mean annual incidence of CC and LC based on the year of onset of symptoms was 2.6/105 inhabitants (95% confidence interval [CI], 1.9–3.3), and 2.2/105 inhabitants (95% CI, 1.5–3.0), respectively. Incidence rates for CC based on the year of onset of symptoms were significantly higher in the period 2004–2008 than in 1993–1997 (2.6 versus 1.1/105; P = 0.012). The increase in CC incidence was more marked in women (P = 0.047) than in men (P = 0.19). Conclusions: The annual incidence of CC in Terrassa increased over time, mainly in women. Nevertheless, the rates were much lower than those observed in northern Europe, suggesting that there is a north–south difference in the incidence of microscopic colitis. (Inflamm Bowel Dis 2011;)

Efficacy of anti-TNF therapies in refractory severe microscopic colitis.

BACKGROUNDnRefractory microscopic colitis is a rare condition with an unknown rate of occurrence. The efficacy of anti-tumor necrosis factor (TNF) therapy for microscopic colitis has never been reported. Aims 1) To report the frequency of refractory microscopic colitis in the database of the participant hospitals. 2) To describe the therapeutic response to anti-TNF therapy among the refractory cases.nnnMETHODSnPatients with a histological diagnosis of collagenous colitis and lymphocytic colitis were identified through the Department of Pathology database and the IBD practice database. Patients refractory to medical treatment and with severe symptoms were offered anti-TNF therapy.nnnRESULTSnFive of 372 MC patients (1.3%; 95% CI, 0.6 to 3.1) presented with severe symptoms refractory to standard medical therapies. One patient was denied therapy from her insurance carrier. The other 4 received infliximab therapy. The response was excellent after one dose experiencing a 60-90% decrease in bowel movements. Three patients were switched to adalimumab (2 allergic reactions and 1 early loss of response to infliximab). Long-term clinical remission (more than 1 year) was achieved in three cases (2 with adalimumab and 1 with infliximab). One patient on adalimumab had an early loss of response and was referred for colectomy.nnnCONCLUSIONSnMicroscopic colitis with severe symptoms refractory to standard medical therapy including immunosuppressives is uncommon. In this setting, anti-TNF therapies may be a good option to avoid colectomy.

Paucicellular Lymphocytic Colitis : Is It a Minor Form of Lymphocytic Colitis? A Clinical Pathological and Immunological Study

OBJECTIVES:It has been suggested that paucicellular lymphocytic colitis (PLC) should be considered to be part of the morphological spectrum of microscopic colitis. The aim of the study was to evaluate whether PLC may be considered to be a true microscopic colitis, and in this case, whether it is a minor form of lymphocytic colitis (LC) or a different entity.METHODS:All incident cases of PLC, LC, and collagenous colitis (CC) during the period 2004–2006 were included. The incidence rate and the clinical, histopathological, and immunological features of PLC were assessed and compared with those of both LC and CC. Immunoreactivities to CD25, c-Kit, and FOXP3 in lamina propria were assessed.RESULTS:In all, 19 patients with CC, 19 with LC, and 26 with PLC were identified. CD25+FOXP3+ expression was seen only in classical forms of microscopic colitis: 12 of 19 LC, 14 of 20 CC, and none of 20 PLC cases (P<0.0001). Diarrhea ceased in 21 of the 26 patients, with a decrease in the daily stool number from 5.08±0.44 to 1.7±0.2 (P<0.005). The five patients with no response to therapy fulfilled the Rome II criteria of irritable bowel syndrome (IBS).CONCLUSIONS:The incidence rate of PLC, identified using objective histological criteria, was higher than those of CC and LC. The lack of expression of CD25+FOXP3+ cells in PLC, in contrast to those seen in both LC and CC, would suggest the existence of different pathophysiological mechanisms and does not support that PLC is a minor form of LC.

Intestinal spirochetosis and chronic watery diarrhea: Clinical and histological response to treatment and long-term follow up

Background:u2002 The clinical significance of intestinal spirochetosis is uncertain, therefore the aim of the present paper was to assess the prevalence of histological intestinal spirochetosis in patients with and without chronic watery diarrhea and to evaluate its clinical relevance.

The prevalence of coeliac disease is significantly higher in children compared with adults.

Backgroundu2002 Some limited studies of coeliac disease have shown higher frequency of coeliac disease in infancy and adolescence than in adulthood. This finding has remained unnoticed and not adequately demonstrated.

Diagnostic value of duodenal antitissue transglutaminase antibodies in gluten-sensitive enteropathy

Backgroundu2002 In gluten‐sensitive enteropathy, antitissue transglutaminase antibodies are synthesized in the duodenum.

Randomized clinical trial comparing two one-week triple-therapy regimens for the eradication of Helicobacter pylori infection and duodenal ulcer healing☆

Abstract Objective: One-week triple therapy has been shown to be effective in Helicobacter pylori eradication and duodenal ulcer healing. However, the optimal therapeutic combination has not yet been identified. Bismuth-containing regimens have the advantage of requiring only one antibiotic. It has been suggested that high doses of omeprazole improve the bactericidal efficacy of antimicrobial regimens against H. pylori . We evaluated the efficacy of two 1-wk triple-therapy regimens for H. pylori eradication and duodenal ulcer healing. Methods: On an intention-to-treat basis, 182 patients with H. pylori -associated duodenal ulcer were randomized. Group OCB patients (n = 91) were given omeprazole 40 mg b.i.d. , clarithromycin 500 mg b.i.d. , and colloidal bismuth subcitrate 120 mg q.i.d. for 7 days. Group OCA patients (n = 91) were treated with omeprazole and clarithromycin at the same doses plus amoxicillin 1 g b.i.d. , also for 7 days. Endoscopies were performed at entry and at 4 wk after the end of treatment. The presence of H. pylori was assessed by urease test, histology, Gram stain, and culture. No patient received follow-up treatment. Results: H. pylori eradication rates achieved in the OCB and OCA groups were similar whether by intention-to-treat (82.4% vs 88.9%; p = 0.21) or per protocol analysis (83.3% vs 89.9%; p = 0.19). Duodenal ulcer healing rates also were the same for OCB and OCA in intention-to treat (91.2% vs 91.1%) and per protocol analysis (92.2% vs 92.1%), respectively ( p = 0.98). Conclusions: High rates of H. pylori eradication and duodenal ulcer healing were obtained with both short-treatment regimens, which were safe and well-tolerated. Colloidal bismuth subcitrate seems to be a good alternative to amoxicillin in the triple-therapy combination with omeprazole and clarithromycin. The omeprazole dose does not seem to play a major role in H. pylori eradication in these therapeutic combinations.

Lymphocytic duodenosis: Aetiology and long-term response to specific treatment

BACKGROUNDnThe clinical significance of lymphocytic duodenosis remains unclear.nnnAIMnTo prospectively assess the aetiology of lymphocytic duodenosis and the patterns of clinical presentation.nnnMETHODSnNinety consecutive patients with lymphocytic duodenosis and clinical symptoms of the coeliac disease spectrum were prospectively included. All subjects underwent serological testing and HLA genotyping for coeliac disease, assessment of Helicobacter pylori infection, and parasite stool examination. Intake of non-steroidal anti-inflammatory drugs was also recorded. The final aetiology of lymphocytic duodenosis was evaluated on the basis of the long-term response to specific therapy.nnnRESULTSnMore than one initial potential aetiology was observed in 44% of patients. The final diagnosis was gluten-sensitive enteropathy alone or associated with Helicobacter pylori infection in 43.3%, Helicobacter pylori infection (without gluten-sensitive enteropathy) in 24.4%, non-steroidal anti-inflammatory drugs intake in 5.5%, autoimmune disease in 3.3%, and parasitic infection in 2.2%. Among first degree relatives and patients with chronic diarrhoea, the most common final diagnosis was gluten-sensitive enteropathy. In contrast, in the group presenting with chronic dyspepsia the most common diagnosis was Helicobacter pylori infection (Diarrhoea vs Dyspepsia groups, p=0.008).nnnCONCLUSIONSnLymphocytic duodenosis is often associated with more than one potential initial aetiology. Clinical presentation may be useful to decide the initial therapeutic approach with these patients.

Apoptosis resistance of mucosal lymphocytes and IL-10 deficiency in patients with steroid-refractory Crohn's disease.

Background: Apoptosis resistance of T‐cells is considered an abnormality of immune pathways in Crohns disease (CD). It has been previously shown that corticosteroids induce apoptosis of cells involved in inflammation. Thus, our aim was to assess the apoptosis of mononuclear cells and pro/antiinflammatory cytokines in the intestinal mucosa of patients with active CD, related to steroid response, and identify cellular and molecular factors that may predict this response to therapy. Methods: Patients with CD (n = 26), ulcerative colitis (UC) (n = 32), and controls (n = 10) were prospectively studied with mucosal biopsies before and 7‐10 days after corticosteroid treatment. Immunophenotype and apoptosis of T and B lymphocytes, plasma cells, and macrophages were assessed by flow cytometry, immunohistochemistry, and immunofluorescence. The cytokine expression pattern was evaluated by quantitative polymerase chain reaction (PCR). Results: Apoptosis resistance of T and B lymphocytes was observed only in steroid‐refractory and ‐dependent CD patients as compared to responsive patients (P = 0.032; P = 0.004, respectively), being evident after steroid treatment. Interleukin (IL)‐10 was markedly increased at baseline in steroid‐responsive patients compared to the nonresponders (P = 0.006; sensitivity: 88.8%; specificity: 66.6% to predict steroid response). Conclusions: Apoptosis resistance of mucosal T and B cells in steroid‐refractory and ‐dependent CD patients appears during the evolution of the acute phase, limiting its clinical application as a predictor marker. In contrast, increased expression of IL‐10 at an early stage of active steroid‐sensitive CD patients supports its usefulness at predicting a good steroid response. Steroid‐dependent and ‐refractory CD patients share similar molecular and cellular pathophysiological mechanisms. (Inflamm Bowel Dis 2010;)