Dario Sorrentino

Oleate uptake by cardiac myocytes is carrier mediated and involves a 40-kD plasma membrane fatty acid binding protein similar to that in liver, adipose tissue, and gut.

Uptake of [3H]oleate by canine or rat cardiac myocytes is saturable, displays the countertransport phenomenon, and is inhibited by phloretin and trypsin. Cardiac myocytes contain a basic (pI approximately 9.1) 40-kD plasma membrane fatty acid binding protein (FABPPM) analogous to those recently isolated from liver, adipose tissue, and gut, unrelated to the 12-14-kD cytosolic FABP in these same tissues. An antibody to rat liver FABPPM selectively inhibits specific uptake of [3H]oleate by rat heart myocytes at 37 degrees C, but has no influence on nonspecific [3H]oleate uptake at 4 degrees C or on specific uptake of [3H]glucose. Uptake of long-chain free fatty acids by cardiac muscle cells, liver, and adipose tissue and absorption by gut epithelial cells is a facilitated process mediated by identical or closely related plasma membrane FABPs.

Low-Dose Maintenance Therapy With Infliximab Prevents Postsurgical Recurrence of Crohn's Disease

BACKGROUND & AIMS Infliximab might prevent postsurgical recurrence of Crohns disease. However, it is unclear whether long-term therapy is necessary and whether alternative strategies could be applied to minimize potential side effects and reduce the costs of treatment. METHODS We performed a prospective cohort study in 12 consecutive patients, treated immediately after surgery with maintenance infliximab (5 mg/kg), who did not have clinical or endoscopic evidence of disease recurrence after 24 months; they were followed up for an additional year. Infliximab treatment was then discontinued; patients with disease recurrence, based on endoscopy (Rutgeerts score, >or=2), were given lower doses of infliximab (starting with 1 mg/kg) to re-establish mucosal integrity. Surrogate markers of disease activity (fecal calprotectin [FC], C-reactive protein, and erythrocyte sedimentation rate) were assessed after each infliximab dose. RESULTS None of the patients had clinical or endoscopic recurrence of Crohns disease 3 years after surgery. However, discontinuation of infliximab caused endoscopic recurrence after 4 months in 10 of 12 patients (83%). All 10 patients then were treated again with infliximab, which, at a dose of 3 mg/kg every 8 weeks, restored and maintained mucosal integrity for 1 year. Among the surrogate markers, FC levels correlated with endoscopic scores (Wald test, P < .0001). CONCLUSIONS Long-term maintenance therapy with infliximab is required to maintain mucosal integrity in patients after surgery for Crohns disease. However, a dose of 3 mg/kg (a 40% reduction from the standard dose) was sufficient to avoid disease recurrence, determined by endoscopy, in all patients at 1 year. FC levels correlate with mucosal status at different infliximab doses.

MRI scoring system including dynamic motility evaluation in assessing the activity of Crohn's disease of the terminal ileum

RATIONALE AND OBJECTIVES We sought to investigate the value of a MRI scoring system including dynamic motility evaluation in the assessment of small bowel Crohns disease activity. MATERIALS AND METHODS From March 2005 to December 2006, 52 patients with suspected Crohns disease onset or relapse underwent MRI on a 1.5-T magnet. Bowel distention was achieved orally assuming a mean of 1.6 L of a polyethyleneglycol (PEG) preparation. Per-patient assessment of disease activity was based on a scoring system including evaluation of morphology and motility of the small bowel and perivisceral structures (true-FISP, cine-true-FISP, and HASTE T2W sequences) and dynamic assessment of parietal contrast enhancement (FLASH T1W sequence). Patients were included in three categories, using endoscopic biopsy as the standard reference: no activity/quiescent disease, mild activity, or moderate-to-severe activity. Patients without terminal ileum involvement were excluded from data analysis. RESULTS MRI allowed a detailed and panoramic evaluation of the small bowel in all subjects examined. MRI properly assessed 14 of 16 (87.5%) cases of no activity/quiescent disease, 12 of 14 (85.7%) cases of mild activity, and 15 of 15 (100%) cases of severe activity. Overall, activity score led to a per-patient misdiagnosis of disease activity in a nonsignificant proportion of subjects (4 of 45; 8.8%) (P > .05), determining two false-positive and two false-negative results of mild disease activity. Sensitivity, specificity, PPV, NPV, and overall accuracy in assessing disease activity were 93.1%, 87.5%, 93.1%, 87.5%, and 91.1%, respectively. CONCLUSION Accurate assessment of Crohns disease activity is achieved by using an activity score providing an overall interpretation of MRI findings.

Recommendations for the treatment of Crohn's disease with tumor necrosis factor antagonists: An expert consensus report

Background: Symptom relief is the traditional treatment goal in Crohns disease (CD). New goals including mucosal healing and bowel preservation are now achievable with tumor necrosis factor (TNF) antagonists. Infliximab and adalimumab are approved as second‐line treatments for severe, active CD. Certolizumab pegol is approved only in the U.S. and Switzerland as second‐line treatment for moderate‐to‐severe, active CD. Data from trials of infliximab suggest that high‐risk patients and patients with active inflammation (CRP elevation and/or ileocolonic ulcers) may benefit from earlier use of this drug. Methods: A Delphi survey was used to obtain consensus on issues surrounding bowel preservation and use of TNF antagonists. At the time of this survey, infliximab was the only TNF antagonist approved for the treatment of CD in Europe, Canada, and Australia. An expert panel of 12 gastroenterologists with substantial clinical experience using infliximab in clinical practice and trials in these areas participated. Results: The experts agreed that bowel preservation and mucosal healing are relevant and achievable goals, and form a rationale for using TNF antagonists in CD patients. Control of inflammation and induction of mucosal healing were considered essential for bowel preservation. Consensus areas: 1) mucosal healing is predictive of improved long‐term disease course and increases the likelihood of steroid‐free remission; 2) infliximab induces sustained mucosal healing, promotes bowel preservation, and reduces hospitalizations and surgeries; 3) benefits of infliximab in relation to mucosal healing, bowel preservation, and clinical remission increase when therapy is initiated earlier. Conclusions: Treatment with TNF antagonists helps preserve the bowel in CD patients. (Inflamm Bowel Dis 2011;)

Prevention of postoperative recurrence of Crohn's disease by infliximab

The prevention of the recurrence of Crohns disease after surgery remains difficult. The monoclonal antibody anti-TNF-alpha, infliximab, is very effective in inducing and maintaining the remission of uncomplicated, active Crohns disease. We present here the case of a 23-year-old white woman who underwent resection for a sigmoid stricture caused by Crohns disease. Surgery removed the involved colon, and pathology confirmed the stricture to be fibrotic. Two weeks after the operation she was given infliximab at the dose of 5 mg/kg body weight and followed in time. Since then, she has been disease free for approximately 4 years after surgery on clinical, radiological and endoscopic/histological grounds (Crohns Disease Activity Index < or = 110 on all occasions). Up to now, she has had no increase in inflammatory indices, no anaemia and no abnormal blood tests. In contrast, all of five control patients operated in the same period with colonic or ileocolonic resection for symptomatic strictures and treated with mesalamine or no medication developed endoscopic or clinical recurrence (abdominal pain or diarrhoea) by year 3. This is the first case, to our knowledge, in which infliximab has been successfully used to prevent the postsurgical recurrence of Crohns disease, an event so far considered to be inescapable. We believe that, with this aim in mind, clinical trials with this drug are warranted.

B cell clonality in gastric lymphoid tissues of patients with Sjögren's syndrome.

OBJECTIVE: To determine the prevalence of mucosa associated lymphoid tissue (MALT) in the stomach and of a possible antigen driven proliferation, in patients with Sjögrens syndrome (SS). METHODS: Twenty one patients with primary SS and 80 dyspeptic controls underwent upper endoscopy. Lymphoid tissue and Helicobacter pylori were assessed by histopathological analysis. Epstein-Barr virus (EBV) or human herpes virus-6 (HHV-6) genome were studied by polymerase chain reaction (PCR) DNA amplification. Two PCR VDJ procedures were used to detect immunoglobulin heavy chain (IgH) gene rearrangement. RESULTS: Organised MALT was found in 33.3% of the patients, compared with 21.5% of the controls (NS). H pylori infection was seen in 71% of patients and 63% of controls. Genomic EBV or HHV-6 was found in a minor portion of SS gastric tissues. B cell expansion was detected in nine of the 21 patients. Infectious agents in the stomach might have contributed to B cell clonality only in 55.5% of the cases. No strict relationship was found between lymphoid follicles and clonality. CONCLUSION: Lymphoid accumulation in the gastric mucosa is common in Sjögrens syndrome, but full evidence for an antigen driven B cell expansion could not be demonstrated. Only a portion of those with clonal B cell expansion had evidence of an infectious agent. Other unknown infectious agents or factors related to the underlying disease (autoantigen) and its tissue environment may have a further role as possible causes of B clonal expansion in the gastric mucosa.

B-cell clonality and infection with Helicobacter pylori: implications for development of gastric lymphoma.

BACKGROUND: Although Helicobacter pylori has been implicated in the pathogenesis of gastric mucosa associated lymphoid tissue (MALT) and MALT lymphoma, it is not known how it may trigger these lesions and whether there is an identifiable pre-neoplastic stage. AIMS: To investigate the relation between MALT, H pylori infection, and B-cell clonality (a potential marker of pre-neoplastic lesions). PATIENTS: 141 subjects with simple dyspepsia. METHODS: Gastric biopsy specimens from all patients were examined for MALT and H pylori. Of these, 25 consecutive MALT positive specimens were scored for features of MALT lymphoma and VDJ clonality studied by polymerase chain reaction. RESULTS: Overall, prevalence was 62% for H pylori and 46% for MALT. VDJ clonality was frequent in the sub-group studied (nine of 25), mostly associated with lymphoid follicles (eight of nine or 89%), and with a high scoring for MALT lymphoma. VDJ clonality was equally frequent in patients with and without H pylori (seven of 20 and two of five or 35% and 40% respectively). CONCLUSIONS: B-cell clonality is unexpectedly common in subjects with simple dyspepsia and MALT raising clinical management questions. These findings also suggest that the cascade MALT formation--B-cell clonality--MALT lymphoma may not be uniquely associated with H pylori infection.

Isolation and partial characterization of plasma membrane fatty acid binding proteins from myocardium and adipose tissue and their relationship to analogous proteins in liver and gut

We describe a general method for isolating a class of 40 kDa plasma membrane fatty acid binding proteins which have been identified previously only in rat liver and jejunum. Proteins extracted with 2 M salt from rat adipocyte and cardiac myocyte plasma membranes were subjected to preparative isoelectric focusing. Fractions with pIs greater than or equal to 9.0 were further purified by oleate-agarose affinity chromatography and HPLC. Each tissue yielded a single 40 kDa protein which co-chromatographed with [3H]-oleate on gel permeation HPLC, and reacted on Western blots with an antibody to the corresponding hepatic membrane protein. Related plasma membrane fatty acid binding proteins have now been isolated from each of the major sites of fatty acid transport.

Recommendations for the treatment of ulcerative colitis with infliximab: A gastroenterology expert group consensus

BACKGROUND AND AIMS Infliximab is currently the only biologic approved for treatment of adults with moderate to severe, active ulcerative colitis (UC) unresponsive to conventional therapies. It rapidly controls symptoms, induces and sustains steroid-free remission, stimulates mucosal healing, and reduces serious complications. Although infliximab tends to be reserved for patients with severe disease, it may be even more beneficial for moderate disease earlier in the disease course. Therefore, it is important to identify which patients are candidates for infliximab therapy. METHODS A collaborative Delphi survey was used to obtain consensus on use of biologic therapy in patients with UC from an expert panel of 12 gastroenterologists with substantial experience using infliximab in clinical practice and clinical trials. The panel also addressed issues that influence the use of infliximab in UC, including its potential as an alternative to surgery. RESULTS The panel agreed that: (1) it is necessary to adopt additional treatment goals beyond symptom control, i.e., complete mucosal healing, steroid-free remission, improved QoL, and reduced long-term complications; (2) it may be possible to achieve these treatment goals with infliximab, especially if it is used earlier in the course of UC; and (3) infliximab should be offered as an alternative to surgery in patients being considered for colectomy. The panel also agreed on factors for identifying candidates for infliximab therapy (e.g., persistently active UC, steroid-dependent/refractory disease, and high C-reactive protein). CONCLUSIONS This consensus statement provides useful and practical information on how to achieve evolving treatment goals with infliximab in moderate to severe UC.

Internet use among inflammatory bowel disease patients : an Italian multicenter survey

Background The internet has been increasingly used as a resource for accessing health-related information. A recent US survey found that approximately half of inflammatory bowel disease (IBD) patients in an IBD clinic use the internet to gather IBD-specific information. Aim The aim of this study was to evaluate the use of the internet among Italian IBD patients. Methods The study was performed in seven Italian IBD referral centers by using a 28-item anonymous questionnaire. Results In all, 495 questionnaires were returned for analysis, in which 305 of 495 patients (61.6%) indicated that they are able to access the internet. A large proportion used the internet to gather health-related information (180 of 305, 59.1%) and IBD-related information (226 of 305, 74.2%). The use of the internet increased significantly with level of education (P<0.0001) and household income (P<0.0001). In addition, the use of the internet to gather IBD-related information increased significantly with the increase of disease activity and severity. Conclusion Approximately half of the patients in Italian IBD referral centers used the internet to gather IBD-related information. This use positively correlated with disease activity and severity. The great majority of patients indicated that it was very important for IBD referral centers to have their own IBD-dedicated website.