Reflux symptoms in professional opera soloists.

BACKGROUND: Professions distinguished by repeated vocal stress carry a high risk of developing gastroesophageal reflux symptoms (GERS) which may affect vocal performance. AIMS: To investigate the prevalence of self-reported GERS in professional opera soloists. METHODS: A validated questionnaire regarding self-reported GERS (heartburn, regurgitation, chest pain, dysphagia, hoarseness, and cough) and lifestyle habits was administered to 116 professional opera soloists (mean age 34.1 ±â€¯7.3 years, F:M ratio 1:1.1). Age and sex-matched opera choristers and control subjects were used as control. Prevalence rate ratios (PRRs) adjusted for confounding factors were evaluated. RESULTS: Among GERS, belching (33.6%), heartburn (19.8%), and dysphagia (15.5%) were the most commonly reported by soloists. In particular, a higher risk of heartburn (PRR 2.61, 95% CI 1.45-4.69) and dysphagia (PRR 2.58, 95% CI 1.31-5.10) was reported in soloists as compared to choristers. The prevalence of obesity and late dinner was higher in both choristers and soloists in comparison to the population sample (p < 0.001). GERS was more common among soloists who received pharmacologic treatment and their prevalence was unrelated to the years of singing activity. CONCLUSIONS: Professional opera soloists, regardless of the length of their career, are predisposed to developing GERS. Physicians should encourage patients to correct preventable risk factors. A prolonged pharmacological treatment might be needed.

Effect of tumor necrosis factor-α blockade on mucosal addressin cell-adhesion molecule-1 in Crohn's disease.

BACKGROUND: Mucosal addressin cell-adhesion molecule (MAdCAM)-1, which is overexpressed on gut endothelium in active Crohn's disease (CD), promotes intestinal recruitment of integrin α(4)ß(7)(*) T cells that sustain chronic inflammation. As tumor necrosis factor alpha (TNF)-α, a cytokine centrally involved in CD, modulates gut endothelial adhesion molecules, we here explored the in vivo and ex vivo effects of TNF-α blockade on MAdCAM-1 expression in CD. METHODS: MAdCAM-1 was determined by immunoblotting in colonic biopsies collected before and 10 weeks after either infliximab or adalimumab treatment in CD patients, and in CD biopsies incubated with either infliximab or adalimumab or control IgG(1). Integrin ß(7)(*) circulating T cells were analyzed by flow cytometry. RESULTS: MAdCAM-1 significantly decreased after either infliximab or adalimumab treatment in responder but not in nonresponder patients. In parallel, an increase of circulating ß(7)(*) T cells was found in responder patients only. A marked downregulation of MAdCAM-1 was observed in CD biopsies cultured with either infliximab or adalimumab in comparison to IgG(1)-treated biopsies. CONCLUSIONS: Our findings showing that MAdCAM-1 is downregulated by TNF-α blockade point to a novel mechanism of action of anti-TNF-α antibodies in CD.

Recent advances in understanding Crohn's disease.

Crohn's disease is a chronic inflammatory bowel disorder resulting from an inappropriate innate and acquired immune response to commensal microorganisms in genetically susceptible individuals. This disease has a fluctuating course, with alternating periods of remission and relapses, and it is characterized by a remarkable clinical heterogeneity; it may be complicated by perianal fistulas, abscesses, and intestinal strictures leading to obstructions, besides several systemic manifestations. However, a complete resolution of the disease is currently not possible, yet Crohn's disease can be managed with established and novel therapies, which achieve long-term remission and acceptable quality of life. This review is focused on novel advances in basic and clinical aspects of Crohn's disease, although it also deals with new trends in diagnosis and treatment.

Mucosal changes induced by ischemia-reperfusion injury in a jejunal loop transplanted in oropharynx.

Tissues exposed to ischemia and reperfusion develop an inflammatory response. We investigate the morphological and immunological changes occurring in the mucosa of a jejunal loop transplanted in the oropharynx of a man undergoing circular pharyngolaryngectomy. Jejunal biopsies were collected during the transplantation procedures (cold and warm ischemia, reperfusion), during the 7 post-operative days through an exteriorized jejunal segment for flap monitoring, and 45 days after transplantation through an upper endoscopy. Matrix metalloproteinase (MMP)-3 and MMP-12 increase was accompanied by a parallel rise in apoptotic enterocytes, and by a concomitant reduction of surface area to volume ratio and enterocyte height. Goblet cell hyperplasia is coupled with Paneth cell disappearance at the crypt base. CD8-positive intraepithelial lymphocytes initially decrease, then they increase in accordance with the peak of enterocyte apoptosis. We identified alterations in lymphocyte infiltration, mucosal architecture and epithelial cell turnover, which may give a window to mechanisms of small bowel ischemia-reperfusion in humans.

Abnormal anandamide metabolism in celiac disease.

The endocannabinoid system has been extensively investigated in experimental colitis and inflammatory bowel disease, but not in celiac disease, where only a single study showed increased levels of the major endocannabinoid anandamide in the atrophic mucosa. On this basis, we aimed to investigate anandamide metabolism in celiac disease by analyzing transcript levels (through quantitative real-time reverse transcriptase-polymerase chain reaction), protein concentration (through immunoblotting) and activity (through radioassays) of enzymes responsible for anandamide synthesis (N-acylphosphatidyl-ethanolamine specific phospholipase D, NAPE-PLD) and degradation (fatty acid amide hydrolase, FAAH) in the duodenal mucosa of untreated celiac patients, celiac patients on a gluten-free diet for at least 12 months and control subjects. Also, treated celiac biopsies cultured ex vivo with peptic-tryptic digest of gliadin were investigated. Our in vivo experiments showed that mucosal NAPE-PLD expression and activity are higher in untreated celiac patients than treated celiac patients and controls, with no significant difference between the latter two groups. In keeping with the in vivo data, the ex vivo activity of NAPE-PLD was significantly enhanced by incubation of peptic-tryptic digest of gliadin with treated celiac biopsies. On the contrary, in vivo mucosal FAAH expression and activity did not change in the three groups of patients, and accordingly, mucosal FAAH activity was not influenced by treatment with peptic-tryptic digest of gliadin. In conclusion, our findings provide a possible pathophysiological explanation for the increased anandamide concentration previously shown in active celiac mucosa.

Involvement of CD40-CD40 ligand in uncomplicated and refractory celiac disease.

OBJECTIVES: Cognate interaction between CD40 on antigen-presenting cells and CD40 ligand (CD40L) on T cells is a crucial costimulatory signal in T-cell activation. In this study, we investigated CD40-CD40L expression in the duodenum of uncomplicated and refractory celiac disease patients, and explored the ex vivo effects of CD40L blockade on cytokine production and the T-helper cell type 1-specific transcription factor T-bet. METHODS: CD40L and colocalization of CD40 with the dendritic cell markers CD11c and CD123 were investigated by confocal microscopy on tissue sections of duodenal biopsy samples obtained from 14 uncomplicated celiac patients before and after 12 months of gluten-free diet, 5 refractory celiac patients, and 12 controls. CD40 was also analyzed by flow cytometry on single cell suspension of mucosal biopsies. Treated celiac biopsies were stimulated with peptic-tryptic digest of gliadin (PT-gliadin) with or without an anti-CD40L-neutralizing antibody. Interferon (IFN)-γ and interleukin (IL)-17 were measured by ELISA (enzyme-linked immunosorbent assay). T-bet, CD40, and CD40L were determined by immunoblotting. RESULTS: CD40 and CD40L expression was higher in uncomplicated untreated and refractory celiac patients than in controls; the expression returned to normal after gluten-free diet in uncomplicated patients. Flow cytometric analysis confirmed that most CD40(+) cells were dendritic cells. The addition of the anti-CD40L antibody to treated celiac biopsies significantly inhibited the PT-gliadin-induced production of IFN-γ and IL-17, and mucosal T-bet. CONCLUSIONS: Our results indicate that the CD40-CD40L pathway has a key role in celiac disease. Disruption of CD40-CD40L interaction may offer a therapeutic alternative in refractory celiac disease.

Role of IL-15 in immune-mediated and infectious diseases.

IL-15 has a broad spectrum of biological activities. It is crucial for the development, proliferation, survival and differentiation of multiple cells from both innate and adaptive immune systems. However, IL-15 up-regulation has a central role in the development of several autoimmune or chronic inflammatory disorders. Therefore, targeting IL-15 or its receptor may have a valuable impact on the treatment of immune-mediated diseases. On the other hand, in some infectious diseases, IL-15 production is compromised but IL-15 given exogenously can potentially enhance immune responses to pathogens. Here, we discuss the current understanding of IL-15 role in immune-mediated and infectious diseases as well as its therapeutic use.

Increased CD8+ intraepithelial lymphocyte infiltration and reduced surface area to volume ratio in the duodenum of patients with ulcerative colitis.

OBJECTIVE: Recent evidence suggests the involvement of the upper gastrointestinal tract in ulcerative colitis (UC). By conducting a prospective controlled study, we explored the immunological abnormalities in the duodenal mucosa of UC patients. METHODS: Duodenal and colonic biopsies were collected from 24 corticosteroid-free UC patients and 21 controls. Colonization by Helicobacter pylori and positivity for anti-endomysial antibodies was an exclusion criteria. The severity of duodenal and colonic inflammation was determined by endoscopic and histologic scores. Morphometry was performed to measure the surface area to volume ratio (SV). Duodenal CD3(+) and CD8(+) intraepithelial lymphocytes (IELs) and lamina propria mononuclear cells (LPMCs) were detected by immunohistochemistry. RESULTS: Fifteen UC patients and 14 controls were Helicobacter pylori and anti-endomysial antibody negative and were thus included in the study. Microscopic duodenitis was reported in 4 of the 15 UC patients (26.6%), and in none of the controls. A significantly higher number of CD3(+) and CD8(+) IELs and LPMCs was found in UC patients than in controls. A significant positive correlation between the percentage of both CD3(+) and CD8(+) IELs and disease activity was found in UC patients. SV was significantly reduced in UC patients compared to controls, and inversely correlated with the percentage of CD8(+) IELs. CONCLUSIONS: The duodenum of UC patients is infiltrated by a higher number of CD8(+) IELs which correlates with the degree of villous flattening and disease activity, but not with extent of the colonic lesions. Further studies are needed to clarify whether the duodenum is a target organ in UC.

Diagnostic assessment and therapeutic approach for immunodeficiency due to chylous dysplasia: A case report.

Among possible causes of a condition of immunodeficiency, we have to consider the presence of a serious chylous dysplasia, due to the great loss of proteins through the intestinal lumen. A 20-year-old male, suffered from diarrhoea (2-4 times a day), weight loss (8 kilos in 5 years), and malnutrition (hypogammaglobulinemia, hypoalbuminemia, leukocytopenia with lymphocytopenia). Accurate diagnostic assessment allowed to diagnose a protein-losing enteropathy. Conventional oil contrast lymphangiography allowed to accurately assess the case and to establish a proper therapeutic approach. The operation consisted in multiple antigravitational ligatures of dilated and incompetent chylous vessels and chylous vessel-mesenteric vein microanastomoses. Parameters concerning albumin and leukocytes normalized in 1 week after operation and remained stable with time; there were no more episodes of diarrhoea and the patient recovered weight. An accurate diagnostic assessment and above all lymphangiography allow to diagnose properly difficult cases of immunodeficiency due to intestinal protido-dispersion and to plan a correct therapeutic functional approach.