ABSTRACT
BACKGROUND: The irritable bowel syndrome (IBS) is a functional gastrointestinal disorder whose pathogenesis is not completely understood. Its high prevalence and the considerable effects on quality of life make IBS a disease with high social cost. Recent studies suggest that low grade mucosal immune activation, increased intestinal permeability and the altered host-microbiota interactions that modulate innate immune response, contribute to the pathophysiology of IBS. However, the understanding of the precise molecular pathophysiology remains largely unknown. METHODOLOGY AND FINDINGS: In this study our objective was to evaluate the TLR expression as a key player in the innate immune response, in the colonic mucosa of IBS patients classified into the three main subtypes (with constipation, with diarrhea or mixed). TLR2 and TLR4 mRNA expression was assessed by real time RT-PCR while TLRs protein expression in intestinal epithelial cells was specifically assessed by flow cytometry and immunofluorescence. Mucosal inflammatory cytokine production was investigated by the multiplex technology. Here we report that the IBS-Mixed subgroup displayed a significant up-regulation of TLR2 and TLR4 in the colonic mucosa. Furthermore, these expressions were localized in the epithelial cells, opening new perspectives for a potential role of epithelial cells in host-immune interactions in IBS. In addition, the increased TLR expression in IBS-M patients elicited intracellular signaling pathways resulting in increased expression of the mucosal proinflammatory cytokines IL-8 and IL1ß. CONCLUSIONS: Our results provide the first evidence of differential expression of TLR in IBS patients according to the disease subtype. These results offer further support that microflora plays a central role in the complex pathophysiology of IBS providing novel pharmacological targets for this chronic gastrointestinal disorder according to bowel habits.
Subject(s)
Colon/metabolism , Intestinal Mucosa/metabolism , Irritable Bowel Syndrome/metabolism , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 4/metabolism , Adult , Aged , Case-Control Studies , Colon/immunology , Colon/pathology , Cytokines/metabolism , Female , Gene Expression , Humans , Inflammation Mediators/metabolism , Intestinal Mucosa/immunology , Intestinal Mucosa/pathology , Irritable Bowel Syndrome/immunology , Irritable Bowel Syndrome/pathology , Lipopolysaccharide Receptors/metabolism , Male , Middle Aged , PPAR gamma/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Toll-Like Receptor 2/genetics , Toll-Like Receptor 4/genetics , Up-RegulationABSTRACT
Mucosal surfaces play a major role in human immunodeficiency virus type 1 (HIV-1) transmission and pathogenesis. Since the role of intestinal macrophages as viral reservoirs during chronic HIV-1 infection has not been elucidated, we investigated the effects of successful therapy on intestinal HIV-1 persistence. Intestinal macrophage infection was demonstrated by the expression of p24 antigen by flow cytometry and by the presence of proviral DNA, assessed by PCR. Proviral DNA was detected in duodenal mucosa of HIV-infected patients under treatment with undetectable plasma viral load. These findings confirm that intestinal macrophages can act as viral reservoirs and permit HIV-1 production even after viral suppression following antiretroviral therapy.
Subject(s)
Antiretroviral Therapy, Highly Active/methods , Duodenum/virology , HIV Infections/drug therapy , HIV Infections/virology , HIV-1/isolation & purification , HIV-1/pathogenicity , Macrophages/virology , DNA, Viral/analysis , Female , Flow Cytometry , HIV Core Protein p24/analysis , Humans , Male , Polymerase Chain Reaction , Proviruses/geneticsABSTRACT
AIM: To determine prospectively the long-term evolution of patients with neurological diseases after insertion of percutaneous endoscopic gastrostomy (PEG). METHODS: 109 PEG were performed in 99 consecutive patients (49 females, 50 males), mean age 75 years (range: 20-97 years) as an alternative to a nasogastric tube. Patients were enterally fed because of chronic neurological swallowing difficulties: cerebrovascular disease 38, dementia 27, disordered swallowing mechanisms in elderly patients 10, motor neurona disease and multiple sclerosis 10, neuro-surgical disease 6, Parkinson's disease 3, brain tumor 3, neo-natal encephalopathy 1, HIV encephalopathy 1. The procedure took place in a dedicated endoscopy room. In all cases, prophylatic antibiotics were given and the PEG tube was inserted by the "pull" technique. RESULTS: PEG insertion was technically succesful in all cases. After PEG insertion, all patients were subsequently discharged to local nursing home facilities. 85/99 patients were long-term followed-up on an outpatient basis, 25% of them were followed for more than a year. The mean follow-up time was 3 months (range: 1-24 months). The most frequent complication were minor: local wound infection 6, ostomy leakage 8, silicon degradation 16, leading to the removal of the PEG and the placement of a new PEG tubes in 10 cases. Two major complications were observed : one gastric perforation and death 2 months after the PEG placement and one gastrocolic fistula. No aspiration pneumonia was reported. In one patient, PEG was removed after recuperation of a normal swallowing. All patients had a nutritional improvement. A total of 11 deaths occurred during the follow-up, related to the neurological disorder in 10/11 cases. Nursing home team, patient's physicians and patient's families found PEG manipulations easier than naso-gastric tube. CONCLUSION: Our study suggests that PEG is a method of choice for enteral feeding of patients with chronic neurological disorders. PEG is well-tolerated, leading to an improvement in nutritional status and offering good facilities for home nursing.
Subject(s)
Deglutition Disorders/therapy , Gastroscopy , Gastrostomy/methods , Nervous System Diseases/therapy , Adult , Aged , Aged, 80 and over , Deglutition Disorders/etiology , Enteral Nutrition , Female , Follow-Up Studies , Gastrostomy/adverse effects , Gastrostomy/standards , Humans , Male , Middle Aged , Nervous System Diseases/complications , Prospective StudiesABSTRACT
AIM: To determine prospectively the long-term evolution of patients with neurological diseases after insertion of percutaneous endoscopic gastrostomy (PEG). METHODS: 109 PEG were performed in 99 consecutive patients (49 females, 50 males), mean age 75 years (range: 20-97 years) as an alternative to a nasogastric tube. Patients were enterally fed because of chronic neurological swallowing difficulties: cerebrovascular disease 38, dementia 27, disordered swallowing mechanisms in elderly patients 10, motor neurona disease and multiple sclerosis 10, neuro-surgical disease 6, Parkinsons disease 3, brain tumor 3, neo-natal encephalopathy 1, HIV encephalopathy 1. The procedure took place in a dedicated endoscopy room. In all cases, prophylatic antibiotics were given and the PEG tube was inserted by the [quot ]pull[quot ] technique. RESULTS: PEG insertion was technically succesful in all cases. After PEG insertion, all patients were subsequently discharged to local nursing home facilities. 85/99 patients were long-term followed-up on an outpatient basis, 25
of them were followed for more than a year. The mean follow-up time was 3 months (range: 1-24 months). The most frequent complication were minor: local wound infection 6, ostomy leakage 8, silicon degradation 16, leading to the removal of the PEG and the placement of a new PEG tubes in 10 cases. Two major complications were observed : one gastric perforation and death 2 months after the PEG placement and one gastrocolic fistula. No aspiration pneumonia was reported. In one patient, PEG was removed after recuperation of a normal swallowing. All patients had a nutritional improvement. A total of 11 deaths occurred during the follow-up, related to the neurological disorder in 10/11 cases. Nursing home team, patients physicians and patients families found PEG manipulations easier than naso-gastric tube. CONCLUSION: Our study suggests that PEG is a method of choice for enteral feeding of patients with chronic neurological disorders. PEG is well-tolerated, leading to an improvement in nutritional status and offering good facilities for home nursing.
ABSTRACT
Opportunistic esophageal infections (Candida, cytomegalovirus, herpes simplex virus) and idiophatic esophageal ulcerations are commonly found in HIV patients. However, motility disorders of the esophagus have seldom been investigated in this population. The aim of this prospective study was to determine the presence of motility disorders in HIV patients with esophageal symptoms (with or without associated lesions detected by endoscopy) and in HIV patients without esophageal symptoms and normal esophagoscopy. Eigthteen consecutive HIV patients (10 male, 8 female, ages 20-44 years, mean age 33.5; 8 HIV positive and 10 AIDS) were studied prospectively. Nine patients complained of esophageal symptoms, e.g, dysphagia/odynophagia (group 1) and 9 had symptoms not related to esophageal disease, such as diarrhea, abdominal pain, or gastrointestinal bleeding (group 2). All patients underwent upper endoscopy; mucosal biopsies were taken when macroscopic esophageal lesions were identified or when the patients were symptomatic even if the esophageal mucosa was normal. Esophageal manometry was performed in the 18 patients, using a 4-channel water-perfused system according to a standardized technique. Sixteen of the 18 patients (88.8%) had baseline manometric abnormalities. In group 1, 8/9 patients had esophageal motility disorders: nutcrackeresophagus in 1, hypertensive lower esophageal sphincter (LES) with incomplete relaxation in 2, nonspecific esophageal motility disorders (NEMD) in 3, diffuse esophageal spasm in 1, esophageal hypocontraction with low LES pressure in 1. Six of these 9 patients had lesions detected by endoscopy: CMV ulcers in 2, idiopathic ulcers in 1, candidiasis in 1, idiopathic ulcer + candidiasis in 1, nonspecific esophagitis in 1; and 3/9 had normal endoscopy and normal esophageal biopsies. In group 2, 8/9 patients had abnormal motility: hypertensive LES with incomplete relaxation in 1, nutcracker esophagus in 2, esophageal hypocontraction in 3, and NEMD in 2. All these patients had a normal esophageal mucosa at endoscopy. In conclusion, our findings suggest that HIV patients have esophageal motility disorders independent of esophageal symptoms and/or the presence of mucosal esophageal lesions.
Subject(s)
Esophageal Motility Disorders/epidemiology , HIV Infections/epidemiology , Acquired Immunodeficiency Syndrome/diagnosis , Acquired Immunodeficiency Syndrome/epidemiology , Adult , Comorbidity , Esophageal Motility Disorders/diagnosis , Esophagoscopy , Female , Follow-Up Studies , HIV Infections/diagnosis , Humans , Incidence , Male , Manometry/methods , Prospective Studies , Risk Factors , Sampling Studies , Severity of Illness Index , Sex DistributionABSTRACT
La enfermedad por reflujo gastroesofágico es una de las situaciones clínicas más comunes. El esófago de Barrett(EB) es su consecuencia evolutiva más importante y está asociado con un riesgo incrementado de adenocarcinoma. Ultimamente se han desarrollado nuevos marcadores para detectar la psobilidad de malignización. La cirugía antirreflujo es la alternativa del tratamiento médico. No se han podido establecer si se consigue la regresión del epitelio columnar especializado y displasia para evitar la progresión al cáncer. Por consiguiente, debe realizarse la vigilancia endoscópica por el riesgo de adenocarcinoma. La ablación endoscópica de la mucosa con metaplasia intestinal parece ser una técnica prometedora en este grupo de pacientes
Subject(s)
Humans , Adult , Barrett Esophagus/diagnosis , Barrett Esophagus/physiopathology , Barrett Esophagus/therapy , Gastroesophageal Reflux/surgery , Gastroesophageal Reflux/physiopathology , General Surgery , Digestive System , GastroenterologyABSTRACT
La enfermedad por reflujo gastroesofágico es una de las situaciones clínicas más comunes. El esófago de Barrett(EB) es su consecuencia evolutiva más importante y está asociado con un riesgo incrementado de adenocarcinoma. Ultimamente se han desarrollado nuevos marcadores para detectar la psobilidad de malignización. La cirugía antirreflujo es la alternativa del tratamiento médico. No se han podido establecer si se consigue la regresión del epitelio columnar especializado y displasia para evitar la progresión al cáncer. Por consiguiente, debe realizarse la vigilancia endoscópica por el riesgo de adenocarcinoma. La ablación endoscópica de la mucosa con metaplasia intestinal parece ser una técnica prometedora en este grupo de pacientes