Second-generation colon capsule endoscopy compared with colonoscopy

Colon capsule endoscopy (CCE) represents a noninvasive technology that allows visualization of the colon without requiring sedation and air insufflation. A second-generation colon capsule endoscopy system (PillCam Colon 2) (CCE-2) was developed to increase sensitivity for colorectal polyp detection compared with the first-generation system. OBJECTIVE: To assess the feasibility, accuracy, and safety of CCE-2 in a head-to-head comparison with colonoscopy. DESIGN AND SETTING: Prospective, multicenter trial including 8 European sites. PATIENTS: This study involved 117 patients (mean age 60 years). Data from 109 patients were analyzed. INTERVENTION: CCE-2 was prospectively compared with conventional colonoscopy as the criterion standard for the detection of colorectal polyps that are >/=6 mm or masses in a cohort of patients at average or increased risk of colorectal neoplasia. Colonoscopy was independently performed within 10 hours after capsule ingestion or on the next day. MAIN OUTCOME MEASUREMENTS: CCE-2 sensitivity and specificity for detecting patients with polyps >/=6 mm and >/=10 mm were assessed. Capsule-positive but colonoscopy-negative cases were counted as false positive. Capsule excretion rate, level of bowel preparation, and rate of adverse events also were assessed. RESULTS: Per-patient CCE-2 sensitivity for polyps >/=6 mm and >/=10 mm was 84% and 88%, with specificities of 64% and 95%, respectively. All 3 invasive carcinomas were detected by CCE-2. The capsule excretion rate was 88% within 10 hours. Overall colon cleanliness for CCE-2 was adequate in 81% of patients. LIMITATIONS: Not unblinding the CCE-2 results at colonoscopy; heterogenous patient population; nonconsecutive patients. CONCLUSION: In this European, multicenter study, CCE-2 appeared to have a high sensitivity for the detection of clinically relevant polypoid lesions, and it might be considered an adequate tool for colorectal imaging

Colonic Biopsies to Assess the Neuropathology of Parkinson's Disease and Its Relationship with Symptoms

The presence of Lewy bodies and Lewy neurites (LN) has been demonstrated in the enteric nervous system (ENS) of Parkinson's disease (PD) patients. The aims of the present research were to use routine colonoscopy biopsies (1) to analyze, in depth, enteric pathology throughout the colonic submucosal plexus (SMP), and (2) to correlate the pathological burden with neurological and gastrointestinal (GI) symptoms.A total of 10 control and 29 PD patients divided into 3 groups according to disease duration were included. PD and GI symptoms were assessed using the Unified Parkinson's Disease Rating Scale part III and the Rome III questionnaire, respectively. Four biopsies were taken from the ascending and descending colon during the course of a total colonoscopy. Immunohistochemical analysis was performed using antibodies against phosphorylated alpha-synuclein, neurofilaments NF 220 kDa (NF) and tyrosine hydroxylase (TH). The density of LN, labeled by anti-phosphorylated alpha-synuclein antibodies, was evaluated using a quantitative rating score. Lewy pathology was apparent in the colonic biopsies from 21 patients and in none of the controls. A decreased number of NF-immunoreactive neurons per ganglion was observed in the SMP of PD patients compared to controls. The amount of LN in the ENS was inversely correlated with neuronal count and positively correlated with levodopa-unresponsive features and constipation.Analysis of the ENS by routine colonoscopy biopsies is a useful tool for pre-mortem neuropathological diagnosis of PD, and also provides insight into the progression of motor and non-motor symptoms

The French national prospective cohort of patients co-infected with HIV and HCV (ANRS CO13 HEPAVIH): Early findings, 2006-2010

<p>Abstract</p> <p>Background</p> <p>In France, it is estimated that 24% of HIV-infected patients are also infected with HCV. Longitudinal studies addressing clinical and public health questions related to HIV-HCV co-infection (HIV-HCV clinical progression and its determinants including genetic dimension, patients' experience with these two diseases and their treatments) are limited. The ANRS CO 13 HEPAVIH cohort was set up to explore these critical questions.</p> <p>To describe the cohort aims and organization, monitoring and data collection procedures, baseline characteristics, as well as follow-up findings to date.</p> <p>Methods</p> <p>Inclusion criteria in the cohort were: age > 18 years, HIV-1 infection, chronic hepatitis C virus (HCV) infection or sustained response to HCV treatment. A standardized medical questionnaire collecting socio-demographic, clinical, biological, therapeutic, histological, ultrasound and endoscopic data is administered at enrolment, then every six months for cirrhotic patients or yearly for non-cirrhotic patients. Also, a self-administered questionnaire documenting socio-behavioral data and adherence to HIV and/or HCV treatments is administered at enrolment and yearly thereafter.</p> <p>Results</p> <p>A total of 1,175 patients were included from January 2006 to December 2008. Their median age at enrolment was 45 years and 70.2% were male. The median CD4 cell count was 442 (IQR: 304-633) cells/μl and HIV RNA plasma viral load was undetectable in 68.8%. Most participants (71.6%) were on HAART. Among the 1,048 HIV-HCV chronically co-infected patients, HCV genotype 1 was predominant (56%) and cirrhosis was present in 25%. As of January, 2010, after a median follow-up of 16.7 months (IQR: 11.3-25.3), 13 new cases of decompensated cirrhosis, nine hepatocellular carcinomas and 20 HCV-related deaths were reported, resulting in a cumulative HCV-related severe event rate of 1.9/100 person-years (95% CI: 1.3-2.5). The rate of HCV-related severe events was higher in cirrhotic patients and those with a low CD4 cells count, but did not differ according to sex, age, alcohol consumption, CDC clinical stage or HCV status.</p> <p>Conclusion</p> <p>The ANRS CO 13 HEPAVIH is a nation-wide cohort using a large network of HIV treatment, infectious diseases and internal medicine clinics in France, and thus is highly representative of the French population living with these two viruses and in care.</p

Characterisation of early mucosal and neuronal lesions following Shigella flexneri infection in human colon.

BACKGROUND: Shigella, an enteroinvasive bacteria induces a major inflammatory response responsible for acute rectocolitis in humans. However, early effect of Shigella flexneri (S. flexneri) infection upon the human mucosa and its microenvironement, in particular the enteric nervous system, remains currently unknown. Therefore, in this study, we sought to characterize ex vivo the early events of shigellosis in a model of human colonic explants. In particular, we aimed at identifying factors produced by S. flexneri and responsible for the lesions of the barrier. We also aimed at determining the putative lesions of the enteric nervous system induced by S. flexneri. METHODOLOGY/PRINCIPAL FINDINGS: We first showed that, following 3 h of infection, the invasive but not the non-invasive strain of S. flexneri induced significant desquamation of the intestinal epithelial barrier and a reduction of epithelial height. These changes were significantly reduced following infection with SepA deficient S. flexneri strains. Secondly, S. flexneri induced rapid neuronal morphological alterations suggestive of cell death in enteric submucosal neurones. These alterations were associated with a significant increase in the proportion of vasoactive intestinal peptide (VIP) immunoreactive (IR) neurons but not in total VIP levels. The NMDA receptor antagonist MK-801 blocked neuronal morphological changes induced by S. flexneri, but not the increase in the proportion of VIP-IR. CONCLUSIONS/SIGNIFICANCE: This human explant model can be used to gain better insight into the early pathogenic events following S. flexneri infection and the mechanisms involved

Functional esophageal disorders

Functional esophageal disorders represent processes accompanied by typical esophageal symptoms (heartburn, chest pain, dysphagia, globus) that are not explained by structural disorders, histopathology-based motor disturbances, or gastroesophageal reflux disease. Gastroesophageal reflux disease is the preferred diagnosis when reflux esophagitis or excessive esophageal acid exposure is present or when symptoms are closely related to acid reflux events or respond to antireflux therapy. A singular, well-defined pathogenetic mechanism is unavailable for any of these disorders; combinations of sensory and motor abnormalities involving both central and peripheral neural dysfunction have been invoked for some. Treatments remain empirical, although the efficacy of several interventions has been established in the case of functional chest pain. Management approaches that modulate central symptom perception or amplification often are required once local provoking factors (eg, noxious esophageal stimuli) have been eliminated. Future research directions include further determination of fundamental mechanisms responsible for symptoms, development of novel management strategies, and definition of the most cost-effective diagnostic and treatment approache

6-(Arylvinylene)-3-bromopyridine derivatives as lego building blocks for liquid crystal, nonlinear optical, and blue light emitting chromophores

International audienceA novel general synthetic strategy, based on a convergent approach, allowed us to prepare a series of conjugated 6,6′-distyryl-3,3′-bipyridine derivatives via the Suzuki reaction. First, the key electron-donor and electron-acceptor 6-(arylvinylene)-3-bromopyridine building blocks were synthesized by Knoevenagel-or Siegrist-type reactions. Second, some of them were transformed to the corresponding pyridylboronic esters. Finally, for the first time, we successfully demonstrated that such blocks can be homo- and cross-coupled in high yields and multigram scales, leading to noncentrosymmetic or symmetric chromophores. Their mesogenic, electrochemical, and optical properties have been investigated depending on the electronic structure. In this series, push-pull compounds are liquid crystals and promising for NLO applications. Whatever the structure, all of these compounds exhibit a high electron affinity and are strongly fluorescent. As an application, lasing properties of one push-pull and one symmetrical compound are reported. In addition, a blue-emitting LED was fabricated whose performances at 10 mA/cm 2 are a luminous efficiency of 3.9 cd/A, a power efficiency of 1.4 lmAV, and an external quantum efficiency of 2.9%. Thus, this versatile synthetic route is of particular interest due to the potential applications of the chromophores in several optoelectronic fields

Effects of <i>S. flexneri</i> on the expression of vasoactive intestinal peptide (VIP) in submucosal neurones.

<p>In tissues infected with the non-invasive strain of <i>S. flexneri</i> (BS176), some NSE-immunoreactive (IR) neurons (A) were faintly VIP-IR (B). In contrast, following M90T infection, NSE-IR neurons (C) were strongly VIP-IR (D). Analysis of VIP content in submucosal preparation containing submucosal plexus revealed no difference in VIP content between tissue infected with M90T, BS176 or non-infected control tissue (n = 11). Bar: 25 µm.</p

Transmission electronic microscopy of submucosal ganglia from human colonic explants infected or not with the invasive strain of <i>S. flexneri</i> (M90T).

<p>(A) Submucosal ganglia from non-infected control tissues showed neurons with normal size and shape (double arrows indicating maximal cellular diameter). (B) In contrast, submucosal ganglia from tissues infected with M90T for 3 h showed neuronal cell shrinkage. (C) Submucosal ganglia containing neurons with various stages of cell shrinkage: intact neuron (empty arrow), neuron with beginning cell shrinkage (filled arrow), neuron with advanced cell shrinkage (white square). (D) Magnified view of the selected area in C showing the presence of multilamellar bodies (empty arrow), the presence of lipofuscin granula (filled arrow) and also swollen neuronal processes (arrowhead). (E) Nerve fiber bundle observed in tissue infected with M90T showing axonal swelling (arrowhead) and also the presence of pycnotic enteric glial cell nucleus (arrow). (F) Magnified view of the selected area in E showing condensed heterochromatine of cell nucleus and the presence of lysosomatic vesicle (arrowhead) in an enteric glial cell. Bar: 10 µm (A, B, C), 2 µm (D, E), 1 µm (F).</p

IL-8 secretion by colonic explants following infection with strains of <i>S.flexneri</i>.

<p>Following 3 h culture, IL-8 levels were significantly reduced following infection with the invasive strain (M90T) as compared to control non-infected tissue. In addition, no significant difference in IL-8 secretion following infection with the non-invasive strain (BS176) was observed as compared to control or following M90T infection. Data are expressed as mean±SEM (n = 4, * p<0.05).</p