New diagnostic and therapeutic frontiers in eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a relatively new disease that is increasingly recognized as a chronic inflammatory condition with currently evolving diagnostic and therapeutic aspects. There is data to support the rising prevalence of EOE especially in western countries. EoE is an emerging cause of dysphagia and food bolus impaction in adults as well as abdominal pain, feeding disorders, and gastroesophageal reflux-like symptoms in younger patients. EoE is ever more recognized as a separate disease process that is more complicated than eosinophilic infiltration from gastroesophageal reflux disease. Food and environmental antigens both play significant roles in stimulating T-helper (Th-2) inflammatory response. Current therapeutic options include use of proton-pump inhibitors, immunosuppressive drugs, elimination diets, and esophageal dilatation. Simple elimination of food and environmental antigen exposure can be challenging in adults due to the difficulty in accurately identifying triggering antigens and adherence to restrictive diets from a wide range of putative food allergens. Novel therapeutic options are being presented as potential treatments that target chemokines and specific immunologic mechanisms for EoE. This review will aim to summarize the latest and evolving approaches to EoE diagnosis and management. In the future, biomarkers of inflammatory response may help diagnose, treat, and stratify individual patients for better treatment outcomes with this chronic disease.

Predictive biomarkers for Barrett's esophagus: so near and yet so far.

Barrett's esophagus (BE) is the strongest risk factor for the development of esophageal adenocarcinoma. However, the risk of cancer progression is difficult to ascertain in individuals, as a significant number of patients with BE do not necessarily progress to esophageal adenocarcinoma. There are several issues with the current strategy of using dysplasia as a marker of disease progression. It is subject to sampling error during biopsy acquisition and interobserver variability among gastrointestinal pathologists. Ideal biomarkers with high sensitivity and specificity are needed to accurately detect high-risk BE patients for early intervention and appropriate cost-effective surveillance. To date, there are no available molecular tests in routine clinical practice despite known genetic and epigenetic aberrations in the Barrett's epithelium. In this review, we present potential biomarkers for the prediction of malignant progression in BE. These include markers of genomic instability, tumor suppressor loci abnormalities, epigenetic changes, proliferation markers, cell cycle predictors, and immunohistochemical markers. Further work in translating biomarkers for routine clinical use may eventually lead to accurate risk stratification.

Medical and endoscopic management of high-grade dysplasia in Barrett's esophagus.

The management of high-grade dysplasia in Barrett's esophagus has clearly changed over recent years. The risk of cancer development is still substantial, with about one in three patients developing cancer, but a number of patients do not develop cancer. The nature of high-grade dysplasia has also been genetically elucidated with more evidence of chromosomal instability being present at this stage than previously thought. Therapy of the condition has evolved more toward endoscopic therapy, given the good results of radio-frequency ablation and photodynamic therapy in eliminating dysplasia and decreasing cancer development in randomized controlled trial. The best candidates for treatment include compliant patients that have relatively short segments of Barrett's esophagus, an anatomically straight segment, lack of nodularity, and an intact p16. However, even with excellent long-term results similar to surgical resection, the risk of recurrence is present in over 14% of patients, which indicates that there will be a need to continue surveillance endoscopy in these patients.

Early treatment improves outcomes in acute hepatitis C virus infection: a meta-analysis.

Acute hepatitis C virus infection is associated with high rates of spontaneous clearance and variable rates of treatment-induced clearance. The benefit of early treatment versus awaiting spontaneous clearance is unknown, as is the optimal timing of treatment.We performed a MEDLINE and EMBASE search for the time period 1950 to October 2008. All English language abstracts using the search terms acute hepatitis C, hepatitis C and acute and hepatitis C and acute disease or acute infection were reviewed. Bibliographies were reviewed.Twenty-two studies including 1075 patients met the inclusion criteria. The sustained virologic response (SVR) rate for treated patients was 78%, significantly higher than 55.1% in untreated patients (OR = 3.08, 95% CI: 1.8-4.8 P value <0.0001). Mean time from diagnosis to spontaneous clearance was 9.7 weeks (SD 6.5). SVR rates varied inversely with time from acute HCV diagnosis. SVR rates for treatment within 12 weeks was 82.5% (95% CI: 75.6-89.3), significantly better than the clearance rates in untreated patients (P < 0.001). Response rates fell to 66.9% for treatment between 12 and 24 weeks, and decreased further to 62.5% for treatment beyond 24 weeks. Rates of viral clearance in treated patients with acute hepatitis C virus infection were significantly higher than that in untreated patients. Treatment rates were highest when treatment was initiated within 12 weeks of diagnosis. Based on these findings, we would advocate a 12 week period of observation for spontaneous clearance before treatment initiation. If no clearance has occurred by 12 weeks, treatment should be initiated.

La Tomografía por Emisión de Positrones (PET) en la práctica clínica oncológica / Positron emission tomography (PET) in oncological clinical practice

La Tomografía por Emisión de Positrones con 18F-fluorodeoxiglucosa (PET-FDG) es una técnica de diagnóstico por imagen cuyo uso se ha generalizado en España durante la última década. Existen una serie de indicaciones concretas, en las cuales la PET-FDG ha demostrado sobradamente su superioridad con respecto a los métodos convencionales de diagnóstico. Es recomendable, por ello, realizar un estudio PET-FDG únicamente en las siguientes situaciones: la estadificación de tumores pulmonares y linfomas, la re-estadificación de tumores de tiroides, colorrectales, de cabeza-cuello, linfomas y melanomas; la localización de tumores de origen desconocido; la caracterización del nódulo pulmonar solitario; y, por último, el diagnóstico diferencial recidiva/radionecrosis en tumores cerebrales (AU)

Cambios post-quirúrgicos en cirugía abdominal. A propósito de un caso / Post-surgical changes in abdominal surgery. Based on one case

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17. Utility of Metabolic Imaging in Oral Squamous Cell Carcinoma (SCC) Staging. Experience in 30 Patients.

Purpose: SCC represents nearly 90% of all oral malignancies, with an increasing incidence. Accurate Tumour-Node-Metastasis staging (TNM) is mandatory for planning surgical options and chemotherapy-radiotherapy management. Positron Emission Tomography (PET) using 18F-Fluorodeoxyglucose (FDG) provides functional information about tumoral tissues that may improve preoperative staging obtained by conventional morphologic procedures (CT-MRI). The purpose of this study is to evaluate the accuracy of FDG-PET in oral SCC staging and to compare those data from conventional and PET studies according to the pathologic results obtained from surgical specimen.Methods: A prospective study of 30 patients was carried out, through a 26 months period. Inclusion criteria include positive biopsy for Oral SCC, no other malignancies during the past 5 year and surgery as preferred therapeutic option. All patients underwent CT, MRI, and FDG-PET studies consecutively. Results obtained from conventional and PET preoperative staging were compared with those from postoperative histopathological studiesResults: FDG-PET modified preoperative staging obtained by conventional morphologic studies in 21% cases, which was confirmed postoperatively by histological findings. Kappa test showed higher values for PET studies (0.89) than conventional studies (0.41), when compared with postoperative controlConclusion: FDG-PET may be helpful to improve the accuracy of conventional studies in oral SCC preoperative TNM staging, although no definitive conclusions can be withdrawn due to the limited size of the sample. Modifications of preoperative staging showed by PET are a matter of controversy and must be kept in mind for further studies.

In vivo anti-hypertensive effect of Pterocarpus indicus aqueous leaf extract in male cats

This study aimed to investigate the anti-hypertensive potential of crude leaf extracts of Pterocarpus indicus (Narra). Hypertension was induced using Epinephrine HCI, 15-20 ug/kg body weight IV in 6 male cats, followed by an administration of Narra leaf extracts with a concentration of 0.25 g/kg BW IV at the peak of the epinephrines hypertensive effect. To test for the possible dose-response effect, the procedure was repeated using 0.5 and 1 g/kg BW IV Narra extracts. The systolic, diastolic and mean arterial blood pressures, pulse pressure, respiratory rate (SBP, OBP, MABP, PP and RR, respectively), respiratory and ECG (Q-R interval) amplitude, and the time for the Narra extract to effect were monitored using GrassO polygraph. Analysis of the data using General Linear Model (GLM) Repeated Measures showed that crude Narra leaf extracts at 0.25, 0.5 and 1 g/kg BW significantly lowered an epinephrine-induced rise in SBP (p=0.001), MABP (p=0.001), PP (p=0.0001) and ECG (Q-R interval) amplitude (p=0.05). However, there was no observed effect on the DBP (p=0.698), HR (p=0.9), RR (p=0.846) and respiratory amplitude (p=0.762). Moreover, no dose-response relationship was observed among the 3 doses of the narra extract on all physiologic parameters mentioned. Also, none of the doses was able to return the MABP to baseline (p=0.053). The observed decline in the SBP may have probably been due to the resultant decrease in the amplitude or force of contraction of the heart. Concomitantly, this may cause a decrease in the anti-hypertensive effect. (Author)

Molecular pharmacological differences in the interaction of serotonin with 5-hydroxytryptamine1C and 5-hydroxytryptamine2 receptors.

5-Hydroxytryptamine (5HT)1C and 5HT2 receptors appear to be closely related, from a molecular viewpoint, displaying similar second messenger systems and a high degree of sequence homology. However, there are striking differences in the interactions of 5HT with 5HT1C and 5HT2 receptors; 5HT is generally more potent in stimulating responses mediated through 5HT1C receptors than responses mediated through 5HT2 receptors. Also [3H]5HT labels 5HT1C receptors and not 5HT2 receptors. In order to explore more fully the molecular rationale for these differences, radioligand binding studies were performed in rat, human, and porcine brain and choroid plexus tissues and in mammalian cells transfected with rat 5HT1C or 5HT2 receptors; second messenger studies (inositol phosphate accumulation) were performed in the transfected cells. The second messenger studies confirmed the approximately 10-fold higher potency of 5HT in stimulating intracellular responses through 5HT1C receptors (EC50 = 8.3 nM) than in stimulating intracellular responses through 5HT2 receptors (EC50 = 101 nM). An agonist radioligand selective for the 5HT1C and 5HT2 receptors, 2,5-dimethoxy-(4-[125I]iodo)phenylisopropylamine, was used, as well as [3H]5HT, [3H]mesulergine (antagonist radioligand for 5HT1C receptors), and [3H]ketanserin (antagonist radioligand for 5HT2 receptors). Computer-assisted analyses of the binding data revealed two agonist affinity states for the 5HT1C receptor. The agonist high affinity state of the receptor was modifiable by guanyl nucleotides. The proportion of agonist high affinity states, relative to the total receptor population, was approximately 10% for both receptors. The apparent higher affinity of 5HT for the radiolabeled 5HT1C receptors was due to the higher affinity 5HT displayed for the agonist low affinity state of the 5HT1C receptor, compared with the affinity of 5HT for the agonist low affinity state of the 5HT2 receptor. The correspondence between the higher affinity of 5HT for the agonist low affinity state of the 5HT1C receptor, relative to the 5HT2 receptor, and the higher potency of 5HT in stimulating 5HT1C responses indicates that 5HT interacts with the agonist low affinity state of the 5HT1C and 5HT2 receptors in initiating its biological effects. These observations indicate that guanine nucleotide-binding protein (G protein)-coupled receptors can exhibit high affinity for neurotransmitters in both the free receptor and the G protein-coupled states and that receptors exhibiting this property may represent a novel subfamily of G protein-coupled receptors.