Obscure gastrointestinal bleeding: diagnostic and therapeutic approach

Obscure gastrointestinal bleeding (OGIB) is defined as an intermittent or continuous loss of blood in which the source has not been identified after upper endoscopy and colonoscopy. It constitutes a diagnostic and therapeutic challenge for the general internist and the gastroenterologist. This article provides an overview of the etiology, clinical presentation, and diagnostic modalities of OGIB including push enteroscopy, double balloon enteroscopy, wireless capsule endoscopy, enteroclysis, angiography, bleeding scanning with labeled red blood cells, and surgery with intraoperative enteroscopy. Therapeutic modalities including iron replacement, combined hormones, octreotide acetate, therapeutic endoscopy, and surgery are also discussed. In addition, a rational approach to patients with OGIB according to the clinical presentation is presented herein.     

HER2 status in breast cancer: experience of a Spanish National Reference Centre

Background  

Accurate HER2 testing is of great clinical value for the identification of breast cancer patients who are eligible for trastuzumab therapy. The aim of this study is to review breast carcinomas diagnosed from 2001 to 2007 at a Spanish National Reference Centre for HER2 testing, evaluating the agreement between HER2 immunohistochemical (IHC) tests and fluorescence in situ hybridisation (FISH) tests.     

Conserved mechanism for sensor phosphatase control of two-component signaling revealed in the nitrate sensor NarX

Two-component signal transduction mediates a wide range of phenotypes in microbes and plants. The sensor transmitter module controls the phosphorylation state of the cognate-response-regulator receiver domain. Whereas the two-component autokinase and phosphotransfer reactions are well-understood, the mechanism by which sensors accelerate the rate of phospho-response regulator dephosphorylation, termed "transmitter phosphatase activity," is unknown. We identified a conserved DxxxQ motif adjacent to the phospho-accepting His residue in the HisKA_3 subfamily of two-component sensors. We used site-specific mutagenesis to make substitutions for these conserved Gln and Asp residues in the nitrate-responsive NarX sensor and analyzed function both in vivo and in vitro. Results show that the Gln residue is critical for transmitter phosphatase activity, but is not essential for autokinase or phosphotransfer activities. The documented role of an amide moiety in phosphoryl group hydrolysis suggests an analogous catalytic function for this Gln residue in HisKA_3 members. Results also indicate that the Asp residue is important for both autokinase and transmitter phosphatase activities. Furthermore, we noted that sensors of the HisKA subfamily exhibit an analogous E/DxxT/N motif, the conserved Thr residue of which is critical for transmitter phosphatase activity of the EnvZ sensor. Thus, two-component sensors likely use similar mechanisms for receiver domain dephosphorylation.     

(TTA)n Polymorphism in 3‐Hydroxy‐3‐Methylglutaryl‐Coenzyme A and Response to Atorvastatin in Coronary Artery Disease Patients

Abstract: 3‐Hydroxy‐3‐methylglutaryl‐coenzyme A reductase inhibitors have been used clinically for lowering total and low‐density lipoprotein cholesterol. Interindividual pharmacological differences observed with this treatment have been attributed to genetic differences. The aim of this study was to assess the association in the low‐density lipoprotein cholesterol reduction by atorvastatin and (TTA)n polymorphism in the 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase gene in patients with coronary artery disease. Changes in total cholesterol levels, triglycerides, high‐sensitivity C‐reactive protein and free F₂‐isoprostanes were also evaluated. In an open study, patients received 40 mg atorvastatin daily for 8 weeks. Genotyping was done through polymerase chain reaction. The genotype distribution of the 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (TTA)n polymorphism was: >10/>10 in 22 out of 64 patients (34%), >10/10 in 14 out of 64 patients (22%) and 10/10 in 28 out of 64 patients (44%). The reduction of low‐density lipoprotein cholesterol levels by atorvastatin was not different between allelic variants (TTA)n repeat polymorphism. Reductions in high‐sensitivity C‐reactive protein were observed in atorvastatin‐treated patients with alleles >10/>10 and 10/10. Free F₂‐isoprostanes and total cholesterol were also significantly lower after treatment for all alleles, irrespective of type of polymorphism. In conclusion, the changes induced by atorvastatin treatment on low‐density lipoprotein cholesterol, total cholesterol, triglycerides, high‐sensitivity C‐reactive protein and free F₂‐isoprostane concentrations were not related to the presence of 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase polymorphism (TTA)n.     

The expression of TNF-alpha receptors 1 and 2 on peripheral blood mononuclear cells in chronic inflammatory demyelinating polyneuropathy

The proportion of peripheral blood mononuclear cells (PBMCs) expressing TNF-alpha and its receptors (TNFR1, TNFR2) and the serum concentrations of its soluble forms were analyzed by FACS and ELISA in the patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and in controls. Elevated levels of TNFR2 were observed on blood T cells in CIDP and idiopathic polyneuropathy. Low levels of TNFR1 were detected on monocytes in the subgroup of patients with CIDP examined after treatment with intravenous immunoglobulin. However, the proliferative activity of PBMCs in CIDP was not influenced by soluble recombinant TNFR1. Our limited data suggested the exact role of TNF-alpha and its receptors need to study further in CIDP, as well as in idiopathic neuropathies.     

Diffuse large B-cell lymphoma in a renal allograft associated with Epstein-Barr virus in the recipient: a case report and a review of lymphomas presenting in a transplanted kidney

Abstract:  The purpose of this review was to evaluate the case reports with lymphoproliferative disorders exclusively localized in the allograft transplanted kidney. We also report a rare case of diffuse large B-cell lymphoma originated from the lymphocytes of the recipient with exclusive localization in the kidney allograft. We searched the medical literature for case reports of this condition. We found only 16 cases of lymphoma presenting in the kidney allograft without systemic affectation. The most frequent clinical manifestations were graft dysfunction and fever. In the majority of patients included in this review, the diagnosis was established from the tissue of explanted allograft. Seven patients were diagnosed with B-cell lymphoma, and the relationship with Epstein-Barr virus could only be demonstrated in four patients. However, the outcome was satisfactory in all cases, except in one case in which death was not related with the lymphoma etiology. Health care providers should be aware of this clinical entity and heightened index of suspicion should be used so as not to delay diagnosis and not to lose the allograft.     

The histological spectrum of non-granulomatous localized mucosal leishmaniasis caused by Leishmania infantum

Although human mucosal leishmaniasis is much more common in Latin America, a few cases that are the result of local transmission occur in Europe. A suspected case of leishmaniasis is usually confirmed by the demonstration of amastigotes in smears, the culture of promastigotes from blood or tissue samples, or the PCR-based demonstration of leishmanial DNA. Biopsies may contain too few parasites to be found positive by microscopy or culture, however, and then a diagnosis may be difficult, especially in regions where human leishmaniasis in general or particular forms of the disease are rarely seen. The aim of the present study was to investigate the histopathological characteristics of three Spanish cases of non-granulomatous mucosal leishmaniasis caused by Leishmania infantum. The hope was that the information collected will help European clinicians diagnose such cases, even when amastigotes cannot be readily demonstrated.     

Thalamic diffusion and volumetry in temporal lobe epilepsy with and without mesial temporal sclerosis

PURPOSE: As an important connection within the limbic system, considerable attention has been paid to thalamic pathology in temporal lobe epilepsy (TLE). Magnetic resonance imaging (MRI) volumetric studies have yielded variable results and have largely been focused on TLE with mesial temporal sclerosis (TLE+). Diffusion tensor imaging (DTI) provides unique information on microstructure based on the measurement of water diffusion. To date, DTI properties of thalamus have not been well characterized in adult TLE patients with unilateral MTS or without MTS (TLE-). The purpose of this study was to investigate the status of thalamic integrity by using DTI as well as volumetric MRI in adult TLE+ and TLE- patients. METHOD: In 17 unilateral TLE+ patients, 10 TLE- patients and 26 controls, the thalamus was segmented by using an automated atlas-based method. Mean diffusivity (MD), fractional anisotropy (FA) and volume were then quantified from DTI and 3D T1-weighted scans. RESULTS: No significant changes were found in either DTI parameters or volume of thalamus in TLE- patients, as compared to healthy controls. However, both DTI parameters and MRI volumetry showed bilateral thalamic pathology in TLE+ patients, as compared to healthy controls. Also, TLE+ patients showed significant reduction of thalamic volume as compared to TLE- patients. In addition, thalamic FA ipsilateral to seizure focus showed significant correlation with age at onset of epilepsy in TLE+ patients. CONCLUSION: Our finding demonstrates bilateral pathology of thalamus in unilateral TLE+ patients. The discrepancy in thalamic pathology between TLE+ and TLE- patients suggests that along with differences in mesial temporal pathology, TLE+ and TLE- have unique extratemporal structural abnormalities.     

Non invasive ventilation after extubation in paediatric patients: a preliminary study

Background  

Non-invasive ventilation (NIV) may be useful after extubation in children. Our objective was to determine postextubation NIV characteristics and to identify risk factors of postextubation NIV failure.