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Santa Maria Nuova, Italy

Kusnik B.,Pathology
Zeitschrift für Gastroenterologie

Lymphocytic colitis is a disease characterised by chronic watery diarrhoea that can only be diagnosed histologically, since colonoscopy reveals macroscopically normal mucosa. A causal relationship to the administration of certain drugs has repeatedly been described. In this report we describe a case of lymphocytic colitis that developed after initiation of treatment with duloxetine - a selective serotonin- and noradrenaline-reuptake inhibitor - and remitted after discontinuation of the drug. Since a causal relationship between the onset of lymphocytic colitis and the use of duloxetine is highly probable, duloxetine should be included among those drugs capable of inducing lymphocytic colitis. Georg Thieme Verlag KG Stuttgart. New York. Source

Chou S.-J.,Orthodontics | Alawi F.,Pathology
Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology

Emerging evidence suggests that an intact DNA damage response (DDR) serves as a potent barrier to malignant transformation. Using immunohistochemistry and patient-derived biopsy samples, we investigated whether the same may hold true during oral carcinogenesis. DNA damage accumulates early in the development of oral squamous cell carcinoma (OSCC) as evidenced by the detection of surrogate DDR biomarkers γ-H2A.X and phosphorylated CHK2threonine-68 (phospho-CHK2Thr68) in epithelial hyperplasias. However, whereas γ-H2A.X expression peaked in dysplastic epithelium, its levels were significantly reduced in OSCCs (χ2 = 7.655; P = .02). In contrast, there was a trend toward increased phospho-CHK2Thr68 expression with increasing severity of the pathology. Nonetheless, combined expression of the biomarkers was significantly greater in the nontransformed tissues relative to OSCCs (χ2 = 6.42; P = .04). Thus, our findings suggest that early therapeutic exploitation of the DDR may be worthy of investigation as a means by which to limit OSCC development. © 2011 Mosby, Inc. Source

Clementsen P.F.,Copenhagen University | Skov B.G.,Pathology | Vilmann P.,Copenhagen University | Krasnik M.,Copenhagen University
Journal of Bronchology and Interventional Pulmonology

Background: Mediastinoscopy is the gold standard for preoperative mediastinal staging of patients with suspected or proven lung cancer. Since the development of endoscopic ultrasound-guided biopsy via the trachea (EBUS-TBNA), this status has been challenged. The purpose of the study was to examine whether mediastinoscopy is necessary, when EBUS-TBNA is performed in a center with (1) a high level of expertise, (2) "bed side" microscopy by a pathologist, (3) general anesthesia, and (4) achievement of representative tissue from station 4R, 7 and 4L, that is, the same mediastinal stations that mediastinoscopy gives access to. Methods: A total of 95 consecutive patients with known or suspected lung cancer were referred for staging by EBUS-TBNA, which was performed as described.Results: Benign and malignant disease was found in the mediastinum of 6 and 13 patients, respectively. The remaining 76 patients were operated, resulting in 9 benign and 67 malignant diagnoses; spread was found to station 4R, 5, and 5 and 6 in 4 patients. The negative predictive value (NPV) was 63/67=0.94. However, if you exclude station 5 and 6, as they cannot be reached by neither EBUS nor mediastinoscopy, NPV was 66/ 67=0.99. The sensitivity was 0.76, and the specificity was 1.0. Conclusions: When EBUS-TBNA is performed under optimal conditions including general anesthesia and "bed side" microscopy performed by a pathologist resulting in representative biopsies from station 4R, 7, and 4L, the NPV is so high that mediastinoscopy seems unnecessary. © 2014 by Lippincott Williams & Wilkins. Source

Kinra P.,Pathology | Dutta V.,AFMC
Tropical Biomedicine

Complicated Plasmodium falciparum infection is associated with a 6.4% mortality rate in India, yet its prognostication is incompletely understood. The conventional prognostic markers of falciparum malaria include clinical, haematological and biochemical parameters. However these factors are non-specific. Hence there is a need of an accurate inexpensive objective marker for prognosticating falciparum malaria infection outcomes. Angiopoietins, angiogenic factors, eotaxins, adhesion molecules and inflammatory cytokines have been studied for prognostication of this common disease. Determination of the first four is technically difficult and requires a high level of expertise and equipment. Intermediary cytokines have the most promising role. This study was conducted with the aim to evaluate the serum level of TNF-α in patients with P. falciparum malaria and carry out statistical analysis of levels of serum TNF-α with parasite index, age, severity of anaemia, hypoglycaemia, hepatic and renal dysfunction. In our study the average TNF alpha level in 91healthy controls was 46.42 pg/ml whereas that in mild falciparum malaria was 100.45 pg/ml, in severe malaria - 278.63 pg/ml and in cerebral malaria it was 532.6 pg/ml. The mean TNF alpha level was significantly different in severe malaria and cerebral malaria compared to that in healthy controls (p < 0.02). The difference in levels of TNF alpha was significantly higher in falciparum malaria patients with anaemia, altered liver functions, hyperparasitemia, leucocytosis, hepatosplenomegaly and hypoglycaemia. The TNF levels did not correlate well with haemolysis markers and patients with altered renal function. Hence a raised TNF alpha can predict the likelihood of oncoming anaemia, hypoglycaemia, altered hepatic function and leucocytosis but not the grades of malaria. The duration of stay in hospital and change in parasite index between the 5th day and the 1st day of admission was used a clinical outcome marker in this study. The analysis showed that serum TNF alpha was raised significantly (p= 0.001) in patients with longer duration stay in hospital. The cytokine was significantly raised in patients having disorientation /cognitive disorder /coma and ARDS (p= 0.001, 0.0023 respectively). The study concluded that serum TNF alpha if done at time of admission and on day 3 can indicate the severity of disease and its complications. Source

Favaloro E.J.,Institute of Clinical Pathology and Medical Research ICPMR | Bonar R.,RCPA Haematology QAP | Marsden K.,Pathology
Seminars in Thrombosis and Hemostasis

In addition to the presence of appropriate clinical features, the diagnosis of the antiphospholipid antibody syndrome (APS) fundamentally requires the finding of positive antiphospholipid antibody (aPL) test result(s), with these comprising clot-based assays for the identification of lupus anticoagulant (LA) and immunologic ("solid-phaseo") assays such as anticardiolipin antibodies (aCL) and anti-glycoprotein I antibodies (aPI). This article is the second of two that review the process for, and provide recommendations to improve, internal quality control (IQC) and external quality assurance (EQA; or proficiency testing) for aPL assays. These processes are critical for ensuring the quality of laboratory test results, and thence the appropriate clinical diagnosis and management of APS. This article covers LA testing. We provide some updated findings from the Royal College of Pathologists of Australasia Haematology Quality Assurance Program, and cover testing results for the past 3 years (2009 to 2011 inclusive). In brief: (1) essentially all laboratories currently perform LA testing using activated partial thromboplastin time (APTT) and dilute Russell viper venom time (dRVVT) methods, and about one-third also employ the kaolin clotting time (KCT); (2) KCT usage has dropped slightly, from around 50% of laboratories in 2009, to around 35% in 2011, presumably reflecting take up of the latest consensus recommendations; (3) other methodologies such as silica clotting time (SCT) and the platelet neutralization procedure (PNP) are only used by <5% of laboratories; (4) interlaboratory coefficients of variation (CVs) are in general moderate, and substantially better than those reported for solid-phase assays such as aCL and aPI, with median (range) values being 11.6% (9.2 to 25.5%) for APTT ratios, 16.7% (10.1 to 19.2%) for KCT ratios, and 11.7% (5.7 to 17.4%) for dRVVT ratios; (5) CVs increase slightly with increasing LA positivity; (6) most laboratories correctly interpreted test findings for LA, reporting normal samples as normal, and LA-positive samples as positive (albeit with varying gradings of positivity); and (7) however, some laboratories found interpretation to be challenging for some samples, namely a weak LA sample (which was reported as normal by around 50% of laboratories) and a very strong LA sample (which was reported as normal by around 10% of laboratories, primarily those that did not perform mixing studies). Copyright © 2012 by Thieme Medical Publishers, Inc. Source

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