Asymptomatic stage I sarcoidosis complicated by pulmonary tuberculosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Sarcoidosis is a multisystem granulomatous disorder characterized pathologically by the presence of non-caseating granulomas in involved tissues. Depressed cellular immunity predisposes patients to infections with certain intracellular organisms, mostly fungi, <it>Mycobacterium tuberculosis </it>and <it>Nocardia </it>species. As these infections are mainly insidious and difficult to differentiate from the underlying disease, a possible misdiagnosis may lead to fatal complications for the patient.</p> <p>Case presentation</p> <p>We present a case of a 67-year-old woman with undiagnosed asymptomatic stage I sarcoidosis for at least 8 years before her admission and a 1-month history of fever, exertional dyspnea and dry cough, in whom pulmonary tuberculosis was documented.</p> <p>Conclusion</p> <p>This case highlights the need for great vigilance among physicians in order to rule out any possible infection before establishing the diagnosis of sarcoidosis.</p

Targeted therapy for gastrointestinal stromal tumors: current status and future perspectives

Gastrointestinal stromal tumors (GISTs) present 80% of gastrointestinal tract mesenchymal tumors, with systemic chemotherapy and radiotherapy being unable to improve survival of patients with advanced disease. The identification of activating mutations in either KIT cell surface growth factor receptor or platelet-derived growth factor receptor alpha, which lead to ligand-independent signal transduction, paved the way for the development of novel agents that selectively inhibit key molecular events in disease pathogenesis. The development of imatinib mesylate in the treatment of metastatic GIST represents a therapeutic breakthrough in molecularly targeted strategies, which crucially improved patients’ prognosis while its usefulness in adjuvant and neoadjuvant setting is under study. Sunitinib malate is available in the second-line setting, with ongoing studies evaluating its role in an earlier disease stage, while other targets are under intense investigation in order to enrich the therapeutical armamentarium for this disease. GIST phenotype seems to be an essential indicator of treatment response; thus, obtaining genotype information of each patient may be critical in order to tailor individualized treatment strategies and achieve maximal therapeutic results

Sunitinib A Multitargeted Receptor Tyrosine Kinase Inhibitor in the Era of Molecular Cancer Therapies

Sunitinib is an oral oxindole multitargeted kinase inhibitor that inhibits certain receptor tyrosine kinases (RTKs). These include vascular endothelial growth factor receptors (VEGFR type I and 2), platelet-derived growth factor receptors (PDGFR-alpha and PDGFR-beta), stem cell factor receptor (KIT), FMS-like tyrosine kinase-3 (FLT3), glial cell-line derived neurotrophic factor receptor (RET) and the receptor of macrophage-colony stimulating factor (CSF1 R). Examination of the antitumor effect of sunitinib in a variety of cell lines in vitro suggested an anti proliferative activity that is dependent on the presence of constitutively active RTK targets. The use of sunitinib as first-line therapy in advanced renal cell carcinoma (RCC) has improved the overall survival compared with that observed after cytokine therapy, while its administration in patients with gastrointestinal stromal tumors (GISTs) after progression or intolerance to imatinib achieved an objective response of 7%. Sunitinib is currently approved for the treatment of GISTs in this setting, and as first-line therapy for the treatment of advanced RCC. The relatively long half-life of sunitinib and its major metabolite allow for a once-daily dosing schedule. An interesting antitumor activity of sunitinib was reported in phase 11 studies of patients with a variety of malignancies, such as hepatocellular cancer, pancreatic neuroendocrine tumors, and non-small cell lung cancer; results of phase III studies are urgently anticipated. Fatigue is one of the most common adverse effects of sunitinib, as 50-70% of patients with advanced RCC and GIST complained of this adverse effect. Other adverse effects are diarrhea, anorexia, nausea and vomiting, oral changes and bleeding events. Most toxicities are reversible and should not result in discontinuation of sunitinib. If necessary, dose adjustments or interruptions should be made. Hypothyroidism has been described in the first 2 weeks of sunitinib therapy and its incidence increases progressively with the duration of therapy. Sunitinib may exert its hypertensive activity through a direct effect on the vasculature, while its most important cardiac adverse effect is left ventricular dysfunction. A variety of skin adverse effects have been described with the use of sunitinib such as hand-foot syndrome, yellow discoloration of the skin, dry skin, subungual splinter hemorrhages, acral erythema, and generalized skin rashes. Administration of sunitinib in the adjuvant and neoadjuvant setting of patients with RCC and of its combination with chemotherapy and other targeted therapies are currently under intense investigation

Chlamydophila pneumoniae infection and COPD: More evidence for lack of evidence?

Chlamydophila pneumoniae has been recognized as a common cause of respiratory tract infections affecting all age groups. The organism has been implicated as an infectious trigger for acute exacerbations of CCPD. Moreover, the intracellular existence of this pathogen and the ability to cause chronic respiratory infections have led to a number of studies that investigated its possible association with disease development. The present paper examines and discusses the possible association of acute C pneumoniae infection in episodes of acute exacerbation of COPD. It also reviews the existing evidence of chronic C. pneumoniae infection with disease pathogenesis and severity. The significant interstudy variation of the choice of diagnostic methods and criteria applied is most likely responsible for the great diversity of results observed. The use of well-standardized, commercially available diagnostic tools, as well as the adoption of a more unified diagnostic approach is probably the key element missing in order to clarify the exact role of C. pneumoniae in COPD. (C) 2009 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved

Central obesity, type 2 diabetes and insulin: exploring a pathway full of thorns

The prevalence of type 2 diabetes (T2D) is rapidly increasing. This is strongly related to the contemporary lifestyle changes that have resulted in increased rates of overweight individuals and obesity. Central (intra-abdominal) obesity is observed in the majority of patients with T2D. It is associated with insulin resistance, mainly at the level of skeletal muscle, adipose tissue and liver. The discovery of macrophage infiltration in the abdominal adipose tissue and the unbalanced production of adipocyte cytokines (adipokines) was an essential step towards novel research perspectives for a better understanding of the molecular mechanisms governing the development of insulin resistance. Furthermore, in an obese state, the increased cellular uptake of non-esterified fatty acids is exacerbated without any subsequent beta-oxidation. This in turn contributes to the accumulation of intermediate lipid metabolites that cause defects in the insulin signaling pathway. This paper examines the possible cellular mechanisms that connect central obesity with defects in the insulin pathway. It discusses the discrepancies observed from studies organized in cell cultures, animal models and humans. Finally, it emphasizes the need for therapeutic strategies in order to achieve weight reduction in overweight and obese patients with T2D

Spontaneous Rupture of a Bicuspid Aortic Valve in a Middle-Aged Weightlifter

We describe a 58-year-old Caucasian male weightlifter who presented with acute shortness of breath after finishing his extensive exercise routine. Acute aortic valve regurgitation, due to spontaneous rupture of a bicuspid aortic valve, was diagnosed. Urgent surgical intervention was carried out, during which the bicuspid aortic valve was resected and replaced with an On-X bileaflet mechanical valve. The patient remains asymptomatic and is treated with warfarin, being in excellent physical condition 4 years after aortic valve replacement