Sepsis, a systemic inflammatory syndrome, is a response to infection and when associated with multiple organ dysfunction is termed, severe sepsis. It remains a leading cause of mortality in the critically ill. The response to the invading bacteria may be considered as a balance between proinflammatory and antiinflammatory reaction. While an inadequate proinflammatory reaction and a strong antiinflammatory response could lead to overwhelming infection and death of the patient, a strong and uncontrolled proinflammatory response, manifested by the release of proinflammatory mediators may lead to microvascular thrombosis and multiple organ failure. Endotoxin triggers sepsis by releasing various mediators including tumor necrosis factor-alpha and interleukin-1(IL-1). These cytokines activate the complement and coagulation systems, release adhesion molecules, prostaglandins, leukotrienes, reactive oxygen species and nitric oxide (NO). Other mediators involved in the sepsis syndrome include IL-1, IL-6 and IL-8; arachidonic acid metabolites; platelet activating factor (PAF); histamine; bradykinin; angiotensin; complement components and vasoactive intestinal peptide. These proinflammatory responses are counteracted by IL-10. Most of the trials targeting the different mediators of proinflammatory response have failed due a lack of correct definition of sepsis. Understanding the exact pathophysiology of the disease will enable better treatment options. Targeting the coagulation system with various anticoagulant agents including antithrombin, activated protein C (APC), tissue factor pathway inhibitor (TFPI) is a rational approach. Many clinical trials have been conducted to evaluate these agents in severe sepsis. While trials on antithrombin and TFPI were not so successful, the double-blind, placebo-controlled, phase III trial of recombinant human activated protein C worldwide evaluation in severe sepsis (PROWESS) was successful, significantly decreasing mortality when compared to the placebo group. Better understanding of the pathophysiologic mechanism of severe sepsis will provide better treatment options. Combination antithrombotic therapy may provide a multipronged approach for the treatment of severe sepsis.

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The multi tumor suppressor genes MTS1 (CDKN2, p16INK4A) and MTS2 (CDKN1, p15INK4B) located at 9p21-22 are inactivated in some human cancers via several mechanisms including deletion and hypermethylation. In hematological malignancies, deletion of p16/p15 locus has been shown to be highly specific to lymphoid malignancies, and more particularly to T-cell acute lymphoblastic leukemia (TALL). We have investigated the deletion, methylation and p16 protein expression status of MTS1 in Tcell childhood acute lymphoblastic leukemia (19 cases) and cell lines[11]. On Southern blot homozygous deletions or hemizygous deletion with rearangement were detected in 4/19 T-ALL. The expression of p16 protein was not observed on Western blot in 4/15 T-ALL with intact p16 gene. The p16 gene was methylated 3/15 in T-ALL. Only one of three expressed p16 protein. The other 11/15 T-ALL had p16 protein expression but different level. Loss of MTS1 was observed in 3/11 cell lines. Cell line with MTS1 gene had p16 protein expression in 6/8. After treatment with the demethylating agent (5-AzoCyt) RD cell line showed p16 expression. This has not been observed with the other cell lines. Thus hypermethylation of MTS1 is rare in childhood T-ALL. Although inactivation of MTS1 by deletion is common in T-ALL and cell lines. Furthermore our data show that the p16 gene inactivation by hypermethylation and deletion may play a role in the leukemogenesis.

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ABO incompatibility is not a contraindication for allogeneic bone marrow transplantation, but this procedure requires an extra effort for erythrocyte or plasma depletion in certain well established conditions. Some acute or delayed immunohematological complications such as acute or chronic hemolysis and pure red cell aplasia may be encountered. In this study the outcome and transplant related complications of ABO incompatible and identical cases, who have received allogeneic peripheral blood stem cells from their HLA identical siblings were compared with each other. Ninety-one patients (CML 36, AML 37, other 18) were analyzed retrospectively including 51 (60.4%) ABO identical patients and 36 (39.6%) ABO mismatched (MM) patients, who have a bi-directional MM (n= 5), major MM (n= 16), minor MM (n= 9) and Rh MM (n= 6). Median follow up was 13 (0.5-43.0) months. We did not observed any significant differences between two groups (identical vs non-identical) in terms of acute hemolysis preceding stem cell infusion, peritransplant transfusion demand, acute- and chronic graft versus host disease. There was no change in estimated disease free survival and overall survival durations. We did not observed any influence of ABO/Rh incompatibility on short term outcome in allogeneic peripheral blood stem cell transplantation in our series and did not recommend further manipulation of the infused stem cells.

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A 4.5 year-old girl presented with abdominal distention, failure to thrive, visual and hearing loss. In her medical history there was meningitis in the neonatal period, convulsions, enlargement of her head, nistagmus and exophtalmus at the tenth month. When she was 15 month-old, she had ventriculoperitoneal shunt and surgical transection of the filum terminale due to tethered cord. When she was 3 yearold she had headaches and swallowing difficulties and she underwent suboccipital craniectomi and C1 laminectomi. On admission to our Center she had normal mental and motor development, high arched palate, only three teeth, hepatosplenomegaly, weight and height below 3 percentile, leukoerythroblastic anemia and thrombocytopenia. Roentgenograms of bones showed sclerosis and no medullary tissue could be obtained in bone marrow biopsy. Diagnosis was infantile malignant osteopetrosis but the patient can not be referred to bone marrow transplantation due to delay in diagnosis and irreversible visual and hearing loss and lack of medullary space for marrow engraftment.

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A 67-year-old patient was admitted to the hospital to perform an esophagogastrectomy because a lesion at the lower esophagus was strongly suspicious for cancer. Her medical history and her family history were negative for bleeding tendency or thrombosis. Her activated partial thromboplastin time (aPTT) was prolonged (44 s) whereas her prothrombin time (PT) was normal (11 s) presurgery. Mixing of her plasma with normal plasma corrected her prolonged aPTT (27.9 s). Prolonged incubation shortened the patient’s aPTT (36.3 s). Fletcher factor activity was found to be 50%. The patient underwent an esophagogastrectomy without bleeding complications under spinal anesthesia. Fletcher factor deficiency, a rare disorder, should be considered in patients who have no history of bleeding tendency with a prolonged aPTT. Surgical interventions are safe in these patients.

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Multiple myeloma is characterized by plasma cell infiltration of the bone marrow and the presence of a monoclonal protein in the plasma or the urine in 90% of cases. Major manifestations of the disease are bone pain, anemia, renal insufficiency and recurrent infections. Less frequent presentations are hepatic and splenic enlargement (5% of cases), lymphadenopathy (4%) and biclonal gammopathy (1%). In this report we describe a biclonal multiple myeloma presenting with cervical lymphadenopathy and sternal mass. The immunohistochemical study of the lymph node and the flow cytometric analysis of the bone marrow showed IgGk and IgAk biclonality. In this report the features of lymph node involvement and biclonality constitute a rare presentation of multiple myeloma.

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Methotrexate is an antineoplastic drug used commonly in leukemia treatment. Because of becoming resistant to standard doses after 1970s, it is used intermediate or high doses. The complications of high doses are mucositis, vomiting, dermatitis exfoliativa, B-cell dysfunction, hepatotoxicity, nephrotoxicity and bone marrow depression. There were only two studies in literature about Stevens-Johnson syndrome occuring in two patients with acute lymphocytic leukemia and non-Hodgkin lymphoma after receiving high doses methotrexate and leukoverin. We have reported a two-year-old boy patient suffering from acute lymphocytic leukemia (ALL) developed a severe skin reaction two days after administration of high dose methotrexate. The skin lesions simulated Stevens-Johnson syndrome with ulceration of the oral mucosa and erythema multiforme-like target lesions.

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