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- Hemorrhagic Stroke in an Adolescent Female with HIV-Associated Thrombotic Thrombocytopenic Purpura. [JOURNAL ARTICLE]
- J AIDS Clin Res 2014 Jun; 5(6)
HIV-1 infection can trigger acute episodes of Idiopathic Thrombocytoponic Purpura (ITP), and Thrombotic Thrombocytopenic Purpura (TTP), particularly in populations with advanced disease and poor adherence to antiretroviral therapy (ART). These diseases should be distinguished because they respond to different treatments. Previous studies done in adults with HIV-TTP have recommended the prompt initiation or re-initiation of ART in parallel with plasma exchange therapy to improve the clinical outcome of these patients. Here, we describe a case of HIV-TTP resulting in an acute hemorrhagic stroke in a 16 year old female with perinatally acquired HIV infection and non-adherence to ART, who presented with severe thrombocytopenia, microangiopathic hemolytic anemia, and a past medical history of HIV-ITP. Both differential diagnosis and treatments for HIV-ITP and HIV-TTP were considered simultaneously. A decrease in plasma ADAMTS13 activity (<5%) without detectable inhibitory antibodies confirmed the diagnosis of HIV-TTP. Re-initiation of ART and plasma exchange resulted in a marked decrease in the HIV-RNA viral load, recovery of the platelet count, and complete recovery was achieved with sustained virologic suppression.
- Hemodynamic effects of ambrisentan-tadalafil combination therapy on progressive portopulmonary hypertension. [JOURNAL ARTICLE]
- World J Hepatol 2014 Nov 27; 6(11):825-829.
Intravenous epoprostenol is recommended for World Health Organization functional class (WHO-FC) IV patients with pulmonary arterial hypertension (PAH) in the latest guidelines. However, in portopulmonary hypertension (PoPH) patients, advanced liver dysfunction and/or thrombocytopenia often makes the use of intravenous epoprostenol challenging. Here we report the cases of two WHO-FC IV PoPH patients who were successfully treated with a combination of two oral vasodilators used to treat PAH: ambrisentan and tadalafil. Oral vasodilator therapy using a combination of ambrisentan and tadalafil may be a safe and effective therapeutic option for WHO-FC IV PoPH patients and should be considered for selected patients with severe and rapidly progressing PoPH.
- Gemcitabine plus capecitabine (Gem-Cape) biweekly in chemorefractory metastatic colorectal cancer. [JOURNAL ARTICLE]
- Clin Transl Oncol 2014 Nov 27.
A proportion of patients with metastatic colorectal cancer (mCRC) are still able to continue with active therapy after their progression to fluoropyrimidines, oxaliplatin, and irinotecan regimens. Studies suggest that gemcitabine and fluoropyrimidines are synergic antimetabolites. The purpose was to evaluate gemcitabine-capecitabine (Gem-Cape) in heavily pretreated mCRC and to thus assess possible predictive factors for progression-free survival (PFS) and overall survival (OS).This analysis was performed on 119 evaluable patients pretreated with fluoropyrimidines, oxaliplatin, irinotecan, and biological agents between June 2001 and July 2011. Patients received gemcitabine 1,000 mg/m(2) day 1 and capecitabine 1,000 mg/m(2) bid for 7 days every 2 weeks.The general characteristics were ECOG 0-1, 89 %; male, 68 %, and median age 63 years. In total, 61 % had received two chemotherapy lines, while 39 % had received three or more. Objective response rates and stable disease rates at 3 months were 6.72 and 37.81 %, equalling a clinical benefit of 44.53 %. The median PFS and OS were 2.87 months [95 % confidence interval (CI) 2.53-3.17 months] and 6.53 months (95 % CI 5.33-8.77), respectively. The most frequent toxicities were grades 1-2, anemia (22 %), thrombocytopenia (10 %), and hand-foot syndrome (9 %); grade ≥3, diarrhea (2 %), with no treatment-related discontinuations. No treatment-related deaths were reported. Statistical significance was obtained by subgroups, assessing clinical benefits and objective responses for PFS and OS. Moreover, patients under 65 tended to have a better PFS.These data suggest that Gem-Cape is a tolerable and feasible regimen, associated with clinical benefit in non-selected, heavily pretreated, mCRC patients.
- Heparin-induced thrombocytopenia following plasma exchange in patients with demyelinating neurological disease. [LETTER]
- Int J Lab Hematol 2014 Nov 27.
- Is there a predictive significance of ABO blood group on chemotherapy-induced thrombocytopenia in patients with stage III colon cancer? [JOURNAL ARTICLE]
- Med Oncol 2015 Jan; 32(1):384.
Chemotherapy-induced thrombocytopenia (CIT) is the most important cause of thrombocytopenia in cancer patients. In this paper, I discussed the effect of ABO blood group on CIT in patients with stage III colon cancer. In a pilot study, a total of 131 (72 men, 55 %) eligible patients with stage III colon cancer were divided into two groups according to whether they had CIT. Both groups were compared using demographic, histopathological, and laboratory variables. CIT was detected in 51 (40 %) of 131 patients. The incidence of CIT had a significant increased in patients with 0 blood group compared to other blood groups. It was concluded that the relationship between blood group 0 and the presence of CIT in patients with stage III colon cancer is independent of other study variables (P = 0.035, OR 3.14, 95 % CI 1.16-7.01). In conclusion, I hypothesized that 0 blood group may predict to differentiate high-risk patients for CIT.
- Immune thrombocytopenic purpura (ITP) associated with vaccinations: a review of reported cases. [JOURNAL ARTICLE]
- Immunol Res 2014 Nov 27.
Immune thrombocytopenic purpura (ITP) is an autoimmune condition characterized by low platelet count with mucocutaneous and other bleedings. Clinical manifestations may range from spontaneous formation of purpura and petechiae, especially on the extremities, to epistaxis, bleeding at the gums or menorrhagia, any of which occur usually if the platelet count is below 20,000 per μl. A very low count may result in the spontaneous formation of hematomas in the mouth or on other mucous membranes. Fatal complications, including subarachnoid or intracerebral, lower gastrointestinal or other internal bleeding can arise due to an extremely low count. Vaccines may induce ITP by several mechanisms. Vaccine-associated autoimmunity may stem not only from the antigen-mediated responses but also from other constituents of the vaccine, such as yeast proteins, adjuvants, and preservatives diluents. The most likely is through virally induced molecular mimicry. The binding of pathogenic autoantibodies to platelet and megakaryocytes may cause thrombocytopenia by different mechanisms, such as opsonization, direct activation of complement, or apoptotic pathways. The autoantibodies hypothesis is not sufficient to explain all ITP cases: In the anti-platelet antibody-negative cases, a complementary mechanism based on T cell immune-mediated mechanism has been suggested. In particular, T cell subsets seem dysregulated with an increased production of pro-inflammatory cytokines, as IFN-γ and TNF, and chemokines, as CXCL10. Vaccines are one of the most striking discoveries in human history that changed dramatically life expectancy. Nonetheless, the occurrence of adverse events and autoimmune phenomena has been described following vaccination, and ITP may represent one of this.
- The Effects of Alcohol and Aldehyde Dehydrogenases on Disorders of Hematopoiesis. [JOURNAL ARTICLE]
- Adv Exp Med Biol 2015.:349-359.
Hematopoiesis involves the orderly production of millions of blood cells per second from a small number of essential bone marrow cells termed hematopoietic stem cells (HSCs). Ethanol suppresses normal hematopoiesis resulting in leukopenia, anemia, and thrombocytopenia and may also predispose to the development of diseases such as myelodysplasia (MDS) and acute leukemia. Currently the exact mechanisms by which ethanol perturbs hematopoiesis are unclear. The aldehyde dehydrogenase (ALDH) gene family plays a major role in the metabolism of reactive aldehydes derived from ethanol in the liver and other organs. At least one of the ALDH isoforms, ALDH1A1, is expressed at high levels in HSCs in humans, mice, and other organisms. Recent data indicate that ALDH1A1 and possibly other ALDH isoforms may metabolize reactive aldehydes in HSCs and other hematopoietic cells as they do in the liver and elsewhere. In addition, loss of these ALDHs leads to perturbation of a variety of cell processes that may predispose HSCs to disorders in growth and leukemic transformation. From these findings, we suggest a hypothesis that the cytopenias and possible increased risk of MDS and acute leukemia in heavy alcohol users is due to polymorphisms in genes responsible for metabolism of alcohol derived reactive aldehydes and repair of their DNA adducts in HSCs and other hematopoietic cells. In the article, we will summarize the biological properties of hematopoietic cells and diseases related to ethanol consumption, discuss molecular characteristics of ethanol metabolism, and describe a model to explain how ethanol derived reactive aldehydes may promote HSC damage.
- 2-Arachidonoylglycerol enhances platelet formation from human megakaryoblasts. [JOURNAL ARTICLE]
- Cell Cycle 2014 Nov 26.:0.
ABSTRACT Platelets modulate vascular system integrity, and their loss is critical in haematological pathologies and after chemotherapy. Therefore, identification of molecules enhancing platelet production would be useful to counteract thrombocytopenia. We have previously shown that 2-arachidonoylglycerol (2-AG) acts as a true agonist of platelets, as well as it commits erythroid precursors towards the megakaryocytic lineage. Against this background, we sought to further interrogate the role of 2-AG in megakaryocyte/platelet physiology by investigating terminal differentiation, and subsequent thrombopoiesis. To this end, we used MEG-01 cells, a human megakaryoblastic cell line able to produce in vitro platelet-like particles. 2-AG increased the number of cells showing ruffled surface and enhanced surface expression of specific megakaryocyte/platelet surface antigens, typical hallmarks of terminal megakaryocytic differentiation and platelet production. Changes in cytoskeleton modelling also occurred in differentiated megakaryocytes and blebbing platelets. 2-AG acted by binding to CB1 and CB2 receptors, because specific antagonists reverted its effect. Platelets were split off from megakaryocytes and were functional: they contained the platelet-specific surface markers CD61 and CD49, whose levels increased following stimulation with a natural agonist like collagen. Given the importance of 2-AG for driving megakaryopoiesis and thrombopoiesis, not surprisingly we found that its hydrolytic enzymes were tightly controlled by classical inducers of megakaryocyte differentiation. In conclusion 2-AG, by triggering megakaryocyte maturation and platelet release, may have clinical efficacy to counteract thrombocytopenia-related diseases.
- Dengue fever: a Wikipedia clinical review. [REVIEW]
- Open Med 2014; 8(4):e105-e115.
Dengue fever, also known as breakbone fever, is a mosquito-borne infectious tropical disease caused by the dengue virus. Symptoms include fever, headache, muscle and joint pains, and a characteristic skin rash that is similar to measles. In a small proportion of cases, the disease develops into life-threatening dengue hemorrhagic fever, which results in bleeding, thrombocytopenia, and leakage of blood plasma, or into dengue shock syndrome, in which dangerously low blood pressure occurs. Treatment of acute dengue fever is supportive, with either oral or intravenous rehydration for mild or moderate disease and use of intravenous fluids and blood transfusion for more severe cases. Along with attempts to eliminate the mosquito vector, work is ongoing to develop a vaccine and medications targeted directly at the virus.
- Analyses of Entry Mechanisms of Novel Emerging Viruses Using Pseudotype VSV System. [JOURNAL ARTICLE]
- Trop Med Health 2014 Jun; 42(2 Suppl):71-82.
Emerging infectious diseases include newly identified diseases caused by previously unknown organisms or diseases found in new and expanding geographic areas. Viruses capable of causing clinical disease associated with fever and bleeding are referred to as viral hemorrhagic fevers (VHFs). Arenaviruses and Bunyaviruses, both belonging to families classified as VHFs are considered major etiologies of hemorrhagic fevers caused by emerging viruses; having significant clinical and public health impact. Because these viruses are categorized as Biosafety Level (BSL) 3 and 4 pathogens, restricting their use, biological studies including therapeutic drug and vaccine development have been impeded. Due to these restrictions and the difficulties in handling such live viruses, pseudotype viruses bearing envelope proteins of VHF viruses have been developed using vesicular stomatitis virus (VSV) as a surrogate system. Here, we report the successful developments of two pseudotype VSV systems; bearing the envelope proteins of Lujo virus and severe fever with thrombocytopenia syndrome (SFTS) virus, both recently identified viruses of the family Arenaviridae and Bunyaviridae, respectively. My presentation will summarize the characterization of the envelope proteins of Lujo virus including its cellular receptor use and cell entry mechanisms. In addition, I will also present a brief introduction of SFTS reported in Japan and the diagnostic studies in progress using these newly pseudotype VSV system.