Tratamiento del síndrome antifosfolípido

The antiphospholipid syndrome (APS) is a disorder of recurrent thrombosis and/or pregnancy loss associated with the presence of antiphospholipid antibodies and persistently positive lupus anticoagulant, anticardiolipin or anti beta2-glycoprotein1. Oral anticoagulants are the best available and most effective treatment for the secondary prevention of recurrent venous or arterial thrombosis. Patients with APS are treated with long-term therapy to prolong the INR to 2.0-3.0. Low-molecular-weight heparin in combination with low-aspirin dose is a reasonable strategy to avoid pregnancy loss in women with this syndrome

Acute generalized, widespread bleeding. Diagnosis and management

BACKGROUND AND OBJECTIVE: Acute generalized, widespread bleeding is often related to disseminated intravascular coagulation (DIC), a pathologic process which complicates the clinical course of many diseases and is characterized by huge amounts of thrombin and plasmin within the circulation. The final result is the consumption of platelets, coagulation factors and inhibitors, as well as secondary hyperfibrinolysis, all leading to diffuse hemorrhage and microthromboses. This review article examines the present attitudes to the diagnosis and treatment of overt DIC in clinical practice, emphasizing the importance of an accurate differential diagnosis from some other processes characterized by acute generalized, widespread bleeding. INFORMATION SOURCES: The authors have been working in this field, both at experimental and clinical levels, contributing original papers for many years. In addition, material examined in this review includes articles published in journals covered by MedLine, recent reviews in journals with high impact factor and in relevant books on hemostasis and thrombosis. STATE OF ART AND PERSPECTIVES: DIC is an intermediary mechanism of disease which complicates the clinical course of many well-known disorders. Although the systemic hemorrhagic syndrome is the predominant clinical manifestation, massive intravascular thrombosis frequently occurs contributing to ischemia and associated organ damage, making the mortality rate of this condition high. Current concepts on the pathophysiology, laboratory diagnosis and management of DIC are presented. Complex pathophysiological interrelations make the diagnosis of the etiology of the DIC difficult in clinical practice, although simple tests are useful for identification of patients with the process. Laboratory diagnosis of DIC is mainly based on screening assays, which allow a rapid diagnosis, whereas some other highly sensitive but more complex assays are not always available to routine clinical laboratories. The management of DIC is based on the treatment of the underlying disease, supportive and replacement therapies and the control of the coagulation mechanisms. Although some advances have been achieved, management decisions are still controversial, so that therapy should be highly individualized depending on the nature of the DIC and severity of clinical symptoms. Many syndromes sharing common findings with DIC, such as primary hyperfibrinolysis or thrombotic thrombocytopenic purpura, should be excluded. Finally, new therapeutic approaches to the management of this potentially catastrophic syndrome are require

Do the low molecular weight heparins improve efficacy and safety of the treatment of deep venous thrombosis? A meta-analysis

We compared the efficacy and safety of low molecular weight heparins (LMWH) and unfractionated heparin (UFH) in the treatement of deep venous thrombosis (DVT). A comparison between two daily subcutaneous injections of LMWH against a single injection was also performed. DESIGN AND METHODS: The study was performed by a meta-analysis. Clot improvement in venography, recurrency, total mortality and major hemorrhages were assessed in 4,472 patients with DVT from 21 studies treated with subcutaneous LMWH or UFH. RESULTS: An improvement in clot reduction (odds ratio 0.73, 95% confidence interval 0.59 to 0.90, p = 0.004), a decrease in total mortality (0. 68, 0.50 to 0.91, p = 0.012) and a lower incidence of hemorrhage (0. 65, 0.43 to 0.98, p = 0.047) were observed in LMWH treated patients. There were no differences in recurrences (0.78, 0.59 to 1.04, p = 0. 10). A single dose of LMWH was better than two in reducing major bleeding (c2 = 4.99, p = 0.025); however, the two dose regimen was more effective in clot reduction (c2 = 8.56, p = 0.004). INTERPRETATION AND CONCLUSIONS: LMWH is superior to UFH in terms of safety and efficacy. A single daily dose of LMWH dose is a suitable therapeutic regimen and could facilitate the outpatient treatment of venous thromboembolism

Investigation of wear mechanics and behaviour of NiCr metallic foam abradables

Current aero-engine sealing materials are reaching their operating limit, as manufacturers seek more efficient engines with longer service lives. Even when utilised in optimum conditions, current materials have inconsistencies in performance due to variabilities in their microstructure, which lead to undesirable responses and events. As such, a new generation of sealing materials is required. Metallic foams are one such material, given the opportunities that exist to both engineer material properties, and achieve relatively consistent microstructures when compared to the current class of thermally sprayed abradable materials. In this study, the abradability of a nickel (70%)–chromium (30%) (NiCr) alloy foam is investigated, with the role of cell size and filler material considered. Tests are performed on a representative high-speed test rig, where a flat blade is used to simulate an aero-engine incursion event. A series of in situ measurement techniques, such as force, temperature and stroboscopic wear measurements are used to characterise the incursion, with DIC (Digital Image Correlation) techniques also employed to investigate breakdown of the foam. Unfilled foams were shown to lead to high blade wear, with the inclusion of filler materials leading to load transfer and collapse of the foam away from the incursion site, along with improved fracture. Both load transfer and ligament collapse mechanisms were found to promote more favourable rub mechanics at all incursion rates tested

Emergence of Secondary Acute Leukemia in a Patient Treated for Osteosarcoma: Implications of Germline TP53 Mutations

Secondary leukemia and myelodysplastic syndromes have been reported in patients following treatment for a wide range of neoplastic disorders. However second malignancies after chemotherapy and/or irradiation for osteosarcoma are unusual. PROCEDURE: We report the case of a 15-year-old girl who developed a myelodysplastic syndrome with evolution to acute nonlymphocytic leukemia after treatment for osteosarcoma. Therapy-related acute leukemia karyotype findings such as abnormalities of chromosomes 5, 7, and 17 were found in the cytogenetic analysis. Moreover, using denaturing gradient gel electrophoresis and DNA sequencing, we detected the presence of a double germline mutation in exon 7 of the TP53 gene. CONCLUSION: This observation supports the possibility of a causal relationship between germline TP53 mutations and the development of secondary leukemia and myelodysplasi

Long-term cardiac rehabilitation program favorably influences fibrinolysis and lipid concentrations in acute myocardial infarction

BACKGROUND AND OBJECTIVE: The control of well-known atherosclerotic risk factors represents the optimal strategy in the prevention of acute coronary syndromes. It was the aim of this work to analyze the effects of a long-term cardiac rehabilitation program on the changes of fibrinolysis parameters and plasma lipid profile in coronary patients. DESIGN AND METHODS: The study was carried out in 30 (M/F:22/8, mean age 47 years) survivors of a first acute myocardial infarction (AMI) and in 30 healthy controls who underwent a cardiac rehabilitation program (9 months duration). Samples were taken before, at 3 and 9 months after the beginning of the program to measure: tissue-type plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI-1) activity and antigen. A lipid profile including cholesterol (both HDL and LDL) and lipoprotein(a) was also assessed. The Wilcoxon and Mann-Whitney tests were used for statistical comparisons. RESULTS: There was a marked decrease of functional PAI-1 after 3 and 9 months as compared with baseline in AMI patients (p < 0.01). Results showed a significant increase of HDL-cholesterol (p < 0.01) and decrease of lipoprotein(a) levels after the exercise program (p < 0.01). INTERPRETATION AND CONCLUSIONS: The cardiac rehabilitation program improved fibrinolysis, by reducing the functional levels of PAI-1, and ameliorated the lipid profile by decreasing lipoprotein(a) and increasing HDL-cholesterol in patients with AMI. A long-term cardiac rehabilitation has positive effects on some risk factors for coronary disease

In-situ measurements of thermal-mechanical wear in blade-abradable liner contacts

The abradable coating on the casing of a jet engine minimises any air gaps by allowing blades to cut a path into the abradable, reducing efficiency losses. Unfortunately, abradable cutting performance varies significantly with rub conditions and abradable type, leading to poor cutting performance and potentially damaging the blades. This study further develops the abradable testing capabilities of a 200ms−1 spindle test rig by applying previously researched stroboscopic imagining techniques to record the front of the blade alongside thermal imaging of the blade and the abradable. The front camera makes it possible to see how adhesions are forming along the width of the blade, and how the adhesion growth differs between materials. The thermal camera can then be used to identify hot spots on both the blade and the abradable, providing an insight into how hot spots relate to adhesions both spatially and temporally. These tools have been proven with testing of Metco 601 at a range of incursion rates. At the incursion rate of 0.2μm/pass the tools were able to provide conclusive results, with video footage of the front, side, blade temperature and abradable temperatures being aligned temporally and spatially. Numerical data could then be extracted to produce rub maps of adhesion height, blade temperature, and abradable temperature on separate plots which is a powerful tool when looking for relationships between the data sets, and for identifying time-based patterns. Further benefits of this tool set were shown when focusing on individual adhesions events within a rub, allowing for the delays between abradable heating, adhesions forming, and blade heating to be observed and quantified. When applied to multiple materials and at different test conditions this tool will provide further insight into how adhesion formation differs, and potentially into why adhesions form

Association of EWS-FLI1 Type 1 Fusion with Lower Proliferative Rate in Ewing’s Sarcoma

The Ewing's sarcoma (ES) family of tumors, including peripheral neuroectodermal tumor (PNET), is defined genetically by specific chromosomal translocations resulting in fusion of the EWS gene with a member of the ETS family of transcription factors, either FLI1 (90-95%) or ERG (5-10%). A second level of molecular genetic heterogeneity stems from the variation in the location of the translocation breakpoints, resulting in the inclusion of different combinations of exons from EWS and FLI1 (or ERG) in the fusion products. The most common type of EWS-FLI1 fusion transcript, type 1, is associated with a favorable prognosis and appears to encode a functionally weaker transactivator, compared to other fusion types. We sought to determine whether the observed covariation of structure, function, and clinical course correlates with tumor cell kinetic parameters such as proliferative rate and apoptosis, and with expression of the receptor for insulin-like growth factor I (IGF-1R). In a group of 86 ES/PNET with defined EWS-ETS fusions (45 EWS-FLI1 type 1, 27 EWS-FLI1 non-type 1, 14 EWS-ERG), we assessed proliferation rate by immunostaining for Ki-67 using MIB1 antibody (n = 85), apoptosis by TUNEL assay (n = 66), and IGF-1R expression by immunostaining with antibody 1H7 (n = 78). Ki-67 proliferative index was lower in tumors with EWS-FLI1 type 1 than those with non-type 1 EWS-FLI1, whether analyzed as a continuous (P = 0.049) or categorical (P = 0.047) variable. Logistic regression analysis suggests that this association was secondary to the association of type 1 EWS-FLI1 and lower IGF-1R expression (P = 0.04). Comparing EWS-FLI1 to EWS-ERG cases, Ki-67 proliferative index was higher in the latter (P = 0.01, Mann-Whitney test; P = 0.02, Fisher's exact test), but there was no significant difference in IGF-1R. TUNEL results showed no significant differences between groups. Our results suggest that clinical and functional differences between alternative forms of EWS-FLI1 are paralleled by differences in proliferative rate, possibly mediated by differential regulation of the IGF-1R pathway