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Tirado-Velez J.M.,Hospital Universitario Puerta del Mar
Annals of hematology | Year: 2012

Multiple myeloma (MM) is an incurable disease accompanied by low plasma levels of low-density lipoprotein cholesterol (LDL-c). The significance of altered cholesterol metabolism in the pathophysiology of MM remains elusive. Although it has been hypothesized that myeloma cells depend on exogenous cholesterol for its survival, the role of LDL-c on myeloma cells has not been elucidated. To evaluate the impact of exogenous LDL-c on cell viability, three human myeloma cell lines (RPMI-8226, NCI-H929, and U-266B1) were grown in the presence or absence of lipoproteins. Cell viability was markedly reduced in the absence of lipoproteins in sera. However, exogenous LDL-c improved cell viability. We showed that reduced cell viability was associated with increased levels of cleaved caspase-3, whereas proliferation rate remained unchanged. Interestingly, exogenous LDL-c counteracted apoptosis in human myeloma cell lines and primary cultures of human myeloma cells. Thus, our results demonstrated that LDL-c is an important anti-apoptotic factor for myeloma cells and begin to explain the hypocholesterolemia observed in patients with MM.

Physicians need fast access to quality information about the best diagnostic tests and treatments in each case. To meet this need, a new publishing format has emerged. Critically appraised topics (CATs) are elaborated following the five steps of evidence-based medicine. CATs are structured summaries of research articles that deal with a specific clinical query, presenting a critical evaluation of the best evidence available to support the validity of the available options. CATs have proven useful in teaching evidence-based radiology and this publishing format is becoming more common. Radiology CATs can be found on medical websites and in journals, including those dedicated to general medicine as well as those specifically dedicated to radiology. Radiología encourages the publication of CATs because we consider that they can be useful for daily decision making. © 2010 SERAM. Published by Elsevier Espana, S.L. All rights reserved.

Evidence-based radiology is defined as the decision that results from integrating clinical information to select the most appropriate imaging test on the basis of the best available evidence, the physician's experience, and the patient's expectations. The practice of evidence-based radiology consists of five steps: formulating the question, performing an efficient search of the literature, critically evaluating the literature, applying the results of the search and evaluation while taking into account our experience and the patient's values, and evaluating the results obtained within our own practice. In diagnostic imaging, the number of resources available for evidence-based radiology is increasing: apart from books, articles, and web pages on this subject, evidence-based radiology is receiving more attention at diagnostic imaging conferences. The principles of evidence-based radiology will help promote the appropriate use of resources, greatly benefiting patients (decreasing the use of examinations that use ionizing radiation), professionals (less overload), and managers (more efficient use of resources). © 2010 SERAM. Published by Elsevier España, S.L. All rights reserved.

Rodriguez-Bayona B.,Hospital Universitario Puerta del Mar
Arthritis research & therapy | Year: 2010

Systemic lupus erythematosus (SLE) is characterized by B cell hyper-activation and auto-reactivity resulting in pathogenic auto-antibody generation. The phenotypic analysis of blood B cell subsets can be used to understand these alterations. The combined detection of CD19, CD27 and IgD (or IgM) by flow cytometry (FC) analysis delineates five well-defined blood B cell-subsets: naive, switched (S) memory, double negative (DN) memory and CD27 IgD IgM (non-switched memory) B lymphocytes, and plasma cells (PCs). This phenotypic study was performed in 69 consecutive SLE patients and 31 healthy controls. SLE patients exhibited several abnormalities in the distribution of these B cell subsets, including elevated levels of DN memory B cells and PCs, and decreased CD27 IgD IgM B cells. Active SLE patients also showed decreased presence of S memory B cells and increased proportions of naive B lymphocytes. Nevertheless, when the patients in remission who did not require treatment were studied separately, the only remaining abnormality was a reduction of the CD27 IgD IgM B cell-subset detectable in most of these patients. The level of reduction of CD27 IgD IgM B cells was associated with elevated values of serum SLE auto-antibodies. Further analysis of this latter B cell-subset specifically showed increased expression of CD80, CD86, CD95, 9G4 idiotype and functional CXCR3 and CXCR4. The presence of a reduced blood CD27 IgD IgM B cell-subset, exhibiting an activated state and enriched for auto-reactivity, is a consistent B cell abnormality in SLE. These findings suggest that CD27 IgD IgM B lymphocytes play a role in the pathogenesis of this disease.

Montes-de-Oca M.,Hospital Universitario Puerta del Mar
Liver international : official journal of the International Association for the Study of the Liver | Year: 2011

Analysis of the influence of the effects of increased intestinal permeability on haemodynamic alterations in human immunodeficiency virus (HIV)-infected patients with decompensated hepatitis C virus (HCV)-related liver disease. Forty HIV/HCV co-infected patients and 40 HCV mono-infected patients, 20 of them with compensated cirrhosis and 20 with a previous decompensation, and 20 healthy controls, were studied. Intestinal permeability was determined by serum levels of lipopolysaccharide-binding protein (LBP). Monocyte expression of toll-like receptor 4 (TLR-4), serum levels of interleukin (IL)-6 and soluble receptors of tumour necrosis factor (sTNFRI) were analysed. Cardiac index, systemic vascular resistance (SVR), plasma renin activity (PRA) and aldosterone concentration were also determined in cirrhotic patients. Serum levels of LBP, TLR-4, IL-6 and sTNFRI were significantly higher in HIV-HCV co-infected and HCV mono-infected patients with decompensated cirrhosis compared with those with compensated liver disease. Significantly lower values of SVR and higher values of cardiac index, PRA and aldosterone concentration were observed in patients with decompensated cirrhosis compared with those with compensated liver disease, particularly in those with elevated levels of IL-6. There were no significant differences between HIV/HCV co-infected and HCV mono-infected patients. Higher intestinal permeability and consequent macrophage activation is observed in patients with cirrhosis; this permeability is even higher in those with portal hypertension. Serum values of IL-6 are associated with the characteristic haemodynamic derangement observed in advanced phases of cirrhosis. HIV/HCV co-infected cirrhotic patients present inflammatory and systemic haemodynamic alterations similar to those observed in HCV mono-infected patients. © 2011 John Wiley & Sons A/S.

Different types of critically appraised topics (CATs) can be elaborated in diagnostic imaging: comparison of diagnostic tests, evaluation of techniques for early detection (screening), economical analyses, or therapeutic aspects, among others. Their design will vary in function of the question they aim to answer. For example, for treatment evaluation, clinical trials are the best, but if there are secondary studies (systematic reviews or meta-analyses) that synthesize information from several studies, the results will be more important and the scientific conclusions will be more relevant. Regardless of the study design used, the elaboration of a CAT will involve six steps: 1) question; 2) systematic and efficient bibliographic search; 3) levels of evidence (choosing the articles that have the best level); 4) critical reading of the articles chosen; 5) applying conclusions to the context, and 6) recommendations. In this article, we will describe these steps and the nuances for different types of studies in each step. © 2013 SERAM.

Rodriguez-Bayona B.,Hospital Universitario Puerta del Mar | Ramos-Amaya A.,Hospital Universitario Puerta del Mar | Lopez-Blanco R.,Hospital Universitario Puerta del Mar | Campos-Caro A.,Hospital Universitario Puerta del Mar | Brieva J.A.,Hospital Universitario Puerta del Mar
Journal of Immunology | Year: 2013

Maturation and survival of plasma cells (PCs) depends on extrinsic factors provided in specialized niches. In addition, B lymphocyte differentiation into PCs requires the activation of the JAK-STAT-3 pathway. However, whether STAT-3 is needed only during the transition of B lymphocytes to PC, or it is also involved in the survival and function of PCs at different stages of maturation, has not been unequivocally clarified. This study analyzes the effect of IL-10, IL-21, and IL-6 on human in vivo-generated PCs isolated from secondary lymphoid organs, blood (circulating, recently Ag-induced PCs), and bone marrow. PCs from these different organs show specific profiles of receptors for, and responsiveness to, these cytokines required for their survival and sustained Ab secretion. However, IL-10, IL-21, and IL-6 commonly induce STAT-3 phosphorylation in the three PC subsets, and all of their effects are exerted strictly through the STAT-3 activation. The inhibition or nonactivation of this pathway in the three PC populations impairs not only the effect of STAT-3-activating cytokines, but also the action of other cytokines important at the PC level, including a proliferation-induced ligand, BAFF, insulin-like growth factor 1, vascular endothelial growth factor, and stromal cell-derived factor-1α. These results indicate that STAT-3 activation is critical for human PCs throughout their maturation. © 2013 by The American Association of Immunologists, Inc.

Garcia-Martos P.,Hospital Universitario Puerta Del Mar | Garcia-Agudo L.,Hospital General Of Tomelloso
Enfermedades Infecciosas y Microbiologia Clinica | Year: 2012

Rapidly growing mycobacteria (RGM) are ubiquitous in nature and widely distributed in water, soil and animals. During the past three decades we have observed a notable increment of infections caused by RGM, both localized and disseminated, as well as nosocomial outbreaks of contaminated medical equipment. The microbiological diagnosis of RGM infections includes direct microscopic observation and culture. The taxonomic identification is performed by phenotypic, biochemical, chromatographic and molecular biology techniques. The treatment differs from that of other mycobacteriosis like tuberculosis, owing to the variable in vitro susceptibility of the species of this group. The RGM are resistant to conventional antituberculous drugs, but can be susceptible to broad spectrum antimicrobial agents. In this study we comment on the significant aspects of human infections by RGM, including their biology, epidemiology, pathology, microbiological diagnosis, taxonomic identification, antimicrobial susceptibility and treatment.

De Cos C.,Hospital Universitario Puerta Del Mar | Rodriguez-Martorell J.,Hospital Universitario Virgen Del Rocio
Blood Coagulation and Fibrinolysis | Year: 2014

We present the case of a pediatric patient born in July 1991, diagnosed with severe hemophilia A at 8 months of life after a hemarthrosis. He was treated with regular factor replacement therapy on-demand until an inhibitor was detected (1.75-2.5 BU) at the age of 6. The patient started an immunotolerance induction (ITI) program, which was discontinued 3 months later because of parental decision based on inhibitor persistence (3.75-6.75 BU). On-demand treatment with recombinant activated FVII in bleeding episodes was applied. Titer peaked 13 months later (37 BU). On May 2003 (age 11), rescue ITI with plasma-derived FVIII (Fanhdi, 100IU/kg per 24h daily) and intravenous immunoglobulin (IVIg) (Flebogamma, 1g/kg per 24h for 2 days every 3 weeks) was started. Inhibitor eradication was achieved after 16 months of ITI. The patient continued with FVIII+IVIg treatment for 3 additional months when he was switched to FVIII prophylaxis (40IU/kg 3 times a week). At present, the patient is inhibitor-free. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Arnedillo Munoz A.,Hospital Universitario Puerta del Mar
Archivos de Bronconeumologia | Year: 2010

During the natural history of patients with chronic obstructive pulmonary disease (COPD), an increase in symptom severity can occur, called exacerbated COPD (ECOPD), sometimes requiring hospital admission. Although there is ongoing debate on the definition of ECOPD -leading to a lack of homogeneity in the numerous studies performed- exacerbations negatively affect patients, producing clinical and pulmonary function deterioration in the long term. Exacerbations also decrease quality of life in the medium- and long-term and have a high social and health cost, especially during hospital admission. Finally, ECOPD increases mortality in patients in the short-term, during hospital admission, and after discharge. In view of all of the above, prevention of ECOPD has become one of the main objectives in these patients. © 2010 Sociedad Española de Neumología y Cirugía Torácica.

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