Clinica Davila

Santiago, Chile

Clinica Davila

Santiago, Chile
Time filter
Source Type

Gonzalez-Hormazabal P.,University of Chile | Reyes J.M.,Clinica Las Condes | Blanco R.,University of Chile | Bravo T.,National Cancer Society Corporacion Nacional Del Cancer CONAC | And 10 more authors.
Molecular Biology Reports | Year: 2012

Since the discovery of the BRCA1 and BRCA2 genes, much work has been carried out to identify further breast cancer (BC) susceptibility genes. BARD1 (BRCA1-associated ring domain) was originally identified as a BRCA1-interacting protein but has also been described in tumor-suppressive functions independent of BRCA1. Some association studies have suggested that the BARD1 Cys557Ser variant might be associated with increased risk of BC, but others have failed to confirm this finding. To date, this variant has not been analyzed in Spanish or South-American populations. In this study, using a case-control design, we analyzed the C-terminal Cys557Ser change in 322 Chilean BC cases with no mutations in BRCA1 or BRCA2 and in 570 controls in order to evaluate its possible association with BC susceptibility. BARD1 Cys557Ser was associated with an increased BC risk (P = 0.04, OR = 3.4 [95 % CI 1.2-10.2]) among cases belonging to families with a strong family history of BC. No difference between single cases affected with age <50 years at diagnosis (n = 117) and controls was observed for carriers of Cys/Ser genotype. It is likely that this variant is not involved in BC risk in this group of women. We also analyzed a possible interaction between BARD1 557Ser/XRCC3 241Met variants considering the role of both genes in the maintenance of genome integrity. The combined genotype Cys/Ser-carrier with the XRCC3 241Met allele was associated with an increased BC risk (P = 0.02, OR = 5.01 [95 % CI 1.36-18.5]) among women belonging to families with at least three BC and/or ovarian cancer cases. Our results suggest that BARD1 557Ser and XRCC3 241Met may play roles in BC risk in women with a strong family history of BC. Nevertheless there is no evidence of an interaction between the two SNPs. These findings should be confirmed by other studies and in other populations. © 2012 Springer Science+Business Media B.V.

Jara L.,University of Chile | Gonzalez-Hormazabal P.,University of Chile | Cerceno K.,University of Chile | Di Capua G.A.,University of Chile | And 13 more authors.
Breast Cancer Research and Treatment | Year: 2013

Genome-Wide Association Studies have identified several loci associated with breast cancer (BC) in populations of different ethnic origins. One of the strongest associations was found in the FGFR2 gene, and MAP3K1 has been proposed as a low-penetrance BC risk factor. In this study, we evaluated the associations among FGFR2 SNPs rs2981582, rs2420946, and rs1219648; and MAP3K1 rs889312, with BC risk in 351 BRCA1/2-negative Chilean BC cases and 802 controls. All the SNPs studied were significantly associated with increased BC risk in familial BC and in non-familial early-onset BC, in a dose-dependent manner. Subjects with 3 risk alleles were at a significantly increased risk of BC compared with subjects with 0-2 risk alleles, in both familial BC and early-onset non-familial BC (OR = 1.47, 95 % CI 1.04-2.07, P = 0.026 and OR = 2.04 95 % CI 1.32-3.24, P < 0.001, respectively). In the haplotype analysis, the FGFR2 rs2981582 T / rs2420946 T / rs1219648 G haplotype (ht2) was associated with a significantly increased BC risk compared with the rs2981582 C / rs2420946 C / rs1219648 A haplotype in familial BC and in non-familial early-onset BC (OR = 1.32, 95 % CI 1.06-1.65, P = 0.012; OR = 1.46, 95 % CI 1.11-1.91, P = 0.004, respectively). When the FGFR2 ht2 and MAP3K1 rs889312 were evaluated as risk alleles, the risk of BC increased in a dose-dependent manner as the number of risk alleles increased (P trend <0.0001), indicating an additive effect. Nevertheless, there is no evidence of an interaction between FGFR2 ht2 and the MAP3K1 rs889312 C allele. These findings suggest that genetic variants in the FGFR2 and MAP3K1 genes may contribute to genetic susceptibility to BC. © 2012 Springer Science+Business Media New York.

PubMed | Clinica Davila and Instituto Nacional del Torax
Type: | Journal: Asian cardiovascular & thoracic annals | Year: 2017

Background Durable mechanical support devices are prohibitively expensive in our health system and may be unsuitable for critically ill patients. CentriMag is an alternative bridge to transplantation or recovery. Methods We retrospectively reviewed 28 patients (23 males) aged 13-60 years who received CentriMag support. The etiology was ischemic in 13 (46%), dilated cardiomyopathy in 8 (29%), and others in 7 (25%). All patients were in Interagency Registry for Mechanically Assisted Circulatory Support class I, and 27 (96%) had multiorgan failure; 2 (7%) were post-cardiotomy and 12 (43%) had a previous cardiac arrest (mean arrest time 2117min). Results Thirty-day post-implant survival was 79% (22 patients). Twenty (71%) patients were successfully bridged to transplantation or recovery. The mean support time was 40 days; 12 (43%) patients had >4-weeks support (longest was 292 days). Eight (29%) patients died on support. Complications included bleeding in 10 (36%) cases, immediate stroke in 4 (14%), and dialysis in 8 (29%). There was no stroke during subsequent support. Eighteen (64%) patients underwent transplantation, and 17 of them were discharged. Two (7%) patients recovered and were discharged. Two-year survival was 62%10%. Mean follow-up was 21 months (total follow-up 579 months). Two (7%) patients died during follow-up. All survivors were in New York Heart Association class I. Conclusions CentriMag is useful for medium-term support for cardiogenic shock in a developing country. Support for >4 weeks is feasible. The stroke rate is low during support. The major drawback is prolonged intensive care unit stay.

Jara L.,University of Chile | Dubois K.,University of Chile | Gaete D.,University of Chile | De Mayo T.,University of Chile | And 11 more authors.
Breast Cancer Research and Treatment | Year: 2010

The double-strand break (DSB) DNA repair pathway has been implicated in breast cancer (BC). RAD51 and its paralogs XRCC3 and RAD51D play an important role in the repair of DSB through homologous recombination (HR). Some polymorphisms including XRCC3-Thr241Met, RAD51-135G>C, and RAD51D-E233G have been found to confer increased BC susceptibility. In order to detect novel mutations that may contribute to BC susceptibility, 150 patients belonging to 150 Chilean BRCA1/2-negative families were screened for mutations in XRCC3. No mutations were detected in the XRCC3 gene. In addition, using a case-control design we studied the XRCC3-Thr241Met, and RAD51D-E233G polymorphisms in 267 BC cases and 500 controls to evaluate their possible association with BC susceptibility. The XRCC3 Met/Met genotype was associated with an increased BC risk (P = 0.003, OR = 2.44 [95%CI 1.34-4.43]). We did not find an association between E233G polymorphism and BC risk. We also analyzed the effect of combined genotypes among RAD51-135G>C, Thr241Met, and E233G polymorphisms on BC risk. No interaction was observed between Thr241Met and 135G>C. The combined genotype Thr/Met-E/G was associated with an increased BC risk among women who (a) have a family history of BC, (b) are BRCA1/2-negative, and (c) were <50 years at onset (n = 195) (P = 0.037, OR = 10.5 [95%CI 1.16-94.5]). Our results suggested that the variability of the DNA HR repair genes XRCC3 and RAD51D may play a role in BC risk, but this role may be underlined by a mutual interaction between these genes. These findings should be confirmed in other populations. © 2010 Springer Science+Business Media, LLC.

Ojeda D.,Clinica Davila | Gomez R.,University of Los Andes, Chile | Burgos A.,University of Los Andes, Chile
Revista Medica de Chile | Year: 2016

Medical research is constantly looking for causality. Among study designs, randomized controlled trials are the most reliable way to estimate causal effects but are not always feasible. When this is the case, observational studies must be performed but this type of design unavoidably implies bias. Propensity scores, defined as the probability to receive a treatment conditional to a set of covariables allows to overcome confusion bias when searching for causal effects. © 2016, Sociedad Medica de Santiago. All Rights Reserved.

Espinoza F.,Clinica Davila | Espinoza F.,University of Los Andes, Chile | Romeo R.,University of Los Andes, Chile | Ursu M.,Clinica Davila | And 3 more authors.
Revista Medica de Chile | Year: 2013

Background: The frequency of pregnancies during dialysis is increasing. This condition requires changes in the dialysis schedule and nutritional approach. Aim: To report the experience in six patients with terminal kidney disease who became pregnant. Material and Methods: Retrospective review of medical records of women with terminal kidney disease in dialysis who became pregnant in a period of 27 years. Results: We recorded six successful pregnancies among women in hemodialysis treatment aged 32 ± 4 years. The mean dialysis-time per week was 19.5 ± 2.7 hours and Kt/V was 1.55 ± 0.17. The mean systolic blood pressure was 130 ± 13.3 mmHg. The mean packed cell volume of the group increased from 22.7% during pregestational stage to 30.2% during third trimester of pregnancy. All patients received an intensive treatment for anemia. The most common symptom of pregnancy was hyperemesis. The mean gestational age (GA) at diagnosis was 13.4 ± 4.7 weeks. All patients had preterm deliveries at a GA of 33 ± 1.7 weeks, and 66% of offspring were appropriate for gestational age. Conclusions: A multidisciplinary approach allows high rate of successful pregnancies during hemodialysis.

Vukusich A.,University of Los Andes, Chile | Kunstmann S.,University of Los Andes, Chile | Varela C.,Clinica Davila | Gainza D.,University of Los Andes, Chile | And 5 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2010

Background and objectives: Hemodialysis patients (HD) display high rates of cardiac diseases and mortality. In chronic kidney disease, vascular injury leads to coronary artery disease, heart failure, and stroke. Carotid intima-media thickness (CIMT) measurements are currently widely used in randomized controlled trials (RCTs) to study the efficacy of interventions. An RCT was designed for the assessment of the safety and effectiveness of spironolactone to inhibit the progression of CIMT in HD patients as a primary outcome. Secondary outcomes included measurements of plasma potassium. Design, setting, participants, & measurements: HD patients were randomly assigned to receive 50 mg spironolactone or placebo thrice weekly after dialysis. In between dialysis sessions, plasma potassium concentrations were measured every month. Ultrasonographic measurements of CIMT were done at the beginning of the study and after 2 years. Results: Fifty-three age- and sex-adjusted patients (30 with drug and 23 with placebo) successfully completed the trial. There were no significant differences between the two groups in all profiles studied at baseline. Measurements of CIMT after 2 years showed a progression in the placebo group, whereas in the spironolactone group a significant decrease or even reversed CIMT was observed. Progression rates (mm/yr) were: common carotid, placebo: 0.06 ± 0.07, spironolactone: 0.01 ± 0.04; carotid bifurcation, placebo: 0.15 ± 0.27, spironolactone: 0.0001 ± 0.01; internal carotid, placebo: 0.10 ± 0.12, spironolactone: -0.10 ± 0.15. No episodes of hyperkalemia were observed, but a slight increase in plasma potassium was found in the spironolactone group. Conclusions: Fifty milligrams of spironolactone thrice weekly significantly reduced the progression of CIMT in HD patients. Copyright © 2010 by the American Society of Nephrology.

Sobrevia L.,University of Santiago de Chile | Abarzua F.,University of Santiago de Chile | Nien J.K.,Clinica Davila | Salomon C.,University of Santiago de Chile | And 7 more authors.
Placenta | Year: 2011

Human endothelial dysfunction is a common feature in many diseases of pregnancy, such as gestational diabetes (GD). Metabolic changes include abnormal synthesis of nitric oxide (NO) and abnormal membrane transport of l-arginine and adenosine in primary cultures of human umbilical vein (HUVEC, macrovascular) and placental microvillus (hPMEC, microvascular) endothelial cells. These alterations are associated with modifications in the expression and activity of endothelial (eNOS) and inducible (iNOS) NO synthases, respectively, an effect that is maintained at least up to passage 5 in culture. HUVEC and hPMEC exhibit expression and activity of the human cationic amino acid transporter 1 (hCAT-1), equilibrative nucleoside transporters 1 (hENT1) and hENT2, as well as the corresponding SLC7A1, SLC29A1 and SLC29A2 gene promoter activities. Altered gene expression results from increased NO level, protein kinase C, mitogen-activated protein kinases, and hCHOP-C/EBPα transcription factor activation. Reduced ENT-mediated adenosine transport in GD is associated with stimulation of the l-arginine/NO pathway, and mainly due to reduced expression and activity of hENT1. In addition, hENT2 activity seems able to restore the reduced adenosine transport in GD. Additionally, insulin exerts a differential modulation of endothelial cells from macrocirculation compared with microcirculation, possibly due to expression of different insulin receptor isoforms. It is suggested that a common functional characteristic leading to changes in the bioavailability of adenosine and metabolism of l-arginine is evidenced by human fetal micro and macrovascular endothelium in GD.

Guzman-Gutierrez E.,University of Santiago de Chile | Abarzua F.,University of Santiago de Chile | Belmar C.,University of Santiago de Chile | Nien J.K.,Clinica Davila | And 9 more authors.
Current Vascular Pharmacology | Year: 2011

Gestational diabetes mellitus (GDM) is a syndrome compromising the health of the mother and the fetus. Endothelial damage and reduced metabolism of the vasodilator adenosine occur and fetal hyperinsulinemia associated with deficient insulin response and a metabolic rather than mitogenic phenotype is characteristic of this pathology. These phenomena lead to endothelial dysfunction of the fetoplacental unit. Major databases were searched for the relevant literature in the field. Special attention was placed on publications related with diabetes and hormone/metabolic disorders. We aimed to summarize the information regarding insulin sensitivity changes in GDM and the role of adenosine in this phenomenon. Evidence supporting the possibility that fetal endothelial dysfunction involves a functional link between adenosine and insulin signaling in the fetal endothelium from GDM pregnancies is summarized. Since insulin acts via membrane receptors type A (preferentially associated with mitogenic responses) or type B (preferentially associated with metabolic responses), a differential activation of these receptors in this syndrome is proposed. © 2011 Bentham Science Publishers.

Loading Clinica Davila collaborators
Loading Clinica Davila collaborators