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1.
Transplant Proc ; 51(2): 324-327, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30879533

RESUMEN

BACKGROUND: The development of chronic kidney disease is a common complication after a lung transplantation, especially since the introduction of immunosuppressive treatments based on calcineurin inhibitors. Many of these patients reach end-stage renal disease and even need renal replacement therapy. Among the different options of renal replacement therapy, we consider kidney transplantation as a feasible option for these patients. METHODS: A single center, observational retrospective study including 8 lung transplanted patients who have received a kidney transplant in the period between 2013 and 2017 with at least 1 year of follow-up was used. RESULTS: Seven patients maintained an adequate function of the graft 1 year after kidney transplantation, and 1 patient died because of a pulmonary condition in spite of a previous kidney transplant. Two patients presented delayed graft function in the first days after surgery. CONCLUSIONS: The kidney transplantation is a technique of renal replacement therapy that should be considered in patients with previous lung transplantation. Experienced centers in double sequential lung and kidney transplantation should be established to assess and treat these types of patients.


Asunto(s)
Trasplante de Riñón/métodos , Trasplante de Pulmón , Insuficiencia Renal Crónica/cirugía , Adulto , Anciano , Inhibidores de la Calcineurina/efectos adversos , Funcionamiento Retardado del Injerto/epidemiología , Femenino , Humanos , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/inducido químicamente , Estudios Retrospectivos
2.
Clin Microbiol Infect ; 24(2): 192-198, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28652112

RESUMEN

OBJECTIVES: To assess the risk factors for development of late-onset invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT). METHODS: We performed a multinational case-control study that retrospectively recruited 112 KT recipients diagnosed with IPA between 2000 and 2013. Controls were matched (1:1 ratio) by centre and date of transplantation. Immunosuppression-related events (IREs) included the occurrence of non-ventilator-associated pneumonia, tuberculosis, cytomegalovirus disease, and/or de novo malignancy. RESULTS: We identified 61 cases of late (>180 days after transplantation) IPA from 24 participating centres (accounting for 54.5% (61/112) of all cases included in the overall study). Most diagnoses (54.1% (33/61)) were established within the first 36 post-transplant months, although five cases occurred more than 10 years after transplantation. Overall mortality among cases was 47.5% (29/61). Compared with controls, cases were significantly older (p 0.010) and more likely to have pre-transplant chronic obstructive pulmonary disease (p 0.001) and a diagnosis of bloodstream infection (p 0.016) and IRE (p <0.001) within the 6 months prior to the onset of late IPA. After multivariate adjustment, previous occurrence of IRE (OR 19.26; 95% CI 2.07-179.46; p 0.009) was identified as an independent risk factor for late IPA. CONCLUSION: More than half of IPA cases after KT occur beyond the sixth month, with some of them presenting very late. Late IPA entails a poor prognosis. We identified some risk factors that could help the clinician to delimit the subgroup of KT recipients at the highest risk for late IPA.


Asunto(s)
Aspergilosis Pulmonar Invasiva/etiología , Trasplante de Riñón/efectos adversos , Estudios de Casos y Controles , Femenino , Salud Global/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo
3.
Transplant Proc ; 48(9): 2862-2866, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27932093

RESUMEN

BACKGROUND: The systematic use of grafts from controlled donors after cardiac death (cDCD) started in our country in 2012 and expanded with the strategic support of National Transplant Organization. We present our experience in kidney transplantation with organs from cDCD donors with a mean follow-up of 3 years. METHODS: Observational prospective study of all transplants performed in our center in 2012-2013 followed to 2016. The immunosuppression protocols were triple therapy for low-risk recipients from a standard brain death donor (DBD), adding basiliximab or thymoglobulin induction for extended-criteria donor or high-risk recipient, respectively, and thymoglobulin induction plus triple therapy for all cDCD recipients. RESULTS: A total of 42 donors were included (84 grafts in total, but 1 discarded due to multiple cysts); 25 DBD and 17 cDCD without differences in age or sex. The graft use rate was 98.9% for cDCD; 55 grafts were implanted in our hospital (26 DBD and 29 cDCD), and the remaining 28 grafts were transferred to other centers. There were no differences in primary failure (3.4% cDCD vs 7.4% DBD), but the cDCD organs had a higher incidence of delayed graft function (51.7% vs 25.9%). Despite that, graft and patient survivals, as well as glomerular filtration rate (66.3 vs 59.6 mL/min) were similar in both groups. Only 1 patient died at home with a functioning graft in the cDCD group. CONCLUSIONS: Despite a higher rate of delayed graft function with cDCD, the midterm outcomes are at least similar to those with DBD. The cDCD programs should be promoted to increase the chances of a transplant in our patients.


Asunto(s)
Causas de Muerte , Supervivencia de Injerto , Trasplante de Riñón/métodos , Donantes de Tejidos , Adulto , Suero Antilinfocítico/metabolismo , Muerte Encefálica , Muerte , Funcionamiento Retardado del Injerto/epidemiología , Funcionamiento Retardado del Injerto/etiología , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Terapia de Inmunosupresión/métodos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Trasplantes , Resultado del Tratamiento
4.
Clin Microbiol Infect ; 22(8): 732.e1-8, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27181408

RESUMEN

It is important to know the spectrum of the microbial aetiology of prosthetic joint infections (PJIs) to guide empiric treatment and establish antimicrobial prophylaxis in joint replacements. There are no available data based on large contemporary patient cohorts. We sought to characterize the causative pathogens of PJIs and to evaluate trends in the microbial aetiology. We hypothesized that the frequency of antimicrobial-resistant organisms in PJIs has increased in the recent years. We performed a cohort study in 19 hospitals in Spain, from 2003 to 2012. For each 2-year period (2003-2004 to 2011-2012), the incidence of microorganisms causing PJIs and multidrug-resistant bacteria was assessed. Temporal trends over the study period were evaluated. We included 2524 consecutive adult patients with a diagnosis of PJI. A microbiological diagnosis was obtained for 2288 cases (90.6%). Staphylococci were the most common cause of infection (1492, 65.2%). However, a statistically significant rising linear trend was observed for the proportion of infections caused by Gram-negative bacilli, mainly due to the increase in the last 2-year period (25% in 2003-2004, 33.3% in 2011-2012; p 0.024 for trend). No particular species contributed disproportionally to this overall increase. The percentage of multidrug-resistant bacteria PJIs increased from 9.3% in 2003-2004 to 15.8% in 2011-2012 (p 0.008), mainly because of the significant rise in multidrug-resistant Gram-negative bacilli (from 5.3% in 2003-2004 to 8.2% in 2011-2012; p 0.032). The observed trends have important implications for the management of PJIs and prophylaxis in joint replacements.


Asunto(s)
Artritis Infecciosa/epidemiología , Artritis Infecciosa/etiología , Infecciones Relacionadas con Prótesis/epidemiología , Infecciones Relacionadas con Prótesis/etiología , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Artritis Infecciosa/historia , Artroplastia/efectos adversos , Bacterias/efectos de los fármacos , Estudios de Cohortes , Comorbilidad , Farmacorresistencia Bacteriana , Femenino , Hongos/efectos de los fármacos , Historia del Siglo XXI , Humanos , Masculino , Persona de Mediana Edad , Infecciones Relacionadas con Prótesis/historia , España/epidemiología
5.
Am J Transplant ; 16(11): 3220-3234, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27105907

RESUMEN

The prognostic factors and optimal therapy for invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT) remain poorly studied. We included in this multinational retrospective study 112 recipients diagnosed with probable (75.0% of cases) or proven (25.0%) IPA between 2000 and 2013. The median interval from transplantation to diagnosis was 230 days. Cough, fever, and expectoration were the most common symptoms at presentation. Bilateral pulmonary involvement was observed in 63.6% of cases. Positivity rates for the galactomannan assay in serum and bronchoalveolar lavage samples were 61.3% and 57.1%, respectively. Aspergillus fumigatus was the most commonly identified species. Six- and 12-week survival rates were 68.8% and 60.7%, respectively, and 22.1% of survivors experienced graft loss. Occurrence of IPA within the first 6 months (hazard ratio [HR]: 2.29; p-value = 0.027) and bilateral involvement at diagnosis (HR: 3.00; p-value = 0.017) were independent predictors for 6-week all-cause mortality, whereas the initial use of a voriconazole-based regimen showed a protective effect (HR: 0.34; p-value = 0.007). The administration of antifungal combination therapy had no apparent impact on outcome. In conclusion, IPA entails a dismal prognosis among KT recipients. Maintaining a low clinical suspicion threshold is key to achieve a prompt diagnosis and to initiate voriconazole therapy.


Asunto(s)
Rechazo de Injerto/mortalidad , Aspergilosis Pulmonar Invasiva/mortalidad , Fallo Renal Crónico/complicaciones , Trasplante de Riñón/mortalidad , Complicaciones Posoperatorias/mortalidad , Aspergillus , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Supervivencia de Injerto , Humanos , Agencias Internacionales , Aspergilosis Pulmonar Invasiva/etiología , Aspergilosis Pulmonar Invasiva/patología , Fallo Renal Crónico/cirugía , Pruebas de Función Renal , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Receptores de Trasplantes
6.
Am J Transplant ; 16(7): 2148-57, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26813515

RESUMEN

Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case-control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09-90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08-10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04-339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63-456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group.


Asunto(s)
Funcionamiento Retardado del Injerto/etiología , Rechazo de Injerto/etiología , Aspergilosis Pulmonar Invasiva/etiología , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Estudios de Casos y Controles , Funcionamiento Retardado del Injerto/patología , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/patología , Supervivencia de Injerto , Humanos , Aspergilosis Pulmonar Invasiva/patología , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Receptores de Trasplantes
7.
Forensic Sci Int Genet ; 18: 160-70, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26243589

RESUMEN

Sudden cardiac death in the young is a very traumatic event that occurs often in apparently healthy individuals without an explainable cause of death after a comprehensive medico-legal investigation. Knowledge about the pathologies with a risk of sudden death is increasingly showing a greater underlying genetic heterogeneity, which provides one of the main handicaps for molecular autopsy. On the other hand the enormous technological advances in sequencing technologies, allow us to analyse as many genes as we want at a cost increasingly reduced. The sum of these two factors (increased knowledge of genetics and available technologies) allow us to make an individualized study of the causes of sudden cardiac death in young adults, through massive sequencing of all potential genes involved in the process. We define this approach as massive genomic autopsy, and with this review we will try to explain the possible scenarios and methods available for its implementation.


Asunto(s)
Autopsia/métodos , Cardiomiopatías/genética , Muerte Súbita Cardíaca/patología , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Adulto , Humanos , Incidencia , Reproducibilidad de los Resultados , Adulto Joven
8.
Forensic Sci Int Genet ; 17: 110-121, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25955683

RESUMEN

Next generation sequencing (NGS) offers the opportunity to analyse forensic DNA samples and obtain massively parallel coverage of targeted short sequences with the variants they carry. We evaluated the levels of sequence coverage, genotyping precision, sensitivity and mixed DNA patterns of a prototype version of the first commercial forensic NGS kit: the HID-Ion AmpliSeq™ Identity Panel with 169-markers designed for the Ion PGM™ system. Evaluations were made between three laboratories following closely matched Ion PGM™ protocols and a simple validation framework of shared DNA controls. The sequence coverage obtained was extensive for the bulk of SNPs targeted by the HID-Ion AmpliSeq™ Identity Panel. Sensitivity studies showed 90-95% of SNP genotypes could be obtained from 25 to 100pg of input DNA. Genotyping concordance tests included Coriell cell-line control DNA analyses checked against whole-genome sequencing data from 1000 Genomes and Complete Genomics, indicating a very high concordance rate of 99.8%. Discordant genotypes detected in rs1979255, rs1004357, rs938283, rs2032597 and rs2399332 indicate these loci should be excluded from the panel. Therefore, the HID-Ion AmpliSeq™ Identity Panel and Ion PGM™ system provide a sensitive and accurate forensic SNP genotyping assay. However, low-level DNA produced much more varied sequence coverage and in forensic use the Ion PGM™ system will require careful calibration of the total samples loaded per chip to preserve the genotyping reliability seen in routine forensic DNA. Furthermore, assessments of mixed DNA indicate the user's control of sequence analysis parameter settings is necessary to ensure mixtures are detected robustly. Given the sensitivity of Ion PGM™, this aspect of forensic genotyping requires further optimisation before massively parallel sequencing is applied to routine casework.


Asunto(s)
Genética Forense/métodos , Técnicas de Genotipaje/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Polimorfismo de Nucleótido Simple , ADN/análisis , ADN/genética , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Análisis de Secuencia de ADN
9.
Transplant Proc ; 47(1): 27-9, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25645762

RESUMEN

To increase the number of kidney donors, new strategies are needed such as living donor programs, expanded criteria donors, or donors after circulatory death (DCD) kidney transplantation programs. The GEODAS group has started an observational, prospective, multicenter clinical study, collecting data from all DCD type-3 kidney transplantations performed in seven Spanish hospitals from January 2012 to January 2014. The preliminary results have shown a delayed graft function of 40.4% and graft survival of 93.7% with a nadir creatinine of 1.3 mg/dL. From all 33 potential donors included in the study, 32 were effective and 63 kidney grafts were transplanted with a utilization rate of 98.5%. Creatinine evolution (median [range]) was in the first month: 2.1 [0.6-5.6]; third month: 1.6 [0.8, 4.2]; first year: 1.6 [0.9-2.2]. These results are similar to kidney transplantation from donors after brain death as shown in the literature, especially in the graft and recipient survival rates. In addition, the controlled programs are easier and less expensive than uncontrolled DCD programs with a higher rate of graft use.


Asunto(s)
Muerte , Selección de Donante , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Choque , Adulto , Anciano , Creatinina , Funcionamiento Retardado del Injerto/epidemiología , Femenino , Supervivencia de Injerto , Humanos , Fallo Renal Crónico/mortalidad , Masculino , Persona de Mediana Edad , Estudios Prospectivos , España , Resultado del Tratamiento , Adulto Joven
10.
Acta Diabetol ; 51(3): 377-83, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24121872

RESUMEN

In hospitalized diabetic patients, the recommended insulin therapy is basal bolus plus correction-dose regimen instead of sliding-scale insulin. The purpose of this study was to evaluate the effect of the implementation of a new protocol based on basal bolus therapy on managing diabetes in a university hospital setting. We performed a cross-sectional study before and 12 months after a 4-month intervention period to implement a basal bolus regimen in hospitalized patients. Non-critical patients admitted into the hospital for at least 72 h were included. Changes in prescribing habits, glucose control and incidence of hypoglycemia were evaluated. An increase in the use of the new protocol and a decrease in sliding scale were observed after the intervention. In the pre-intervention group, a total of 59.2% glucose readings were between 70 and 180 mg/dL versus 57.1% after the intervention, without observing statistical differences. Significant reductions in hypoglycemia between pre- and post-intervention (13.04 vs. 4.08%, p = 0.0215) were observed. The percentage of hospitalized diabetic patients who had HbA1c was 10.43 and 4.08% in pre- and post-intervention phases, respectively. The protocol showed beneficial outcomes in terms of fewer hypoglycemia episodes and reflected a change in prescription habits, but it did not improve glycemic control. Furthermore, the percentage of patients who had an HbA1c test during their hospitalization remained very low after the intervention. This fact may seriously limit the correct management of hyperglycemia after the hospital discharge.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Quimioterapia/métodos , Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Glucemia/metabolismo , Estudios Transversales , Diabetes Mellitus Tipo 2/metabolismo , Manejo de la Enfermedad , Quimioterapia/instrumentación , Femenino , Hemoglobina Glucada/metabolismo , Hospitalización , Humanos , Hiperglucemia/metabolismo , Pacientes Internos , Masculino , Persona de Mediana Edad
11.
Clin Microbiol Infect ; 20(1): O33-8, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23889700

RESUMEN

The role of Streptococcus species as an aetiological microorganism of vertebral osteomyelitis (VO) is considered to be of little relevance. We aimed to describe a large number of cases of streptococcal vertebral osteomyelitis (SVO), to analyze the clinical features associated with different Streptococcus species, and to compare them with a cohort of patients with VO caused by Staphylococcus aureus. An incidence study and a retrospective, multicenter, observational clinical study of cases of SVO (1991-2011) were performed. Statistical comparison of SVO by different species and between them and staphylococcal VO was carried out. Over the whole period there was an increasing incidence in the number of VOs and SVOs per year (p <0.05). Among 58 cases of SVO, those caused by non-viridans streptococcus (Streptococcus pneumoniae, Streptococcus agalactiae and Streptococcus pyogenes; n = 26) mimicked VO by S. aureus, and presented with more fever, neurological symptoms and paravertebral abscesses in comparison with those caused by the viridans group (remaining species). In contrast, the latter have a sub-acute clinical picture and were associated with the presence of endocarditis (p <0.05). Among non-viridans SVOs, concomitant infection was specifically related to S. pneumoniae (p <0.05). In conclusion, SVO presents a wide range of clinical patterns. The relationship between VO and diagnosis of endocarditis was established with SVO caused by the viridans group. Whereas non-viridans SVO mimics acute characteristics of VO caused by S. aureus, cases of viridans SVO are significantly more likely to have a sub-acute clinical presentation. The increased incidence of SVO during the last decades could support a new epidemiological scenario.


Asunto(s)
Osteomielitis/epidemiología , Osteomielitis/microbiología , Espondilitis/epidemiología , Espondilitis/microbiología , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/microbiología , Streptococcus/aislamiento & purificación , Anciano , Endocarditis Bacteriana/complicaciones , Endocarditis Bacteriana/epidemiología , Endocarditis Bacteriana/microbiología , Humanos , Incidencia , Persona de Mediana Edad , Osteomielitis/complicaciones , Estudios Retrospectivos , España/epidemiología , Infecciones Estreptocócicas/complicaciones , Streptococcus/clasificación
12.
Clin Chim Acta ; 417: 8-11, 2013 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-23247049

RESUMEN

OBJECTIVE: Using candidate gene approach, we have investigated the effect of single nucleotide polymorphism (SNP) in genes related to lipid metabolism and atherosclerosis on dyslipidemia and atorvastatin response. METHODS: The study included 157 patients treated with atorvastatin and 145 controls. Genomic DNA was isolated and genotyped using SNPlex technology. RESULTS: Allele and genotype disease association test revealed that APOB rs693 (OR: 2.2 [1.5-3.2], p=0.0001) and CD36 rs1984112 (OR: 3.7 [1.9-7.0], p=0.0002) SNPs were independent risk factors for hypercholesterolemia. Only APOB rs693 T variant allele was associated with increased LDL cholesterol levels (>160mg/dL). After atorvastatin treatment (10mg/day/4weeks), LIPC -514T allele was positively associated with LDL cholesterol reduction. CONCLUSION: The current study reinforces the current knowledge that carrying APOB rs693 is an independent risk factor for dyslipidemia and higher LDL levels. Furthermore, we found that a variant of CD36 was associated with dyslipidemia as a risk (rs1984112) factor. Finally, atorvastatin response could be predicted by LIPC -514C>T SNP and physical activity. In conclusion, our data evidences the contribution of genetic markers and their interaction with environmental factor in the variability of statin response.


Asunto(s)
Aterosclerosis/complicaciones , Dislipidemias/tratamiento farmacológico , Dislipidemias/genética , Ácidos Heptanoicos/farmacología , Metabolismo de los Lípidos/genética , Polimorfismo de Nucleótido Simple , Pirroles/farmacología , Atorvastatina , Dislipidemias/complicaciones , Dislipidemias/metabolismo , Femenino , Genotipo , Ácidos Heptanoicos/farmacocinética , Ácidos Heptanoicos/uso terapéutico , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Pirroles/farmacocinética , Pirroles/uso terapéutico , Resultado del Tratamiento
13.
Biosens Bioelectron ; 27(1): 40-5, 2011 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-21752625

RESUMEN

A new electrochemical approach for an accurate quantification of DNA base pairs in genomic human DNA amplified by polymerase chain reaction (PCR) is described. The method is based on the immobilization of the sample (a thiolated DNA fragment) on the surface of a screen-printed gold electrode through the -SH group at the 5'-end and the subsequent intercalation of a ruthenium pentaamin complex as a redox indicator. The determination of the base pair number in the sequence is achieved by measuring the changes in the electroactivity of the ruthenium complex using Differential Pulse Voltammetry. Calibration curves correlating current intensity with the base pair number allow determining the size of DNA samples, even when very large (over 100 base pairs) sequences are assayed. The method has been successfully applied to detect the DNA cleavage by a site-specific restriction enzyme. The electrochemical approach developed offers the advantage of ease of performance in comparison to other previously described approaches, which are time-consuming and require sophisticated and expensive instrumentation.


Asunto(s)
Emparejamiento Base , División del ADN , ADN/química , Desoxirribonucleasa HpaII/química , Técnicas Electroquímicas , Electrodos , Oro , Humanos , Compuestos de Rutenio/química
14.
Forensic Sci Int ; 203(1-3): 15-24, 2010 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-20705407

RESUMEN

Sudden cardiac death (SCD) is a major health problem and constitutes one of the most important unsolved challenges in the practice of forensic pathology due to the failure to determine the cause of death. Particularly, an important number of previously healthy young people who have died suddenly and unexpectedly are consequence of genetic heart disorders, either structural cardiomyopathies or arrhythmogenic abnormalities. The technological approach to analyze this type of genetically heterogeneous disorders is far from easy but nowadays the variety of chemistries and methodologies improves choice. This review offers to the reader a state of the art of the available technologies for the study of genetics of sudden cardiac death, including mutation screening approaches, genome wide association studies, and the recently developed next-generation sequencing.


Asunto(s)
Muerte Súbita Cardíaca/etiología , Pruebas Genéticas , Estudio de Asociación del Genoma Completo , Mutación , Análisis de Secuencia por Matrices de Oligonucleótidos , Análisis de Secuencia de ADN , Arritmias Cardíacas/genética , Cardiomiopatías/genética , Cartilla de ADN , Genética Forense , Perfilación de la Expresión Génica , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Polimerasa Taq
15.
Mol Psychiatry ; 15(10): 1023-33, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19528963

RESUMEN

Copy number variants (CNVs) are a substantial source of human genetic diversity, influencing the variable susceptibility to multifactorial disorders. Schizophrenia is a complex illness thought to be caused by a number of genetic and environmental effects, few of which have been clearly defined. Recent reports have found several low prevalent CNVs associated with the disease. We have used a multiplex ligation-dependent probe amplification-based (MLPA) method to target 140 previously reported and putatively relevant gene-containing CNV regions in 654 schizophrenic patients and 604 controls for association studies. Most genotyped CNVs (95%) showed very low (<1%) population frequency. A few novel rare variants were only present in patients suggesting a possible pathogenic involvement, including 1.39 Mb overlapping duplications at 22q11.23 found in two unrelated patients, and duplications of the somatostatin receptor 5 gene (SSTR5) at 16p13.3 in three unrelated patients. Furthermore, among the few relatively common CNVs observed in patients and controls, the combined analysis of gene copy number genotypes at two glutathione S-transferase (GST) genes, GSTM1 (glutathione S-transferase mu 1) (1p13.3) and GSTT2 (glutathione S-transferase theta 2) (22q11.23), showed a statistically significant association of non-null genotypes at both loci with an additive effect for increased vulnerability to schizophrenia (odds ratio of 1.92; P=0.0008). Our data provide complementary evidences for low prevalent, but highly penetrant chromosomal variants associated with schizophrenia, as well as for common CNVs that may act as susceptibility factors by disturbing glutathione metabolism.


Asunto(s)
Dosificación de Gen/genética , Glutatión Transferasa/genética , Esquizofrenia/genética , Adulto , Anciano , Femenino , Duplicación de Gen/genética , Predisposición Genética a la Enfermedad/epidemiología , Variación Genética , Genómica , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Esquizofrenia/epidemiología
16.
Radiología (Madr., Ed. impr.) ; 51(2): 198-203, mar.-abr. 2009. ilus
Artículo en Español | IBECS | ID: ibc-96604

RESUMEN

Objetivo Valorar los hallazgos radiológicos (ecografía, tomografía computarizada y resonancia magnética) de las diferentes manifestaciones abdominales de la enfermedad de von Hippel Lindau (EVHL). Material y métodosSe revisaron de forma retrospectiva los estudios de imagen de 7 pacientes diagnosticados de EVHL en nuestro hospital. Resultados Se detectó afectación abdominal en todos los pacientes estudiados. Todos mostraron algún tipo de afectación renal: quistes y carcinomas renales. También se detectó afectación pancreática en la práctica totalidad de los casos: quistes pancreáticos simples, varios cistoadenomas serosos y un tumor neuroendocrino. Una paciente presentó un cistoadenoma papilar del ligamento ancho. Conclusiones Las técnicas de imagen desempeñan un papel esencial, tanto en el diagnóstico inicial de las distintas manifestaciones abdominales como en el control y seguimiento de estos pacientes (AU)


Objective To evaluate the radiologic findings (ultrasound, computed tomography and magnetic resonance) of the abdominal manifestations in von Hippel-Lindau disease (VHL). Material and methods We retrospectively reviewed the imaging studies performed to seven patients diagnosed of VHL in our hospital. Results In all exmined patients, abdominal involvement was found. All of them showed renal affectation: cysts or renal cell carcinoma. Pancreatic involvement was found in the majority of patients: simple cysts, serous cystadenomas and one neuroendocrine tumor. One patient had a papillary cystadenoma of the broad ligament (AU)


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Enfermedad de von Hippel-Lindau/complicaciones , Neoplasias Renales/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Estudios Retrospectivos , Quistes/diagnóstico , Carcinoma de Células Renales/diagnóstico , Cistadenocarcinoma Seroso/diagnóstico , Tumores Neuroendocrinos/diagnóstico
17.
Radiologia ; 51(2): 198-203, 2009.
Artículo en Español | MEDLINE | ID: mdl-19286236

RESUMEN

OBJECTIVE: To evaluate the radiologic findings (ultrasound, computed tomography and magnetic resonance) of the abdominal manifestations in von Hippel-Lindau disease (VHL). MATERIAL AND METHODS: We retrospectively reviewed the imaging studies performed to seven patients diagnosed of VHL in our hospital. RESULTS: In all exmined patients, abdominal involvement was found. All of them showed renal affectation: cysts or renal cell carcinoma. Pancreatic involvement was found in the majority of patients: simple cysts, serous cystadenomas and one neuroendocrine tumor. One patient had a papillary cystadenoma of the broad ligament.


Asunto(s)
Enfermedad de von Hippel-Lindau/diagnóstico , Abdomen , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Enfermedad de von Hippel-Lindau/complicaciones
18.
Forensic Sci Int Genet ; 1(2): 180-5, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19083752

RESUMEN

Using a 52 SNP marker set previously developed for forensic analysis, a novel 49plex assay has been developed based on the Genplex typing system, a modification of SNPlex chemistry (both Applied Biosystems) using oligo-ligation of pre-amplified DNA and dye-labeled, mobility modified detection probes. This gives highly predictable electrophoretic mobility of the allelic products generated from the assay to allow detection with standard capillary electrophoresis analyzers. The loci chosen comprise the 48 most informative autosomal SNPs from the SNPforID core discrimination set supplemented with the amelogenin gender marker. These SNPs are evenly distributed across all 22 autosomes, exhibit balanced polymorphisms in three major population groups and have been previously shown to be effective markers for forensic analysis. We tested the accuracy and reproducibility of the Genplex system in three SNPforID laboratories, each using a different Applied Biosystems Genetic Analyzer. Genotyping concordance was measured using replicates of 44 standardized DNA controls and by comparing genotypes for the same samples generated by the TaqMan, SNaPshot and Sequenom iPLEX SNP typing systems. The degree of informativeness of the 48 SNPs for forensic analysis was measured using previously estimated allele frequencies to derive the cumulative match probability and in paternity analysis using 24 trios previously typed with 18 STRs together with three CEPH families with extensive sibships typed with the 15 STRs in the Identifiler kit.


Asunto(s)
Dermatoglifia del ADN/métodos , Genética Forense/métodos , Marcadores Genéticos , Polimorfismo de Nucleótido Simple , Alelos , ADN/genética , ADN/aislamiento & purificación , Dermatoglifia del ADN/estadística & datos numéricos , Electroforesis Capilar , Femenino , Genética Forense/estadística & datos numéricos , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Repeticiones de Microsatélite , Paternidad , Reacción en Cadena de la Polimerasa , Reproducibilidad de los Resultados , Programas Informáticos
19.
Int J Legal Med ; 119(1): 10-5, 2005 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15095093

RESUMEN

Analysis of Y-chromosome haplogroups defined by binary polymorphisms, has became a standard approach for studying the origin of modern human populations and for measuring the variability between them. Furthermore, the simplicity and population specificity of binary polymorphisms allows inferences to be drawn about the population origin of any male sample of interest for forensic purposes. From the 245 binary polymorphisms that can be analysed by PCR described in the Y Chromosome Consortium tree, we have selected 30 markers. The set of 30 has been grouped into 4 multiplexes in order to determine the most frequent haplogroups in Europe, using only 1 or 2 multiplexes. In this way, we avoid typing unnecessary SNPs to define the final haplogroup saving effort and cost, since we only need to type 9 SNPs in the best case and in the worst case, no more than 17 SNPs to define the haplogroup. The selected method for allele discrimination was a single base extension reaction using the SNaPshot multiplex kit. A total of 292 samples from 8 different districts of Galicia (northwest Spain) were analysed with this strategy. No significant differences were detected among the different districts, except for the population from Marina Lucense, which showed a distant haplogroup frequency but not higher Phi(st) values.


Asunto(s)
Cromosomas Humanos Y , Dermatoglifia del ADN , Genética de Población , Polimorfismo de Nucleótido Simple , Secuencia de Bases , Marcadores Genéticos , Haplotipos , Humanos , Masculino , Reacción en Cadena de la Polimerasa , España
20.
Arch. Fac. Med. Zaragoza ; 43(2): 49-51, ago. 2003. ilus, tab
Artículo en Es | IBECS | ID: ibc-34183

RESUMEN

En genética forense, el análisis de SNPs resulta interesante debido a su abundancia en el genoma, su baja tasa de mutación y la posibilidad de automatizar el análisis. Sin embargo, el número de SNPs que necesitan ser analizados para obtener el mismo poder de discriminación que con 13 STRs es de 50-80. Por lo tanto, es necesario el desarrollo de tecnologías que nos permitan tipar un gran número de SNPs simultáneamente. En este trabajo se presentan los resultados obtenidos con los chips electrónicamente activos de NanogenTM para el tipado de SNPs de cromosoma Y mediante dos estrategias: "amplicon down" y "capture down". Las ventajas y desventajas de cada una de ellas son analizadas (AU)


Asunto(s)
Humanos , Antropología Forense/métodos , Genética/instrumentación , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Cromosoma Y/genética
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