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1.
BMC Psychiatry ; 18(1): 74, 2018 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-29566656

RESUMEN

BACKGROUND: Data from primary health care in Spain show a high prevalence of the major depressive disorder. Blended treatment (combination of face-to-face and online components) seems to be a very promising tool for the optimization and dissemination of psychological treatments in a cost-effective form. Although there is growing data that confirm the advantages of blended therapies, few studies have analyzed their application in regular clinical practice. The objective of the present paper is to describe the protocol for a clinical study aimed at exploring the clinical and cost-effectiveness of a blended cognitive behavioral therapy (b-CBT) for depression, compared to treatment as usual (TAU) in a primary health care setting. METHODS: A two-arm randomised controlled non-inferiority trial will be carried out, with repeated measures (baseline, 3 months, 6 months, and 12 months) under two conditions: b-CBT and TAU. The b-CBT program will consist in three face-to-face sessions and eight online sessions. The TAU is defined as the routine care delivered by the general practitioner for the treatment of depression in primary care. The primary outcome is a symptomatic change of depressive symptoms on the patient-health questionnaire (PHQ-9). Other secondary outcomes will be considered (e.g., quality of life, treatment preference). All participants must be 18 years of age or older and meet the diagnostic criteria for major depressive disorder according to the Diagnostic and Statistical Manual of Mental disorders 4th edition. 156 participants will be recruited (78 per arm). DISCUSSION: It is expected that b-CBT is clinically non-inferior when compared to TAU. This is the first study in Spain to use a b-CBT format in primary and specialized care, and this format could be an efficacious and cost-effective therapeutic strategy for the treatment of depression. TRIAL REGISTRATION: ClinicalTrials.gov NCT02361684. Registered on 8 January 2015. Currently recruiting participants.


Asunto(s)
Terapia Cognitivo-Conductual , Análisis Costo-Beneficio , Depresión/terapia , Estudios de Equivalencia como Asunto , Atención Primaria de Salud , Ensayos Clínicos Controlados Aleatorios como Asunto , Adolescente , Adulto , Femenino , Humanos , Masculino , Satisfacción del Paciente , Relaciones Profesional-Paciente , Calidad de Vida , España , Resultado del Tratamiento , Adulto Joven
2.
Genome Res ; 23(2): 281-91, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23070852

RESUMEN

Human U1 small nuclear (sn)RNA, required for splicing of pre-mRNA, is encoded by genes on chromosome 1 (1p36). Imperfect copies of these U1 snRNA genes, also located on chromosome 1 (1q12-21), were thought to be pseudogenes. However, many of these "variant" (v)U1 snRNA genes produce fully processed transcripts. Using antisense oligonucleotides to block the activity of a specific vU1 snRNA in HeLa cells, we have identified global transcriptome changes following interrogation of the Affymetrix Human Exon ST 1.0 array. Our results indicate that this vU1 snRNA regulates expression of a subset of target genes at the level of pre-mRNA processing. This is the first indication that variant U1 snRNAs have a biological function in vivo. Furthermore, some vU1 snRNAs are packaged into unique ribonucleoproteins (RNPs), and many vU1 snRNA genes are differentially expressed in human embryonic stem cells (hESCs) and HeLa cells, suggesting developmental control of RNA processing through expression of different sets of vU1 snRNPs.


Asunto(s)
Empalme Alternativo , Regulación de la Expresión Génica , ARN Nuclear Pequeño/genética , Técnicas de Silenciamiento del Gen , Células HeLa , Humanos , Datos de Secuencia Molecular , Seudogenes , ARN Nuclear Pequeño/metabolismo , Ribonucleoproteínas/metabolismo , Transcripción Genética
3.
J Gastroenterol Hepatol ; 29(1): 173-8, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24219115

RESUMEN

BACKGROUND AND AIM: There are few data of fibrosis development in chronic hepatitis B (CHB) patients classified as inactive carriers. The aim of this study is to determinate the prevalence of significant fibrosis and probable cirrhosis measured by FibroScan in real inactive CHB carriers and investigate the relationship with virological, epidemiological, and metabolic factors. METHODS: Cross-sectional cohort study including CHB inactive carriers. Liver stiffness measurement was performed with transient elastography (FibroScan). Significant fibrosis (≥ F2) was defined as stiffness > 7.5 kPa, and probable cirrhosis as > 11.8 kPa. Factors associated with significant fibrosis were explored with univariate and multivariate adjusted logistic regression analyses. RESULTS: Ninety-six CHB inactive carriers were analyzed. Of them, 24 (25%) had significant fibrosis and 7 (7%) probable cirrhosis; mean stiffness was 6.2 ± 2.3 kPa. Of them, 24% had metabolic syndrome, with higher FibroScan value than those without (8.4 kPa vs 5.5 kPa, P < 0.001). Factors associated with significant fibrosis were (odds ratio, 95% confidence interval, P value): central obesity (7.1, 1.8-27.9, 0.005), elevated fasting glucose (4.3, 1.3-27.9, 0.036), reduced high-density lipoprotein cholesterol (5.2, 1.2-23.6, 0.032) and elevated triglycerides (6.2, 1.4-28.3, 0.019). Factors as age, sex, transaminases, hepatitis B virus DNA or genotype were not related with liver fibrosis. The presence of metabolic syndrome has a 69% of positive predictive value and 89% of negative predictive value for significant fibrosis. CONCLUSION: Different components of metabolic syndrome are associated with fibrosis development in CHB inactive carriers. In the absence of metabolic syndrome, significant fibrosis is uncommon in this population.


Asunto(s)
Portador Sano , Hepatitis B Crónica/complicaciones , Cirrosis Hepática/etiología , Síndrome Metabólico/complicaciones , Adulto , Anciano , Estudios Transversales , Diagnóstico por Imagen de Elasticidad , Femenino , Humanos , Cirrosis Hepática/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Análisis de Regresión , Estudios Retrospectivos , Activación Viral
4.
Biomedicines ; 12(2)2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38397958

RESUMEN

Intermediate CAG expansions in the gene ataxin-2 (ATXN2) are a known risk factor for ALS, but little is known about their role in FTD risk. Moreover, their contribution to the risk and phenotype of patients might vary in populations with different genetic backgrounds. The aim of this study was to assess the relationship of intermediate CAG expansions in ATXN2 with the risk and phenotype of ALS and FTD in the Spanish population. Repeat-primed PCR was performed in 620 ALS and 137 FTD patients in three referral centers in Spain to determine the exact number of CAG repeats. In our cohort, ≥27 CAG repeats in ATXN2 were associated with a higher risk of developing ALS (odds ratio [OR] = 2.666 [1.471-4.882]; p = 0.0013) but not FTD (odds ratio [OR] = 1.446 [0.558-3.574]; p = 0.44). Moreover, ALS patients with ≥27 CAG repeats in ATXN2 showed a shorter survival rate compared to those with <27 repeats (hazard ratio [HR] 1.74 [1.18, 2.56], p = 0.005), more frequent limb onset (odds ratio [OR] = 2.34 [1.093-4.936]; p = 0.028) and a family history of ALS (odds ratio [OR] = 2.538 [1.375-4.634]; p = 0.002). Intermediate CAG expansions of ≥27 repeats in ATXN2 are associated with ALS risk but not with FTD in the Spanish population. ALS patients carrying an intermediate expansion in ATXN2 show more frequent limb onset but a worse prognosis than those without expansions. In patients carrying C9orf72 expansions, the intermediate ATXN2 expansion might increase the penetrance and modify the phenotype.

5.
Hum Mutat ; 34(1): 79-82, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22936364

RESUMEN

A hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9orf72) can cause amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD). We assessed its frequency in 781 sporadic ALS (sALS) and 155 familial ALS (fALS) cases, and in 248 Spanish controls. We tested the presence of the reported founder haplotype among mutation carriers and in 171 Ceph Europeans from Utah (CEU), 170 Yoruba Africans, 81 Han Chinese, and 85 Japanese subjects. The C9orf72 expansion was present in 27.1% of fALS and 3.2% of sALS. Mutation carriers showed lower age at onset (P = 0.04), shorter survival (P = 0.02), greater co-occurrence of FTD (P = 8.2 × 10(-5)), and more family history of ALS (P = 1.4 × 10(-20)), than noncarriers. No association between alleles within the normal range and the risk of ALS was found (P = 0.12). All 61 of the mutation carriers were tested and a patient carrying 28 hexanucleotide repeats presented with the founder haplotype. This haplotype was found in 5.6% Yoruba Africans, 8.9% CEU, 3.9% Japanese, and 1.6% Han Chinese chromosomes.


Asunto(s)
Esclerosis Amiotrófica Lateral/genética , Expansión de las Repeticiones de ADN/genética , Predisposición Genética a la Enfermedad/genética , Proteínas/genética , África/etnología , Anciano , Anciano de 80 o más Años , Esclerosis Amiotrófica Lateral/etnología , Pueblo Asiatico/genética , Proteína C9orf72 , China/etnología , Análisis Mutacional de ADN , Etnicidad/genética , Europa (Continente)/etnología , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/etnología , Haplotipos , Heterocigoto , Humanos , Japón/etnología , Estimación de Kaplan-Meier , Masculino , Mutación , Polimorfismo de Nucleótido Simple , España
6.
Rev Chilena Infectol ; 30(2): 156-61, 2013 Apr.
Artículo en Español | MEDLINE | ID: mdl-23677154

RESUMEN

INTRODUCTION: The development of malignancies is a problem associated with HIV infection. The incidence and spectrum of malignancies has been modified with the addition of highly active antiretroviral therapy (HAART). AIM: To describe the clinical and epidemiological characteristics and prognosis of HIV patients who have developed a malignancy. METHODS: Retrospective observational study was conducted in HIV + patients who developed a malignancy between 1993-2010 in a referral hospital. AIDS-defining malignancies (ADN) and non-AIDS-defining malignancies (NADN) were compared. RESULTS: 125 patients were identified with at least one malignancy. The most frequent malignancies were: non-Hodgkin lymphoma (n; 39; 30.2%), Kaposi's sarcoma (n: 20; 15.5%), Hodgkin's disease (n: 11; 8.8%), lung cancer (n: 20; 15.5%) and hepatocellular carcinoma (n: 9; 6.9 %). The mean age was 42 ± 11 years, 84% male, 55.8% were coinfected with HBV and or HCV. The risk behaviors were: 45.6% intravenous drug users, 16.8% men who have sex with men and 20% heterosexuals). There were 67 (52%) NADN and 62 (48%) ADN; NADN patients had a longer story of HIV infection and longer exposure to HAART, better level of immunodeficiency and better virological control than ADN patients. Four patients developed a second malignancy. Overall survival was 34.7%. CONCLUSIONS: We found an increased incidence of NADN, appearing in patients with better virological and immunological control than ADN group. Mortality of patients with HIV infection and malignancy is still very high.


Asunto(s)
Infecciones por VIH/complicaciones , Neoplasias/etiología , Adulto , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Estudios de Cohortes , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/epidemiología , Pronóstico , Estudios Retrospectivos , España/epidemiología , Análisis de Supervivencia
7.
Cell Metab ; 35(9): 1630-1645.e5, 2023 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-37541251

RESUMEN

Neddylation is a post-translational mechanism that adds a ubiquitin-like protein, namely neural precursor cell expressed developmentally downregulated protein 8 (NEDD8). Here, we show that neddylation in mouse liver is modulated by nutrient availability. Inhibition of neddylation in mouse liver reduces gluconeogenic capacity and the hyperglycemic actions of counter-regulatory hormones. Furthermore, people with type 2 diabetes display elevated hepatic neddylation levels. Mechanistically, fasting or caloric restriction of mice leads to neddylation of phosphoenolpyruvate carboxykinase 1 (PCK1) at three lysine residues-K278, K342, and K387. We find that mutating the three PCK1 lysines that are neddylated reduces their gluconeogenic activity rate. Molecular dynamics simulations show that neddylation of PCK1 could re-position two loops surrounding the catalytic center into an open configuration, rendering the catalytic center more accessible. Our study reveals that neddylation of PCK1 provides a finely tuned mechanism of controlling glucose metabolism by linking whole nutrient availability to metabolic homeostasis.


Asunto(s)
Diabetes Mellitus Tipo 2 , Ratones , Animales , Fosfoenolpiruvato/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Proteínas/metabolismo , Hígado/metabolismo , Lisina/metabolismo , Glucosa/metabolismo
8.
Antibiotics (Basel) ; 11(12)2022 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-36551411

RESUMEN

An 8-year-old girl diagnosed with cardiofaciocutaneous syndrome presented to our department with gingival pain, inflammation, and bleeding. Her medical history included hypoplasia of the corpus callosum, intellectual disability, trichothiodystrophy, global developmental delay, myopia, laryngomalacia, hypothyroidism, and osteoporosis. A diagnosis was reached of "periodontitis as a direct manifestation of systemic diseases". During 9 years of follow-up, there were exacerbation episodes with spontaneous gum bleeding, ulcers in the interdental papilla, tooth mobility, and progressive tooth loss. Some of these exacerbation episodes resolved clinically with the administration of amoxicillin and metronidazole. We therefore proposed an oral microbiome study (subgingival and saliva samples) before and after antibiotic therapy. The most abundant genera at the subgingival level before administering antibiotics were Prevotella, Streptococcus, Fusobacterium, Leptotrichia, and Aggregatibacter. Of the 94 genera sequenced, 57 were less abundant in the post-treatment state than at baseline, particularly certain Gram-negative periodontal pathogens such as Porphyromonas, Treponema, Aggregatibacter, Fusobacterium, and Campylobacter. In contrast, other genera related to oral health, such as Haemophilus, Granulicatella, and Abiotrophia, showed an increase after administering the antibiotic. In conclusion, periodontitis exacerbations as a direct manifestation of systemic disease can occasionally be controlled exclusively with systemic antibiotics, without the need for performing mechanical periodontal therapy. This clinical recovery is correlated to substantial changes in the oral microbiome, which lead to the recovery of eubiosis of the microbiota.

9.
PLoS One ; 17(11): e0277606, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36409695

RESUMEN

BACKGROUND: The main international guidelines indicate DTG/3TC therapy as one of the preferred regimens for people living with HIV (PLWH), due to its observed efficacy in randomized clinical trials. However, information in real-life cohorts is relatively scarce for first-line use. METHODS: A retrospective multicenter study of adult PLWH starting DTG+3TC as a first-line regimen before January 31st, 2020. Virological failure (VF) was defined as 2 consecutive HIV RNA viral load (VL) >50 copies/mL. RESULTS: 135 participants were included. Treatment was started without knowing baseline drug resistance testing (bDRT) results in 71.9% of cases, with baseline resistance mutations being later confirmed in 17 patients (12.6%), two of them with presence of M184V mutation. Effectiveness at week 48 was 85.2% (CI95%: 78.1-90.7%) (ITT missing = failure [M = F]) and 96.6% (CI 95%: 91.6-99.1%) (per-protocol analysis). Six patients (4.4%) discontinued treatment. One developed not confirmed VF after discontinuing treatment due to poor adherence; no resistance-associated mutations emerged. Three discontinued treatments due to central nervous system side effects (2.2%), and two due to a medical decision after determining the M184V mutation in bDRT. Finally, 14 (10.4%) were lost to follow-up, most of them due to the COVID-19 pandemic. CONCLUSIONS: In a real-life multicenter cohort of ART-naïve PLWH, treatment initiation with DTG + 3TC showed high effectiveness and favorable safety results, comparable to those of randomized clinical trials, without treatment-emergent resistance being observed through week 48. Starting treatment before receiving the results of baseline drug resistance testing did not have an impact on the regimen's effectiveness.


Asunto(s)
Fármacos Anti-VIH , COVID-19 , Infecciones por VIH , VIH-1 , Adulto , Humanos , Lamivudine/farmacología , Fármacos Anti-VIH/efectos adversos , Pandemias , VIH-1/genética , Antirretrovirales/uso terapéutico
10.
Amyotroph Lateral Scler ; 11(5): 475-7, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20509746

RESUMEN

ALSFRS-R is a tool designed to measure disease progress in ALS patients. It consists of 12 items grouped into four functions designed to assess disabilities according to the Activities of daily living (ADL). Our objective was to validate the Spanish version of ALSFRS-R based on the original version. Four examiners assessed 73 ALS patients, applying the ALSFRS-R, ALSAQ-40 and the respiratory function variable assessed by the SRI scale, which measures respiratory insufficiency. Internal consistency and test-retest correlations were measured using Cronbach's alpha and Spearman's Rho tests. Factor analysis was performed by applying Varimax rotation and Kaiser standardization. Validity was analysed based on correlations between items in the ALSFRS-R scales and equivalents in the ALSAQ-40 and SRI questionnaires. The results showed high internal consistency (0.77-0.95) and a good test-retest correlation (0.80-0.95). Factor analysis showed a 73.3% principal component contribution; the weight of each item regarding their corresponding factors was 0.7-0.9. High correlations were observed (rs >0.60) between corresponding factors of ALSFRS-R/ALSAQ-40 and ALSFRS-R/SRI. We conclude that the version obtained from the ALSFRS-R maintains the internal consistency and validity of the construct of the original scale. The Spanish version of ALSFRS-R is available for readers at http://www.fundela.es/verOtras.php.


Asunto(s)
Esclerosis Amiotrófica Lateral/fisiopatología , Evaluación de la Discapacidad , Lenguaje , Encuestas y Cuestionarios/normas , Actividades Cotidianas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Reproducibilidad de los Resultados , España
11.
Aging Dis ; 10(2): 278-292, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31011479

RESUMEN

The identification of more reliable diagnostic or prognostic biomarkers in age-related neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis (ALS), is urgently needed. The objective in this study was to identify more reliable prognostic biomarkers of ALS mirroring neurodegeneration that could be of help in clinical trials. A total of 268 participants from three cohorts were included in this study. The muscle and blood cohorts were analyzed in two cross-sectional studies, while the serial blood cohort was analyzed in a longitudinal study at 6-monthly intervals. Fifteen target genes and fourteen proteins involved in muscle physiology and differentiation, metabolic processes and neuromuscular junction dismantlement were studied in the three cohorts. In the muscle biopsy cohort, the risk for a higher mortality in an ALS patient that showed high Collagen type XIX, alpha 1 (COL19A1) protein levels and a fast progression of the disease was 70.5% (P < 0.05), while in the blood cohort, this risk was 20% (P < 0.01). In the serial blood cohort, the linear mixed model analysis showed a significant association between increasing COL19A1 gene levels along disease progression and a faster progression during the follow-up period of 24 months (P < 0.05). Additionally, higher COL19A1 levels and a faster progression increased 17.9% the mortality risk (P < 0.01). We provide new evidence that COL19A1 can be considered a prognostic biomarker that could help the selection of homogeneous groups of patients for upcoming clinical trial and may be pointed out as a promising therapeutic target in ALS.

12.
PLoS One ; 13(4): e0195068, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29649309

RESUMEN

TRIAL DESIGN: The QoLKAMON study evaluated quality of life, efficacy and treatment safety in HIV patients receiving lopinavir/ritonavir in monotherapy (MT) versus continuing combined antiretroviral triple treatment with a boosted protease inhibitor (TT). METHODS: This was a 24-week, open-label, multicentre study in virologically-suppressed HIV-infected participants (N = 225) with a 2:1 randomization: 146 patients who switched to MT were compared with 79 patients who remained on a TT regimen. The primary endpoint was change in patient-reported outcomes in quality of life as measured by the MOS-HIV and EQ-5D questionnaires. Secondary endpoints included treatment adherence, patient satisfaction, incidence of adverse events and differences in plasma HIV-1 RNA viral load (VL) and CD4 cell counts. RESULTS: Baseline quality of life, measured with the MOS-HIV score, was very good (overall score of 83 ± 10.5 in the MT arm and 82.3 ± 11.3 in the TT arm) and suffered no change during the study in any of the arms (at week 24, 83.5 ± 12.2 in MT arm and 81.9 ± 12.7 in TT arm), without statistically significant differences when compared. In regards to adherence to therapy and patient satisfaction, some aspects (number of doses forgotten in the last week and satisfaction of treatment measured with the CESTA score, dimension 1) improved significantly with MT. There were also no differences in the incidence and severity of adverse events, even though 22.8% of those in the MT arm switched their treatment when they were included in the study. Moreover, there was also no significant difference between the immunological and virological evolution of MT and TT. In the MT arm, the VL was always undetectable in 83% of patients (vs 90.7% in the TT arm) and there were only 6.7% of virological failures with VL > 50 copies/mL (vs 2.3% in the TT arm), without resistance mutations and with resuppression of VL after switching back to TT. CONCLUSIONS: In a new clinical trial, monotherapy as a treatment simplification strategy in HIV-1 infected patients with sustained viral suppression has demonstrated quality of life, safety and efficacy profiles comparable to those of conventional triple therapy regimens.


Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Lopinavir/administración & dosificación , Calidad de Vida , Ritonavir/administración & dosificación , Adulto , Recuento de Linfocito CD4 , Femenino , Inhibidores de la Proteasa del VIH/administración & dosificación , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1/genética , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , España , Encuestas y Cuestionarios , Resultado del Tratamiento , Carga Viral/efectos de los fármacos
15.
J Periodontol ; 75(10): 1413-6, 2004 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15562920

RESUMEN

BACKGROUND: This report describes the surgical treatment of a gingival recession in a hemophiliac HIV-infected patient. To our knowledge, mucogingival surgery has not been described previously in these patients. METHODS: Under the supervision of the patient's hematologist, a subepithelial connective tissue graft procedure was carried out to treat the recession. The treatment was performed after substitution therapy with factor VIII concentrate, supported by local antifibrinolytic treatment with epsilonaminocaproic acid. RESULTS: One week after surgery, the grafted zone showed a normal healing, but an area of necrosis appeared at the donor palatal site with spontaneous bleeding. The administration of factor VIII concentrate had to be prolonged to arrest the hemorrhage. In total, 44,500 units of factor VIII concentrate were used, the cost of which reached around $20,000. After 1 month the donor site had re-epithelialized by secondary intention. The root coverage was around 85% successful. CONCLUSIONS: Because of the surgical risk and the high economic cost in the use of the factor VIII concentrate, we do not recommend performing mucogingival surgery in HIV-infected hemophiliacs unless it is absolutely necessary. Prevention and early treatment must be the goal in the management of these patients.


Asunto(s)
Recesión Gingival/cirugía , Infecciones por VIH/complicaciones , Hemofilia A/complicaciones , Adulto , Ácido Aminocaproico/uso terapéutico , Antifibrinolíticos/uso terapéutico , Coagulantes/economía , Coagulantes/uso terapéutico , Tejido Conectivo/trasplante , Costos de los Medicamentos , Factor VIII/economía , Factor VIII/uso terapéutico , Encía/trasplante , Recesión Gingival/economía , Supervivencia de Injerto , Hemofilia A/economía , Humanos , Masculino , Necrosis , Hemorragia Bucal/etiología , Hemorragia Posoperatoria/etiología
16.
PLoS One ; 7(3): e32632, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22412900

RESUMEN

The pathophysiological mechanisms of both familial and sporadic Amyotrophic Lateral Sclerosis (ALS) are unknown, although growing evidence suggests that skeletal muscle tissue is a primary target of ALS toxicity. Skeletal muscle biopsies were performed on transgenic SOD1(G93A) mice, a mouse model of ALS, to determine genetic biomarkers of disease longevity. Mice were anesthetized with isoflurane, and three biopsy samples were obtained per animal at the three main stages of the disease. Transcriptional expression levels of seventeen genes, Ankrd1, Calm1, Col19a1, Fbxo32, Gsr, Impa1, Mef2c, Mt2, Myf5, Myod1, Myog, Nnt, Nogo A, Pax7, Rrad, Sln and Snx10, were tested in each muscle biopsy sample. Total RNA was extracted using TRIzol Reagent according to the manufacturer's protocol, and variations in gene expression were assayed by real-time PCR for all of the samples. The Pearson correlation coefficient was used to determine the linear correlation between transcriptional expression levels throughout disease progression and longevity. Consistent with the results obtained from total skeletal muscle of transgenic SOD1(G93A) mice and 74-day-old denervated mice, five genes (Mef2c, Gsr, Col19a1, Calm1 and Snx10) could be considered potential genetic biomarkers of longevity in transgenic SOD1(G93A) mice. These results are important because they may lead to the exploration of previously unexamined tissues in the search for new disease biomarkers and even to the application of these findings in human studies.


Asunto(s)
Esclerosis Amiotrófica Lateral/genética , Proteínas Mutantes/genética , Superóxido Dismutasa/genética , Animales , Biopsia , Desnervación , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Marcadores Genéticos , Humanos , Longevidad/genética , Masculino , Ratones , Ratones Transgénicos , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Superóxido Dismutasa-1 , Transcripción Genética
17.
Int J Radiat Oncol Biol Phys ; 84(5): 1151-8, 2012 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-22516806

RESUMEN

PURPOSE: Management of locally advanced rectal cancer (RC) consists of neoadjuvant chemoradiotherapy (CRT) with fluoropyrimidines, followed by total mesorectal excision. We sought to evaluate the expression of selected genes, some of which were derived from a previous undirected SAGE (serial analysis of gene expression)-based approach, before and after CRT, to identify mechanisms of resistance. METHODS: This retrospective cohort study included 129 consecutive patients. Quantitative polymerase chain reaction of 53 candidate genes was performed on the biopsy specimen before treatment and on the surgical specimen after CRT. A paired-samples t test was performed to determine genes that were significantly changed after CRT. The result was correlated with patients' disease-free survival. RESULTS: Twenty-two genes were significantly upregulated, and two were significantly downregulated. Several of the upregulated genes have roles in cell cycle control; these include CCNB1IP1, RCC1, EEF2, CDKN1, TFF3, and BCL2. The upregulation of TFF3 was associated with worse disease-free survival on multivariate analyses (hazard ratio, 2.64; P=.027). Patients whose surgical specimens immunohistochemically showed secretion of TFF3 into the lumen of the tumoral microglands had a higher risk of relapse (hazard ratio, 2.51; P=.014). In vitro experiments showed that DLD-1 cells stably transfected with TFF3 were significantly less sensitive to 5-fluorouracil and showed upregulation of genes involved in the transcriptional machinery and in resistance to apoptosis. CONCLUSION: Upregulation of TFF3 after CRT for RC is associated with a higher risk of relapse. The physiological role of TFF3 in restoring the mucosa during CRT could be interfering with treatment efficacy. Our results could reveal not only a novel RC prognostic marker but also a therapeutic target.


Asunto(s)
Adenocarcinoma/metabolismo , Quimioradioterapia Adyuvante , Proteínas de Neoplasias/metabolismo , Recurrencia Local de Neoplasia , Péptidos/metabolismo , Neoplasias del Recto/metabolismo , Neoplasias del Recto/terapia , Adenocarcinoma/genética , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Línea Celular Tumoral , Quimioradioterapia Adyuvante/métodos , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos/genética , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Proteínas de Neoplasias/genética , Péptidos/genética , Reacción en Cadena de la Polimerasa , Pronóstico , Análisis por Matrices de Proteínas/métodos , Neoplasias del Recto/genética , Estudios Retrospectivos , Transfección/métodos , Factor Trefoil-3 , Regulación hacia Arriba , Adulto Joven
18.
J Am Geriatr Soc ; 58(1): 18-22, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20122037

RESUMEN

OBJECTIVES: To describe the clinical characteristics and outcomes of tuberculosis (TB) in elderly people. DESIGN: Observational analysis of a prospective cohort of adults with TB (1995-2004). A case-control study to determine attributable mortality to TB in very old people was done. RESULTS: Of 319 patients with TB, 109 (34.2%) were aged 65 and older. The older group was more likely to have comorbidities (1.4% vs 0.4%; P<.001), extrapulmonary and disseminated TB (50.4% vs 26.1%; P<.001), toxicity (22% vs 9.8%; P=.006), and 30-day mortality (18.3% vs 1.6%; P<.001). When patients aged 65 to 79 were compared with those aged 80 and older, only differences in TB-related mortality were detected (9.8% vs 44.4%; P=.01). In the attributable mortality analysis, 30-day and 6-month mortality were higher in very old patients with TB than in controls without TB (41.7% vs 11.1%, P=.005; 45.8% and 19.4%, P=.01, respectively). No differences in mortality were shown when excluding patients with postmortem TB diagnosis or those who died within the first 72 hours of diagnosis. CONCLUSION: Older people with TB had a higher frequency of atypical features, more adverse drug reactions, and greater TB-related mortality than younger people. Data suggest that very old patients with TB have higher mortality, but if diagnosed early and adequately treated, very old patients with TB do not have greater mortality than those without.


Asunto(s)
Tuberculosis/mortalidad , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto Joven
19.
Gerokomos (Madr., Ed. impr.) ; 25(1): 48-51, mar. 2014. ilus, tab
Artículo en Español | IBECS (España) | ID: ibc-125379

RESUMEN

El cáncer de mama masculino es una patología poco frecuente y particular que suele afectar a hombres de más 60 años. El presente trabajo tiene como objetivo establecer un plan de trabajo enfermero, centrado en el cuidado de un hombre que presenta una lesión sangrante en una mama, durante su asistencia al Servicio de Urgencias Hospitalarias. Desarrollaremos el caso a través de la valoración de enfermería según el modelo de Virginia Henderson, los principales diagnósticos, criterios de resultados e intervenciones realizadas. Una vez estabilizado el sangrado de la herida, se realizan las pruebas pertinentes para diagnosticar al paciente un cáncer de mama derecha en estadio avanzado; se opta por tratamiento paliativo, sin olvidar que los pacientes que reciben estos cuidados buscan preservar la mayor calidad de vida posible y tener una muerte digna


Male breast cancer is a rare disease and usually affects men over 60 years. This paper aims to establish a work plan nurse focus on care for a man who has a bleeding lesion in right breast, while attending to the Emergency Room. We develop the case through nursing assessment on the model of Virginia Henderson, using a nursing diagnosis, outcome criteria and interventions. Stabilized the bleeding from the wound, relevant tests are performed to diagnose the patient a right breast cancer in advanced stage. Palliative treatment is chosen, keeping in mind that patients receiving this care seek to preserve the highest quality of life possible and have dignified death


Asunto(s)
Humanos , Masculino , Anciano , Úlcera Cutánea/enfermería , Neoplasias de la Mama Masculina/complicaciones , Hemorragia/enfermería , Atención de Enfermería/métodos , Servicios Médicos de Urgencia , Tratamiento de Urgencia/métodos , Factores de Riesgo
20.
Rev. chil. infectol ; 30(2): 156-161, abr. 2013. ilus, tab
Artículo en Español | LILACS | ID: lil-673997

RESUMEN

Introduction: The development of malignancies is a problem associated with HIV infection. The incidence and spectrum of malignancies has been modified with the addition of highly active antiretroviral therapy (HAART). Aim: To describe the clinical and epidemiological characteristics and prognosis of HIV patients who have developed a malignancy. Methods: Retrospective observational study was conducted in HIV + patients who developed a malignancy between 1993-2010 in a referral hospital. AIDS-defining malignancies (ADN) and non-AIDS-defining malignancies (NADN) were compared. Results: 125 patients were identified with at least one malignancy. The most frequent malignancies were: non-Hodgkin lymphoma (n; 39; 30.2%), Kaposi's sarcoma (n: 20; 15.5%), Hodgkin's disease (n: 11; 8.8%), lung cancer (n: 20; 15.5%) and hepatocellular carcinoma (n: 9; 6.9 %). The mean age was 42 ± 11 years, 84% male, 55.8% were coinfected with HBV and or HCV. The risk behaviors were: 45.6% intravenous drug users, 16.8% men who have sex with men and 20% heterosexuals). There were 67 (52%) NADN and 62 (48%) ADN; NADN patients had a longer story of HIV infection and longer exposure to HAART, better level of immunodeficiency and better virological control than ADN patients. Four patients developed a second malignancy. Overall survival was 34.7%. Conclusions: We found an increased incidence of NADN, appearing in patients with better virological and immunological control than ADN group. Mortality of patients with HIV infection and malignancy is still very high.


Introducción: Uno de los problemas asociados a la infección por VIH es el desarrollo de neoplasias. La incidencia y espectro de los distintos cánceres se ha visto modificada con la incorporación del tratamiento anti-retroviral de gran actividad (TARGA). El objetivo del presente estudio es describir las características clínicas y epidemiológicas y el pronóstico de pacientes infectados con VIH que han desarrollado una neoplasia. Material y Métodos: Estudio observacional retrospectivo de una cohorte de pacientes con infección por VIH que desarrollaron algún cáncer en el periodo comprendido entre 1993-2010 en un hospital de referencia. Se compararon las variables entre los casos de neoplasias definitorias de SIDA (NDS) y no definitorios de SIDA (NNDS). Resultados: Se identificaron 125 pacientes con al menos una neoplasia. Los cánceres más frecuentes fueron: linfoma no Hodgkin (n: 39; 30,2%), sarcoma de Kaposi (n: 20; 15,5%), enfermedad de Hodgkin (n: 11; 8,8%), neoplasia pulmón (n: 20; 16%) y hepatocarcinoma (n: 9; 6,9 %). La edad media fue 42 ± 11 años, 84% varones, 55,8% estaban co-infectados por VHB y/o VHC. Las conductas de riesgo fueron: 45,6% usuarios de drogas vía parenteral, 16,8% hombres con relaciones sexuales con hombres y 20% heterosexuales. Se encontraron 67 NNDS (52%) y 62 (48%) NDS; los pacientes con NNDS presentaron mayor tiempo de evolución de la infección por VIH y de exposición a TARGA, mayor recuento de CD4 y mejor control virológico que los del grupo de NDS. Desarrollaron un segundo tumor cuatro pacientes. La supervivencia global fue de 34,7%. Conclusiones: Se constata un aumento en la incidencia de NNDS, que se presentan en pacientes con mejor control virológico e in-munológico que los NDS. La mortalidad de los pacientes con infección por VIH y enfermedad tumoral continúa siendo muy elevada.


Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones por VIH/complicaciones , Neoplasias/etiología , Terapia Antirretroviral Altamente Activa , Estudios de Cohortes , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Neoplasias/epidemiología , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , España/epidemiología
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