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1.
Colorectal Dis ; 26(2): 317-325, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38182552

RESUMO

AIM: The aim of this work was to evaluate the concordance between the low anterior resection syndrome (LARS) and preoperative LARS (POLARS) scores regarding the incidence of LARS in a Chilean population undergoing rectal surgery for cancer in a high-volume hospital. METHOD: The LARS score questionnaire, following telephone requests, was used to determine the presence and severity of LARS. The POLARS score was calculated based on variables described previously. Correlations and qualitative and quantitative concordance were evaluated using Spearman's correlation coefficient, the kappa coefficient and the Bland-Altman plot with Lin's concordance correlation coefficient. RESULTS: A total of 120 patients met the inclusion criteria: 37.5% underwent neoadjuvant radiotherapy, 61% underwent total mesorectal excision (TME) and 51.6% underwent ostomy. A total of 49% of patients did not present with LARS, whereas 28% had major LARS. The correlation between scales was poor, with a fair qualitative concordance to determine the presence/absence of LARS and a slight qualitative concordance to determine the degree of the intensity. The quantitative concordance was poor. CONCLUSION: In the Chilean population, concordance between the LARS and POLARS scores was qualitatively fair to determine the presence/absence of the disease and qualitatively slight to determine the degree of intensity. We do not suggest using the POLARS score in the perioperative period in the Chilean population deliberately, as the score may help to determine the presence/absence of LARS but cannot determine its degree of intensity. Additional evaluations are required to determine the factors contributing to the degree of agreement between the scales.


Assuntos
Neoplasias Retais , Humanos , Neoplasias Retais/cirurgia , Neoplasias Retais/complicações , Síndrome de Ressecção Anterior Baixa , Complicações Pós-Operatórias/etiologia , Incidência , Chile/epidemiologia , Hospitais com Alto Volume de Atendimentos , Qualidade de Vida
2.
J Clin Periodontol ; 50(11): 1420-1443, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37608638

RESUMO

AIM: To determine the accuracy of biomarker combinations in gingival crevicular fluid (GCF) and saliva through meta-analysis to diagnose periodontitis in systemically healthy subjects. METHODS: Studies on combining two or more biomarkers providing a binary classification table, sensitivity/specificity values or group sizes in subjects diagnosed with periodontitis were included. The search was performed in August 2022 through PUBMED, EMBASE, Cochrane, LILACS, SCOPUS and Web of Science. The methodological quality of the articles selected was evaluated using the QUADAS-2 checklist. Hierarchical summary receiver operating characteristic modelling was employed to perform the meta-analyses (CRD42020175021). RESULTS: Twenty-one combinations in GCF and 47 in saliva were evaluated. Meta-analyses were possible for six salivary combinations (median sensitivity/specificity values): IL-6 with MMP-8 (86.2%/80.5%); IL-1ß with IL-6 (83.0%/83.7%); IL-1ß with MMP-8 (82.7%/80.8%); MIP-1α with MMP-8 (71.0%/75.6%); IL-1ß, IL-6 and MMP-8 (81.8%/84.3%); and IL-1ß, IL-6, MIP-1α and MMP-8 (76.6%/79.7%). CONCLUSIONS: Two-biomarker combinations in oral fluids show high diagnostic accuracy for periodontitis, which is not substantially improved by incorporating more biomarkers. In saliva, the dual combinations of IL-1ß, IL-6 and MMP-8 have an excellent ability to detect periodontitis and a good capacity to detect non-periodontitis. Because of the limited number of biomarker combinations evaluated, further research is required to corroborate these observations.


Assuntos
Interleucina-6 , Periodontite , Humanos , Quimiocina CCL3 , Metaloproteinase 8 da Matriz , Periodontite/diagnóstico , Biomarcadores/análise , Interleucina-1beta , Líquido do Sulco Gengival/química , Saliva/química
3.
Artigo em Inglês | MEDLINE | ID: mdl-36906068

RESUMO

Clinical Pathways are care plans that are applied to clinical processes with a predictable course, with the intention of protocolizing these processes and reducing the variability in their management. Our objective was to develop a clinical pathway for 131I metabolic therapy in its application to differentiated thyroid cancer. A work team was organized consisting of doctors (Endocrinology and Nuclear Medicine), nursing staff (Hospitalization Unit and Nuclear Medicine), Radiophysics and the Clinical Management and Continuity of Care Support Service. For the design of the clinical pathway, several team meetings were held, in which the literature reviews were pooled and the design and development of the clinical pathway was undertaken in accordance with current clinical guidelines. This team achieved consensus on the development of the care plan, establishing its key points and drafting the different documents that make up the Clinical Pathway: Timeframe-based schedule, Clinical Pathway Variation Record Document, Patient Information Documents, Patient Satisfaction Survey, Pictogram Brochure, Quality Assessment Indicators. Finally, the clinical pathway was presented to all the clinical departments involved and to the Medical Director of the Hospital and is now being implemented in clinical practice.


Assuntos
Procedimentos Clínicos , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/radioterapia
4.
Br J Dermatol ; 184(6): 1085-1093, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33270213

RESUMO

BACKGROUND: Melanoma aetiology has been proposed to have two pathways, which are determined by naevi and type of sun exposure and related to the anatomical site where melanoma develops. OBJECTIVES: We examined associations with melanoma by anatomical site for a comprehensive set of risk factors including pigmentary and naevus phenotypes, ultraviolet radiation exposure and polygenic risk. METHODS: We analysed harmonized data from 2617 people with incident first invasive melanoma and 975 healthy controls recruited through two population-based case-control studies in Australia and the UK. Questionnaire data were collected by interview using a single protocol, and pathway-specific polygenic risk scores were derived from DNA samples. We estimated adjusted odds ratios using unconditional logistic regression that compared melanoma cases at each anatomical site with all controls. RESULTS: When cases were compared with control participants, there were stronger associations for many naevi vs. no naevi for melanomas on the trunk, and upper and lower limbs than on the head and neck (P-heterogeneity < 0·001). Very fair skin (vs. olive/brown skin) was more weakly related to melanoma on the trunk than to melanomas at other sites (P-heterogeneity = 0·04). There was no significant difference by anatomical site for polygenic risk. Increased weekday sun exposure was positively associated with melanoma on the head and neck but not on other sites. CONCLUSIONS: We found evidence of aetiological heterogeneity for melanoma, supporting the dual pathway hypothesis. These findings enhance understanding of risk factors for melanoma and can guide prevention and skin examination education and practices.


Assuntos
Melanoma , Neoplasias Cutâneas , Austrália/epidemiologia , Humanos , Melanoma/etiologia , Melanoma/genética , Fatores de Risco , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/genética , Raios Ultravioleta
6.
Biochem Pharmacol ; 177: 113985, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32311347

RESUMO

The 5-HT2A receptor is a homodimeric G protein-coupled receptor implied in multiple diseases, including schizophrenia. Recently, its co-crystallisation with the antipsychotic drugs zotepine and risperidone has revealed the importance of its extracellular domains in its pharmacology. Previous studies have shown that the non-specific disruption of extracellular disulphide bridges in the 5-HT2A receptor decreases ligand binding and receptor activation. There is enough evidence to hypothesize that this decrease may be due to a reduction of the disulphide bridge that links transmembrane domain 3 (TM-3) and extracellular loop 2 (ECL-2) of the 5-HT2A receptor via cysteine 148 (C148) and C227. Thus, to study the influence of the C148-C227 disulphide bridge on 5-HT2A receptor pharmacology, we substituted C148 and C227 in the human 5-HT2A receptor (WT) with alanines, to obtain two single mutants (C148A and C227A) and a double mutant (C148A/C227A), and the resultant DNA constructs were used to generate four stable cell lines. These substitutions reduced the binding of the 5-HT2A receptor to [3H]lysergic acid diethylamide ([3H]LSD) and impeded the 5-HT2A receptor-mediated activation of phospholipase C (PLC). Furthermore, bioluminescence resonance energy transfer (BRET) and western blotting analysis revealed that these mutations did not alter the homodimeric nature of the 5-HT2A receptor. However, fluorescence microscopy showed that these mutations hindered receptor trafficking to the cell membrane. These results illustrate the importance of the disulphide bridge between TM-3 and ECL-2 in maintaining the correct 5-HT2A receptor conformation to allow ligand binding and migration of the homodimeric receptor to the cell membrane.


Assuntos
Cálcio/metabolismo , Membrana Celular/metabolismo , Dissulfetos/química , Receptor 5-HT2A de Serotonina/química , Fosfolipases Tipo C/metabolismo , Sequência de Aminoácidos , Substituição de Aminoácidos , Sítios de Ligação , Linhagem Celular , Membrana Celular/química , Membrana Celular/efeitos dos fármacos , Efeito Fundador , Expressão Gênica , Células HEK293 , Humanos , Ligantes , Dietilamida do Ácido Lisérgico/farmacologia , Mutação , Ligação Proteica , Multimerização Proteica , Transporte Proteico , Receptor 5-HT2A de Serotonina/genética , Receptor 5-HT2A de Serotonina/metabolismo , Proteínas Recombinantes , Serotonina/farmacologia , Fosfolipases Tipo C/genética
7.
Ann Oncol ; 30(8): 1335-1343, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31185496

RESUMO

BACKGROUND: Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of seroconversion is unknown. PATIENTS AND METHODS: We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4 years (IQR = 6-11 years, range = 0-40 years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay). RESULTS: HPV16-E6 seropositivity was present in 0.4% of controls (22/5814; 95% CI 0.2% to 0.6%) and 26.2% (195/743; 95% CI 23.1% to 29.6%) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95% CI 62.1-155.4) in whites and 17.2-fold (95% CI 1.7-170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9% pre-1996 to 68.4% in 2005 onwards, in those with blood collection near diagnosis (lead time <5 years). HPV16-E6 seropositivity increased with lead time: 0.0%, 13.5%, 23.7%, and 38.9% with lead times of >30 years (N = 24), 20-30 years (N = 148), 10-20 years (N = 228), and <10 years (N = 301 cases) (p-trend < 0.001). Of the 47 HPV16-E6 seropositive cases with serially-collected blood samples, 17 cases seroconverted during follow-up, with timing ranging from 6 to 28 years before diagnosis. For the remaining 30 cases, robust seropositivity was observed up to 25 years before diagnosis. CONCLUSIONS: The immune response to HPV16-driven tumorigenesis is most often detectable several decades before OPSCC diagnosis. HPV16-E6 seropositive individuals face increased risk of OPSCC over several decades.


Assuntos
Anticorpos Antivirais/sangue , Papillomavirus Humano 16/imunologia , Neoplasias Orofaríngeas/diagnóstico , Infecções por Papillomavirus/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Adulto , Idoso , Carcinogênese/imunologia , Estudos de Casos e Controles , Feminino , Seguimentos , Papillomavirus Humano 16/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Oncogênicas Virais/imunologia , Neoplasias Orofaríngeas/sangue , Neoplasias Orofaríngeas/imunologia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/sangue , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Estudos Prospectivos , Proteínas Repressoras/imunologia , Soroconversão , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Fatores de Tempo
8.
Nanoscale Adv ; 1(9): 3626-3638, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-36133537

RESUMO

The efficient targeting of cancer cells depends on the success of obtaining the active targeting of overexpressed receptors. A very accurate design of nanoconjugates should be done via the selection of the conjugation strategy to achieve effective targeted nanoconjugates. Here, we present a detailed study of cetuximab-conjugated nonspherical gold nanocages for the active targeting of triple-negative breast cancer cells, including MDA-MB-231 and MDA-MB-468. A few different general strategies were selected for monoclonal antibody conjugation to the nanoparticle surface. By varying the bioconjugation conditions, including antibody orientation or the presence of a polymeric spacer or recombinant protein biolinker, we demonstrate the importance of a rational design of nanoconjugates. A quantitative study of gold content via ICP-AES allowed us to compare the effectiveness of cellular uptake as a function of the conjugation strategy and confirmed the active nature of nanoparticle internalization in cancer cells via epidermal growth factor receptor recognition, corroborating the importance of the rational design of nanomaterials for nanomedicine.

9.
Sci Rep ; 8(1): 18003, 2018 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-30573746

RESUMO

The objective of the present study was to determine cytokine thresholds derived from predictive models for the diagnosis of chronic periodontitis, differentiating by smoking status. Seventy-five periodontally healthy controls and 75 subjects affected by chronic periodontitis were recruited. Sixteen mediators were measured in gingival crevicular fluid (GCF) using multiplexed bead immunoassays. The models were obtained using binary logistic regression, distinguishing between non-smokers and smokers. The area under the curve (AUC) and numerous classification measures were obtained. Model curves were constructed graphically and the cytokine thresholds calculated for the values of maximum accuracy (ACC). There were three cytokine-based models and three cytokine ratio-based models, which presented with a bias-corrected AUC > 0.91 and > 0.83, respectively. These models were (cytokine thresholds in pg/ml for the median ACC using bootstrapping for smokers and non-smokers): IL1alpha (46099 and 65644); IL1beta (4732 and 5827); IL17A (11.03 and 17.13); IL1alpha/IL2 (4210 and 7118); IL1beta/IL2 (260 and 628); and IL17A/IL2 (0.810 and 1.919). IL1alpha, IL1beta and IL17A, and their ratios with IL2, are excellent diagnostic biomarkers in GCF for distinguishing periodontitis patients from periodontally healthy individuals. Cytokine thresholds in GCF with diagnostic potential are defined, showing that smokers have lower threshold values than non-smokers.


Assuntos
Periodontite Crônica/diagnóstico , Citocinas/análise , Líquido do Sulco Gengival/química , Fumar , Adulto , Estudos de Casos e Controles , Periodontite Crônica/complicações , Periodontite Crônica/epidemiologia , Periodontite Crônica/metabolismo , Estudos Transversais , Citocinas/metabolismo , Diagnóstico Diferencial , Feminino , Líquido do Sulco Gengival/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fumar/epidemiologia , Fumar/metabolismo , Fumar/patologia
10.
Eur J Surg Oncol ; 42(6): 808-12, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27038996

RESUMO

INTRODUCTION: Minimally invasive surgery for rectal cancer (RC) is now widely performed via the laparoscopic approach, but robotic-assisted surgery may overcome some limitations of laparoscopy in RC treatment. We compared the rate of positive circumferential margins between robotic, laparoscopic and open total mesorectal excision (TME) for RC in our institution. METHODS: Mid and low rectal adenocarcinoma patients consecutively submitted to robotic surgery were compared to laparoscopic and open approach. From our prospective database, 59 patients underwent robotic-assisted rectal surgery from 2012 to 2015 (RTME group) were compared to our historical control group comprising 200 open TME (OTME group) and 41 laparoscopic TME (LTME group) approaches from July 2008 to February 2012. Primary endpoint was to compare the rate of involved circumferential resection margins (CRM) and the mean CRM between the three groups. Secondary endpoint was to compare the mean number of resected lymph nodes between the three groups. RESULTS: CRM involvement was demonstrated in 20 patients (15.5%) in OTME, 4 (16%) in LTME and 9 (16.4%) in the RTME (p = 0.988). The mean CRM in OTME, LTME and RTME were respectively 0.6 cm (0-2.7), 0.7 cm (0-2.0) and 0.6 cm (0-2.0) (p = 0.960). Overall mean LN harvest was 14 (0-56); 16 (0-52) in OTME, 13 (1-56) in LTME and 10 (0-45) in RTME (p = 0.156). CONCLUSION: Our results suggest that robotic TME has the same oncological short-term results when compared to the open and laparoscopic technique, and it could be safely offered for the treatment of mid and low rectal cancer.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/instrumentação , Laparoscopia , Margens de Excisão , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Procedimentos Cirúrgicos Robóticos , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Feminino , Humanos , Laparoscopia/métodos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Duração da Cirurgia , Estudos Retrospectivos , Resultado do Tratamento
11.
Rev. mex. ing. bioméd ; 37(1): 7-16, ene.-abr. 2016. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: lil-789469

RESUMO

Abstract The electrospinning device is used in the biomaterials research field nowadays for fabricating nanofibers that can be used for manufacturing artificial skin and muscular tissue, blood vessels (vascular grafts), orthopedic components (bones, cartilages, and ligaments/tendon), and peripheral or central nervous system components. Electrospun nanofibers act as ideal scaffolds for tissue engineering and drug delivery systems because they can mimic the functions of native extracellular matrices. A low cost electrospinning device was designed and built for undergraduate practical learning in the Biomaterials course in the area of Bioengineering at Universidad Autónoma de Baja California, México. The methodology includes 3D CAD designing, manufacturing of the acrylic cabinet, different collectors and the fabrication of poly (vinyl alcohol) nanofibrous scaffolds, in order to validate the functionality of the electrospinning system. The prototype is an affordable device; its cost is 95% less than the laboratory commercial devices.


Resumen El dispositivo de electrohilado es actualmente empleado en la investigación de biomateriales, utilizado para sintetizar nanofibras que ofrecen un potencial para la manufactura de piel artificial y tejido muscular, vasos sanguíneos (implantes vasculares), componentes ortopédicos (hueso, cartílago y tendones/ligamentos) y componentes del sistema nervioso central y periférico. Las nanofibras producidas por electrohilado pueden ser usadas como andamios ideales para ingeniería de tejidos y liberación controlada de fármacos debido a que mimetizan las funciones de la matriz extracelular. El dispositivo de electrohilado de bajo costo fue diseñado y construido para al aprendizaje practico de estudiantes de licenciatura en la asignatura de Biomateriales de la carrera de Bioingeniería. La metodología incluye diseños CAD 3D, manufactura del gabinete de acrílico, diferentes colectores y fabricación de los andamios de nanofibras de Poli (vinil alcohol) para validar la correcta funcionalidad del sistema de electrohilado. El prototipo es un dispositivo accesible económicamente, su costo es un 95% más barato que los dispositivos de tipo comercial.

12.
J Environ Manage ; 170: 37-49, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26789201

RESUMO

A portfolio of agricultural practices is now available that can contribute to reaching European mitigation targets. Among them, the management of agricultural soils has a large potential for reducing GHG emissions or sequestering carbon. Many of the practices are based on well tested agronomic and technical know-how, with proven benefits for farmers and the environment. A suite of practices has to be used since none of the practices can provide a unique solution. However, there are limitations in the process of policy development: (a) agricultural activities are based on biological processes and thus, these practices are location specific and climate, soils and crops determine their agronomic potential; (b) since agriculture sustains rural communities, the costs and potential for implementation have also to be regionally evaluated and (c) the aggregated regional potential of the combination of practices has to be defined in order to inform abatement targets. We believe that, when implementing mitigation practices, three questions are important: Are they cost-effective for farmers? Do they reduce GHG emissions? What policies favour their implementation? This study addressed these questions in three sequential steps. First, mapping the use of representative soil management practices in the European regions to provide a spatial context to upscale the local results. Second, using a Marginal Abatement Cost Curve (MACC) in a Mediterranean case study (NE Spain) for ranking soil management practices in terms of their cost-effectiveness. Finally, using a wedge approach of the practices as a complementary tool to link science to mitigation policy. A set of soil management practices was found to be financially attractive for Mediterranean farmers, which in turn could achieve significant abatements (e.g., 1.34 MtCO2e in the case study region). The quantitative analysis was completed by a discussion of potential farming and policy choices to shape realistic mitigation policy at European regional level.


Assuntos
Dióxido de Carbono/química , Conservação dos Recursos Naturais/economia , Efeito Estufa/prevenção & controle , Solo/química , Agricultura/métodos , Análise Custo-Benefício , Produtos Agrícolas , Monitoramento Ambiental , Humanos , Políticas , Espanha
13.
Pharmacogenomics J ; 16(2): 137-40, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25896535

RESUMO

Genetic biomarkers could be useful for orienting treatment of patients with rheumatoid arthritis (RA), but none has been convincingly validated yet. Putative biomarkers include 14 single nucleotide polymorphisms that have shown association with response to TNF inhibitors (TNFi) in candidate gene studies and that we assayed here in 755 RA patients. Three of them, in the PTPRC, IL10 and CHUK genes, were significantly associated with response to TNFi. The most significant result was obtained with rs10919563 in PTPRC, which is a confirmed RA susceptibility locus. Its RA risk allele was associated with improved response (B=0.33, P=0.006). This is the second independent replication of this biomarker (P=9.08 × 10(-8) in the combined 3003 RA patients). In this way, PTPRC has become the most replicated genetic biomarker of response to TNFi. In addition, the positive but weaker replication of IL10 and CHUK should stimulate further validation studies.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Quinase I-kappa B/genética , Interleucina-10/genética , Antígenos Comuns de Leucócito/genética , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/uso terapêutico , Artrite Reumatoide/genética , Feminino , Estudos de Associação Genética , Marcadores Genéticos , Humanos , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Risco
14.
Hipertens Riesgo Vasc ; 32(2): 48-55, 2015.
Artigo em Espanhol | MEDLINE | ID: mdl-26179965

RESUMO

INTRODUCTION: Cardiovascular diseases and related risk factors suppose a challenge to public health due to the mortality and health costs involved. This study has aimed to assess the blood pressure control in a population cohort and to identify the factors associated with poor control. MATERIAL AND METHODS: A cardiovascular health examination was carried out in a random sample of 4013 individuals aged 15 years and above who were living in Castilla y Leon in 2004. The study included the medical history, physical exam and blood tests. A new health study was performed in 2009, including 2954 people from the initial sample, 1306 of whom were patients with hypertension. Strict blood pressure control was defined as <140/90 mm Hg. Bivariate analysis was performed and odds ratio was calculated by a regression logistic model. RESULTS: Blood pressure levels were above the established levels in 55.9%, without differences between men and women. The regression model showed that diabetes, obesity, smoking habit and previous systolic blood pressure values, with odds ratio of 3.87, 1.58, 1.49 and 1.13 per 5 mm Hg, respectively, are independently associated with uncontrolled blood pressure. Age did not show statistical significance. CONCLUSION: More than half of the patients with hypertension are not well controlled. This study provides information about the characteristics of the patients with poor control of hypertension in Castilla y León, which will allow policy makers to develop new primary and secondary prevention activities.


Assuntos
Pressão Sanguínea , Hipertensão/epidemiologia , Determinação da Pressão Arterial/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Feminino , Humanos , Hipertensão/diagnóstico , Modelos Logísticos , Masculino , Prevalência , Risco , Fatores de Risco , Fumar/efeitos adversos , Espanha/epidemiologia
15.
Clin Transl Oncol ; 17(8): 596-603, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25775918

RESUMO

PURPOSE: To show the clinical results of the treatment of brain metastases via radiosurgery using Volumetric Modulated Arc Therapy (VMAT). MATERIALS AND METHODS: 52 patients having lung (62 %), breast (17 %), colorectal (8 %) and other cancers (13 %) with one to three brain metastases were treated with 5 non-coplanar VMAT arcs. The treatment dose varied from 12 to 20 Gy, administered in one single session. The volume of metastases ranged from 0.04 to 24.92 cc. Radiosurgery alone was used for 54 % of cases, while 19 % received whole brain radiotherapy due to relapse. Patients were classified according to the Disease-specific graded prognostic assessment (DS-GPA) index and survival was assessed via the Kaplan-Meier model. RESULTS: The median survival time was 7.2 months from the date of radiosurgery. The Karnofsky and DS-GPA indices were the most significant with regard to survival. Patients with a Karnofsky performance status (KPS) over 70 had a longer survival time of 9.2 months, as opposed to those with a KPS below 70 of 3.5 months. No significant differences were found with regard to the type of cancer or the number of lesions. Local tumour control was achieved for 42 metastases (82 %), of which a complete response was achieved for 7 lesions, a partial response for 21; 15 lesions were stabilized. Local progression was observed in 8 lesions (15 %). The median treatment time per patient was 29 min. CONCLUSIONS: The VMAT technique proves to be safe and effective for treating brain metastases via radiosurgery.


Assuntos
Neoplasias Encefálicas/cirurgia , Neoplasias/cirurgia , Radiocirurgia/mortalidade , Radioterapia de Intensidade Modulada/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/mortalidade , Neoplasias/patologia , Prognóstico , Planejamento da Radioterapia Assistida por Computador/métodos , Taxa de Sobrevida
16.
Eur J Cell Biol ; 94(2): 78-89, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25613364

RESUMO

Invadopodia are actin-driven membrane protrusions that show oscillatory assembly and disassembly causing matrix degradation to support invasion and dissemination of cancer cells in vitro and in vivo. Profilin1, an actin and phosphoinositide binding protein, is downregulated in several adenocarcinomas and it is been shown that its depletion enhances invasiveness and motility of breast cancer cells by increasing PI(3,4)P2 levels at the leading edge. In this study, we show for the first time that depletion of profilin1 leads to an increase in the number of mature invadopodia and these assemble and disassemble more rapidly than in control cells. Previous work by Sharma et al. (2013a), has shown that the binding of the protein Tks5 with PI(3,4)P2 confers stability to the invadopodium precursor causing it to mature into a degradation-competent structure. We found that loss of profilin1 expression increases the levels of PI(3,4)P2 at the invadopodium and as a result, enhances recruitment of the interacting adaptor Tks5. The increased PI(3,4)P2-Tks5 interaction accelerates the rate of invadopodium anchorage, maturation, and turnover. Our results indicate that profilin1 acts as a molecular regulator of the levels of PI(3,4)P2 and Tks5 recruitment in invadopodia to control the invasion efficiency of invadopodia.


Assuntos
Neoplasias da Mama/patologia , Estruturas da Membrana Celular/metabolismo , Profilinas/metabolismo , Actinas/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Matriz Extracelular/metabolismo , Humanos , Fosfatidilinositóis/metabolismo
17.
Int J Legal Med ; 129(1): 1-10, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24832006

RESUMO

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare cardiac disease characterized by myocardial fibrofatty replacement, which can lead to sudden death. Previous studies have described a reduction of plakoglobin (PKG) protein at the level of intercalated disks as the hallmark of ARVC. The main objective of this study was to investigate the involvement of desmosome mutations in the histological phenotype of ARVC. We performed a genetic analysis of ARVC cases, and histological characterization of ARVC heart tissue samples. We genetically analyzed 48 ARVC cases distributed into two groups: 42 human tissue heart samples with conclusive diagnoses of ARVC after post-mortem examination; and six DNA samples from peripheral blood of living patients who were clinically diagnosed. Sequenom MassARRAY analysis revealed three ARVC-associated variants in three patients in 42 tissue samples (7.14 %). Three individuals carried one single pathogenic mutation, p.R811S _PKP2, p.S824L_DSC2, and p.T526M_PKP2 in postmortem samples. In the living patients group, Sequenom MassARRAY revealed no mutation, however, later Sanger sequencing analysis identified three ARVC mutations in 2/6 patients not included in the Sequenom design. In post-mortem tissue samples we performed immunohistochemical labeling for desmosomal proteins and Connexin 43. This study revealed that PKP2 carriers present either absent or clearly reduced PKG immunolabeling, while the DSC2 carrier showed PKG immunolabeling similar to control samples. Immunolabeling for Cx43 did not show any differences compared to controls. The present Sequenom MassARRAY design is a useful tool for post-mortem genetic diagnosis of ARVC. Plakoglobin reduction occurs at intercalated disks, while other desmosome proteins and Cx43 remain unaltered.


Assuntos
Displasia Arritmogênica Ventricular Direita/genética , Displasia Arritmogênica Ventricular Direita/patologia , Análise Mutacional de DNA , Desmossomos/genética , Miocárdio/patologia , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Adulto , Conexina 43/genética , Feminino , Genética Forense , Patologia Legal , Heterozigoto , Humanos , Imuno-Histoquímica , Masculino , Mutação , Placofilinas/genética
18.
Int J Med Robot ; 11(2): 188-93, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24574007

RESUMO

BACKGROUND: Anterior resection with total mesorectal excision (TME) is the standard method of rectal cancer resection. However, this procedure remains technically difficult. A robotic transanal approach could overcome some of these limitations. An initial laboratory experience with robotic transanal TME using a new designed port on human cadavers is reported. METHODS: The feasibility of robotic transanal TME and ideal set-up were evaluated in human cadavers. For the da Vinci Si HD system transanal access and total mesorectal excision, a specifically designed port was used. RESULTS: It was possible to complete a proctectomy with transanal total mesorectal excision. The port proved to be very reliable and facilitated docking of the robotic arms. CONCLUSION: Using the robotic technology and a specifically designed port for robotic transanal access, TME was shown to be feasible and one specific preferred set-up was determined. Further clinical trials will be necessary to assess the safety and efficacy of this technique.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Neoplasias Retais/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Canal Anal/anatomia & histologia , Canal Anal/cirurgia , Cadáver , Procedimentos Cirúrgicos do Sistema Digestório/instrumentação , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Humanos , Laparoscopia/instrumentação , Laparoscopia/métodos , Masculino , Modelos Anatômicos , Cirurgia Endoscópica por Orifício Natural/instrumentação , Cirurgia Endoscópica por Orifício Natural/métodos , Reto/anatomia & histologia , Reto/cirurgia , Procedimentos Cirúrgicos Robóticos/instrumentação
19.
Case Rep Pulmonol ; 2014: 192146, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25295210

RESUMO

There are not many articles about the chronic bronchial infection/colonization in patients with underlying lung disease other than cystic fibrosis (CF), especially with non-CF bronchiectasis (NCFBQ). The prevalence of B. cepacia complex is not well known in NCFBQ. The vast majority of published clinical data on Burkholderia infection in individuals with CF is comprised of uncontrolled, anecdotal, and/or single center experiences, and no consensus has emerged regarding treatment. We present two cases diagnosed with bronchiectasis (BQ) of different etiology, with early pulmonary infection by B. cepacia complex, which was eradicated with inhaled aztreonam lysine.

20.
HIV Med ; 15(6): 321-9, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24314004

RESUMO

BACKGROUND: Pulmonary abnormalities are often present in patients infected with the human immunodeficiency virus (HIV). OBJECTIVES: The aim of the study was to determine the prevalence and characteristics of, and risk factors for, pulmonary abnormalities in HIV-positive patients. METHODS: A total of 275 HIV-positive patients [mean (± standard deviation) age 48.5 ± 6.6 years] were included in the study, of whom 95.6% had been receiving highly active antiretroviral therapy (HAART) for a mean (± standard deviation) duration of 11.9 ± 5.4 years. The median (interquartile range) CD4 lymphocyte count was 541 (392-813) cells/µL, and 92% of the patients had an undetectable viral load. We determined: (1) spirometry, static lung volumes, lung diffusing capacity, pulmonary gas exchange and exercise tolerance, and (2) the amount of emphysema via a computed tomography (CT) scan. RESULTS: Chronic cough and expectoration (47%) and breathlessness during exercise (33.9%) were commonly reported. Airflow limitation (AL) was present in 17.2%, low pulmonary diffusing capacity in 52.2% and emphysema in 10.5-37.7% of patients, depending on the method used for quantification. Most of these abnormalities had not been diagnosed or treated previously. Smoking exposure and previous tuberculosis were the main risk factors for AL, whereas smoking exposure and several variables related to HIV infection appeared to contribute to the risk of emphysema and low diffusing capacity. CONCLUSIONS: Despite HAART, pulmonary structural and functional abnormalities are frequent in HIV-positive patients. They are probably attributable to both environmental (smoking and tuberculosis) and HIV-related factors. Most of these abnormalities remain unnoticed and untreated. Given the relatively young age of these patients, these results anticipate a significant health problem in the next few years as, thanks to the efficacy of HAART, patients survive longer and experience the effects of aging.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Pneumopatias/diagnóstico , Adulto , Idoso , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , Infecções por HIV/fisiopatologia , Humanos , Pneumopatias/epidemiologia , Pneumopatias/etiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Capacidade de Difusão Pulmonar , Testes de Função Respiratória , Fatores de Risco , Fumar/efeitos adversos , Tomografia Computadorizada por Raios X , Carga Viral
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