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1.
Cureus ; 16(5): e59805, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38846234

RESUMEN

Background Postoperative complications (POC) are undesirable consequences of surgery and are a major area of concern adversely affecting the quality of surgical care and patient safety. Emergency surgery has been observed to have a higher incidence of different POC. The analysis of POC is of great importance due to their impact on the quality of life of patients and because they have become an indicator to measure the quality of hospital services. Objective This study aimed to describe the POC of emergency surgeries in patients from the general surgery department of a referral hospital in eastern Venezuela. Methodology A cross-sectional retrospective study was conducted, including patients undergoing emergency surgery at "Dr. Luis Razetti" University Hospital, Barcelona, Venezuela, between November 2022 and May 2023. Results Medical records of 178 patients were analyzed. Most were male (53.7%), with an average age of 34.98 and a standard deviation of 18.2 years. POC was registered in 28 (15.7%) patients, with surgical site infection being the most common in 21 (39.62%) patients. Those over 65 years old (21.4% vs. 6.4%, p=0.013), patients with a history of hypertension (25% vs. 6.3%, p=0.002), hypoalbuminemia (100% vs. 43.8%, p=0.027), diagnosed with peritonitis due to hollow viscus perforation (21.4% vs. 6%, p=0.007), trauma (25% vs. 9.3%, p=0.018), and those with a midline incision (75% vs. 31.3%, p<0.001) had a higher frequency of POC. There was a mortality rate of 2.8% with no significant difference based on the development of POC. Conclusion POC represents a significant cause of morbidity and mortality in patients undergoing emergency surgeries. The studied sample showed a similar frequency of POC compared to previous reports but with lower mortality. Complications were associated with higher frequencies of hypertension, midline approach, hypoalbuminemia, and emergency surgery for peritonitis due to hollow viscus perforation and trauma.

2.
J Alzheimers Dis ; 98(2): 601-618, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38427484

RESUMEN

Background: Microglial dysfunction plays a causative role in Alzheimer's disease (AD) pathogenesis. Here we focus on a germline insertion/deletion variant mapping SIRPß1, a surface receptor that triggers amyloid-ß(Aß) phagocytosis via TYROBP. Objective: To analyze the impact of this copy-number variant in SIRPß1 expression and how it affects AD molecular etiology. Methods: Copy-number variant proxy rs2209313 was evaluated in GERALD and GR@ACE longitudinal series. Hippocampal specimens of genotyped AD patients were also examined. SIRPß1 isoform-specific phagocytosis assays were performed in HEK393T cells. Results: The insertion alters the SIRPß1 protein isoform landscape compromising its ability to bind oligomeric Aß and its affinity for TYROBP. SIRPß1 Dup/Dup patients with mild cognitive impairment show an increased cerebrospinal fluid t-Tau/Aß ratio (p = 0.018) and a higher risk to develop AD (OR = 1.678, p = 0.018). MRIs showed that Dup/Dup patients exhibited a worse initial response to AD. At the moment of diagnosis, all patients showed equivalent Mini-Mental State Examination scores. However, AD patients with the duplication had less hippocampal degeneration (p < 0.001) and fewer white matter hyperintensities. In contrast, longitudinal studies indicate that patients bearing the duplication allele show a slower cognitive decline (p = 0.013). Transcriptional analysis also shows that the SIRPß1 duplication allele correlates with higher TREM2 expression and an increased microglial activation. Conclusions: The SIRPß1 internal duplication has opposite effects over MCI-to-Dementia conversion risk and AD progression, affecting microglial response to Aß. Given the pharmacological approaches focused on the TREM2-TYROBP axis, we believe that SIRPß1 structural variant might be considered as a potential modulator of this causative pathway.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Receptores de Superficie Celular , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Péptidos beta-Amiloides/metabolismo , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/genética , Disfunción Cognitiva/metabolismo , Microglía/metabolismo , Fagocitosis , Receptores de Superficie Celular/metabolismo
3.
Antioxidants (Basel) ; 12(2)2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36829907

RESUMEN

We hypothesized that fetal exposure to the oxidative stress induced by the combined challenge of preeclampsia (PE) and high altitude would induce a significant impairment in the development of pulmonary circulation. We conducted a prospective study in La Paz (Bolivia, mean altitude 3625 m) in which newborns from singleton pregnancies with and without PE were compared (PE group n = 69, control n = 70). We conducted an echocardiographic study in these infants at the median age of two days. The percentage of cesarean deliveries and small for gestational age (SGA) infants was significantly higher in the PE group. Heart rate, respiratory rate, and oxygen saturation did not vary significantly between groups. Estimated pulmonary arterial pressure and pulmonary vascular resistance were 30% higher in newborns exposed to PE and high altitude compared with those exposed only to high altitude. We also detected signs of right ventricular hypertrophy in infants subjected to both exposures. In conclusion, this study provides evidence that the combination of PE and pregnancy at high altitude induces subclinical alterations in the pulmonary circulation of the newborn. Follow-up of this cohort may provide us with valuable information on the potential increased susceptibility to developing pulmonary hypertension or other pulmonary and cardiovascular disorders.

4.
J Alzheimers Dis ; 91(4): 1459-1469, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36641676

RESUMEN

BACKGROUND: Souvenaid® is a medical food that contains nutrients that can help synapse synthesis in Alzheimer's disease (AD). The potential effectiveness of combination therapy of Souvenaid with cholinesterase inhibitors (AChEI) is currently not well-known. OBJECTIVE: To look into the effect of combination therapy with Souvenaid plus AChEI in people with mild AD in the real-world. METHODS: We carried out a retrospective analysis in mild AD patients attending a memory clinic. Three groups were studied according to the treatment they received: Souvenaid alone (n = 66), AChEI alone (n = 84), and Souvenaid+AChEI (n = 70). Treatment effects were evaluated at baseline, 6 and 12 months. Cognitive functioning was assessed by Mini-Mental State Examination (MMSE), Rey Auditory Verbal Learning Test (RAVLT), Symbol Digit Modalities Test (SDMT), Boston Naming Test (BNT), Trail Making Test (TMT/A-B), Phonemic and Semantic Verbal Fluency Test (PVFT/SVFT); neuropsychiatric symptoms were evaluated by the Neuropsychiatric Inventory (NPI); functional capacity was assessed by the Bayer Activities Daily Living Scale (BAYER-S). A Mixed Model for Repeated Measures analysis was carried out to evaluate changes in outcome scores. RESULTS: After 12 months Souvenaid+AChEI showed significant improvement in MMSE (p < 0.001), RAVLT (p < 0.0001), SVFT (p = 0.002), PVFT (p = 0.007), TMTA (p = 0.039), TMTB (p = 0.001), and NPI (p < 0.0001) compared to AChEI alone. CONCLUSION: Souvenaid showed cognitive and behavioral benefits in mild AD patients. These effects increased when Souvenaid and AChEI were used in combination. This study can serve as a model for the design of prospective controlled trials that help to support the combined use of Souvenaid and antidementia drugs in AD.


Asunto(s)
Enfermedad de Alzheimer , Inhibidores de la Colinesterasa , Suplementos Dietéticos , Humanos , Acetilcolinesterasa , Enfermedad de Alzheimer/tratamiento farmacológico , Inhibidores de la Colinesterasa/uso terapéutico , Estudios Prospectivos , Estudios Retrospectivos , Resultado del Tratamiento
5.
BMJ Open ; 12(11): e063182, 2022 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-36450427

RESUMEN

INTRODUCTION: Death following surgical procedures is a global health problem, accounting for 4.2 million deaths annually within the first 30 postoperative days. The fourth indicator of The Lancet Commission on Global Surgery is essential as it seeks to standardise postoperative mortality. Consequently, it helps identify the strengths and weaknesses of each country's healthcare system. Accurate information on this indicator is not available in Colombia, limiting the possibility of interventions applied to our population. We aim to describe the in-hospital perioperative mortality of the surgical procedures performed in Colombia. The data obtained will help formulate public policies, improving the quality of the surgical departments. METHODS AND ANALYSIS: An observational, analytical, multicentre prospective cohort study will be conducted throughout Colombia. Patients over 18 years of age who have undergone a surgical procedure, excluding radiological/endoscopic procedures, will be included. A sample size of 1353 patients has been projected to achieve significance in our primary objective; however, convenience sampling will be used, as we aim to include all possible patients. Data collection will be carried out prospectively for 1 week. Follow-up will continue until hospital discharge, death or a maximum of 30 inpatient days. The primary outcome is perioperative mortality. A descriptive analysis of the data will be performed, along with a case mix analysis of mortality by procedure-related, patient-related and hospital-related conditions ETHICS AND DISSEMINATION: The Fundación Cardioinfantil-Instituto de Cardiología Ethics Committee approved this study (No. 41-2021). The results are planned to be disseminated in three scenarios: the submission of an article for publication in a high-impact scientific journal and presentations at the Colombian Surgical Forum and the Congress of the American College of Surgeons. TRIAL REGISTRATION NUMBER: NCT05147623.


Asunto(s)
Estudios Prospectivos , Humanos , Adolescente , Adulto , Colombia/epidemiología , Tamaño de la Muestra , Mortalidad Hospitalaria , Resultado del Tratamiento , Estudios Observacionales como Asunto , Estudios Multicéntricos como Asunto
6.
Alzheimers Dement (N Y) ; 8(1): e12338, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35929002

RESUMEN

Introduction: Mild cognitive impairment (MCI) is a neurocognitive state between normal aging and dementia. There is currently no approved treatment for MCI, with acetylcholinesterase inhibitors (AChEI) being the commonly prescribed drugs. The Ginkgo biloba extract EGb 761 is an herbal remedy used for cognitive disorders, including dementia. This study aims to explore the potential synergistic effect of combination therapy with EGb 761 plus AChEI in patients with amnestic MCI in a real-life setting. Methods: We retrospectively identified 133 patients with amnestic MCI who were attending a memory clinic. Patients had received treatment with any of the following drugs: G. biloba extract EGb 761, donepezil, galantamine, or rivastigmine at their standard doses. Subjects were divided into three treatment groups: EGb 761, AChEI, and EGb 761+AChEI. Patients were assessed by Mini-Mental State Examination (MMSE), Rey Auditory Verbal Learning Test (RAVLT), Symbol Digit Modalities Test, Boston Naming Test, Trail Making Test (TMT Parts A and B), Letter and Category Fluency Test (LFT, CFT), Neuropsychiatric Inventory (NPI), and Interview for Deterioration in Daily Living. Mixed-effects model analysis was carried out to evaluate changes in cognitive, functional, and behavioral outcomes over a 12-month follow-up. Results: After 12 months, EGb 761+AChEI showed significant improvement in MMSE, RAVLT, CFT, TMT A-B, and NPI compared to AChEI and in MMSE and RAVLT compared to EGb 761. At 12 months, EGb 761 was superior to AChEI on the CFT, TMT A-B, and NPI. Discussion: Our findings suggest that combined therapy with EGb 761 plus AChEI may provide added cognitive and functional benefits in patients with MCI and provides additional real-world evidence for the combined use of EGb 761 and anti-dementia drugs in patients with MCI. This study can serve as a model for the design of clinical trials that help to support the combined use of EGb 761 and anti-dementia drugs in patients with MCI.

7.
J Alzheimers Dis ; 88(2): 707-720, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35694919

RESUMEN

BACKGROUND: Depression is a common manifestation in Alzheimer's disease (AD). In clinical practice, antidepressant medication is often used for depression in AD. OBJECTIVE: We explore the effectiveness of the atypical antidepressant tianeptine compared with other conventional antidepressants in AD patients with depression in a real-life setting. METHODS: We retrospectively identified 126 AD patients who had received antidepressant treatment for 12 months with tianeptine or other antidepressants. Subjects were divided into two groups according to the treatment they had received: tianeptine group (n = 38) or other antidepressant group (n = 88). Drug effects on depression, cognition, behavior, and functional performance were evaluated at baseline, 6, and 12 months. A Mixed Effects Model Analysis was carried out to evaluate changes in performance scores. RESULTS: Both tianeptine and other antidepressants showed an antidepressant effect after 12 months with significant improvement on the Cornell Scale for Depression in Dementia, the Hamilton Depression Rating Scale, and the Neuropsychiatric Inventory-Depression subscale. A statistically significant improvement at 12 months was shown in the tianeptine group versus the other antidepressants group on most of the cognitive measures such as the Mini-Mental State Examination, the Letter and Category Fluency Test, the Rey Auditory Verbal Learning Test, and the Boston Naming Test. CONCLUSION: Our results suggest that tianeptine reduces depressive symptoms and improves cognition in AD patients. This could be considered clinically relevant and should inspire the design of future long-term randomized controlled trials that contribute to supporting the use of tianeptine for improving cognitive function in AD patients.


Asunto(s)
Enfermedad de Alzheimer , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/tratamiento farmacológico , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Cognición , Depresión/complicaciones , Depresión/tratamiento farmacológico , Humanos , Estudios Retrospectivos , Tiazepinas
8.
Clin Drug Investig ; 42(5): 391-402, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35349093

RESUMEN

BACKGROUND: Vascular dementia (VaD) is the most severe manifestation of cognitive impairment caused by cerebrovascular disease. There are currently no specific drug treatments approved for VaD, with cholinesterase inhibitors (AChEI) being frequently used in VaD. However, the benefits they provide are small and short-lived. The standardized extract of Ginkgo biloba EGb 761 has demonstrated protective properties against neuronal and vascular damage and has been used as a pharmacological treatment for VaD. OBJECTIVES: This study aims to study the efficacy of EGb 761 alone and in combination with AChEI in a real-life setting. We carried out a retrospective analysis of data over a 12-month period in a sample of people suffering from VaD. METHODS: We retrospectively identified 77 patients with a diagnosis of VaD who had received treatment with any of the following drugs: Ginkgo biloba extract EGb 761 (240 mg daily), donepezil (10 mg daily), galantamine (16 or 24 mg daily), or rivastigmine patch (9.5 or 13.3 mg daily). Subjects were divided into three groups according to the treatment they had received: EGb 761 alone (n = 25), AChEI alone (n = 26), and EGb 761+AChEI (n = 26). Cognitive functioning was assessed by Mini-Mental State Examination (MMSE), Rey Auditory Verbal Learning Test (RAVLT), Symbol Digit Modalities Test (SDMT), Boston Naming Test (BNT), Trail Making Test forms A (TMTA) and B (TMTB), Letter (LFT) and Category Fluency Test (CFT); neuropsychiatric symptoms were assessed by the Neuropsychiatric Inventory (NPI); functional capacity was assessed by Interview for Deterioration in Daily Living (IDDD). RESULTS: A statistically significant improvement was observed in the EGb 761 group versus the AChEI group at 12 months' follow-up in CFT (+1.74, p < 0.001), TMTA (-17.91, p = 0.031) and NPI (-5.89, p < 0.001). With regard to the combined treatment, a statistically significant improvement was shown in the EGb 761 plus AChEI treatment group versus AChEI group at the 12-month follow-up in MMSE (+2.0, p = 0.001), RAVLT (+2.23, p = 0.007), CFT (+1.15, p = 0.013), TMTA (-19.92, p = 0.012), TMTB (-46.50, p < 0.001) and NPI (-6.77, p < 0.001). In the same line, a statistically significant improvement was observed in the EGb 761 plus AChEI treatment group versus EGb 761 at 12-month follow-up regarding MMSE (+2.11, p = 0.001), RAVLT (+2.35, p = 0.004) and TMTB (-25.25, p = 0.015). CONCLUSION: After 12 months of treatment EGb 761 alone or combined with AChEI showed cognitive and behavioral benefits in patients suffering from VaD. This study thus provides additional real-world evidence for the combined use of EGb 761 and anti-dementia drugs in VaD patients.


Asunto(s)
Inhibidores de la Colinesterasa , Demencia Vascular , Extractos Vegetales , Acetilcolinesterasa , Inhibidores de la Colinesterasa/uso terapéutico , Demencia Vascular/diagnóstico , Demencia Vascular/tratamiento farmacológico , Ginkgo biloba , Humanos , Extractos Vegetales/uso terapéutico , Estudios Retrospectivos
9.
J Pers Med ; 11(12)2021 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-34945790

RESUMEN

Emerging studies have suggested several chromosomal regions as potential host genetic factors involved in the susceptibility to SARS-CoV-2 infection and disease outcome. We nested a COVID-19 genome-wide association study using the GR@ACE/DEGESCO study, searching for susceptibility factors associated with COVID-19 disease. To this end, we compared 221 COVID-19 confirmed cases with 17,035 individuals in whom the COVID-19 disease status was unknown. Then, we performed a meta-analysis with the publicly available data from the COVID-19 Host Genetics Initiative. Because the APOE locus has been suggested as a potential modifier of COVID-19 disease, we added sensitivity analyses stratifying by dementia status or by disease severity. We confirmed the existence of the 3p21.31 region (LZTFL1, SLC6A20) implicated in the susceptibility to SARS-CoV-2 infection and TYK2 gene might be involved in COVID-19 severity. Nevertheless, no statistically significant association was observed in the COVID-19 fatal outcome or in the stratified analyses (dementia-only and non-dementia strata) for the APOE locus not supporting its involvement in SARS-CoV-2 pathobiology or COVID-19 prognosis.

10.
Int J Alzheimers Dis ; 2021: 3064224, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34557314

RESUMEN

Alzheimer's disease is the most common cause of dementia worldwide, and longitudinal studies are crucial to find the factors affecting disease development. Here, we describe a novel initiative from southern Spain designed to contribute in the identification of the genetic component of the cognitive decline of Alzheimer's disease patients. The germline variant rs9320913 is a C>A substitution mapping within a gene desert. Although it has been previously associated to a higher educational achievement and increased fluid intelligence, its role on Alzheimer's disease risk and progression remains elusive. A total of 407 subjects were included in the study, comprising 153 Alzheimer disease patients and 254 healthy controls. We have explored the rs9320913 contribution to both Alzheimer disease risk and progression according to the Mini-Mental State Exams. We found that rs9320913 maps within a central nervous system lincRNA AL589740.1. eQTL results show that rs9320913 correlated with the brain-frontal cortex (beta = -0.15, p value = 0.057) and brain-spinal cord (beta of -0.23, p value = 0.037). We did not find rs9320913 to be associated to AD risk, although AA patients seemed to exhibit a less pronounced Mini-Mental State Exam score decline.

11.
Int J Geriatr Psychiatry ; 35(11): 1292-1300, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32584440

RESUMEN

OBJECTIVES: An increasing evidence suggests hypertension (HTN) could be linked to cognitive impairment and incident Alzheimer's disease (AD). The precise mechanisms linking HTN and AD are not well-known. The aim of this study was to assess the putative association between HTN and AD. METHODS: We assessed in patients with AD associations between HTN and demographic and clinical data, vascular risk factors, treatments, APOE genotypes, brain white matter hyperintensities (WMH), and medial temporal atrophy (MTA) in multivariate analysis of covariance. RESULTS: We studied 92 patients with AD (mean ± SD age: 72.12 ± 6.91; women: 66.30%). Patients with HTN had significantly worse cognitive and functional status and higher frequency and severity of neuropsychiatric symptoms (P = .010). Magnetic resonance imaging analyzes showed significant increases in WMH (P = .018) and in MTA (P = .012) in patients with AD with HTN compared with those without HTN. CONCLUSIONS: Neuroimaging burden (MTA and higher degree of severity of WMH) among patients with AD and HTN are associated with the impaired cognitive function and neuropsychiatric symptoms.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Hipertensión , Sustancia Blanca , Anciano , Enfermedad de Alzheimer/patología , Atrofia/patología , Cognición , Disfunción Cognitiva/patología , Femenino , Humanos , Hipertensión/patología , Imagen por Resonancia Magnética , Lóbulo Temporal/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología
12.
Podium (Pinar Río) ; 15(1): 99-110, ene.-abr. 2020.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1091740

RESUMEN

Resumen En la actualidad, el interés de los sistemas educativos se sitúa en la gestión del aprendizaje, basada en las plataformas virtuales, sobre todo, en cómo se propicia la construcción del conocimiento social desde el e-learning. El propósito del artículo fue aportar a este tema, al reflexionar acerca del comportamiento que tiene la utilización de e- learning en el proceso de enseñanza-aprendizaje de la cultura física, a partir de un estudio a los profesores de la carrera de Cultura Física, en universidades ecuatorianas. Se realizó una investigación cuantitativa, con el empleo de métodos y técnicas que permitieron recopilar información para el respectivo análisis, en la carrera de Cultura Física, en la Universidad de Guayaquil, explorando, mediante encuestas, a docentes y estudiantes, así como observaciones sistemáticas al proceso de enseñanza-aprendizaje en las plataforma e-learning y las experiencias didácticas que se utilizan en la carrera, lo cual ha podido dejar en evidencia aspectos inherentes a las posibilidades y limitaciones del e-learning en la enseñanza de la mencionada carrera, puesto que este ha tenido una amplia recepción en la educación universitaria ya que posibilita en los estudiantes, la apropiación de conocimientos, desarrollo de habilidades y actitudes que les permitirán desenvolverse en el contexto social.


Síntese Atualmente, o interesse dos sistemas educativos está na gestão da aprendizagem baseada em plataformas virtuais, sobretudo na forma como se promove a construção do conhecimento social a partir do e-learning. O objetivo deste artigo foi contribuir para este tema, refletindo sobre o comportamento do uso do e-learning no processo de ensino e aprendizagem da cultura física, com base em um estudo de professores de cultura física em universidades equatorianas. Foi realizada uma pesquisa quantitativa utilizando métodos e técnicas que permitiram a recolha de informação para a respectiva análise na carreira de Cultura Física na Universidade de Guayaquil, explorando através de um levantamento de professores e alunos, bem como observações sistemáticas do processo ensino-aprendizagem nas plataformas de e-learning e as experiências didáticas utilizadas na carreira, Isto tornou evidentes aspectos inerentes às possibilidades e limitações do e-learning no ensino da referida carreira, uma vez que o e-learning tem tido um amplo acolhimento no ensino universitário, uma vez que facilita nos estudantes a apropriação de conhecimentos, o desenvolvimento de competências e atitudes que lhes permitirão desenvolver-se no contexto social.


Abstract At present, the interest of educational systems is in the management of learning based on virtual platforms, especially in how the construction of social knowledge from e-learning is encouraged. The purpose of the article was to contribute to thistopic, by reflecting on the behavior of the use of e-learning in the teaching-learning process of physical culture, from a study of the professors of the Physical Culture career, in Ecuadorian universities. A quantitative investigation was carried out using methods and techniques that allowed to gather information for the respective analysis in the Physical Culture degree, at the University of Guayaquil, exploring through a survey of teachers and students, as well as systematic observations of the teaching-learning process in the e-learning platform and the didactic experiences that are used in the race, which has been able to leave in evidence aspects inherent to the possibilities and limitations of e-learning in the teaching of the mentioned race, since e-learning has had a wide reception in university education because it facilitates in students the appropriation of knowledge, development of skills and attitudes that will allow them to function in the social context.

13.
J Infect Dis ; 219(12): 2015-2025, 2019 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-30715407

RESUMEN

Rocio virus (ROCV) is a highly neuropathogenic mosquito-transmitted flavivirus responsible for an unprecedented outbreak of human encephalitis during 1975-1976 in Sao Paulo State, Brazil. Previous studies have shown an increased number of inflammatory macrophages in the central nervous system (CNS) of ROCV-infected mice, implying a role for macrophages in the pathogenesis of ROCV. Here, we show that ROCV infection results in increased expression of CCL2 in the blood and in infiltration of macrophages into the brain. Moreover, we show, using CCR2 knockout mice, that CCR2 expression is essential for macrophage infiltration in the brain during ROCV infection and that the lack of CCR2 results in increased disease severity and mortality. Thus, our findings show the protective role of CCR2-mediated infiltration of macrophages in the brain during ROCV infection.


Asunto(s)
Encefalitis/metabolismo , Infecciones por Flavivirus/metabolismo , Flavivirus/patogenicidad , Macrófagos/metabolismo , Receptores CCR2/metabolismo , Animales , Encéfalo , Brasil , Encefalitis/virología , Femenino , Infecciones por Flavivirus/virología , Macrófagos/virología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados
14.
Appl. cancer res ; 37: 1-7, 2017. ilus
Artículo en Inglés | LILACS, Inca | ID: biblio-915434

RESUMEN

Acute myeloid leukemia (AML) is a clonal hematologic neoplasm characterized by heterogeneity of genetic abnormalities found at diagnosis. These abnormalities serve to classify patients by risk group into low, intermediate, and high risk. It also provides specific targets for the development of new combinational therapies. However, because of the heterogeneity of genetic abnormalities, targeted therapy is not always possible. Altered mitochondrial metabolism is a common feature in cancer cells, a phenomenon first described by Otto Warburg. In AML patients, the discovery of mutations in the isocitrate dehydrogenase gene provided for the first time a link between altered mitochondrial metabolism and AML. This raised the possibility of testing drugs known as mitocans for new combinational therapeutic approaches. Mitocans are a diverse group of anti-cancer compounds that target mitochondria. They disrupt energy production leading to enhanced generation of reactive oxygen species along with the activation of the intrinsic pathway of apoptosis. The present review discusses the different types of mitocans and their mechanism of action along with preclinical and clinical studies in AML (AU)


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Leucemia Mieloide Aguda/genética , Heterogeneidad Genética , Neoplasias Hematológicas , Mitocondrias
15.
Clin Cancer Res ; 22(15): 3782-90, 2016 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-26927662

RESUMEN

PURPOSE: EGFR is a well-validated target for patients with non-small cell lung cancer (NSCLC). CIMAvax-EGF is a therapeutic cancer vaccine composed of human recombinant EGF conjugated to a carrier protein and Montanide ISA51 as adjuvant. The vaccine is intended to induce antibodies against self EGFs that block EGF-EGFR interaction. EXPERIMENTAL DESIGN: To evaluate overall survival, safety, immunogenicity, and EGF concentration in serum after CIMAvax-EGF, a randomized phase III trial was done in patients with advanced NSCLC. Four to 6 weeks after first-line chemotherapy, 405 patients with stage IIIB/IV NSCLC were randomly assigned to a vaccine group, which received CIMAvax-EGF or a control group, treated with best supportive care. RESULTS: Long-term vaccination was very safe. Most frequent adverse reactions were grade 1 or 2 injection-site pain, fever, vomiting, and headache. Vaccination induced anti-EGF antibodies and decreased serum EGF concentration. In the safety population, median survival time (MST) was 10.83 months in the vaccine arm versus 8.86 months in the control arm. These differences were not significant according the standard log rank (HR, 0.82; P = 0.100), but according a weighted log rank (P = 0.04) that was applied once the nonproportionality of the HR was verified. Survival benefit was significant (HR, 0.77; P = 0.036) in the per-protocol setting (patients receiving at least four vaccine doses): MST was 12.43 months for the vaccine arm versus 9.43 months for the control arm. MST was higher (14.66 months) for vaccinated patients with high EGF concentration at baseline. CONCLUSIONS: Switch maintenance with CIMAvax-EGF was well tolerated and significantly increased MST of patients that completed induction vaccination. Baseline EGF concentration predicted survival benefit. Clin Cancer Res; 22(15); 3782-90. ©2016 AACR.


Asunto(s)
Vacunas contra el Cáncer/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Factor de Crecimiento Epidérmico/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Adyuvantes Inmunológicos , Vacunas contra el Cáncer/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Factor de Crecimiento Epidérmico/sangre , Femenino , Humanos , Inmunoterapia Activa , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Masculino , Estadificación de Neoplasias , Pronóstico , Retratamiento , Resultado del Tratamiento
16.
Asunción; s.n; Febr. 2013. 102 p. ilus.
Tesis en Español | LILACS, BDNPAR | ID: lil-681481

RESUMEN

La leucemia mieloide crónica (LMC) es una neoplasia mieloproliferativa asociada a la presencia del gen de fusión BCR-ABL1 en la célula madre hematopoyética producto de la translocación t(9;22) 8q34;q11.2). Este nuevo gen codifica para una proteína tirosin quinasa con actividad oncogénica. Este estudio descriptivo de corte transverso tuvo como objetivo identificar y cuantificar los transcriptos BCR-ABL1 mediante técnicas de biología molecular en pacientes con sospecha clínica y en tratamiento de LMC, que concurrieron al laboratorio de Genética Molecular del Instituto de Investigaciones en Ciencias de la Salud desde tres hospitales públicos de referencia. Se estudiaron un total de 69 pacientes a partir de los cuales se obtuvieron 19 muestras antes del inicio del tratamiento y 57 a distintos tiempo durante el tratamiento con inhibidor de tirosin quinasa. Se analizó el tipo de transcripto en 42 muestras hallándose la isoforma b3a2 en el 64%, la b2a2 en el 31% y ambas en el 5%. A partir de las cuantificaciones realizadas en 57 muestras en tratamiento se determinó la respuesta molecular a los inhibidores de la tirosina quinsa. El 61% no alcanzó la RM Mayor y el 30% obtuvo una RM Mayor o Completa. Este estudio logró implementar por primera vez a nivel nacional la detección y cuantificación del transcripto BCR-ABL1 en pacientes con LMC, introduciéndose una herramientanecesaria para el diagnóstico y seguimiento de la respuesta al tratamiento.


Asunto(s)
Fusión Génica/genética , Reacción en Cadena de la Polimerasa , Transcripción Reversa , Tesis Académicas como Asunto
17.
Ginecol Obstet Mex ; 74(3): 158-63, 2006 Mar.
Artículo en Español | MEDLINE | ID: mdl-16886758

RESUMEN

Eosinophilic pustular folliculitis, which was first described by Ofuji, is a type of dermatosis characterized by pruritic, follicular, papules and pustules that gradually extend peripherally and have central tendency. Ofuji's disease has been rarely reported, and has not been reported in pregnancy. It's possible that hypersensitivity reaction plays an important role. There is no consensus on treatment approaches. We present the case of a 27 year-old woman during the 12.5 weeks of her first pregnancy; she had developed Ofuji's disease for 17 years. Previously, she had been treated with corticosteroid and azatioprine for 15 years, which were suspended by the time she was diagnosed with pregnancy. Then, she was referred to our maternal fetal medicine department, and was treated with prednisone 25 mg a day. The patient had urinary infection and vulvovaginitis at the week 14.2, with peripheral blood eosinophilia. She had exacerbations at the weeks 35.2 and 38.1, which were treated only with prednisone and topical management; furthermore she had a total of 4 kg of weight gain during the whole pregnancy. Cesarean delivery was performed for nonreassuring fetal heart rate. Perinatal results were: woman with lower birth weight: 2,450 g, Apgar 5.8, placenta with calcifications on 60% of it and single nuchal cord. She had exacerbations in late puerperium. A healthy newborn was obtained and no clinical findings of dermatoses were found. Maternal autoimmune diseases may induce remission or exacerbation during pregnancy. Nevertheless, in this case the induced exacerbations during puerperium and the fact that a low birth weight was obtained are problems commonly associated with the prolonged use of corticosteroids during pregnancy.


Asunto(s)
Eosinofilia , Foliculitis , Complicaciones del Embarazo , Enfermedades Cutáneas Vesiculoampollosas , Adulto , Eosinofilia/tratamiento farmacológico , Femenino , Foliculitis/tratamiento farmacológico , Humanos , Embarazo , Complicaciones del Embarazo/tratamiento farmacológico , Enfermedades Cutáneas Vesiculoampollosas/tratamiento farmacológico
18.
Ginecol Obstet Mex ; 74(4): 187-92, 2006 Apr.
Artículo en Español | MEDLINE | ID: mdl-16886764

RESUMEN

BACKGROUND: Diabetes mellitus complicates 3-5% of all pregnancies and is a major cause of perinatal morbidity and mortality. The diet and insulin have revolutionized the care related with pregnancy complicated by diabetes mellitus. OBJECTIVE: To report the management experience in patients with diabetes and pregnancy at the Instituto Materno Infantil, Estado de Mexico. PATIENTS AND METHOD: A descriptive, retrospective, observational and cross-sectional study of pregnant women with diabetes and pregnancy was conducted from 2003 to 2004. RESULTS: We included 55 pregnant women who had: gestational diabetes 30 (54.4%), pregestational diabetes 24 (43.6%), and carbohydrate intolerance 1 (1.8%); every one of them were controlled either with diet, insulin or both. The mean age was 30.6, 80% with family history of type 2 diabetes mellitus, 9% gestational diabetes. Gestational diabetes was diagnosed in 33.3% by abnormal 50 g glucose screening and 46.6% with oral glucose tolerance test (OGTT). The main complications among the patients were urinary disease (61.3%) and the major fetal malformation were those related with cardiovascular disease (9.09%). The most frequent mode of delivery was cesarean section (58%) and birth weight was of 3,146 g. CONCLUSIONS: The main risk factors identified among women in the study group were as follow: More than 25 years of age and family history of diabetes mellitus. We observed a progressive increase in the insulin dosage. The most consistent complications among the patients were urinary infection and the major fetal malformation was cardiovascular disease.


Asunto(s)
Diabetes Gestacional , Embarazo en Diabéticas , Adulto , Estudios Transversales , Diabetes Gestacional/diagnóstico , Femenino , Humanos , Recién Nacido , Embarazo , Resultado del Embarazo , Embarazo en Diabéticas/diagnóstico , Estudios Retrospectivos
19.
SITUA ; (15): 49-54, set. 1999-feb. 2000. tab, graf
Artículo en Español | LILACS, LIPECS | ID: lil-289612

RESUMEN

El glaucoma constituye un problema de salud pública muy importante, ya que es la segunda causa de ceguera en el mundo después de la catarata. El presente estudio tiene como objetivo determinar las características clinico-epidemiológicas de glaucoma en mayores de 40 años de la ciudad del Cusco. La muestra estuvo constituida por 450 personas de ambos sexos mayores de 40 años de edad seleccionados al azar. El promedio de edad fue 55.68(DE igual 11.94). El promedio de presión intraocular (PIO) de toda la población estudiada fue 16.22 mmHg(DE igual 3.07), con un rango de 10-41 mmHg y una moda de 17mmHg. No hallamos diferencia estadística significativa (p mayor 0.05) entre los promedios de ambos ojos ni con respecto al sexo en la población total. El promedio de PIO incrementa con la edad para ambos sexos y lado de ojo. No encontramos diferencia estadística entre los promedios de PIO respecto al sexo y lado de ojo en las personas normales. La PIO promedio en los hipertensos oculares fue 22.75 (DE igual 2.33), no hubo diferencia estadística significativa entre los promedios de ambos ojos. La PIO promedio en glaucomatosos fue 25.97 (DE igual 8.26) y un 25 por ciento presentaba PIO en valores normales, con una diferencia significativa mayor para el ojo derecho. La relación copa/disco promedio del total fue 0.28 (DE igual 0.1), no hubo diferencia entre los promedios para ambos ojos, pero sí entre los grupos de normales, hipertensos oculares y glaucomatosos. La prevalencia de glaucoma crónico simple fue 1.78 por ciento y para hipertensión ocular 2.22 por ciento. Hallamos una asociación del glaucoma con PIO elevada, edad avanzada, nivel socioeconómico bajo y antecedente familiar de glaucoma en primer grado (p menor 0.05), pero no con el tabaquismo, sexo, antecedentes de hipertensión ocular, diabetes y miopía.


Asunto(s)
Glaucoma de Ángulo Abierto , Hipertensión Ocular
20.
Cuad. Esc. Salud Pública ; (55): 55-77, dic. 1990. tab
Artículo en Español | LILACS | ID: lil-97683

RESUMEN

Se realizó un estudio epidemiológico en el Distrito Sanitario Juan Griego a fin de caracterizar las ETA. Este estudio arrojó que el mayor número de casos de intoxicación por alimentos provenían del Barrio "Tari-Tari" y especialmente los menores de 5 años (57%) eran quienes se enfermaban y de ellos el 40% eran menores de un (1) año. Las condiciones higiénico-sanitarias del Distrito no son las más adecuadas ya que presentan graves fallas en los servicios básicos (agua, basura, eliminación de excretas. etc.); además, en los últimos años han venido creciendo barrios marginales que agravan la situación del Distrito, tal es el caso del Barrio "Francisco Adrián", ubicado cerca de uno de los basureros. Esto motivó la aplicación de la metodología de Análisis de Riesgos y Puntos Críticos de Control en los barrios mencionados. El trabajo fue dirigido a la aplicación del RPCC en la preparación de fórmulas lácteas para los menores de un (1) año. Se estudiaron 18 familias (9 en cada barrio) en las cuales había 20 niños menores de un (1) año. En muestreo se llevó acabo durante 7 semanas. Se realizaron análisis de Laboratorio para la determinación de salmollas, Staphylococcus aureus, coliformes totales y fecales en materia prima, alimentos y equipos usados durante la preparación de los teteros; así como también medición de la temperatura ambiente, de neveras y de la mezcla de harina para la preparación de teteros. Los resultados indicaron que en las materias primas empleadas (leche, harina, cereal) no se detectó salmonella; en las muestras de teteros hervidos, ,manos, pezones, agua, se identificaron Staphylococcus aureus y cifras elevadas de NMP Coliformes totales y fecales. Estos resultados microbiológicos en general indican deficiente higiene sanitaria de los habitantes fallas en la manipulación y conservación de los teteros, situación favorecida por la presencia de altas temperaturas ambientales y deficiente refrigeración que permite el crecimiento de los microorganismos


Asunto(s)
Lactante , Humanos , Masculino , Femenino , Sustitutos de la Leche Humana , Riesgo , Intoxicación Alimentaria por Salmonella
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