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1.
Clin Rheumatol ; 2020 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-32676922

RESUMEN

Patients with clinically amyopathic dermatomyositis (CADM) have a risk of developing rapidly progressive interstitial lung disease (ILD). CADM-ILD is associated with the anti-MDA-5 antibody. In the USA, however, patients with CADM have these antibodies less frequently than those in Japan. In addition, those with this disorder are less often complicated with rapidly progressive ILD than those in Japan. We present a case of a 42-year-old Japanese-American female with a 3-month history of a rash on her hands and face with joint pain. Based on the negative results from lupus tests, her primary care provider and a rheumatologist treated her with steroids, hydroxychloroquine, and methotrexate. During treatment, the patient started noticing shortness of breath because of pneumonia, which was revealed by a CT scan. The woman was finally diagnosed with acute respiratory failure due to CADM with ILD. She underwent a double lung transplant as well as treatment with multiple immunosuppressive agents and repeated plasma exchange but died 15 days after transplantation. Her clinical course is similar to that of Japanese patients with CADM-ILD. Outside Japan, primary care providers, rheumatologists, and dermatologists, as well as pulmonary physicians, may be less familiar with this disorder than those in Japan. Since CADM-ILD progresses very quickly and could be fatal, these doctors should be aware of this disease to treat such patients as soon as possible, particularly when seeing a patient of Japanese descent.

2.
Int J Mol Sci ; 21(7)2020 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-32244398

RESUMEN

Bronchopulmonary dysplasia (BPD)-associated pulmonary hypertension (PH) is a significant lung morbidity of infants, and disrupted lung angiogenesis is a hallmark of this disease. We observed that extracellular signal-regulated kinases (ERK) 1/2 support angiogenesis in vitro, and hyperoxia activates ERK1/2 in fetal human pulmonary microvascular endothelial cells (HPMECs) and in neonatal murine lungs; however, their role in experimental BPD and PH is unknown. Therefore, we hypothesized that Tie2 Cre-mediated deficiency of ERK2 in the endothelial cells of neonatal murine lungs would potentiate hyperoxia-induced BPD and PH. We initially determined the role of ERK2 in in vitro angiogenesis using fetal HPMECs. To disrupt endothelial ERK2 signaling in the lungs, we decreased ERK2 expression by breeding ERK2flox/flox mice with Tie-Cre mice. One-day-old endothelial ERK2-sufficient (eERK2+/+) or -deficient (eERK2+/-) mice were exposed to normoxia or hyperoxia (FiO2 70%) for 14 d. We then performed lung morphometry, gene and protein expression studies, and echocardiography to determine the extent of inflammation, oxidative stress, and development of lungs and PH. The knockdown of ERK2 in HPMECs decreased in vitro angiogenesis. Hyperoxia increased lung inflammation and oxidative stress, decreased lung angiogenesis and alveolarization, and induced PH in neonatal mice; however, these effects were augmented in the presence of Tie2-Cre mediated endothelial ERK2 deficiency. Therefore, we conclude that endothelial ERK2 signaling is necessary to mitigate hyperoxia-induced experimental BPD and PH in neonatal mice. Our results indicate that endothelial ERK2 is a potential therapeutic target for the management of BPD and PH in infants.

3.
Am J Pathol ; 190(3): 711-722, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32093901

RESUMEN

Bronchopulmonary dysplasia (BPD)-associated pulmonary hypertension (PH) is an infantile lung disease characterized by aberrant angiogenesis and impaired resolution of lung injury. Adrenomedullin (AM) signals through calcitonin receptor-like receptor and receptor activity-modifying protein 2 and modulates lung injury initiation. However, its role in lung injury resolution and the mechanisms by which it regulates angiogenesis remain unclear. Consequently, we hypothesized that AM resolves hyperoxia-induced BPD and PH via endothelial nitric oxide synthase (NOS3). AM-sufficient (ADM+/+) or -deficient (ADM+/-) mice were exposed to normoxia or hyperoxia through postnatal days (PNDs) 1 to 14, and the hyperoxia-exposed mice were allowed to recover in normoxia for an additional 56 days. Lung injury and development and PH were quantified at different time points. Human pulmonary microvascular endothelial cells were also used to examine the effects of AM signaling on the NOS3 pathway and angiogenesis. Lung blood vessels and NOS3 expression decreased and the extent of hyperoxia-induced BPD and PH increased in ADM+/- mice compared with ADM+/+ mice. Hyperoxia-induced apoptosis and PH resolved by PND14 and PND70, respectively, in ADM+/+ mice but not in ADM+/- mice. Knockdown of ADM, calcitonin receptor-like receptor, and receptor activity-modifying protein 2 in vitro decreased NOS3 expression, nitric oxide generation, and angiogenesis. Furthermore, NOS3 knockdown abrogated the angiogenic effects of AM. Collectively, these results indicate that AM resolves hyperoxic lung injury via NOS3.


Asunto(s)
Adrenomedulina/farmacología , Displasia Broncopulmonar/tratamiento farmacológico , Hiperoxia/complicaciones , Hipertensión Pulmonar/tratamiento farmacológico , Óxido Nítrico Sintasa de Tipo III/metabolismo , Animales , Displasia Broncopulmonar/etiología , Displasia Broncopulmonar/fisiopatología , Células Endoteliales/patología , Femenino , Humanos , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/fisiopatología , Pulmón/fisiopatología , Lesión Pulmonar/tratamiento farmacológico , Lesión Pulmonar/fisiopatología , Masculino , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico Sintasa de Tipo III/genética , Proteína 2 Modificadora de la Actividad de Receptores/genética , Proteína 2 Modificadora de la Actividad de Receptores/metabolismo , Transducción de Señal
4.
An. Fac. Cienc. Méd. (Asunción) ; 52(2): 39-48, 20190700.
Artículo en Español | LILACS-Express | ID: biblio-1007017

RESUMEN

Introducción: La descentralización ha sido una política de Estado en Paraguay desde la promulgación de la Constitución Nacional en 1992 y la ley del Sistema Nacional de Salud en 1996. Aunque el marco legal es favorable el proceso es incipiente y está estancado. Objetivos: describir la importancia de ciertos factores políticos, jurídicos, institucionales, financieros y técnicos como limitantes de la descentralización sanitaria en Paraguay. Materiales y Métodos: se aplicó una encuesta a 511 informantes claves seleccionados por conveniencia para valorar sus percepciones sobre 8 factores identificados mediante entrevistas. Respondieron utilizando una escala ordinal de 1 a 4 referidos a que tan críticos son para ellos estos factores limitantes. Se calculó una resultante para cada factor y se categorizó como mínimo, incipiente, moderado y máximo. Previamente se realizaron entrevistas en profundidad exploratorias para identificar estos factores. Resultados: sobre la percepción de los encuestados señalan que el marco legal inadecuado es un determinante moderado (3 de la escala) con 81,0% mientras que los demás son valorados como máximos (4 de la escala): reticencia a delegar autoridad 81,7%; capacidad técnica limitada 84,7%; acceso limitado a tecnologías 85,4%; capacidad de gestión limitada 86,6%; afinidad política 87,9%; burocracia excesiva 90,9% y presupuesto insuficiente 92,7%. Conclusión: el hecho que la descentralización sanitaria haya avanzado poco se debe a un conjunto de factores, algunos más críticos que otros, que deberían ser considerados en las políticas sectoriales.


Introduction: Decentralization has been a state policy in Paraguay since the promulgation of both the National Constitution in 1992 and the law of the National Health System in 1996. Although the legal framework is favorable, the process is incipient and it's stagnating. Objective: describe the importance of certain political, legal, institutional, financial and technical factors as limitations of the health decentralization in Paraguay. Material and Methods: a poll was applied to 511 key informants selected for convenience to value their perceptions about 8 identified factors through interviews. They answered using an ordinal scale from 1 to 4 referring to how critical these limiting factors are to them. Was calculated a resultant for every factor and was categorized as minimum, incipient, moderate, and maximum. First, exploratory interviews were conducted to identify these factors. Results: about perceptions of the surveyed demonstrate that inadequate legal framework is a moderate determinant (3 from the scale) with 81.0% while others are evaluated as maximums (4 from the scale); reluctance to delegate authority 81.7%; limited technical capacity 84.7%; limited access to technology 85.4%; limited management capacity 86.6%; political affinity 87.9%; excessive bureaucracy 90.9% and insufficient budget 92.7%. Conclusion: the fact that health decentralization has advance poorly is due to a set of factors, some more critical than others, that should be considered in sectoral policies.

5.
Circ Arrhythm Electrophysiol ; 12(6): e006942, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31164004

RESUMEN

Background The autonomic nervous system response to apnea and its mechanistic connection to atrial fibrillation (AF) are unclear. We hypothesize that sensory neurons within the ganglionated plexi (GP) play a role. We aimed to delineate the autonomic response to apnea and to test the effects of ablation of cardiac sensory neurons with resiniferatoxin (RTX), a neurotoxic TRPV1 (transient receptor potential vanilloid 1) agonist. Methods Sixteen dogs were anesthetized and ventilated. Apnea was induced by stopping ventilation until oxygen saturations decreased to 80%. Nerve recordings from bilateral vagal nerves, left stellate ganglion, and anterior right GP were obtained before and during apnea, before and after RTX injection in the anterior right GP (protocol 1, n=7). Atrial effective refractory period and AF inducibility on single extrastimulation were assessed before and during apnea, and before and after intrapericardial RTX administration (protocol 2, n=9). GPs underwent immunohistochemical staining for TRPV1. Results Apnea increased anterior right GP activity, followed by clustered crescendo vagal bursts synchronized with heart rate and blood pressure oscillations. On further oxygen desaturation, a tonic increase in stellate ganglion activity and blood pressure ensued. Apnea-induced effective refractory period shortening from 110.20±31.3 ms to 90.6±29.1 ms ( P<0.001), and AF induction in 9/9 dogs versus 0/9 at baseline. After RTX administration, increases in GP and stellate ganglion activity and blood pressure during apnea were abolished, effective refractory period increased to 126.7±26.9 ms ( P=0.0001), and AF was not induced. Vagal bursts remained unchanged. GP cells showed cytoplasmic microvacuolization and apoptosis. Conclusions Apnea increases GP activity, followed by vagal bursts and tonic stellate ganglion firing. RTX decreases sympathetic and GP nerve activity, abolishes apnea's electrophysiological response, and AF inducibility. Sensory neurons play a role in apnea-induced AF.


Asunto(s)
Apnea/terapia , Fibrilación Atrial/prevención & control , Diterpenos/farmacología , Ganglios Simpáticos/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Corazón/inervación , Simpatectomía Química/métodos , Vías Aferentes/efectos de los fármacos , Vías Aferentes/metabolismo , Vías Aferentes/fisiopatología , Animales , Apnea/complicaciones , Apnea/metabolismo , Apnea/fisiopatología , Fibrilación Atrial/etiología , Fibrilación Atrial/metabolismo , Fibrilación Atrial/fisiopatología , Presión Sanguínea/efectos de los fármacos , Modelos Animales de Enfermedad , Perros , Ganglios Simpáticos/metabolismo , Ganglios Simpáticos/fisiopatología , Canales Catiónicos TRPV/agonistas , Canales Catiónicos TRPV/metabolismo , Nervio Vago/fisiopatología
6.
Ann Diagn Pathol ; 41: 43-50, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31132651

RESUMEN

CONTEXT: Invasive micropapillary adenocarcinoma (MPC) is an aggressive variant of lung adenocarcinoma, frequently manifesting with advanced stage lymph node metastasis and decreased survival. OBJECTIVE: Identification of this morphology is important, as it is strongly correlated with poor prognosis regardless of the amount of MPC component. To date, no study has investigated the morphological criteria used to objectively diagnose it. DESIGN: Herein, we selected 30 cases of potential MPC of lung, and distributed 2 digital images per case among 15 pulmonary pathology experts. Reviewers were requested to diagnostically interpret, assign the percentage of MPC component, and record the morphological features they identified. The noted features included: columnar cells, elongated slender cell nests, extensive stromal retraction, lumen formation with internal epithelial tufting, epithelial signet ring-like forms, intracytoplasmic vacuolization, multiple nests in the same alveolar space, back-to-back lacunar spaces, epithelial nest anastomosis, marked pleomorphism, peripherally oriented nuclei, randomly distributed nuclei, small/medium/large tumor nest size, fibrovascular cores, and spread through air-spaces (STAS). RESULTS: Cluster analysis revealed three subgroups with the following diagnoses: "MPC", "combined papillary and MPC", and "others". The subgroups correlated with the reported median percentage of MPC. Intracytoplasmic vacuolization, epithelial nest anastomosis/confluence, multiple nests in the same alveolar space, and small/medium tumor nest size were the most common criteria identified in the cases diagnosed as MPC. Peripherally oriented nuclei and epithelial signet ring-like forms were frequently identified in both the "MPC" and "combined papillary and MPC" groups. CONCLUSIONS: Our study provides objective diagnostic criteria to diagnose MPC of lung.


Asunto(s)
Adenocarcinoma Papilar/diagnóstico , Adenocarcinoma Papilar/patología , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Patólogos , Patología Quirúrgica/normas , Reproducibilidad de los Resultados
7.
Am J Physiol Lung Cell Mol Physiol ; 316(1): L229-L244, 2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-30307313

RESUMEN

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of infants that is characterized by interrupted lung development. Postnatal sepsis causes BPD, yet the contributory mechanisms are unclear. To address this gap, studies have used lipopolysaccharide (LPS) during the alveolar phase of lung development. However, the lungs of infants who develop BPD are still in the saccular phase of development, and the effects of LPS during this phase are poorly characterized. We hypothesized that chronic LPS exposure during the saccular phase disrupts lung development by mechanisms that promote inflammation and prevent optimal lung development and repair. Wild-type C57BL6J mice were intraperitoneally administered 3, 6, or 10 mg/kg of LPS or a vehicle once daily on postnatal days (PNDs) 3-5. The lungs were collected for proteomic and genomic analyses and flow cytometric detection on PND6. The impact of LPS on lung development, cell proliferation, and apoptosis was determined on PND7. Finally, we determined differences in the LPS effects between the saccular and alveolar lungs. LPS decreased the survival and growth rate and lung development in a dose-dependent manner. These effects were associated with a decreased expression of proteins regulating cell proliferation and differentiation and increased expression of those mediating inflammation. While the lung macrophage population of LPS-treated mice increased, the T-regulatory cell population decreased. Furthermore, LPS-induced inflammatory and apoptotic response and interruption of cell proliferation and alveolarization was greater in alveolar than in saccular lungs. Collectively, the data support our hypothesis and reveal several potential therapeutic targets for sepsis-mediated BPD in infants.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Lipopolisacáridos/toxicidad , Alveolos Pulmonares/crecimiento & desarrollo , Linfocitos T Reguladores/metabolismo , Animales , Animales Recién Nacidos , Relación Dosis-Respuesta a Droga , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/patología , Ratones , Alveolos Pulmonares/metabolismo , Alveolos Pulmonares/patología , Linfocitos T Reguladores/patología
8.
An. Fac. Cienc. Méd. (Asunción) ; 51(3): 41-52, 20181200.
Artículo en Español | LILACS-Express | ID: biblio-980795

RESUMEN

Introducción: La cobertura universal de salud es una meta de salud de los Objetivos del Desarrollo Sostenible de las NNUU para el 2030. Un componente de la cobertura en salud es la protección financiera para recibir atención médica ante una enfermedad. Y, un indicador de la protección financiera es la incidencia de Gastos Catastróficos por motivos de salud. Objetivo: El objetivo de este trabajo es describir la evolución del Gasto Catastrófico de salud de los hogares paraguayos entre el 2000 y el 2015. Materiales y Métodos: El material utilizado fue la Encuesta Permanente de Hogares de la DGEEC. El Gasto Catastrófico fue definido como aquellos gastos de bolsillo ≥ al 30% de la capacidad de pago de los hogares. Resultados: Los resultados indican que, durante ese periodo, la proporción de hogares afectados por gastos catastróficos varió entre 2,8% y 4,33%, siendo la mediana 4,10%. Los más afectados fueron los hogares rurales y los pobres. La proporción de hogares afectados presentó una tendencia al descenso, sobre todo para hogares urbanos y no pobres. Conclusión: La conclusión es que los hogares paraguayos están expuestos a gastos catastróficos por motivos de salud. La ocurrencia es mayor según las referidas características socioeconómicas. El desempeño actual del sistema nacional de salud no será suficiente para alcanzar la cobertura universal con protección financiera para todos. Por tanto, es necesario implementar nuevas políticas para la población más expuesta.


Introduction: Universal health coverage is a health goal of the UN Sustainable Development Goals by 2030. One component of health coverage is the financial protection to receive medical care for a disease. And, an indicator of financial protection is the incidence of Catastrophic Expenditures for health reasons. The objective of this paper is to describe the evolution of the Catastrophic Health Expenditure of Paraguayan households between 2000 and 2015. Materials and Methods: The material used was the Permanent Household Survey of the DGEEC. Catastrophic Expenditure was defined as those out-of-pocket expenses ≥ 30% of the household's payment capacity. Results: The results indicate that during this period, the proportion of households affected by catastrophic expenses ranged between 2.8% and 4.33%, with the median being 4.10%. Rural households and the poor were the most affected. The proportion of affected households showed a downward trend, especially for urban and non-poor households. Conclusion: In conclusion, Paraguayan households are exposed to catastrophic expenses for health reasons. The occurrence is greater according to the referred socioeconomic characteristics. The current performance of the national health system will not be enough to achieve universal coverage with financial protection for all. Therefore, it is necessary to implement new policies for the most exposed population.

11.
Int J Mol Sci ; 19(5)2018 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-29783779

RESUMEN

Hyperoxia contributes to the pathogenesis of bronchopulmonary dysplasia (BPD), a chronic lung disease of infants that is characterized by interrupted alveologenesis. Disrupted angiogenesis inhibits alveologenesis, but the mechanisms of disrupted angiogenesis in the developing lungs are poorly understood. In pre-clinical BPD models, hyperoxia increases the expression of extracellular signal-regulated kinases (ERK) 1/2; however, its effects on the lung endothelial ERK1/2 signaling are unclear. Further, whether ERK1/2 activation promotes lung angiogenesis in infants is unknown. Hence, we tested the following hypotheses: (1) hyperoxia exposure will increase lung endothelial ERK1/2 signaling in neonatal C57BL/6J (WT) mice and in fetal human pulmonary artery endothelial cells (HPAECs); (2) ERK1/2 inhibition will disrupt angiogenesis in vitro by repressing cell cycle progression. In mice, hyperoxia exposure transiently increased lung endothelial ERK1/2 activation at one week of life, before inhibiting it at two weeks of life. Interestingly, hyperoxia-mediated decrease in ERK1/2 activation in mice was associated with decreased angiogenesis and increased endothelial cell apoptosis. Hyperoxia also transiently activated ERK1/2 in HPAECs. ERK1/2 inhibition disrupted angiogenesis in vitro, and these effects were associated with altered levels of proteins that modulate cell cycle progression. Collectively, these findings support our hypotheses, emphasizing that the ERK1/2 pathway is a potential therapeutic target for BPD infants with decreased lung vascularization.


Asunto(s)
Hiperoxia/metabolismo , Pulmón/irrigación sanguínea , Sistema de Señalización de MAP Quinasas , Neovascularización Fisiológica , Animales , Apoptosis , Ciclo Celular , Células Cultivadas , Células Endoteliales/metabolismo , Células Endoteliales/patología , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Femenino , Humanos , Hiperoxia/patología , Pulmón/crecimiento & desarrollo , Masculino , Ratones , Ratones Endogámicos C57BL , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo
12.
Int J Biochem Cell Biol ; 94: 119-124, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29223466

RESUMEN

Pulmonary hypertension (PH) frequently occurs in infants with bronchopulmonary dysplasia (BPD), causing increased mortality and right ventricular (RV) dysfunction that persists into adulthood. A first step in developing better therapeutic options is identifying and characterizing an appropriate animal model. Previously, we characterized the short-term morbidities of a model in which C57BL/6J wild-type (WT) mice were exposed to 70% O2 (hyperoxia) during the neonatal period. Here, we aimed to determine the long-term morbidities using lung morphometry, echocardiography (Echo), and cardiac magnetic resonance imaging (cMRI). The major highlight of this study is the use of the state-of-the art imaging technique, cMRI, in mice to characterize the long-term cardiac effects of neonatal hyperoxia exposure. To this end, WT mice were exposed to 21% O2 (normoxia) or hyperoxia for two weeks of life, followed by recovery in normoxia for six weeks. Alveolarization, pulmonary vascularization, pulmonary hypertension, and RV function were quantified at eight weeks. We found that hyperoxia exposure resulted in persistent alveolar and pulmonary vascular simplification. Furthermore, the Echo and cMRI studies demonstrated that hyperoxia-exposed mice had signs of PH and RV dysfunction as indicated by increased RV pressure, mass, and end-systolic and -diastolic volumes, and decreased RV stroke volume and ejection fractions. Taken together, our results demonstrate that neonatal hyperoxia exposure in mice cause cardiopulmonary morbidities that persists into adulthood and provides evidence for the use of this model to develop novel therapies for BPD infants with PH.


Asunto(s)
Modelos Animales de Enfermedad , Corazón/fisiopatología , Hiperoxia/fisiopatología , Hipertensión Pulmonar/etiología , Pulmón/patología , Circulación Pulmonar , Disfunción Ventricular Derecha/etiología , Animales , Animales Recién Nacidos , Camaras de Exposición Atmosférica , Displasia Broncopulmonar/fisiopatología , Ecocardiografía , Estudios de Factibilidad , Femenino , Corazón/diagnóstico por imagen , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/patología , Pulmón/irrigación sanguínea , Pulmón/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Ratones Endogámicos C57BL , Miocardio/patología , Tamaño de los Órganos , Volumen Sistólico , Factores de Tiempo , Ultrasonografía Doppler de Pulso , Disfunción Ventricular Derecha/diagnóstico por imagen , Disfunción Ventricular Derecha/patología
13.
Arch Pathol Lab Med ; 142(1): 120-126, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28613913

RESUMEN

CONTEXT: - Hypersensitivity pneumonitis (HP) is a lung disease that develops in susceptible individuals after inhalational exposure to an organic antigen or chemical compound. Pathogenesis is attributed to a combination of type III (immune complex-mediated) and type IV (delayed) hypersensitivity reactions to the inciting agent. OBJECTIVE: - To provide an overview of the current status of the medical literature regarding hypersensitivity pneumonitis. DATA SOURCES: - A literature search was performed using PubMed and Google search engines. The terms "hypersensitivity pneumonitis" and "extrinsic allergic alveolitis" were used, with the search starting on January 9, 2017, and concluding March 8, 2017. CONCLUSIONS: - As a pathologist, it is important to consider hypersensitivity pneumonitis when examining lung specimens because it is often clinically and pathologically overlooked. Recognizing the often subtle findings and correlating them with the patient's history or suggesting a thorough clinical investigation of potential exposures can be of help in identifying the underlying condition so that the patient can be appropriately managed.


Asunto(s)
Alveolitis Alérgica Extrínseca/diagnóstico , Alveolitis Alérgica Extrínseca/etiología , Alveolitis Alérgica Extrínseca/patología , Diagnóstico Diferencial , Humanos , Pulmón/patología , Patología Clínica , Sociedades Médicas
14.
J Surg Case Rep ; 2017(11): rjx214, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29230281

RESUMEN

Jejunoileal bypass (JIB) was developed as a surgical treatment for morbid obesity in the early 1950s. However, this procedure is now known to be associated with multiple metabolic complications and has subsequently been abandoned as a viable bariatric procedure. Some of these known complications include renal stone formation, liver failure, migratory arthritis, fat-soluble deficiencies, blind-loop syndrome and severe diarrhea. Additionally, there have been animal models suggesting colon dysplasia after JIB. To our knowledge however, in humans, no colon cancers have been attributed to JIB in the literature. Here we report a 63-year-old morbidly obese female who had a JIB surgery in 1973 and subsequently was found to have numerous sessile colonic polyps throughout her colon and adenocarcinoma of the ascending colon without any family history of colonic polyposis syndromes or colon cancer.

15.
Arch Pathol Lab Med ; 141(11): 1529-1532, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28829153

RESUMEN

CONTEXT: - Programmed death ligand-1 (PD-L1) expression in non-small cell lung carcinoma (NSCLC) is heterogeneous and known to be underestimated on small biopsies. Correlation of PD-L1 expression with clinicopathologic features may provide additional useful information. To our knowledge, the clinicopathologic features of NSCLC have not been reported for subsets defined by PD-L1 expression in either tumor cells or tumor-infiltrating immune cells. OBJECTIVE: - To investigate the clinicopathologic characteristics of NSCLC subsets defined by PD-L1 expression in either tumor cells or tumor-infiltrating immune cells. DESIGN: - PD-L1 immunohistochemistry with the SP142 clone was performed on whole-tissue sections and given semiquantitative scores (0/1/2/3) according to percent of PD-L1+ tumor cells (TCs) and percent tumor area with PD-L1+ tumor-infiltrating immune cells (ICs). RESULTS: - Adenocarcinoma cases that were scored either TC 1/2/3 or IC 1/2/3 included most (22 of 34; 65%) high-histologic grade cases and most (25 of 36; 69%) solid subtype cases. Compared with the adenocarcinoma TC 0 and IC 0 subset, the TC 1/2/3 or IC 1/2/3 subset correlated with higher histologic grade (P = .005, χ2 test for trend) and solid subtype (P < .001, Fisher exact test). Compared with the adenocarcinoma TC 0/1 or IC 0/1 subset, the TC 2/3 or IC 2/3 subset correlated with higher histologic grade (P = .002, χ2 test for trend), solid subtype (P < .001, Fisher exact test), and higher smoking pack-years (P = .01, Mann-Whitney test). CONCLUSIONS: - Lung adenocarcinoma subsets defined by PD-L1 expression in either tumor cells or tumor-infiltrating immune cells correlated with high histologic grade, solid subtype, and high smoking pack-years.


Asunto(s)
Adenocarcinoma/metabolismo , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias Pulmonares/metabolismo , Pulmón/metabolismo , Linfocitos Infiltrantes de Tumor/metabolismo , Adenocarcinoma/inmunología , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adenocarcinoma del Pulmón , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Estudios de Cohortes , Femenino , Humanos , Inmunohistoquímica , Pulmón/inmunología , Pulmón/patología , Pulmón/cirugía , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Estudios Retrospectivos , Fumar/efectos adversos , Carga Tumoral
16.
Toxicol Sci ; 157(1): 260-271, 2017 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-28201809

RESUMEN

Prolonged hyperoxia contributes to bronchopulmonary dysplasia (BPD) in preterm infants. ß-Naphthoflavone (BNF) is a potent inducer of cytochrome P450 (CYP)1A enzymes, which have been implicated in hyperoxic injuries in adult mice. In this investigation, we tested the hypothesis that newborn mice lacking the Cyp1a1 gene would be more susceptible to hyperoxic lung injury than wild-type (WT) mice and that postnatal BNF treatment would rescue this phenotype by mechanisms involving CYP1A and/or NAD(P)H quinone oxidoreductase (NQO1) enzymes. Newborn WT or Cyp1a1-null mice were treated with BNF (10 mg/kg) or the vehicle corn oil (CO) i.p., from postnatal day (PND) 2 to 14 once every other day, while being maintained in room air or hyperoxia (85% O2) for 14 days. Both genotypes showed lung injury, inflammation, and alveolar simplification in hyperoxia, with Cyp1a1-null mice displaying increased susceptibility compared to WT mice. BNF treatment resulted in significant attenuation of lung injury and inflammation, with improved alveolarization in both WT and Cyp1a1-null mice. BNF exposed normoxic or hyperoxic WT mice showed increased expression of hepatic CYP1A1/1A2, pulmonary CYP1A1, and NQO1 expression at both mRNA and protein levels, compared with vehicle controls. However, BNF caused greater induction of hepatic CYP1A2 and pulmonary NQO1 enzymes in the Cyp1a1-null mice, suggesting that BNF protects against hyperoxic lung injury in WT and Cyp1a1-null mice through the induction of CYP1A and NQO1 enzymes. Further studies on the protective role of flavonoids against hyperoxic lung injury in newborns could lead to novel strategies for the prevention and/or treatment of BPD.


Asunto(s)
Displasia Broncopulmonar/etiología , Citocromo P-450 CYP1A1/genética , Recien Nacido Prematuro , Oxígeno/administración & dosificación , beta-naftoflavona/administración & dosificación , Animales , Animales Recién Nacidos , Western Blotting , Displasia Broncopulmonar/genética , Predisposición Genética a la Enfermedad , Humanos , Recién Nacido , Ratones , Ratones Noqueados , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/enzimología
17.
Arch Pathol Lab Med ; 141(3): 437-444, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27819763

RESUMEN

CONTEXT: - The diagnosis and grading of acute cellular and antibody-mediated rejection (AMR) in lung allograft biopsies is important because rejection can lead to acute graft dysfunction and/or failure and may contribute to chronic graft failure. While acute cellular rejection is well defined histologically, no reproducible specific features of AMR are currently identified. Therefore, a combination of clinical features, serology, histopathology, and immunologic findings is suggested for the diagnosis of AMR. OBJECTIVE: - To describe the perspective of members of the Pulmonary Pathology Society (PPS) on the workup of lung allograft transbronchial biopsy and the diagnosis of acute cellular rejection and AMR in lung transplant. DATA SOURCES: - Reports by the International Society for Heart and Lung Transplantation (ISHLT), experience of members of PPS who routinely review lung allograft biopsies, and search of literature database (PubMed). CONCLUSIONS: - Acute cellular rejection should be assessed and graded according to the 2007 working formulation of the ISHLT. As currently no specific features are known for AMR in lung allografts, the triple test (clinical allograft dysfunction, donor-specific antibodies, pathologic findings) should be used for its diagnosis. C4d staining might be performed when morphologic, clinical, and/or serologic features suggestive of AMR are identified.


Asunto(s)
Rechazo de Injerto/diagnóstico , Rechazo de Injerto/inmunología , Inmunidad Celular , Inmunidad Humoral , Trasplante de Pulmón , Biopsia , Humanos , Patología Quirúrgica , Sociedades Médicas
18.
Int J Chron Obstruct Pulmon Dis ; 11: 1597-605, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27478373

RESUMEN

Bronchopulmonary dysplasia (BPD) and chronic obstructive pulmonary disease (COPD) are chronic lung diseases of human infants and adults, respectively, that are characterized by alveolar simplification. One-third of the infants with severe BPD develop pulmonary hypertension (PH). More importantly, PH increases morbidity and mortality in BPD patients. Additionally, COPD is a common respiratory morbidity in former BPD patients. The lack of an appropriate small animal model wherein echocardiography (Echo) can demonstrate PH is one of the major barriers to understand the molecular mechanisms of the disease and, thereby, develop rational therapies to prevent and/or treat PH in BPD patients. Thus, the goal of this study was to establish a model of experimental BPD and PH and investigate the feasibility of Echo to diagnose PH in neonatal mice. Since hyperoxia-induced oxidative stress and inflammation contributes to the development of BPD with PH, we tested the hypothesis that exposure of newborn C57BL/6J mice to 70% O2 (hyperoxia) for 14 days leads to lung oxidative stress, inflammation, alveolar and pulmonary vascular simplification, pulmonary vascular remodeling, and Echo evidence of PH. Hyperoxia exposure caused lung oxidative stress and inflammation as evident by increased malondialdehyde adducts and inducible nitric oxide synthase, respectively. Additionally, hyperoxia exposure caused growth restriction, alveolar and pulmonary vascular simplification, and pulmonary vascular remodeling. At 14 days of age, Echo of these mice demonstrated that hyperoxia exposure decreased pulmonary acceleration time (PAT) and PAT/ejection time ratio and increased right ventricular free wall thickness, which are indicators of significant PH. Thus, we have demonstrated the feasibility of Echo to phenotype PH in neonatal mice with experimental BPD with PH, which can aid in discovery of therapies to prevent and/or treat BPD with PH and its sequelae such as COPD in humans.


Asunto(s)
Displasia Broncopulmonar/etiología , Ecocardiografía Doppler de Pulso , Hiperoxia/complicaciones , Hipertensión Pulmonar/diagnóstico por imagen , Pulmón/irrigación sanguínea , Arteria Pulmonar/diagnóstico por imagen , Enfermedad Pulmonar Obstructiva Crónica/prevención & control , Actinas/metabolismo , Animales , Animales Recién Nacidos , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/fisiopatología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Estudios de Factibilidad , Femenino , Hemodinámica , Hiperoxia/metabolismo , Hiperoxia/fisiopatología , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/fisiopatología , Pulmón/metabolismo , Pulmón/fisiopatología , Masculino , Malondialdehído/metabolismo , Ratones Endogámicos C57BL , Óxido Nítrico Sintasa de Tipo II/metabolismo , Estrés Oxidativo , Valor Predictivo de las Pruebas , Arteria Pulmonar/metabolismo , Arteria Pulmonar/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/etiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Factores de Tiempo , Remodelación Vascular , Factor de von Willebrand/metabolismo
19.
Arch Pathol Lab Med ; 140(4): 322-5, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27028391

RESUMEN

Landmark events in the field of lung cancer in the past year have the potential to significantly alter the practice of pathology. Three key events are (1) approval of payment for low-dose computed tomography screening for lung cancer, (2) publication of an extensively revised World Health Organization classification of lung cancers, and (3) approval of immunohistochemistry based companion diagnostics by the US Food and Drug Administration. We briefly review these milestones in the context of their impact on the practice of pathology.


Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias Pulmonares/patología , Patología Clínica/métodos , Humanos , Inmunohistoquímica/normas , Neoplasias Pulmonares/clasificación , Patología Clínica/economía , Patología Clínica/tendencias , Tomografía Computarizada por Rayos X/economía , Estados Unidos , United States Food and Drug Administration , Organización Mundial de la Salud
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