RESUMEN
Spontaneous coronary artery dissection (SCAD) is diagnosed in a very small percentage of patients with suspected acute coronary syndromes who undergo emergency coronary angiography. Although fibromuscular dysplasia (FMD) is known to coexist in patients with SCAD, the vascular sites of FMD and their frequency have not yet been clarified. We retrospectively reviewed the medical records of 16 patients who were diagnosed with and treated for SCAD at our hospital between 1 January 2011 and 31 January 2023. We have summarized their baseline and clinical characteristics and medical variables, including coronary and upper extremity angiography and in-hospital outcomes. One of our patients had concurrent cardiac tamponade requiring pericardial drainage, and another went into hemorrhage shock the following day from dissection of the gastric retroperitoneal artery. Characteristic angiographic features of partial or diffuse nonatherosclerotic stenosis were observed mainly in the distal parts of the coronary arteries or their branches. Notably, in six patients with SCAD who underwent upper extremity angiography, FMD of the brachial artery was revealed. For the first time, to our knowledge, we found a high prevalence of multifocal FMD of the brachial artery in patients with SCAD.
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Anomalías de los Vasos Coronarios , Displasia Fibromuscular , Enfermedades Vasculares , Humanos , Estudios Retrospectivos , Vasos Coronarios/diagnóstico por imagen , Arteria Braquial/diagnóstico por imagen , Displasia Fibromuscular/diagnóstico , Displasia Fibromuscular/diagnóstico por imagen , Enfermedades Vasculares/diagnóstico por imagen , Enfermedades Vasculares/etiología , Angiografía Coronaria , Extremidad Superior , Anomalías de los Vasos Coronarios/diagnóstico , Anomalías de los Vasos Coronarios/diagnóstico por imagenRESUMEN
OBJECTIVE: To compare pulmonary high-resolution CT (HRCT) findings in patients with Pseudomonas aeruginosa pneumonia to HRCT findings in patients with Cytomegalovirus (CMV) pneumonia. METHODS: We studied 124 patients (77 men, 47 women; age range, 20-89 years; mean age, 65.4 years) with P. aeruginosa pneumonia and 44 patients (22 men, 22 women; age range, 36-86 years; mean age, 63.2 years) with CMV pneumonia. RESULTS: CT findings of consolidation (p < 0.005), bronchial wall thickening (p < 0.001), cavity (p < 0.05), and pleural effusion (p < 0.001) were significantly more frequent in patients with P. aeruginosa pneumonia than in those with CMV pneumonia. Centrilobular nodules, a crazy-paving appearance, and nodules were significantly more frequent in patients with CMV pneumonia than in those with P. aeruginosa pneumonia (all p < 0.001). CONCLUSION: Pulmonary HRCT findings, such as bronchial wall thickening, crazy-paving appearance, and nodules may be useful in distinguishing between P. aeruginosa pneumonia and CMV pneumonia. KEY POINTS: Distinguishing Pseudomonas aeruginosa pneumonia from Cytomegalovirus pneumonia is important. Characteristic features of underlying conditions are present in each pneumonia species. Bronchial wall thickening and cavities are more frequent in Pseudomonas aeruginosa pneumonia. Nodules and a crazy-paving appearance are more frequent in Cytomegalovirus pneumonia.
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Infecciones por Citomegalovirus/diagnóstico por imagen , Citomegalovirus/aislamiento & purificación , Neumonía Bacteriana/diagnóstico por imagen , Neumonía Viral/diagnóstico por imagen , Infecciones por Pseudomonas/diagnóstico por imagen , Pseudomonas aeruginosa/aislamiento & purificación , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Infecciones por Citomegalovirus/virología , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neumonía Bacteriana/microbiología , Neumonía Viral/virología , Infecciones por Pseudomonas/microbiología , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE: Mechanical circulatory support (MCS) using a venoarterial extracorporeal membrane oxygenation (VA-ECMO) device or a catheter-type heart pump (Impella) is critical for the rescue of patients with severe cardiogenic shock. However, these MCS devices require large-bore cannula access (14-Fr and larger) at the femoral artery or vein, which often requires surgical decannulation. METHODS: In this retrospective study, we evaluated post-closure method using a percutaneous suture-mediated vascular closure system, Perclose ProGlide/ProStyle (Abbott Vascular, Lake Bluff, IL, Perclose), as an alternative procedure for MCS decannulation. Closure of 83 Impella access sites and 68 VA-ECMO access sites performed using Perclose or surgical method between January 2018 and March 2023 were evaluated. RESULTS: MCS decannulation using Perclose was successfully completed in all access sites without surgical hemostasis. The procedure time of ProGlide was shorter than surgical decannulation for both Impella and VA-ECMO (13 min vs. 50 min; p < 0.001, 21 min vs. 65 min; p < 0.001, respectively). There were no significant differences in the 30-day survival rate and major adverse events by decannulation including arterial dissection requiring endovascular treatment, hemorrhage requiring a large amount of red blood cell transfusion, and access site infection. CONCLUSION: Our results suggest that the post-closure technique using the percutaneous suture-mediated closure system appears to be a safe and effective method for large-bore MCS decannulation.
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Cateterismo Periférico , Oxigenación por Membrana Extracorpórea , Corazón Auxiliar , Técnicas Hemostáticas , Punciones , Dispositivos de Cierre Vascular , Humanos , Estudios Retrospectivos , Masculino , Femenino , Resultado del Tratamiento , Persona de Mediana Edad , Anciano , Oxigenación por Membrana Extracorpórea/efectos adversos , Oxigenación por Membrana Extracorpórea/instrumentación , Factores de Tiempo , Técnicas Hemostáticas/instrumentación , Técnicas Hemostáticas/efectos adversos , Cateterismo Periférico/efectos adversos , Cateterismo Periférico/instrumentación , Remoción de Dispositivos/efectos adversos , Técnicas de Sutura/instrumentación , Técnicas de Sutura/efectos adversos , Arteria Femoral , Choque Cardiogénico/terapia , Choque Cardiogénico/mortalidad , Choque Cardiogénico/fisiopatología , Choque Cardiogénico/diagnóstico , Factores de Riesgo , Hemorragia/etiología , Hemorragia/prevención & controlRESUMEN
Therapeutics based on RNA interference (RNAi) have emerged as a potential new class of drugs for treating human disease by silencing the target messenger RNA (mRNA), thereby reducing levels of the corresponding pathogenic protein. The major challenge for RNAi therapeutics is the development of safe delivery vehicles for small interfering RNAs (siRNAs). We previously showed that cholesterol-conjugated siRNAs (chol-siRNA) associate with plasma lipoprotein particles and distribute primarily to the liver after systemic administration to mice. We further demonstrated enhancement of silencing by administration of chol-siRNA pre-associated with isolated high-density lipoprotein (HDL) or low-density lipoprotein (LDL). In this study, we investigated mimetic lipoprotein particle prepared from recombinant apolipoprotein A1 (apoA) and apolipoprotein E3 (apoE) as a delivery vehicle for chol-siRNAs. We show that apoE-containing particle (E-lip) is highly effective in functional delivery of chol-siRNA to mouse liver. E-lip delivery was found to be considerably more potent than apoA-containing particle (A-lip). Furthermore, E-lip-mediated delivery was not significantly affected by high endogenous levels of plasma LDL. These results demonstrate that E-lip has substantial potential as delivery vehicles for lipophilic conjugates of siRNAs.
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Lipoproteínas/administración & dosificación , Lipoproteínas/química , ARN Interferente Pequeño/administración & dosificación , Animales , Apolipoproteína A-I/administración & dosificación , Apolipoproteína A-I/química , Apolipoproteínas E/administración & dosificación , Apolipoproteínas E/química , Lipoproteínas HDL/administración & dosificación , Lipoproteínas HDL/química , Lipoproteínas LDL/administración & dosificación , Lipoproteínas LDL/química , Masculino , Ratones , Ratones Endogámicos C57BL , Interferencia de ARN/fisiología , ARN Interferente Pequeño/genéticaRESUMEN
Of the idiopathic interstitial pneumonias (IIPs), usual interstitial pneumonia (UIP) and diffuse alveolar damage (DAD) usually have poor prognoses. The prognoses of cryptogenic organizing pneumonia (COP) and nonspecific interstitial pneumonia (NSIP) are usually more favorable. Although several reports have described neovascularization in COP and UIP, this aspect of UIP has not been compared with NSIP. In this study, we evaluated neovascularization in intra-alveolar fibrotic lesion of cases of fibrosing NSIP (f-NSIP) (n = 26) and UIP (n = 25). In the f-NSIP group, a considerable degree of neovascularization was observed compared to the UIP group and bud type intra-alveolar fibrosis showed a greater degree of neovascularization compared to the mural-incorporation and obliterative types of intra-alveolar fibrosis. Real-time reverse transcription polymerase chain reaction revealed a significantly greater expression of VEGF-A mRNA in f-NSIP than in UIP. The expression of matrix metalloproteinase-2 (MMP-2) mRNA also showed significantly higher in f-NSIP than UIP. The greater VEGF-A and MMP-2 expression may play a role in the pathogenesis of neovascularization in early intra-alveolar fibrotic lesions in f-NSIP.
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Fibrosis Pulmonar Idiopática/patología , Enfermedades Pulmonares Intersticiales/patología , Pulmón/irrigación sanguínea , Fibrosis Pulmonar/patología , Neumonía en Organización Criptogénica/patología , Matriz Extracelular , Humanos , Neumonías Intersticiales Idiopáticas/patología , Pulmón/patología , Metaloproteinasa 2 de la Matriz/metabolismo , Neovascularización Patológica , Pronóstico , ARN Mensajero/genética , Tomografía Computarizada por Rayos X , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Rapid and accurate diagnosis and management can be lifesaving for patients with acute dyspnea. However, making a differential diagnosis and selecting early treatment for patients with acute dyspnea in the emergency setting is a clinical challenge that requires complex decision-making in order to achieve hemodynamic balance, improve functional capacity, and decrease mortality. In the present study, we examined the screening potential of rapid evaluation by lung-cardiac-inferior vena cava (LCI) integrated ultrasound for differentiating acute heart failure syndromes (AHFS) from primary pulmonary disease in patients with acute dyspnea in the emergency setting. METHODS: Between March 2011 and March 2012, 90 consecutive patients (45 women, 78.1 ± 9.9 years) admitted to the emergency room of our hospital for acute dyspnea were enrolled. Within 30 minutes of admission, all patients underwent conventional physical examination, rapid ultrasound (lung-cardiac-inferior vena cava [LCI] integrated ultrasound) examination with a hand-held device, routine laboratory tests, measurement of brain natriuretic peptide, and chest X-ray in the emergency room. RESULTS: The final diagnosis was acute dyspnea due to AHFS in 53 patients, acute dyspnea due to pulmonary disease despite a history of heart failure in 18 patients, and acute dyspnea due to pulmonary disease in 19 patients. Lung ultrasound alone showed a sensitivity, specificity, negative predictive value, and positive predictive value of 96.2, 54.0, 90.9, and 75.0%, respectively, for differentiating AHFS from pulmonary disease. On the other hand, LCI integrated ultrasound had a sensitivity, specificity, negative predictive value, and positive predictive value of 94.3, 91.9, 91.9, and 94.3%, respectively. CONCLUSIONS: Our study demonstrated that rapid evaluation by LCI integrated ultrasound is extremely accurate for differentiating acute dyspnea due to AHFS from that caused by primary pulmonary disease in the emergency setting.
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Disnea/diagnóstico por imagen , Disnea/etiología , Ecocardiografía/métodos , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/diagnóstico por imagen , Enfermedades Pulmonares/complicaciones , Enfermedades Pulmonares/diagnóstico por imagen , Vena Cava Inferior/diagnóstico por imagen , Anciano , Diagnóstico Diferencial , Servicios Médicos de Urgencia/métodos , Femenino , Humanos , Pulmón/diagnóstico por imagen , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Integración de SistemasRESUMEN
Aim: Extracorporeal cardiopulmonary resuscitation (E-CPR) using veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a novel lifesaving method for refractory cardiac arrest. Although VA-ECMO preserves end-organ perfusion, it may affect left ventricular (LV) recovery due to increased LV load. An emerging treatment modality, ECPELLA, which combines VA-ECMO and a transcatheter heart pump, Impella, can simultaneously provide circulatory support and LV unloading. In this single-site cohort study, we assessed impact of ECPELLA support on clinical outcomes of refractory cardiac arrest patients. Method: We retrospectively reviewed 165 consecutive cardiac arrest patients, who underwent E-CPR by VA-ECMO with or without intra-aortic balloon pump (IABP) or ECPELLA from January 2012 to September 2021. We assessed 30-day survival rate, neurological outcome, hemodynamic data, and safety profiles including hemolysis, acute kidney injury, blood transfusion and embolic cerebral infarction. Results: Among 165 E-CPR patients, 35 patients were supported by ECPELLA, and 130 patients were supported by conventional VA-ECMO with or without IABP. Following propensity score matching of 30 ECPELLA and 30 VA-ECMO patients, the 30-day survival (ECPELLA: 53%, VA-ECMO: 20%, p < 0.01) and favorable neurological outcome determined by the Cerebral Performance Category score 1 or 2 (ECPELLA: 33%, VA-ECMO: 7%, p < 0.01) were significantly higher with ECPELLA. Patients receiving ECPELLA also showed significantly higher total mechanical circulatory support flow and lower arterial pulse pressure for the first 3 days (p < 0.01) of treatment. There were no statistical differences in safety profiles between treatment groups. Conclusion: ECPELLA may be associated with improved 30-day survival and neurological outcome in patients with refractory cardiac arrest.
RESUMEN
The Aurora kinases are essential for the regulation of chromosome segregation and cytokinesis during mitosis. Aberrant expression and activity of these kinases occur in a wide range of human tumors, and lead to aneuploidy and tumorigenesis. Here we report the discovery of a highly potent and selective small-molecule inhibitor of Aurora kinases, VX-680, that blocks cell-cycle progression and induces apoptosis in a diverse range of human tumor types. This compound causes profound inhibition of tumor growth in a variety of in vivo xenograft models, leading to regression of leukemia, colon and pancreatic tumors at well-tolerated doses. Our data indicate that Aurora kinase inhibition provides a new approach for the treatment of multiple human malignancies.
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Inhibidores Enzimáticos/metabolismo , Inhibidores Enzimáticos/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Piperazinas/uso terapéutico , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Animales , Apoptosis/fisiología , Aurora Quinasas , Ciclo Celular/fisiología , Línea Celular Tumoral , Inhibidores Enzimáticos/química , Femenino , Histonas/metabolismo , Humanos , Ratones , Ratones Desnudos , Estructura Molecular , Piperazinas/química , Piperazinas/farmacología , Proteínas Serina-Treonina Quinasas/metabolismo , RatasRESUMEN
Acute aortic syndrome (AAS) can be life-threatening owing to a variety of complications, and it is managed in the intensive care unit (ICU). Although Stanford type-B AAS may involve hypoxemia, its predictors are not yet clearly understood. We studied clinical factors and imaging parameters for predicting hypoxemia after the onset of type-B AAS. We retrospectively analyzed patients diagnosed with type-B AAS in our hospital between January 2012 and April 2020. We defined hypoxemia as PaO2/FiO2 ≤ 200 within 7 days after AAS onset and used logistic regression analysis to evaluate prognostic factors for hypoxemia. We analyzed 224 consecutive patients (140 males, mean age 70 ± 14 years) from a total cohort of 267 patients. Among these, 53 (23.7%) had hypoxemia. The hypoxemia group had longer ICU and hospital stays compared with the non-hypoxemia group (median 20 vs. 16 days, respectively; p = 0.039 and median 7 vs. 5 days, respectively; p < 0.001). Male sex (odds ratio [OR] 2.87; 95% confidence interval [CI] 1.24-6.63; p = 0.014), obesity (OR 2.36; 95% CI 1.13-4.97; p = 0.023), patent false lumen (OR 2.33; 95% CI 1.09-4.99; p = 0.029), and high D-dimer level (OR 1.01; 95% CI 1.00-1.02; p = 0.047) were independently associated with hypoxemia by multivariate logistic analysis. This study showed a significant difference in duration of ICU and hospital stays between patients with and without hypoxemia. Furthermore, male sex, obesity, patent false lumen, and high D-dimer level may be significantly associated with hypoxemia in patients with type-B AAS.
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Enfermedades de la Aorta/epidemiología , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Hipoxia/epidemiología , Anciano , Anciano de 80 o más Años , Enfermedades de la Aorta/metabolismo , Femenino , Humanos , Hipoxia/metabolismo , Unidades de Cuidados Intensivos , Tiempo de Internación , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
Cholesterol-conjugated siRNAs can silence gene expression in vivo. Here we synthesize a variety of lipophilic siRNAs and use them to elucidate the requirements for siRNA delivery in vivo. We show that conjugation to bile acids and long-chain fatty acids, in addition to cholesterol, mediates siRNA uptake into cells and gene silencing in vivo. Efficient and selective uptake of these siRNA conjugates depends on interactions with lipoprotein particles, lipoprotein receptors and transmembrane proteins. High-density lipoprotein (HDL) directs siRNA delivery into liver, gut, kidney and steroidogenic organs, whereas low-density lipoprotein (LDL) targets siRNA primarily to the liver. LDL-receptor expression is essential for siRNA delivery by LDL particles, and SR-BI receptor expression is required for uptake of HDL-bound siRNAs. Cellular uptake also requires the mammalian homolog of the Caenorhabditis elegans transmembrane protein Sid1. Our results demonstrate that conjugation to lipophilic molecules enables effective siRNA uptake through a common mechanism that can be exploited to optimize therapeutic siRNA delivery.
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Técnicas de Transferencia de Gen , Interferencia de ARN , ARN Interferente Pequeño/genética , Animales , Apolipoproteínas B/genética , Apolipoproteínas B/metabolismo , Colesterol , Cricetinae , Lipoproteínas HDL , Lipoproteínas LDL/genética , Lipoproteínas LDL/metabolismo , Mesocricetus , Ratones , Receptores de Lipoproteína/metabolismoRESUMEN
Salivary duct carcinoma (SDC) of the extra-glandular segment of Stensen's duct is a very rare but aggressive neoplasm. Ultrasonography, computed tomography, and magnetic resonance imaging findings in a patient pathologically proven to have SDC of the extra-glandular segment of Stensen's duct are reported. When an early peak enhancement region in the mass with a well-enhanced dilated and thickened Stensen's duct wall is apparent on dynamic studies, a SDC of the extra-glandular segment of Stensen's duct should be strongly suspected.
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Diagnóstico por Imagen/métodos , Conductos Salivales/diagnóstico por imagen , Conductos Salivales/patología , Neoplasias de las Glándulas Salivales/diagnóstico , Sialografía/métodos , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estadística como Asunto , UltrasonografíaRESUMEN
The aim of this study was to assess the clinical and pulmonary thin-section CT findings in patients with acute Klebsiella pneumoniae pneumonia. We retrospectively evaluated thin-section CT examinations performed between January 1991 and December 2007 from 962 patients with acute Klebsiella pneumoniae pneumonia. Seven hundred and sixty-four cases with concurrent infectious diseases were excluded. Thus, our study group comprised 198 patients (118 male, 80 female; age range 18-97 years, mean age 61.5). Underlying diseases and clinical findings were assessed. Parenchymal abnormalities were evaluated along with the presence of enlarged lymph nodes and pleural effusion. CT findings in patients with acute Klebsiella pneumoniae pneumonia consisted mainly of ground-glass attenuation (100%), consolidation (91.4%), and intralobular reticular opacity (85.9%), which were found in the periphery (96%) of both sides of the lungs (72.2%) and were often associated with pleural effusion (53%). The underlying conditions in patients with Klebsiella pneumoniae pneumonia were alcoholism or smoking habit.
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Infecciones por Klebsiella/diagnóstico , Klebsiella pneumoniae/metabolismo , Neumonía/diagnóstico , Neumonía/microbiología , Tomografía Computarizada por Rayos X/métodos , Adolescente , Adulto , Anciano , Alcoholismo , Diagnóstico por Imagen/métodos , Femenino , Humanos , Infecciones por Klebsiella/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Neumonía/diagnóstico por imagen , Estudios Retrospectivos , FumarRESUMEN
An 82-year old man was admitted to our hospital for evaluation of progressive general malaise. He had previously been in good health. His chest roentgenogram showed reticular shadows and we suspected interstitial lung disease. On admission, his roentgenographic images showed deterioration compared with previous images. Acute lung injury was diagnosed by transbronchial lung biopsy, and steroid administration was started. He initially responded to treatment, but bilateral spontaneous pneumothorax occurred. Despite treatment, he died of respiratory failure. Amitani disease (idiopathic pulmonary upper lobe fibrosis) was suspected based on postmortem pathology, but his lung parenchyma was poor due to the presence of changes producing diffuse alveolar damage. We report and discuss this case because there are apparently no previous similar cases.
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Fibrosis Pulmonar/fisiopatología , Anciano de 80 o más Años , Humanos , MasculinoRESUMEN
We report a case of gastrointestinal manifestation of hereditary angioedema. Computed tomography (CT) revealed wall thickening of the gastric antrum, duodenum, and jejunum. Dilatation of the third part of the duodenum, thickening of the small bowel mesentery and omentum, and retroperitoneal edema were present. The importance of considering this condition in patients presenting such CT findings correlated with the appropriate history is discussed.
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Angioedemas Hereditarios/diagnóstico por imagen , Tracto Gastrointestinal/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Dolor Abdominal/etiología , Angioedemas Hereditarios/complicaciones , Angioedemas Hereditarios/tratamiento farmacológico , Proteína Inhibidora del Complemento C1/administración & dosificación , Inactivadores del Complemento/administración & dosificación , Diagnóstico Diferencial , Edema/etiología , Femenino , Humanos , Persona de Mediana Edad , Náusea/etiologíaRESUMEN
A 31-year-old woman was admitted to our hospital because of progressive dyspnea and chest X-ray abnormality. She was given a diagnosis of bronchial asthma 3 years previously. She had received medical treatment, but her dyspnea did not improve. Chest CT showed multiple thin-walled cysts and centrilobular nodules throughout both lungs. Video-assisted thoracoscopic lung biopsy revealed remarkable plasmacytic infiltration in the bronchioles and its surrounding interstitium. Small cystic lesions were detected and with remarkable mural plasmacytic infiltration. The immunohistochemistry showed infiltrated plasmacytes with polyconal characteristics. Her biochemical examinations showed polyclonal hyperimmunoglobulinemia and a high range of serum IL-6. In addition, CT scans showed multiple mediastinal and intraperitoneal lymphadenopathy. From these examinations, she was given a diagnosis of multicentric Castleman disease (MCD) with pulmonary involvement showing diffuse cystic change. This case showed an unusual pattern of MCD with pulmonary involvement. However, we suggest that MCD also should be considered as a differential diagnosis in cases with diffuse lung cystic changes.
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Enfermedad de Castleman/patología , Quistes/patología , Enfermedades Pulmonares/patología , Adulto , Enfermedad de Castleman/diagnóstico por imagen , Quistes/diagnóstico por imagen , Quistes/etiología , Diagnóstico Diferencial , Femenino , Humanos , Enfermedades Pulmonares/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
A 68-year-old woman had been given a diagnosis of interstitial pneumonia (NSIP pattern) and followed up at our hospital for 3 years. She was admitted to our hospital because of dyspnea, lower limb edema and myalgia. On admission, serum CPK and CRP levels were elevated and an electromyogram suggested inflammatory myopathy. We diagnosed polymyositis (PM) with progressive interstitial pneumonia (IP). Although methylprednisolone pulse therapy and immunosuppressive agents were administered, pulmonary lesions became aggravated. The patient died due to respiratory failure as a result of the progress of IP. The autopsy lung revealed diffuse alveolar damage (DAD) at the both acute and fibrotic phases, suggesting that DAD could coincide with PM. We report here a rare case of polymyositis with diffuse alveolar damage (DAD).
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Enfermedades Pulmonares Intersticiales/complicaciones , Polimiositis/etiología , Alveolos Pulmonares/patología , Fibrosis Pulmonar/etiología , Anciano , Electromiografía , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/patología , Polimiositis/diagnóstico , Fibrosis Pulmonar/patologíaRESUMEN
RATIONALE AND OBJECTIVES: Nocardiosis is difficult to diagnose, and the diagnosis is thus frequently delayed. High-resolution computed tomography (HRCT) findings of patients with pulmonary nocardiosis have been documented in few reports. Our study objective was to assess HRCT findings of patients with pulmonary nocardiosis. MATERIALS AND METHODS: This was a retrospective study of 20 consecutive patients with pulmonary Nocardia infections who underwent HRCT of the chest at our institutions from January 2011 to August 2014. After the exclusion of two patients with concurrent infections, the study group comprised 18 patients (11 men, 7 women; age range, 39-83 years; mean, 67.9 years) with pulmonary Nocardia infections. Parenchymal abnormalities, enlarged lymph nodes, and pleural effusion were evaluated on HRCT. RESULTS: Underlying conditions included respiratory disease (n = 6, 33.3%), collagen diseases (n = 5, 27.8%), and diabetes mellitus (n = 4, 22.2%). All patients showed abnormal HRCT findings, including the presence of a nodule/mass (n = 17, 94.4%), ground-glass opacity (n = 14, 77.8%), interlobular septal thickening (n = 14, 77.8%), and cavitation (n = 12, 66.7%). Pleural effusion was seen in two patients. There were no cases of lymph node enlargement. CONCLUSIONS: Among the HRCT findings in patients with pneumonia, a nodule/mass with interlobular septal thickening and/or cavitation are suggestive of pulmonary nocardiosis.
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Tomografía Computarizada Multidetector/métodos , Nocardiosis/diagnóstico por imagen , Neumonía Bacteriana/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades del Colágeno/complicaciones , Complicaciones de la Diabetes/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Pulmón/diagnóstico por imagen , Ganglios Linfáticos/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Derrame Pleural/diagnóstico por imagen , Enfermedades Respiratorias/complicaciones , Estudios Retrospectivos , Nódulo Pulmonar Solitario/diagnóstico por imagenRESUMEN
INTRODUCTION: A requisite step in developing a therapeutic to modulate the levels of hepcidin is the development of a quantitative method for measuring the concentration of serum hepcidin. METHODS: To this end, an LC-MS method, based on selected reaction monitoring (SRM) with a triple quadrupole MS and an isotopically labeled hepcidin as internal standard, was developed to measure hepcidin in mouse and monkey sera. RESULTS: Initially, 40 normal cynomolgus monkeys and 40 normal mice were studied to determine the normal endogenous levels of hepcidin, and an average of 50ng/mL was found in the monkeys and 46ng/mL in the mice. Next, experiments were conducted where an siRNA, targeting hepcidin, was administered to cynomolgus monkeys, resulting in effective hepcidin reduction (inhibition rate) of 87% after 24h and 74% after 48h, demonstrating to effectively reduce serume level of hepcidin. CONCLUSIONS: For better sensitivity, especially for the low volumes available for mouse sera, a second LC-MS method, based on parallel reaction monitoring (PRM) using a Orbitrap MS was developed and shown to be at least 10 fold lower in detection limits (or consumption of serum volume) than the SRM approach.
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Hepcidinas/biosíntesis , Hepcidinas/sangre , ARN Interferente Pequeño/farmacología , Animales , Cromatografía Líquida de Alta Presión , Haplorrinos , Hepcidinas/genética , Espectrometría de Masas , Ratones , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/genéticaRESUMEN
The Rho kinases (ROCK1 and ROCK2) are highly homologous serine/threonine kinases that act on substrates associated with cellular motility, morphology, and contraction and are of therapeutic interest in diseases associated with cellular migration and contraction, such as hypertension, glaucoma, and erectile dysfunction. Beginning with compound 4, an inhibitor of ROCK1 identified through high-throughput screening, systematic exploration of SAR, and application of structure-based design, led to potent and selective ROCK inhibitors. Compound 37 represents significant improvements in inhibition potency, kinase selectivity, and CYP inhibition and possesses pharmacokinetics suitable for in vivo experimentation.
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Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Piridinas/química , Piridinas/farmacología , Quinasas Asociadas a rho/antagonistas & inhibidores , Humanos , Simulación del Acoplamiento Molecular , Inhibidores de Proteínas Quinasas/síntesis química , Piridinas/síntesis química , Relación Estructura-Actividad , Quinasas Asociadas a rho/química , Quinasas Asociadas a rho/metabolismoRESUMEN
Samples of blood or other animal fluids contain a variety of substances that inhibit the polymerase chain reaction (PCR), meaning that isolation of DNA, involving multiple labor-intensive steps, is generally necessary prior to PCR. We have developed a novel reagent cocktail that effectively suppresses these inhibitory substances. Using this reagent cocktail, DNA from various targets can be efficiently amplified directly from various forms of blood samples without DNA isolation. 1. DNA sequences within the beta-globin gene could be amplified directly from human blood samples treated with various anticoagulants. Either fresh blood or blood samples stored frozen for up to 4 years could be used for PCR. 2. DNA sequences of up to 2056 bp within the beta-globin gene could be amplified directly from human blood samples. 3. Human chromosomal and mitochondrial DNA from different individuals could be amplified directly from blood samples. 4. Low titers of hepatitis B virus could be amplified directly from human blood samples. 5. DNA could be amplified directly from various target sequences using dried blood in a PCR tube or on a filter paper. 6. Transgenes could be detected directly in blood samples from transgenic mice.