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1.
Biochem Biophys Res Commun ; 710: 149843, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38593617

RESUMEN

The success rate of flap tissue reconstruction has increased in recent years owing to advancements in microsurgical techniques. However, complications, such as necrosis, are still more prevalent in diabetic patients compared to non-diabetic individuals, presenting an ongoing challenge. To address this issue, many previous studies have examined vascular anastomoses dilation and stability, primarily concerning surgical techniques or drugs. In contrast, in the present study, we focused on microvascular damage of the peripheral microvessels in patients with diabetes mellitus and the preventative impact of nafamostat mesylate. Herein, we aimed to investigate the effects of hyperglycemia on glycocalyx (GCX) levels in mice with type 2 diabetes. We examined the endothelial GCX (eGCX) in skin flap tissue of 9-12-week-old type 2 diabetic mice (db/db mice) using a perforator skin flap and explored treatment with nafamostat mesylate. The growth rates were compared after 1 week. Heterotype (db/+) mice were used as the control group. Morphological examination of postoperative tissues was performed at 1, 3, 5, and 7 days post-surgery. In addition, db/db mice were treated with 30 mg/kg/day of nafamostat mesylate daily and were evaluated on postoperative day 7. Seven days after surgery, all db/db mice showed significant partial flap necrosis. Temporal observation of the skin flaps revealed a stasis-like discoloration and necrosis starting from the contralateral side of the remaining perforating branch. The control group did not exhibit flap necrosis, and the flap remained intact. In the quantitative assessment of endothelial glycans using lectins, intensity scoring showed that the eGCX in the db/db group was significantly thinner than that in the db/+ group. These results were consistent with the scanning electron microscopy findings. In contrast, treatment with nafamostat mesylate significantly improved the flap engraftment rate and suppressed eGCX injury. In conclusion, treatment with nafamostat mesylate improves the disrupted eGCX structure of skin flap tissue in db/db mice, potentially ameliorating the impaired capillary-to-venous return in the skin flap tissue.


Asunto(s)
Benzamidinas , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Guanidinas , Enfermedades Vasculares , Humanos , Ratones , Animales , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Experimental/tratamiento farmacológico , Glicocálix , Modelos Animales de Enfermedad , Ratones Endogámicos , Necrosis/tratamiento farmacológico
2.
Artículo en Inglés | MEDLINE | ID: mdl-38845460

RESUMEN

BACKGROUND AND AIM: Endoscopic ultrasound-guided gastroenterostomy is a procedure used to connect the stomach and dilated afferent loop using a stent under endoscopic ultrasound for afferent loop syndrome. However, the actual efficacy and safety of this procedure remain unclear. Therefore, this retrospective study aimed to evaluate the efficacy and safety of endoscopic ultrasound-guided gastroenterostomy using a laser-cut-type fully covered self-expandable metallic stent and an anchoring plastic stent for afferent loop syndrome. METHODS: Technical and clinical success rates, adverse events, recurrent intestinal obstruction rates, time to recurrent intestinal obstruction, and technical and clinical success rates of re-intervention were evaluated in intended patients who underwent endoscopic ultrasound-guided gastroenterostomy for afferent loop syndrome from October 2018 to August 2022. RESULTS: In 25 intended patients with afferent loop syndrome who intended endoscopic ultrasound-guided gastroenterostomy, the technical success rate was 100% (25/25), whereas the clinical success rate was 96% (24/25). Two patients experienced grade ≥ 3 early adverse events, including one with intra-abdominal abscess and one with hypotension. Both events were attributed to intestinal fluid leakage. No late adverse events were observed. The recurrent intestinal obstruction rate was 32% (8/25), and the median time to recurrent intestinal obstruction was 6.5 months (95% confidence interval: 2.8-not available). The technical and clinical success rates of re-intervention were both 100% (8/8). CONCLUSIONS: Endoscopic ultrasound-guided gastroenterostomy using a fully covered self-expandable metallic stent and an anchoring plastic stent is effective and safe as a treatment procedure for afferent loop syndrome.

3.
Artículo en Inglés | MEDLINE | ID: mdl-38421093

RESUMEN

BACKGROUND AND AIM: The 10-mm self-expandable metal stent (SEMS) is the standard for endoscopic transpapillary biliary drainage before pancreatic cancer surgery. However, the efficacy of stents thinner than 10 mm has not been adequately validated. Therefore, we aimed to evaluate the safety of a 6-mm fully covered SEMS (FCSEMS) for distal malignant biliary obstruction (DMBO) during preoperative chemotherapy for pancreatic cancer. METHODS: This was a single-arm, multicenter, prospective phase II study of endoscopic transpapillary initial biliary drainage for DMBO before pancreatic cancer surgery. The primary endpoint was stent-related adverse events, and the key secondary endpoint was the non-recurrent biliary obstruction (non-RBO) rate during the observation period for both resectable (R) and borderline resectable (BR) pancreatic cancers. RESULTS: The study enrolled 33 patients, among whom 32 received the study treatment. There were 23 and 9 cases of R and BR pancreatic cancers, respectively. The technical and clinical success rates were 97.0% and 90.1%, respectively. The stent-related adverse event rate was 3.1% (n = 1, acute pancreatitis) (95% confidential interval, 0.00-16.2), which met the criteria to be considered safe. The overall non-RBO rate during the observation period (median 96 days) was 78.1% (82.6% and 66.7% for R and BR pancreatic cancer cases, respectively). CONCLUSIONS: The 6-mm FCSEMS is an extremely safe metallic stent with a low stent-related adverse event rate of 3.1% for preoperative biliary drainage in pancreatic cancer. It is considered the optimal stent for preoperative biliary drainage in terms of the non-RBO rate. UMIN Clinical Trial Registry (UMIN-CTR 000041704).

4.
Exp Cell Res ; 431(1): 113740, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37557977

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is a type of steatosis not associated with excessive alcohol intake and includes nonalcoholic steatohepatitis (NASH), which can progress to advanced fibrosis and hepatocellular carcinoma. Mitochondrial dysfunction causes oxidative stress, triggering hepatocyte death and inflammation; therefore, the present study aimed to explore relationship between mitochondrial carriers and oxidative stress. Firstly, we established a high fat diet (HFD)-fed ICR mouse NAFLD model characterized by obesity with insulin resistance and found transcriptional upregulation of Slc25a17 and downregulation of Slc25a3 (isoform B) and Slc25a13 in their fatty liver. A mitochondrial phosphate and Cu carrier, SLC25A3, was further studied in wild-type (wt) and SLC25A3-defective HepG2 cells (C1 and C3). SLC25A3 deficiency had insignificant effect on mitochondrial membrane potential (MtMP) and oxygen consumption rate (OCR) in untreated cells but suppressed them when cells were exposed to oleic acid. C1 and C3 cells were prone to produce reactive oxygen species (ROS), and increased ROS was associated with reduced mRNA expression of glutathione peroxidase (GPX) 1 and glutathione disulfide reductase (GSX) in these cell lines. Interestingly, cytoplasmic and mitochondrial Cu accumulation significantly reduced in C1 cells, demonstrating a predominant contribution of SLC25A3 to Cu transport into mitochondrial matrix. Cytotoxicity of free fatty acids was unchanged between wt and SLC25A3-deficient cells. These results indicate that reduced expression of SLC25A3 in fatty liver contributes to electron leak from mitochondria by limiting Cu availability, rendering hepatocytes more susceptible to oxidative stress. This study provides evidence that SLC25A3 is a novel risk factor for developing NASH.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Hígado/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ratones Endogámicos ICR , Estrés Oxidativo , Mitocondrias/metabolismo , Proteínas de Transporte de Membrana Mitocondrial/metabolismo
5.
J Infect Chemother ; 30(2): 111-117, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37717607

RESUMEN

INTRODUCTION: This study aimed to determine the impact of augmented renal clearance (ARC) on anticoagulation therapy in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: This retrospective cohort study included adult patients with severe COVID-19 with ARC who had been treated at our hospital between 2020 and 2021. We measured the estimated glomerular filtration rate calculated by the Chronic Kidney Disease Epidemiology Collaboration formula (eGFRCKD-EPI) every morning, and ARC condition was defined as eGFRCKD-EPI ≥ 130 mL/min/1.73 m2. Multivariate regression analysis with Huber-White sandwich estimator was performed to examine the association of unfractionated heparin (UH) dosage between blood test timings with activated partial thromboplastin time (APTT) compared with and without ARC. RESULTS: We identified 38 enrolled patients: seven and 31 in the ARC and non-ARC groups, respectively. In the ARC coexisting condition, a higher dose of UH, which corresponded to the total dose in 24 h from the previous day, was required to achieve the same APTT prolongation, with a significant difference (p < 0.001). CONCLUSIONS: Our study suggests that careful monitoring and consideration of higher UH doses in critically ill patients with COVID-19 is necessary because anticoagulation failure can occur during ARC.


Asunto(s)
COVID-19 , Insuficiencia Renal Crónica , Adulto , Humanos , Heparina/uso terapéutico , Estudios Retrospectivos , Enfermedad Crítica , Insuficiencia Renal Crónica/inducido químicamente , Anticoagulantes/uso terapéutico , Creatinina
6.
Fetal Diagn Ther ; : 1-8, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38768565

RESUMEN

INTRODUCTION: Total anomalous pulmonary venous connection (TAPVC) has a low prenatal diagnostic rate. Therefore, we investigated whether Doppler waveforms with a low pulsatility in the pulmonary veins can indicate fetal TAPVC. METHODS: This retrospective study included 16 fetuses with TAPVC, including 10 with complex congenital heart disease and 104 healthy fetuses that underwent fetal echocardiography. Pulmonary venous S and D wave flow velocities and the valley (representing the lowest velocity between the S and D waves) were measured. Valley indices I and II were then calculated as (velocity of valley/greater of the S and D wave velocities) and (velocity of valley/lesser of the S and D wave velocities), respectively. RESULTS: Supra/infracardiac TAPVC cases exhibited significantly greater valley indices than that of the healthy group. After adjusting for gestational age at fetal echocardiography, valley indices I (odds ratio [OR] 7.26, p < 0.01) and II (OR: 9.23, p < 0.01) were significant predictors of supra/infracardiac TAPVC. Furthermore, valley indices I and II exhibited a high area under the curve for detecting supra/infracardiac TAPVC, regardless of the presence of pulmonary venous obstruction. CONCLUSION: The valley index may be a useful tool for the detection of fetal TAPVC.

7.
Pancreatology ; 23(8): 911-918, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37981522

RESUMEN

BACKGROUND/OBJECTIVE: Acute pancreatitis is an aseptic inflammation caused by pathologically activated pancreatic enzymes and inflammatory mediators produced secondarily by neutrophils and other inflammatory cells and is one of the most difficult diseases to treat. This study aimed to investigate the role of neutrophils in pancreatitis by examining tissue dynamics. METHODS: We created a model of caerulein-induced pancreatitis in 12-week-old male granulocyte colony-stimulating factor knockout mice (G-CSF-KO) and wild-type littermate control mice (six intraperitoneal injections of caerulein [80 µg/kg body weight] at hourly intervals for 2 days). Mice were sacrificed 0, 3, 6, 12, 24, 36, 48, 72, and 168 h after caerulein administration and examined histologically. RESULTS: The survival rate after one week of caerulein administration was 100 % in the control mice, whereas it was significantly lower (10 %) in the G-CSF-KO mice. Histological examination revealed significant hemorrhage and inflammatory cell migration in the G-CSF-KO mice, indicating prolonged inflammation. CONCLUSION: Prolonged inflammation was observed in the G-CSF-KO mice. Tissue cleanup by neutrophils during the acute phase of inflammation may influence healing through the chronic phase.


Asunto(s)
Pancreatitis , Ratones , Masculino , Animales , Pancreatitis/inducido químicamente , Pancreatitis/patología , Neutrófilos , Ceruletida/toxicidad , Enfermedad Aguda , Inflamación/patología , Ratones Noqueados , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Páncreas/patología , Modelos Animales de Enfermedad
8.
Dig Endosc ; 35(1): 124-133, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35993898

RESUMEN

OBJECTIVES: Comprehensive genomic profiling (CGP) has been approved in Japan since June 2019, enabling mutation-specific therapy. Although tissue sampling via endoscopic ultrasound-guided tissue acquisition (EUS-TA) is standard in pancreatic cancer, reports on obtaining appropriate samples for CGP, especially for the OncoGuide NCC Oncopanel System (NOP) and FoundationOne CDx (FOne), are lacking. Therefore, we investigated the success rate and factors related to appropriate EUS-TA sampling for CGP analysis suitability in unresectable pancreatic ductal adenocarcinoma (UR-PDAC). METHODS: Participants comprised 150 UR-PDAC patients who underwent EUS-TA and tumor sample evaluation for CGP analysis suitability between June 2019 and December 2021. The proportion of patients meeting the criteria was evaluated considering tumor size, puncture lesion, presence of metastasis, type and size of puncture needle, suction method, number of punctures, and puncture route. RESULTS: In total, 39.2% (60/153) of samples met NOP analysis suitability criteria and 0% met FOne analysis suitability criteria. The suitability rate was significantly higher with 19G fine-needle biopsy (FNB) (56.0%; 42/75) than with 22G FNB (32.6%; 14/43) and 22G fine-needle aspiration (11.4%; 4/35). Nineteen-gauge needle (odds ratio [OR] 2.53; 95% confidence interval [CI] 1.15-5.57; P = 0.021) and FNB (OR 3.57; 95% CI 1.05-12.20; P = 0.041) were independent factors contributing to NOP analysis suitability. Among 30 patients who underwent actual NOP analysis, the analysis success rate was 100% (30/30). CONCLUSION: In sample collection via EUS-TA, 19G and FNB needles contribute to NOP analysis suitability.


Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Páncreas/diagnóstico por imagen , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Adenocarcinoma/patología , Genómica , Neoplasias Pancreáticas
9.
Am J Pathol ; 191(9): 1526-1536, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34116023

RESUMEN

Sepsis-induced endothelial acute respiratory distress syndrome is related to microvascular endothelial dysfunction caused by endothelial glycocalyx disruption. Recently, recombinant antithrombin (rAT) was reported to protect the endothelial glycocalyx from septic vasculitis; however, the underlying mechanism remains unknown. Here, we investigated the effect of rAT administration on vascular endothelial injury under endotoxemia. Lipopolysaccharide (LPS; 20 mg/kg) was injected intraperitoneally into 10-week-old male C57BL/6 mice, and saline or rAT was administered intraperitoneally at 3 and 24 hours after LPS administration. Subsequently, serum and/or pulmonary tissues were examined for inflammation and cell proliferation and differentiation by histologic, ultrastructural, and microarray analyses. The survival rate was significantly higher in rAT-treated mice than in control mice 48 hours after LPS injection (75% versus 20%; P < 0.05). Serum interleukin-1ß was increased but to a lesser extent in response to LPS injection in rAT-treated mice than in control mice. Lectin staining and ultrastructural studies showed a notable attenuation of injury to the endothelial glycocalyx after rAT treatment. Microarray analysis further showed an up-regulation of gene sets corresponding to DNA repair, such as genes involved in DNA helicase activity, regulation of telomere maintenance, DNA-dependent ATPase activity, and ciliary plasm, after rAT treatment. Thus, rAT treatment may promote DNA repair, attenuate inflammation, and promote ciliogenesis, thereby attenuating the acute respiratory distress syndrome caused by endothelial injury.


Asunto(s)
Antitrombinas/farmacología , Endotelio Vascular/efectos de los fármacos , Endotoxemia/complicaciones , Pulmón/efectos de los fármacos , Síndrome de Dificultad Respiratoria , Animales , Modelos Animales de Enfermedad , Endotelio Vascular/patología , Glicocálix/efectos de los fármacos , Glicocálix/patología , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas Recombinantes/farmacología , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/metabolismo , Síndrome de Dificultad Respiratoria/fisiopatología
10.
Surg Endosc ; 36(12): 9001-9010, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35817882

RESUMEN

BACKGROUND: In recent years, the number of patients with hepaticojejunostomy anastomotic strictures has increased. Balloon dilation and placement of multiple plastic stents have proven effective for hepaticojejunostomy anastomotic strictures. However, for refractory strictures, there is often a need for repeated endoscopic procedures within a short period. This study aimed to assess the efficacy and safety of the new saddle-cross technique, which uses two fully covered self-expandable metallic stents. METHODS: This was a retrospective analysis of 20 patients with benign hepaticojejunostomy anastomotic strictures who underwent placement of two fully covered self-expandable metallic stents at the National Cancer Center, Japan, from November 2017 to June 2021. RESULTS: The technical and clinical success rates were 100% (20/20). The median time of the procedure was 61 (range 25-122) min. The scheduled stent removal rate was 70% (14/20). Spontaneous dislodgement of the stent was observed on computed tomography in five patients (25.0%). The non-restenosis rate 12 months after the saddle-cross technique was 88.2% (15/17). Procedure-related early adverse events included mild ascending cholangitis in three patients (15.0%) and sepsis in one patient (5.0%). Procedure-related late adverse events included mild ascending cholangitis in three patients (15.0%) and bile duct hyperplasia in one patient (5.0%). CONCLUSIONS: The saddle-cross technique performed using two fully covered self-expandable metallic stents resulted in promising long-term stricture resolution with a high technical success rate. Based on these findings, the saddle-cross method can be considered an option for the standard procedure for benign hepaticojejunostomy anastomotic strictures.


Asunto(s)
Colangitis , Stents Metálicos Autoexpandibles , Humanos , Constricción Patológica/etiología , Constricción Patológica/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Stents/efectos adversos , Colangitis/etiología , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos
11.
Heart Vessels ; 37(1): 142-151, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34089363

RESUMEN

Absent pulmonary valve (APV) syndrome with tricuspid atresia or tricuspid stenosis (TA/TS) is an extremely rare malformation recently reported as a variant of APV with intact ventricular septum (VS). The condition, however, has univentricular physiology and unique structural and clinical features. The purpose of this study was to update the current knowledge about this condition by describing long-term outcomes of three new cases and reviewing the available literatures. A systematic literature search was performed to collect clinical and anatomical data of APV with TA/TS. Institutional medical records were retrospectively reviewed to identify APV with TA/TS patients. In a total of 62 (59 reported and 3 new) cases, patent ductus arteriosus was present in 98% of APV patients with TA/TS. A large ventricular septal defect, dilatation of the pulmonary arteries, which is typically found in APV with tetralogy of Fallot, and respiratory distress at birth were rarely reported. Most of the recent cases were successfully managed by the Glenn or Fontan procedure. Coronary artery anomaly and ventricular arrhythmia were more frequently reported as the cause of death or severe neurological sequelae (9/16 and 3/8, respectively). Additional surgical intervention was required in the mid/long-term period in three cases due to left-ventricular outflow obstruction and in two due to aortic dilatation. The Fontan and Glenn procedures improved the survival in the last two decades. In addition to coronary artery anomaly and ventricular arrhythmia, left-ventricular outflow tract obstruction and aortic dilatation should be carefully monitored.


Asunto(s)
Válvula Pulmonar , Atresia Tricúspide , Constricción Patológica , Humanos , Atresia Pulmonar , Válvula Pulmonar/diagnóstico por imagen , Válvula Pulmonar/cirugía , Estudios Retrospectivos
12.
Echocardiography ; 39(2): 375-380, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34994012

RESUMEN

Abnormal pulmonary venous flow patterns on fetal echocardiography and a nutmeg lung pattern on fetal magnetic resonance imaging are seen in patients with pulmonary venous stenosis. The association between these findings and the degree of pulmonary venous stenosis remains unknown. We report an extremely rare case of a fetus diagnosed with hypoplastic left heart syndrome complicated by an absent atrial septum and supracardiac total anomalous pulmonary venous connection with left pulmonary venous congestion. This case suggests that compared to non-pulsatile continuous pulmonary venous flow, the nutmeg lung pattern can only be observed with severe pulmonary congestion and advanced pulmonary lymphangiectasia.


Asunto(s)
Tabique Interatrial , Síndrome del Corazón Izquierdo Hipoplásico , Venas Pulmonares , Síndrome de Cimitarra , Feto , Humanos , Síndrome del Corazón Izquierdo Hipoplásico/complicaciones , Síndrome del Corazón Izquierdo Hipoplásico/diagnóstico por imagen , Venas Pulmonares/anomalías , Síndrome de Cimitarra/complicaciones , Síndrome de Cimitarra/diagnóstico por imagen
13.
Echocardiography ; 39(8): 1142-1145, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35871719

RESUMEN

INTRODUCTION: Agenesis of the venous duct is rare, with an incidence rate of .04%-.6%. Abnormal drainage of the umbilical vein (UV) to superior vena cava (SVC) is seen in .5% of agenesis of the venous duct cases. We present a case of agenesis of the venous duct with drainage of the UV into the SVC accompanied by tetralogy of Fallot. CASE PRESENTATION: The fetus was diagnosed with agenesis of the venous duct and tetralogy of Fallot at 29 gestational weeks. The UV directly returned to the SVC. Cardiomegaly and pericardial effusion were observed but did not deteriorate. The female infant was born at 40 gestational weeks. Contrast-enhanced computed tomography showed that the UV was occluded at its proximal aspect. No abnormality of the portal system was noted. The infant underwent intracardiac repair and was doing well at 16 months of age. DISCUSSION/CONCLUSION: Although the extrahepatic drainage type of agenesis of the venous duct is occasionally associated with heart failure and hydrops, severe hydrops was absent in this case. It was speculated that vascular resistance in the long pathway to the SVC restricted direct inflow from the UV. Portosystemic shunts and agenesis of the portal system are reported complications of agenesis of the venous duct. Prenatal agenesis of the venous duct diagnosis may be crucial for early postnatal diagnosis of these conditions.


Asunto(s)
Tetralogía de Fallot , Vena Cava Superior , Edema , Femenino , Humanos , Embarazo , Ultrasonografía Prenatal , Venas Umbilicales
14.
Dig Endosc ; 34(3): 420-427, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34233051

RESUMEN

Autoimmune pancreatitis (AIP), which is characterized by pancreatic enlargement and irregular narrowing of the main pancreatic duct, is difficult to differentiate from malignancy. The irregular narrowing of the pancreatic duct, which can be detected via endoscopic retrograde cholangiopancreatography, is a characteristic feature of AIP; however, distinguishing between localized AIP and pancreatic cancer based on pancreatic duct imaging is difficult. This study overviews the efficacy of endoscopic ultrasound (EUS)-guided pancreatic sampling for the histopathological diagnosis of AIP. Recent enhancements in needle biopsy methodologies and technologies have contributed to improvement in the diagnostic efficacy of this technique. The guidance provided in this study for the histological diagnosis of AIP is anticipated to further advance in the histopathological diagnosis of AIP using EUS-guided pancreatic sampling.


Asunto(s)
Enfermedades Autoinmunes , Pancreatitis Autoinmune , Neoplasias Pancreáticas , Pancreatitis , Enfermedades Autoinmunes/diagnóstico por imagen , Pancreatitis Autoinmune/diagnóstico por imagen , Humanos , Páncreas/diagnóstico por imagen , Páncreas/patología , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Pancreatitis/diagnóstico por imagen , Ultrasonografía Intervencional
15.
J Pediatr ; 233: 169-174.e1, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33631169

RESUMEN

OBJECTIVES: To describe blood pressure (BP) responses during cardiopulmonary exercise testing (CPET) and propose criteria for abnormal BP responses in children with normal hearts. STUDY DESIGN: Treadmill CPET data of children <18 years with normal hearts were retrospectively analyzed to evaluate BP responses to exercise at the Children's Hospital of Michigan over an 8-year period (2011-2018). RESULTS: Our cohort included 1085 children (boys, 59%) aged 7-17 years. Analysis of variance for systolic BP at peak exercise (peak SBP) and SBP change (Δ) showed significant age and sex effects and age-sex interaction effects (P < .01). In the multiple linear regression model (P < .001, R square 0.298, standard error of the estimate 17.15), peak SBP (mm Hg) was predicted as 132.27 + 1.37 × age (years) + (3.31 × age (years) - 31.88) × sex [boys 1, girls 0]. The following criteria for abnormal BP responses in children were proposed: hypertensive BP response was defined by peak SBP with a 90% CI upper limit of reference values based on age and sex, and blunted BP response as ΔSBP <10 mm Hg for aged 7-11 years, <20 mm Hg for boys aged 12-17 years, and ΔSBP <10 mm Hg in girls. CONCLUSIONS: BP responses to treadmill CPET depend on age and sex in children with normal hearts. The proposed criteria for abnormal BP responses in children during CPET will need to be verified in a large pediatric cohort.


Asunto(s)
Presión Sanguínea/fisiología , Prueba de Esfuerzo , Adolescente , Factores de Edad , Niño , Femenino , Humanos , Hipertensión/diagnóstico , Modelos Lineales , Masculino , Valores de Referencia , Estudios Retrospectivos , Factores Sexuales
16.
Bioorg Med Chem ; 50: 116459, 2021 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-34700240

RESUMEN

An aromatic substituent has been introduced into a known hydroxyethylamine (HEA)-type BACE1 inhibitor containing the superior substrate sequence to enhance inhibitory activity. The HEA-type isosteres bearing different hydroxyl group and methyl group configurations were prepared through a branched synthesis approach using intra- and inter-molecular epoxide opening reactions. The effect of their configuration was evaluated, showing that an R-configuration improved the inhibitory activity, while introduction of a methyl group on the isostere decreased the activity. Based on the non-substituted isostere with an R-configuration, 21 derivatives containing various substituents at the P1' site were synthesized. Our evaluation of the derivatives showed that the structure of the P1' site had a clear effect on activity, and highly potent inhibitor 40g, which showed sub-micromolar activity against recombinant BACE1 (rBACE1), was identified. The docking simulation of 40g with rBACE1 suggested that a carboxymethyl group at the para-position of the P1' benzene ring interacted with Lys285 in the S1' pocket.


Asunto(s)
Inhibidores Enzimáticos/farmacología , Etilaminas/farmacología , Secretasas de la Proteína Precursora del Amiloide , Ácido Aspártico Endopeptidasas , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Etilaminas/síntesis química , Etilaminas/química , Humanos , Estructura Molecular , Proteínas Recombinantes , Relación Estructura-Actividad
17.
Heart Vessels ; 36(8): 1246-1255, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33590306

RESUMEN

Fenestration closure is considered to remove the persistent right-to-left shunt after the Fontan operation. However, the criteria for effective transcatheter closure of fenestration to avoid both acute and chronic Fontan failure have not been clarified. The objective of this study was to describe the hemodynamic data with test occlusion of the Fontan fenestration for patients who underwent a closure and those who did not, along with subsequent development of Fontan-associated diseases (FAD) at follow-up. This was a retrospective study conducted to assess the outcome of Fontan fenestration closure at Children's Hospital of Michigan over 27 years (1993-2019). The inclusion criteria were patients undergoing cardiac catheterization indicated for Fontan fenestration closure. Data were compared between the two groups: closure and non-closure patients. Baseline characteristics and hemodynamic variables with the fenestration occlusion test were analyzed. The primary outcome was the development of composite events of death/transplant, deteriorated New York Heart Association class symptoms, or FAD. Among the 38 patients who were brought to the catheterization laboratory, 33 received fenestration closure and 5 did not. On a median follow-up of 3.4 years (range, 1 month-12.6 years), the incidence of primary adverse outcomes was 13% (5/38). The incidence of primary outcome was significantly higher in the non-closure group (60% vs. 6%, p < 0.01). The non-closure group had a higher incidence of moderate or severe atrioventricular valve regurgitation, New York Heart Association class III symptoms, use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, furosemide use, and sildenafil use. The multivariable logistic regression model showed that the hemodynamic variables associated with the non-closure group were mean left atrial pressure (odds ratio 1.74, p < 0.05) and change of mean Fontan pressure at the balloon occlusion (odds ratio 2.2, p < 0.05). The judgment of fenestration closure appeared appropriate in our cohort. Fontan fenestration closure may not be advisable in cases with a high baseline left atrial pressure or a significant increase in Fontan pressure on balloon occlusion testing.


Asunto(s)
Procedimiento de Fontan , Cardiopatías Congénitas , Cateterismo Cardíaco , Flavina-Adenina Dinucleótido , Procedimiento de Fontan/efectos adversos , Cardiopatías Congénitas/cirugía , Hemodinámica , Humanos , Estudios Retrospectivos
18.
Echocardiography ; 38(10): 1809-1812, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34510535

RESUMEN

A congenital left atrial appendage aneurysm (LAAA) is a rare cardiac malformation, that is, usually diagnosed in adulthood. It is rarely diagnosed prenatally. In most cases, surgical resection is recommended soon after the diagnosis has been made due to the risk of arrhythmia and thrombotic events. The present report describes a case of LAAA that was prenatally diagnosed and was asymptomatic postnatally. Imaging revealed the relation of the cardiac and airway structures around the LAAA in detail. The patient underwent surgical resection of the LAAA successfully at 7 months of age and is currently healthy at 5 years of age.


Asunto(s)
Apéndice Atrial , Aneurisma Cardíaco , Cardiopatías Congénitas , Adulto , Apéndice Atrial/diagnóstico por imagen , Ecocardiografía , Aneurisma Cardíaco/diagnóstico por imagen , Aneurisma Cardíaco/cirugía , Humanos , Tomografía Computarizada por Rayos X
19.
Cardiol Young ; 31(2): 300-302, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33140713

RESUMEN

Total anomalous pulmonary venous connection is a rare congenital heart defect. We report an infant with a mixed form of supracardiac TAPVC, in whom all pulmonary veins, except the right upper, entered a pulmonary venous confluence that is connected to a vertical vein and drained into the superior vena caval-right atrial junction. Several segmental right upper pulmonary veins entered the superior vena cava, superior to the entry of the vertical vein. Surgical repair consisted of the Warden procedure combined with direct anastomosis of the vertical vein to the left atrium. Separate pulmonary venous drainage pathways decreased the risk of post-operative pulmonary venous obstruction. Our patient had an uneventful post-operative course and encouraging 2-month follow-up echocardiography. Careful follow-up is warranted to detect post-operative complications, including obstruction of the pulmonary venous and cavoatrial anastomoses.


Asunto(s)
Cardiopatías Congénitas , Venas Pulmonares , Síndrome de Cimitarra , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/cirugía , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/cirugía , Humanos , Lactante , Venas Pulmonares/diagnóstico por imagen , Venas Pulmonares/cirugía , Síndrome de Cimitarra/diagnóstico por imagen , Síndrome de Cimitarra/cirugía , Vena Cava Superior/diagnóstico por imagen , Vena Cava Superior/cirugía
20.
Arch Psychiatr Nurs ; 35(4): 341-346, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34176574

RESUMEN

This study clarifies the association between postpartum depression (PPD) and satisfaction with social support after childbirth through an anonymous survey of 427 postpartum mothers. Mothers' PPD was found to be significantly associated with satisfaction levels regarding formal-instrumental support (OR: 0.32, 95% CI: 0.162-0.632), informal-instrumental support (OR: 0.547, 95% CI: 0.313-0.955), and informal-psychological support (OR: 0.591, 95% CI: 0.384-0.912) in a multivariate logistic regression analysis. To prevent PPD, specialists as formal support providers must provide qualified care based on comprehensive judgments, and families as informal support providers should help with childcare, housework, and mental support.


Asunto(s)
Depresión Posparto , Femenino , Humanos , Madres , Parto , Satisfacción Personal , Periodo Posparto , Embarazo , Factores de Riesgo , Apoyo Social
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