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BACKGROUND: Laser hemorrhoidoplasty has demonstrated significant therapeutic effectiveness. To diminish postoperative bleeding and enhance overall outcomes, we have additionally adopted suture ligating the feeding vessels. This study aimed to understand the treatment outcomes and any associated complications. METHODS: This study comprised patients with symptomatic grade II-III hemorrhoids who underwent laser hemorrhoidoplasty with feeding vessel suture ligation and Milligan-Morgan hemorrhoidectomy between 1 September 2020, and 31 August 2022. Surgical-related details, postoperative pain, discomfort after discharge, hemorrhoid recurrence, and any complications were collected from inpatient records, outpatient follow-ups, and telephone interviews. Initially, we will analyze the distinctions between the laser group and the traditional group, followed by an investigation into complications and satisfaction within the laser surgery subgroup. RESULTS: The study included 323 patients, with 173 undergoing laser hemorrhoidoplasty (LHP) and 150 undergoing Milligan-Morgan hemorrhoidectomy. Regarding pain assessment, the LHP group exhibited superior performance compared to traditional surgery at postoperative 4 h, before discharge, and during the first and second outpatient visits, with statistically significant differences. Additionally, the LHP group had a lower rate of urinary retention and experienced significantly less pain, with statistically significant differences. CONCLUSIONS: Laser hemorrhoidoplasty with feeding vessels suture ligation has been shown to reduce postoperative pain and appears to be a promising minimally invasive treatment option for symptomatic grade II and III hemorrhoids.
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Hemorroidectomia , Hemorroidas , Terapia a Laser , Dor Pós-Operatória , Técnicas de Sutura , Humanos , Hemorroidas/cirurgia , Ligadura/métodos , Feminino , Estudos Retrospectivos , Masculino , Hemorroidectomia/métodos , Hemorroidectomia/efeitos adversos , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto , Dor Pós-Operatória/etiologia , Terapia a Laser/métodos , Idoso , Recidiva , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Satisfação do Paciente , SuturasRESUMO
OBJECTIVE: To investigate the role of human serum albumin (hsa)_circular (circ)_0000711 in hepatocellular carcinoma (HCC). Circular ribonucleic acids (circRNAs) are proven in numerous studies to play crucial role in tumor biology, but their roles in HCC remain unknown to a great extent. PATIENTS AND METHODS: The circRNA expression profile microarray was employed to screen differentially expressed circRNAs in tumor tissues and adjacent tissues from HCC patients, and Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) assay was performed for further verification. Next, the target micro RNAs (miRNAs) and their messenger RNAs (mRNAs) of key circRNAs were predicted by bioinformatics software, and a circRNA-miRNA-mRNA regulatory network was constructed. Subsequently, KEGG and GO enrichment analyses were applied to predict the possible biological processes regulated by hsa_circ_0000711 and relevant signaling pathways. The miRNAs playing a key role in the circRNA-miRNA-mRNA regulatory network were then selected as the objects, and their direct binding to hsa_circ_0000711 was confirmed via luciferase reporter gene assay. Thereafter, hsa_circ_0000711 was overexpressed or knocked out, and the biological function of hsa_circ_0000711 was detected by cell counting kit-8 (CCK-8) assay, apoptosis detection, and 5-Ethynyl-2'-deoxyuridine (EdU) staining assay in vitro. RESULTS: The results of expression profile screening revealed that there was a significant difference in the expression profile of circRNAs between tumor tissues and adjacent tissues in HCC patients. Based on the circRNA expression profile and RT-qPCR results, the expression level of hsa_circ_0000711 was overtly reduced in HCC tissues. In addition, miR-103a-3p had the highest eigenvector centrality in the circRNA-miRNA-mRNA regulatory network, suggesting that miR-103a-3p is a vital participant in the pathological mechanism of hsa_circ_0000711. The KEGG enrichment analysis results pointed out that the target genes regulated by hsa_circ_0000711 were clearly enriched in the tumor-associated signaling pathways. Besides, the results of GO enrichment analysis demonstrated that the biological processes regulated by hsa_circ_0000711 were mainly related to cell cycle regulation, so cell proliferation might be affected. The results of luciferase reporter gene and RT-qPCR assays showed that hsa_circ_0000711 directly bound to has-miR-103a-3p to serve as a molecular sponge. The results of CCK-8 and EdU staining assays revealed that the proliferation of hepatoma cells in hsa_circ_0000711 overexpression group was evidently enhanced. In addition, it was further found via flow cytometry that the apoptosis rate of cells was significantly raised in hsa_circ_0000711 low-expression group and dramatically declined in hsa_circ_0000711 overexpression group. CONCLUSIONS: Overexpression of hsa_circ_0000711 promoted the proliferation and inhibited the apoptosis of hepatoma cells via targeting has-miR-103a-3p.
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Apoptose , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , RNA Circular/genética , Proliferação de Células , Humanos , RNA Circular/metabolismo , Células Tumorais CultivadasRESUMO
The effective treatment for hepatocellular carcinoma (HCC) with American Joint Committee on Cancer stage IIIB remains controversial and challenging because of the high recurrence rate after resection and low survival rate. The median survival of those with macroscopic portal vein tumor thrombus (PVTT) is short. We reported such a case which received liver transplantation (LT) after successful consecutive downstaging therapies. A 40-year-old man with alcohol related liver cirrhosis and repeated esophageal varices bleeding had HCC with tumor thrombi in right main portal vein and the second portal branch of segment VI (stage IIIB). The received percutaneous alcohol injection, radiofrequency ablation, 8 sessions of transcatheter hepatic arterial chemoembolization, radiotherapy, and target therapy with sorafenib. Computed tomography (CT) scan and magnetic resonance imaging after treatments showed no viable fragments in the tumor and revealed both the right main portal vein and V1 branch were patent. One month later, the patient received a deceased LT. The perioperative course was rather smooth. After discharge, the interval follow-up CT studies of the chest and liver and whole body bone scan showed no tumor recurrence or metastasis up to 20 months postoperation.
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Carcinoma Hepatocelular/terapia , Terapia Combinada/métodos , Neoplasias Hepáticas/terapia , Transplante de Fígado/métodos , Adulto , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Veia Porta/patologia , Trombose/patologia , Resultado do Tratamento , Estados UnidosRESUMO
INTRODUCTION: The glenoid track concept was used to confirm the engaging Hill-Sachs lesion (HSL) as a risk factor for recurrent instability following arthroscopic Bankart repair (ABR). However, the post-operative condition of soft tissue in vivo was not comparable to that designed in the intact condition in vitro in the original study of the glenoid track concept. Herein, the possibility of engagement may be underestimated. HYPOTHESIS: A threshold of the Hill-Sachs interval to glenoid track width ratio (H/G ratio) that is related to recurrent instability after ABR could be found, in order to adjust the original glenoid track concept. PATIENTS AND METHODS: Patients who underwent ABR with minimum 24-months follow-up were reviewed retrospectively. The primary outcome was evaluated with the recurrent instability. The H/G ratio of individual patients was used to calculate the sensitivity, specificity, and a receiver operating characteristic (ROC) curve, which aimed to establish a H/G ratio threshold related to recurrent instability after ABR. RESULTS: From June 2005 to December 2013, 160 patients with a mean age of 27.7years were enrolled. The mean follow-up period was 77.2 months. The ROC curve indicated that H/G ratio≥0.7 had the sensitivity and specificity of 0.74 and 0.71, respectively, in predicting recurrent instability. On univariate logistic regression analysis, the H/G ratio≥0.7 was a significant predictor of higher risk for recurrent instability (p<0.001). DISCUSSION: H/G ratio seems to be a reliable parameter for predicting recurrent instability. H/G ratio≥0.7 may be considered as a positive predictor for recurrent instability after ABR. LEVEL OF EVIDENCE: Level IV: retrospective diagnostic study.
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Lesões de Bankart/diagnóstico por imagem , Lesões de Bankart/cirurgia , Cavidade Glenoide/diagnóstico por imagem , Instabilidade Articular/cirurgia , Articulação do Ombro/cirurgia , Adolescente , Adulto , Artroscopia , Lesões de Bankart/complicações , Feminino , Seguimentos , Humanos , Instabilidade Articular/etiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Curva ROC , Radiografia , Recidiva , Estudos Retrospectivos , Adulto JovemRESUMO
Harnessing the spin-momentum locking of topological surface states in conjunction with magnetic materials is the first step to realize novel topological insulator-based devices. Here, we report strong interfacial coupling in Bi2Se3/yttrium iron garnet (YIG) bilayers manifested as large interfacial in-plane magnetic anisotropy (IMA) and enhancement of damping probed by ferromagnetic resonance. The interfacial IMA and damping enhancement reaches a maximum when the Bi2Se3 film approaches its two-dimensional limit, indicating that topological surface states play an important role in the magnetization dynamics of YIG. Temperature-dependent ferromagnetic resonance of Bi2Se3/YIG reveals signatures of the magnetic proximity effect of TC as high as 180 K, an emerging low-temperature perpendicular magnetic anisotropy competing the high-temperature IMA, and an increasing exchange effective field of YIG steadily increasing toward low temperature. Our study sheds light on the effects of topological insulators on magnetization dynamics, essential for the development of topological insulator-based spintronic devices.
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Current clinical outcomes using chimeric-antigen receptors (CARs) against multiple myeloma show promise in the eradication of bulk disease. However, these anti-BCMA (CD269) CARs observe relapse as a common phenomenon after treatment due to the reemergence of either antigen-positive or -negative cells. Hence, the development of improvements in CAR design to target antigen loss and increase effector cell persistency represents a critical need. Here, we report on the anti-tumor activity of a CAR T-cell possessing two complete and independent CAR receptors against the multiple myeloma antigens BCMA and CS1. We determined that the resulting compound CAR (cCAR) T-cell possesses consistent, potent and directed cytotoxicity against each target antigen population. Using multiple mouse models of myeloma and mixed cell populations, we are further able to show superior in vivo survival by directed cytotoxicity against multiple populations compared to a single-expressing CAR T-cell. These findings indicate that compound targeting of BCMA and CS1 on myeloma cells can potentially be an effective strategy for augmenting the response against myeloma bulk disease and for initiation of broader coverage CAR therapy.
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Mieloma Múltiplo/imunologia , Receptores de Antígenos Quiméricos/imunologia , Animais , Antígeno de Maturação de Linfócitos B/imunologia , Linhagem Celular Tumoral , Citotoxicidade Imunológica/imunologia , Humanos , Células K562 , Masculino , Camundongos , Camundongos Endogâmicos NOD , Recidiva Local de Neoplasia/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Família de Moléculas de Sinalização da Ativação Linfocitária/imunologia , Linfócitos T/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
The outlook for T-cell malignancies remain poor due to the lack of effective therapeutic options. Chimeric antigen receptor (CAR) immunotherapy has recently shown promise in clinical trials for B-cell malignancies, however, designing CARs for T-cell based disease remain a challenge due to the shared surface antigen pool between normal and malignant T-cells. Normal T-cells express CD5 but NK (natural killer) cells do not, positioning NK cells as attractive cytotoxicity cells for CD5CAR design. Additionally, CD5 is highly expressed in T-cell acute lymphoblastic leukemia (T-ALL) and peripheral T-cell lymphomas (PTCLs). Here, we report a robust anti-CD5 CAR (CD5CAR) transduced into a human NK cell line NK-92 that can undergo stable expansion ex vivo. We found that CD5CAR NK-92 cells possessed consistent, specific, and potent anti-tumor activity against a variety of T-cell leukemia and lymphoma cell lines as well as primary tumor cells. Furthermore, we were able to demonstrate significant inhibition and control of disease progression in xenograft mouse models of T-ALL. The data suggest that CAR redirected targeting for T-cell malignancies using NK cells may be a viable method for new and complementary therapeutic approaches that could improve the current outcome for patients.
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Antígenos de Neoplasias/imunologia , Antígenos CD5/imunologia , Imunoterapia Adotiva/métodos , Células Matadoras Naturais/imunologia , Linfoma de Células T Periférico/terapia , Terapia de Alvo Molecular , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Proteínas Recombinantes de Fusão/imunologia , Ligante 4-1BB/genética , Ligante 4-1BB/imunologia , Animais , Antígenos CD28/imunologia , Complexo CD3/genética , Complexo CD3/imunologia , Antígenos CD8/imunologia , Linhagem Celular Tumoral , Técnicas de Cocultura , Citotoxicidade Imunológica , Humanos , Células Matadoras Naturais/transplante , Linfoma de Células T Periférico/patologia , Camundongos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Terapia de Salvação , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/imunologia , Transdução Genética , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Living donor liver transplantation may put the donor at risk of physical and psychological impacts. Recovery of physical and psychological function as well as quality of life (QOL) in living liver donors warrants investigation. OBJECTIVES: This study aims to examine the recovery of liver function, emotional status, and QOL in living liver donors through a comparison with the general population and reference values. METHODS: This descriptive, comparative study included 97 living liver donors who underwent surgery from 2008 to 2012 and were divided into 4 groups according to their postoperative period (1 year [n = 31], 2 years [n = 31], 3 years [n = 21], and 4 years above [n = 14]). Data were collected retrospectively in a medical center in northern Taiwan. RESULTS: The mean aspartate aminotransferase level was 20.2-32.1 U/L, the mean alanine aminotransferase level was 14.7-33.5 U/L, and the mean total bilirubin level was 10.8-15.5 µmol/L among the 4 groups. Among donors of the 4 groups, 23.8%-51.6% and 0%-29% were defined as having a mild level of anxiety and depression, respectively. Donors in the 1- and 2-year groups had poorer QOL in the physical function, role physical, vitality, and mental health domains than did the general population of Taiwan (P < .05). CONCLUSIONS: Liver function was at normal levels in all 4 groups. The emotional and psychological function of living liver donors should be monitored and health-related QOL should be promoted during the first and second year after liver donation.
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Emoções , Transplante de Fígado/psicologia , Fígado/fisiologia , Doadores Vivos/psicologia , Qualidade de Vida , Adulto , Ansiedade/psicologia , Depressão/psicologia , Feminino , Humanos , Masculino , Saúde Mental , Recuperação de Função Fisiológica/fisiologia , Estudos Retrospectivos , Taiwan , Fatores de TempoRESUMO
BACKGROUND: Hepatic artery pseudoaneurysm (PA) after liver transplantation (LT) is a rare but potentially fatal complication. Among a series of 50 patients of LT, we experienced 3 such cases. Some authors also have reported cases of PA, either intrahepatic or extrahepatic. The aim of this study was to investigate the important factors that affect the treatment outcome. METHODS: Three patients were presented. To analyze the factors, not only our patients but also the patients with PA reported in the literature (including 10 case series and 23 case reports) were enrolled for analysis. The possible factors probably affecting the survival were compared statistically, including age, sex, clinical manifestation as bleeding (including gastrointestinal bleeding, hemobilia, or intra-abdominal bleeding), treatment (with embolization or surgical exploration or stent), diagnosis establishment before or after bleeding, and so forth. RESULTS: From univariate analysis, the significant factors that affect survival are sex (female) (P = .036), stent treatment (P = .006), and early detection (P = .036), whereas age (P = .493) and presentation with hemorrhage (P = .877) are not significant factors. However, according to multivariate analysis, stent treatment has a borderline significance (P = .056). CONCLUSIONS: Early detection of such a life-threatening complication is a key determinant of survival. "Early" does not refer to early postoperative days but means the detection prior to the rupture of the pseudoaneurysm. Postoperative imaging studies such as computed tomographic scan or magnetic resonance cholangiopancreatography early and periodically to follow up the graft status is recommended, especially for those who had received other interventions before or after the liver transplantation.
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Falso Aneurisma/diagnóstico por imagem , Diagnóstico Precoce , Artéria Hepática/diagnóstico por imagem , Transplante de Fígado , Complicações Pós-Operatórias/diagnóstico , Adulto , Idoso , Falso Aneurisma/complicações , Falso Aneurisma/mortalidade , Falso Aneurisma/terapia , Angiografia por Tomografia Computadorizada , Embolização Terapêutica , Hemorragia Gastrointestinal/etiologia , Hemobilia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/terapia , Stents , Taxa de Sobrevida , Resultado do Tratamento , Procedimentos Cirúrgicos VascularesRESUMO
BACKGROUND: Living-donor kidney transplantation has a positive influence on recipients' life expectancy and improves quality of life for patients with end-stage renal disease compared with dialysis patients. Evaluation of the physical and mental quality of life for donors can promote positive perceptions about donation and help potential donors in their decision-making process. The aim of this study was to explore the predictive factors of quality of life for living kidney donors. METHODS: A cross-sectional and descriptive design was used, and the study was conducted from January to July 2013. The donors were a convenience sample of 34 participants who had undergone kidney transplant surgery >1 year earlier. RESULTS: The results showed that kidney donors had a low to moderate physical and mental quality of life. Multiple regression analysis revealed that financial concerns and anxiety explained 27.8% of the total variance of quality of life in the physical component. Anxiety and paid work explained 61.4% of the total variance of quality of life in the mental component. CONCLUSIONS: After renal transplantation, living kidney donors experienced low to moderate quality of life. Because donors are family members (siblings, sons or daughters, spouses, or parents), monthly family income is a significant issue that influences both the decision to donate and quality of life after transplantation. Our findings suggest that pre-transplantation assessment must include social workers as part of the health care team to evaluate the impact of a donor's financial status on post-transplantation quality of life.
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Doadores Vivos/psicologia , Qualidade de Vida , Ansiedade , Estudos Transversais , Feminino , Humanos , Renda , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Taiwan , TrabalhoRESUMO
Esophagitis is the second most common gastrointestinal manifestation of cytomegalovirus (CMV) infection after colitis. CMV esophagitis has been reported in patients who have undergone transplantation, are on long-term renal dialysis, or who have the human immunodeficiency virus infection. This study aimed to investigate the clinical characteristics and manifestations of CMV esophagitis in patients who underwent diagnostic endoscopy. A total of 16 patients with histologically proven CMV infection were identified from 1539 patients with esophageal ulcers and analyzed retrospectively (January 2006 to December 2013). Patients' personal data (age, smoking, and alcohol consumption), underlying systemic diseases (diabetes mellitus, end-stage renal disease, and chronic obstructive pulmonary disease), malignancy, indication for esophagogastroduodenoscopy, endoscopic characteristics, and diagnostic methods (pathological or serological findings) were collected for further analysis. Among the patients with CMV esophagitis, the mean age was 59.94 years (range, 23-84 years). The male : female ratio was 1.67:1. Odynophagia and epigastralgia were common symptoms. Of the 16 patients, 3 (18.75%) were infected with the human immunodeficiency virus and 9 (56.25%) had an underlying malignancy, including lung cancer (6 patients), esophageal cancer (2 patients), gastric cancer (1 patient), ampulla of Vater cancer (1 patient), and lymphoma (1 patient). Six of the 9 patients (66.7%) with malignancy had been administered concurrent chemoradiotherapy (CCRT). In this study, patients with malignancy who had been administered CCRT were at increased risk for CMV esophagitis, which had not been reported before in the literature. CMV esophagitis should be considered as a potential treatment-related complication of CCRT.
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Quimiorradioterapia/efeitos adversos , Infecções por Citomegalovirus , Esofagite , Infecções por HIV/epidemiologia , Neoplasias , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/fisiopatologia , Endoscopia do Sistema Digestório/métodos , Esofagite/diagnóstico , Esofagite/epidemiologia , Esofagite/fisiopatologia , Esofagite/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/terapia , Estudos Retrospectivos , Fatores de Risco , Avaliação de Sintomas/métodos , Taiwan/epidemiologiaRESUMO
BACKGROUND: Intrahepatic segmental portal vein thrombosis after living-related liver transplantation (LRLT) is uncommon. The cause remains unclear. METHODS: After providing written informed consent, 25 recipients receiving LRLT at our institution from January 2011 to September 2013 were enrolled in this study. We performed triphase computerized tomographic (CT) study of the liver graft of each recipient 1 month after LRLT. The patencies of hepatic artery, portal vein, and hepatic vein were evaluated in detail. The triphase CT scans of the liver of each donor before transplantation also were reviewed. Thrombosis of the intrahepatic segmental portal vein was defined as the occlusion site of the portal vein being intrahepatic. Extrahepatic portal vein thrombosis was excluded in this study. RESULTS: Among the 25 patients, 2 (8%) developed thrombosis of intrahepatic segmental portal vein. One 47-year-old man received LRLT for hepatitis B viral infection-related liver cirrhosis (Child-Pugh class C) with 3 hepatocellular carcinomas (total tumor volume <8 cm). Another 53-year-old man received LRLT for alcoholic liver cirrhosis (Child-Pugh class C). Both had developed progressive jaundice and cholangitis 1 month after surgery. Intrahepatic biliary stricture was found on the follow-up magnetic resonance images. However, liver triphase CT study demonstrated occlusion of intrahepatic portal vein of segment 8 in each patient. Radiologic interventions and balloon dilatation therapy via percutaneous transhepatic biliary drainage route improved the symptoms and signs of cholangitis and obstructive jaundice for both. CONCLUSIONS: Thrombosis of intrahepatic segmental portal vein is not common but is usually associated with complications of intrahepatic bile duct. Early detection is important, and follow-up CT study of liver is suggested.
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Transplante de Fígado/efeitos adversos , Doadores Vivos , Veia Porta/patologia , Trombose/etiologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Early detection of Budd-Chiari syndrome (BCS) to give the appropriate therapy in time is crucial. Angiography remains the golden standard to diagnose BCS. However, to establish the diagnosis of BCS in complicated cirrhotic patients remains a challenge. We used maximum intensity projection (Max IP) and minimum intensity projection (Min IP) from computed tomographic (CT) images to detect this syndrome in such a patient. CASE REPORT: A 55-year-old man with a history of chronic hepatitis B infection and alcoholism had undergone previously a left lateral segmentectomy for hepatic epitheloid angiomyolipoma (4.6 × 3.5 × 3.3 cm) with a concomitant splenectomy. Liver decompensation with intractable ascites and jaundice occurred 4 months later. The reformed images of the venous phase of enhanced CT images with Max IP and Min IP showed middle hepatic vein thrombosis. He then underwent a living-related donor liver transplantation with a right liver graft from his daughter. Intraoperatively, we noted thrombosis of his middle hepatic vein protruding into inferior vena cava. The postoperative course was unevenful. Microscopic findings revealed micronodular cirrhosis with mixed inflammation in the portal areas. Some liver lobules exhibited congestion and sinusoidal dilation compatible with venous occlusion clinically. CONCLUSIONS: We recommend Max IP and Min IP of CT images as simple and effective techniques to establish the diagnosis of BCS, especially in complicated cirrhotic patients, thereby avoiding invasive interventional procedures.
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Síndrome de Budd-Chiari/diagnóstico , Cirrose Hepática/complicações , Síndrome de Budd-Chiari/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: Hypoxic pulmonary vasoconstriction (HPV) is a well known phenomenon to temporarily offset a ventilation-perfusion mismatch. Sustained HPV may lead to pulmonary hypertension. In this protocol, we studied the relationships between the HPV response and inducible cyclooxygenase II (COX II) activation after hypoxia-reoxygenation (H-R) challenge in an isolated perfused lung model. METHODS: An in situ isolated perfused rat lung model underwent inaction of hypoxia by ventilation with 5% CO(2)-95% N(2) for 10 minutes instead of 5% CO(2)-95% air; they were then reoxygenated with 5% CO(2)-95% air. We measured pulmonary arterial pressure (PAP) changes before, during, and after H-R challenge. We also estimated changes in blood concentrations of hydroxyl radicals, nitric oxide (NO) and thromboxane B(2) (TxB(2)) before and after H-R as well as mRNA expressions of COX II in lung tissue thereafter. A COX II inhibitor, celecoxib (10 mg/kg), was administered between 2 consecutive challenges. RESULTS: Hypoxia induced pulmonary vasoconstriction by increasing PAP (4.1 ± 0.8 mm Hg). Consecutive hypoxic challenges did not show tachyphylaxis (P > .05). H-R of lung tissues induced significant increases in blood concentrations of hydroxyl radicals (48.5 ± 7.6 vs 75.8 ± 11.5 mmol/L; P < .01), NO (54.3 ± 12.3 vs 77.7 ± 15.7 pmol; P < .05), and TxB(2) (42.3 ± 6.9 vs 58.7 ± 8.6 pg/mL; P < .05). Lung tissue H-R also significantly increased COX II mRNA expression compared with sham tissues (1 ± 0 vs 4.0 ± 2.8; P < .001). The COX II inhibitor celecoxib significantly attenuated HPV responses (P < .05) and attenuated the elevated blood concentrations of TxB(2) (P < .05), hydroxyl radicals (P < .01), nitric oxide (P < .05), and COX II mRNA expression (P < .05) after H-R challenge. CONCLUSIONS: Lung tissue H-R induced significant increases blood concentrations of inflammatory mediators and tissue mRNA expression of COX related to elevation of HPV responses. COX II inhibitor celecoxib attenuated the HPV responses by reducing TxB(2) release.
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Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/metabolismo , Hipóxia/tratamento farmacológico , Artéria Pulmonar/efeitos dos fármacos , Pirazóis/farmacologia , Sulfonamidas/farmacologia , Vasoconstrição/efeitos dos fármacos , Animais , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Celecoxib , Ciclo-Oxigenase 2/genética , Modelos Animais de Doenças , Radical Hidroxila/sangue , Hipóxia/sangue , Hipóxia/enzimologia , Hipóxia/fisiopatologia , Mediadores da Inflamação/sangue , Óxido Nítrico/sangue , Estresse Oxidativo/efeitos dos fármacos , Perfusão , Artéria Pulmonar/enzimologia , Artéria Pulmonar/fisiopatologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Tromboxano B2/sangue , Fatores de TempoRESUMO
OBJECTIVE: Reactive oxygen species generated during liver reperfusion have been implicated in remote lung injury. In this study, we evaluate the protective effects of melatonin pretreatment against the increased pulmonary microvascular permeability. METHODS: Male Sprague-Dawley rats were divided into three groups: shame-operated, liver ischemia-reperfusion (I/R), and melatonin pretreated (15 mg/kg, intraperitoneally) 15 minutes prior to the liver I/R). The duration of ischemia was 30 minutes, followed by 2 hours of reperfusion. Lungs were isolated in situ and parameters of the capillary filtration coefficient (K(fc)), lung wet-to-dry weight ratio (W/D), lung weight-to-body weight (LW/BW), and protein concentration in bronchial lavage fluid (PCBAL), the percentage of macrophages and neutrophils in bronchial lavage fluid (BALF), and lung tissue malonedealdehyde were used to assess the lung injury. RESULTS: Liver I/R-induced lung injury was noted by the markedly increased K(fc), W/D, LW/BW, PCBAL, and the presence of neutrophils and macrophages in BALF. Lipid peroxidation was also increased (P < .05). All indicators were markedly decreased in melatonin-pretreated rats (P < .05), suggesting that lung injury was attenuated. CONCLUSIONS: Melatonin pretreatment prior to liver I/R can effectively reduce the pulmonary microvascular permeability and attenuate lipid peroxidation in the lungs.
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Lesão Pulmonar Aguda/prevenção & controle , Antioxidantes/farmacologia , Hepatopatias/tratamento farmacológico , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Melatonina/farmacologia , Microvasos/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Permeabilidade Capilar/efeitos dos fármacos , Citoproteção , Modelos Animais de Doenças , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Hepatopatias/complicações , Hepatopatias/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Malondialdeído/metabolismo , Microvasos/metabolismo , Microvasos/patologia , Infiltração de Neutrófilos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Edema Pulmonar/etiologia , Edema Pulmonar/prevenção & controle , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/metabolismoRESUMO
BACKGROUND: Toll-like receptor (TLR) 9 is the pattern recognition receptor for microbial DNA. Genetic variation within pattern recognition receptors for bacterial endotoxin and exotoxin has been shown to be associated with the risk of sepsis and organ dysfunction in critical illness. However, little is known about the clinical relevance of TLR9 gene polymorphisms in critical illness. METHODS: A total of 557 patients with major blunt trauma were included in the study. Genetic variation data for the entire TLR9 gene were obtained from the HapMap Project. The genotypes of TLR9 gene polymorphisms were determined using a pyrosequencing method. Whole peripheral blood samples obtained immediately after admission were stimulated with bacterial DNA and production of tumour necrosis factor (TNF) α was then determined. Sepsis morbidity rate and multiple organ dysfunction (MOD) scores were assessed. RESULTS: Of five single-nucleotide polymorphisms (SNPs) genotyped, four (rs187084, rs352139, rs352140 and rs352162) existed as common SNPs and were in strong linkage disequilibrium. Both rs187084 and rs352162 were significantly associated with TNF-α production by peripheral blood leucocytes in response to bacterial DNA stimulation and a higher sepsis morbidity rate in patients with major trauma. In addition, the rs352162 polymorphism was significantly associated with MOD scores, whereas rs187084 showed a trend to be associated with MOD score. CONCLUSION: TLR9 polymorphisms rs187084 and rs352162 might be used to provide relevant risk estimates for the development of sepsis and MOD in patients with major trauma.
Assuntos
Insuficiência de Múltiplos Órgãos/genética , Polimorfismo de Nucleotídeo Único/genética , Sepse/genética , Receptor Toll-Like 9/genética , Ferimentos não Penetrantes/genética , Adulto , Idoso , Feminino , Frequência do Gene , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/metabolismo , Adulto JovemRESUMO
OBJECTIVES: To explore the relationship between preterm placental calcification and adverse pregnancy outcome, including maternal and fetal outcomes. METHODS: In this prospective cohort study, monthly ultrasonography was performed starting at 28 weeks' gestation to establish the diagnosis of Grade III placental calcification. Women were classified into three groups: Group 1, the early preterm group, with placental calcification found prior to 32 weeks (n = 63); Group 2, the late preterm group, with placental calcification found between 32 and 36 weeks (n = 192); and Group 3, the control group, without placental calcification noted between 28 and 36 weeks (n = 521). Women who smoked cigarettes or drank alcohol during pregnancy, or who had hypertension, diabetes, significant antenatal anemia or placenta previa were all excluded. Logistic regression analysis was used to estimate the risks of adverse pregnancy outcome in Groups 1 and 2 by calculating odds ratios (OR) with 95% CIs, adjusted by maternal age, body mass index, economic status, marital status, type of delivery and parity. RESULTS: Risks for adverse maternal outcome including postpartum hemorrhage (OR, 3.43; 95% CI, 1.251-9.388), placental abruption (OR, 6.52; 95% CI, 1.356-31.382) and maternal transfer to the intensive care unit (OR, 9.76; 95% CI, 1.826-52.195) and for adverse fetal outcomes including preterm birth (OR, 4.20; 95% CI, 1.775-9.940), low birth weight (OR, 4.58; 95% CI, 2.201-9.522), low Apgar score (OR, 6.53; 95% CI, 2.116-20.142) and neonatal death (OR, 9.04; 95% CI, 1.722-47.411) were much higher in Group 1 than in Group 3. In contrast, there were no significant differences in adverse pregnancy outcome between Groups 2 and 3. CONCLUSIONS: Early preterm placental calcification is associated with a higher incidence of adverse pregnancy outcome, and may serve as an indicator of adverse maternal and fetal outcomes when noted on ultrasonography. Conversely, women with late preterm placental calcification are not at greater risk for adverse pregnancy outcome.
Assuntos
Calcinose/diagnóstico por imagem , Doenças Placentárias/diagnóstico por imagem , Placenta/diagnóstico por imagem , Adulto , Calcinose/complicações , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Complicações na Gravidez/etiologia , Resultado da Gravidez , Nascimento Prematuro , Estudos Prospectivos , Fatores de Risco , Fumar/efeitos adversos , Fatores Socioeconômicos , UltrassonografiaRESUMO
OBJECTIVES: Ischemia-reperfusion (I/R) of the rat pancreas induces acute pancreatitis with a systemic inflammatory response. Activated inflammatory cells are sequestered in the lung, and the consequent respiratory burst may increase airway reactivity. In this study, we characterized the effect of the antioxidant curcumin on airway hyperreactivity induced by pancreatic I/R. METHODS: Ischemia of the pancreas was induced by clamping the gastroduodenal and the splenic artery for 2 hours followed by reperfusion for 6 hours. The pulmonary function data of Penh, a measurement of airway resistance, were used to show the airway responses to a methacholine challenge. The blood concentration of oxygen radicals, nitric oxide, and tumor necrosis factor-alpha (TNFalpha) were measured after pancreatic I/R. mRNA expressions of inducible nitric oxide synthase (iNOS) and TNFalpha in lung tissues were measured after pancreatic I/R. Pretreatment with curcumin (20 mg/kg) was administered by intraperitoneal injection 2 hours before pancreatic I/R. RESULTS: The protocol resulted in significant elevations of the blood concentrations of amylase, hydroxyl radical, nitric oxide, TNFalpha, and white cells among the I/R group. iNOS and TNFalpha mRNA expressions also significantly increased in lung tissues. Pulmonary function data showed that pancreatic I/R induced significant increases in responses to methacholine challenge: Penh increased significantly in the I/R group when compared with the sham group. Pretreatment with curcumin significantly attenuated the inflammatory, oxidative, and nitrosative responses and lung tissue iNOS and TNFalpha expressions. Curcumin also attenuated airway reactivity to methacholine challenge. CONCLUSIONS: I/R of the pancreas induced systemic inflammatory responses with respiratory burst, nitrosative stress, and hyperresponses in the airways. Curcumin, which has antioxidant and anti-inflammatory effects, significantly attenuated the inflammatory responses and airway hyperreactivity induced by pancreatic I/R.
Assuntos
Hiper-Reatividade Brônquica/tratamento farmacológico , Curcumina/uso terapêutico , Pâncreas/irrigação sanguínea , Traumatismo por Reperfusão/complicações , Amilases/sangue , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Hiper-Reatividade Brônquica/etiologia , Hiper-Reatividade Brônquica/fisiopatologia , Masculino , Metilguanidina/sangue , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo II/sangue , Óxido Nítrico Sintase Tipo II/genética , Pâncreas/metabolismo , Pâncreas/patologia , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/fisiopatologia , Testes de Função Respiratória , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genéticaRESUMO
This study sought to determine whether oxygen radical scavengers of dimethylthiourea (DMTU), superoxide dismutase (SOD), or catalase (CAT) pretreatment attenuated ischemia-reperfusion (I/R)-induced lung injury. After isolation from a Sprague-Dawley rat, the lungs were perfused through the pulmonary artery cannula with rat whole blood diluted 1:1 with a physiological salt solution. An acute lung injury was induced by 10 minutes of hypoxia with 5% CO2-95% N2 followed by 65 minutes of ischemia and then 65 minutes of reperfusion. I/R significantly increased microvascular permeability as measured by the capillary filtration coefficient (Kfc), lung weight-to-body weight ratio (LW/BW), and protein concentration in bronchoalveolar lavage fluid (PCBAL). DMTU pretreatment significantly attenuated the acute lung injury. The capillary filtration coefficient (P<.01), LW/BW (P<.01) and PCBAL (P<.05) were significantly lower among the DMTU-treated rats than hosts pretreated with SOD or CAT. The possible mechanisms of the protective effect of DMTU in I/R-induced lung injury may relate to the permeability of the agent allowing it to scavenge intracellular hydroxyl radicals. However, whether superoxide dismutase or catalase antioxidants showed protective effects possibly due to their impermeability of the cell membrane not allowing scavenging of intracellular oxygen radicals.
Assuntos
Edema/etiologia , Sequestradores de Radicais Livres/uso terapêutico , Lesão Pulmonar/etiologia , Traumatismo por Reperfusão/fisiopatologia , Tioureia/análogos & derivados , Animais , Peso Corporal , Edema/tratamento farmacológico , Pulmão/anatomia & histologia , Lesão Pulmonar/tratamento farmacológico , Microcirculação/efeitos dos fármacos , Microcirculação/fisiologia , Tamanho do Órgão , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , Tioureia/uso terapêuticoRESUMO
Dantrolene is the drug of choice in treatment of malignant hyperthermia. However, dantrolene is hepatotoxic; thus prolonged use is not recommended in patients with active hepatic disease such as acute hepatitis or active cirrhosis because it may result in fatal hepatic failure. Use of dantrolene in a patient with end-stage liver disease undergoing liver transplantation (LTx) in whom suspected malignant hyperthermia developed has been reported rarely. Its effect on the liver allograft, which has sustained cold, warm, and reperfusion injuries, is currently unknown. We report a case in which low-dose dantrolene administered intravenously during LTx was effective in treating hyperthermia, hypercapnia, and hyperkalemia. Furthermore, its reported hepatotoxic effect seemed to not affect recovery of the allograft after LTx.