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61.
Diagnostic efficacy of liquid‐based cytology for solid pancreatic lesion samples obtained with endoscopic ultrasound‐guided fine‐needle aspiration: Propensity score‐matched analysis
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Endoscopic transpapillary bile duct biopsy with the combination of intraductal ultrasonography in the diagnosis of biliary strictures 总被引:6,自引:0,他引:6
BACKGROUND: When endoscopic retrograde cholangiopancreatography (ERCP) guided bile duct biopsy fails to demonstrate malignancy, it remains unclear how to manage patients with presumably malignant strictures. AIMS: To evaluate the value of intraductal ultrasonography (IDUS) when bile duct biopsy is negative. METHODS: Sixty two patients with strictures of the bile duct were studied prospectively. During ERCP, IDUS was performed using an ultrasonic probe (diameter 2.0 mm; frequency 20 MHz). Following IDUS, a bile duct biopsy was performed using forceps (diameter 1.8 mm). The IDUS images of the tumour were classified as polypoid lesions, localised wall thickening, intraductal sessile tumours, sessile tumour outside of the bile duct, or absence of apparent lesion. The bile duct wall structures at the site of the tumour as well as the maximum diameter of the tumour were also analysed. The IDUS findings were compared with the histological findings or clinical course. RESULTS: When the IDUS images showed a polypoid lesion (n=19), localised wall thickening (n=8), intraductal sessile tumour (n=13), and sessile tumour outside of the bile duct (n = 20), the sensitivities of the biopsy were 80%, 50%, 92%, and 53%, respectively. Multiple regression analysis showed that the presence of sessile tumour (intraductal or outside of the bile duct: p<0.05), tumour size greater than 10.0 mm (p<0.001), and interrupted wall structure (p<0.05) were independent variables that predicted malignancy. CONCLUSION: When biopsy fails to demonstrate evidence of malignancy, the presence of sessile tumour (intraductal or outside of the bile duct), tumour size greater than 10.0 mm, and interrupted wall structure on IDUS images are factors that can predict malignancy. 相似文献
65.
Moges S. Ido Michael R. Frankel Ike S. Okosun Richard B. Rothenberg 《The American journal of emergency medicine》2018,36(2):262-265
Introduction
Intravenous alteplase reduces disability and improves functionality among acute ischemic stroke patients. Two decades after its approval, only a small fraction of patients get the treatment, and demonstrating its impact on mortality may make a strong case for its wider use. This study assessed the impact of thrombolytic treatment by alteplase on 1-year mortality and readmission among acute ischemic stroke patients.Method
The 2008–2013 Georgia Coverdell Acute Stroke Registry data were linked with the 2008–2013 hospital discharge and the 2008–2014 death data in Georgia. Multiple imputation was applied; a propensity score measuring the probability of receiving intravenous alteplase was calculated and used for matching. A conditional logistic regression was applied to compare 1-year mortality and readmission among propensity score matched pairs.Results
Overall, 20.3% of 9620 acute ischemic stroke patients died and 22.4% were readmitted in one year. The multivariable regression result showed that patients who did not receive IV alteplase had a 1.49 (95%CI: 1.09–2.04; p-value = 0.01) times higher odds of dying at one year than those who were treated with the thrombolytic agent. Among patients discharged home, no statistically significant difference was documented in the odds of being readmitted at least once within 365 days post-stroke discharge.Discussion and conclusion
After accounting for patient differences and missing value, intravenous alteplase is associated with reduction in long-term mortality. The results of this study suggest that patients who are identified as eligible for intravenous alteplase need to be offered the treatment. 相似文献66.
Tahata Yuki Hikita Hayato Mochida Satoshi Enomoto Nobuyuki Kawada Norifumi Kurosaki Masayuki Ido Akio Miki Daiki Yoshiji Hitoshi Takikawa Yasuhiro Sakamori Ryotaro Hiasa Yoichi Nakao Kazuhiko Kato Naoya Ueno Yoshiyuki Yatsuhashi Hiroshi Itoh Yoshito Tateishi Ryosuke Suda Goki Takami Taro Nakamoto Yasunari Asahina Yasuhiro Matsuura Kentaro Yamashita Taro Kanto Tatsuya Akuta Norio Terai Shuji Shimizu Masahito Sobue Satoshi Miyaki Tomokatsu Moriuchi Akihiro Yamada Ryoko Kodama Takahiro Tatsumi Tomohide Yamada Tomomi Takehara Tetsuo 《Journal of gastroenterology》2022,57(2):120-132
Journal of Gastroenterology - Direct-acting antiviral (DAA) therapy enables a high rate of sustained virologic response (SVR) in patients with hepatitis C virus associated cirrhosis. However, the... 相似文献
67.
Nakayama Nobuaki Uemura Hayato Uchida Yoshihito Imai Yukinori Tomiya Tomoaki Terai Shuji Yoshiji Hitoshi Genda Takuya Ido Akio Inoue Kazuaki Kato Naoya Sakaida Isao Shimizu Masahito Takikawa Yasuhiro Abe Masanori Abe Ryuzo Chayama Kazuaki Hasegawa Kiyoshi Inui Ayano Kasahara Mureo Ohira Hiromasa Tanaka Atsushi Takikawa Hajime Mochida Satoshi 《Journal of gastroenterology》2021,56(12):1092-1106
Journal of Gastroenterology - The significance of the 2018 Japanese diagnostic criteria for acute-on-chronic liver failure (ACLF) has not yet been evaluated. A nationwide survey was performed for... 相似文献
68.
OBJECTIVE: The chronic inflammation and progressive joint destruction observed in rheumatoid arthritis (RA) are mediated in part by macrophages. A paucity of apoptosis has been observed in RA synovial tissues, yet the mechanism remains unknown. The present study sought to characterize the expression of Fas, Fas ligand (FasL), and Fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein (FLIP), and to quantify the apoptosis induced by agonistic anti-Fas antibody, using mononuclear cells (MNC) isolated from the peripheral blood (PB) and synovial fluid (SF) of RA patients. METHODS: The expression of Fas, FasL, and FLIP and apoptosis induced by agonistic anti-Fas antibody in MNC from the PB and SF of RA patients were determined by flow cytometry. Immunohistochemistry employing a monospecific anti-FLIP antibody was performed on RA and osteoarthritis (OA) synovial tissue. RESULTS: CD14-positive monocyte/macrophages from normal and RA PB and from RA SF expressed equivalent levels of Fas and FasL. Furthermore, unlike the CD14-positive PB monocytes, RA SF monocyte/macrophages were resistant to the addition of agonistic anti-Fas antibody. In contrast, both CD14-positive PB and SF monocyte/macrophages were sensitive to apoptosis mediated by a phosphatidylinositol 3-kinase inhibitor. Intracellular staining of the caspase 8 inhibitor, FLIP, in CD14-positive SF monocyte/macrophages revealed a significant up-regulation of FLIP compared with normal and RA PB monocytes. Immunohistochemical analysis of synovial tissue from RA and OA patients revealed increased FLIP expression in the RA synovial lining compared with the OA synovial lining. Furthermore, FLIP expression was observed in the CD68positive population in the RA synovial lining. Forced reduction of FLIP by a chemical inhibitor resulted in RA SF macrophage apoptosis that was enhanced by agonistic anti-Fas antibody, indicating that FLIP is necessary for SF macrophage survival. CONCLUSION: These data suggest that up-regulation of FLIP in RA macrophages may account for their persistence in the disease. Thus, the targeted suppression of FLIP may be a potential therapeutic strategy for the amelioration of RA. 相似文献
69.
An increase in cytosolic free calcium (Cai) has been shown to occur early during ischemia in perfused rat, ferret, and rabbit hearts. It has been proposed that this increase in Cai may occur as a result of exchange of Nai for Cao, which occurs as a result of an increase in Nai arising from exchange of Nao for H+i. The latter exchange is stimulated by the intracellular acidification that occurs during ischemia. To test this hypothesis, we examined Cai, Nai, ATP, and pHi during ischemia in rats in the presence and absence of 1 mM amiloride, a Na-H exchange inhibitor. Cai was measured using 19F nuclear magnetic resonance (NMR) of 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetra-acetic acid (5F-BAPTA)-loaded rat hearts. Nai was measured using 23Na NMR, and the shift reagent 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetramethylenephosph onate (Tm[DOTP]-5) was used to separate Nai and Nao. ATP and pH were determined from 31P NMR measurements. During 20 minutes of ischemia, amiloride did not significantly alter the ATP decline but did significantly attenuate the rise in Nai and Cai. After 20 minutes of ischemia, time-averaged Cai was 1.0 +/- 0.2 microM (mean +/- SEM) in amiloride-treated hearts compared with 2.3 +/- 0.9 microM in nontreated hearts. After 20 minutes of ischemia, Nai in the untreated heart was threefold greater than control, whereas in the amiloride-treated heart, Nai was not significantly different from control. These data are consistent with the involvement of Na-Ca exchange in the rise in Cai during ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
70.
Michelle L. Parker Diana M. Penarete-Vargas Phineas T. Hamilton Amandine Guérin Jitender P. Dubey Steve J. Perlman Furio Spano Maryse Lebrun Martin J. Boulanger 《Proceedings of the National Academy of Sciences of the United States of America》2016,113(2):398-403
Plasmodium falciparum and Toxoplasma gondii are widely studied parasites in phylum Apicomplexa and the etiological agents of severe human malaria and toxoplasmosis, respectively. These intracellular pathogens have evolved a sophisticated invasion strategy that relies on delivery of proteins into the host cell, where parasite-derived rhoptry neck protein 2 (RON2) family members localize to the host outer membrane and serve as ligands for apical membrane antigen (AMA) family surface proteins displayed on the parasite. Recently, we showed that T. gondii harbors a novel AMA designated as TgAMA4 that shows extreme sequence divergence from all characterized AMA family members. Here we show that sporozoite-expressed TgAMA4 clusters in a distinct phylogenetic clade with Plasmodium merozoite apical erythrocyte-binding ligand (MAEBL) proteins and forms a high-affinity, functional complex with its coevolved partner, TgRON2L1. High-resolution crystal structures of TgAMA4 in the apo and TgRON2L1-bound forms complemented with alanine scanning mutagenesis data reveal an unexpected architecture and assembly mechanism relative to previously characterized AMA–RON2 complexes. Principally, TgAMA4 lacks both a deep surface groove and a key surface loop that have been established to govern RON2 ligand binding selectivity in other AMAs. Our study reveals a previously underappreciated level of molecular diversity at the parasite–host-cell interface and offers intriguing insight into the adaptation strategies underlying sporozoite invasion. Moreover, our data offer the potential for improved design of neutralizing therapeutics targeting a broad range of AMA–RON2 pairs and apicomplexan invasive stages.Phylum Apicomplexa comprises >5,000 parasitic protozoan species, many of which cause devastating diseases on a global scale. Two of the most prevalent species are Toxoplasma gondii and Plasmodium falciparum, the causative agents of toxoplasmosis and severe human malaria, respectively (1, 2). The obligate intracellular apicomplexan parasites lead complex and diverse lifestyles that require invasion of many different cell types. Despite this diversity of target host cells, most apicomplexans maintain a generally conserved mechanism for active invasion (3). The parasite initially glides over the surface of a host cell and then reorients to place its apical end in close contact to the host-cell membrane. After this initial attachment, a circumferential ring of adhesion (termed the moving or tight junction) is formed, through which the parasite actively propels itself while concurrently depressing the host-cell membrane to create a nascent protective vacuole (4).Formation of the moving junction relies on a pair of highly conserved parasite proteins: rhoptry neck protein 2 (RON2) and apical membrane antigen 1 (AMA1). Initially, parasites discharge RON2 into the host cell membrane where an extracellular portion (domain 3; D3) serves as a ligand for AMA1 displayed on the parasite surface (5–8). Intriguingly, recent studies have shown that the AMA1–RON2 complex is an attractive target for therapeutic intervention (9–12). The importance of the AMA1–RON2 pairing is also reflected in the observation that many apicomplexan parasites encode functional paralogs that are generally expressed in a stage-specific manner (13–15). We recently showed that, in addition to AMA1 and RON2, T. gondii harbors three additional AMA paralogs and two additional RON2 paralogs (14, 15): TgAMA2 forms a functional invasion complex with TgRON2 (15), TgAMA3 (also annotated as SporoAMA1) selectively coordinates TgRON2L2 (14), and TgAMA4 binds TgRON2L1 (15). Despite substantial sequence divergence, structural characterization of all AMA–RON2D3 complexes solved to date [TgAMA1–TgRON2D3 (16), PfAMA1–PfRON2D3 (17), and TgAMA3–TgRON2L2D3 (14)] reveal a largely conserved architecture and binding paradigm. Intriguingly, however, sequence analysis indicates that TgAMA4 and TgRON2L1 are likely to adopt substantially divergent structures with an atypical assembly mechanism.To investigate the functional implications of the AMA4–RON2L1 complex in T. gondii, we first established that TgAMA4 is part of a highly divergent AMA clade that includes the functionally important malaria vaccine candidate Plasmodium merozoite apical erythrocyte-binding ligand (MAEBL) (18–20) and that TgRON2L1 displays a similar divergence consistent with coevolution of receptor and ligand. We then show that TgAMA4 and TgRON2L1 form a high-affinity binary complex and probe its overall architecture and underlying mechanism of assembly using crystal structures of TgAMA4 in the apo and TgRON2L1D3 bound forms. Finally, we show proof of principle that TgAMA4 and TgRON2L1 form a functional pairing capable of supporting host-cell invasion. Collectively, our study reveals exceptional molecular diversity at the parasite–host-cell interface that we discuss in the context of the unique invasion barriers encountered by the sporozoite. 相似文献