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World Journal of gastroenterology 2014年第26期20卷 8458-8470页

作者： Daniel Delitto Eva Vertes-george steven J Hughes Kevin E Behrns Jose g Trevino Department of Surgery University of Florida-Gainesville Department of Pathology University of Florida-Gainesville

Pancreatic ductal adenocarcinoma is the 4th leading cause of cancer deaths in the United States. The majority of patients are candidates only for palliative chemotherapy, which has proven largely ineffective in halting tumor progression. One proposed mechanism of chemoresistance involves signaling via the mesenchymal-epithelial transition factor protein (MET), a previously established pathway critical to cell proliferation and migration. Here, we review the literature to characterize the role of MET in the development of tumorigenesis, metastasis and chemoresistance, highlighting the potential of MET as a therapeutic target in pancreatic cancer. In this review, we characterize the role of c-Met in the development of tumorigenesis, metastasis and chemoresistance, highlighting the potential of c-Met as a therapeutic target in pancreatic cancer.

关键词： Pancreatic adenocarcinoma c-Met Chemoresistance Receptor tyrosine kinase

Colonic ulcerations may predict steroid-refractory course in patients with ipilimumab-mediated enterocolitis

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World Journal of gastroenterology 2017年第11期23卷 2023-2028页

作者： Animesh Jain Evan J Lipson William H Sharfman steven R Brant Mark g Lazarev Division of gastroenterology and Hepatology Department of Internal MedicineUniversity of North Carolina Chapel Hill Department of Oncology Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center Division of gastroenterology and Hepatology Department of Internal MedicineJohns Hopkins University School of Medicine

AIM To investigate management of patients who develop ipilimumab-mediated enterocolitis, including association of endoscopic findings with steroid-refractory symptoms and utility of infliximab as second-line *** We retrospectively reviewed all patients at our centerwith metastatic melanoma who were treated with ipilimumab between March 2011 and May 2014. All patients received a standard regimen of intravenous ipilimumab 3 mg/kg every 3 wk for four doses or until therapy was stopped due to toxicity or disease progression. Basic demographic and clinical data were collected on all patients. For patients who developed grade 2 or worse diarrhea(increase of 4 bowel movements per day), additional data were collected regarding details of gastrointestinal symptoms, endoscopic findings and treatment course. Descriptive statistics were *** A total of 114 patients were treated with ipilimumab during the study period and all were included. Sixteen patients(14%) developed ≥ grade 2 diarrhea. All patients were treated with high-dose corticosteroids(1-2 mg/kg prednisone daily or equivalent). Nine of 16 patients(56%) had ongoing diarrhea despite highdose steroids. Steroid-refractory patients received one dose of intravenous infliximab at 5 mg/kg, and all but one had brisk resolution of diarrhea. Fourteen of the patients underwent either colonoscopy or sigmoidoscopy with variable endoscopic findings, ranging from mild erythema to colonic ulcers. Among 8 patients with ulcers demonstrated by sigmoidoscopy or colonoscopy, 7 patients(88%) developed steroidrefractory symptoms requiring infliximab. With a median follow-up of 264 d, no major adverse events associated with prednisone or infliximab were *** In patients with ipilimumab-mediated enterocolitis, the presence of colonic ulcers on endoscopy was associated with a steroid-refractory course.

关键词： Ipilimumab Melanoma Enterocolitis Colitis Infliximab Corticosteroid Colonic ulcer

Hemoglobin Adducts as Biomarkers of Exposure to and metabolic Activation of Carcinogenic Tobacco-Specific Nitrosamines

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Biomedical and Environmental Sciences 1991年第1期4卷 93-103页

作者： STEPHEN S.HECHT steven g.CARMELLA SHARON E.MURPHY Dana Road American Health Foundation ValhallaDana Road American Health Foundation ValhallaDana Road American Health Foundation Valhalla New York 10595New York 10595 New York 10595

The carcinogenic tobacco-specific nitrosamines N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-l-(3-pyridyl)-l-butanone (NNK) form hemoglobin adducts in laboratory animals and humans. These adducts release 4-hydroxy-l-(3-pyridyl)-l-butanone (HPB) upon mild base hydrolysis. HPB released from human hemoglobin can be quantified by gas chromatography-mass spectrometry. It is the only available biochemical marker for determination of exposure to, and metabolic activation of, carcinogens present only in tobacco. Levels of HPB were highest in snuff-dippers, followed by smokers and nonsmokers. Large interindividual variations in adduct levels were observed. The relationship between HPB levels in globin and DNA of rats treated with NNK has been investigated in order to aid in interpretation of the data from humans. These studies have provided the initial database for understanding the metabolic activation of tobacco-specific nitrosamines in humans.

关键词： Hemoglobin Adducts as Biomarkers of Exposure to and metabolic Activation of Carcinogenic Tobacco-Specific Nitrosamines

Recent advances in the management of hyponatremia in cancer patients

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Journal of Cancer Metastasis and Treatment 2019年第10期4卷 21-32页

作者： Maryam I.Khan steven g.Waguespack Intekhab Ahmed Division of Endocrinology Diabetes and MetabolismJefferson HealthVoorheesNJ 08043USA Department of Endocrine Neoplasia and Hormonal disorders University of Texas M.D.Anderson Cancer CenterHoustonTX 77030USA Division of Endocrinology Diabetes and MetabolismJefferson HealthPhiladelphiaPA 19107USA.

Hyponatremia is the most frequently encountered electrolyte disorder in cancer patients and is usually multifactorial in its *** this review,we discuss the predisposing factors,pathophysiology,clinical symptomatology,and currently available diagnostic and therapeutic options for the management of *** addition to paraneoplastic syndromes,concurrent chemotherapy and comorbidities predispose oncology patients to the risk of *** symptoms and signs can be subtle and the prompt evaluation and initiation of treatment is of paramount importance to prevent neurocognitive and other *** syndrome of inappropriate antidiuresis(SIAD)is the most common cause of hyponatremia,and the use of serum and urine parameters that distinguish SIAD from other etiologies is *** treatment is preferred depending on the underlying cause and severity of *** treatment of hyponatremia is reviewed and the importance of avoiding rapid overcorrection of the sodium level to reduce the risk of osmotic demyelination syndrome is *** receptor antagonists(vaptans)offer a direct approach to the management of euvolemic and hypervolemic hyponatremia,but the indications for their use and long-term safety need to be *** treatment of hyponatremia is likely to reduce complications and improve survival in cancer patients.

关键词： Hyponatremia electrolyte abnormalities dysnatremias cancer

Introduction to IEEE 802.3av 10gbit/s Ethernet Passive Optical Networks(10g EPON)

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China Communications 2009年第4期6卷 136-147页

作者： steven Scott gorshe Jeff Mandin ICs for Optical Transmission and Access Systems United States Transmission Access and Optical Systems Technical Committee United States PMC-Sierra's Fiber-to-the-Home Business Unit United States

In the competitive broadband access environment, providing access to"triple play"services(voice, video, and high-speed data) is an important way for both telephone and CATV network providers to increase their *** Optical Networks(PONs) are a cost-effective, flexible, and future-proof medium for providing triple play *** 1 gbit/s IEEE 802.3ah Ethernet PON(EPON) and ITU-T g.984 2.5 gbit/ s PON(gPON) are currently being deployed for triple play service ***, high definition switched digital video service such as IPTV will require more *** paper provides a tutorial overview of the IEEE 802.3av 10gbit/s Ethernet PON(10g EPON) standard, including the ways in which it differs from EPON.

关键词： IEEE 以太网计算机网络电子邮件

Validation of the age-adjusted shock index for pediatric casualties in Iraq and Afghanistan

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Military Medical Research 2021年第1期8卷 17-24页

作者： Camaren M.Cuenca Matthew A.Borgman Michael D.April Andrew D.Fisher steven g.Schauer JUS Army Institute of Surgical Research 3698 Chambers PassJBSA Fort Sam HoustonSan AntonioTX 78234-7767USA Brooke Army Medical Center JBSA Fort Sam HoustonSan AntonioTXUSA Uniformed Services University of the Heath Sciences BethesdaMDUSA Texas Army National guard AustinTXUSA Department of Surgery UNM School of MedicineAlbuquerqueNMUSA 59th Medical Wing JBSA LacklandSan AntonioTXUSA

Background: Pediatric casualties account for a notable proportion of encounters in the deployed setting based on the humanitarian medical care mission. Previously published data demonstrates that an age-adjust shock index may be a useful tool in predicting massive transfusion and death in children. We seek to determine if those previous findings are applicable to the deployed, combat trauma ***: We queried the Department of Defense Trauma Registry(DODTR) for all pediatric subjects admitted to US and Coalition fixed-facility hospitals in Iraq and Afghanistan from January 2007 to January 2016. This was a secondary analysis of casualties seeking to validate previously published data using the shock index, pediatric age adjusted. We then used previously published thresholds to determine patients outcome for validation by age grouping, 1–3 years(1.2), 4–6 years(1.2), 7–12 years(1.0), 13–17 years(0.9).Results: From January 2007 through January 2016 there were 3439 pediatric casualties of which 3145 had a documented heart rate and systolic pressure. Of those 502(16.0%) underwent massive transfusion and 226(7.2%) died prior to hospital discharge. Receiver operating characteristic(ROC) thresholds were inconsistent across age groups ranging from 1.0 to 1.9 with generally limited area under the curve(AUC) values for both massive transfusion and death prediction characteristics. Using the previously defined thresholds for validation, we reported sensitivity and specificity for the massive transfusion by age-group: 1–3(0.73, 0.35), 4–6(0.63, 0.60), 7–12(0.80, 0.57), 13–17(0.77, 0.62). For death, 1–3(0.75, 0.34), 4–6(0.66–0.59), 7–12(0.64, 0.52), 13–17(0.70, 0.57). However, negative predictive values(NPV) were generally high with all greater than ***: Within the combat setting, the age-adjusted pediatric shock index had moderate sensitivity and relatively poor specificity for predicting massive transfusion and death. Better scoring systems are needed to p

关键词： Pediatric Massive Transfusion Shock Index Age

Natural history,clinical characteristics,outcomes,and long-term follow-up of pain-free chronic pancreatitis

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gastroenterology Report 2023年第1期11卷 309-315页

作者： Awais Ahmed Ishani Shah Rachel Bocchino steven D.Freedman Darshan J.Kothari Sunil g.Sheth Department of Medicine Division of GastroenterologyBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Department of Medicine Division of Internal MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Department of Medicine Division of GastroenterologyDuke UniversityDurhamNCUSA

Background:Chronic pancreatitis(CP)is characterized by chronic abdominal pain and functional ***,a small subset of patients with prior acute pancreatitis(AP)and/or underlying risk factors for developing CP may be pain-free at diagnosis and may have a different clinical *** aimed to compare the clinical characteristics,outcomes,and healthcare utilization between CP patients with and without ***:Reviewed patients with established CP were followed in our Pancreas Center between January 2016 and April *** without risk factors for developing CP and/or without AP prior to their diagnosis and only with incidental radiologic features of CP were excluded,so as tominimize confounding factors of pancreatopathy unrelated to *** were divided into painful and pain-free groups to analyze differences in demographics,outcomes,and healthcare ***:Of 368 CP patients,49(13.3%)were pain-free at diagnosis and had remained so for>9 *** were no significant differences in body mass index,race,sex,or co-morbidities between the two ***-free patients were older at diagnosis(53.9 vs 45.7,P=0.004)and had less recurrent AP(RAP)(43.8%vs 72.5%,Pgery(0.0%vs 15.0%,P=0.059),and therapeutic interventions(0.0%vs 16.4%,P=0.005)for ***:We described a unique subset of patients with underlying risk factors for CP and/or prior AP who were painfree at *** were older at diagnosis,had less EPI and RAP,and overall favorable outcomes with minimal resource utilization.

关键词： chronic pancreatitis pain-free pancreatic insufficiency diabetes

Luminescence of Er^(3+) in Oxyfluoride Transparent glass-Ceramics

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Journal of Rare Earths 2006年第6期24卷 699-705页

作者： Akira Ueda steven H Morgan Richard Mu Department of Physics Fisk University NashvilleTN 37208 USA

Erbium doped silicate, germanate, and tellurium-germanate oxyfluoride glasses were prepared in a bulk form. Through appropriate heat treatment of the as-prepared glasses, transparent glass-ceramics （TgCs） were obtained with the formation of β-PbF2：Er^3＋ nanocrystals in the glass matrix were confirmed by X-ray ***-defined diffraction peaks were observed in the samples after heat-treatment. The average crystal diameter of these precipitated crystals from full-width at half-maximum （FWHM） of the diffraction peak was estimated to be between 8 and 13 nm. Optical absorption, photoluminescence, and upconversion luminescence were measured on as-prepared glass and glass-ceramics. Luminescence spectra in the TgC samples revealed well-resolved, sharp stark-splitting peaks, which indicates that a majority of Er^3＋ ions has been incorporated into the crystalline phase of the nanocrystals. The intensity of the visible and near infrared luminescence mostly increases in TSg compared to that in the as-prepared glass. In 1.53 μm absorption and emission bands, the maximum absorption peak is blue-shifted from 1531 to 1507 nm, whereas the maximum emission peak is redshifted from 1535 to 1543 nm in TgC, as compared with that in glass. The bandwidth at half-maximum （BWHM） of the emission band is significantly broader in TgC than in glass, which is beneficial to the erbium-doped fiber amplifier （EDFA）. Upconversion luminescence was measured using 800 nm near-infrared light excitation. Drastically increased upconversion 1 was observed from the TgC as compared to that from their corresponding as-prepared glasses. In addition to a strong green emission centered at 545 nm because of ^4S3/2→^4I15/2 transition and a weaker red emission centered at 662 nm because of ^4F9/2→^4I15/2 transition, generally seen from the Er^3＋ doped glasses, two violet emissions centered at 410 nm because of ^2H9/2→^4I15/2 transition and centered at 379 nm because of ^4g11/2→^4I15/2 transition were also o

关键词： luminescence transparent glass-ceramics rare earths

Current status of aggressive blood pressure control

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World Journal of Cardiology 2011年第3期3卷 65-71页

作者： steven g Chrysant Oklahoma Cardiovascular and Hypertension Center Oklahoma City

The concept of treatment of hypertension has gone through wide swings over the *** ignoring blood pressure(BP)treatment initially,to aggressive BP control *** newer and more effective drugs were developed,it was possible to lower BP to very low ***,recent studies have shown that aggressive BP control might not be in the best interest of the *** levels of diastolic BP(DBP)have been associated with increased cardiovascular events, a situation known as the J-curve *** has been seen mostly with low DBP,since the coronary arteries are perfused during the diastolic phase of the cardiac *** to an autoregulatory mechanism,the heart is protected against wide fluctuations of ***, the presence of coronary heart disease,hypertension, especially with left ventricular hypertrophy,shift the curve to higher BP levels and makes the heart more liable to DBP *** J-Curve effect has been reported by most investigators,but not by ***,a J-Curve effect has been observed with systolic BP(SBP),as *** contrast to the heart,the brain is very infrequently subjected to J-curve effect,and in contrast to the heart,the brain's blood flow autoregulation depends mostly on the SBP.A Medline search of the English literature on this subject was conducted between 1992 and 2010 and 11 pertinent articles were *** articles with collateral literature will be discussed in this concise review.

关键词： Hypertension Treatment J-curve Coronary heart disease Stroke

Overview and Comparison of the IEEE EPON and ITU-T gPON Protocols

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China Communications 2007年第2期4卷 69-78页

作者： steven S.gorshe

Providing the "triple play" services of voice,video,and high-speed data access is an important way for carriers to increase their revenue and compete with other access providers such as the CATV *** most flexible and "future-proof" medium for providing triple play services is fiber,with its virtually unlimited bandwidth *** providing a direct optical connection between the CO and each subscriber is cost prohibitive, most optical access systems use a passive optical network (PON) to connect multiple subscribers to the same CO optical *** white paper provides a tutorial overview and comparison of the two most popular very high-speed PON access network standards:the ITU-T g. 984 series gigabit PON(gPON) and IEEE 802.3ah Ethernet PON(EPON) standards.

关键词：街面