tbuckley/cabot-search huggingface dataset:
Describing the role of ethnicity in the progression of NAFLD: Easier said than done?
Authors: Edward William Holt
Journal: Hepatology (2012)

I read with interest the article by Bambha et al.1 examining the role of ethnicity in nonalcoholic fatty liver disease (NAFLD). Using the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network database, the authors examined associations between ethnicity and NAFLD with greater scrutiny than has previously been published. There are challenges, however, in separating the role of ethnicity from other risk factors for NAFLD. Two potential confounding variables were underemphasized by the authors. Age has been confirmed as a risk factor for fibrosis in NASH time and again.2 The age difference between Latinos and non-Latino whites in this study (44.2 versus 50.9, P < 0.0001) may have resulted in the assessment of these patients at different stages of disease progression. This is highlighted by the finding that age was independently associated with advanced fibrosis and ethnicity was not. The authors acknowledged this limitation and accounted for age in the logistic regression analysis. However, this difference makes the groups inhomogeneous and may influence other comparisons between them. As reported, Latinos had more grade ≥2 lobular inflammation (61% versus 48%, P = 0.008) and less stage >2 fibrosis (23% versus 30%, P = 0.004) than non-Latino whites. How many of the Latino patients with inflammation would have developed fibrosis if they had been studied, on average, 6.7 years later? The authors demonstrated that homeostasis model assessment-insulin resistance (HOMA-IR) was independently associated with NASH in non-Latino whites but not in Latinos, despite the fact that HOMA-IR scores for these groups did not differ (5.1 versus 4.6, P = 0.55). Because the frequency of biopsy-proven NASH in Latinos and non-Latino whites was the same (63% versus 62%, no P value), there must be additional risk factors that are more prevalent in Latinos. The authors acknowledged that the PNPLA3 rs738409 polymorphism—more prevalent in Latinos than non-Latino whites3—may be such a risk factor but underemphasize its potential importance. Speliotes et al. recently showed that the rs738409 G allele showed an independent association with histologic measures of NAFLD but not with metabolic traits.4 Thus PNPLA3 polymorphism status may act as a confounder for potential associations between ethnicity and NAFLD, and must be accounted for in future analyses. With this meticulous analysis, Bambha et al. set a precedent for future studies looking at the role of ethnicity in the progression of NAFLD. But toward the goal of understanding the complex relationships among the many risk factors for this disease, there is still much work to do. Edward William Holt M.D.*, * Department of Hepatology, California Pacific Medical Center, San Francisco, CA.
Costs and Benefits of Hepatitis Prophylaxis
Authors: David Egilman
Journal: JAMA (1984)

<h3>To the Editor.—</h3> Dr Hamiltons<sup>1</sup>article evaluating criteria for the use of hepatitis prophylaxis in medical personnel is misleading in several respects. Dr Hamilton states that prior to the initiation of a prevention strategy, it is necessary to "assess the costs and expected benefits of these strategies." This is contrary to the Occupational Health and Safety Administration (OHSA) Act of 1970, and the interpretation of that law as expressed by the Supreme Court in the case of American Textile Manufacturers Institute, Inc, et al<i>v</i>Donovan et al. The OHSA Act states that preventive measures must be implemented when they are<i>feasible</i>(Public Law 91-596). While economics is a part of feasibility, the Supreme Court has ruled that unless the control measure would put an entire industry out of business, an economic argument cannot prevent the implementation of a control measure. Furthermore, Dr Hamilton's argument is troubling from an
Randomized Phase II Trial of Matrix Metalloproteinase Inhibitor COL-3 in AIDS-Related Kaposi's Sarcoma: An AIDS Malignancy Consortium Study
Authors: Bruce J. Dezube, Susan E. Krown, Jeannette Y. Lee, Kenneth S. Bauer, David M. Aboulafia
Journal: Journal of Clinical Oncology (2006)

Purpose Matrix metalloproteinases (MMPs) are involved in tumor metastasis and are overexpressed in Kaposi's sarcoma (KS) cells. In a phase I trial of the MMP inhibitor COL-3 in patients with AIDS-related KS, the drug was well tolerated, KS regression was observed, and MMP-2 levels decreased significantly in responders compared with nonresponders. The aim of this trial was to extend these initial observations. Patients and Methods This was a randomized, parallel-group, phase II study. COL-3 was administered orally once daily at one of two doses (group A received 50 mg and group B received 100 mg) to patients with AIDS-related KS. Antiretroviral therapy was permitted but not required. Serial tumor assessments and plasma levels of MMPs were obtained. Study end points were progressive KS and recurrent dose-limiting toxicity. Results Seventy-five patients received COL-3: 37 in group A and 38 in group B. Fifty-seven patients (76%) had received prior KS therapy. Thirty-three patients (44%) had more than 50 KS lesions. The response rate in group A was 41%, which was significantly greater than the prespecified target rate of 20% (95% CI, 25% to 58%; P = .003); the response rate of group B was 29% (P = not significant). There were significant declines in MMP-2 and MMP-9 plasma levels from baseline to minimum value with treatment (MMP-2, P &lt; .001; MMP-9, P = .001). The most common adverse events were photosensitivity and rash. Conclusion COL-3, when administered as 50 mg/d, is both active and well tolerated in the treatment of AIDS-related KS. COL-3 is a promising agent for the treatment of this opportunistic neoplasm of AIDS.
Abstract 3922: A comparative study of affibody, antibody and EGF for near-infrared fluorescence imaging of EGFR- and EGFRvIII-expressing tumors.
Authors: Haibiao Gong, Joy L. Kovar, Lael Cheung, Eben L. Rosenthal, David M. Olive
Journal: Cancer Research (2013)

Abstract Aberrant overexpression and/or activation of epidermal growth factor receptor (EGFR) is associated with many types of cancers. EGFR variant III (EGFRvIII) is a common in-frame deletion mutant, which lacks a large part of the extracellular portion (exons 2-7), including components of the ligand-binding domain. Although EGFR has been extensively studied as a molecular imaging target, information about EGFRvIII-targeted molecular imaging is lacking. In this study, an EGFR-specific affibody, a therapeutic antibody (panitumumab) and the ligand EGF were labeled with IRDye 800CW (Ex/Em: 774/789 nm), and named as Aff800, Pan800 and EGF800 respectively. The binding affinities of the labeled agents were compared in cell-based assays using a rat glioma cell line F98 parental (F98-p) lacking EGFR, and two F98-derived transgenic cell lines expressing EGFR or EGFRvIII (designated as F98-EGFR and F98-vIII respectively). Results showed that all agents could bind to F98-EGFR, with Pan800 having the highest binding affinity, followed by Aff800 and EGF800. Pan800 and Aff800, but not EGF800, bound to F98-vIII with similar affinities. In vivo animal imaging studies demonstrated that compared to F98-p tumor signals, F98-EGFR tumor generated higher signals for all three agents. However, in the case of F98-vIII, only Pan800 and Aff800 signals were higher. Analysis of tissue lysates showed that a large portion of Pan800 was degraded into small fragments in F98-EGFR and F98-vIII tumors, possibly due to proteolytic digestion after its specific binding and internalization. In conclusion, Pan800 and Aff800 could be used as imaging agents for both wild type EGFR and EGFRvIII, whereas EGF800 only targets wild type EGFR. Citation Format: Haibiao Gong, Joy L. Kovar, Lael Cheung, Eben L. Rosenthal, David M. Olive. A comparative study of affibody, antibody and EGF for near-infrared fluorescence imaging of EGFR- and EGFRvIII-expressing tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3922. doi:10.1158/1538-7445.AM2013-3922
Development of Kaposi's Sarcoma in a Surgical Wound
Authors: Jennifer Webster-Cyriaque
Journal: New England Journal of Medicine (2002)

A patient infected with the human immunodeficiency virus (HIV) who had xerostomia and enlargement of the parotid glands underwent a diagnostic biopsy of a labial salivary gland. Within six days, a rapidly growing, fungating mass had appeared at the biopsy site. The lesion had the histologic features of Kaposi's sarcoma and contained antigens of human herpesvirus 8. After treatment with local radiotherapy, the lesion resolved.
Increased intracranial pressure in a porcine model of fulminant hepatic failure using amatoxin and endotoxin
Authors: Yasutsugu Takada, Shingo Ishiguro, Kiyoshi Fukunaga, Mei Gu, Hideki Taniguchi, Ken-Ichiro Seino, Kenji Yuzawa, Masaaki Otsuka, Takeshi Todoroki, Katashi Fukao
Journal: Journal of Hepatology (2001)
Appendectomy and Protection against Ulcerative Colitis
Authors: Roland E. Andersson, Gunnar Olaison, Curt Tysk, Anders Ekbom
Journal: New England Journal of Medicine (2001)

A history of appendectomy is rare in patients with ulcerative colitis. This suggests a protective effect of appendectomy or that appendicitis and ulcerative colitis are alternative inflammatory responses. We sought to characterize this inverse relation further.
Enhanced processing of threatening stimuli: The case of face recognition
Authors: Linda Mealey
Journal: Behavioral and Brain Sciences (1995)

Abstract Because of their evolutionary importance, threat-detection mechanisms are likely to exist at a variety of levels. A recent study of face recognition suggests that novel stimuli receive enhanced processing when presented as fear-related. This suggests the existence of a complex, context-dependent threat-detection mechanism that can adaptively respond to spatiotemporally varying and unique environmental features.
TIGAR Has a Dual Role in Cancer Cell Survival through Regulating Apoptosis and Autophagy
Authors: Jia-Ming Xie, Bin Li, Hong-Pei Yu, Quan-Geng Gao, Wei Li, Hao-Rong Wu, Zheng-Hong Qin
Journal: Cancer Research (2014)

The p53-induced glycolysis and apoptosis regulator (TIGAR) inhibits glycolysis, resulting in higher intracellular NADPH, lower reactive oxygen species (ROS) and autophagy activity. In this study, we investigated whether TIGAR might exert dual impacts on cancer cell survival based on its ability to inhibit both apoptosis and autophagy. In liver or lung cancer cells treated with the anticancer drug epirubicin, TIGAR levels increased in a dose- and time-dependent manner. TIGAR silencing enhanced epirubicin-induced elevations in ROS levels and apoptosis rates, in a manner that was blocked by ectopic addition of NADPH or N-acetyl cysteine. These findings were correlated with reduced tumorigenicity and increased chemosensitivity in mouse xenograft tumor assays. In parallel, TIGAR silencing also enhanced the epirubicin-induced activation of autophagy, in a manner that was also blocked by ectopic addition of NADPH. Notably, TIGAR silencing also licensed epirubicin-mediated inactivation of the mTOR pathway, suggesting TIGAR also exerted a negative impact on autophagy. However, genetic or pharmacologic inhibition of autophagy increased epirubicin-induced apoptosis in TIGAR-silenced cells. Overall, our results revealed that TIGAR inhibits both apoptosis and autophagy, resulting in a dual impact on tumor cell survival in response to tumor chemotherapy. Cancer Res; 74(18); 5127-38. ©2014 AACR.
Dependency of Contractile Reserve on Myocardial Blood Flow
Authors: Hans H. Lee, Victor G. Dávila-Román, Philip A. Ludbrook, Michael Courtois, John F. Walsh, Deborah A. Delano, Patricia J. Rubin, Robert J. Gropler
Journal: Circulation (1997)

Background Contractile reserve, improvement in contractile function during inotropic stimulation, is a proposed marker of viable myocardium. This study was designed to address, in patients with left ventricular dysfunction due to chronic coronary artery disease, whether contractile reserve depends on myocardial blood flow. Methods and Results We studied 19 patients, at rest and during dobutamine, with 2D echocardiography for regional mechanical function and PET for regional myocardial blood flow ([ 15 O]water) and oxygen consumption ([ 11 C]acetate). Of 166 myocardial segments, 21 had normal systolic function, 56 were dysfunctional but contractile reserve–positive, and 89 were dysfunctional and contractile reserve–negative. Myocardial blood flow at rest was lower in contractile reserve–negative (0.41±0.18 mL · g −1 · min −1 ) than in contractile reserve–positive (0.50±0.22 mL · g −1 · min −1 ) and normal segments (0.55±0.20 mL · g −1 · min −1 , P &lt;.009). After dobutamine infusion, blood flow increased less in contractile reserve–negative (0.63±0.38 mL · g −1 · min −1 ) than in contractile reserve–positive (1.28±0.65 mL · g −1 · min −1 ) and normal segments (1.93±0.83 mL · g −1 · min −1 , P &lt;.0001). Likewise, myocardial oxygen consumption was lower at rest in contractile reserve–negative (clearance rate of [ 11 C]acetate, 0.043±0.012 min −1 ) than in contractile reserve–positive (0.048±0.01 min −1 ) and normal segments (0.058±0.008 min −1 , P &lt;.02). Myocardial oxygen consumption with dobutamine increased less in contractile reserve–negative (0.060±0.013 min −1 ) than in contractile reserve–positive (0.077±0.016 min −1 ) and normal segments (0.092±0.024 min −1 , P &lt;.0001). Of segments defined as viable by PET, 54% were contractile reserve–negative and exhibited lower blood flow with dobutamine (0.72±0.36 mL · g −1 · min −1 ) than with viable, contractile reserve–positive segments (1.29±0.70 mL · g −1 · min −1 , P &lt;.0001). Conclusions Contractile reserve depends, in part, on the level of myocardial blood flow at rest and during inotropic stimulation.
Unique Cell Surface Expression of Receptor Tyrosine Kinase ROR1 in Human B-Cell Chronic Lymphocytic Leukemia
Authors: Sivasubramanian Baskar, Ka Yin Kwong, Thomas Hofer, Jessica M. Levy, Michael G. Kennedy, Elinor Lee, Louis M. Staudt, Wyndham H. Wilson, Adrian Wiestner, Christoph Rader
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Gene expression profiling identified receptor tyrosine kinase ROR1, an embryonic protein involved in organogenesis, as a signature gene in B-cell chronic lymphocytic leukemia (B-CLL). To assess the suitability of ROR1 as a cell surface antigen for targeted therapy of B-CLL, we carried out a comprehensive analysis of ROR1 protein expression. Experimental Design: Peripheral blood mononuclear cells, sera, and other adult tissues from B-CLL patients and healthy donors were analyzed qualitatively and quantitatively for ROR1 protein expression by flow cytometry, cell surface biotinylation, Western blotting, and ELISA. Results: ROR1 protein is selectively expressed on the surface of B-CLL cells, whereas normal B cells, other normal blood cells, and normal adult tissues do not express cell surface ROR1. Moreover, cell surface expression of ROR1 is uniform and constitutive, i.e., independent of anatomic niches, independent of biological and clinical heterogeneity of B-CLL, independent of B-cell activation, and found at similar levels in all B-CLL samples tested. The antibody binding capacity of B-CLL cell surface ROR1 was determined to be in the range of 103 to 104 molecules per cell. A portion of B-CLL cell surface ROR1 was actively internalized upon antibody binding. Soluble ROR1 protein was detectable in sera of &amp;lt;25% of B-CLL patients and a similar fraction of healthy donors at concentrations below 200 ng/mL. Conclusions: The restricted, uniform, and constitutive cell surface expression of ROR1 protein in B-CLL provides a strong incentive for the development of targeted therapeutics such as monoclonal antibodies.
Recent advances in the imaging of hepatocellular carcinoma
Authors: Myung-Won You, So Yeon Kim, Kyoung Won Kim, So Jung Lee, Yong Moon Shin, Jin Hee Kim, Moon-Gyu Lee
Journal: Clinical and Molecular Hepatology (2015)

The role of imaging is crucial for the surveillance, diagnosis, staging and treatment monitoring of hepatocellular carcinoma (HCC). Over the past few years, considerable technical advances were made in imaging of HCCs. New imaging technology, however, has introduced new challenges in our clinical practice. In this article, the current status of clinical imaging techniques for HCC is addressed. The diagnostic performance of imaging techniques in the context of recent clinical guidelines is also presented. Keywords: Hepatocellular carcinoma; Diagnostic imaging; Ultrasonography; Computed tomography; Magnetic resonance imaging
What Determines Severity in Sickle-Cell Disease?
Authors: Alan N. Schechter, H. Franklin Bunn
Journal: New England Journal of Medicine (1982)

A paradox has always troubled investigators of sickle-cell anemia. Although this disorder has been defined at the level of a single, specific nucleotide change in the genomic DNA and the corresponding amino acid substitution in the β-chain of hemoglobin, the clinical manifestations of sickle-cell anemia are more diverse than those of most other genetic diseases. In fact, the spectrum of severity in this disease is as broad as that in many of the "polymorphic" diseases, such as diabetes.Attempts to explain this wide range of severity have been thwarted by the lack of concordance between hematologic measurements and clinical events . . .
Abstract P2-11-14: Does the Nottingham prognostic index further refine survival within the breast cancer subtypes?
Authors: V Caggiano, C Parise
Journal: Cancer Research (2013)

Abstract Background The Nottingham Prognostic Index (NPI), based on tumor size, lymph node status, and histologic grade, is a well established method of predicting survival of operable breast cancer. Breast cancer survival of the luminal, triple negative, and HER2 overexpressing subtypes has been previously described. The purpose of this study is to determine if the NPI can further refine survival of these subtypes within the AJCC stages of breast cancer. Method We identified 118,923 cases of stages 1-3 first primary female invasive breast cancer from the California Cancer Registry diagnosed between January 1, 2000 and December 31, 2010 with known ER/PR/HER2 status. The subtypes were classified as Luminal A (ER and/or PR-positive, HER2-negative), Luminal B (ER and/or PR-positive, HER2-positive), triple negative (ER-/PR-/HER2-), or HER2-overexpressing (ER-/PR-/HER2+). The NPI was computed and cases were stratified as having good (NPI &amp;lt;3.4), moderate (3.4-5.4) or poor (&amp;gt;5.4) prognosis. Kaplan Meier survival analysis (95% CIs) was used to compare survival among the NPI categories within each subtype and stage. Results The table shows that in stage 1, there was a statistically significant difference in survival between the good versus the moderate and poor NPI categories for luminal A, luminal B, and the triple negative subtypes. For the HER2-overexpressing subtype, the only difference was between the good and poor NPI category. For stage 2, the only difference in survival was for Luminal A where both the moderate (94.6%; 93.4%, 95.8%) and poor (84.3%; 83.6%, 85.0%) NPI categories had worse survival than the good category (99.9%; 97.1%, 100.0%). For stage 3, there were no differences among the NPI categories for any of the subtypes. Eight year survival of stage 1 breast cancer subtypes within the NPI categories 8-Year Survival95% LCL*95% UCL*Luminal A Good95.695.196.2Moderate94.493.994.9Poor90.389.191.5Luminal B Good95.894.097.5Moderate94.393.195.5Poor88.686.291.0Triple Negative Good93.690.197.0Moderate88.186.090.1Poor86.084.287.8HER2-overexpressing Good92.387.697.1Moderate89.786.992.4Poor86.483.389.5*CL = Confidence Limit For stage 2, the only difference in survival was for Luminal A where both the moderate (94.6%; 93.4%, 95.8%) and poor (84.3%; 83.6%,85.0%) NPI categories had worse survival than the good category (99.9%; 97.1%, 100.0%). For stage 3, there were no differences among the NPI categories for any of the subtypes. Conclusion The NPI is a valuable addition to AJCC stage 1 for all breast cancer subtypes. The NPI and AJCC staging systems both incorporate lymph node status and tumor size. However, histologic grade, found only in the NPI, may improve the accuracy of survival, especially in stage 1. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-11-14.
Extradural haematoma: effect of delayed treatment.
Authors: A D Mendelow, F J Gillingham
Journal: BMJ (1979)

The case records of patients with extradural haematomas treated in the Lothian region during 1951-60 and 1968-77 were analysed to assess the effect of delay in treatment on morbidity and mortality. Delay was defined as the time from deterioration in level of consciousness to surgical evacuation of clot. There were 83 supratentorial extradural haematomas unassociated with intradural clot or contusion. The mean delay in patients who died was 15.7 hours, while in good-quality survivors the mean delay was 1.9 hours. Mortality decreased from 33.3% during 1951-60 to 8.9% during 1968-77. In addition, good recovery without morbidity occurred in 40.7% of patients in the earlier period and 67.9% in the later period. Mean delays from deterioration in level of consciousness to operation were 9.8 and 2.4 hours in the earlier and later periods respectively. The results emphasise the need for immediate operation in patients deteriorating with extradural haematomas. Direct admission of all head-injured patients to a head and spinal injuries unit staffed by neurosurgeons resulted in minimal delay times as well as a reduction in morbidity and mortality.
Diagnosis of thrombotic thrombocytopenic purpura with normal ADAMTS13 activity and absence of its inhibitor (anti‐ADAMTS13 antibodies)
Authors: Fouad N. Boctor, John A. Smith
Journal: American Journal of Hematology (2007)

Diagnosis of thrombotic thrombocytopenic purpura with normal ADAMTS13 activity and absence of its inhibitor (anti-ADAMTS13 antibodies)To the Editor: We read with interest the case report by Martin et al. [1], who described a Jehovah's Witness patient, who was treated for dysuria by trimethoprim-sulfamethoxazole and later found to be febrile, tachycardic, hypotensive, and to have a diffuse urticarial rash.Patient laboratory results revealed anemia, thrombocytopenia with platelets of 76,000 Â 10 9 , elevated lactate dehydrogenase up to 10,041 U/L, and blood smear with >50 schistocytes per 100Â field.The patient's ADAMTS13 activity and its inhibitor (autologous anti-ADAMTS13 antibodies) were normal.The patient was diagnosed with thrombotic thrombocytopenic purpura (TTP) and treated with IVIG, steroids and rituximab.In the light of the recent discovery that inhibition of ADAMTS13 activity (a von Willebrand factor cleaving protease) by its autoantibodies is a hallmark and specific for autoimmune TTP [2,3], normal ADAMTS13 activity and absence of inhibitors in this patient made TTP diagnosis questionable.The moderate thrombocytopenia, increase of LDH and presence of schistocytes could result from HUS, DIC, and other microangiopathic conditions.The authors suggested the hypersensitivity to the drug as a cause of TTP.The hypersensitivity and damage of endothelium or a problem with the complement system points to HUS rather than TTP.In addition, if patient was negative for the autoantibody, what is the rational in using rituximab for the treatment?We understand that there is a lot of confusion in differentiation among different causes of microangiopathic hemolysis and thrombocytopenia (MIHT), because the pathogenesis of microvascular thrombosis is unknown [2].However, let us agree that an autoimmune nonhereditary TTP diagnosis in patient with MIHT must have low ADAMTS13 activity and the presence of inhibitory anti-ADAMTS13 antibodies.