125 results on '"Samuel Gross"'
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2. Code-Reuse Attacks for the Web: Breaking Cross-Site Scripting Mitigations via Script Gadgets.
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Sebastian Lekies, Krzysztof Kotowicz, Samuel Groß, Eduardo A. Vela Nava, and Martin Johns
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- 2017
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3. WiLIS: Architectural modeling of wireless systems.
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Kermin Elliott Fleming, Man Cheuk Ng, Samuel Gross, and Arvind
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- 2011
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4. Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA
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M.C. Liu, G.R. Oxnard, E.A. Klein, C. Swanton, M.V. Seiden, Minetta C. Liu, Geoffrey R. Oxnard, Eric A. Klein, David Smith, Donald Richards, Timothy J. Yeatman, Allen L. Cohn, Rosanna Lapham, Jessica Clement, Alexander S. Parker, Mohan K. Tummala, Kristi McIntyre, Mikkael A. Sekeres, Alan H. Bryce, Robert Siegel, Xuezhong Wang, David P. Cosgrove, Nadeem R. Abu-Rustum, Jonathan Trent, David D. Thiel, Carlos Becerra, Manish Agrawal, Lawrence E. Garbo, Jeffrey K. Giguere, Ross M. Michels, Ronald P. Harris, Stephen L. Richey, Timothy A. McCarthy, David M. Waterhouse, Fergus J. Couch, Sharon T. Wilks, Amy K. Krie, Rama Balaraman, Alvaro Restrepo, Michael W. Meshad, Kimberly Rieger-Christ, Travis Sullivan, Christine M. Lee, Daniel R. Greenwald, William Oh, Che-Kai Tsao, Neil Fleshner, Hagen F. Kennecke, Maged F. Khalil, David R. Spigel, Atisha P. Manhas, Brian K. Ulrich, Philip A. Kovoor, Christopher Stokoe, Jay G. Courtright, Habte A. Yimer, Timothy G. Larson, Charles Swanton, Michael V. Seiden, Steven R. Cummings, Farnaz Absalan, Gregory Alexander, Brian Allen, Hamed Amini, Alexander M. Aravanis, Siddhartha Bagaria, Leila Bazargan, John F. Beausang, Jennifer Berman, Craig Betts, Alexander Blocker, Joerg Bredno, Robert Calef, Gordon Cann, Jeremy Carter, Christopher Chang, Hemanshi Chawla, Xiaoji Chen, Tom C. Chien, Daniel Civello, Konstantin Davydov, Vasiliki Demas, Mohini Desai, Zhao Dong, Saniya Fayzullina, Alexander P. Fields, Darya Filippova, Peter Freese, Eric T. Fung, Sante Gnerre, Samuel Gross, Meredith Halks-Miller, Megan P. Hall, Anne-Renee Hartman, Chenlu Hou, Earl Hubbell, Nathan Hunkapiller, Karthik Jagadeesh, Arash Jamshidi, Roger Jiang, Byoungsok Jung, TaeHyung Kim, Richard D. Klausner, Kathryn N. Kurtzman, Mark Lee, Wendy Lin, Jafi Lipson, Hai Liu, Qinwen Liu, Margarita Lopatin, Tara Maddala, M. Cyrus Maher, Collin Melton, Andrea Mich, Shivani Nautiyal, Jonathan Newman, Joshua Newman, Virgil Nicula, Cosmos Nicolaou, Ongjen Nikolic, Wenying Pan, Shilpen Patel, Sarah A. Prins, Richard Rava, Neda Ronaghi, Onur Sakarya, Ravi Vijaya Satya, Jan Schellenberger, Eric Scott, Amy J. Sehnert, Rita Shaknovich, Avinash Shanmugam, K.C. Shashidhar, Ling Shen, Archana Shenoy, Seyedmehdi Shojaee, Pranav Singh, Kristan K. Steffen, Susan Tang, Jonathan M. Toung, Anton Valouev, Oliver Venn, Richard T. Williams, Tony Wu, Hui H. Xu, Christopher Yakym, Xiao Yang, Jessica Yecies, Alexander S. Yip, Jack Youngren, Jeanne Yue, Jingyang Zhang, Lily Zhang, Lori (Quan) Zhang, Nan Zhang, Christina Curtis, and Donald A. Berry
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0301 basic medicine ,medicine.medical_specialty ,Bisulfite sequencing ,Rectum ,Gastroenterology ,Article ,cell-free DNA ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,Positron Emission Tomography Computed Tomography ,Internal medicine ,Biomarkers, Tumor ,medicine ,cancer ,Humans ,Mass Screening ,Prospective Studies ,Esophagus ,Early Detection of Cancer ,business.industry ,Stomach ,DNA, Neoplasm ,Hematology ,DNA Methylation ,Plasma cell neoplasm ,16. Peace & justice ,Anus ,Confidence interval ,3. Good health ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Cell-free fetal DNA ,030220 oncology & carcinogenesis ,Feasibility Studies ,Female ,next-generation sequencing ,methylation ,business ,Cell-Free Nucleic Acids - Abstract
Background Early cancer detection could identify tumors at a time when outcomes are superior and treatment is less morbid. This prospective case-control sub-study (from NCT02889978 and NCT03085888) assessed the performance of targeted methylation analysis of circulating cell-free DNA (cfDNA) to detect and localize multiple cancer types across all stages at high specificity. Participants and methods The 6689 participants [2482 cancer (>50 cancer types), 4207 non-cancer] were divided into training and validation sets. Plasma cfDNA underwent bisulfite sequencing targeting a panel of >100 000 informative methylation regions. A classifier was developed and validated for cancer detection and tissue of origin (TOO) localization. Results Performance was consistent in training and validation sets. In validation, specificity was 99.3% [95% confidence interval (CI): 98.3% to 99.8%; 0.7% false-positive rate (FPR)]. Stage I–III sensitivity was 67.3% (CI: 60.7% to 73.3%) in a pre-specified set of 12 cancer types (anus, bladder, colon/rectum, esophagus, head and neck, liver/bile-duct, lung, lymphoma, ovary, pancreas, plasma cell neoplasm, stomach), which account for ∼63% of US cancer deaths annually, and was 43.9% (CI: 39.4% to 48.5%) in all cancer types. Detection increased with increasing stage: in the pre-specified cancer types sensitivity was 39% (CI: 27% to 52%) in stage I, 69% (CI: 56% to 80%) in stage II, 83% (CI: 75% to 90%) in stage III, and 92% (CI: 86% to 96%) in stage IV. In all cancer types sensitivity was 18% (CI: 13% to 25%) in stage I, 43% (CI: 35% to 51%) in stage II, 81% (CI: 73% to 87%) in stage III, and 93% (CI: 87% to 96%) in stage IV. TOO was predicted in 96% of samples with cancer-like signal; of those, the TOO localization was accurate in 93%. Conclusions cfDNA sequencing leveraging informative methylation patterns detected more than 50 cancer types across stages. Considering the potential value of early detection in deadly malignancies, further evaluation of this test is justified in prospective population-level studies.
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- 2020
5. Evaluation of cell-free DNA approaches for multi-cancer early detection
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Arash Jamshidi, Minetta C. Liu, Eric A. Klein, Oliver Venn, Earl Hubbell, John F. Beausang, Samuel Gross, Collin Melton, Alexander P. Fields, Qinwen Liu, Nan Zhang, Eric T. Fung, Kathryn N. Kurtzman, Hamed Amini, Craig Betts, Daniel Civello, Peter Freese, Robert Calef, Konstantin Davydov, Saniya Fayzullina, Chenlu Hou, Roger Jiang, Byoungsok Jung, Susan Tang, Vasiliki Demas, Joshua Newman, Onur Sakarya, Eric Scott, Archana Shenoy, Seyedmehdi Shojaee, Kristan K. Steffen, Virgil Nicula, Tom C. Chien, Siddhartha Bagaria, Nathan Hunkapiller, Mohini Desai, Zhao Dong, Donald A. Richards, Timothy J. Yeatman, Allen L. Cohn, David D. Thiel, Donald A. Berry, Mohan K. Tummala, Kristi McIntyre, Mikkael A. Sekeres, Alan Bryce, Alexander M. Aravanis, Michael V. Seiden, and Charles Swanton
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Chemical Biology & High Throughput ,Signalling & Oncogenes ,Human Biology & Physiology ,Cancer Research ,Ecology,Evolution & Ethology ,Oncology ,Genome Integrity & Repair ,Tumour Biology ,Genetics & Genomics ,Computational & Systems Biology - Abstract
In the Circulating Cell-free Genome Atlas (NCT02889978) substudy 1, we evaluate several approaches for a circulating cell-free DNA (cfDNA)-based multi-cancer early detection (MCED) test by defining clinical limit of detection (LOD) based on circulating tumor allele fraction (cTAF), enabling performance comparisons. Among 10 machine-learning classifiers trained on the same samples and independently validated, when evaluated at 98% specificity, those using whole-genome (WG) methylation, single nucleotide variants with paired white blood cell background removal, and combined scores from classifiers evaluated in this study show the highest cancer signal detection sensitivities. Compared with clinical stage and tumor type, cTAF is a more significant predictor of classifier performance and may more closely reflect tumor biology. Clinical LODs mirror relative sensitivities for all approaches. The WG methylation feature best predicts cancer signal origin. WG methylation is the most promising technology for MCED and informs development of a targeted methylation MCED test.
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- 2022
6. Airblue: a system for cross-layer wireless protocol development.
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Man Cheuk Ng, Kermin Elliott Fleming, Mythili Vutukuru, Samuel Gross, Arvind, and Hari Balakrishnan
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- 2010
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7. Abstract 139: cfDNA methylation profiling distinguishes lineage-specific hematologic malignancies
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Zhao Dong, Alexander P. Fields, Rita Shaknovich, Arash Jamshidi, Oliver Venn, Kathryn N. Kurtzman, Xiaoji Chen, Samuel Gross, Eric T. Fung, Anne-Renee Hartman, M. C. Maher, Qinwen Liu, Alex Aravanis, Earl Hubbell, and Jan Schellenberger
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Cancer Research ,Myeloid ,Methylation ,Disease ,Plasma cell neoplasm ,Biology ,Genome ,chemistry.chemical_compound ,Lineage specific ,medicine.anatomical_structure ,Oncology ,chemistry ,Methylation profiling ,medicine ,Cancer research ,Heme - Abstract
Introduction: Hematologic (heme) malignancies and their precursor conditions are highly prevalent. They are also diverse in biology, clinical presentation, and outcomes, underlining the importance of differentiating them. Previously, we demonstrated that a blood-based targeted methylation assay detected multiple cancer types across stages. Here, we examined test performance on various heme cancers, identifying specific methylation signatures. Methods: From the second substudy (training set) of the Circulating Cell-free Genome Atlas (CCGA) study (NCT02889978), we evaluated 325 participants from 17 different heme disease subtypes and 3,211 non-cancer controls enrolled without a cancer diagnosis. A cross-validated mutual information-based algorithm was used to identify features that discriminated heme subtypes. The resulting feature distribution was visualized using uniform manifold approximation and projection (UMAP) dimensionality reduction on held-out data. In cross validation with feature selection, we then trained a multinomial classifier to distinguish from among the major heme cancers and non-cancer and correlated the model's class probabilities to positions in feature space. Results: Dimensionality reduction and visualization of input features demonstrated that heme malignancies separated into five major clusters reflecting developmental lineages and disease ontogeny: myeloid, circulating lymphomas, hodgkin lymphomas, non-hodgkin lymphomas, and plasma cell neoplasm. The position of samples within each heme cluster correlated with the cancer signal strength. At 99.4% specificity [95% CI: 99.1, 99.7], heme cancer detection was 74.5% [69.4, 79.1] overall, 67.7% [41.1, 87.8] for myeloid, 77.9% [66.3, 86.9] for circulating lymphomas, 90.7% [73.2, 98.4] for hodgkin lymphomas, 68.6% [60.4, 76.1] for other non-hodgkin lymphomas, and 78.8% [67.0, 87.9] for plasma cell neoplasms. Of 18 non-cancer participants who were classified as having heme cancers, 4 were predicted as myeloid, 6 as circulating lymphoid, and 8 as other non-hodgkin lymphoid neoplasms ( Conclusion: Methylation features of cfDNA in patients with heme malignancies delineated five major clusters that reflected disease ontogeny and heme lineage. Lineage-specific signals followed a gradient suggestive of variation in disease-related methylation or tumor DNA shedding. These findings contribute to the understanding of biological signals that arise from various heme conditions. Since in general, most cfDNA arises from blood lineages, this knowledge will guide further efforts towards removing interfering biological signals from cfDNA-based cancer detection assays and achieving even more sensitive detection of multiple cancer types. Citation Format: Qinwen Liu, Rita Shaknovich, Xiaoji Chen, Zhao Dong, M. C. Maher, Samuel Gross, Alexander P. Fields, Jan Schellenberger, Kathryn N. Kurtzman, Eric T. Fung, Anne-Renee Hartman, Earl Hubbell, Arash Jamshidi, Alexander M. Aravanis, Oliver Venn. cfDNA methylation profiling distinguishes lineage-specific hematologic malignancies [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 139.
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- 2020
8. Tumor methylation patterns to measure tumor fraction in cell-free DNA
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Vasiliki Demas, Yasushi Saito, Pranav Parmjit Singh, Matthew H. Larson, Sarah Stuart, Colin Melton, Arash Jamshidi, Lily Zhang, Joshua Newman, Samuel Gross, Gordon Cann, Christopher Chang, Oliver Venn, Alex Aravanis, and Earl Hubbell
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Cancer Research ,business.industry ,Cell ,Cancer ,Methylation ,medicine.disease ,Free dna ,chemistry.chemical_compound ,medicine.anatomical_structure ,Oncology ,chemistry ,Cancer research ,medicine ,business ,DNA - Abstract
3052 Background: Cell-free DNA (cfDNA) tumor fraction (TF), the proportion of tumor molecules in a cfDNA sample, is a direct measurement of signal for cfDNA cancer applications. The Circulating Cell-free Genome Atlas study (CCGA; NCT02889978) is a prospective, multi-center, observational, case-control study designed to support development of a methylation-based, multi-cancer detection test in which a classifier is trained to distinguish cancer from non-cancer. Here we leveraged CCGA data to examine the relationship between cfDNA containing tumor DNA methylation patterns, TF, and cancer classification performance. Methods: The CCGA classifier was trained on whole-genome bisulfite sequencing (WGBS) and targeted methylation (TM) sequencing data to detect cancer versus non-cancer. 822 samples had biopsy WGBS performed; of those, 231 also had cfDNA targeted methylation (TM) and cfDNA whole-genome sequencing (WGS). Biopsy WGBS identified somatic single nucleotide variants (SNV) and methylation variants (MV; defined as methylation patterns in sequenced DNA fragments observed commonly in biopsy but rarely [ < 1/10,000] in the cfDNA of non-cancer controls [n = 898]). Observed tumor fragment counts (SNV in WGS; MV in TM), were modeled as a Poisson process with rate dependent on TF. TF and classifier limits of detection (LOD) were each assessed using Bayesian logistic regression. Results: Across biopsy samples, a median of 2,635 MV was distributed across the genome, with a median of 86.8% shared with ≥1 participant, and a median of 69.3% targeted by the TM assay. TF LOD from MV was 0.00050 (95% credible interval [CI]: 0.00041 - 0.00061); MV and SNV estimates were concordant (Spearman’s Rho: 0.820). MV TF estimates explained classifier performance (Spearman’s Rho: 0.856) and allowed determination of the classifier LOD (0.00082 [95% CI: 0.00057 - 0.00115]). Conclusions: These data demonstrate the existence of methylation patterns in tumor-derived cfDNA fragments that are rarely found in individuals without cancer; their abundance directly measured TF, and was a major factor influencing classification performance. Finally, the low classifier LOD (~0.1%) motivates further clinical development of a methylation-based assay for cancer detection. Clinical trial information: NCT02889978 .
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- 2020
9. Tu1836 TUMOR AREA AND MICROSCOPIC EXTENT OF INVASION DETERMINE CIRCULATING TUMOR CELL-FREE DNA FRACTION IN PLASMA AND DETECTABILITY OF COLORECTAL CANCER
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Tony J. Wu, Samuel Gross, Nan Zhang, Joerg Bredno, Brian C. Allen, John F. Beausang, Earl Hubbell, Alexander P. Fields, Hai Liu, Jackie Brooks, Oliver Venn, Lori Zhang, Alex Aravanis, Margarita Lopatin, Arash Jamshidi, Xiaoji Chen, Anne-Renee Hartman, Jafi A. Lipson, and Qinwen Liu
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Circulating tumor cell ,Hepatology ,Chemistry ,Colorectal cancer ,Gastroenterology ,Cancer research ,medicine ,Fraction (chemistry) ,medicine.disease ,Free dna - Published
- 2020
10. Su1772 MULTI-CANCER DETECTION OF EARLY-STAGE CANCERS WITH SIMULTANEOUS TISSUE LOCALIZATION USING A PLASMA CIRCULATING TUMOR CELL-FREE DNA-BASED TARGETED METHYLATION ASSAY
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Oliver Venn, Samuel Gross, Eric T. Fung, Peter T. Yu, Hai Liu, Minetta C. Liu, Anne-Renee Hartman, Nan Zhang, Earl Hubbell, Geoffrey R. Oxnard, Michael V. Seiden, Eric A. Klein, Alex Aravanis, Mikkael A. Sekeres, Kathryn N. Kurtzman, Donalds Richards, John F. Beausang, Brian C. Allen, Alexander P. Fields, and Arash Jamshidi
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Circulating tumor cell ,Hepatology ,Chemistry ,Gastroenterology ,Cancer research ,Cancer detection ,Methylation ,Stage (cooking) ,Free dna - Published
- 2020
11. Tumor area and microscopic extent of invasion to determine circulating tumor DNA fraction in plasma and detectability of colorectal cancer (CRC)
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Joerg Bredno, Tony Wu, Earl Hubbell, Oliver Venn, Lori Zhang, Xiaoji Chen, Jacqueline D. Brooks, Rita Lopatin, Anne-Renee Hartman, Jafi A. Lipson, Qinwen Liu, Brian C. Allen, Arash Jamshidi, Hai Liu, Alexander P. Fields, Samuel Gross, Nan Zhang, John F. Beausang, and Alex Aravanis
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Cancer Research ,Oncology ,Colorectal cancer ,business.industry ,Circulating tumor DNA ,medicine ,Cancer research ,medicine.disease ,business ,Genome - Abstract
243 Background: Circulating Cell-free Genome Atlas (CCGA; NCT02889978) is a multi-center, case-control, observational study with longitudinal follow-up to develop a cfDNA assay in which classifiers were trained on whole-genome bisulfite sequencing (WGBS) and targeted methylation (TM) sequencing data for detection of multiple cancer types. Previously, we showed that the fraction of ctDNA fragments (TF) was a stronger predictor of cancer detection than clinical stage and an equivalent predictor for survival. Given that CRC tumors can be described via surface area (TSA) and microscopic tumor extent (microinvasion), CRC was used as a model to examine the biophysical determinants of TF. Methods: Detection of multiple cancers with WGBS at 98% and TM at > 99% specificity, and methods for determining TF, were previously reported. A model to predict the presence of detectable cfDNA fragments for CRC adenocarcinomas of stages I, II, and III included TSA and microinvasion beyond the subserosa. Predictors were combined assuming a linear increase of cfDNA shedding with tumor size, with scaling factors depending on microinvasion. Model parameters were determined for 27 participants (7, 11, 9 for stages I, II, III, resp.) with WGBS and applied to 40 participants (12, 15, 13 for I, II, III, resp.) with TM assay and information on tumor size and microinvasion. Results: CRC detection at stages I/II/III was 33/46, 61/73, 57/74% for WGBS/TM. TF predicted detection with AUC = 97.6. The model predicted TF as TSA multiplied by 3.81*10−6 / mm2 for tumors that invaded beyond the subserosa (p < 0.001). This was 4.4x higher than estimates for tumors below the subserosa. The model trained on the WGBS assay predicted CRC detection in the TM assay with an AUC of 0.844. Conclusions: This model used TSA (number of tumor cells) and microinvasion (bloodstream access) to predict the fraction of CRC ctDNA fragments in blood without needing to account for stage. Tumors not penetrating the subserosa had low ctDNA shedding that likely limited detection. These findings may generalize to other cancer types, providing principles to predict ctDNA shedding and thus cancer detectability based on microinvasion and surface area. Clinical trial information: NCT02889978.
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- 2020
12. Code-Reuse Attacks for the Web
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Martin Johns, Eduardo A. Vela Nava, Krzysztof Kotowicz, Sebastian Lekies, and Samuel Groß
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0301 basic medicine ,Source code ,business.industry ,Computer science ,Cross-site scripting ,media_common.quotation_subject ,02 engineering and technology ,Content Security Policy ,Web application security ,computer.software_genre ,Computer security ,JavaScript ,HTML element ,World Wide Web ,03 medical and health sciences ,030104 developmental biology ,Scripting language ,020204 information systems ,0202 electrical engineering, electronic engineering, information engineering ,Web application ,business ,computer ,Vulnerability (computing) ,media_common ,computer.programming_language - Abstract
Cross-Site Scripting (XSS) is an unremitting problem for the Web. Since its initial public documentation in 2000 until now, XSS has been continuously on top of the vulnerability statistics. Even though there has been a considerable amount of research and developer education to address XSS on the source code level, the overall number of discovered XSS problems remains high. Because of this, various approaches to mitigate XSS have been proposed as a second line of defense, with HTML sanitizers, Web Application Firewalls, browser-based XSS filters, and the Content Security Policy being some prominent examples. Most of these mechanisms focus on script tags and event handlers, either by removing them from user-provided content or by preventing their script code from executing. In this paper, we demonstrate that this approach is no longer sufficient for modern applications: We describe a novel Web attack that can circumvent all of theses currently existing XSS mitigation techniques. In this attack, the attacker abuses so called script gadgets (legitimate JavaScript fragments within an application's legitimate code base) to execute JavaScript. In most cases, these gadgets utilize DOM selectors to interact with elements in the Web document. Through an initial injection point, the attacker can inject benign-looking HTML elements which are ignored by these mitigation techniques but match the selector of the gadget. This way, the attacker can hijack the input of a gadget and cause processing of his input, which in turn leads to code execution of attacker-controlled values. We demonstrate that these gadgets are omnipresent in almost all modern JavaScript frameworks and present an empirical study showing the prevalence of script gadgets in productive code. As a result, we assume most mitigation techniques in web applications written today can be bypassed.
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- 2017
13. The Circulating Cell-free Genome Atlas (CCGA) Study: Follow-up (F/U) on non-cancer participants with cancer-like cell-free DNA signals
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Kathryn N. Kurtzman, David M. Waterhouse, Michael V. Seiden, Anne-Renee Hartman, Oliver Venn, Allen Lee Cohn, Eric A. Klein, Minetta C. Liu, Geoffrey R. Oxnard, Samuel Gross, Eric T. Fung, and Earl Hubbell
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Cancer Research ,medicine.diagnostic_test ,business.industry ,Non cancer ,Cancer detection ,Cell free ,Genome ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Oncology ,Cell-free fetal DNA ,chemistry ,030220 oncology & carcinogenesis ,Cancer research ,Medicine ,Blood test ,business ,DNA ,030215 immunology - Abstract
5574 Background: A noninvasive cell-free DNA (cfDNA)-based cancer detection assay offers the hope of a blood test that might reduce morbidity and mortality of cancers, particularly those without recommended screening tests (eg, some gynecologic cancers). CCGA (NCT02889978) is a prospective, multi-center, longitudinal, case-control study evaluating models for discriminating cancer versus non-cancer. Here, we report F/U of control participants (pts) who demonstrated a cancer-signal in CCGA. Methods: Clinically evaluable samples (N = 2508) from pts enrolled without a cancer diagnosis (dx; NC) and treatment-naive pts with newly diagnosed cancer (C) were divided into training (n = 1564; 580 NC, 984 C) and test (n = 944; 368 NC, 576 C) sets. Classification performance (cancer/non-cancer) was assessed via 3 prototype assays: whole-genome bisulfite (WGBS), whole-genome (WGS), and targeted (507 gene) sequencing. Notable outlier NC pts were identified with cancer-like scores in either ≥2 assay classification results or by the presence of known cancer drivers with ≥1 assay classification result suggesting cancer. All pts are currently in F/U in accordance with study protocol (to date: 80% with > 10 mo and 15% with > 22 mo F/U). Results: Among training and test sets, 8 ( < 1%) NC pts were identified with a cancer-like signal. To-date, 2 have been diagnosed with a gynecologic malignancy: 1 stage IIIc clear cell endometrial carcinoma and 1 stage IIIc ovarian cancer, 3 and 2 months (mo) post-enrollment [PE], respectively. Among C pts in the study, sensitivity (at 98% specificity; WGBS) in these cancer types was: uterine/endometrial: 11% (n = 27 train) and 22% (n = 9 test); ovarian: 82% (n = 17) and 71% (n = 7). In addition, a third NC pt was diagnosed with a stage IV lung cancer 15 mo PE. Conclusions: This cfDNA-based assay detected a cancer-like signal that anticipated a clinical presentation of cancer in undiagnosed pts as early as 15 months prior to the actual dx. High specificity ( > 99%) requires accounting for undiagnosed cancers in study design and analysis. Together, these data suggest that this prototype assay may have high performance detecting a variety of gynecological and other cancers. Clinical trial information: NCT02889978.
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- 2019
14. The Circulating Cell-free Genome Atlas (CCGA) Study: Size selection of cell-free DNA (cfDNA) fragments
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Nicula Virgil, Matthew H. Larson, Christopher Yakym, Alex Aravanis, Monica Pimentel, M. Cyrus Maher, Samuel Gross, Calef Robert Abe Paine, Ting-Chun Liu, Joshua Newman, Yiqi Zhou, Darya Filippova, Arash Jamshidi, and Jennifer Berman
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Cancer Research ,Somatic cell ,business.industry ,Cell free ,Computational biology ,Genome ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,Cell-free fetal DNA ,Atlas (anatomy) ,030220 oncology & carcinogenesis ,Medicine ,Copy number aberration ,business ,030215 immunology - Abstract
3103 Background: Detection of somatic copy number aberrations in individuals with cancer via cfDNA whole-genome sequencing (WGS) is challenging at low tumor fractions. Given that tumor-derived cfDNA fragments are shorter than those from healthy tissues, this exploratory analysis evaluated the potential effect of size selection on the ability to detect cancer. Methods: CCGA WGS libraries were in silico and in vitro size selected to estimate the change in tumor fraction by tumor types (breast, lung, and colorectal [CRC]) and stage (I-III vs IV). In silico analyses used clinically evaluable training set samples with WGS assay results (n = 1422: 560 non-cancer [NC], 862 cancer [C] stages I-IV); classification (cancer/non-cancer) performance was estimated using fragments within the 90-150 bp range. In vitro analyses used a subset of samples (n = 93: 28 NC, 65 C stages I-IV), including C cases sampled within a range of tumor fractions; tumor fraction was also measured at each progressive removal of maximum-length fragments (intervals of 10 bp: 150 bp down to 50 bp). Results: In silico and in vitro analyses, respectively, resulted in median 2.00±0.58-fold (at 6.91±2.64X depth) and 2.00±0.52-fold (at 23±4.45X depth) increases, in overall tumor fraction (compared to non-size-selected 36X depth). This was consistent across tumor types ( in silico: 1.78±0.73 breast, 2.00±0.58 CRC, 2.00±0.41 lung; in vitro: 2.00±0.82 breast, 2.51±0.52 CRC, 2.53±0.94 lung) and stages ( in silico: 2.00±0.74 I-III, 1.78±0.52 IV; in vitro: 2.00±0.55 I-III, 1.68±0.29 IV). Tumor fraction increased with initial fragment length titrations, but not following size selection to shorter lengths ( < 140 bp). Classifier trained on in silico size-selected data had increased sensitivity at 98% specificity compared to those trained on non-size-selected data (p < 1e-5). Conclusions: In silico and in vitro size selection consistently increased tumor fraction across cancer types and stages, and this increase was maximized by tuning the length range of size selection. Relative to full-depth data, classification performance improved significantly. These data suggest that size selection targeting cfDNA under 140 bp may enhance cfDNA-based cancer detection. Clinical trial information: NCT02889978.
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- 2019
15. Race and Wrongful Convictions in the United States
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Klara Stephens, Klara Stephens, Maurice Possley, Samuel Gross, Klara Stephens, Klara Stephens, Maurice Possley, and Samuel Gross
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African Americans are only 13% of the American population but a majority of innocent defendants wrongfully convicted of crimes and later exonerated. They constitute 47% of the 1,900 exonerations listed in the National Registry of Exonerations (as of October 2016), and the great majority of more than 1,800 additional innocent defendants who were framed and convicted of crimes in 15 large-scale police scandalsand later cleared in "group exonerations." This report examines this racial disparity in the context of the three types of crime that produce the largest numbers of exonerations in the Registry: murder, sexual assault, and drug crimes.
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- 2017
16. Abstract LB-343: Development of plasma cell-free DNA (cfDNA) assays for early cancer detection: first insights from the Circulating Cell-Free Genome Atlas Study (CCGA)
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Arash Jamshidi, Timothy J. Yeatman, Tara Maddala, Daniel Civello, Chenlu Hou, Anne-Renee Hartman, Roger Jiang, Rosanna Lapham, Kristan Steffen, Samuel Gross, Craig Betts, Ling Shen, Donald A. Richards, Byoungsok Jung, Seyedmehdi Shojaee, Collin Melton, Onur Sakarya, Hui Xu, Ravi Vijaya Satya, Konstantin Davydov, Jeanne Yue, Geoffrey R. Oxnard, Jonathan Newman, Robert Tibshirani, Cosmos Nicolaou, Earl Hubbell, José Baselga, Shivani Nautiyal, John A. Beausang, David J. Smith, Christina Curtis, Charles Swanton, Hamed Amini, Sante Gnerre, Michael V. Seiden, Darya Filippova, Oliver Venn, Kathryn N. Kurtzman, Saniya Fazullina, Richard P. Rava, Richard J. Williams, Nan Zhang, Eric A. Klein, Alex Aravanis, Joshua Newman, Minetta C. Liu, Daron G. Davis, Anton Valouev, and Sylvia K. Plevritis
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Concordance ,Bisulfite sequencing ,Newly diagnosed ,Cell free ,Plasma cell ,Biology ,Free dna ,Genome ,03 medical and health sciences ,030104 developmental biology ,medicine.anatomical_structure ,Internal medicine ,medicine ,Early Cancer Detection - Abstract
CCGA [NCT02889978] is the largest study of cfDNA-based early cancer detection; the first CCGA learnings from multiple cfDNA assays are reported here. This prospective, multi-center, observational study has enrolled 10,012 of 15,000 demographically-balanced participants at 141 sites. Blood was collected from participants with newly diagnosed therapy-naive cancer (C, case) and participants without a diagnosis of cancer (noncancer [NC], control) as defined at enrollment. This preplanned substudy included 878 cases, 580 controls, and 169 assay controls (n=1627) across 20 tumor types and all clinical stages. All samples were analyzed by: 1) Paired cfDNA and white blood cell (WBC)-targeted sequencing (60,000X, 507 gene panel); a joint caller removed WBC-derived somatic variants and residual technical noise; 2) Paired cfDNA and WBC whole-genome sequencing (WGS; 35X); a novel machine learning algorithm generated cancer-related signal scores; joint analysis identified shared events; and 3) cfDNA whole-genome bisulfite sequencing (WGBS; 34X); normalized scores were generated using abnormally methylated fragments. In the targeted assay, non-tumor WBC-matched cfDNA somatic variants (SNVs/indels) accounted for 76% of all variants in NC and 65% in C. Consistent with somatic mosaicism (i.e., clonal hematopoiesis), WBC-matched variants increased with age; several were non-canonical loss-of-function mutations not previously reported. After WBC variant removal, canonical driver somatic variants were highly specific to C (e.g., in EGFR and PIK3CA, 0 NC had variants vs 11 and 30, respectively, of C). Similarly, of 8 NC with somatic copy number alterations (SCNAs) detected with WGS, 4 were derived from WBCs. WGBS data revealed informative hyper- and hypo-fragment level CpGs (1:2 ratio); a subset was used to calculate methylation scores. A consistent “cancer-like” signal was observed in 99% specificity for invasive cancer, and support the promise of cfDNA assay for early cancer detection. Additional data will be presented on detected plasma:tissue variant concordance and on multi-assay modeling. Citation Format: Alexander A. Aravanis, Geoffrey R. Oxnard, Tara Maddala, Earl Hubbell, Oliver Venn, Arash Jamshidi, Ling Shen, Hamed Amini, John A. Beausang, Craig Betts, Daniel Civello, Konstantin Davydov, Saniya Fazullina, Darya Filippova, Sante Gnerre, Samuel Gross, Chenlu Hou, Roger Jiang, Byoungsok Jung, Kathryn Kurtzman, Collin Melton, Shivani Nautiyal, Jonathan Newman, Joshua Newman, Cosmos Nicolaou, Richard Rava, Onur Sakarya, Ravi Vijaya Satya, Seyedmehdi Shojaee, Kristan Steffen, Anton Valouev, Hui Xu, Jeanne Yue, Nan Zhang, Jose Baselga, Rosanna Lapham, Daron G. Davis, David Smith, Donald Richards, Michael V. Seiden, Charles Swanton, Timothy J. Yeatman, Robert Tibshirani, Christina Curtis, Sylvia K. Plevritis, Richard Williams, Eric Klein, Anne-Renee Hartman, Minetta C. Liu. Development of plasma cell-free DNA (cfDNA) assays for early cancer detection: first insights from the Circulating Cell-Free Genome Atlas Study (CCGA) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-343.
- Published
- 2018
17. Genome-wide sequencing for early stage lung cancer detection from plasma cell-free DNA (cfDNA): The Circulating Cancer Genome Atlas (CCGA) study
- Author
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Donald A. Richards, Charles Swanton, Darya Filippova, Nan Zhang, Ling Shen, Alex Aravanis, Richard Thomas Williams, Karthik A. Jagadeesh, Anton Valouev, John F. Beausang, Sylvia K. Plevritis, Samuel Gross, Shilpen Patel, Earl Hubbell, Oliver Venn, Geoffrey R. Oxnard, Minetta C. Liu, Arash Jamshidi, Tara Maddala, and Anne-Renee Hartman
- Subjects
0301 basic medicine ,Oncology ,Whole genome sequencing ,Cancer Research ,medicine.medical_specialty ,business.industry ,Plasma cell ,medicine.disease ,Genome ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Internal medicine ,White blood cell ,medicine ,Copy-number variation ,Lung cancer ,Indel ,business ,Gene - Abstract
LBA8501 Background: Plasma cfDNA genomic analysis is used widely for the care of advanced lung cancer, but its suitability for early stage lung cancer detection is not well established. CCGA (NCT02889978) is a prospective, multi-center, observational study launched for the development of a noninvasive assay for cancer detection. Methods: Blood was prospectively collected (N = 1627) from 749 controls (no cancer diagnosis) and 878 participants (pts) with newly-diagnosed untreated cancer in this preplanned substudy, including 127 pts with lung cancer. Three prototype sequencing assays were performed: paired cfDNA and white blood cell (WBC) targeted sequencing (507 genes, 60,000X) for single nucleotide variants/indels; paired cfDNA and WBC whole genome sequencing (WGS) for copy number variation (30X); and cfDNA whole genome bisulfite sequencing (WGBS) for methylation (30X). For each assay, a classification model using 10-fold cross-validation was developed for all pts with cancer, then evaluated in the pts with lung cancer; sensitivity was estimated at 95% specificity. Results: We evaluated pts with lung cancer (127) and a subset of controls (580) with similar ages (mean±SD yrs: 67±9, 60±13), 85% and 43% were ever-smokers, and 46% and 22% were men, respectively. Of 3055 nonsynonymous mutations detected across 122 evaluable pts with lung cancer, > 50% were detected in WBC consistent with clonal hematopoiesis (CH). Accounting for CH, sensitivity in 63 stage I-IIIA pts evaluable across all 3 assays was 48% (35-61, targeted), 54% (41-67, WGS), and 56% (43-68, WGBS); in 54 stage IIIB-IV pts it was 85% (73-93, targeted), 91% (80-97, WGS), and 93% (82-98, WGBS) . Similar sensitivities were observed across histological subtypes (adenocarcinoma, squamous cell, small cell). Comparison to tumor WGS and multi-assay classification will be reported. Conclusions: Early stage lung cancers are detectable in cfDNA using a genome-wide sequencing approach. For lung cancer detection using targeted assays, CH must be accounted for to minimize false positives. Assay optimization is ongoing to allow further clinical development in the intended use population. Clinical trial information: NCT02889978.
- Published
- 2018
18. Prevalence of clonal hematopoiesis of indeterminate potential (CHIP) measured by an ultra-sensitive sequencing assay: Exploratory analysis of the Circulating Cancer Genome Atlas (CCGA) study
- Author
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José Baselga, Minetta C. Liu, John F. Beausang, Samuel Gross, Ling Shen, Nan Zhang, Richard Thomas Williams, Oliver Venn, Arash Jamshidi, Geoffrey R. Oxnard, Charles Swanton, Timothy J. Yeatman, Alex Aravanis, Tara Maddala, Anne-Renee Hartman, Michael V. Seiden, Darya Filippova, Kelly L. Bolton, Anton Valouev, and Earl Hubbell
- Subjects
0301 basic medicine ,Cancer Research ,business.industry ,Clonal hematopoiesis ,Exploratory analysis ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Cancer genome ,Cancer research ,Hematopoietic progenitor cells ,Medicine ,Indeterminate ,business ,Ultra sensitive - Abstract
12003Background: CHIP is defined by the presence of age-dependent acquired mutations in hematopoietic progenitor cells and has been reported to occur in up to 30% of individuals 60-70 years of age....
- Published
- 2018
19. Breast cancer cell-free DNA (cfDNA) profiles reflect underlying tumor biology: The Circulating Cell-Free Genome Atlas (CCGA) study
- Author
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Anne-Renee Hartman, Richard Thomas Williams, Anton Valouev, Oliver Venn, Nan Zhang, Eric A. Klein, Samuel Gross, Arash Jamshidi, Ling Shen, David Smith, Tara Maddala, John F. Beausang, Earl Hubbell, Christina Curtis, Fergus J. Couch, Alex Aravanis, Darya Filippova, José Baselga, Minetta C. Liu, and Kathryn N. Kurtzman
- Subjects
0301 basic medicine ,congenital, hereditary, and neonatal diseases and abnormalities ,Cancer Research ,medicine.diagnostic_test ,business.industry ,Tumor biology ,Cell free ,Free dna ,Genome ,03 medical and health sciences ,Breast cancer screening ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Medicine ,Mammography ,Breast cancer cells ,business - Abstract
536Background: New breast cancer screening approaches are needed to detect clinically aggressive subtypes that may not be detected by mammography or are detected late in unscreened populations. CCG...
- Published
- 2018
20. Family Studies of Neutrophil Alloantigens in Bone Marrow Transplantation
- Author
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Roger H. Herzig, James M. Kadushin, Bernice Schacter, Peter Preis, and Samuel Gross
- Subjects
Male ,Isoantigens ,Pathology ,medicine.medical_specialty ,Adolescent ,Bone marrow transplantation ,Neutrophils ,Immunology ,Human leukocyte antigen ,Biology ,Biochemistry ,Serology ,Gene Frequency ,Antigen ,Agglutination Tests ,Genetics ,medicine ,Animals ,Humans ,Transplantation, Homologous ,Immunology and Allergy ,Typing ,Child ,Crosses, Genetic ,Bone Marrow Transplantation ,Leukemia ,Histocompatibility Testing ,Chromosome Mapping ,General Medicine ,Phenotype ,Meiosis ,Haematopoiesis ,medicine.anatomical_structure ,Female ,Rabbits ,Bone marrow - Abstract
In order to evaluate the utility of the neutrophil specific antigens NA1, NA2, Vaz (NC1), NB1 and 9a in the documentation of bone marrow chimeras in recipients of allogeneic bone marrow grafts, neutrophil antigen typing was performed by EDTA microagglutination on the families of 17 patients with hematopoietic disorders under evaluation for bone marrow transplantation. Mendelian segregation independent of HLA and mutually independent was noted for the NA, NB and 9a systems. Vaz (NC1) segregated with and was included in NA2. Serological complexity was noted for NA1 and NA2. Typing for neutrophil antigens was achieved for 13 of 17 patients. Eight of 10 patients with HLA identical siblings had neutrophil antigen markers differing between donor and recipient. Conversion to donor neutrophil phenotype was documented for four recipients of bone marrow grafts. The neutrophil antigens, particularly of the NA system, appear to be useful additional markers for allogeneic bone marrow engraftment.
- Published
- 2008
21. Remote Effect of Malignancy on the Nervous System in Children
- Author
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Thaddeus W. Kurczynski, Samuel J. Horwitz, Samuel Gross, Uros Roessmann, and Amimul A. Choudhury
- Subjects
Male ,Gynecology ,Nervous system ,medicine.medical_specialty ,Adolescent ,business.industry ,Malignancy ,medicine.disease ,Hodgkin Disease ,Nerve Fibers, Myelinated ,Surgery ,medicine.anatomical_structure ,Spinal Cord ,Sural Nerve ,Developmental Neuroscience ,Nerve Degeneration ,Pediatrics, Perinatology and Child Health ,medicine ,Humans ,Neurology (clinical) ,Nervous System Diseases ,business - Abstract
SUMMARY A 13-year-old boy with Hodgkin's disease developed acute polyneuropathy and autoimmune hemolytic anemia. Sural nerve biopsy and postmortem examination demonstrated no metastatic involvement and a lack of cellular inflammatory infiltration in the nervous system. There was significant axonal degeneration in peripheral nerves and the dorsal funiculus. These findings suggest a non-metastatic polyneuropathy associated with Hodgkin's disease, and similar cases, predominantly in adult patients, have been reported. This case emphasizes the occurrence of a paraneoplastic syndrome in children, though such syndromes appear to be rare compared with adults. RESUME Effet eloigne sur le systeme nerveux d'affections malignes Un garcon de 13 ans atteint de maladie d'Hodgkin a presente une polyneuropathie aigue et une anemie hemolytique autoimmune. La biopsie du nerf sural et Fexamen anatomique montrerent l'absence de metastase et d'infiltration inflammatoire cellulaire dans le systeme nerveux. II existait une degeneration axonale significative dans les nerfs peripheriques et les cordons posterieurs. Ces donnees suggerent l'existence d'une polyneuropathie non metastatique associee a une maladie d'Hodgkin; des cas semblables ont ete rapportes mais generalement chez I'adulte. Ce cas demontre la possibilite de syndrome paraneoplasique dans I'enfance, mais de tels cas apparaissent rares par comparaison avec ce qui se voit chez I'adulte. ZUSAMMENFASSUNG Einflus einer malignen Erkrankung auf das Nervensystem im Kindesalter Ein 13 jahriger Junge mit einem Morbus Hodgkin entwickelte eine akute Polyneuropathie und eine autoimmune haemolytische Anaemic Die Untersuchung einer Suralisbiopsie und die Sektion ergaben keine Metastasen und keine cellulare entziindliche Infiltration im Nervensystem. Es fand sich eine signifikante Degeneration der peripheren Nerven und der dorsalen Wurzel. Diese Befunde weisen auf eine nicht durch Metastasen hervorgerufene Polyneuropathie im Zusammenhang mit einem Morbus Hodgkin hin. Es sind ahnliche Falle, jedoch vorwiegend im Erwachsenenalter beschrieben worden. Dieser Fall schilderte ein paraneoplastisches Syndrom im Kindesalter, was im Vergleich zu Erwachsenen selten zu sein scheint. RESUMEN Efecto remoto de la malignidad sobre el sistema nervioso Un nino de 13 afios de edad con enfermedad de Hodgkin desarrollo una polineuropatia aguda y una anemia hemolitica autoinmune. La biopsia del nervio sural y el examen postmortem demostro que no existia ninguna metastasis, asi como falta de infiltration inflamatoria celular en el sistema nervioso. Existia una degeneraction axdnica significativa en los nervios perifericos y en los cordones posteriores. Esos hallazgos sugieren una polineuropatia no metastasica asociada con la enfermedad de Hodgkin. Casos similares, especialmente en pacientes adultos, han sido tambien descritos. Este caso demuestra la existancia del sindrome paraneoplasico en la infancia, si bien estos casos parece que son raros en comparacion con la edad adulta.
- Published
- 2008
22. Survey of parents, nurses, and school principals on their perceptions of the controversial role of schools in health promotion
- Author
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Herman A. Cohen, Samuel Gross, and Ernesto Kahan
- Subjects
Parents ,media_common.quotation_subject ,education ,Nurses ,Special needs ,Health Promotion ,School nursing ,Health services ,Nursing ,Hygiene ,Surveys and Questionnaires ,Perception ,School Nursing ,Humans ,Medicine ,Israel ,School Health Services ,media_common ,Schools ,business.industry ,Administrative Personnel ,Role ,Health promotion ,Pediatrics, Perinatology and Child Health ,Health education ,business ,First aid - Abstract
Background: The aim of this paper was to study the perceptions of parents, nurses, and school principals of the role of the health services in elementary schools. Methods: A questionnaire was distributed to the heads of parents’ committees, school nurses, and school principals of 35 randomly selected elementary public schools in Israel. Respondents were asked to qualify the degree of importance of the traditional and contemporary roles of the school health-care team. Results: Response rates were 80.0% for parents, 100% for nurses, and 97.1% for principals. All respondents agreed that both the traditional and new roles are very important. Nurses rated three interconnected roles significantly lower than parents and school principals: ‘Evaluation of students with behavioral problems’, ‘Evaluation of students with low academic performance’, and ‘Follow up and care of students with behavioral problems and low performance’. Conclusions: Nurses, parents and school principals in Israel agree that the traditional roles of health teams in elementary schools, that is, providing first aid and ensuring school hygiene, are very important. Most are ready to accept a move from an illness-based to a social-based model, with less time spent on screening and surveillance and more on identifying and managing special needs of children and staff.
- Published
- 2006
23. High-dose chemotherapy with marrow reinfusion and hyperfractionated irradiation for children with high-risk brain tumors
- Author
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Amos Kedar, Bernard L. Maria, Robert B. Marcus, Deborah M. Ringdahl, John Graham-Pole, Ronald G. Quisling, Samuel Gross, J. Parker Mickle, and Nancy P. Mendenhall
- Subjects
Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,ThioTEPA ,Transplantation, Autologous ,Internal medicine ,Glioma ,medicine ,Brainstem glioma ,Humans ,Child ,Cyclophosphamide ,neoplasms ,Bone Marrow Transplantation ,Chemotherapy ,Brain Neoplasms ,business.industry ,medicine.disease ,Combined Modality Therapy ,Magnetic Resonance Imaging ,nervous system diseases ,Surgery ,Radiation therapy ,Treatment Outcome ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Female ,Oligodendroglioma ,business ,Progressive disease ,Brain Stem ,medicine.drug ,Anaplastic astrocytoma - Abstract
Between November 1990 and March 1993, nine pediatric patients with newly diagnosed brain tumors having a high risk of failure with standard treatment received high-dose thiotepa/cyclophosphamide chemotherapy followed by autologous bone marrow infusion and involved-field hyperfractionated radiation therapy. The presenting diagnoses were brainstem glioma (BSG) [6], parietal mixed high-grade oligodendro-glioma-astrocytoma [1], thalamic anaplastic astrocytoma [1], and high-grade parietal glioma [1]. Following chemotherapy there were two partial responses, one minor response, three with stable disease, and one with progressive disease. Responses were not evaluated in two patients who had toxic deaths. Following radiation two patients, one with brainstem glioma and one with anaplastic mixed glioma, achieved complete remission. The overall survival is no better than conventional therapy. © 1994 Wiley-Liss, Inc.
- Published
- 1994
24. Immunomagnetic Purging of T8 Cells from Peripheral Blood and Bone Marrow: A Preclinical Study for Allogeneic Bone Marrow Transplantation
- Author
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Samuel Gross, Yair Gazitt, Yun-Ju He, and Angie Rios
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,biology ,business.industry ,Hematology ,Immunomagnetic separation ,Purge ,Peripheral blood mononuclear cell ,Transplantation ,medicine.anatomical_structure ,Oncology ,biology.protein ,medicine ,Cytotoxic T cell ,Bone marrow ,Antibody ,Stem cell ,business - Abstract
Methodology for T-cell subset depletion in allogeneic BMT was developed using anti-T8 antibody and magnetic microspheres. Anti-T8 antibodies bound effectively to the cytotoxic/suppressor T-cell subset and were subsequently removed by anti-mouse IgG coated magnetic microspheres. Following optimization of antibodyxell binding, microsphere:cell ratios and flow rate, T8-cells in peripheral blood were effectively removed (95-99% depletion), with an overall recovery of 37.8% ± 5.8%, and with little, if any, differential damage to either stem cells or to NK-cells. When T8 cells were removed from bone marrow mononuclear cells, an average recovery of 76% ± 8.5% was observed, with 90% ± 4.3% removal of T8 cells. This method was developed both for peripheral blood and bone marrow and could therefore be readily used in a clinical purge setting for allogeneic BMT.
- Published
- 1992
25. Suppression of Bone Marrow by Low-Density Lipoproteins in Renal Disease Patients
- Author
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R S Fennell rd, Samuel Gross, and D A Worthington-White
- Subjects
medicine.medical_specialty ,business.industry ,Hematology ,Neutropenia ,medicine.disease ,Pathogenesis ,Endocrinology ,medicine.anatomical_structure ,Oncology ,Erythropoietin ,Internal medicine ,Pediatrics, Perinatology and Child Health ,Cohort ,medicine ,Erythropoiesis ,Population study ,Bone marrow ,business ,medicine.drug ,Lipoprotein - Abstract
Patients with chronic renal disease in whom erythropoietin production is inadequate invariably experience moderate to severe debilitation-induced fatigue. Unlike the direct humeral control of erythropoiesis, neutropenia in the same cohort of patients appears to be under indirect control, very likely brought about by the suppressive effect of increased levels of low-density lipoprotein (LDL) on granulocyte-monocyte colony formation. Markedly elevated LDL levels were identified in plasma samples obtained from a study population of 179 chronic renal disease patients. The effect of the elevated LDL levels in the plasma of these patients resulted in a greater than 60% decrease in granulocyte-macrophage colony-forming unit in comparison with age-matched plasma from normal individuals. Careful review of all nutritional and therapeutic events in these patients did not offer any evidence, other than the elevated LDL levels, in support of the etiology of the chronically low absolute neutrophil counts.
- Published
- 1991
26. High-dose chemoradiotherapy supported by marrow infusions for advanced neuroblastoma: a Pediatric Oncology Group study
- Author
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John Graham Pole, Robert Marcus, William J. Janssen, Jonathan J. Shuster, Adrian P. Gee, Samuel Gross, James T. Casper, P. A. Koch, Terry Pick, and G. J. Elfenbein
- Subjects
Male ,Melphalan ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Pilot Projects ,Gastroenterology ,Neuroblastoma ,Internal medicine ,medicine ,Humans ,Combined Modality Therapy ,Child ,Survival rate ,Bone Marrow Transplantation ,business.industry ,Remission Induction ,Infant ,Radiotherapy Dosage ,Total body irradiation ,Surgery ,Survival Rate ,Clinical trial ,Regimen ,Oncology ,Child, Preschool ,Toxicity ,Feasibility Studies ,Female ,business ,Chemoradiotherapy ,Follow-Up Studies ,medicine.drug - Abstract
We conducted a pilot protocol at seven Pediatric Oncology Group (POG) institutions to examine the feasibility, toxicity, and efficacy of using a common regimen of high-dose chemoradiotherapy (HD CT/RT) supported by autologous or allogeneic marrow infusions in children with metastatic neuroblastoma (NBL) in first or second remission. During a 57-month period, we accrued 101 patients. We report here results for the 81 who completed treatment at least 2 years ago. The HD CT/RT regimen consisted of melphalan 60 mg/m2/d for three doses, and total body irradiation (TBI) either 1.5 Gy (n = 27) or 2.0 Gy (n = 54) twice daily for six doses. Twenty-three patients also received irradiation consisting of 1.2 Gy twice daily for 10 doses to persisting disease sites. Seventy-four were given autologous and seven allogeneic marrow, 64 autologous marrows being purged immunomagnetically. Fifty-four children were in first complete (CR) or partial (PR) remission and 27 in second CR or PR. As of October 1, 1990, follow-up was from 32 to 72 months. Forty-seven of these 81 children relapsed, 10 died of complications, one of unknown cause, and 23 continue in remission, including 21 of the 54 treated in first remission, and 16 who completed treatment more than 3 years ago. The 2-year actuarial event-free survival (EFS) probabilities are first CR (CR1) 32% (SE 10%), first PR (PR1) 43% (SE 9%), second CR (CR2) 33% (SE 27%), and second PR (PR2) 5% (SE 5%). Probability of EFS correlated with remission number (first better than second, P less than .001), with interval from diagnosis to HD CT/RT (greater than 9 months better than less than 9 months, P = .055), and with TBI dose (12 Gy better than 9 Gy, P = .031). These encouraging results may partly reflect selection for this treatment of patients with NBL who have a slower disease pace.
- Published
- 1991
27. Successful Strategy for Prevention of Cytomegalovirus Interstitial Pneumonia After Human Leukocyte Antigen-Identical Bone Marrow Transplantation
- Author
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Gerald J. Elfenbein, John Graham-Pole, Tariq Siddiqui, Samuel Gross, Robert B. Marcus, Terri Wikle-Fisher, Nancy P. Mendenhall, Kenneth H. Rand, Theresa M. Goedert, and Roy S. Weiner
- Subjects
Adult ,Microbiology (medical) ,Adolescent ,Pulmonary Fibrosis ,Attack rate ,Congenital cytomegalovirus infection ,Graft vs Host Disease ,Human leukocyte antigen ,Antigen ,HLA Antigens ,Risk Factors ,Pulmonary fibrosis ,Humans ,Transplantation, Homologous ,Medicine ,Interstitial pneumonia ,Child ,Bone Marrow Transplantation ,Biological Products ,biology ,business.industry ,Immunization, Passive ,Infant ,virus diseases ,medicine.disease ,Infectious Diseases ,Child, Preschool ,Cytomegalovirus Infections ,Immunology ,biology.protein ,Antibody ,business ,Complication - Abstract
Cytomegalovirus (CMV) interstitial pneumonia is a frequent and often fatal complication of allogeneic bone marrow transplantation. Because therapy for CMV pneumonia was, until recently, largely ineffective, prophylactic methods were explored. This study shows that the strategy of using CMV seronegative blood products for seronegative patients with seronegative donors or weekly administration of intravenous immunoglobulin for all other patients reduced the attack rate of CMV pneumonia. The results of this study are put into the perspective of previously published data.
- Published
- 1990
28. Response of osteogenic sarcoma to the combination of etoposide and cyclophosphamide as neoadjuvant chemotherapy
- Author
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William F. Cassano, John Graham-Pole, Nancy Dickson, Robert A. Vander Griend, Ramy A. Saleh, T. Heare, Paulete Metha, Samuel Gross, Frank Abbot, Marj Heare, and Amos Kedar
- Subjects
Cancer Research ,medicine.medical_specialty ,Chemotherapy ,Cyclophosphamide ,business.industry ,medicine.medical_treatment ,Cancer ,Neutropenia ,medicine.disease ,Gastroenterology ,Primary tumor ,Surgery ,Oncology ,Internal medicine ,Toxicity ,medicine ,Sarcoma ,business ,Etoposide ,medicine.drug - Abstract
A Phase I1 study of the combination of etoposide (VP-16) and cyclophosphamide (CPM) was conducted in an attempt to identify active and potentially less toxic agents for treating patients with osteogenic sarcoma (0s). VP-16 was given as a 72-hour infusion for a total dose of 600 mg/m2. CPM was given as six pulses of 300 mg/m2 every 12 hours for a total dose of 1800 mg/m2. Seventeen newly diagnosed patients, including five (29%) with metastatic disease, were evaluated before and after two courses of VP16 and CPM for clinical, radiologic, and biochemical (serum alkaline phosphatase [SAP]) responses of the primary tumor and metastases. Fifteen (88%) patients achieved complete or partial clinical responses. Fourteen (82%) patients achieved radiologic responses. Thirteen (87%) of 15 patients with higher than normal SAP levels for their age showed partial or complete responses. Three (60%) of the five patients with metastatic disease achieved complete or partial responses. The only major toxicity was myelosuppression, which led to 21 (62%) brief admissions after 34 courses of chemotherapy for intravenous antibiotic therapy for fever and neutropenia, without associated mortality. It was concluded that the combination of VP-16 and CPM is effective chemotherapy for lboth primary and metastatic 0s. Although myelosuppression is inevitable, it is rapidly reversible in the drug dosages used. Further studies are needed to evaluate the effect of these drugs in combination with established agents in improving the disease-free survival of patients with 0s. Cancer 65:861-865, 1990.
- Published
- 1990
29. Immunomagnetic Purging of Bone Marrow
- Author
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William J. Janssen, Adrian P. Gee, John Graham Pole, Carlos Lee, and Samuel Gross
- Subjects
Pathology ,medicine.medical_specialty ,Latex ,medicine.drug_class ,Cell Separation ,Immunomagnetic separation ,Monoclonal antibody ,Transplantation, Autologous ,Magnetics ,Neuroblastoma ,Breast cancer ,Bone Marrow ,Neoplasms ,medicine ,Humans ,Immunosorbent Techniques ,Bone Marrow Transplantation ,Leukemia ,business.industry ,Hematology ,medicine.disease ,Microspheres ,Transplantation ,Haematopoiesis ,medicine.anatomical_structure ,Oncology ,Evaluation Studies as Topic ,Pediatrics, Perinatology and Child Health ,Cancer cell ,Neoplastic Stem Cells ,Cancer research ,Bone marrow ,business - Abstract
Many in vitro techniques have been developed for removing cancer cells from the marrow of patients who are to undergo autologous bone marrow transplantation (ABMT). These purging techniques can be classified as immunological or pharmacological. The immunomagnetic technique has been widely used in neuroblastoma patients. It depends on an interaction between target neuroblastoma cells in the marrow and a complex of specific monoclonal antibodies and magnetized microspheres, the target cells being selectively removed by passage through a magnetic field. Laboratory studies with neuroblastoma and acute lymphoblastic leukemia cells have shown the high efficiency of this technique in selectively removing cancer cells while retaining adequate numbers of normal hematopoietic cells for subsequent reinfusion into the patient. Clinical studies in several hundred neuroblastoma patients, as well as small numbers of acute lymphoblastic leukemia, breast cancer, and myeloma patients, suggest that this is a clinically safe and effective technique. However, no clinical trial has been conducted comparing ABMT with and without in vitro marrow purging. Until such time, we will regard immunomagnetic purging as "standard of care" for neuroblastoma patients receiving ABMT.
- Published
- 1990
30. Fixed Drug Eruption of the Penis Due to Hydroxyzine Hydrochloride
- Author
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Herman A. Cohen, Asher Barzilai, Andre Matalon, Samuel Gross, and Liora Harel
- Subjects
Male ,medicine.medical_specialty ,Migration inhibiting factor ,Drug discontinuation ,Guinea Pigs ,030226 pharmacology & pharmacy ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Drug rash ,Animals ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Child ,Macrophage Migration-Inhibitory Factors ,Psychomotor Agitation ,Hydroxyzine ,business.industry ,Infant ,medicine.disease ,Complete resolution ,Dermatology ,Hydroxyzine Hydrochloride ,Surgery ,Drug eruption ,medicine.anatomical_structure ,Anti-Anxiety Agents ,Drug Eruptions ,business ,Penis ,medicine.drug - Abstract
Objective To report four cases of fixed drug eruption induced by hydroxyzine hydrochloride (Otarex, Teva, Israel). Case Summary Four children with restlessness who were treated with hydroxyzine hydrochloride developed fixed drug eruption of the penis. Drug discontinuation was followed by complete resolution of the skin eruption. Rechallenge resulted in the same drug rash. Macrophage migration inhibiting factor (MIF) assay with hydroxyzine hydrochloride was positive. Discussion The pathogenesis of fixed drug eruption and the role of macrophage MTF assay in diagnosis is discussed. Conclusions A fixed drug eruption induced by hydroxyzine hydrochloride is possible, but is a rare phenomenon.
- Published
- 1997
31. Pediatrician attitudes to exclusion of ill children from child-care centers in Israel: pressure on ambulatory practices
- Author
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Zahi Grosman, Ernesto Kahan, Herman A. Cohen, Zeev Horev, and Samuel Gross
- Subjects
Response rate (survey) ,Child care ,Pediatrics ,medicine.medical_specialty ,business.industry ,Attitude of Health Personnel ,Health Policy ,Infant ,Signs and symptoms ,General Medicine ,Primary care ,Child Day Care Centers ,Affect (psychology) ,Sick child ,Cross-Sectional Studies ,Antibiotic therapy ,Child, Preschool ,Ambulatory ,Communicable Disease Control ,medicine ,Humans ,Israel ,business - Abstract
Background The exclusion of ill children from child-care centers may be associated with high social, economic and medical costs. Objective To assess the opinions of pediatricians working in an outpatient setting in Israel on the exclusion/return of children in child-care centers. Methods A questionnaire on practices of exclusion/return of children in child-care centers, in general and according to specific signs and symptoms, was administered to a random computer-selected cross-sectional sample of 192 primary care community pediatricians in Israel. Results One hundred and seventy-three pediatricians completed the questionnaires, for a response rate of 90%; 147 were board-certified and 26 were not. About half the pediatricians felt pressured by parents requesting antibiotic therapy to accelerate the return of their sick child to the child-care center. The majority also believed their practice was overloaded by often unnecessary demands for medical notes by the child-care centers before children could return. More than half based their decision to exclude children on “common sense” and the remainder, on accepted guidelines. Except for scabies and lice, there were no significant correlations between the physicians’ stipulation for a note on return of the child and the specific illness guidelines. Conclusions This study shows that a high proportion of pediatricians based their exclusion practices on “common sense” and personal understanding instead of established guidelines, and that the guidelines did not affect their opinion on the duration of illness that warrant a note. Furthermore, half were subjected to parental pressure to employ inappropriate practices. These findings, combined with our earlier survey of child-care centers staff, indicate that better education of parents and day-care staff about ill child-care-center-exclusion policy in Israel would increase their common understanding with pediatricians.
- Published
- 2004
32. Adverse reactions to accidental forearm injection of Bacille Calmette-Guerin vaccine in schoolchildren: 12-month cohort follow-up
- Author
-
Ofra Havkin, Samuel Gross, Alex Leventhal, Ernesto Kahan, and Liora Vesterman
- Subjects
Microbiology (medical) ,medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,Incidence ,Injections, Subcutaneous ,education ,Surgery ,Vaccination ,Forearm ,Infectious Diseases ,medicine.anatomical_structure ,Accidental ,Cohort ,Toxicity ,medicine ,BCG Vaccine ,Humans ,Complication ,business ,Child ,Local Reaction ,Skin ,Skin Tests - Abstract
This study examined the natural history of reaction after accidental intradermal administration of bacille Calmette-Guerin (BCG) vaccine instead of purified protein derivative (PPD) in 226 schoolchildren. At 18 days after vaccination, a local reaction with a diameter of 4.5-14 mm was found in 62% of the students, and ulceration with discharge was found in 26.6%; corresponding rates at 120 days were 72.3% and 38% and at 281 days were 73% and 6%. At 345 days, 85% of the students had a dry scar measuring 5-14 mm in diameter, and none had ulceration or discharge.
- Published
- 2003
33. Exclusion of ill children from child-care centers in Israel
- Author
-
Herman A. Cohen, Samuel Gross, and Ernesto Kahan
- Subjects
Adult ,Diarrhea ,Pediatrics ,medicine.medical_specialty ,Consensus ,Fever ,Attitude of Health Personnel ,Vomiting ,media_common.quotation_subject ,Surveys and Questionnaires ,Absenteeism ,medicine ,Animals ,Humans ,Israel ,Child ,Respiratory Tract Infections ,media_common ,Response rate (survey) ,business.industry ,Administrative Personnel ,Pediculus ,General Medicine ,Child Day Care Centers ,Exanthema ,Lice Infestations ,Rash ,Organizational Policy ,Bloody ,Feeling ,Cough ,Scalp Dermatoses ,Needs assessment ,Communicable Disease Control ,Earache ,Practice Guidelines as Topic ,Guideline Adherence ,medicine.symptom ,Morbidity ,business ,Needs Assessment - Abstract
The aim of the study was to examine criteria for ill children in child-care centers. A questionnaire on practices of exclusion/return of children according to specific signs and symptoms was mailed to the directors of care centers in central Israel. Thirty-six of the 60 questionnaires (60%) were returned by mail and the reminded were completed in personal visits to the CCCs achieving a response rate of 100%. About half (51.7%) used "common sense" and "personal feelings" to exclude children and to allow their return, and 29 (48.3%) used the guidelines of the Ministries of Education and Health or other authorities. The percentage of centers excluding children by signs/symptoms was as follows: high fever (>38 degrees C), 100%; low-grade fever, 76.7%; asthma exacerbation, 80.0%; heavy cough, 75.0%; eye discharge or conjunctivitis, 83.3%; diarrhea and vomiting more than twice per day, 100%; rash, 72.3%; otalgia, 46.7%; and infected skin lesion, 66.7%. Only four centers excluded children with head lice. Most centers required a physician's note on return of a child after high fever (76.7%), eye discharge or conjunctivitis (48.3%), and from 75 to 80%, respectively, for frequent vomiting and bloody or mucinous diarrhea. The results show that exclusion practices among child-care centers (CCCs) vary widely, suggesting the need for the establishment of a uniform exclusion and return policy in Israel, with distribution of clear, up-to-date guidelines on the prevention and control of communicable diseases to all day-care centers. In a simple way, this study identified attitudes concerning the exclusion/return of sick children in CCCs and was useful for the discussion of the related policy with CCCs responsible and national health and educational authorities.
- Published
- 2003
34. [Thomas Eakins: Gross' clinic, 1875]
- Author
-
Samuel, Gross
- Subjects
Education, Medical ,Famous Persons ,General Surgery ,Medicine in the Arts ,History, 19th Century ,Paintings ,United States - Published
- 2003
35. To Purge or Not to Purge Is Not the Question
- Author
-
Samuel Gross
- Subjects
medicine.medical_specialty ,Bone marrow transplantation ,business.industry ,Immunology ,medicine ,Hematology ,business ,Purge ,Bone marrow purging ,Surgery - Published
- 1992
36. High-Dose Carboplatinum and VP-16 in Treatment of Metastatic Adrenal Carcinoma
- Author
-
Mouhab Ayass, Samuel Gross, and James Harper
- Subjects
Male ,medicine.medical_specialty ,medicine.medical_treatment ,Adrenal carcinoma ,Carboplatin ,Metastasis ,Diagnosis, Differential ,Cushing syndrome ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Carcinoma ,Humans ,Neoplasm Metastasis ,Cushing Syndrome ,Etoposide ,Chemotherapy ,Epithelioma ,business.industry ,Infant ,Hematology ,medicine.disease ,Debulking ,Adrenal Cortex Neoplasms ,Surgery ,Radiography ,Oncology ,Pediatrics, Perinatology and Child Health ,business ,medicine.drug - Abstract
We describe a case of a patient that presented to our center with Cushing syndrome and was found to have an extensive metastatic adrenal carcinoma. He underwent debulking of the abdominal disease followed by eight courses of VP-16/carboplatinum. The patient had a remarkable response and is currently alive and in complete remission.
- Published
- 1991
37. Increased erythrocyte and protein binding of codeine in patients with sickle cell disease
- Author
-
Samuel Gross, Sumia S. Mohammed, Hartmut Derendorf, Amos Kedar, Paulette Mehta, and Mary M. Christopher
- Subjects
medicine.medical_specialty ,Erythrocytes ,Bilirubin ,Pharmaceutical Science ,Plasma protein binding ,Anemia, Sickle Cell ,Cell membrane ,chemistry.chemical_compound ,Internal medicine ,medicine ,Humans ,Binding site ,chemistry.chemical_classification ,Chemistry ,Codeine ,Blood Proteins ,Orosomucoid ,medicine.disease ,Blood Protein Electrophoresis ,Blood proteins ,Sickle cell anemia ,Red blood cell ,medicine.anatomical_structure ,Endocrinology ,Biochemistry ,Glycoprotein ,Protein Binding - Abstract
Erythrocyte binding and plasma protein binding of codeine in sickle cell patients and healthy controls were determined. A reversed-phase HPLC procedure was used for codeine analysis. Codeine was extracted from alkalinized plasma, separated on a CN column, and assayed by fluorescence detection. The erythrocyte-buffer partition coefficient was significantly higher in sickle cell patients (1.72 +/- 0.21) than in healthy controls (1.25 +/- 0.14). No time dependence of partitioning was observed. The fraction of codeine bound to plasma proteins, determined by ultrafiltration, was significantly higher in sickle cell patients (66.0% +/- 8.6%) than in healthy controls (30.5% +/- 2.7%). No concentration dependence of erythrocyte or protein binding was observed. Further studies were performed to elucidate the binding mechanisms. From a ghost cell binding study it was concluded that the major binding sites for codeine are in the cell membrane. A decrease in codeine binding was observed in the presence of bilirubin. Codeine binding to alpha 1-acid glycoprotein was found to be minimal. The levels of alpha 1-acid glycoprotein and other glycoproteins in sickle cell patients and healthy controls were measured by glycoprotein electrophoresis. The results showed no significant difference between the two groups. Plasma protein electrophoresis was performed for the two groups. The results showed a significant difference in gamma-globulin levels between sickle cell patients and healthy controls. Codeine is known to bind to gamma-globulin, a fact that may explain in part the observed increase in the plasma protein binding of codeine in sickle cell patients.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1993
38. Codeine disposition in sickle cell patients compared with healthy volunteers
- Author
-
Samuel Gross, Mohab Ayass, Amos Kedar, Paulette Mehta, Sumia S. Mohammed, and Hartmut Derendorf
- Subjects
Pharmacology ,Volume of distribution ,Adult ,medicine.medical_specialty ,Dose-Response Relationship, Drug ,Chemistry ,Codeine ,Area under the curve ,Cmax ,Anemia, Sickle Cell ,Endocrinology ,Pharmacokinetics ,Oral administration ,In vivo ,Anesthesia ,Internal medicine ,Blood plasma ,medicine ,Humans ,Pharmacology (medical) ,medicine.drug ,Half-Life - Abstract
The pharmacokinetics of codeine were determined after oral administration of codeine sulfate (60 mg) with sickle cell patients (SCPs) and healthy controls (HCs). Plasma concentrations of codeine were measured by reversed-phase high-pressure liquid chromatography with fluorescence detection. Pharmacokinetic parameters were calculated using both compartmental and noncompartmental analysis. No significant differences were observed in time to reach maximum peak plasma concentration (tmax) (1.0 +/- 0.4 versus 1.4 +/- 1.0 hours), maximum peak plasma concentration (Cmax) (172 +/- 25 versus 225 +/- 97 ng/mL), area under the curve (AUC infinity) (590 +/- 96 versus 779 +/- 234 ng*h/mL), and Cl/F (104 +/- 17 versus 89 +/- 27 L/h) between SCPs and HCs. Conversely, significant differences were observed in mean residence time (MRT) (3.7 +/- 0.3 versus 4.7 +/- 0.3 hours) and half-life (t1/2) (1.7 +/- 0.2 versus 2.8 +/- 0.3 hours). In a separate study, significant differences were observed in the in vitro plasma protein binding of codeine in SCPs (66.0 +/- 8.6%) and HCs (30.5 +/- 2.7%) as well as in vivo binding (68.4 +/- 11.1% for SCPs versus 29.2 +/- 3.4% for HCs). Codeine is a relatively high-extraction drug that is primarily eliminated by metabolism in the liver. Generally, the clearance of such drugs is approximately equal to hepatic blood flow and is not affected by changes in protein binding. Therefore, the change in t1/2 observed in SCPs can be attributed to changes in volume of distribution rather than clearance.
- Published
- 1993
39. Treatment of chronic idiopathic thrombocytopenic purpura with ascorbate
- Author
-
Moshe Nussinovitch, Jacob Hart, Herman A. Cohen, Moshe Frydman, and Samuel Gross
- Subjects
Male ,Chemotherapy ,Purpura, Thrombocytopenic, Idiopathic ,Adolescent ,business.industry ,Platelet Count ,medicine.medical_treatment ,Thrombotic thrombocytopenic purpura ,Chronic idiopathic thrombocytopenic purpura ,Ascorbic Acid ,medicine.disease ,Ascorbic acid ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Immunology ,Chronic Disease ,medicine ,Humans ,Female ,business ,Child - Published
- 1993
40. Prevention of recurrent intracranial hemorrhage in a factor X-deficient infant
- Author
-
Eric Sandler and Samuel Gross
- Subjects
Male ,medicine.medical_specialty ,Catheterization, Central Venous ,business.industry ,Factor X ,Infant, Newborn ,Central venous line ,Hematology ,Factor X deficiency ,medicine.disease ,Blood Coagulation Factors ,Surgery ,chemistry.chemical_compound ,Text mining ,Oncology ,chemistry ,Pediatrics, Perinatology and Child Health ,medicine ,Coagulopathy ,Humans ,business ,Factor X Deficiency ,PROTHROMBIN COMPLEX ,Cerebral Hemorrhage - Abstract
We describe a case of a child with severe Factor X deficiency who had three episodes of intracranial hemorrhage during the first 6 months of life. Since that time he has been successfully managed with prophylactic therapy using prothrombin complex infusions via an indwelling central venous line. This prophylactic therapy may prevent the poor outcome usually described in these patients.
- Published
- 1992
41. 24. COMPARATIVE TOXICITY (tox) OF BONE MARBOW TRANSPLANT (BMT) CONDITIONING WITH CYCLOPHOSPHAMIDE (CY) AND CYTOSINE ARABINOSIDE (araC)
- Author
-
G. J. Elfenbein, R. Saleh, Samuel Gross, P. Marcus, J. Graham-Pole, T. Coedert, and Roy S. Weiner
- Subjects
Cyclophosphamide ,business.industry ,Hematology ,Pharmacology ,chemistry.chemical_compound ,Oncology ,chemistry ,Pediatrics, Perinatology and Child Health ,Toxicity ,medicine ,Conditioning ,business ,Cytosine ,medicine.drug - Published
- 1990
42. High-risk ewing's sarcoma: end-intensification using autologous bone marrow transplantation
- Author
-
Dempsey S. Springfield, Gerald J. Elfenbein, Robert B. Marcus, William F. Enneking, Nancy P. Mendenhall, Rodney R. Million, John Fort, Samuel Gross, John Graham-Pole, and Roy S. Weiner
- Subjects
Male ,Melphalan ,Cancer Research ,medicine.medical_specialty ,Cyclophosphamide ,medicine.medical_treatment ,Sarcoma, Ewing ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Survival rate ,Bone Marrow Transplantation ,Chemotherapy ,Radiation ,business.industry ,Ewing's sarcoma ,Total body irradiation ,medicine.disease ,Combined Modality Therapy ,Surgery ,Radiation therapy ,Regimen ,Oncology ,Female ,business ,Whole-Body Irradiation ,medicine.drug - Abstract
Because of a retrospective analysis showing survival to be related to primary tumor size, in February 1982 a study to test this hypothesis prospectively was begun at the University of Florida. Patients with primary tumors 8 cm or less in maximum diameter and no metastases received adjuvant chemotherapy consisting of vincristine, cyclophosphamide, doxorubicin, and dactinomycin plus radiotherapy or surgery (standard-risk protocol). All others received a similar regimen followed by end-intensification with high-dose melphalan and autologous bone marrow transplantation (Protocol HR-2). Because of poor results of HR-2, another high-risk protocol (HR-3) was initiated in January 1985. Patients on HR-3 received 2 cycles of chemotherapy containing vincristine, cyclophosphamide, and doxorubicin followed by local radiation therapy and maintenance chemotherapy. At the end of this therapy, autologous bone marrow transplantation (ABMT) was performed, using a preparatory regimen of total body irradiation and intensive chemotherapy. The 2-year disease-free survival rate was 70% for the standard-risk protocol, 20% for HR-2, and 80% for HR-3. The follow-up on HR-3 is still short, but the results are promising enough to warrant further clinical trials.
- Published
- 1988
43. The effects of PGF2α, PGI2, and TXB2 on human CFU-C in healthy and leukemic patients
- Author
-
Diana A. Worthington-White and Samuel Gross
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Alpha (ethology) ,Prostaglandin ,Granulocyte ,Biology ,Dinoprost ,Colony-Forming Units Assay ,chemistry.chemical_compound ,Internal medicine ,medicine ,Humans ,Child ,Stem Cells ,Prostaglandins F ,Infant ,Thromboxanes ,Prostanoid ,Hematology ,medicine.disease ,Epoprostenol ,In vitro ,Leukemia, Lymphoid ,Thromboxane B2 ,Leukemia ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Child, Preschool ,cardiovascular system ,Female ,lipids (amino acids, peptides, and proteins) ,Bone marrow ,Linear growth ,circulatory and respiratory physiology - Abstract
This study was undertaken to test the effects of certain arachidonate derivatives, PGF2 alpha, PGI2 and TxB2 on in vitro bone marrow granulocyte colony growth (CFU-C) in leukemia patients receiving maintenance chemotherapy and in normal controls. The addition of PGF2 alpha did not result in increased numbers of colonies, but it did cause a shift in the size of the colonies so that there was a significant increase in larger colonies (P less than 0.001) and significantly fewer small colonies (P less than 0.05) as compared to untreated samples. Of the prostenoids tested in a Tris-buffered system, PGI2 affected the greatest increase in CFU-C (P less than 0.01) followed by PGF2 alpha (P less than 0.05) whereas 6-keto-PGF1 alpha (the stable hydrate of PGI2) did not affect colony growth. Time-response curves revealed a linear growth pattern for PGF2 alpha with a peak at 10 days, whereas there was a 6-day growth lag with PGI2 followed by linear growth with a peak at 13 days. TxB2 added to cultures significantly reduced the number of bone marrow CFU-C at all doses tested. The prostanoid effects on CFU-C derived from leukemic patients on maintenance chemotherapy and from normal individuals were identical in every respect.
- Published
- 1984
44. Lymphocyte aromatic hydrocarbon responsiveness in acute leukemia of childhood
- Author
-
Toyoko S. Yamashita, Jeffrey L. Blumer, Rebecca F. Dunn, Samuel Gross, and Esterhay
- Subjects
Acute leukemia ,business.industry ,Lymphocyte ,Immunology ,Cell Biology ,Hematology ,Benzanthracene ,medicine.disease ,Malignancy ,Biochemistry ,Leukemia ,medicine.anatomical_structure ,Cell culture ,medicine ,Analysis of variance ,business ,Carcinogen - Abstract
Aryl hydrocarbon hydroxylase (AHH) activity and inducibility were examined in mitogen-stimulated cultured lymphocytes from children with acute leukemia in remission, with nonleukemic malignancies, and with no family or personal history of malignant disease. Neither morphological differences nor differences in mitogen responsiveness were observed among the three sources of cells studied. Levels of constitutive and dibenzanthracene-induced AHH activity were found to be similar among the three groups by analysis of variance. However, when results were analyzed in terms of inducibility ratios, it was found that cells from leukemic children were significantly less inducible (p less than 0.005) than cells from unaffected children or children with nonleukemic malignancies. The reason for this difference became apparent when statistical criteria were employed for the pheontypic separation of individuals who were highly aromatic hydrocarbon responsive and minimally responsive. A significantly larger proportion (p less than 0.001) of leukemic children than unaffected children or children with nonleukemic malignancy were found to be minimally aromatic hydrocarbon responsive. Moreover, in patients with acute lymphoblastic leukemia relapsing while on therapy, longer durations of the first remission were correlated (r = 0.63, p less than 0.05) with the highly inducible AHH phenotype.
- Published
- 1981
45. Tumor and urine catecholamines (CATs) in neurogenic tumors: Correlations with other prognostic factors and survival
- Author
-
John Graham-Pole, Samuel Gross, Toivo Salmi, Carlos R. Abramowsky, and Aaron H. Anton
- Subjects
Cancer Research ,medicine.medical_specialty ,CATS ,business.industry ,Catabolism ,Urinary system ,Physiology ,Urine ,medicine.disease ,Excretion ,Endocrinology ,Oncology ,Internal medicine ,Neuroblastoma ,Catecholamine ,Medicine ,Stage (cooking) ,business ,medicine.drug - Abstract
This study was undertaken to better define the relationship between catecholamine (CAT) metabolism within the malignant neuroblast and other factors known to influence clinical outcome in neuroblastoma (NB). Several CATs and their metabolites were measured in 32 tumors and 47 urines from 60 newly diagnosed children with neurogenic tumors. Absolute and relative CAT concentrations were correlated with age, clinical stage, histologic differentiation and survival duration. The major findings are: (1) urinary CAT excretion patterns often differ markedly from tumor CAT patterns in the same child, which may be explained by the continuous nature of tumor metabolism, hepatic and renal catabolism, and sampling errors; (2) definite patterns of biochemical maturation are apparent in tumors and urines, but standard light microscopy is insufficient to correlate this with degree of histologic differentiation; (3) more differentiated patterns of CAT metabolism, both in tumor and urine, are significantly associated with age less than 1 year at diagnosis, and with more favorable clinical Stage (I, II, IVS). Tumor NE was increased relative to DM and DA, and urine NMN and VMA were increased relative to DM and HVA, in these patients. (4) this more differentiated CAT pattern in infants and in less advanced stages was reflected in their better survival. Greater maturity of tumor enzyme systems is the probable reason for the better prognosis of NB in infants less than 1 year. Individual enzymes should be measured in fresh tumor tissues, and related to relative and absolute CAT concentrations in tumor and urine, to try to categorize patients on the basis of clearcut biological differences when planning new treatment strategies for NB.
- Published
- 1983
46. Vitamin E-dependent anemia in the premature infant
- Author
-
Samuel Gross and David K. Melhorn
- Subjects
Vitamin ,medicine.medical_specialty ,Erythrocytes ,Anemia ,Iron ,medicine.medical_treatment ,Phospholipid ,Administration, Oral ,Infant, Premature, Diseases ,Hemoglobins ,chemistry.chemical_compound ,Internal medicine ,medicine ,Birth Weight ,Humans ,Vitamin E ,Vitamin E Deficiency ,Tocopherol ,Phospholipids ,business.industry ,Infant, Newborn ,Infant ,Metabolism ,medicine.disease ,Endocrinology ,chemistry ,Pediatrics, Perinatology and Child Health ,Immunology ,Erythrocyte Count ,Vitamin E deficiency ,Hemoglobin ,business - Abstract
Studies on serum tocopherol levels, hematopoietic responses, and erythrocyte phospholipid fractions were carried out in agroup of low-birth-weight (mean, 1,530 gm) premature infants whose diets were supplemented with either water-soluble (TPGS) or fat-soluble (TA) forms of d-alpha tocopheryl (25 IU/day). Significantly higher serum tocopherol levels and early maintenance of higher hemoglobin values were observed in the infants who received the water-soluble tocopheryl preparation. Comparable but less marked differences in these values were identified in similarly paired groups fed lower concentrations of the tocopheryls in combination with iron. The lowest hemoglobin levels were recorded in the infants fed formulas containing TA and iron. Among a selected group of vitamin E-deficient infants, evidence of lipid instability in the erythrocyte membrane was manifested by decreased values of phosphatidyl ethanolamine.
- Published
- 1974
47. Cyclic parenteral nutrition during bone marrow transplantation in children
- Author
-
Marcia P. Husak, Michael D. Reed, Roger H. Herzig, Hillard M. Lazarus, Jeffrey L. Blumer, Thomas C. Halpin, and Samuel Gross
- Subjects
chemistry.chemical_classification ,Cancer Research ,Nitrogen balance ,medicine.medical_specialty ,Bone marrow transplantation ,biology ,business.industry ,Serum albumin ,Antitumor therapy ,Gastroenterology ,Surgery ,Transthyretin ,Parenteral nutrition ,Oncology ,chemistry ,Transferrin ,Internal medicine ,medicine ,biology.protein ,Liver function ,business - Abstract
Nine children underwent ten bone marrow transplants for malignancies and were supported by parenteral alimentation administered in cyclic fashion 18 hours daily. Children received cyclic parenteral nutrition for an average of 29 days, which provided a caloric intake (mean +/- SD) of 55.9 +/- 18.1 Kcal/kg/day, and a nitrogen intake of 0.28 +/- 0.08 g/kg/day. Nutritional status was assessed using nitrogen balance, creatinine-height index, and visceral protein concentrations including serum albumin, transferrin, and prealbumin. Minimal transient elevation in tests of liver function were observed without marked derangement in blood glucose, electrolytes, or osmolality. Unlike prealbumin, determinations of nitrogen balance, creatinine-height index, serum albumin and transferrin concentrations did not parallel changes in clinical status. Cyclic parenteral alimentation is a practical approach to the maintenance of nutrition during intensive antitumor therapy and provides an infusion-free period for the administration of drugs and blood transfusions without interfering with nutritional support. Prealbumin accurately reflects changes in the patient's clinical status at any point and is easily and reliably determined.
- Published
- 1983
48. Increased Colony-Stimulating Activity in the Plasma of a Patient with Lymphoepithelioma Metastatic to the Liver
- Author
-
Arthur J. Newman, Kamran Tebbi, and Samuel Gross
- Subjects
Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Adolescent ,Leukocytosis ,business.industry ,Liver Neoplasms ,General Medicine ,medicine.disease ,Granulopoiesis ,Colony-Stimulating Factors ,Oncology ,Immunology ,Carcinoma, Squamous Cell ,medicine ,Humans ,medicine.symptom ,business ,Lymphoepithelioma - Abstract
Leukocytosis with predominance of poly morphonuclear leukocytes is not unusual in a variety of primary or metastatic hepatic tumors. However, to date no apparent explanation for this event is available. This paper describes extreme leukocytosis in a 17-year-old black male with lymphoepithelioma after development of metastases to the liver. In order to identify the source of leukocytosis, studies of granulocytic colony-stimulating activity (CSA) of the patient's plasma and leukocyte-conditioned media (LCM) were carried out and compared with normal controls. The assay system consisted of nonadherent marrow cells of hematologically normal individuals and normal mice cultured in semi-solid culture media. In this system, the number of granulocytic colony-forming units (CFU-C) is proportional to the amount of stimulating activity present, and therefore allows for quantitative comparison. The number of colonies produced under the influence of patient's plasma was significantly higher (p less than 0.001) than those obtained from the patient's LCM or from control plasma or LCM. This pattern is the reverse of that seen in normal individuals in whom the major sources of CSA are macrophages and monocytes. It is conceivable that malignant cells are the source of additional CSA.
- Published
- 1979
49. The Hydrogen Peroxide Fragility Test and Serum Tocopherol Level in Anemias of Various Etiologies
- Author
-
Gordon A. Lake, James A. Leu, Samuel Gross, and David K. Melhorn
- Subjects
medicine.medical_specialty ,Red Cell ,Vitamin E ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Peroxide ,Hemolysis ,chemistry.chemical_compound ,Endocrinology ,Blood serum ,chemistry ,Internal medicine ,medicine ,Tocopherol ,Vitamin E deficiency ,Hydrogen peroxide - Abstract
Increased in vitro erythrocyte sensitivity to the hemolytic effects of hydrogen peroxide (H2O2) in the H2O2 fragility test has been widely associated with vitamin E deficiency. In the present study, H2O2 red cell fragility was abnormally elevated in many types of acquired and congenital anemias in children who were tocopherol sufficient. In addition to abnormal red cell H2O2 sensitivity known to occur in vitro in conditions involving defects in cellular devices for disposal of peroxides, it is likely that a wide variety of erythrocyte dysfunctions result in increased in vitro H2O2 hemolysis even in situations where the usually adequate mechanisms for peroxide detoxification are present.
- Published
- 1971
50. Electron Microscopy of the Red Cells in Erythropoietic Porphyria
- Author
-
Samuel Gross, Virgil R. Mumaw, and Melvin D. Schoenberg
- Subjects
Red Cell ,biology ,Chemistry ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Molecular biology ,Porphyrin ,law.invention ,Cell biology ,Ferritin ,Cell nucleus ,chemistry.chemical_compound ,medicine.anatomical_structure ,Porphyria ,law ,Erythropoietic porphyria ,medicine ,biology.protein ,Hemoglobin ,Electron microscope - Abstract
With the aid of electron microscopy two different red cell lines have been identified in erythropoietic porphyria. A normal red cell series has been found in association with hemoglobin containing normoblastic nuclei and ferritin laden reticulocytes. The abnormal line presumably represents the porphyrin containing cells. A possible explanation to account for the abnormality in heme synthesis has been proposed.
- Published
- 1965
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