tbuckley/cabot-search huggingface dataset:
Abstract 17081: Long-term Administration of Eicosapentaenoic Acid Ameliorates Vascular Endothelial Dysfunction Through the Renin-angiotensin-aldosterone System Inhibition Resulting in the Improvement of Muscle Oxygen Metabolism in Patients With Lifestyle Related Disease
Authors: Takeshi Nakamura, Takashi Masuda, Misao N Ogura, Ryosuke Shimizu, Daisuke Kamekawa, Ayako Akiyama, Yumi Kamada, Shinya Tanaka, Nobuaki Hamazaki, Akihiro Aoyama, Kanae Yabu, Emi Maekawa, Junya Ako
Journal: Circulation (2015)

Background: Elevated activity of renin-angiotensin-aldosterone system (RAAS) is known to induce vascular endothelial dysfunction in patients with lifestyle related disease such as diabetes mellitus (DM), hypertension (HT) and dyslipidemia (DL). Because the vascular endothelial dysfunction disturbs an appropriate blood flow to skeletal muscles, it is considered that the oxygen metabolism is impaired in them. Although eicosapentaenoic acid (EPA) has been reported to inhibit the RAAS, it is unclear whether EPA ameliorates vascular endothelial dysfunction via the RAAS inhibition resulting in the improvement of muscle oxygen metabolism. This study investigated the effects of EPA on vascular endothelial function and muscle oxygen metabolism during exercise in patients with lifestyle related disease. Methods: Ninety-two patients (68±8 years, 50 males) were divided into two groups based on the EPA administration in crossover method, after their DM, HT and/or DL were optimally treated. When patients took 1,800 mg of EPA daily for 8 months or not, they were in the EPA(+) group or in the EPA(-) group. In the end of each treatment period, cardiopulmonary exercise test was performed to measure oxygen uptake (VO 2 ) at anaerobic threshold (VO 2 AT ), peak VO 2 and the time from the start of the test to the AT (Time AT ) and endpoint (Time EP ). We measured serum EPA, plasma renin activity (PRA), aldosterone (ALD), adrenalin (ADRN) and noradrenalin (NORA), and reactive hyperemia index (RHI). We used the changes in PRA, ALD, ADRN and NORA before and after a cycle ergometer exercise test (ΔPRA, ΔALD, ΔADRN and ΔNORA) as neurohumoral factors, RHI as a parameter of vascular endothelial function and Time EP as an exercise capacity. Results: There were no significant differences in ΔPRA, ΔALD, ΔNORA, peak VO 2 and Time EP between the two groups. The PRA, ALD and ΔADRN were significantly lower in the EPA(+) group than in the EPA(-) group (P&lt;0.05, respectively). The RHI, VO 2 AT and Time AT were significantly higher in the EPA(+) group than in the EPA(-) group (P&lt;0.05, respectively). Conclusion: Long-term administration of EPA ameliorated vascular endothelial dysfunction via the RAAS inhibition resulting in the improvement of muscle oxygen metabolism in lifestyle related disease patients.
Interethnic differences in Cyp3A4 inhibition by ketoconazole on docetaxel pharmacokinetics (PK) and pharmacodynamics (PD)
Authors: Y. Lim, B. Goh, L. Wang, M. T. Cordero, B. Y. Chuah, S. Lim, S. Tan, S. A. Buhari, R. Soo, S. Lee
Journal: Journal of Clinical Oncology (2009)

2526 Background: Use of concomitant medications that inhibit drug metabolizing enzymes such as Cyp3A4 is common and may affect chemotherapy PK/PD. We studied the effects of Cyp3A4 inhibition with ketoconazole on docetaxel PK/PD in 3 Asian ethnic groups. Methods: Two cohorts of chemonaive breast cancer patients were compared. The first cohort comprised of 95 patients (62 Chinese, 26 Malay, 7 Indian) treated with 75mg/m 2 docetaxel unmodulated by ketoconazole, while the second cohort comprised of 31 patients (14 Chinese, 14 Malay, 3 Indian) treated with docetaxel 70mg flat dose modulated by oral ketoconazole, a regimen we previously reported to result in comparable docetaxel AUC as 75mg/m 2 docetaxel. Plasma docetaxel concentrations were obtained at 0, 0.5, 1, 2, 5, 7 and 24 hours, and blood counts monitored on days 8 and 15 of cycle 1. Results: No significant differences in docetaxel PK or neutropenia between the races were observed in response to 75mg/m 2 docetaxel unmodulated by ketoconazole (docetaxel clearance 36.4±16.9, 34.3±12.5, 44.2±27.7L/h, p=0.702; docetaxel AUC 3.6±2.7, 3.5±1.2, 2.9±1.3mg/L h, p=0.418; day 8 neutrophil count 0.5±0.6, 0.8±0.8, 0.4±0.3x10 9 /L, p=0.138; grade 4 neutropenia 66%, 50%, 86%, p=0.157). In contrast, when docetaxel was administered with ketoconazole to inhibit Cyp3A4, inter-ethnic differences in docetaxel PK/PD were observed, with Chinese having the lowest docetaxel clearance and highest docetaxel AUC, followed by Malays and Indians (docetaxel clearance 18.6±5.7, 23.7±9.3, 30.6±6.7L/h, p=0.048; p=0.017 trend test; docetaxel AUC 4.2±1.4, 4.1±3.9, 2.4±0.5 mg/L h, p=0.048, p=0.017 trend test), although there were no statistically significant differences in body weight or surface area between the races. In concordance, Chinese patients experienced greatest degree of myelosuppression, followed by Malays and Indians (day 8 neutrophil count 0.8±0.8, 1.5±1.1, 1.7±1.1x10 9 /L, p=0.046, p=0.013 trend test), and were more likely to develop grade 4 neutropenia (57%, 14%, 0%, p=0.024) from docetaxel + ketoconazole. Conclusions: Inter-ethnic differences in CYP3A inhibition by ketoconazole exist, and are important when evaluating the impact of concomitant medications with chemotherapy that may inhibit Cyp3A4. No significant financial relationships to disclose.
Signaling Inhibitors in the Clinic: New Agents and New Challenges
Authors: Gary Hudes
Journal: Journal of Clinical Oncology (1999)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.4.1093 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10561165 Signaling Inhibitors in the Clinic: New Agents and New Challenges Gary HudesxGary HudesSearch for articles by this author Show More Fox Chase Cancer Center, Philadelphia, PA https://doi.org/10.1200/JCO.1999.17.4.1093 Full Text PDF Figures and Tables "Signaling Inhibitors in the Clinic: New Agents and New Challenges." Journal of Clinical Oncology, 17(4), p. 1093© 1999 by American Society of Clinical Oncology
Second Primary Neoplasms Following Ovarian Cancer
Authors: Ronald R. Reimer, Robert Hoover, Joseph F. Fraumeni, Robert C. Young
Journal: JNCI Journal of the National Cancer Institute (1978)

Follow-up surveys of patients with ovarian cancer revealed an increased risk of second primary cancers of the uterine corpus, colon, bladder, breast, and hematopoietic system. The excess risk or uterine corpus cancer was independent of therapy. The risk of colon cancer was increased in all treatment groups but was especially high among patients receiving radiation or chemotherapy. The predisposition to other neoplasms was limited to certain treatment groups: bladder cancer to irradiation, leukemia to chemotherapy, and lymphoma to either modality. The pattern of second neoplasms following ovarian cancer appears to be influenced by therapy as well as by common etiologic factors.
Plasma angiopoietin-2 (ANG2) as an angiogenic biomarker in renal cell carcinoma (RCC).
Authors: A. J. Bullock, L. Zhang, A. M. O’Neill, A. Percy, V. Sukhatme, J. W. Mier, M. B. Atkins, R. S. Bhatt
Journal: Journal of Clinical Oncology (2010)

4630 Background: Several small molecules targeting angiogenic receptor tyrosine kinases (TKIs) are approved for treatment of advanced RCC. While many patients (pts) respond to TKIs, resistance develops in all. Ang2 is a secreted glycoprotein that is upregulated at sites of angiogenesis and has been implicated in cancer neovascularization. Ang2 is elevated in many cancer states, and higher levels are associated with poor prognosis. Recent studies have also suggested efficacy of combined angiopoietin and VEGFR inhibition as therapy in advanced RCC. Methods: Levels of circulating angiogenic cytokines, including Ang2, FGF, PlGF, sVEGFR, and VEGF, were measured in plasma collected from 34 pts with metastatic RCC. Plasma Ang2 concentration was measured by ELISA in duplicate samples collected at baseline, on treatment with sunitinib (median 34.5 days after starting sunitinib), and at resistance to sunitinib. Ang2 was also measured in plasma collected from 8 pts with stage I RCC prior to nephrectomy and 8 controls without RCC. Statistical significance was calculated by Wilcoxon sign rank test for paired data and Wilcoxon rank sum test for unpaired data. Results: Ang2 is significantly higher in pts with metastatic RCC (n=34) compared to controls (n=8) (median 3870 vs 1618 pg/ml; p<0.01) and pts with stage I RCC (n=8, median 2489 pg/ml; p=0.02). There is a trend toward higher Ang2 among pts with stage I disease vs controls (p=0.10). Among the 26 pts with metastatic RCC evaluated at baseline and on treatment with sunitinib, Ang2 decreased in 88% (23/26; p<0.01). Of the 20 pts who had progressed and had on treatment Ang2 levels at the time of analysis, Ang2 decreased with initiation of sunitinib in 90% (18/20; p<0.01), and then increased at resistance in 70% (14/20; p=0.08). Conclusions: Our data show that plasma Ang2 concentration is elevated in pts with RCC, and that this may correlate with disease burden. Ang2 decreases in pts treated with sunitinib and increases at the time of resistance to sunitinib. These data are consistent with the hypothesis that VEGFR inhibition leads to a loss of Ang2 expression, and that disease progression may be mediated at least in part by a rise in Ang2. Thus, Ang2 is a potential therapeutic target in TKI resistant RCC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Pfizer Pfizer
Psychiatric disorders in the mentally retarded: types, problems, and challenges
Authors: L F Eaton, F J Menolascino
Journal: American Journal of Psychiatry (1982)

Because of their high incidence of CNS impairment and low overall interpersonal coping abilities, retarded persons have a greater than average risk for developing associated psychiatric disorders. The authors describe the types of disorders and their incidence and review allied treatment challenges. Advances in recognition of developmental issues and medical management support the trend toward decreased institutionalization and the concurrent increased normalization of the retarded individual.
Purpura in Congenital and Acquired Rubella
Authors: William L. Bayer, Frank E. Sherman, Richard H. Michaels, Isabel L. F. Szeto, Jessica H. Lewis
Journal: New England Journal of Medicine (1965)

THE observation of a newborn infant with widespread petechiae and thrombocytopenia born to a mother who had had rubella during the 1964 epidemic stimulated us to seek other newborn and older children with purpura associated with rubella. Twenty-two such patients were found, and the clinical and morphologic observations relevant to this hemorrhagic phenomenon form the basis for this report.Several manifestations of congenital rubella have been added to the cataracts and heart defects described by Gregg1 in 1941, but purpura has not been a conspicuous feature until recently. In a report of the teratogenic effects of rubella in Great Britain . . .
The Sequelae of Eastern Equine Encephalomyelitis
Authors: John C. Ayres, Roy F. Feemster
Journal: New England Journal of Medicine (1949)

WHEN cases of eastern equine encephalomyelitis occurred among human beings in Massachusetts in 1938, it was noted that profound damage to the central nervous system led to marked sequelae. To determine whether these changes are permanent and progressive or whether improvement can be expected, all the survivors who could be located were reinvestigated. The purpose of this paper is to report the present condition of these survivors.Since several years have elapsed since the outbreak, a few facts regarding it are given for the information of those not familiar with the previous papers.Review of Outbreak Epidemiology In July, 1938, . . .
The Significance of Decreased Body Potassium Concentrations in Patients with Muscular Dystrophy and Nondystrophic Relatives
Authors: William H. Blahd, Marianne Lederer, Benedict Cassen
Journal: New England Journal of Medicine (1967)

PATIENTS with muscular dystrophy and also some of their nondystrophic relatives, particularly mothers and female siblings, have diminished total-body potassium concentrations.1 , 2 The diminution of body potassium in these patients appears to correlate with the severity of muscle involvement. On the other hand, the reduced body potassium concentrations observed in some nondystrophic relatives have suggested a biochemical trait with possible genetic implications.There are several possible explanations for such diminished levels of body potassium. It would be logical to assume that the dystrophic patient's loss of body potassium is related to the gradual replacement of normal muscle tissue by potassium-poor fat . . .
Isolation of Erythrocytes with Normal Protoporphyrin Levels in Erythropoietic Protoporphyria
Authors: Neil Kaplowitz, Norman Javitt, Leonard C. Harber
Journal: New England Journal of Medicine (1968)

In erythropoietic protoporphyria less than half the circulating erythrocytes fluoresce, but all erythrocytes hemolyze in vitro on exposure to 400 nanometer radiation. It was shown that 400 nanometer irradiation of mixtures of normal erythrocytes with erythrocytes from patients with erythropoietic protoporphyria leads to photohemolysis of all erythrocytes in the same mixture, presumably owing to the transfer of protoporphyrin. The photosensitization of the normal erythrocytes could be prevented by the addition of albumin. Erythrocytes from patients with erythropoietic protoporphyria, with the addition of albumin, could be separated into two populations, one with an elevated and the other with a normal protoporphyrin level.
Proteome analysis identifies L1CAM/CD171 and DPP4/CD26 as novel markers of human skin mast cells
Authors: M. Gschwandtner, V. Paulitschke, M. Mildner, P. M. Brunner, S. Hacker, G. Eisenwort, W. R. Sperr, P. Valent, C. Gerner, E. Tschachler
Journal: Allergy (2016)

The function of skin mast cells has been well documented in IgE-mediated allergic reactions, whereas other mast cell functions are poorly defined. This study aimed at identifying novel mast cell proteins by proteome analysis of primary human skin mast cells.The proteome of skin mast cells was compared to other cell types and analyzed using bioinformatics. The expression and function of two proteins hitherto not described in skin mast cells was investigated in isolated mast cells as well as in mast cells in situ.Within the mast cell proteome, we identified 49 highly expressed proteins previously not described in mast cells; 21 of these proteins were found to be selectively expressed in mast cells. Two proteins, the neural cell adhesion molecule L1 and dipeptidyl peptidase 4, were further studied. L1 was found to be highly expressed in mast cells in normal, psoriasis, and mastocytosis skin. Dipeptidyl peptidase 4 was found to be expressed in mast cells in normal, psoriasis, and mastocytosis skin as well as in bone marrow mast cells in patients with systemic mastocytosis. In normal skin, mast cells were identified as a major source of dipeptidyl peptidase 4 and we also found that skin mast cells and fibroblasts secrete an active form of this enzyme.In a systematic proteomics approach we identified two novel mast cell proteins potentially relevant to skin homeostasis: neural cell adhesion molecule L1 and dipeptidyl peptidase 4.
Quality of Life in Eosinophilic Esophagitis
Authors: Shreya N. Patel, John Oppenheimer, Tamara Feldman, Annette Langseder, Peter Wilmot, Oren Koslowe, Joel Rosh, Maria Perez, Barbara Verga, Alycia Leiby, Neha Pandey
Journal: Journal of Allergy and Clinical Immunology (2016)
Abstract IA28: New targeted approaches for high-risk pediatric malignancies
Authors: Kimberly Stegmaier
Journal: Cancer Research (2016)

Abstract While significant progress has been made in treating many pediatric malignancies, cancer remains the leading cause of death from disease in children. A number of childhood cancer subtypes remain particularly recalcitrant to dose-intensified cytotoxic treatment suggesting that new approaches are needed. Initial optimism that massively parallel sequencing efforts would reveal imminently targetable lesions has been tempered by a major finding that pediatric cancers often have simple genomes. While a signature mutation is frequently present, the product is often considered a difficult drug target, such as an aberrant transcription factor. Thus, the hope that cancer can be treated with combinations of drugs targeting specific gene mutations is unlikely to be imminently viable for most pediatric cancers. We hypothesized that while there is a notable paucity of events in easily druggable enzymes, a small number of sentinel lesions in an otherwise quiet genome may enable the discovery of synthetic lethal relationships with these key genetic events. Thus, we are applying unbiased approaches to identify key dependencies in pediatric cancers using functional genomic screening (shRNA and CRISPR) and chemical genomic screening. The primary goal is to connect key genetic lesions or disease lineages to new gene targets or small-molecule perturbations in the highest risk subtypes of pediatric cancers. Illustrative examples of our early findings will be presented. Citation Format: Kimberly Stegmaier. New targeted approaches for high-risk pediatric malignancies. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr IA28.
Case 38-1995
Authors: J.L. Ochoa, E.T. Hedley-Whyte
Journal: New England Journal of Medicine (1995)

Presentation of CaseA 68-year-old, right-handed man was admitted to the neurologic clinic because of paresthesias and severe pain in the hands.The patient had been in stable health until 46 days earlier, when he had the sudden onset of increasingly severe paroxysms of “burning” pain in his hands, especially the right hand, accompanied by constant milder pain with persistent numbness and tingling, which were also more severe on the right side, with weakness of the hands. The paroxysms varied in severity and occurred in any position of recumbency; he could sleep for only a few hours on a recliner. . . .
Genomic profiling of mammary duct carcinoma in situ (DCIS) using array comparative genomic hybridization
Authors: Nona C. Arneson, Susan J. Done
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

3605 

Duct carcinoma in situ (DCIS), the earliest recognized form of breast cancer, is being diagnosed with increased frequency due in part to mammographic screening. Until recently, the standard treatment for DCIS was mastectomy. Moves to breast conserving surgery (lumpectomy) have shown reduced recurrence rates when local excision is accompanied by radiation therapy. However, it is only a small proportion of women that will benefit from this adjuvant therapy. The ability to identify this population will help to reduce over-treatment of this group of breast cancer patients. Attempts to classify DCIS based on size and other histologic features have been disappointing. We propose that the identification of a specific set of genetic alterations will allow categorization of DCIS and allow prediction of which cases are most likely to progress. One hundred patients with DCIS have been identified from the University Health Network, Department of Pathology. Approximately half of the cases are pure DCIS and the other half have concurrent invasive carcinoma. Using tissue microdissection from formalin-fixed paraffin-embedded (FFPE) tissues, whole genome amplification (WGA) and array comparative genomic hybridization (aCGH) we are conducting a full genome scan of these lesions (DCIS and invasive carcinoma) to identify common or different regions of amplification and/or deletion. The status of genes identified as lost or gained will be confirmed using quantitative PCR or fluorescence in situ hybridization. In feasibility studies conducted in our lab we have investigated several methods of WGA and different array CGH platforms in order to overcome the limitations associated with using genomic DNA from FFPE tissues. We have been successful at generating CGH profiles from microdissected DCIS lesions with and without WGA using 19K human cDNA arrays containing 19,000 cDNA’s and ESTs (Clinical Genomics Centre, University Health Network) and Nimblegen’s HumanWhole Genome Array CGH platform. In this pilot study, we have identified regions of amplification in the microdissected DCIS samples that are commonly associated with breast cancer, including 1q, 8q and 17q. In addition we have observed both simple (relatively few genomic alterations) and complex molecular profiles. A molecular classification of DCIS that can be employed in the routine clinical setting will be invaluable for use in treatment planning.
P275 Prevalence and Strain Typing Results Of Gram-negative Emerging Bacterial Pathogens in Patients Attending a Large UK Adult CF Centre
Authors: HD Green, R Bright-Thomas, D Kenna, AM Jones
Journal: Thorax (2015)

<h3>Introduction</h3> In recent years Gram-negative bacterial emerging pathogens (EP) have been noted to infect the airways of patients with CF. Prevalence of EP is increasing but much remains unknown. This study aimed to determine prevalence of EP at a large adult UK centre and whether these organisms may be capable of cross infection. <h3>Methods</h3> Prevalence of <i>Burkhoderia multivorans</i>; <i>Stenotrophomonas maltophilia</i> and <i>Achromobacter</i>; <i>Ralstonia</i> and <i>Pandoraea</i> species was calculated in October 2013 and 2014. Strain typing was performed on EP isolated from patients from January 2008 to present using pulsed-field gel electrophoresis following restriction with <i>Xba</i>I. Epidemiology of patients with shared strains was analysed by reviewing patient addresses, outpatient appointments, admissions, paediatric centres and asking patients about their social behaviours. <h3>Results</h3> In October 2013, 358 patients had at least 1 sputum culture result in the previous 12 months and were included in the prevalence calculation. This increased to 368 patients in October 2014. Prevalence of most EP increased between 2013 and 2014. EP prevalence in 2014 ranged from 1.9% (<i>Ralstonia</i> species) to 6.2% (<i>B. multivorans</i>) (Table 1). 96 patients had ≥ 1 isolation of an EP between January 2008 and July 2015. Of these, 20 (21%) have had &gt;2 strains of EP isolated from their sputum within that timeframe. To date, strain typing has been performed on 97 of 115 identified isolates from 96 patients. Shared strains of EP in unrelated patients with epidemiological connexions other than place of home residence were found in cases of infection with <i>Achromobacter</i>, <i>Ralstonia</i> and <i>Pandoraea</i> species. Shared strains of <i>B. multivorans</i> were found in a sibling pair, an unrelated pair with no temporal overlap in positive cultures and in 4 patients with no clear opportunities for cross infection to have occurred. <h3>Conclusions</h3> Prevalence of EP is low at our centre but is slowly increasing. History of EP infection appears to be a risk factor for infection with other EPs. Shared strains of <i>Achromobacter</i>, <i>Ralstonia</i> and <i>Pandoraea</i> species have been identified in our centre in patients with epidemiological connexions. Numbers are too small to establish whether cross infection or a common environmental source is responsible.