tbuckley/cabot-search huggingface dataset:
CDC Initiative Targets HIV Research Gaps in Black and Hispanic Communities
Authors: Richard Trubo
Journal: JAMA (2004)

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UGT1A7 and UGT1A9 Polymorphisms Predict Response and Toxicity in Colorectal Cancer Patients Treated with Capecitabine/Irinotecan
Authors: Leslie E. Carlini, Neal J. Meropol, John Bever, Michael L. Andria, Todd Hill, Philip Gold, Andre Rogatko, Hao Wang, Rebecca L. Blanchard
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Capecitabine and irinotecan are commonly used in the treatment of metastatic colorectal cancer (CRC). We hypothesized that germline polymorphisms within genes related to drug target (thymidylate synthase) or metabolizing enzymes (UDP-glucuronosyltransferase, UGT) would impact response and toxicity to the combination of capecitabine plus irinotecan (CPT-11). Experimental Design: Sixty-seven patients with measurable CRC were treated with irinotecan i.v. (100 or 125 mg/m2) on days 1 and 8 and capecitabine orally (900 or 1,000 mg/m2, twice daily) on days 2 through 15 of each 3-week cycle. Genomic DNA was extracted from peripheral blood and genotyped using Pyrosequencing, GeneScan, and direct sequencing (Big Dye terminator) technologies. Results: The overall objective response rate was 45% with 21 patients (31%) exhibiting grade 3 or 4 diarrhea and 3 patients (4.5%) demonstrating grade 3 or 4 neutropenia in the first two cycles. Low enzyme activity UGT1A7 genotypes, UGT1A7*2/*2 (six patients) and UGT1A7*3/*3 (seven patients), were significantly associated with antitumor response (p = 0.013) and lack of severe gastrointestinal toxicity (p = 0.003). In addition, the UGT1A9 −118 (dT)9/9 genotype was significantly associated with reduced toxicity (p = 0.002) and increased response (p = 0.047). There were no statistically significant associations between UGT1A1, UGT1A6, or thymidylate synthase genotypes and toxicity or tumor response. Conclusions: These data strongly suggest that UGT1A7 and/or UGT1A9 genotypes may be predictors of response and toxicity in CRC patients treated with capecitabine plus irinotecan. Specifically, patients with genotypes conferring low UGT1A7 activity and/or the UGT1A9 (dT)9/9 genotype may be particularly likely to exhibit greater antitumor response with little toxicity.
Differences in Repair of DNA Cross-links between Lymphocytes and Epithelial Tumor Cells from Colon Cancer Patients Measured <i>In vitro</i> with the Comet Assay
Authors: Mercedes Herrera, Gemma Dominguez, Jose M. Garcia, Cristina Peña, Carmen Jimenez, Javier Silva, Vanesa Garcia, Irene Gomez, Raquel Diaz, Paloma Martin, Felix Bonilla
Journal: Clinical Cancer Research (2009)

The more common approach to comet assay studies with cancer patients involves indirect measurement of the effect of antineoplastic drug or radiation regimen by assessing DNA damage in surrogate cells, such as peripheral blood lymphocytes of cancer patients, to predict how tumor cells may be affected. The aim of the present study was to compare the capability of different cells isolated from a series of 23 colon cancer patients to repair the damage induced by a cancer drug.We adapted the in vitro comet repair assay for nucleotide excision repair to measure the ability of lymphocytes and normal and tumor epithelial colon cells to remove DNA cross-links induced by oxaliplatin. The excision repair rate was measured quantitatively by the tail parameters: tail DNA, tail length, extent tail moment, and olive tail moment.Kruskal-Wallis analysis revealed significant differences in recognition and excision activity between different cell types (P < 0.001) for all the comet parameters studied. Hence, colon cells showed higher recognition and excision activity than lymphocytes and tumor cells displayed the highest repair capability. We found no significant correlation between the repair activity of tumor colon cells and lymphocytes in any of the comet parameters considered.Our data support the view that lymphocyte repair activity is not predictive of the repair ability of the tumor and that lymphocytes cannot act as surrogate cells.
The practice of primary care sports medicine in the USA
Authors: J J Diehl, J J Pirozzolo, T M Best
Journal: British Journal of Sports Medicine (2008)

To investigate and to characterise the practice patterns, academic rank, and income variables that exist in order to better understand the career of a sports medicine physician in the USA.A cross-sectional survey of family physicians holding a Certificate of Added Qualifications in Sports Medicine through the American Board of Family Medicine as of January 2006.The survey was completed by 325 of 862 physicians (a return rate of 38%). Of all respondents, 212 (65%) reported completing a Primary Care Sports Medicine Fellowship, 276 (85%) were male and 49 (15%) were female, and 300 (92%) reported having a MD, while 25 (8%) had a DO. Clinical duties represented the largest proportion of the physicians' schedules (7.94 half days/week), and the majority of physicians performed routine athletic event coverage. The average salary for all physicians was $166,000 US. Higher-income groups included: men ($172,000 vs $132 000 for women); regions including Central, South East, and South West; full professors; and non-student health or urgent care clinical work. With control for all other variables, four groups demonstrated significantly higher odds of being high income earners (annual gross salary > $200,000 US). These groups included age over 40, male sex, practice owner, and seeing over 10 patients per half day.Salary can be related to age, gender, number of patients seen, and practice ownership. No statistical difference among salaries was found between MDs and DOs, osteopathic manipulative therapy (OMT) practice, region of the country, or how practices are marketed.
Pulmonary Embolism
Authors: Ary Ribeiro, Per Lindmarker, Hans Johnsson, Anders Juhlin-Dannfelt, Lennart Jorfeldt
Journal: Circulation (1999)

Background —The long-term prognosis for patients with pulmonary embolism (PE) is dependent on the underlying disease, degree of pulmonary hypertension (PH), and degree of right ventricular (RV) dysfunction. A precise description of the time course of pulmonary artery pressure (PAsP)/RV function is therefore of importance for the early identification of persistent PH/RV dysfunction in patients treated for acute PE. Other objectives were to identify variables associated with persistent PH/RV dysfunction and to analyze the 5-year survival rate for patients alive 1 month after inclusion. Methods and Results —Echocardiography Doppler was performed in 78 patients with acute PE at the time of diagnosis and repeatedly during the next year. A 5-year survival analysis was made. The PAsP decreased exponentially until the beginning of a stable phase, which was ≤38 days. The recovery of RV function occurred during the same time period. Risk factors for persistent PH/RV dysfunction and the 5-year mortality rate were analyzed using multiple logistic regression models. A PAsP of &gt;50 mm Hg at the time of diagnosis of acute PE was associated with persistent PH after 1 year. The 5-year mortality rate was associated with underlying disease. Only patients with persistent PH in the stable phase required pulmonary thromboendarterectomy within 5 years. Conclusions —An echocardiography Doppler investigation performed 6 weeks after diagnosis of acute PE can identify patients with persistent PH/RV dysfunction and may be of value in planning the follow-up and care of these patients.
Impact of Body Mass Index and the Metabolic Syndrome on the Risk of Cardiovascular Disease and Death in Middle-Aged Men
Authors: Johan Ärnlöv, Erik Ingelsson, Johan Sundström, Lars Lind
Journal: Circulation (2009)

Background— The purpose of this study was to investigate associations between combinations of body mass index (BMI) categories and metabolic syndrome (MetS) and the risk of cardiovascular disease and death in middle-aged men. Methods and Results— At age 50 years, cardiovascular risk factors were assessed in 1758 participants without diabetes in the community-based Uppsala Longitudinal Study of Adult Men (ULSAM). According to BMI-MetS status, they were categorized as normal weight (BMI &lt;25 kg/m 2 ) without MetS (National Cholesterol Education Program criteria; n=891), normal weight with MetS (n=64), overweight (BMI 25 to 30 kg/m 2 ) without MetS (n=582), overweight with MetS (n=125), obese (BMI &gt;30 kg/m 2 ) without MetS (n=30), or obese with MetS (n=66). During follow-up (median 30 years), 788 participants died, and 681 developed cardiovascular disease (composite of cardiovascular death or hospitalization for myocardial infarction, stroke, or heart failure). In Cox proportional-hazards models that adjusted for age, smoking, and low-density lipoprotein cholesterol, an increased risk for cardiovascular disease was observed in normal-weight participants with MetS (hazard ratio 1.63, 95% confidence interval 1.11 to 2.37), overweight participants without MetS (hazard ratio 1.52, 95% confidence interval 1.28 to 1.80), overweight participants with MetS (hazard ratio 1.74, 95% confidence interval 1.32 to 2.30), obese participants without MetS (hazard ratio 1.95, 95% confidence interval 1.14 to 3.34), and obese participants with MetS (hazard ratio 2.55, 95% confidence interval 1.81 to 3.58) compared with normal-weight individuals without MetS. These BMI-MetS categories significantly predicted total mortality rate in a similar pattern. Conclusions— Middle-aged men with MetS had increased risk for cardiovascular events and total death regardless of BMI status during more than 30 years of follow-up. In contrast to previous reports, overweight and obese individuals without MetS also had an increased risk. The present data refute the notion that overweight and obesity without MetS are benign conditions.
Impact of poor dental health on pneumonia
Authors: M. P. Wise, D. W. Williams, M. A. Lewis, J. G. Thomas, P. J. Frost
Journal: European Respiratory Journal (2008)

into the dental chair unit and, secondly, suck back of patient's saliva into the line due to lack of anti-retraction valves.Even a small amount of Pseudomonas aeruginosa in a municipal water system can contribute to the dental chair unit contamination problem because dental chair units provide a different environment with small bores, narrow lumens and periods of stagnant water.However, if the water is well maintained according to current hygiene guidelines, the prevalence of Pseudomonas aeruginosa in the public water supply is extremely low [6].As Pseudomonas aeruginosa can be recovered from the oral cavity of ,4% of healthy individuals [7], it is therefore possible that some of these bacteria are aspirated into the dental chair unit waterlines through a defective check valve and are able to colonise in the waterlines.As the suction system hoses and pipe work are frequently wet, they provide an environment that is conducive to the growth and proliferation of biofilms which adhere to the inner surfaces of the lines.This biofilm protects the bacteria both from being washed away by the water flow and from many types of antimicrobial water treatment [8].
Intensified CHOP regimen in aggressive lymphomas:maximal dose intensity and dose density of doxorubicin and cyclophosphamide
Authors: M. Balzarotti, M. Spina, B. Sarina, M. Magagnoli, L. Castagna, I. Milan, C. Ripa, F. Latteri, D. Bernardi, A. Bertuzzi, A. Nozza, M. Roncalli, E. Morenghi, U. Tirelli, A. Santoro
Journal: Annals of Oncology (2002)
Using a Xenograft Model of Human Breast Cancer Metastasis to Find Genes Associated with Clinically Aggressive Disease
Authors: Harriet M. Kluger, Dina Chelouche Lev, Yuval Kluger, Mary M. McCarthy, Galina Kiriakova, Robert L. Camp, David L. Rimm, Janet E. Price
Journal: Cancer Research (2005)

Abstract Metastasis is the primary cause of death from breast cancer. A xenograft model was used to identify genes potentially involved with metastasis, comparing expression in the poorly metastatic GI101A human breast cancer cell line and a highly metastatic variant, GILM2. cDNA microarray analyses of these isogenic variants were done using 16K Operon 70-mer oligonucleotide microarray slides. Differentially expressed genes were identified by ANOVA, and differences of ≥2.5-fold were found for 106 genes. Changes in protein or RNA expression were confirmed for 10 of 12 genes. Three markers, heat shock protein 70 (HSP-70), chemokine (C-X-C motif) ligand 1 (CXCL-1), and secreted leukocyte protease inhibitor (SLPI), were studied further with breast cancer tissue microarrays using a novel method of automated quantitative analysis. This uses cytokeratin to define pixels as breast cancer (tumor mask) within the tissue array spot and then measures intensity of marker expression using a cyanine 5–conjugated antibody within the mask. Scores were correlated with clinicopathologic variables. High HSP-70 expression and high nuclear CXCL-1 expression in primary tumors were both associated with decreased survival (P = 0.05 and 0.027, respectively). Expression of each marker was strongly associated with lymph node involvement (P = 0.0002, 0.008, 0.0012, and 0.012 for HSP-70, nuclear CXCL-1, cytoplasmic CXCL-1, and SLPI, respectively). Identification of genes associated with metastasis in experimental models may have clinical implications for the management of breast cancer, because some of these are associated with lymph node metastasis and survival and might be useful as prognostic markers or molecular targets for novel therapies.
<i>Aspergillus</i>Galactomannan Detection in the Diagnosis of Invasive Aspergillosis in Cancer Patients
Authors: Raoul Herbrecht, Valérie Letscher-Bru, Corina Oprea, Bruno Lioure, Jocelyn Waller, France Campos, Odile Villard, Kun-Lun Liu, Shanti Natarajan-Amé, Patrick Lutz, Patrick Dufour, Jean-Pierre Bergerat, Ermanno Candolfi
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To assess the Aspergillus galactomannan enzyme-linked immunosorbent assay (ELISA) in the diagnosis of invasive aspergillosis (IA) in adult and pediatric oncohematologic patients. PATIENTS AND METHODS: The study was conducted in four patient groups: those with fever of unknown origin (FUO) during neutropenia, suspected pulmonary infection (PI), or nonpulmonary aspergillosis (NPA) and those undergoing surveillance (S) after hematopoietic stem-cell transplantation (HSCT). IA was classified as definite, probable, or possible, according to European Organization for Research and Treatment of Cancer/Mycosis Study Group definitions. RESULTS: A total of 3,294 serum samples were collected during 797 episodes (FUO, 261; PI, 297; NPA, 28; and surveillance, 211), and 153 episodes of IA were diagnosed (31 definite, 67 probable, and 55 possible). Three episodes were first suspected from galactomannan ELISA; the remaining 150 cases were diagnosed from clinical or radiologic evidence. Sensitivity of the ELISA was 64.5%, 16.4%, and 25.5% in definite, probable, and possible episodes of IA, respectively, and was lower in patients positive for anti-Aspergillus antibodies than in antibody-negative patients. Most false-positive results occurred in children and in allogeneic HSCT (allo-HSCT) patients. Overall specificity of the ELISA was 94.8%. It was lower in children compared with adults (P &lt; .0001) and in allo-HSCT patients compared with non–allo-HSCT adults (P = .0002). Lowering the ELISA cutoff value from 1.500 to 0.700 seemed more relevant for non–allo-HSCT adults (sensitivity, 73.1%, 44.3%, and 44.7% in definite, probable, and possible IA, respectively; specificity, 94%). CONCLUSION: Galactomannan ELISA seems less sensitive than previously described, and sensitivity can be further reduced by the presence of anti-Aspergillus antibodies. A new cutoff value for the ELISA of 0.700 is proposed for non–allo-HSCT adults.
Inhibition of hedgehog signaling ameliorates hepatic inflammation in mice with nonalcoholic fatty liver disease
Authors: Hyunjoo Kwon, Kyoungsub Song, Chang Han, Weina Chen, Ying Wang, Srikanta Dash, Kyu Lim, Tong Wu
Journal: Hepatology (2015)

Hedgehog (Hh) signaling plays a critical role in liver development, regeneration, injury repair, and carcinogenesis. Activation of Hh signaling has been observed in patients with nonalcoholic fatty liver diseases (NAFLD); however, the pathobiological function and regulatory mechanism of hepatic Hh signaling in the pathogenesis of NAFLD remain to be further defined. This study was designed to examine the effect and mechanism of hepatic Hh signaling in high‐fat diet‐induced NAFLD by using pharmacological Smoothened (Smo) inhibitors (GDC‐0449 and LED225) and liver‐specific Smo knockout mice. Administration of Smo inhibitors to high‐fat diet‐fed wild‐type mice significantly reduced the numbers of activated macrophages and decreased the expression of proinflammatory cytokines (tumor necrosis factor‐α, interleukin‐1β, monocyte chemoattractant protein 1, and interleukin‐6) as assessed by F4/80 immunohistochemistry and quantitative reverse‐transcription polymerase chain reaction, respectively. The Smo inhibitors were noted to have variable effects on hepatic fat accumulation. Liver‐specific deletion of Smo also reduced macrophage activation and inhibited proinflammatory cytokine expression, while it did not significantly alter fat accumulation in the liver. Mechanistically, we found that activation of glioma‐associated oncogene 1 by Hh signaling in primary hepatocytes increased the production of osteopontin, which subsequently enhanced the macrophage‐mediated proinflammatory response through paracrine signaling. Conclusion: Hepatocyte Hh signaling can promote liver inflammation through osteopontin‐mediated macrophage activation; this mechanism importantly contributes to the progression of NAFLD . (H epatology 2016;63:1155–1169)
Effects of Long-Term Bosentan in Children With Pulmonary Arterial Hypertension
Authors: Erika Berman Rosenzweig, D. Dunbar Ivy, Allison Widlitz, Aimee Doran, Lori R. Claussen, Delphine Yung, Steven H. Abman, Adele Morganti, Ngoc Nguyen, Robyn J. Barst
Journal: Journal of the American College of Cardiology (2005)
Physiologic Effects of Noninvasive Ventilation during Acute Lung Injury
Authors: Erwan L'Her, Nicolas Deye, François Lellouche, Solenne Taille, Alexandre Demoule, Amanda Fraticelli, Jordi Mancebo, Laurent Brochard
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

A prospective, crossover, physiologic study was performed in 10 patients with acute lung injury to assess the respective short-term effects of noninvasive pressure-support ventilation and continuous positive airway pressure. We measured breathing pattern, neuromuscular drive, inspiratory muscle effort, arterial blood gases, and dyspnea while breathing with minimal support and the equipment for measurements, with two combinations of pressure-support ventilation above positive end-expiratory pressure (10-10 and 15-5 cm H2O), and with continuous positive airway pressure (10 cm H2O). Tidal volume was increased with pressure support, and not with continuous positive airway pressure. Neuromuscular drive and inspiratory muscle effort were lower with the two pressure-support ventilation levels than with other situations (p < 0.05). Dyspnea relief was significantly better with high-level pressure-support ventilation (15-5 cm H2O; p < 0.001). Oxygenation improved when 10 cm H2O positive end-expiratory pressure was applied, alone or in combination. We conclude that, in patients with acute lung injury (1) noninvasive pressure-support ventilation combined with positive end-expiratory pressure is needed to reduce inspiratory muscle effort; (2) continuous positive airway pressure, in this setting, improves oxygenation but fails to unload the respiratory muscles; and (3) pressure-support levels of 10 and 15 cm H2O provide similar unloading but differ in their effects on dyspnea.
Molecular Correlates of Renal Function in Kidney Transplant Biopsies
Authors: Sakarn Bunnag, Gunilla Einecke, Jeff Reeve, Gian S. Jhangri, Thomas F. Mueller, Banu Sis, Luis G. Hidalgo, Michael Mengel, Daniel Kayser, Bruce Kaplan, Philip F. Halloran
Journal: Journal of the American Society of Nephrology (2009)

The molecular changes in the parenchyma that reflect disturbances in the function of kidney transplants are unknown. We studied the relationships among histopathology, gene expression, and renal function in 146 human kidney transplant biopsies performed for clinical indications. Impaired function (estimated GFR) correlated with tubular atrophy and fibrosis but not with inflammation or rejection. Functional deterioration before biopsy correlated with inflammation and tubulitis and was greater in cases of rejection. Microarray analysis revealed a correlation between impaired renal function and altered expression of sets of transcripts consistent with tissue injury but not with those consistent with cytotoxic T cell infiltration or IFN-γ effects. Multivariate analysis of clinical variables, histologic lesions, and transcript sets confirmed that expression of injury-related transcript sets independently correlated with renal function. Analysis of individual genes confirmed that the transcripts with the greatest positive or negative correlations with renal function were those suggestive of response to injury and parenchymal dedifferentiation not inflammation. We defined new sets of genes based on individual transcripts that correlated with renal function, and these highly correlated with the previously developed injury sets and with atrophy and fibrosis. Thus, in biopsies performed for clinical reasons, functional disturbances are reflected in transcriptome changes representing tissue injury and dedifferentiation but not the inflammatory burden.
Transplantation Tumors And Immunologically Privileged Sites
Authors: J. William Futrell
Journal: JAMA (1972)

To the Editor.—  The recent article by Hume's group (219:1593, 1972) relating the high incidence of reticulum cell sarcomas in immunosuppressed renal transplant recipients again emphasizes an increasingly frequent problem. That a relatively large number of malignancies should occur in such patients is not unexpected considering the accumulating evidence of a similarly increased malignancy rate associated with other immunodepressed states. 1 What is surprising, and currently unexplained, however, is the predilection for such tumors to occur in the brain. Penn 2 has collected and analyzed 37 cases of malignant tumors arising de novo in transplant recipients at some time after the start of immunosuppressive therapy and subsequent renal transplantation. Twenty-one of these cases comprised a rather heterogeneous group of epithelial tumors while 12 cases were reticulum cell sarcomas; six of these (50%) occurred primarily or exclusively in the brain. Although the vast majority of reticulum cell sarcomas involve primarily hemopoietic