tbuckley/cabot-search huggingface dataset:
Phase I Study of Bevacizumab Added to Fluorouracil- and Hydroxyurea-Based Concomitant Chemoradiotherapy for Poor-Prognosis Head and Neck Cancer
Authors: Tanguy Y. Seiwert, Daniel J. Haraf, Ezra E.W. Cohen, Kerstin Stenson, Mary Ellyn Witt, Allison Dekker, Masha Kocherginsky, Ralph R. Weichselbaum, Helen X. Chen, Everett E. Vokes
Journal: Journal of Clinical Oncology (2008)

We conducted a phase I dose escalation study to determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of bevacizumab, when added to the standard FHX (fluorouracil [FU], hydroxyurea [HU], radiation) chemoradiotherapy platform in poor-prognosis head and neck cancer (HNC) patients.Patients with recurrent, previously radiated or poor-prognosis, treatment-naive HNC were eligible. Treatment was repeated every 14 days for seven cycles: Bevacizumab was escalated 2.5 to 10 mg/kg, FU 600 to 800 mg/m(2) (120 hours continuous infusion), and hydroxyurea from 500 to 1,000 mg (twice daily for 5 days), starting day 1. At the MTD, the cohort was expanded.Forty-three patients were treated. DLT was reached at level 3 (bevacizumab 5 mg/kg, FU 800 mg/m(2), HU 1,000 mg) with two grade 3 transaminase elevations and one grade 4 neutropenia, attributed to the combination of chemotherapy with bevacizumab. For level 4, chemotherapy doses were reduced (FU 600 mg/(2), HU 500 mg), and bevacizumab escalation continued to 10 mg/kg. Treatment of six assessable patients resulted in one venous thrombosis; this dose level was expanded to 26 patients. Late complications included five patients with fistula formation (11.6%) and four with ulceration/tissue necrosis (9.3%). Serious toxicities (hemorrhage/thrombosis/death) were comparable to prior reirradiation reports. Median overall survival for reirradiated patients with recurrent, nonmetastatic disease was 10.3 months [95% CI, 5.6 to 13.5]; 2-year cumulative incidence of death resulting from disease was 51.7% (95% CI, 31.7 to 68.5).Bevacizumab can be integrated with FHX chemoradiotherapy at a dose of 10 mg/m(2) every 2 weeks with decreased chemotherapy doses because of neutropenia. The regimen shows antitumor activity. Observed fistula formation/tissue necrosis may be bevacizumab related, and further investigation should proceed with careful monitoring.
Pretreatment neuropsychological deficits in children with brain tumors
Authors: L. Iuvone, L. Peruzzi, C. Colosimo, G. Tamburrini, M. Caldarelli, C. Di Rocco, D. Battaglia, F. Guzzetta, S. Misciagna, A. Di Giannatale, A. Ruggiero, R. Riccardi
Journal: Neuro-Oncology (2011)

Treatment of childhood brain cancer has been associated with long-term cognitive morbidity in children. In the present study, the cognitive status of children with brain tumors was examined prior to any treatment to single out the role of tumor and tumor-related factors in cognitive deficits. Eighty-three children with newly diagnosed brain tumors (mean age, 8.6 years; range, 7 months to 16.6 years; median, 9.4 years) completed an extensive battery of age-related tests to assess cognitive function before any therapeutic intervention. Magnetic resonance imaging (MRI) was used to determine tumor site and volume and tumor-related factors. Performance under test was compared with symptom duration, neurological status, epilepsy, and MRI. Cognitive difficulties are detected at diagnosis in as many as 50% of patients for some cognitive domains; 6% of patients present with true-diagnosed mental retardation. The location of the tumor is the principal determinant of cognitive deficits, with major impairment in children with cortical tumors. Symptom duration and the presence of epilepsy are significantly associated with neuropsychological disabilities, while neuroradiological tumor-related variables do not correlate clearly with neurocognitive performance. The knowledge of the pre-existing cognitive deficits is critical to evaluate the results of treatment, providing a baseline for assessing the true impact of therapy in determining cognitive decline. In addition, the study suggests that some clinical variables require careful monitoring, because they could be specifically implicated in the neuropsychological outcome; the efforts to reduce the impact of these factors could ameliorate long-term prognosis.
Centripetal skater's manual oedema
Authors: S Naimer
Journal: British Journal of Sports Medicine (2002)

Emergency granulopoiesis refers to the increased production of neutrophils in bone marrow and their release into circulation induced by severe infection. Several studies point to a critical role for G-CSF as the main mediator of emergency granulopoiesis. However, the consequences of G-CSF stimulation on the transcriptome of neutrophils and their precursors have not yet been investigated in humans. In this work, we examine the changes in mRNA expression induced by administration of G-CSF in vivo, as a model of emergency granulopoiesis in humans. Blood samples were collected from healthy individuals after 5 d of G-CSF administration. Neutrophil precursors were sorted into discrete stages of maturation by flow cytometry, and RNA was subjected to microarray analysis. mRNA levels were compared with previously published expression levels in corresponding populations of neutrophil precursors isolated from bone marrow of untreated, healthy individuals. One thousand one hundred and ten mRNAs were differentially expressed &gt;2-fold throughout terminal granulopoiesis. Major changes were seen in pathways involved in apoptosis, cytokine signaling, and TLR pathways. In addition, G-CSF treatment reduced the levels of four of five measured granule proteins in mature neutrophils, including the proantibacterial protein hCAP-18, which was completely deficient in neutrophils from G-CSF–treated donors. These results indicate that multiple biological processes are altered to satisfy the increased demand for neutrophils during G-CSF–induced emergency granulopoiesis in humans.
Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43
Authors: Magdalini Polymenidou, Clotilde Lagier-Tourenne, Kasey R Hutt, Stephanie C Huelga, Jacqueline Moran, Tiffany Y Liang, Shuo-Chien Ling, Eveline Sun, Edward Wancewicz, Curt Mazur, Holly Kordasiewicz, Yalda Sedaghat, John Paul Donohue, Lily Shiue, C Frank Bennett, Gene W Yeo, Don W Cleveland
Journal: Nature Neuroscience (2011)
Evidence for an Age Cutoff Greater Than 365 Days for Neuroblastoma Risk Group Stratification in the Children's Oncology Group
Authors: W.B. London, R.P. Castleberry, K.K. Matthay, A.T. Look, R.C. Seeger, H. Shimada, P. Thorner, G. Brodeur, J.M. Maris, C.P. Reynolds, S.L. Cohn
Journal: Journal of Clinical Oncology (2005)

In the Children's Oncology Group, risk group assignment for neuroblastoma is critical for therapeutic decisions, and patients are stratified by International Neuroblastoma Staging System stage, MYCN status, ploidy, Shimada histopathology, and diagnosis age. Age less than 365 days has been associated with favorable outcome, but recent studies suggest that older age cutoff may improve prognostic precision.To identify the optimal age cutoff, we retrospectively analyzed data from the Pediatric Oncology Group biology study 9047 and Children's Cancer Group studies 321p1-p4, 3881, 3891, and B973 on 3,666 patients (1986 to 2001) with documented ages and follow-up data. Twenty-seven separate analyses, one for each different age cutoff (adjusting for MYCN and stage), tested age influence on outcome. The cutoff that maximized outcome difference between younger and older patients was selected.Thirty-seven percent of patients were younger than 365 days, and 64% were > or = 365 days old (4-year event-free survival [EFS] rate +/- SE: 83% +/- 1% [n = 1,339] and 45% +/- 1% [n = 2,327], respectively; P < .0001). Graphical analyses revealed the continuous nature of the prognostic contribution of age to outcome. The optimal 460-day cutoff we selected maximized the outcome difference between younger and older patients. Forty-three percent were younger than 460 days, and 57% were > or = 460 days old (4-year EFS rate +/- SE: 82% +/- 1% [n = 1,589] and 42% +/- 1% [n = 2,077], respectively; P < .0001). Using a 460-day cutoff (assuming stage 4, MYCN-amplified patients remain high-risk), 5% of patients (365 to 460 days: 4-year EFS 92% +/- 3%; n = 135) fell into a lower risk group.The prognostic contribution of age to outcome is continuous in nature. Within clinically relevant risk stratification, statistical support exists for an age cutoff of 460 days.
Comparison of 85krypton and 133xenon cerebral blood flow measurements before, during, and following focal, incomplete ischemia in the squirrel monkey.
Authors: E J Hanson, R E Anderson, T M Sund
Journal: Circulation Research (1975)

A comparison of regional cerebral blood flow measurements made with beta- and gamma-emitting isotopes revealed good correspondence in areas of normal perfusion and reactive hyperemia but poor correspondence in areas of focal ischemia. After middle cerebral artery occlusion at normocapnia, there was a 65% reduction in regional cerebral blood flow from 1.40 plus or minus 0.27 ml/g min--1 to 0.49 plus or minus 0.10 ml/g min--1 in monkeys studied with 85Kr but only a 27% reduction in regional cerebral blood flow from 0.84 plus or minus 0.09 ml/g min--1 to 0.61 plus or minus 0.08 ml/g min--1 in monkeys studied with 133Xe. The lack of correlation within areas of focal, incomplete ischemia was attributed to an impairment of isotope delivery to the area of ischemia coupled with the inherent lack of spatial resolution of determinations made with 133Xe. This finding may partly explain the numerous discrepancies in experimental and clinical studies of the effects of alterations in the arterial partial pressure of CO2 on regional cerebral blood flow in areas of ischemia; it may also explain the failure of such studies to reflect the true severity of focal ischemia.
Anaphylaxis from cow's milk casein
Authors: A. I. Tabar, M. J. Alvarez, S. Echechipía, S. Acero, B. E. Garcia, J. M. Olaguíbel
Journal: Allergy (1996)

The case of a 35‐ear‐old woman who suffered anaphylaxis after the ingestion of milk or milk‐containing products is presented. Symptoms also appeared after the patient used a cosmetic which contained casein. Skin prick tests, specific IgE measurement, and immunoblotting were carried out with cow's milk extract, and its purified proteins: casein, β‐lactoglobulin, and α‐lactalbumin. Specific IgE to cow's milk casein was detected with the three tests. Immunoblotting revealed one band of 24 kDa approximately corresponding to the β‐fraction of casein. Negative results to β‐lactoglobulin and α‐lactalbumin were obtained with the three methods. Symptoms were controlled by rigorous dietary and behavior measures.
Decreased incidence of nonmelanoma skin cancer in patients with type 2 diabetes mellitus using insulin: a pilot study
Authors: T-Y. Chuang, D.A. Lewis, D.F. Spandau
Journal: British Journal of Dermatology (2005)

Background In order to prevent the propagation of genetic mutations, human keratinocytes irradiated with ultraviolet (UV) B light in vitro undergo premature stress-induced senescence or apoptosis. This response to UVB irradiation is dependent on the functional activation of the insulin-like growth factor-1 receptor (IGF-1R). Based on this in vitro functional data, we hypothesized that the increased serum levels of insulin in patients with type 2 diabetes may activate the IGF-1R in skin and lead to a decreased frequency of skin cancer in these patients. Objectives To determine whether the use of insulin by patients with type 2 diabetes correlated with a change in the incidence in nonmelanoma skin cancer (NMSC). Methods A historical cohort study identifying the incidence of NMSC following the use of two different pharmacological therapies. The patient population was restricted to caucasians who were at least 50 years old when they began the indicated pharmacological therapy. The first group consisted of 1440 patients who used insulin therapy to treat type 2 diabetes and the second group comprised 4135 patients who used cimetidine to treat their gastrointestinal ailments. An additional group of 6131 patients with diabetes who used noninsulin antidiabetics was added to examine the effect of noninsulin therapies. All patients had regular follow-up visits at the Regenstrief Clinics during the study period between 1980 and 1999. The Regenstrief Clinics is an outpatient facility which serves the general population in Metro-Indianapolis, Indiana, U.S.A. Results The incidence of NMSC in patients using insulin was significantly lower than in patients using cimetidine (1·25% vs. 2·35%, P < 0·02). The decrease in NMSC in patients with type 2 diabetes correlated specifically with the use of insulin (NMSC incidence insulin-only patients with diabetes: 1·40% vs. those with diabetes using noninsulin therapies: 2·35%, P = 0·11). Conclusions Patients using exogenous insulin had a lower risk of developing NMSC and the protective effect of insulin use becomes more distinct with increasing age.
Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells
Authors: Luis A. Garza, Chao-Chun Yang, Tailun Zhao, Hanz B. Blatt, Michelle Lee, Helen He, David C. Stanton, Lee Carrasco, Jeffrey H. Spiegel, John W. Tobias, George Cotsarelis
Journal: Journal of Clinical Investigation (2011)

Androgenetic alopecia (AGA), also known as common baldness, is characterized by a marked decrease in hair follicle size, which could be related to the loss of hair follicle stem or progenitor cells. To test this hypothesis, we analyzed bald and non-bald scalp from AGA individuals for the presence of hair follicle stem and progenitor cells. Cells expressing cytokeratin15 (KRT15), CD200, CD34, and integrin, α6 (ITGA6) were quantitated via flow cytometry. High levels of KRT15 expression correlated with stem cell properties of small cell size and quiescence. These KRT15hi stem cells were maintained in bald scalp samples. However, CD200hiITGA6hi and CD34hi cell populations — which both possessed a progenitor phenotype, in that they localized closely to the stem cell–rich bulge area but were larger and more proliferative than the KRT15hi stem cells — were markedly diminished. In functional assays, analogous CD200hiItga6hi cells from murine hair follicles were multipotent and generated new hair follicles in skin reconstitution assays. These findings support the notion that a defect in conversion of hair follicle stem cells to progenitor cells plays a role in the pathogenesis of AGA.
Cardiopulmonary Function and Age-Related Decline Across the Breast Cancer Survivorship Continuum
Authors: Lee W. Jones, Kerry S. Courneya, John R. Mackey, Hyman B. Muss, Edith N. Pituskin, Jessica M. Scott, Whitney E. Hornsby, April D. Coan, James E. Herndon, Pamela S. Douglas, Mark Haykowsky
Journal: Journal of Clinical Oncology (2012)

Purpose To evaluate cardiopulmonary function (as measured by peak oxygen consumption [VO 2peak ]) across the breast cancer continuum and its prognostic significance in women with metastatic disease. Patients and Methods Patients with breast cancer representing four cross-sectional cohorts—that is, (1) before, (2) during, and (3) after adjuvant therapy for nonmetastatic disease, and (4) during therapy in metastatic disease—were studied. A cardiopulmonary exercise test (CPET) with expired gas analysis was used to assess VO 2peak . A Cox proportional hazards model was used to estimate the risk of death according to VO 2peak category (&lt; 15.4 v ≥ 15.4 mL · kg −1 · min −1 ) with adjustment for clinical factors. Results A total of 248 women (age, 55 ± 8 years) completed a CPET. Mean VO 2peak was 17.8 ± a standard deviation of 4.3 mL · kg −1 · min −1 , the equivalent of 27% ± 17% below age-matched healthy sedentary women. For the entire cohort, 32% had a VO 2peak less than 15.4 mL · kg −1 · min −1 —the VO 2peak required for functional independence. VO 2peak was significantly different across breast cancer cohorts for relative (mL · kg −1 · min −1 ) and absolute (L · min −1 ) VO 2peak (P = .017 and P &lt; .001, respectively); VO 2peak was lowest in women with metastatic disease. In patients with metastatic disease (n = 52), compared with patients achieving a VO 2peak ≤ 1.09 L · min −1 , the adjusted hazard ratio for death was 0.32 (95% CI, 0.16 to 0.67, P = .002) for a VO 2peak more than 1.09 L · min −1 . Conclusion Patients with breast cancer have marked impairment in VO 2peak across the entire survivorship continuum. VO 2peak may be an independent predictor of survival in metastatic disease.
Regular Physical Activity Improves Endothelial Function in Patients With Coronary Artery Disease by Increasing Phosphorylation of Endothelial Nitric Oxide Synthase
Authors: R. Hambrecht, V. Adams, S. Erbs, A. Linke, N. Kränkel, Y. Shu, Y. Baither, S. Gielen, H. Thiele, J.F. Gummert, F.W. Mohr, G. Schuler
Journal: Circulation (2003)

Background— In stable coronary artery disease (CAD), exercise training has well-documented positive effects on arterial endothelial function. NO derived from endothelial NO synthase (eNOS) is regarded as a protective factor against atherosclerosis. The aim of the present study was to investigate the effects of exercise training on the endothelial function in relation to the expression of eNOS and Akt-dependent eNOS phosphorylation in the left internal mammary artery (LIMA) of patients with stable CAD. Methods and Results— In 17 training patients (T) and 18 control patients (C), endothelium-dependent vasodilation and average peak flow velocity (APV) in response to acetylcholine were measured invasively at study beginning and after 4 weeks in the LIMA. In LIMA tissue sampled during bypass surgery, eNOS expression and content of pospho-eNOS-Ser 1177 , Akt, and phospho-Akt were determined by Western blot and quantitative reverse transcriptase–polymerase chain reaction. After exercise training, LIMA APV in response to acetylcholine was increased by 56±8% (from +48±8% at beginning to +104±11% after 4 weeks, P &lt;0.001). Patients in T had a 2-fold higher eNOS protein expression (T 1.0±0.7 versus C 0.5±0.3 arbitrary units, P &lt;0.05) and 4-fold higher eNOS Ser 1177 -phosphorylation levels in LIMA-endothelium (1.2±0.9 versus 0.3±0.2 arbitrary units, P &lt;0.01). A linear correlation was confirmed between Akt phosphorylation and phospho-eNOS levels ( R =0.80, P &lt;0.05) and between phospho-eNOS and Δ APV ( R =0.59, P &lt;0.05). Conclusions— Exercise training in stable CAD leads to an improved agonist-mediated endothelium-dependent vasodilatory capacity. The change in acetylcholine-induced vasodilatation was closely related to a shear stress–induced/Akt-dependent phosphorylation of eNOS on Ser 1177 .
Fractional Genomic Alteration Detected by Array-Based Comparative Genomic Hybridization Independently Predicts Survival after Hepatic Resection for Metastatic Colorectal Cancer
Authors: Kshama R. Mehta, Kentaro Nakao, Marlene B. Zuraek, Daniel T. Ruan, Emily K. Bergsland, Alan P. Venook, Dan H. Moore, Taku A. Tokuyasu, Ajay N. Jain, Robert S. Warren, Jonathan P. Terdiman, Frederic M. Waldman
Journal: Clinical Cancer Research (2005)

Although liver resection is the primary curative therapy for patients with colorectal hepatic metastases, most patients have a recurrence. Identification of molecular markers that predict patients at highest risk for recurrence may help to target further therapy.Array-based comparative genomic hybridization was used to investigate the association of DNA copy number alterations with outcome in patients with colorectal liver metastasis resected with curative intent. DNA from 50 liver metastases was labeled and hybridized onto an array consisting of 2,463 bacterial artificial chromosome clones covering the entire genome. The total fraction of genome altered (FGA) in the metastases and the patient's clinical risk score (CRS) were calculated to identify independent prognostic factors for survival.An average of 30 +/- 14% of the genome was altered in the liver metastases (14% gained and 16% lost). As expected, a lower CRS was an independent predictor of overall survival (P = 0.03). In addition, a high FGA also was an independent predictor of survival (P = 0.01). The median survival time in patients with a low CRS (score 0-2) and a high (> or =20%) FGA was 38 months compared with 18 months in patients with a low CRS and a low FGA. Supervised analyses, using Prediction Analysis of Microarrays and Significance Analysis of Microarrays, identified a set of clones, predominantly located on chromosomes 7 and 20, which best predicted survival.Both FGA and CRS are independent predictors of survival in patients with resected hepatic colorectal cancer metastases. The greater the FGA, the more likely the patient is to survive.
STUDIES OF PULMONARY HYPERTENSION. IX. THE EFFECTS OF INTRAVENOUS HEXAMETHONIUM ON PULMONARY CIRCULATION IN PATIENTS WITH MITRAL STENOSIS1
Authors: Paul N. Yu, R. E. Nye, Frank W. Lovejoy, Bernard F. Schreiner, Bernard J. B. Yim
Journal: Journal of Clinical Investigation (1958)

During the past five years, circulatory effects of intravenous hexamethonium have been studied in normal subjects and in patients with various car- diac diseases (1-10).With adequate doses of the drug a significant reduction of the systemic blood pressure was observed in almost all cases.In many patients, particularly those with pulmonary hypertension, a reduction of the pulmonary artery pressure was also seen.However, the pulmonary "capillary" or pulmonary artery wedge pressures were recorded in only a small number of cases and changes of resistances in the pulmonary cir- cuit were seldom studied.The purposes of this paper are: 1) to report the hemodynamic effects of hexamethonium in a se- ries of patients with mitral stenosis, 2) to discuss the probable mechanism of the changes of the re- sistances and pressures in the pulmonary circuit of these patients, and 3) to stress the therapeutic benefit of hexamethonium in patients with acute pulmonary edema secondary to mitral stenosis. CLINICAL MATERIAL AND METHODTwenty-seven patients with predominant mitral steno- sis were studied.There were 10 males and 17 females.Their ages ranged from 13 to 58 years.None of the
Television Viewing and Time Spent Sedentary in Relation to Cancer Risk: A Meta-Analysis
Authors: Daniela Schmid, Michael F. Leitzmann
Journal: JNCI Journal of the National Cancer Institute (2014)

Sedentary behavior is emerging as an independent risk factor for chronic disease and mortality. However, the evidence relating television (TV) viewing and other sedentary behaviors to cancer risk has not been quantitatively summarized. We performed a comprehensive electronic literature search in Cochrane, EMBASE, Medline, and SciSearch databases through February 2014 for published articles investigating sedentary behavior in relation to cancer incidence. Because randomized controlled trials are difficult to perform on this topic, we focused on observational studies that met uniform inclusion criteria. Data were extracted independently by both authors and summarized using random-effects meta-analysis and meta-regression. All statistical tests were two-sided. Data from 43 observational studies including a total of 68936 cancer cases were analyzed. Comparing the highest vs lowest levels of sedentary time, the relative risks (RRs) for colon cancer were 1.54 (95% confidence interval [CI] = 1.19 to 1.98) for TV viewing time, 1.24 (95% CI = 1.09 to 1.41) for occupational sitting time, and 1.24 (95% CI = 1.03 to 1.50) for total sitting time. For endometrial cancer, the relative risks were 1.66 (95% CI = 1.21 to 2.28) for TV viewing time and 1.32 (95% CI = 1.08 to 1.61) for total sitting time. A positive association with overall sedentary behavior was also noted for lung cancer (RR = 1.21; 95% CI = 1.03 to 1.43). Sedentary behavior was unrelated to cancers of the breast, rectum, ovaries, prostate, stomach, esophagus, testes, renal cell, and non-Hodgkin lymphoma. Prolonged TV viewing and time spent in other sedentary pursuits is associated with increased risks of certain types of cancer.