tbuckley/cabot-search huggingface dataset:
An Explicit Quality Indicator Set for Measurement of Quality of Care in Patients With Cirrhosis
Authors: Fasiha Kanwal, Jennifer Kramer, Steven M. Asch, Hashem El–Serag, Brennan M.R. Spiegel, Steven Edmundowicz, Arun J. Sanyal, Jason A. Dominitz, Kenneth R. McQuaid, Paul Martin, Emmet B. Keeffe, Lawrence S. Friedman, Samuel B. Ho, Francisco Durazo, Bruce R. Bacon
Journal: Clinical Gastroenterology and Hepatology (2010)
Cycling Into Depression From a First Episode of Mania: A Case-Comparison Study
Authors: Carlos A. Zarate, Mauricio Tohen, Kenneth Fletcher
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The characteristics of patients who cycle from mania to major depression and the frequencies of these cycles remain poorly understood. METHOD: This study compared 28 patients with a first episode of mania who cycled into a major depressive episode without recovery from their index episode and 148 patients with first-episode mania who did not cycle into depression. Patients were given extensive assessments at baseline and 6-, 12-, and 24-month follow-ups. Comparisons between the two groups were made on demographic variables, clinical ratings, and outcome variables. RESULTS: Approximately 16% of the patients with a first episode of mania cycled into major depression. Patients who cycled into depression were more likely to have higher depressive scores at admission and tended to have the mixed subtype of bipolar disorder. CONCLUSIONS: Patients with first-episode mania who score high for depression at admission may be at greater risk of cycling into a major depressive episode.
Increased Risk for Cancer Following Sarcoidosis
Authors: JOHAN ASKLING, JOHAN GRUNEWALD, ANDERS EKLUND, GUNNAR HILLERDAL, ANDERS EKBOM
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Little is known about the cancer risk following sarcoidosis. In a retrospective cohort study, we tested the hypothesis of an increased risk for malignant lymphomas, lung cancer as well as cancer in other organs frequently involved in sarcoidosis. Four hundred seventy-four patients from an incidence study 1966–1980 and 8,541 patients identified in the Swedish Inpatient Register (IPR) 1964–1994 were linked to the Cancer Register, the Register of Causes of Death, and the Register of Total Population. Relative risks were estimated using standardized incidence ratios (SIR). The overall relative risks for cancer were similar and elevated in both cohorts (IPR presented), SIR = 1.3; 95% confidence interval (CI) 1.2 to 1.4. For lung cancer and non-Hodgkin's lymphoma, the relative risk was doubled during the first decade of follow-up. Thereafter, the risk for lung cancer was significantly decreased whereas the risk for non-Hodgkin's lymphoma equaled unity. Throughout follow-up, elevated risks were found for melanoma (SIR = 1.6; 95% CI 1.0 to 2.3) and nonmelanoma skin cancer (SIR = 2.8; 95% CI 2.0 to 3.8). An increased risk was also found for liver cancer (SIR = 1.4; 95% CI 0.8 to 2.2). Thus, sarcoidosis appears to be associated with a significantly increased risk for cancer in affected organs. Chronic inflammation is a putative mediator of this risk. Askling J, Grunewald J, Eklund A, Hillerdal G, Ekbom A. Increased risk for cancer following sarcoidosis.
Dose banding of chemotherapy doses at the Juravinski Cancer Centre
Authors: H. W. Hirte, S. Kagoma, L. Zhong, I. Collins, D. Burns, C. Rand, T. Simpson, A. Snider
Journal: Journal of Clinical Oncology (2006)

6099 Background: As the number and complexity of chemotherapy regimens increase, the demands on pharmacy services to reduce chemotherapy preparation and checking times continues to increase. Dose banding, a system whereby doses of intravenous cytotoxic drugs calculated on an individual basis are rounded up or down to predetermined standard doses (the maximum variation of the adjustment between standard dose and doses constituting each band is 5% or less) was identified as a strategy that could be used to address some of the issues around time pressures to help reduce patient waiting times for treatment. Methods: The project consisted of 3 phases; Phase I - literature review to identify dose banding publications; Phase II - selection of drugs to be banded for the pilot. The two drugs selected were 5FU and leukovorin, and Phase III - Time studies pre-, interim and post dose banding implementation to determine drug dispensing time and patients’ wait time for pharmacy related procedures. This occurred for a 2 week period (10 working days) either prior to implementation (pre- 819 patients studied), 4 days after implementation (interim - 854 patients studied) and 4 weeks after implementation (post - 785 patients studied). Results: Drug dispensing time did not decrease with dose banding (pre- 7.9 min, interim - 7.6 min and post - 9.4 min). However, the average patient wait time decreased after piloting the dose banding project (pre - 31.6 min, interim 23.7 min, and post - 27.8 min). The percentage of doses that were banded were 37.8% in the interim time study and 58.2% in the post time study. Conclusions: Although dose banding did not reduce dispensing time in this study, likely because the preparation for dispensing 5FU and leukovorin syringes is normally very simple and quick, patient’s wait time for pharmacy related procedures did decrease. This was probably due to contributions of other factors in the pharmacy process. A reduction in dispensing time could likely be achieved if more complex regimens were considered for dose banding. Dose banding could be used to increase capacity within the chemotherapy suite on the day of administration. It also allows for a better work schedule and increases efficiencies within the chemotherapy preparation and administration areas. (Sponsored by funds from Cancer Care Ontario) No significant financial relationships to disclose.
SOME ENERGY RELATIONS IN A HOST-VIRUS SYSTEM
Authors: W. Wilbur Ackermann, R. Bernal Johnson
Journal: The Journal of Experimental Medicine (1953)

It was found that DNP (2,4-dinitrophenol) will inhibit completely the propagation of influenza virus in chorioallantoic membrane. This reagent did not permanently alter those metabolic processes required for the synthesis of virus and at the concentrations employed demonstrated no virucidal effects. In minced preparations of chorioallantoic membrane DNP was shown to have a pronounced stimulatory effect upon ATPase (adenosinetriphosphatase). When DNP was used with intact tissues, an excellent correlation was found between the inhibition of viral propagation and the stimulation of respiration and release of phosphate. Concentrations of DNP which permitted a twofold increase in the endogenous respiration of intact membranes allowed little or no viral synthesis. It is concluded that the energy required for viral synthesis derives from the oxidative phosphorylative activity of the host tissue.
Maintenance of Renal Vascular Reactivity Contributes to Acute Renal Failure during Endotoxemic Shock
Authors: Jean-Jacques Boffa, William J. Arendshorst
Journal: Journal of the American Society of Nephrology (2004)

Septic shock is characterized by hypotension and decreased systemic vascular resistance and impaired vascular reactivity. Renal vasoconstriction markedly contrasts with sepsis-induced generalized systemic vasodilation, which is strongly dependent on nitric oxide. Whether maintained renal vascular reactivity to vasoconstrictors contributes to the decrease in renal blood flow (RBF) and GFR observed during LPS-induced sepsis was tested by assessment of the acute effects of pressor agents on mean arterial pressure (MAP) and renal hemodynamics in endotoxemic and control mice. LPS-injected mice displayed lower MAP, RBF, and GFR than controls (P < 0.001). Despite a lower MAP, basal renal vascular resistance (RVR) was higher during endotoxemia (P < 0.02). Angiotensin II infusion produced a weaker MAP response in septic mice (24 versus 37%; P < 0.005), suggesting impaired vasoconstriction and hyporeactivity. A similar MAP increase was observed between groups during norepinephrine (NE) infusion. The MAP increase to nitric oxide synthase inhibition by N(G)-nitro-L-arginine methyl ester (L-NAME) was much greater in LPS-treated mice (41 versus 15%, P = 0.01), indicating a strong influence of nitric oxide in sepsis. In contrast, the RBF and RVR responses to angiotensin II, NE, or L-NAME were similar in both groups. Moreover, vasopressin produced greater changes in MAP, RBF, and RVR in septic mice than in controls. Among the vasoconstrictor challenges, only NE ameliorated the decrease in GFR 14 h after LPS injection. The in vivo results demonstrate that the renal microvasculature displays a normal or enhanced reactivity to constrictor agents as compared with nonrenal circulatory beds. Such responsiveness may contribute to reduced RBF and GFR during endotoxemia.
493 RESULTS OF LIVER RETRANSPLANTATION IN A MONOCENTRIC COHORT OF HCV INFECTED PATIENTS
Authors: R. Sobesky, B. Roche, T.M. Antonini, V. Delvart, F. Saliba, P. Ichai, R. Adam, D. Azoulay, D. Castaing, M. Sebagh, A.-M. Roque-Afonso, C. Guettier, D. Samuel, J.-C. Duclos-Vallée
Journal: Journal of Hepatology (2010)
“Contextual” Synthetic Lethality and/or Loss of Heterozygosity: Tumor Hypoxia and Modification of DNA Repair
Authors: Norman Chan, Robert G. Bristow
Journal: Clinical Cancer Research (2010)

Hypoxia exists in every solid tumor and is associated with poor prognosis because of both local and systemic therapeutic resistance. Recent studies have focused on the interaction between tumor cell genetics and the dynamic state of oxygenation and metabolism. Hypoxia generates aggressive tumor cell phenotypes in part owing to ongoing genetic instability and a "mutator" phenotype. The latter may be due to suppression of DNA mismatch repair (MMR), nucleotide excision repair (NER), and double-strand break (DSB) repair. We propose a theoretical model in which hypoxia-mediated defects in DNA repair can lead to "contextual loss of heterozygosity" and drive oncogenesis. Additionally, hypoxia-mediated repair defects can be specifically targeted by DNA damaging agents and/or "contextual synthetic lethality" to kill repair-deficient cells and preserve the therapeutic ratio. These proposed concepts support the interrogation of solid tumors to document repair defects in both oxic and hypoxic tumor subregions as a conduit to novel clinical trials within the context of personalized medicine.
Insulin release is glucose anomeric specific in the human.
Authors: A A Rossini, J S Soeldner
Journal: Journal of Clinical Investigation (1976)

The alpha-glucose anomer produces a greater insulin release than beta-glucose in various animal models. These glucose anomers were dissolved rapidly and administered intravenously to human volunteers at a high dose (0.5 g/kg) over a 3-min period or a low dose (3.5 g) over a 20-s period. Blood samples were obtained at frequent time intervals for measurement of whole blood glucose (ferricyanide), plasma glucose (beta-glucose oxidase) and serum immunoreactive insulin. The high-dose infusion test showed no differences between the anomers of either blood glucose or serum insulin levels. However, at the lower dose, the alpha-glucose anomer stimulated a significantly greater insulin release than did beta-glucose. It is concluded that the alpha-glucose anomer stimulates a greater insulin release than the beta-glucose anomer in human subjects at low but not at high doses intravenously and that this response is not apparently related to approximations of the degree of mutarotation. These results suggest that a steric specific glucose receptor site exists on the beta-cell as a rapid insulin release trigger, although the alpha-anomer does not exclusively produce this stimulation.
Angiotensin receptor blockers and risk of myocardial infarction: meta-analyses and trial sequential analyses of 147 020 patients from randomised trials
Authors: S. Bangalore, S. Kumar, J. Wetterslev, F. H. Messerli
Journal: BMJ (2011)

<b>Objectives</b> To evaluate the cardiovascular outcomes and other outcomes associated with angiotensin receptor blockers. <b>Design</b> Systematic review of randomised controlled trials with meta-analysis and trial sequential analysis (TSA). <b>Data sources and study selection</b> Pubmed, Embase, and CENTRAL searches for randomised clinical trials, until August 2010, of angiotensin receptor blockers compared with controls (placebo/active treatment) that enrolled at least 100 participants and had a follow-up of at least one year. <b>Data extraction</b> Myocardial infarction, death, cardiovascular death, angina pectoris, stroke, heart failure, and new onset diabetes. <b>Results</b> 37 randomised clinical trials included 147 020 participants and had a total follow-up of 485 166 patient years. When compared with controls (placebo/active treatment), placebo, or active treatment, angiotensin receptor blockers were not associated with an increase in the risk of myocardial infarction (relative risk 0.99, 95% confidence interval 0.92 to 1.07), death, cardiovascular death, or angina pectoris. Compared with controls, angiotensin receptor blockers were associated with a reduction in the risk of stroke (0.90, 0.84 to 0.98), heart failure (0.87, 0.81 to 0.93), and new onset diabetes (0.85, 0.78 to 0.93), with similar results when compared with placebo or with active treatment. Based on trial sequential analysis, there is no evidence even for an average 5.0-7.5% (upper confidence interval 5-11%) relative increase in myocardial infarction (absolute increase of 0.3%), death, or cardiovascular death with firm evidence for relative risk reduction of stroke (at least 1%, average 10%) (compared with placebo only), heart failure (at least 5%, average 10%), and new onset diabetes (at least 4%, average 10%) with angiotensin receptor blockers compared with controls. <b>Conclusions</b> This large and comprehensive analysis produced firm evidence to refute the hypothesis that angiotensin receptor blockers increase the risk of myocardial infarction (ruling out even a 0.3% absolute increase). Compared with controls, angiotensin receptor blockers reduce the risk of stroke, heart failure, and new onset diabetes.
CpG Motifs in Bacterial DNA and Their Immune Effects
Authors: Arthur M. Krieg
Journal: Annual Review of Immunology (2002)

Unmethylated CpG motifs are prevalent in bacterial but not vertebrate genomic DNAs. Oligodeoxynucleotides (ODN) containing CpG motifs activate host defense mechanisms leading to innate and acquired immune responses. The recognition of CpG motifs requires Toll-like receptor (TLR) 9, which triggers alterations in cellular redox balance and the induction of cell signaling pathways including the mitogen activated protein kinases (MAPKs) and NF kappa B. Cells that express TLR-9, which include plasmacytoid dendritic cells (PDCs) and B cells, produce Th1-like proinflammatory cytokines, interferons, and chemokines. Certain CpG motifs (CpG-A) are especially potent at activating NK cells and inducing IFN-alpha production by PDCs, while other motifs (CpG-B) are especially potent B cell activators. CpG-induced activation of innate immunity protects against lethal challenge with a wide variety of pathogens, and has therapeutic activity in murine models of cancer and allergy. CpG ODN also enhance the development of acquired immune responses for prophylactic and therapeutic vaccination.
Practical Management of Patients With Non–Small-Cell Lung Cancer Treated With Gefitinib
Authors: Neelam T. Shah, Mark G. Kris, William Pao, Leslie B. Tyson, Barbara M. Pizzo, Murk-Hein Heinemann, Leah Ben-Porat, Dana L. Sachs, Robert T. Heelan, Vincent A. Miller
Journal: Journal of Clinical Oncology (2004)

Purpose The use of gefitinib, the first drug approved to inhibit the epidermal growth factor receptor tyrosine kinase, is indicated in patients with non–small-cell lung cancer with tumors progressive after chemotherapy. The unique mechanism of action of this agent leads to distinctive patterns of response and toxicity in persons with lung cancer. Many of the principles of management relevant to gefitinib are distinct from those with conventional cytotoxic drugs. To meet this need, we present practical guidelines on the use of gefitinib in patients with non–small-cell lung cancer. Methods This article reviews gefitinib’s indications, dosing, response phenomena, and patterns of relapse in individuals with radiographic response. Results We present our recommendations for the management of rash and diarrhea caused by this agent. Conclusion This information can guide practitioners and help them inform their patients about what to expect when they receive gefitinib.
Angiomotin-Like Protein 1 Controls Endothelial Polarity and Junction Stability During Sprouting Angiogenesis
Authors: Yujuan Zheng, Simona Vertuani, Staffan Nyström, Stéphane Audebert, Inèz Meijer, Tetyana Tegnebratt, Jean-Paul Borg, Per Uhlén, Arindam Majumdar, Lars Holmgren
Journal: Circulation Research (2009)

We have previously shown that angiomotin (Amot) is essential for endothelial cell migration during mouse embryogenesis. However, approximately 5% of Amot knockout mice survived without any detectable vascular defects. Angiomotin-like protein 1 (AmotL1) potentially compensates for the absence of Amot as it is 62% homologous to Amot and exhibits similar expression pattern in endothelial cells.Here, we report the identification of a novel isoform of AmotL1 that controls endothelial cell polarization and directional migration.Small interfering RNA-mediated silencing of AmotL1 in mouse aortic endothelial cells caused a significant reduction in migration. In confluent mouse pancreatic islet endothelial cells (MS-1), AmotL1 colocalized with Amot to tight junctions. Small interfering RNA knockdown of both Amot and AmotL1 in MS-1 cells exhibited an additive effect on increasing paracellular permeability compared to that of knocking down either Amot or AmotL1, indicating both proteins were required for proper tight junction activity. Moreover, as visualized using high-resolution 2-photon microscopy, the morpholino-mediated knockdown of amotl1 during zebrafish embryogenesis resulted in vascular migratory defect of intersegmental vessels with strikingly decreased junction stability between the stalk cells and the aorta. However, the phenotype was quite distinct from that of amot knockdown which affected polarization of the tip cells of intersegmental vessels. Double knockdown resulted in an additive phenotype of depolarized tip cells with no or decreased connection of the stalk cells to the dorsal aorta.These results cumulatively validate that Amot and AmotL1 have similar effects on endothelial migration and tight junction formation in vitro. However, in vivo Amot appears to control the polarity of vascular tip cells whereas AmotL1 mainly affects the stability of cell-cell junctions of the stalk cells.
A Novel Approach for Treatment of Unresectable Pancreatic Cancer: Design of Radioactive Stents and Trial Studies on Normal Pigs
Authors: Yan Liu, Jun-lou Liu, Zhen-zhai Cai, Zheng Lu, Yuan-hang Dong, Zhao-shen Li, Yan-fang Gong, Xiao-hua Man
Journal: Clinical Cancer Research (2007)

Patients diagnosed with pancreatic cancer typically have a poor prognosis. The aims of these studies were to design radioactive stents and to evaluate the feasibility and safety of the stents in animals.To combine the effects of stents and brachytherapy, plastic stents with inserted iodine-125 seeds were designed and tested in 18 normal pigs. The pigs were divided into five groups on the basis of radiation dose. The estimated radiation dose at a 5-mm radial distance from the axis of the seeds was 50 Gy in group A, 100 Gy in group B, 150 Gy in group C, and 200 Gy in group D, with four pigs in each group. In the control group (n = 2), the same plastic stents with non-radioactive seeds were implanted in the pancreatic duct.The procedures were successfully done on 14 of 18 (78%) pigs, whereas pancreatic duct perforation occurred in four pigs (22%). The thickened wall of the dilated pancreatic duct was clearly observed in the control group. However, the normal morphologic structure of the pancreatic duct wall disappeared in the experimental groups. Histopathologic examination revealed that the stents were surrounded with necrotic tissues and lateral fibrous tissues. During the follow-up period, the width of outside fibrous tissues gradually increased.These results indicate that the radioactive stents are safe in all dose groups, and it is feasible to design a special radioactive stent for each patient according to the size, shape, and position of the pancreatic tumor.
Doppler ultrasound and tibial tuberosity maturation status predicts pain in adolescent male athletes with Osgood-Schlatter's disease: a case series with comparison group and clinical interpretation
Authors: Matthieu Sailly, Rod Whiteley, Amanda Johnson
Journal: British Journal of Sports Medicine (2012)

The pathogenesis of the Osgood-Schlatter's disease (OSD) is still debated. The fragmentation of the ossification centre has been questioned as a definitive sign of OSD and has been seen as a normal development of the anterior tibial tubercle (ATT).
A Phase I Dose-Escalation Trial of Trastuzumab and Alvespimycin Hydrochloride (KOS-1022; 17 DMAG) in the Treatment of Advanced Solid Tumors
Authors: Komal Jhaveri, Kathy Miller, Lee Rosen, Bryan Schneider, Linnea Chap, Alison Hannah, Ziyang Zhong, Weining Ma, Clifford Hudis, Shanu Modi
Journal: Clinical Cancer Research (2012)

We conducted a phase I dose-escalation study to define the maximum tolerated dose (MTD), pharmacokinetics (PK), and pharmacodynamics of alvespimycin (17-DMAG), a heat shock protein 90 (Hsp90) inhibitor, given in combination with trastuzumab.Patients were treated with trastuzumab followed by intravenous alvespimycin on a weekly schedule. Hsp90 client proteins were measured at baseline and serially in peripheral blood lymphocytes (PBL) during cycle 1. Patients with advanced solid tumors progressing on standard therapy were eligible.Twenty-eight patients (25, breast; 3, ovarian) were enrolled onto three dose cohorts: 60 (n = 9), 80 (n = 13), and 100 mg/m(2) (n = 6). Dose-limiting toxicities (DLT) were: grade III left ventricular systolic dysfunction presenting as congestive heart failure in 1 patient (100 mg/m(2)), and reversible grade III keratitis in two patients (80 mg/m(2)). Drug-related grade III toxicity included one episode each of fatigue, diarrhea, myalgia, and back pain. Common mild to moderate toxicities included diarrhea, fatigue, myalgia, arthralgia, nausea, blurry vision, headache, back pain, and dry eyes. There was one partial response and seven cases of stable disease (range, 4-10 months), all in HER2+ MBC. In addition, an ovarian cancer patient had complete resolution of ascites and pleural effusion that lasted 24.8 months. There was no change in PK upon weekly dosing. Hsp70 effect continued to increase across four weeks and was most pronounced at 80 and 100 mg/m(2).The combination of alvespimycin and trastuzumab is safe and tolerable at MTD. Antitumor activity was seen in patients with refractory HER2+ MBC and ovarian cancer. The recommended dose of alvespimycin for further study in this combination is 80 mg/m(2) weekly.
Response to letter “DNA micro- arrays will be instrumental in the future diagnosis of cervical dysplasia and neoplasia”, by P. K. Wright (doi:10.1093/annonc/mdi109)
Authors: E. Barranger, A. Cortez, F. Commo, O. Marpeau, S. Uzan, E. Darai, P. Callard
Journal: Annals of Oncology (2005)