tbuckley/cabot-search huggingface dataset:
Randomized Phase III Study of High-Dose Fluorouracil Given As a Weekly 24-Hour Infusion With or Without Leucovorin Versus Bolus Fluorouracil Plus Leucovorin in Advanced Colorectal Cancer: European Organization of Research and Treatment of Cancer Gastrointestinal Group Study 40952
Authors: C-H. Köhne, J. Wils, M. Lorenz, P. Schöffski, R. Voigtmann, C. Bokemeyer, M. Lutz, U. Kleeberg, K. Ridwelski, R. Souchon, M. El-Serafi, U. Weiss, O. Burkhard, H. Rückle, M. Lichinitser, T. Langenbuch, W. Scheithauer, B. Baron, M.L. Couvreur, H.J. Schmoll
Journal: Journal of Clinical Oncology (2003)

Purpose: This trial was conducted to determine whether high-dose fluorouracil (FU) given as a weekly 24-hour infusion is more active than bolus FU + leucovorin (LV), and whether high-dose infusional FU can be modulated by LV. Patients and Methods: A total of 497 patients with previously untreated metastatic colorectal cancer were randomly assigned to receive bolus FU 425 mg/m 2 intravenously + LV 20 mg/m 2 on days 1 to 5 and repeated on day 28 (FU + LV), or FU 2,600 mg/m 2 as a 24-hour infusion alone (FU 24h ) or in combination with 500 mg/m 2 LV (FU 24h + LV)—all given weekly ×6 followed by a 2-week rest period. Survival was the major study end point. Results: With a median follow-up of more than 3 years, survival did not differ among the treatment groups (median FU + LV, 11.1 months [95% CI, 10.2 to 15.0 months]; FU 24h , 13.0 months [95% CI, 10.4 to 15.4 months]; FU 24h + LV, 13.7 months [95% CI, 12.0 to 16.4 months]; P = .724). Progression-free survival (PFS) was significantly longer for FU 24h + LV (median FU + LV, 4.0 months [95% CI, 3.4 to 4.9]; FU 24h , 4.1 months [95% CI, 3.4 to 5.0]; FU 24h + LV 5.6 months [95% CI, 4.4 to 6.7]; P = .029). The response rates in the subgroup of patients with measurable disease were 12%, 10%, and 17% for FU + LV, FU 24h , and FU 24h + LV, respectively (not significant). Occurrence of grade 3 and 4 diarrhea was higher in the FU 24h + LV arm (22%) compared with the FU 24h (6%) or FU + LV (9%) arms; however, stomatitis (11% in FU + LV v 3% in FU 24h v 5% in FU 24h + LV arms) and hematologic toxicity were higher in the bolus FU + LV arm. Global quality of life did not differ within the three arms. Conclusion: Neither FU 24h + LV nor FU 24h prolong survival, relative to bolus FU + LV. Leucovorin increases PFS if added to FU 24h , but increases toxicity.
Changes after quitting cigarette smoking.
Authors: G D Friedman, A B Siegelaub
Journal: Circulation (1980)

Changes in cardiorespiratory symptoms and coronary disease risk indicators over an average 1 1/2-year period were assessed in 9392 persistent cigarette smokers and 3825 persons who quit smoking between two multiphasic checkups. The prevalence of questionnaire-reported chronic cough fell markedly in subjects who quit a one-or-more-pack/day habit (e.g., from 11.2% to 1.8% in white men, p less than 0.001). However, chest pain, shortness of breath and exertional leg pain showed no consistent improvement in quitters compared with persistent smokers. Weight gain was about 2-3 lbs greater in quitters, but changes in blood pressure were small and not consistent across race-sex groups, nor were there consistent differences between persistent smokers and quitters in trends in trends in vital capacity, cholesterol or prevalence of ECG abnormality. Quitting was associated with increase in serum uric acid levels of about 0.2-0.5 mg/dl and relative falls in hemoglobin, leukocyte count and serum glucose levels, all consistent with smoker-nonsmoker differences previously found in cross-sectional studies. Except for the small increases in weight and uric acid levels, quitting smoking did not appear to increase risk of coronary heart disease by other mechanisms.
Improved disease-free–survival after transplantation of peripheral blood stem cells as compared with bone marrow from HLA-identical unrelated donors in patients with first chronic phase chronic myeloid leukemia
Authors: Ahmet H. Elmaagacli, Semiha Basoglu, Rudolf Peceny, Rudolf Trenschel, Hellmut Ottinger, Andre Lollert, Volker Runde, Hans Grosse-Wilde, Dietrich W. Beelen, Ulrich W. Schaefer
Journal: Blood (2002)
Identification of secondary targets of N-containing bisphosphonates in mammalian cells via parallel competition analysis of the barcoded yeast deletion collection
Authors: Nicoletta Bivi, Milena Romanello, Richard Harrison, Ian Clarke, David C Hoyle, Luigi Moro, Fulvia Ortolani, Antonella Bonetti, Franco Quadrifoglio, Gianluca Tell, Daniela Delneri
Journal: Genome biology (2009)

Nitrogen-containing bisphosphonates are the elected drugs for the treatment of diseases in which excessive bone resorption occurs, for example, osteoporosis and cancer-induced bone diseases. The only known target of nitrogen-containing bisphosphonates is farnesyl pyrophosphate synthase, which ensures prenylation of prosurvival proteins, such as Ras. However, it is likely that the action of nitrogen-containing bisphosphonates involves additional unknown mechanisms. To identify novel targets of nitrogen-containing bisphosphonates, we used a genome-wide high-throughput screening in which 5,936 Saccharomyces cerevisiae heterozygote barcoded mutants were grown competitively in the presence of sub-lethal doses of three nitrogen-containing bisphosphonates (risedronate, alendronate and ibandronate). Strains carrying deletions in genes encoding potential drug targets show a variation of the intensity of their corresponding barcodes on the hybridization array over the time. With this approach, we identified novel targets of nitrogen-containing bisphosphonates, such as tubulin cofactor B and ASK/DBF4 (Activator of S-phase kinase). The up-regulation of tubulin cofactor B may explain some previously unknown effects of nitrogen-containing bisphosphonates on microtubule dynamics and organization. As nitrogen-containing bisphosphonates induce extensive DNA damage, we also document the role of DBF4 as a key player in nitrogen-containing bisphosphonate-induced cytotoxicity, thus explaining the effects on the cell-cycle. The dataset obtained from the yeast screen was validated in a mammalian system, allowing the discovery of new biological processes involved in the cellular response to nitrogen-containing bisphosphonates and opening up opportunities for development of new anticancer drugs.
Palliation of dyspnoea in advanced COPD: revisiting a role for opioids
Authors: G Rocker, R Horton, D Currow, D Goodridge, J Young, S Booth
Journal: Thorax (2009)

Chronic obstructive pulmonary disease (COPD) will be the third leading cause of death worldwide by 2020. The burdens of this increasingly prevalent illness borne by patients, their family caregivers and the healthcare system are substantial. Dyspnoea as the predominant symptom becomes increasingly difficult to palliate as COPD progresses through advanced stages and, for 50% of patients, can become refractory to conventional treatment. This narrative review focuses on the potential role for carefully initiated and titrated opioids in the management of dyspnoea for patients with advanced COPD who are not yet in a terminal stage, yet struggle with symptoms that reflect underlying mechanisms of dyspnoea that lend themselves to this approach. The many barriers that currently exist to the provision of opioids in this setting are addressed, and recommendations are provided for an approach that should engender confidence among patients, their caregivers and the physicians who treat them.
BEAM: A Randomized Phase II Study Evaluating the Activity of Bevacizumab in Combination With Carboplatin Plus Paclitaxel in Patients With Previously Untreated Advanced Melanoma
Authors: Kevin B. Kim, Jeffrey A. Sosman, John P. Fruehauf, Gerald P. Linette, Svetomir N. Markovic, David F. McDermott, Jeffrey S. Weber, Hoa Nguyen, Peter Cheverton, Daniel Chen, Amy C. Peterson, William E. Carson, Steven J. O'Day
Journal: Journal of Clinical Oncology (2011)

Purpose Metastatic melanoma, a highly vascularized tumor with strong expression of vascular endothelial growth factor, has an overall poor prognosis. We conducted a placebo-controlled, double-blind phase II study of carboplatin plus paclitaxel with or without bevacizumab in patients with previously untreated metastatic melanoma. Patients and Methods Patients were randomly assigned in a two-to-one ratio to carboplatin (area under the curve, 5) plus paclitaxel (175 mg/m 2 ) and bevacizumab (15 mg/kg; CPB) or placebo (CP) administered intravenously once every 3 weeks. Progression-free survival (PFS) was the primary end point. Secondary end points included overall survival (OS) and safety. Results Two hundred fourteen patients (73% with M1c disease) were randomly assigned. With a median follow-up of 13 months, median PFS was 4.2 months for the CP arm (n = 71) and 5.6 months for the CPB arm (n = 143; hazard ratio [HR], 0.78; P = .1414). Overall response rates were 16.4% and 25.5%, respectively (P = .1577). With 13-month follow-up, median OS was 8.6 months in the CP arm versus 12.3 months in the CPB arm (HR, 0.67; P = .0366), whereas in an evaluation 4 months later, it was 9.2 versus 12.3 months, respectively (HR, 0.79; P = .1916). In patients with elevated serum lactate dehydrogenase (n = 84), median PFS and OS were longer in the CPB arm (PFS: 4.4 v 2.7 months; HR, 0.62; OS: 8.5 v 7.5 months; HR, 0.52). No new safety signals were observed. Conclusion The study did not meet the primary objective of statistically significant improvement in PFS with the addition of bevacizumab to carboplatin plus paclitaxel. A larger phase III study will be necessary to determine whether there is benefit to the addition of bevacizumab to carboplatin plus paclitaxel in this disease setting.
Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma associated with an annular elastolytic giant cell granuloma
Authors: P. Boussault, M.L. Tucker, J. Weschler, A. Riaux, C. Bervas-Quenehervé, D. Quist, C. Derancourt
Journal: British Journal of Dermatology (2009)

Conflicts of interest: none declared. Sir, We describe herein the first association of a primary cutaneous CD4+ small to medium‐sized pleomorphic T‐cell lymphoma with an annular elastolytic giant cell granuloma, occurring simultaneously in a 62‐year‐old man. The appearance of the annular elastolytic giant cell granuloma some weeks before the cutaneous lymphoma and its regression during the treatment of the neoplasia made us think about the possible link between these two diseases. Primary cutaneous CD4+ small to medium‐sized pleomorphic T‐cell lymphoma (PSMTCL) is a provisional entity in the new WHO–EORTC classification,1 representing about 3% of all primary cutaneous T‐cell lymphomas (CTCL). We describe here an exceptional case of a 62‐year‐old man who simultaneously presented a PSMTCL and an annular elastolytic giant cell granuloma. For 6 months a 62‐year‐old white man had a slowly growing erythematous plaque on the lower left side of the abdomen. It was 6 × 14 cm in size and deeply infiltrated. Furthermore, for 8 months he had had an eruption of annular skin lesions mostly in photoexposed areas; these showed a centrifugal extension, and were atrophic and white in their centre with an infiltrated and erythematous border (Fig. 1). A few lesions were located on nonphotoexposed areas in the cutaneous folds as well. His general health was good and there was no lymphadenopathy or organomegaly. The past medical history was significant for glaucoma (treated with travoprost and picloxydine eye drops), and an iodine and penicillin allergy.
Site of Opioid Action in the Human Brain: Mu and Kappa Agonists' Subjective and Cerebral Blood Flow Effects
Authors: Thomas E. Schlaepfer, Eric C. Strain, Benjamin D. Greenberg, Kenzie L. Preston, Eric Lancaster, George E. Bigelow, Patrick E. Barta, Godfrey D. Pearlson
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: Humans experience the subjective effects of mu and kappa opioid agonists differently: mu agonists produce mainly euphoria, while kappa agonists are more likely to produce dysphoria. This study tested the hypothesis that these subjective effects would be associated with anatomically distinct changes in regional cerebral blood flow (CBF) relative to baseline as assessed with single photon emission computed tomography (SPECT). METHOD: Nine nondependent opioid abusers participated in the study. In the first phase of the study, the participants were acclimated to effects of the study drugs. In the second phase they underwent repeat challenges with the study drugs followed by an assessment of CBF with use of the SPECT tracer [99mTc]HMPAO. Medications tested were the prototypic mu agonist hydromorphone, the mixed agonist/antagonist butorphanol (which has a kappa agonist component of activity), and saline placebo. RESULTS: Subjective effects of the drugs were distinctly different. Hydromorphone produced increased ratings of "good effects," while butorphanol led to more "bad effects." Hydromorphone significantly increased regional CBF in the anterior cingulate cortex, both amygdalae, and the thalamus—all structures belonging to the limbic system. Butorphanol caused a less distinct picture of regional CBF increases, mainly in the area of both temporal lobes. CONCLUSIONS: This study demonstrates that opioids with different subjective effects also produce statistically significant patterns of change in regional CBF from baseline, and the regions of statistical significance appear in different brain regions. In addition, these results demonstrate the applicability of SPECT functional neuroimaging in the study of medications with potential abuse liability.
Best Compliance during a Decremental, But Not Incremental, Positive End-Expiratory Pressure Trial Is Related to Open-Lung Positive End-Expiratory Pressure
Authors: KEITH G. HICKLING
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

A mathematical model of the acute respiratory distress syndrome (ARDS) lung, incorporating simulated gravitational superimposed pressure and alveolar opening and closing pressures, was used to study the mean tidal pressure-volume (PV) slope ("effective compliance") during incremental and decremental positive end-expiratory pressure (PEEP) trials with constant tidal volume (VT) "ventilation." During incremental PEEP, the PEEP giving maximum mean tidal PV slope did not coincide with "open lung PEEP" (minimum PEEP preventing end expiratory collapse of 97.5% of alveoli inflated at end-inspiration), and it varied greatly with varying VT and "lung mechanics." Incremental PEEP with a low VT tests recruitment by the peak pressure, not prevention of collapse by PEEP. During decremental PEEP with a low VT, maximum mean tidal PV slope occurred with PEEP 2-3.5 cm H2O below open-lung PEEP, unless closing pressure was high. High VT, high "specific compliance," and high opening pressures caused slightly greater underestimation of open-lung PEEP. Maximum mean tidal PV slope was always higher (e.g., 93.7 versus 16.69 ml/cm H2O), and the variation in PV slope with PEEP was greater, during decremental PEEP. The maximum PV slope during a decremental PEEP trial with a low VT may be a useful method to determine open-lung PEEP in ARDS, and should be studied clinically.
Tumour production of alkaline phosphatase in a patient with giant-cell carcinoma of bronchus.
Authors: J M Pfeffer, P G Stovin
Journal: Thorax (1978)

A patient with a giant-cell carcinoma of the bronchus was found to have a raised serum alkaline phosphatase without any evidence of bone or liver involvement. After necropsy the excised tumour was found to be producing alkaline phosphatase. The alkaline phosphatase found in the serum during life was heat-labile but that in the tumour was heat-stable. The significance of this is unknown.
Outcome for patients colonised with Burkholderia cepacia in a Birmingham adult cystic fibrosis clinic and the end of an epidemic.
Authors: K Muhdi, F P Edenborough, L Gumery, S O'Hickey, E G Smith, D L Smith, D E Stableforth
Journal: Thorax (1996)

BACKGROUND: There has been increasing concern since 1979 about the emergence of Pseudomonas cepacia (Burkholderia cepacia) in patients with cystic fibrosis in the UK and elsewhere. Colonisation of the sputum has been shown to be associated with increased morbidity and mortality. Evidence suggests person to person transmission and some centres have segregated those colonised with B cepacia from other patients with cystic fibrosis. The outcome of patients colonised by B cepacia has been studied, together with the effects of strict segregation. METHODS: The outcome in 18 patients with sputum colonised by B cepacia was compared with that in age, sex, and severity matched controls with no evidence of B cepacia colonisation by a retrospective case note study. RESULTS: No difference between cases or controls were found in the 24 month period prior to colonisation by B cepacia in lung function, number of days in hospital, or outpatient visits. Colonisation led to an increased rate of loss of lung function and utilisation of hospital services. There was an increase in the numbers of transplants and deaths amongst the cases. Since 1992 there have been only three new cases of B cepacia colonisation and the incidence and prevalence of the organism has fallen dramatically since segregation commenced. CONCLUSIONS: B cepacia appears to be linked to the decline in colonised individuals. There was no evidence that colonisation occurred in patients declining for other reasons. B cepacia colonisation confers a worse prognosis than Pseudomonas aeruginosa alone. Segregation appears to limit the spread of the organism from infected individuals to other patients with cystic fibrosis.
Prevention of hepatitis B virus recurrence after liver transplantation in cirrhotic patients treated with lamivudine and passive immunoprophylaxis
Authors: Alfredo Marzano, Mauro Salizzoni, Wilma Debernardi-Venon, Antonina Smedile, Alessandro Franchello, Alessia Ciancio, Elena Gentilcore, Paolo Piantino, Anna Maria Barbui, Ezio David, Francesco Negro, Mario Rizzetto
Journal: Journal of Hepatology (2001)
Length of Stay in Home Care Before and After the 1997 Balanced Budget Act
Authors: Rachel L. Murkofsky, Russell S. Phillips, Ellen P. McCarthy, Roger B. Davis, Mary Beth Hamel
Journal: JAMA (2003)

Context Prior to 1997, home health agencies (HHAs) were reimbursed on a fee-for-service basis and had incentives to provide more services. The 1997 Balanced Budget Act (BBA) reduced payments for home care services to help control Medicare spending. Objective To examine the length of stay in home care before and after the 1997 BBA. Design and Setting Cross-sectional study of home care patients in the 1996 and 1998 National Home and Hospice Care Surveys, which surveyed 1053 HHAs in 1996 and 1088 HHAs in 1998. Patients Nationally representative random sample of home care patients with Medicare coverage in 1996 (4127 patients) and 1998 (4051 patients). Main Outcome Measure Length of stay in home care (based on the number of days a patient was enrolled in home care services). Results From 1996 to 1998, unadjusted median length of stay decreased by 16 days for all home care patients (60-44 days, P = .002). The decrease affected for-profit HHAs more than not-for-profit HHAs (111-55 days [51% decrease, P = .002] vs 46-36 days [22% decrease, P = .042]). In a Cox proportional hazards model of time to discharge from home care, post-BBA year (1998) was associated with a shorter length of stay in home care (adjusted hazard ratio [aHR] for home care discharge, 1.39 [95% confidence interval {CI}, 1.19-1.61]), and for-profit status was associated with a longer length of stay in home care (aHR, 0.82 [95% CI, 0.71-0.94]) after adjusting for patient demographics, diagnoses, and functional status. Conclusion After the 1997 BBA, length of stay in home care decreased among Medicare patients, particularly among those receiving care from for-profit HHAs.
Follicular Lymphoma Survival in Sweden in the Rituximab Era
Authors: Henna Riikka Junlén, Stefan Peterson, Eva Kimby, Sandra Lockmer, Ola Linden, Herman Nilsson-Ehle, Martin Erlanson, Hans Hagberg, Anders Rådlund, Oskar Hagberg, Björn E Wahlin
Journal: Blood (2014)
Inactivation of influenza A viruses in the environment and modes of transmission: A critical review
Authors: Thomas P. Weber, Nikolaos I. Stilianakis
Journal: Journal of Infection (2008)

ObjectivesThe relative importance of airborne, droplet and contact transmission of influenza A virus and the efficiency of control measures depends among other factors on the inactivation of viruses in different environmental media.MethodsWe systematically review available information on the environmental inactivation of influenza A viruses and employ information on infectious dose and results from mathematical models to assess transmission modes.ResultsDaily inactivation rate constants differ by several orders of magnitude: on inanimate surfaces and in aerosols daily inactivation rates are in the order of 1–102, on hands in the order of 103. Influenza virus can survive in aerosols for several hours, on hands for a few minutes. Nasal infectious dose of influenza A is several orders of magnitude larger than airborne infectious dose.ConclusionsThe airborne route is a potentially important transmission pathway for influenza in indoor environments. The importance of droplet transmission has to be reassessed. Contact transmission can be limited by fast inactivation of influenza virus on hands and is more so than airborne transmission dependent on behavioral parameters. However, the potentially large inocula deposited in the environment through sneezing and the protective effect of nasal mucus on virus survival could make contact transmission a key transmission mode.