tbuckley/cabot-search huggingface dataset:
Leukemia in Patients With Cancer of the Cervix Uteri Treated With Radiation. A Report Covering the First 5 Years of an International Study&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: George B. Hutchison, M.D.
Journal: JNCI Journal of the National Cancer Institute (1968)

A prospective study of patients exposed to radiotherapy for cervical cancer was conducted. Patients under observation were seen twice a year during the first 5 years after diagnosis and annually after the first 5 years. Peripheral blood studies were made at each visit. An accumulated total of 60,000 person-years was assembled from 29 collaborating radiotherapy centers. Four cases of leukemia were reported in exposed patients, including 2 myelocytic and 2 lymphocytic cell types. These numbers and cell types did not differ significantly from expected numbers for a general population of females of the age group studied. A comparison group of cervical cancer patients who did not receive radiotherapy has been followed according to the same protocol and has accumulated 6,000 person-years, with one case of leukemia observed, of lymphocytic cell type. Leukemia incidences for the total population studied and for various subgroups defined by type of therapy and by interval after radiation exposure were all compatible with general population rates. For patients at risk in the interval 4–8 years after exposure, a fivefold increased risk could be excluded, but a fourfold increased risk remained possible. For patients exposed to combined external therapy plus intracavitary radium, observed at all intervals after exposure, a threefold increase was excluded.
Quality of Cardiopulmonary Resuscitation During Out-of-Hospital Cardiac Arrest
Authors: Lars Wik
Journal: JAMA (2005)

First, I like to thank my supervisors, Petter Andreas Steen and Lars Wik, who invited me into their unique collaboration and gave me the opportunity to experience a wonderful time at the Institute and really get absorbed in this exciting and clinically relevant field.In their very own way, both have supported me and been available for questions, opinions, and discussions at all times.Their enthusiasm is commendable and their network of contacts impressive -both these qualities are so valuable for anyone entering the field of science.Over the last few years our group has expanded, and everyone has added their flavour and improved the stew.Elizabeth Dorph was here when I started, a great room-mate and inspiration.Kjetil Sunde soon came back to our group, filled with energy and new ideas.He deserves extra thanks for his supportive role when
Substitution rate variation among sites in mitochondrial hypervariable region I of humans and chimpanzees
Authors: L. Excoffier, Z. Yang
Journal: Molecular Biology and Evolution (1999)

Mitochondrial D-loop hypervariable region I (HVI) sequences are widely used in human molecular evolutionary studies, and therefore accurate assessment of rate heterogeneity among sites is essential. We used the maximum-likelihood method to estimate the gamma shape parameter alpha for variable substitution rates among sites for HVI from humans and chimpanzees to provide estimates for future studies. The complete data of 839 humans and 224 chimpanzees, as well as many subsets of these data, were analyzed to examine the effect of sequence sampling. The effects of the genealogical tree and the nucleotide substitution model were also examined. The transition/transversion rate ratio (kappa) is estimated to be about 25, although much larger and biased estimates were also obtained from small data sets at low divergences. Estimates of alpha were 0.28-0.39 for human data sets of different sizes and 0.20-0.39 for data sets including different chimpanzee subspecies. The combined data set of both species gave estimates of 0.42-0.45. While all those estimates suggest highly variable substitution rates among sites, smaller samples tend to give smaller estimates of alpha. Possible causes for this pattern were examined, such as biases in the estimation procedure and shifts in the rate distribution along certain lineages. Computer simulations suggest that the estimation procedure is quite reliable for large trees but can be biased for small samples at low divergences. Thus, an alpha of 0.4 appears suitable for both humans and chimpanzees. Estimates of alpha can be affected by the nucleotide sites included in the data, the overall tree length (the amount of sequence divergence), the number of rate classes used for the estimation, and to a lesser extent, the included sequences. The genealogical tree, the substitution model, and demographic processes such as population expansion do not have much effect.
THE KINETICS OF IRON METABOLISM IN NORMAL GROWING SWINE
Authors: W. N. Jensen, J. A. Bush, Helen Ashenbrucker, G. E. Cartwright, M. M. Wintrobe
Journal: The Journal of Experimental Medicine (1956)

Plasma and red cell iron turnover rates were determined in 18 normal growing swine by the use of tracer doses of Fe(59). Body surface counting was performed on a representative group of animals following the injection of the isotope. The mean half-time of plasma iron disappearance was 1.19 +/- 0.26 hours. Two exponential rates of disappearance of Fe(59) from the plasma were observed in 15 of the pigs and a single rate was observed in the other 3. The mean plasma iron turnover rate was 1.11 +/- 0.34 mg./kg. day. The average maximum incorporation of Fe(59) into the erythrocytes was 92 +/- 9 per cent. The mean red cell iron incorporation rate was 1.10 mg./kg. day, but an average of 0.42 mg./kg. day of this was calculated as being due to increasing red cell mass incidental to body growth, so that the true mean red cell iron turnover rate was 0.59 +/- 0.19 mg./kg. day. The average "apparent" red cell life span was 63 +/- 16 days. This is in agreement with the red cell life span of 62 days determined previously with glycine-2-C(14).
MMP13 mediates cell cycle progression in melanocytes and melanoma cells: in vitro studies of migration and proliferation
Authors: Svenja Meierjohann, Anita Hufnagel, Elisabeth Wende, Markus A Kleinschmidt, Katarina Wolf, Peter Friedl, Stefan Gaubatz, Manfred Schartl
Journal: Molecular Cancer (2010)

Melanoma cells are usually characterized by a strong proliferative potential and efficient invasive migration. Among the multiple molecular changes that are recorded during progression of this disease, aberrant activation of receptor tyrosine kinases (RTK) is often observed. Activation of matrix metalloproteases goes along with RTK activation and usually enhances RTK-driven migration. The purpose of this study was to examine RTK-driven three-dimensional migration of melanocytes and the pro-tumorigenic role of matrix metalloproteases for melanocytes and melanoma cells. Using experimental melanocyte dedifferentiation as a model for early melanomagenesis we show that an activated EGF receptor variant potentiates migration through three-dimensional fibrillar collagen. EGFR stimulation also resulted in a strong induction of matrix metalloproteases in a MAPK-dependent manner. However, neither MAPK nor MMP activity were required for migration, as the cells migrated in an entirely amoeboid mode. Instead, MMPs fulfilled a function in cell cycle regulation, as their inhibition resulted in strong growth inhibition of melanocytes. The same effect was observed in the human melanoma cell line A375 after stimulation with FCS. Using sh- and siRNA techniques, we could show that MMP13 is the protease responsible for this effect. Along with decreased proliferation, knockdown of MMP13 strongly enhanced pigmentation of melanocytes. Our data show for the first time that growth stimuli are mediated via MMP13 in melanocytes and melanoma, suggesting an autocrine MMP13-driven loop. Given that MMP13-specific inhibitors are already developed, these results support the evaluation of these inhibitors in the treatment of melanoma.
Preventive Vaccination with Telomerase Controls Tumor Growth in Genetically Engineered and Carcinogen-Induced Mouse Models of Cancer
Authors: Carmela Mennuni, Stefano Ugel, Federica Mori, Barbara Cipriani, Manuela Iezzi, Tania Pannellini, Domenico Lazzaro, Gennaro Ciliberto, Nicola La Monica, Paola Zanovello, Vincenzo Bronte, Elisa Scarselli
Journal: Cancer Research (2008)

Abstract The telomerase reverse transcriptase, TERT, is an attractive target for human cancer vaccination because its expression is reactivated in a conspicuous fraction of human tumors. Genetic vaccination with murine telomerase (mTERT) could break immune tolerance in different mouse strains and resulted in the induction of both CD4+ and CD8+ telomerase-specific T cells. The mTERT-derived immunodominant epitopes recognized by CD8+ T cells were further defined in these mouse strains and used to track immune responses. Antitumor efficacy of telomerase-based vaccination was investigated in two cancer models closely resembling human diseases: the TRAMP transgenic mice for prostate cancer and a carcinogen-induced model for colon cancer. TERT overexpression in tumor lesions was shown in both models by immunohistochemistry, thus reinforcing the similarity of these tumors to their human counterparts. Repeated immunizations with mTERT-encoding DNA resulted in a significant delay of tumor formation and progression in both the prostate cancer and the colon cancer models. Moreover, evaluation of the intratumoral infiltrate revealed the presence of telomerase-specific T cells in vaccinated mice. The safety of vaccination was confirmed by the absence of histomorphologic changes on postnecropsy analysis of several organs and lack of adverse effects on blood cell counts. These results indicate that TERT vaccination can elicit antigen-specific immunosurveillance and imply this antigen as a potential candidate for preventive cancer vaccines. [Cancer Res 2008;68(23):9865–74]
Phase I Trial and Pharmacokinetics of Gemcitabine in Children With Advanced Solid Tumors
Authors: Joel M. Reid, Wenchun Qu, Stephanie L. Safgren, Matthew M. Ames, Mark D. Krailo, Nita L. Seibel, John Kuttesch, John Holcenberg
Journal: Journal of Clinical Oncology (2004)

To determine the maximum tolerated dose, toxicity, and pharmacokinetics of gemcitabine in children with refractory solid tumors.Gemcitabine was given as a 30-minute infusion for 2 or 3 consecutive weeks every 4 weeks, to 42 patients aged 1 to 21 years. Doses of 1000, 1200 and 1500 mg/m(2) were administered for 3 weeks. Subsequently, gemcitabine was given for only 2 consecutive weeks at 1500, 1800, and 2100 mg/m(2). Plasma concentrations of gemcitabine and its metabolite, 2'2'-difluorodeoxyuridine, were measured in 28 patients.Forty patients who received 132 courses of gemcitabine were assessable for toxicity. The maximum tolerated dose of gemcitabine given weekly for 3 weeks was 1200 mg/m(2). Dose-limiting toxicity was not seen in one-third of children treated at any doses given for 2 weeks. The major toxicity was myelosuppression in three of five patients at 1500 mg/m(2) for 3 weeks, and one of seven patients at 1800 mg/m(2) for 2 weeks. Other serious adverse events were somnolence, fever and hypotension, and rash in three patients. Gemcitabine plasma concentration-time data were fit to a one- (n = 5) or two-compartment (n = 23) open model. Mean gemcitabine clearance and half-life values were 2140 mL/min/m(2) and 13.7 minutes, respectively. One patient with pancreatic cancer had a partial response. Seven patients had stable disease for 2 to 17 months.Gemcitabine given by 30-minute infusion for 2 or 3 consecutive weeks every 4 weeks was tolerated well by children at doses of 2100 mg/m(2) and 1200 mg/m(2), respectively.
Clopidogrel versus Aspirin and Esomeprazole to Prevent Recurrent Ulcer Bleeding
Authors: Francis K.L. Chan, Jessica Y.L. Ching, Lawrence C.T. Hung, Vincent W.S. Wong, Vincent K.S. Leung, Nelson N.S. Kung, Aric J. Hui, Justin C.Y. Wu, Wai K. Leung, Vivian W.Y. Lee, Kenneth K.C. Lee, Yuk T. Lee, James Y.W. Lau, Ka F. To, Henry L.Y. Chan, S.C. Sydney Chung, Joseph J.Y. Sung
Journal: New England Journal of Medicine (2005)

Concurrent therapy with a proton-pump inhibitor is a standard treatment for patients receiving aspirin who are at risk for ulcer. Current U.S. guidelines also recommend clopidrogel for patients who have major gastrointestinal intolerance of aspirin. We compared clopidogrel with aspirin plus esomeprazole for the prevention of recurrent bleeding from ulcers in high-risk patients.We studied patients who took aspirin to prevent vascular diseases and who presented with ulcer bleeding. After the ulcers had healed, we randomly assigned patients who were negative for Helicobacter pylori to receive either 75 mg of clopidogrel daily plus esomeprazole placebo twice daily or 80 mg of aspirin daily plus 20 mg of esomeprazole twice daily for 12 months. The end point was recurrent ulcer bleeding.We enrolled 320 patients (161 patients assigned to receive clopidogrel and 159 to receive aspirin plus esomeprazole). Recurrent ulcer bleeding occurred in 13 patients receiving clopidogrel and 1 receiving aspirin plus esomeprazole. The cumulative incidence of recurrent bleeding during the 12-month period was 8.6 percent (95 percent confidence interval, 4.1 to 13.1 percent) among patients who received clopidogrel and 0.7 percent (95 percent confidence interval, 0 to 2.0 percent) among those who received aspirin plus esomeprazole (difference, 7.9 percentage points; 95 percent confidence interval for the difference, 3.4 to 12.4; P=0.001).Among patients with a history of aspirin-induced ulcer bleeding whose ulcers had healed before they received the study treatment, aspirin plus esomeprazole was superior to clopidogrel in the prevention of recurrent ulcer bleeding. Our finding does not support the current recommendation that patients with major gastrointestinal intolerance of aspirin be given clopidogrel.
Exposure to Silica Crystals and Poly (I:C) Induces Caspase-Dependent Apoptosis of Human Bronchial Epithelial Cells
Authors: Hirotoshi Unno, Kyoko Futamura, Reiji Kojima, Hideaki Morita, Hirohisa Saito, Kenji Matsumoto, Akio Matsuda
Journal: Journal of Allergy and Clinical Immunology (2013)
Benefits and Harms of Computed Tomography Lung Cancer Screening Strategies: A Comparative Modeling Study for the U.S. Preventive Services Task Force
Authors: Harry J. de Koning, Rafael Meza, Sylvia K. Plevritis, Kevin ten Haaf, Vidit N. Munshi, Jihyoun Jeon, Saadet Ayca Erdogan, Chung Yin Kong, Summer S. Han, Joost van Rosmalen, Sung Eun Choi, Paul F. Pinsky, Amy Berrington de Gonzalez, Christine D. Berg, William C. Black, Martin C. Tammemägi, William D. Hazelton, Eric J. Feuer, Pamela M. McMahon
Journal: Annals of Internal Medicine (2013)

The optimum screening policy for lung cancer is unknown.
Antibiotic Prescribing for Lower Respiratory Tract Infection
Authors: J. S. Stapczynski
Journal: JAMA (2005)

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Effect of off-pump coronary artery bypass surgery on clinical, angiographic, neurocognitive, and quality of life outcomes: randomised controlled trial
Authors: Sharif Al-Ruzzeh, Shane George, Mahmoud Bustami, Jo Wray, Charles Ilsley, Thanos Athanasiou, Mohamed Amrani
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objective</b> To compare the clinical, angiographic, neurocognitive, and quality of life outcomes of off-pump coronary artery bypass surgery with conventional coronary artery bypass grafting surgery using cardiopulmonary bypass. <b>Design</b> Randomised controlled clinical trial. <b>Setting</b> Tertiary cardiothoracic centre in Middlesex, England. <b>Participants</b> 168 patients (27 women) requiring primary isolated coronary artery bypass grafting surgery. <b>Interventions</b> Patients were randomised to conventional coronary artery bypass grafting surgery using cardiopulmonary bypass (n = 84) or off-pump coronary artery bypass surgery (n = 84), carried out by one surgeon. Angiographic examination was carried out at three months postoperatively. Neurocognitive tests were carried out at baseline and at six weeks and six months postoperatively. <b>Main outcome measures</b> Clinical outcome, graft patency at three months, neurocognitive function at six weeks and six months, and health related quality of life. <b>Results</b> Graft patency was evaluated by angiography in 151 (89.9%) patients and was similar between the cardiopulmonary bypass and off-pump groups (risk difference − 1%, 95% confidence interval − 5% to 4%), with the off-pump group considered the treatment group. Patients in the off-pump group required fewer blood transfusions (1.7 units <i>v</i> 1.0 unit, P = 0.02), shorter duration of mechanical ventilation (7.7 hours <i>v</i> 3.9 hours, P = 0.03), and shorter hospital stay (10.8 days <i>v</i> 8.9 days). Scores for neurocognitive function showed a significant difference in three memory subtests at six weeks and two memory subtests at six months in favour of the off-pump group. <b>Conclusions</b> Patients who underwent off-pump coronary artery bypass surgery showed similar patency of grafts, better clinical outcome, shorter hospital stay, and better neurocognitive function than patients who underwent conventional coronary artery bypass grafting surgery using cardiopulmonary bypass.
Three Phase II Cytokine Working Group Trials of gp100 (210M) Peptide Plus High-Dose Interleukin-2 in Patients With HLA-A2–Positive Advanced Melanoma
Authors: Jeffrey A. Sosman, Carole Carrillo, Walter J. Urba, Lawrence Flaherty, Michael B. Atkins, Joseph I. Clark, Janet Dutcher, Kim A. Margolin, James Mier, Jarod Gollob, John M. Kirkwood, David J. Panka, Nancy A. Crosby, Kevin O'Boyle, Bonnie LaFleur, Marc S. Ernstoff
Journal: Journal of Clinical Oncology (2008)

High-dose interleukin-2 (IL-2) induces responses in 15% to 20% of patients with advanced melanoma; 5% to 8% are durable complete responses (CRs). The HLA-A2-restricted, modified gp100 peptide (210M) induces T-cell immunity in vivo and has little antitumor activity but, combined with high-dose IL-2, reportedly has a 42% (13 of 31 patients) response rate (RR). We evaluated 210M with one of three different IL-2 schedules to determine whether a basis exists for a phase III trial.In three separate phase II trials, patients with melanoma received 210M subcutaneously during weeks 1, 4, 7, and 10 and standard high-dose IL-2 during weeks 1 and 3 (trial 1), weeks 7 and 9 (trial 2), or weeks 1, 4, 7, and 10 (trial 3). Immune assays were performed on peripheral-blood mononuclear cells collected before and after treatment.From 1998 to 2003, 131 patients with HLA-A2-positive were enrolled. With 60-month median follow-up time, the overall RR for 121 assessable patients was 16.5% (95% CI, 10% to 26%); the RRs were 23.8% in trial 1 (42 patients), 12.5% in trial 2 (40 patients), and 12.8% in trial 3 (39 patients). There were 11 CRs (9%) and nine partial responses (7%), with 11 patients (9%) progression free at >or= 30 months. Immune studies including assays of CD3-zeta expression and numbers of CD4(+)/CD25(+)/FoxP3(+) regulatory T cells, CD15(+)/CD11b(+)/CD14(-) immature myeloid-derived cells, and CD8(+)gp100 tetramer-positive cells in the blood did not correlate with clinical benefit.The results again demonstrate efficacy of high-dose IL-2 in advanced melanoma but did not demonstrate the promising clinical activity reported with vaccine and high-dose IL-2 in any of three phase II trials.
Value and Limitations of Chest Pain History in the Evaluation of Patients With Suspected Acute Coronary Syndromes
Authors: Clifford J Swap, John T Nagurney
Journal: JAMA (2005)

The chest pain history, physical examination, determination of coronary artery disease (CAD) risk factors, and the initial electrocardiogram compose the information immediately available to clinicians to help determine the probability of acute myocardial infarction (AMI) or acute coronary syndrome (ACS) in patients with chest pain. However, conflicting data exist about the usefulness of the chest pain history and which components are most useful.To identify the elements of the chest pain history that may be most helpful to the clinician in identifying ACS in patients presenting with chest pain.MEDLINE and Ovid were searched from 1970 to September 2005 by using specific key words and Medical Subject Heading terms. Reference lists of these articles and current cardiology textbooks were also consulted.Certain chest pain characteristics decrease the likelihood of ACS or AMI, namely, pain that is stabbing, pleuritic, positional, or reproducible by palpation (likelihood ratios [LRs] 0.2-0.3). Conversely, chest pain that radiates to one shoulder or both shoulders or arms or is precipitated by exertion is associated with LRs (2.3-4.7) that increase the likelihood of ACS. The chest pain history itself has not proven to be a powerful enough predictive tool to obviate the need for at least some diagnostic testing. Combinations of elements of the chest pain history with other initially available information, such as a history of CAD, have identified certain groups that may be safe for discharge without further evaluation, but further study is needed before such a recommendation can be considered reasonable.Although certain elements of the chest pain history are associated with increased or decreased likelihoods of a diagnosis of ACS or AMI, none of them alone or in combination identify a group of patients that can be safely discharged without further diagnostic testing.