tbuckley/cabot-search huggingface dataset:
Phase I and Pharmacologic Study of Irinotecan Administered as a 96-Hour Infusion Weekly to Adult Cancer Patients
Authors: Chris H. Takimoto, Geraldine Morrison, Nancy Harold, Mary Quinn, Brian P. Monahan, Roger A. Band, Jeff Cottrell, Aida Guemei, Victor Llorens, Hilary Hehman, Abdel Salam Ismail, Donald Flemming, David M. Gosky, Haruyo Hirota, Sosamma J. Berger, Nathan A. Berger, Alice P. Chen, Jeremy D. Shapiro, Susan G. Arbuck, John Wright, J. Michael Hamilton, Carmen J. Allegra, Jean L. Grem
Journal: Journal of Clinical Oncology (2000)

We conducted a phase I and pharmacologic study of a weekly 96-hour infusion of irinotecan to determine the maximum-tolerated dose, define the toxicity profile, and characterize the clinical pharmacology of irinotecan and its metabolites.In 26 adult patients with solid tumors, the duration and dose rate of infusion were escalated in new patients until toxicity was observed.In 11 patients who were treated with irinotecan at 12.5 mg/m(2)/d for 4 days weekly for 2 of 3 weeks, dose-limiting grade 3 diarrhea occurred in three patients and grade 3 thrombocytopenia occurred in two patients. The recommended phase II dose is 10 mg/m(2)/d for 4 days given weekly for 2 of 3 weeks. At this dose, the steady-state plasma concentration (Css) of total SN-38 (the active metabolite of irinotecan) was 6.42 +/- 1.10 nmol/L, and the Css of total irinotecan was 28.60 +/- 17.78 nmol/L. No patient experienced grade 3 or 4 neutropenia during any cycle. All other toxicities were mild to moderate. The systemic exposure to SN-38 relative to irinotecan was greater than anticipated, with a molar ratio of the area under the concentration curve (AUC) of SN-38 to irinotecan of 0.24 +/- 0.08. One objective response lasting 12 months in duration was observed in a patient with metastatic colon cancer.The recommended phase II dose of irinotecan of 10 mg/m(2)/d for 4 days weekly for 2 of 3 weeks was extremely well tolerated. Further efficacy testing of this pharmacologic strategy of administering intermittent low doses of irinotecan is warranted.
Lymphocyte Populations Participating in Cellular Antitumor Immune Responses Mediated by Immune RNA2
Authors: David H. Kern, Nancy Chow, Yosef H. Pilch
Journal: JNCI Journal of the National Cancer Institute (1978)

T-lymphocytes were found to be intimately involved in cellular antitumor immune reactions mediated by both syngeneic and xenogeneic immune RNA (I-RNA). Syngeneic I-RNA was extracted from unfractionated spleen cell suspensions and from various subpopulations of spleen cells from inbred Fischer 344/N rats bearing growing transplants of a 3-methylcholanthrene-induced sarcoma (MC3-R) that were incubated separately with non immune syngeneic spleen cells, and their cytotoxicity for MC3-R target cells was determined. Active I-RNA was extracted from populations of donor lymphoid cells enriched in T-lymphocytes. By contrast, RNA from cells adherent to erythrocyte-antibody (EA) monolayers (B-cells) was inactive. The effector cells acted on by the I-RNA also appeared to be T-cells. Cells that formed EA rosettes (mostly B-cells) showed no increase in cytotoxicity for MC3-R target cells, whereas cells not forming EA rosettes and non adherent to nylon fiber (mostly T-cells) became more cytotoxic after incubation with I-RNA. After incubation with xenogeneic I-RNA extracted from the lymphoid organs of guinea pigs immunized with C3H tumor cells, the cytotoxicity of unfractionated, nonimmune C3H spleen cells for tumor target cells was increased. Removal of cells adherent to petridishes did not change the cytotoxicity, but nonadherent cells were inactive. Lymphocytes eluted from nylon fiber columns increased in cytotoxicity after being exposed to I-RNA; however, when these cells were treated with anti-ε serum and complement, this response was abrogated. Therefore, the effector cells mediating cytotoxic antitumor reactions after treatment with I-RNA appeared to be T-lymphocytes. For both syngeneic and xenogeneic I-RNA, the cytotoxic reactions were specific for the tumor used to immunize the I-RNA donors.
Acute promyelocytic leukemia: clinical relevance of two major PML-RAR alpha isoforms and detection of minimal residual disease by retrotranscriptase/polymerase chain reaction to predict relapse
Authors: W Huang, GL Sun, XS Li, Q Cao, Y Lu, GS Jang, FQ Zhang, JR Chai, ZY Wang, S Waxman
Journal: Blood (1993)
Nursing and healthcare-associated pneumonia requiring hospital admission: Microbiology and clinical outcomes
Authors: Nobuaki Mamesaya, Hiromi Tomioka, Shinichiro Nakao, Reina Sekiya, Shuji Yamashita, Toshihiko Kaneda, Yoko Kida, Chihiro Nishio, Masahiro Kaneko
Journal: European Respiratory Journal (2014)

Backgrounds:Guidelines suggest that patients with healthcare-associated pneumonia(HCAP)be treated empirically for multidrug-resistant(MDR)pathogens. However, potentially pathogenic bacteria may be merely colonizers.  The Japan Respiratory Society documented a new category, nursing and healthcare-associated pneumonia(NHCAP).Objectives:The objective of this study was to investigate the role of sputum cultures, and to clarify the strategy for treatment of NHCAP. Methods:We conducted a retrospective study of 408 patients with NHCAP who were hospitalized at a single center between 2010 and 2012. The criteria for NHCAP were:(1)residence in a nursing home or an extended-care ward,(2)a discharge from a hospital in the preceding 90 days,(3)an elderly or handicapped patient who needs long-term care,(4)a patient who regularly requires vascular access in an outpatient setting. Results:Median age; 82±11. The number of sputum samples evaluated for pathogens were 327(80.0%), which included 75(23%)acceptable specimens judged by the criteria of Geckler. The most common pathogens were Methicillin-susceptible  Staphylococcus aureus  (MSSA)(16%), followed by  Pseudomonas aeruginosa (12%)and Methicillin-resistant  Staphylococcus aureus (MRSA)(11%). The most frequently used antimicrobials were penicillins with beta-lactamase inhibitors. Eight of 18 patients in whom MDR pathogens were detected, resolved without anti-MDR antimicrobials.Conclusion:NHCAP patients often provided inadequate sputum samples. Distinguishing true pathogens from colonizers in clinical practice is challenging. Further studies should be performed to avoid the overuse of broad-spectrum antibiotics.
Stem cells, mice, and men: Integrating human and mouse genomics to advance understanding of the biology and treatment of brain tumors
Authors: Richard J. Gilbertson
Journal: Clinical Cancer Research (2006)

PL-09   Despite dedicated efforts by physicians and scientists, significant government support and the tireless advocacy of fundraising groups, a high mortality rate and poor quality of life almost inevitably follow a brain tumor diagnosis. Many reasons have been proposed to explain why brain tumors continue to resist conventional medical treatment. These are summarized well by the real estate adage   location, location.  Simply put, brain tumors are hard to treat because they occur in the brain. Although brain tumors rarely spread outside the nervous system, they infiltrate critical structures, curtailing the use of surgery, chemotherapy, and radiation that can damage normal brain tissue. Thus most patients eventually succumb to the progressive destruction inflicted by their expanding tumor. However, a new hope is now emerging in the war on brain cancer. The new charge is being led by a joint force of basic neuroscientists, cancer biologists, and oncologists. This diverse band is bringing together the most recent understanding of brain development and cancer biology with novel approaches for blocking cancer causing genetic alterations. Spurred on by recent successes in leukemia, breast cancer, and lung cancer, we dare to hope that smart drugs, rationally designed and specifically targeted to each genetically defined subtype of brain tumor, will finally end the scourge of these diseases for ever.
Significance of Arcus Senilis in Caucasians
Authors: Nigel T Cooke
Journal: Journal of the Royal Society of Medicine (1981)

A study of arcus senilis in Caucasian men and women is reported. The prevalence of arcus senilis increases with age in both sexes and occurs more frequently in men. In women arcus senilis is uncommon before the menopause. The occurrence of arcus senilis in Caucasians is not a significant finding, except in men under the age of 40 years, when it is associated with an increased risk of coronary artery disease.
Subclinical Atherosclerosis and Incipient Regional Myocardial Dysfunction in Asymptomatic Individuals
Authors: Verônica R.S. Fernandes, Joseph F. Polak, Thor Edvardsen, Benilton Carvalho, Antoinette Gomes, David A. Bluemke, Khurram Nasir, Daniel H. O’Leary, João A.C. Lima
Journal: Journal of the American College of Cardiology (2006)
Chemically modified mRNA as a novel treatment for cystic fibrosis
Authors: Azita J. Mahiny, Rupert Handgretinger, Dominik Hartl, Michael S.D. Kormann
Journal: European Respiratory Journal (2013)

Monogenetic disorders such as Cystic Fibrosis (CF) may be treated by supplementation with the functional active protein or by administration of a vector encoding the desired gene product. However, current therapeutic efforts with DNA-based or viral vectors remain largely unsuccessful in treating this fatal disease.  As an alternative approach we propose messenger ribonucleic acid (mRNA)- based transcript transfer, which offers several benefits: it excludes the risk of any insertion of nucleic acid, which may come along with mutations and random integration. Immunological side effects can be successfully suppressed by using modified nucleotides, concomitantly increasing the stability of mRNA in vivo.  Administration of mRNA into the murine lung is performed by using an intratracheal spray applicator, which nebulizes the mRNA solution. All mRNA used is modified to mimic endogenous mRNA. Nanoparticles may facilitate the resorption of the administered mRNA into the lung epithelium.  We could already demonstrate that the substitution of Surfactant Protein B (SP-B) by intratracheal administration of SP-B encoding mRNA lead to a healthy status of transgenic SP-B mice (Kormann et al. Nat Biotech 2011; 29: 154-157). Here we establish the substitution of CF transmembrane conductance regulator (CFTR) in a murine gut-corrected CF model by administration of CFTR-encoding, modified mRNA. Inflammatory responses, lung function, electrophysiological as well as histological parameters will be measured.  Our preliminary results demonstrate the potential of using chemically modified CFTR mRNA as a viable treatment for CF. This novel technique is currently optimized in our group.
Blood pressure measurement
Authors: M. Quinn, A R Michell, E. O'Brien, G. Y H Lip, D G. Beevers, T. Marshall, A. Rouse
Journal: BMJ (2001)

# ABC shows absence of evidence in measuring blood pressure during pregnancy {#article-title-2} EDITOR—In the short ABC on blood pressure measurement Beevers et al made several references to problems with measurement in pregnancy that have been discussed for many years without satisfactory resolution.1 There are four main points. 1. Interestingly, the vascular sounds that are caused by vibration of the vessel wall are clearly modulated by consistent changes in patterns of flow in the brachial artery in pregnancy (figure).2 Sequence of vascular sounds in normotensive pregnancy. Vascular sounds were recorded with microphone over brachial artery (Toshiba HSM-05B), with concomitant Doppler recording of brachial artery waveform (Toshiba PLF703ST)
p53 protein accumulation and response to adjuvant chemotherapy in premenopausal women with node-negative early breast cancer.
Authors: P C Clahsen, C J van de Velde, C Duval, C Pallud, A M Mandard, A Delobelle-Deroide, L van den Broek, T M Sahmoud, M J van de Vijver
Journal: Journal of Clinical Oncology (1998)

PURPOSE Thirty percent of women with node-negative breast cancer will have a recurrence within 10 years after diagnosis. Molecular markers may identify those patients and predict whether they benefit from adjuvant therapy. The European Organization for Research and Treatment of Cancer (EORTC) conducted a randomized trial (EORTC 10854) to compare perioperative treatment with one course of fluorouracil, doxorubicin, and cyclophosphamide (FAC) versus no further therapy. We studied tumors from premenopausal patients with node-negative breast cancer randomized in this trial to determine whether p53 accumulation, c-erbB-2 expression, percentage of Ki-67-positive cells, estrogen receptor (ER-immunoassay [IA]), progesterone receptor (PR-IA), and angiogenesis could be used as prognostic factors and predictors of responsiveness to adjuvant chemotherapy. PATIENTS AND METHODS Paraffin-embedded tumor specimens from 441 premenopausal women with node-negative breast cancer were collected from the larger EORTC trial. Paraffin sections from the tumors were analyzed for immunohistochemical expression of p53, c-erbB-2, Ki-67, ER, PR, and angiogenesis. RESULTS Patients with p53-negative tumors showed a significant benefit from perioperative chemotherapy (P &lt; .01), whereas patients who had p53-positive tumors did not (P = .80). At a median follow-up time of 49 months, univariate analyses for disease-free survival (DFS) failed to show prognostic value for p53, c-erbB-2 and angiogenesis. Both univariate and multivariate results showed Ki-67 positivity, ER-IA negativity, and a younger age to be associated with a worse prognosis. CONCLUSION p53 accumulation was associated with a poor response to one perioperative course of FAC chemotherapy. Ki-67, ER-IA, and age are important prognostic factors in premenopausal women with node-negative breast cancer.
Outcome following late marrow relapse in childhood acute lymphoblastic leukemia.
Authors: J Chessells, A Leiper, D Rogers
Journal: Journal of Clinical Oncology (1984)

Thirty-four children with acute lymphoblastic leukemia, who developed bone marrow relapse after treatment was electively stopped, received reinduction, consolidation, continuing therapy, and intrathecal (IT) methotrexate (MTX). Sixteen children who relapsed within six months of stopping treatment had a median second-remission duration of 26 weeks; all next relapses occurred in the bone marrow. In 18 children who relapsed later, the median duration of second remission was in excess of two years, but after a minimum of four years' follow-up, 16 patients have so far relapsed again (six in the CNS). CNS relapse occurred as a next event in four of 17 children who received five IT MTX injections only and in two of 14 children who received additional regular IT MTX. Although children with late marrow relapses may achieve long second remissions, their long-term out-look is poor, and regular IT MTX does not afford adequate CNS prophylaxis. It remains to be seen whether more intensive chemotherapy, including high-dose chemoradiotherapy and bone marrow transplantation, will improve the prognosis in this group of patients.
Monocyte Chemoattractant Protein (MCP)-4 Expression in the Airways of Patients with Asthma
Authors: BOUCHAIB LAMKHIOUED, EDUARDO A. GARCIA-ZEPEDA, SYLVIE ABI-YOUNES, HIDETOSHI NAKAMURA, SEAN JEDRZKIEWICZ, LUDWIG WAGNER, PAOLO M. RENZI, ZOULFIA ALLAKHVERDI, CRAIG LILLY, QUTAYBA HAMID, ANDREW D. LUSTER
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Chemokines are chemotactic cytokines that play an important role in recruiting leukocytes in allergic inflammation. Monocyte chemoacctractant protein (MCP)-4 is a CC chemokine with potent chemotactic activities for eosinophils, monocytes, T lymphocytes, and basophils and therefore represents a good candidate to participate in allergic reactions. To determine if MCP-4 plays a role in asthma, we have investigated the expression of MCP-4 messenger RNA (mRNA) and protein in the airways of patients with asthma and normal control subjects by in situ hybridization and immunohistochemistry. We found that MCP-4 mRNA and protein was significantly upregulated in the epithelium and submucosa of bronchial biopsies and in the bronchoalveolar lavage (BAL) cells of patients with asthma compared with normal control subjects (p < 0.01). In addition, MCP-4 protein was significantly elevated in the BAL fluid of patients with atopic asthma when compared with normal control subjects (p < 0.01) and there was a significant correlation between MCP-4, eotaxin, and eosinophils. In support of our in situ findings demonstrating MCP-4 expression in epithelial cells and mononuclear cells in vivo, we have found that MCP-4 expression can be induced in these cells in vitro by tumor necrosis factor- α (TNF- α ) and interleukin-1 β (IL-1 β ). Interferon- γ (IFN- γ ) acted synergistically with TNF- α and IL-1 β in the induction of mRNA MCP-4 mRNA expression in A549 cells, whereas the glucocorticoid dexamethasone diminished the cytokine-induced expression of MCP-4. Our findings demonstrate that MCP-4 is upregulated in the airways of patients with asthma and suggest that MCP-4 plays a role in the recruitment of eosinophils into the airways of patients with asthma.
Inhaled formoterol during one year in asthma: a comparison with salbutamol
Authors: P Arvidsson, S Larsson, CG Lofdahl, B Melander, N Svedmyr, L Wahlander
Journal: European Respiratory Journal (1991)

Eighteen patients, who had previously taken part in a 2 wk cross-over comparison between formoterol and salbutamol, now took part in a one year double-blind study comparing salbutamol 200 micrograms b.i.d. with formoterol 12 micrograms b.i.d. Additional doses were taken when needed and were recorded. Ten patients were started on formoterol and eight on salbutamol. After one month, the patients were allowed to shift to the alternative drug. Two patients withdrew from the study. At the end of the study, 13 of 16 patients were on formoterol, thus showing a long-lasting preference for this drug. Forced expiratory volume in one second (FEV1) dose-response curves for inhaled salbutamol were repeatedly recorded during the study, and no tachyphylaxis was found. One patient stopped taking inhaled steroids but continued taking formoterol and theophylline. He deteriorated with a decreased response to salbutamol. After re-introduction of inhaled steroids his condition improved. This case indicates that effective bronchodilator therapy may mask the deterioration of asthma.
Principal: A prospective observational study of real-world treatment patterns and treatment outcomes in patients with advanced or metastatic renal cell carcinoma (mRCC) receiving pazopanib.
Authors: Aristotelis Bamias, Petri Bono, Giuseppe Procopio, Edwin Herrmann, Sergio Vazquez-Estevez, Angel Rodriguez Sanchez, Narayanan Srihari, Dirk L. Schrijvers, Robert E. Hawkins, Nicholas J. Vogelzang, Francisco J. Sapunar, Dipak Kothari, Sadya Khan, Faisal Mehmud, Eric Jonasch, Manuela Schmidinger
Journal: Journal of Clinical Oncology (2014)

TPS4600^ Background: Pazopanib is an oral, selective, multikinase inhibitor of VEGF receptors 1/2/3, PDGF receptors α/ß, and stem cell factor receptor (c-Kit) that is approved for first-line treatment of patients with advanced renal cell carcinoma (RCC) and for patients who received prior cytokine therapy. The COMPARZ study of pazopanib versus sunitinib as first-line treatment demonstrated noninferiority of pazopanib for progression-free survival (PFS) in the intention-to-treat population, and pazopanib statistically favored health-related quality of life (HRQoL) in 11 of the 14 domains measured (NEJM 2013;369:722-31). The PISCES patient preference study demonstrated that significantly more patients preferred pazopanib over sunitinib due to overall better HRQoL and less fatigue (JCO 2012;30 suppl 15:CRA4502). The purpose of the PRINCIPAL study is to evaluate the real-world effectiveness and safety of pazopanib in patients with advanced or mRCC. Methods: This is a global, multicenter, prospective, observational study (VEG115232, NCT01649778) designed to enrol up to 700 patients. Primary endpoints include PFS, overall response rate, overall survival, relative dose intensity data, HRQoL data, and safety data. Additional treatment strategies for RCC will be obtained post-progression. Key inclusion criteria include a clinical decision to initiate treatment with pazopanib (before enrolment in the study), no prior systemic therapy for advanced or mRCC, and no participation in an interventional trial. The study has enroled 339 patients to date and is currently recruiting in 15 countries, including Europe, Asia, Latin America, and the United States. This study will determine patient outcomes with pazopanib in a real-world setting in terms of efficacy, safety, and patient compliance outside the normal parameters of a controlled trial. PRINCIPAL will also provide further data in patient groups that were under-represented in the controlled clinical trials to date, such as the elderly and patients with co-morbidities. Clinical trial information: NCT01649778.
Analysis of differentially expressed proteins involved in hand, foot and mouth disease and normal sera
Authors: L. Deng, H.-L. Jia, C.-W. Liu, K.-H. Hu, G.-Q. Yin, J.-W. Ye, C.-H. He, J.-H. Chen, Y.-P. Xie, R. Dang, L. Zhang, N.-Y. Liu, L. Zhu, L. Zhang
Journal: Clinical Microbiology and Infection (2012)
Worrying smoking habits in young Swedish women
Authors: Göran Wennergren, Linda Ekerljung, Bernt Alm, Jan Lötvall, Bo Lundbäck
Journal: European Respiratory Journal (2012)

Background: Following 10 years of decreased smoking among young people in Sweden, we now have indications of a drastically increased smoking prevalence. The aim was to provide up-to-date information on the prevalence of smoking and smoke-associated respiratory symptoms in young adults in Sweden, with special focus on possible gender differences.

Methods: A large-scale, detailed postal questionnaire focusing on asthma and respiratory symptoms, as well as possible risk factors (the West Sweden Asthma Study). The questionnaire was mailed to 30000 randomly selected subjects aged 16-75 years in Gothenburg and the surrounding region in western Sweden, response rate 62%. The analyses are based on responses from 2702 subjects aged 16-25 years (1154 men, 1548 women).

Results: Significantly more young women than men were active smokers (23.5% vs 15.9%; p < 0.001). In addition, women started smoking earlier and smoked more cigarettes per day.

Longstanding cough, sputum production, recurrent wheeze, any wheeze last year, dyspnoea, wheezing with breathlessness or without cold, waking with tight chest, nasal obstruction and rhinorrhea were significantly more common in smokers compared with non-smokers.

The smokers to a great extent had smoking parents, while subjects with non-smoking parents in 75% were non-smokers.

In the multivariate analysis, smoking increased the risk of symptoms, such as recurrent wheeze, OR 2.0 (95% CI 1.4-3.0) and sputum production, OR 2.4 (1.9-3.1).

Conclusion: The fact that smoking today is so common in young women is worrying both in itself and because maternal smoking during pregnancy is a risk factor for wheezing illness in the child. The results call for continuous anti-smoking efforts and not only isolated campaigns.
Measurements of ketoacids in normal and neoplastic rat tissue.
Authors: G. A. LePage
Journal: Cancer Research (1950)

Summary  1.A method is described for chromatography of ketoacids in the form of their 2,4-dinitrophenylhydrazones.  2.The method is used to determine pyruvic, oxalacetic, and α-ketoglutaric acids in extracts of rat tissues which were frozen  in situ  with liquid air.  3.Analyses of tissues from animals frozen with and without nembutal anesthesia indicated the necessity of anesthesia to prevent changes due to stimulation of the tissues on contact with the liquid air.  4.Fasting was found to decrease these ketoacids in rat liver.  5.Pyruvic acid was found to be very low in normal tissues and somewhat elevated in venous blood and in neoplastic tissues.  6.Oxalacetic acid was very low in all tissues studied and was not detectable in blood or brain samples.  7.α-Ketoglutaric acid was highest in kidney and in neoplastic tissues. The levels in most other tissues did not exceed that in blood.