tbuckley/cabot-search huggingface dataset:
Five-Day Oral Etoposide2 Treatment for Advanced Small-Cell Lung Cancer: Randomized Comparison With Intravenous Chemotherapy
Authors: R. L. Souhami, S. G. Spiro, R. M. Rudd, M.-C. R. d. Elvira, L. E. James, N. H. Gower, A. Lamont, P. G. Harper
Journal: JNCI Journal of the National Cancer Institute (1997)

Oral etoposide is an active single agent in small-cell lung cancer (SCLC) and is widely prescribed as first-line treatment as an alternative to intravenous combination chemotherapy in patients with extensive disease.The intention of this study was to determine if the effects of oral etoposide therapy on survival and quality of life are equivalent to those of intravenous chemotherapy.In a randomized trial of palliative treatment in advanced SCLC, oral etoposide (100 mg given twice daily for 5 days) was compared with intravenous chemotherapy consisting of alternating cycles of cisplatin and etoposide (PE) and cyclophosphamide, doxorubicin, and vincristine (CAV). Six cycles of chemotherapy were administered every 21 days in both regimens. Symptom control and quality of life were measured with the Rotterdam Symptom Checklist and a daily diary card. In January 1996, after 155 patients had been randomly assigned from a projected intake of 365 patients, an independent Data Monitoring Committee examined the interim results. Survival was determined by the Kaplan-Meier method, and the logrank test was used to compare treatments. For quality-of-life comparisons, average scores were calculated for each time point. The Mann-Whitney U test was used to determine any significant overall differences between treatments. For the Rotterdam Symptom Checklist, separate analyses were done for each subset (psychological well-being, physical symptoms, lung cancer symptoms, treatment symptoms, activity, and quality of life). Response rates and toxicity scores were compared by using chi2. All statistical tests were two-sided.Survival was inferior at 1 year in the oral etoposide group compared with intravenous therapy (9.8% for oral versus 19.3% for intravenous; difference = 9.5%; 95% confidence interval of difference = 0.3%-18.7%; P<.05), and there was a trend toward inferior overall survival. Median survival was 4.8 months for oral treatment and 5.9 months for intravenous therapy. Progression-free survival was worse in the oral etoposide arm (median = 3.6 months versus 5.6 months; P<.001), as well as overall response rate (32.9% versus 46.3%; P<.01). With the exception of acute nausea and vomiting associated with intravenous chemotherapy, all aspects of symptom control and quality of life were either the same or worse in the oral etoposide group. Study closure was recommended.These interim results show that this schedule of oral etoposide is inferior to intravenous chemotherapy in the treatment of advanced SCLC and should not be used as first-line treatment of this disease.
Immune Responses in Human Colon Cancer. II. Cytotoxic Antibody Detected in Patients' Sera2
Authors: William V. Hahn, Martin F. Kagnoff, Loren H. Hatlen
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Immune Responses in Human Colon Cancer. II. Cytotoxic Antibody Detected in Patients' Sera Get access William V. Hahn, William V. Hahn 3Department of Medicine, University of California at San Diego, La Jolla, Calif. 92093 Search for other works by this author on: Oxford Academic PubMed Google Scholar Martin F. Kagnoff, Martin F. Kagnoff 5 3Department of Medicine, University of California at San Diego, La Jolla, Calif. 92093 5Address reprint requests to Dr. M. Kagnoff, M-013, University of California at San Diego, School of Medicine, La Jolla, Calif. 92093. Search for other works by this author on: Oxford Academic PubMed Google Scholar Loren H. Hatlen Loren H. Hatlen 6Immunodiagnostic Systems, Box 359, Solana Beach, Calif. 92075 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 60, Issue 4, April 1978, Pages 779–784, https://doi.org/10.1093/jnci/60.4.779 Published: 01 April 1978 Article history Received: 25 August 1977 Accepted: 11 November 1977 Published: 01 April 1978
Alison George Selborne ("Joe") Bailey Arthur Reginald Bollen Timothy Cordley Bradford William Frederick Buchanan William David Calderwood Rasiah Dharmaindra Sami Zaki Fouad Stanley Lester Goodman Avinash Khunger Louise-Vaughan Lewis Geoffrey Bertrand Leyton Douglas Robert Mackenzie Noel Myddelton Mann Lex Mitchell David Michael ("Mike") Philip Pullen
Authors: D. Fergusson, R. Jones, P. Bollen, G. J Fowler, J. Suranyi, D. Fergusson, V Jeevananthan, S. S Gill, B. Goodman, D. Goodman, D. Goodman, a. A. Goodman, S. Khunger, W. Levison, J Moir, D. Mansbridge, R. Melville, a. A. Sweenie, G V Feldman, M. Lowe, J. Cox
Journal: BMJ (1998)
Growth and differentiation of colony-forming human hepatocytes in vitro
Authors: Chihiro Yamasaki, Chise Tateno, Akio Aratani, Chimoto Ohnishi, Shigeru Katayama, Toshihiko Kohashi, Hiroshi Hino, Hiroyuki Marusawa, Toshimasa Asahara, Katsutoshi Yoshizato
Journal: Journal of Hepatology (2005)
Doxorubicin and Paclitaxel Versus Doxorubicin and Cyclophosphamide as First-Line Chemotherapy in Metastatic Breast Cancer: The European Organization for Research and Treatment of Cancer 10961 Multicenter Phase III Trial
Authors: L. Biganzoli, T. Cufer, P. Bruning, R. Coleman, L. Duchateau, A.H. Calvert, T. Gamucci, C. Twelves, P. Fargeot, R. Epelbaum, C. Lohrisch, M.J. Piccart
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To compare the efficacy and tolerability of the combination of doxorubicin and paclitaxel (AT) with a standard doxorubicin and cyclophosphamide (AC) regimen as first-line chemotherapy for metastatic breast cancer. PATIENTS AND METHODS: Eligible patients were anthracycline-naive and had bidimensionally measurable metastatic breast cancer. Two hundred seventy-five patients were randomly assigned to be treated with AT (doxorubicin 60 mg/m 2 as an intravenous bolus plus paclitaxel 175 mg/m 2 as a 3-hour infusion) or AC (doxorubicin 60 mg/m 2 plus cyclophosphamide 600 mg/m 2 ) every 3 weeks for a maximum of six cycles. A paclitaxel (200 mg/m 2 ) and cyclophosphamide (750 mg/m 2 ) dose escalation was planned at cycle 2 if no grade ≥ 3 neutropenia occurred in cycle 1. The primary efficacy end point was progression-free survival (PFS). Secondary end points were response rate (RR), safety, overall survival (OS), and quality of life. RESULTS: A median number of six cycles were delivered in the two treatment arms. The relative dose-intensity and delivered cumulative dose of doxorubicin were lower in the AT arm. Dose escalation was only possible in 17% and 20% of the AT and AC patients, respectively. Median PFS was 6 months in the two treatments arms. RR was 58% versus 54%, and median OS was 20.6 versus 20.5 months in the AT and AC arms, respectively. The AT regimen was characterized by a higher incidence of febrile neutropenia, 32% versus 9% in the AC arm. CONCLUSION: No differences in the efficacy study end points were observed between the two treatment arms. Treatment-related toxicity compromised doxorubicin-delivered dose-intensity in the paclitaxel-based regimen
Opposing Effects of C-Reactive Protein Isoforms on Shear-Induced Neutrophil-Platelet Adhesion and Neutrophil Aggregation in Whole Blood
Authors: Tarek Khreiss, Levente József, Lawrence A. Potempa, János G. Filep
Journal: Circulation (2004)

Plasma C-reactive protein (CRP) level is a powerful predictor of cardiovascular events. However, it is not known whether CRP could affect neutrophil-platelet adhesion and neutrophil aggregation, key events in acute coronary syndromes. Emerging in vitro evidence suggests that some bioactivities of CRP are expressed on loss of the pentameric symmetry, resulting in formation of modified or monomeric CRP (mCRP).We studied the impact of human native CRP and bioengineered mCRP that cannot rearrange into the pentameric structure on the kinetics of neutrophil-platelet adhesion and neutrophil aggregation in whole blood subjected to shear (approximately 100 s(-1)) using real-time flow cytometry. Shear resulted in upregulation of platelet P-selectin expression, leading to platelet capture of neutrophils and subsequent neutrophil aggregation, which was dependent on P-selectin, L-selectin, and CD18. Native CRP at clinically relevant concentrations markedly attenuated these changes. The residual amount of neutrophil adhesion was blocked with anti-CD18 or anti-CD11b antibody. By contrast, mCRP concentration-dependently enhanced shear-induced platelet P-selectin expression and increased the rate and extent of formation of both neutrophil-platelet and neutrophil-neutrophil aggregates. Complete abrogation of platelet-neutrophil adhesion and neutrophil aggregation required both anti-P-selectin and anti-CD18 antibodies but not anti-L-selectin antibody. The CRP action was markedly inhibited by an anti-CD32 antibody, whereas the mCRP effects were significantly attenuated by an anti-CD16 antibody.These results indicate that native CRP inhibits platelet activation and prevents platelet capture of neutrophils, whereas mCRP displays potent prothrombotic activities under low levels of shear. Thus, mCRP rather than native CRP may precipitate acute coronary syndromes.
Mediterranean diet is associated with reduced brain shrinkage in older people, study finds
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

A Mediterranean-style diet may be associated with losing fewer brain cells from ageing, a study in the journal Neurology has found.1

The study, carried out by researchers at Columbia University in New York, USA, looked at 674 people with an average age of 80 who did not have dementia and who were included in an ongoing study of ageing and dementia (the Washington Heights-Inwood Community Aging Project; WHICAP).

The participants completed questionnaires about their diet over the past year and then had magnetic resonance imaging (MRI) scans an …
RENAL DEPOSITION OF SOLUBLE IMMUNE COMPLEXES IN MICE BEARING B-16 MELANOMA
Authors: Paula K. F. Poskitt, Thomas R. Poskitt, John H. Wallace
Journal: The Journal of Experimental Medicine (1974)

Histologic and immunofluorescence studies of the kidneys of mice bearing a progressive melanoma show a proliferative glomerulonephritis associated with immune complex deposition in the mesangium and along the glomerular basement membrane This immune complex disease is distinct from the age-associated disease of the C57BL/6J host strain and the complexes can be shown to consist of soluble tumor antigen and antitumor antibody. Furthermore, the intensity of IgG complex deposition correlates directly with tumor progress (size and metastases) and inversely with mononuclear leukocyte infiltration of the tumor. In vitro assays for lymphocyte cytotoxicity and humoral antibody were found to be less reliable indicators of tumor progress. The possible role of circulating soluble tumor antigen in modifying the immune response to tumors is discussed.
Long-Term Results of a Randomized Trial on Extended Use of High Dose <scp>l</scp>-Asparaginase for Standard Risk Childhood Acute Lymphoblastic Leukemia
Authors: Andrea Pession, Maria Grazia Valsecchi, Giuseppe Masera, Willem A. Kamps, Edina Magyarosy, Carmelo Rizzari, Elisabeth R. van Wering, Luca Lo Nigro, Anna van der Does, Franco Locatelli, Giuseppe Basso, Maurizio Aricò
Journal: Journal of Clinical Oncology (2005)

Between September 1991 and May 1997, within the International Berlin-Frankfurt-Muenster Study Group (I-BFM-SG), a randomized study was performed aimed at assessing the efficacy of prolonged use of high-dose l-asparaginase (HD-l-ASP) during continuation therapy in children with standard risk (SR) acute lymphoblastic leukemia (ALL), treated with a reduced BFM-type chemotherapy.The Italian, Dutch, and Hungarian groups participated in this study denominated IDH-ALL-91, and 494 children were enrolled. Treatment consisted of a BFM-type modified backbone with omission of the IB part in induction and elimination of two doses of anthracyclines during reinduction in both arms at the beginning of continuation therapy. Patients were randomly assigned to receive (YES-ASP) or not (NO-ASP) 20 weekly HD-l-ASP (25,000 IU/m2).The event-free-survival and overall survival probabilities at 10 years for the entire group were 82.5% (1.8) and 90.3% (1.3), respectively. Of the 490 patients eligible for random assignment, 355 (72.4%) were randomly assigned (178 YES-ASP and 177 NO-ASP). After a median follow-up of 9 years, the probability of disease-free survival at 10 years was 87.5% (SE, 2.5) for YES-ASP arm versus 78.7% (SE, 3.3) for NO-ASP arm (P = .03). In multivariate analysis, NO-ASP arm (P = .03), male sex (P = .004), and age older than 10 years (P = .0003) had a significantly adverse impact on outcome.In this subset of patients, selected with criteria not including monitoring of minimal residual disease, application of extended HD-l-ASP may improve prognosis, compensating reduced leukemia control that results from adoption of a reduced-intensity BFM-backbone for treatment of children with SR ALL.
Towards early inclusion of children in tuberculosis drugs trials: a consensus statement
Authors: Sharon Nachman, Amina Ahmed, Farhana Amanullah, Mercedes C Becerra, Radu Botgros, Grania Brigden, Renee Browning, Elizabeth Gardiner, Richard Hafner, Anneke Hesseling, Cleotilde How, Patrick Jean-Philippe, Erica Lessem, Mamodikoe Makhene, Nontombi Mbelle, Ben Marais, Helen McIlleron, David F McNeeley, Carl Mendel, Stephen Murray, Eileen Navarro, E Gloria Anyalechi, Ariel R Porcalla, Clydette Powell, Mair Powell, Mona Rigaud, Vanessa Rouzier, Pearl Samson, H Simon Schaaf, Seema Shah, Jeff Starke, Soumya Swaminathan, Eric Wobudeya, Carol Worrell
Journal: The Lancet Infectious Diseases (2015)
Oncolytic viruses as therapeutic cancer vaccines
Authors: David L Bartlett, Zuqiang Liu, Magesh Sathaiah, Roshni Ravindranathan, Zongbi Guo, Yukai He, Zong Sheng Guo
Journal: Molecular Cancer (2013)

Abstract Oncolytic viruses (OVs) are tumor-selective, multi-mechanistic antitumor agents. They kill infected cancer and associated endothelial cells via direct oncolysis, and uninfected cells via tumor vasculature targeting and bystander effect. Multimodal immunogenic cell death (ICD) together with autophagy often induced by OVs not only presents potent danger signals to dendritic cells but also efficiently cross-present tumor-associated antigens from cancer cells to dendritic cells to T cells to induce adaptive antitumor immunity. With this favorable immune backdrop, genetic engineering of OVs and rational combinations further potentiate OVs as cancer vaccines. OVs armed with GM-CSF (such as T-VEC and Pexa-Vec) or other immunostimulatory genes, induce potent anti-tumor immunity in both animal models and human patients. Combination with other immunotherapy regimens improve overall therapeutic efficacy. Coadministration with a HDAC inhibitor inhibits innate immunity transiently to promote infection and spread of OVs, and significantly enhances anti-tumor immunity and improves the therapeutic index. Local administration or OV mediated-expression of ligands for Toll-like receptors can rescue the function of tumor-infiltrating CD8 + T cells inhibited by the immunosuppressive tumor microenvironment and thus enhances the antitumor effect. Combination with cyclophosphamide further induces ICD, depletes Treg, and thus potentiates antitumor immunity. In summary, OVs properly armed or in rational combinations are potent therapeutic cancer vaccines.
Elevated Remnant-Like Particles in Heterozygous Familial Hypercholesterolemia and Response to Statin Therapy
Authors: Pernette R. W. de Sauvage Nolting, Marcel B. Twickler, Geesje M. Dallinga-Thie, Rudolf J.A. Buirma, Barbara A. Hutten, John J.P. Kastelein
Journal: Circulation (2002)

Background— Remnant lipoproteins (RLP-C) are considered important in atherogenesis. Hence, this study was designed to assess RLP-C levels and the effect of statin therapy in patients with familial hypercholesterolemia (FH). Elevated RLP-C levels have been associated with the presence and progression of atherosclerotic disease, and their presence in FH patients has been proposed but never established in a large cohort, nor has their response to statin therapy been confirmed. Methods and Results— FH patients were recruited from 36 lipid clinics. After a washout period of 6 weeks, all patients were started on monotherapy with 80 mg of simvastatin for 2 years. RLP-C levels were assessed by an immune-separation assay. In 327 FH patients, RLP-C measurements could be performed before and after treatment. Mean total cholesterol (10.55±2.17 mmol/L), mean LDL cholesterol (8.40±2.13 mmol/L), and median RLP-C (0.47 mmol/L) levels were all severely elevated at baseline. After treatment, RLP-C levels were reduced by 49% (0.24 mmol/L; P &lt;0.0001). Even patients with normal triglyceride levels had elevated RLP-C levels at baseline, and those with high RLP-C levels were generally characterized by a very atherogenic lipoprotein profile. Conclusions— Baseline RLP-C levels are severely elevated in FH patients and are reduced by simvastatin but do not return to normal. These elevated RLP-C levels could be the consequence of impaired function of the LDL receptor in FH. RLP-C levels in FH contribute to an atherogenic lipoprotein profile and could identify patients who require additional treatment.
Relationship between exercise desaturation and pulmonary haemodynamics in COPD patients
Authors: C.C. Christensen, M.S. Ryg, A. Edvardsen, O.H. Skjønsberg
Journal: European Respiratory Journal (2004)

Pulmonary hypertension (PH) in patients with chronic obstructive pulmonary disease (COPD) has traditionally been explained as an effect of hypoxaemia. Recently, other mechanisms, such as arterial remodelling caused by inflammation, have been suggested. The aim of this study was to investigate whether exercise-induced PH (EIPH) could occur without concurrent hypoxaemia, and whether exercise-induced hypoxaemia (EIH) was regularly accompanied by increased pulmonary artery pressure or pulmonary vascular resistance index (PVRI). Pulmonary haemodynamics in 17 patients with COPD of varying severity, but with no or mild hypoxaemia at rest, were examined during exercise equivalent to the activities of daily living (ADL) and exhaustion. EIPH occurred in 65% of the patients during ADL exercise. Pulmonary arterial pressure during exercise was negatively correlated with arterial oxygen tension, but EIPH was not invariably accompanied by hypoxaemia. Conversely, EIPH was not found in all patients with EIH. The resting PVRI was negatively correlated with arterial oxygen tension during ADL exercise, but an elevated PVRI without EIH occurred in 35% of the patients. In conclusion, exercise-induced pulmonary hypertension occurred during exercise equivalent to the activities of daily living in chronic obstructive pulmonary disease patients with no or mild hypoxaemia at rest. Although pulmonary artery pressure and arterial oxygen tension were negatively correlated during exercise, a consistent relationship between hypoxaemia and pulmonary hypertension could not be demonstrated. This may indicate that mechanisms other than hypoxaemia contribute significantly in the development of pulmonary hypertension in these patients.
Routine biochemistry in suspected vitamin D deficiency
Authors: S. R Peacey
Journal: Journal of the Royal Society of Medicine (2004)

Vitamin D deficiency, which continues to be widespread amongst persons of Asian descent in the UK, is often detected from abnormal results on routine biochemistry. The aim of this study was to assess the frequency of abnormal results from routine baseline tests of serum calcium, phosphate, and alkaline phosphatase in patients who subsequently proved to have vitamin D deficiency and secondary hyperparathyroidism. A retrospective examination was undertaken to assess these baseline indices in a cohort of 84 such patients seen in Bradford—5 male; 80 of Asian descent; median age 46 years (range 16-82); serum 25-hydroxyvitamin D < 10 μg/L; parathyroid hormone >54ng/L. Calcium was normal in 55 patients (66%), phosphate in 68 (81%) and alkaline phosphatase in 24 (29%). In only 5 patients were all three indices outside the normal range. The median parathyroid hormone concentration was significantly greater in patients with abnormal routine biochemistry (145 [range 55-1662] ng/L) than in patients with normal routine biochemistry (88 [59-322] ng/L) but the median 25-hydroxyvitamin D levels did not differ (3.1 [1.3-9.9] and 3.0 [1.5-7.3] μg/L). Routine biochemistry was normal in 20% of cases. If routine biochemistry is relied upon to detect vitamin D deficiency and osteomalacia, a substantial minority of cases will be missed.
Lethal Injection and Physicians
Authors: Lee Black, Robert M Sade
Journal: JAMA (2007)

EGAL EXECUTION BY LETHAL INJECTION HAS MADE NAtionalheadlinesduringthepast2yearsbecauseprisoners have argued that it poses an unnecessary risk of pain as currently performed and therefore constitutesunconstitutionalcruelandunusualpunishment.The most widely used method of lethal injection, developed by aphysician, 1 involvestheintravenousinfusionoflargedoses of sodium thiopental to induce deep sleep, pancuronium bromide as a paralyzing agent, and potassium chloride for cardioplegia. Lethal injectionwas adopted as a means of execution because it seemed more humane than other methods, but it is unclear what consideration was given to the selectionofexecutionpersonnel,theskillstheyneeded,and thetrainingtheymightrequire.Recentcourtchallengeshave revealedthatdrugdosagesarenotuniformamongthestates, sowidedisparitiesinlevelsofsedationmayoccur,andsome inmates may have experienced considerable pain after potassium chloride infusion. 2,3 The legal challenges have also publicly exposed the participation of physicians in executions. 4,5 A number of states suspendedexecutionstoreexaminetheirmethods 6 andhave considered escalating the role of physicians to meet constitutionalchallenges.Theseeventshaveraisedquestionsabout theeffectofprofessionalethicalstandardsonphysicianparticipation in capital punishment and about the response of the medical profession to known instances of physician involvement in executions.
Helicobacter pylori infection density and gastric inflammation in duodenal ulcer and non-ulcer subjects.
Authors: S Khulusi, M A Mendall, P Patel, J Levy, S Badve, T C Northfield
Journal: Gut (1995)

The factors that determine which Helicobacter pylori infected subjects develop duodenal ulcer (DU) are unclear. This study tested the hypothesis that infection density and urease activity are higher in DU than non-DU subjects. Fifty five DU and 55 age and sex matched non-DU subjects were studied. Quantitative methods were used for measuring infection density (viable organism count) and urease activity (Berthelot reaction). DU subjects had a greater antral infection density (geometric mean of colony forming units/mg biopsy protein; 10.5 x 10(5) v 1.3 x 10(5), p &lt; 0.001). They also had higher biopsy urease activity (geometric mean of NH3 nmol/min-1/mg protein-1; 103 v 25, p &lt; 0.001). Urease activity per organism, however, was similar in the two groups showing that high antral urease activity in DU was a reflection of organism density. DU was not present in subjects with an antral infection density less than 10(5) colony forming units/mg protein. A correlation was present between H pylori viable counts and the severity and activity of gastritis. Both severity and activity of gastritis were greater in the antrum of DU compared with non-DU subjects but there was no difference in the body between the two groups. It is concluded that antral H pylori infection density is probably an important determinant of DU development, and that there is a baseline of infection density that is necessary for ulcer formation.