tbuckley/cabot-search huggingface dataset:
The effects of the dialysis membrane on cytokine release.
Authors: P Zaoui, R M Hakim
Journal: Journal of the American Society of Nephrology (1994)

The immune response requires the coordinated release of a network of cytokines including interleukin-1 (IL-1), tumor necrosis factor (TNF), and IL-2. The potential role of the dialysis membrane on the elaboration of these cytokines by peripheral blood mononuclear cells (PBMNC) harvested from hemodialysis patients was investigated in a prospective crossover study. Eight hemodialysis patients, chronically dialyzed with a biocompatible membrane, were sequentially dialyzed for 2 wk with new cuprophane membranes (Phase I), 2 wk with a low-flux, low-complement-activating membrane (Phase II), and then switched back for a further 2 wk of dialysis with a cuprophane membrane (Phase III). At the end of 2 wk of exposure to the cuprophane membrane, during both Phase I and Phase III, the ability of PBMNC to elaborate IL-1 beta, tumor necrosis factor-alpha, and IL-2, as well as soluble IL-2 receptors, in response to phytohemagglutinin was significantly reduced compared with their respective levels at the beginning of the phase; dialysis with a biocompatible membrane increased these levels, and at the end of 2 wk, the response of the PBMNC to phytohemagglutinin was close to that in normal controls. These findings may explain some of the conflicting results in the measurement of cytokine levels in hemodialysis patients and may have clinical implications.
Multicentric phase II trial of gemcitabine plus capecitabine combination in the treatment of previously anthracycline(An)-treated metastatic breast cancer (MBC): SOLTI 0301 study
Authors: E. M. Ciruelos, J. Baselga, H. Cortes-Funes, A. Lluch, J. I. Mayordomo, B. Ojeda, E. Gonzalez, M. Muñoz, C. Rodriguez, J. Cortes
Journal: Journal of Clinical Oncology (2007)

1051 Background: Based on clinical activity of capecitabine(C) and gemcitabine (G) on the treatment of MBC, we performed a multicentric phase II trial of the combination to test its efficacy and safety profile. Methods: Sample size of 72 evaluable MBC patients (pts) previously An-treated (neoadjuvant 8%, adjuvant 69%, advanced 30%). Median age: 59 years (35–76 years). Estrogen Receptor positive: 47 (65%). HER2 overexpression: 16 (22%). Prior hormonal/trastuzumab allowed. Soft tissue/ganglionar/pleural/bone disease: 19 (26%); visceral metastasis: 53(74%). Stratification: previous chemotherapy (CT) for advanced disease (none: group 1; any: group 2). Study treatment: oral bid C 1,660 mg/m 2 /day (d) (d1–14) + iv G 1,000 mg/m 2 /d (d1&amp;8). Cycles repeated every 3 weeks. RECIST/NCI-CTC 2.0 criteria. Primary end point: Objective Response Rate. Results: Response Rates and Clinical Benefit (CB) are detailed in the table . Median follow-up 7.2 months (m) (0.2–18.4). Median time to progression 11.2 m: group 1, 12 m (95%CI: 6.4–14.5); group 2, 8.9 m (95%CI: 6.9–14).Total and median administered cycles/pt: 479 and 8. Delayed cycles: 103(21.5%): 27% due to hematological toxicity, 11% due to non-hematological toxicity, 62% due to other causes. C dose reduced in 27 cycles (5.6%), 12 of them due to non- hematological toxicity. G dose reduced in 169 cycles (35%), mostly on day 8, and due to hematological toxicity (80% of reduced cycles). Grade 3–4 neutropenia: 32 pts (56%), 1 case of febrile neutropenia. Grade 3–4 non-hematological toxicities: asthenia 8 pts (14%), hand- foot syndrome 6 pts (10.5%), mucositis 3 pts (5%), diarrhea 2 pts (3.5%). Conclusions: Combination of C+G in the treatment of previously anthracycline-treated MBC is safe and active, with a manageable toxicity profile and a good clinical activity. [Table: see text] No significant financial relationships to disclose.
Phase II trial of edatrexate in patients with advanced pancreatic adenocarcinoma
Authors: D.F. Moore, R. Pazdur, J.L. Abbruzzese, J.A. Ajani, D.W. Dubovsky, J.L. Wade, R.J. Belt, C. Mangold, B. Bready, R.J. Winn
Journal: Annals of Oncology (1994)
What doctors think would make NHS 111 safer
Authors: Gareth Iacobucci
Journal: BMJ (2016)

Last week England’s health secretary, Jeremy Hunt, promised to change how the NHS 111 telephone triage helpline operates and connects with GPs, after a report into the death of 1 year old William Mead from septicaemia in December 2014.1 Latest figures show a big rise in calls to the helpline, with calls for the weekend of 22-24 January up by more than a quarter on the same weekend last year. The BMJ asked doctors and healthcare leaders for their thoughts on the future of …
Antitumor Polysaccharide Lentinan—A T Cell Adjuvant2
Authors: Gunther Dennert, Derek Tucker
Journal: JNCI Journal of the National Cancer Institute (1973)

Lentinan, a linear β (1–3) glucan with antitumor activity was tested for its activity on various immune responses. Lentinan had only minor effects on the plaqueforming cell response to sheep red blood cells but significantly stimulated antibody-dependent, cell-mediated immunity. This effect was due to stimulation of T helper cell priming by Lentinan, which amplified antibody synthesis. Lentinan, however, could not be demonstrated to increase sensitization of T killer cells in an allogeneic system.
Prognostic impact of Forkhead box-F1 (FOXF1) polymorphisms on the clinical outcome in gastric cancer patients.
Authors: Satoshi Matsusaka, Anna H. Wu, Shu Cao, Nobuyuki Mizunuma, Keisho Chin, Wu Zhang, Dongyun Yang, Yan Ning, Stefan Stremitzer, Yu Sunakawa, Satoshi Okazaki, Anish Parekh, Rita Elie El-Khoueiry, Angela Mendez, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2015)

4039 Background: A recent genome-wide association study reported associations between risk of Barrett’s esophageal and esophageal adenocarcinoma and seven single-nucleotide polymorphisms (SNPs) in region 16q24 on chromosome 16 near the Forkhead box-F1 (FOXF1) gene. The FOXF1 gene is known to regulate mesenchymal-epithelial interactions of the lung and gut morphogenesis and to regulate cancer-associated fibroblasts to stimulate cancer cell migration. We tested whether these SNPs are associated with clinical outcome of gastric cancer (GC) patients from Japan and Los Angeles County (LAC). Methods: We isolated genomic DNA from blood or tissue of GC patients from two independent cohorts. A total of 150 patients with advanced GC from Japan [107 male/43 female; median age 61 year-old; median follow-up time, 3.1 years; median overall survival (OS), 13.8 months; median progression-free survival (PFS), 6.6 months] who were treated with 1st line fluoropyrimidine-based chemotherapy and 214 patients with stage IA-IV GC from LAC [146 male/68 female; median age 62 year-old; median follow-up time, 8.2 years; median OS, 2.6 years] were included. Genomic DNA was analyzed using PCR-based direct DNA sequencing. Multivariate Cox proportional hazard regression was conducted to investigate the relationship between these SNPs with clinical outcome of gastric cancer patients. Results: One FOXF1 SNP, rs3950627, was associated with outcome in patients from Japan and LAC. Japanese patients who had C/C genotype experienced better outcome than those with any A allele (PFS: C/C 8.2 months, any A allele 5.3 months; p = 0.037 and OS: C/C 16.4 months, any A allele 12.2 months; p = 0.043). Similarly, patients in LAC with C/C genotype showed better outcome (OS: C/C 46.8 months, any A allele 27.6 months, p = 0.022). Results were consistently strong when we restricted the analysis to male patients and those with gastric cardia cancer. Conclusions: Our data show for the first time that rs3950627 is a promising a prognostic marker in two cohorts of GC patients. Furthermore, rs3950627 may be useful as a predictive marker in patients treated with fluoropyrimidine-based chemotherapy, which may be gender dependent.
Elevated Levels of α-Globulins in Sera From Germfree Rats With 3-Methylcholanthrene-Induced Tumors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Theodore P. Zacharia, Morris Pollard
Journal: JNCI Journal of the National Cancer Institute (1969)

Mean levels of α-globulins were high in sera from germfree Sprague-Dawley rats with 3-methylcholanthrene-induced tumors, compared to the α-globulin levels in sera from control germfree rats of the same strain. The second fraction in the α-globulin zone of sera from tumor-bearing rats was not detected in the control counterparts. Mean total α-globulin values dropped to normal levels at 3 weeks after extirpation of fibrosarcomas. However, while the second α-globulin fraction values did not disappear completely, they fell to much lower levels, comparatively. The relation of these findings to oncogenesis is discussed.
Two GPs face charges of manslaughter over death of boy in 2012
Authors: Clare Dyer
Journal: BMJ (2016)

Two GPs have appeared in court charged with the manslaughter by gross negligence of a 12 year old patient who died in December 2012 in Wales.

Joanne Rudling, 45, and Lindsey Thomas, 42, entered not guilty pleas at Cardiff Crown Court on 8 February to charges of unlawfully killing Ryan Morse by gross negligence.

Ryan died suddenly at his home in Brynithel, near Abertillery, on 8 December 2012, …
Extended measures for controlling an outbreak of VIM-1 producing imipenem-resistant Klebsiella pneumoniae in a liver transplant centre in France, 2003–2004
Authors: N Kassis-Chikhani, F Saliba, A Carbonne, S Neuville, D Decre, C Sengelin, C Guerin, N Gastiaburu, A Lavigne-Kriaa, C Boutelier, G Arlet, D Samuel, D Castaing, E Dussaix, V Jarlier
Journal: Eurosurveillance (2010)

We report the successful control of an outbreak caused by imipenem-resistant VIM-1-producing Klebsiella pneumoniae (IR-Kp) in France. This outbreak occurred in a care centre for abdominal surgery that includes a 15-bed liver intensive care unit and performs more than 130 liver transplantations per year. The index case was a patient with acute liver failure transferred from a hospital in Greece for urgent liver transplantation who was carrying IR-Kp at admission as revealed by routine culture of a rectal swab. Infection control measures were undertaken and included contact isolation and promotion of hand hygiene with alcohol-based hand rub solution. Nevertheless, secondary IR-Kp cases were identified during the six following months from 3 December 2003 to 2 June 2004. From 2 June to 21 October, extended infection control measures were set up, such as cohorting IR-Kp carriers, contact patients and new patients in distinct sections with dedicated staff, limiting ward admission, and strict control of patient transfer. They led to a rapid control of the outbreak. The global attack rate of the IR-Kp outbreak was 2.5%, 13% in liver transplant patients and 0.4% in the other patients in the care centre (p<0.005). Systematic screening for IR-Kp of all patients admitted to the care centre is still maintained to date and no secondary IR-Kp case has been detected since 2 June 2004.
Abstract 13150: Effect of Cardiac Hybrid 15o-water Pet/ct Imaging Upon Downstream Referral for Invasive Coronary Angiography and Revascularization Rate
Authors: Ibrahim Danad, Pieter G Raijmakers, Hendrik J Harms, Cornelis van Kuijk, Niels van Royen, Michala Diamant, Adriaan A Lammertsma, Mark Lubberink, Albert C van Rossum, Paul Knaapen
Journal: Circulation (2012)

Background:  Hybrid 15O-water positron emission tomography (PET)/CT-based coronary angiography (CTCA) imaging for the diagnosis of coronary artery disease (CAD) provides complementary information on coronary anatomy and myocardial perfusion in a single scan session. The aim of the present study is to assess the impact of PET/CTCA imaging on referral for invasive coronary angiography (ICA) and revascularization rate.   Methods:  A total of 375 patients (mean age 58 ± 10 years, 192 men) without a previous history of CAD underwent hybrid 15O-water PET/CTCA imaging. Downstream treatment strategy within a 60-day period after hybrid PET/CTCA imaging for ICA referral and revascularization procedures (percutaneous coronary intervention or coronary artery bypass surgery) was assessed. CTCA examinations were classified as showing non-obstructive CAD (   Results:  Based on CTCA imaging, 182 (49%) patients displayed nonobstructive CAD. Alternatively, 16 (9%) of the patients with nonobstructive CAD on CTCA had abnormal myocardial perfusion imaging (MPI). Only 10 (5%) patients with nonobstructive CAD on CTCA were referred for ICA, which were all negative. An equivocal CT study was noted in 80 (21%) patients, with 56 (70%) having normal MPI. Referral rate for ICA was 18% (normal MPI) and 71% (abnormal MPI). Interestingly, no revascularizations were performed in the presence of an equivocal CT in combination with normal MPI, while 59% of those with an abnormal MPI were revascularized. CTCA indentified obstructive CAD in 113 (30%) patients accompanied in 59 (52%) patients with abnormal MPI. Referral rate for ICA in this group was 57% for normal MPI and 88% in the group with abnormal MPI, compared with revascularization rates of 26% and 72%.   Conclusion:  Hybrid cardiac 15O-water PET/CTCA imaging impacts clinical decision making with regard to referral for ICA and subsequent myocardial revascularization procedures. Particularly, in the presence of an equivocal or abnormal CTCA, MPI acts as an arbiter to guide a judicious referral to the catheterization laboratory and revascularization strategy.
Reducing deaths among drug misusers
Authors: A. S Trebach, A. Byrne, C. Ford, T. Carnwath, M. Gabbay
Journal: BMJ (2001)

Editor—Gabbay et al argued that tightening controls by extending the licensing system to all controlled drugs is likely to bring about adverse consequences.1 Drug related deaths will increase in number rather than decrease. The hidden message in the editorial, written by four doctors experienced in treating addiction, was equally important. There is a growing and ultimately destructive schism in the United Kingdom's medical profession regarding the proper controls on doctors treating drug misusers.

On the one hand, there are doctors such as Gabbay et al who argue that the British approach to treating drug misusers has enduring value. This means that the judgment of an individual doctor should be trusted in tailoring treatment for each patient. Thus, each drug misuser is treated as a patient with unique needs, and drug misusers in general as constituting a heterogeneous, not a homogeneous, population. Trust in doctors extends to decisions to prescribe narcotics. Doctors operating from the British system assume that there is no specific treatment of drug abuse. This realistic concept has encouraged experimentation and innovation by British doctors, including general practitioners, in taking on and treating difficult patients. Medical practice based on the British system has worked to hold down the spread of addiction and disease.

On the other hand, there are doctors wielding considerable power in the drug misuse establishment who view the clinical freedom accorded by the British system as both an anachronism and a threat to public health. This politically dominant group of doctors has, over the past several decades, imposed increasing control on the clinical freedom of doctors abiding by the British system. This control has been implemented through several editions of clinical guidelines and also through an activist role for the General Medical Council: the GMC disciplines and erases selected doctors who abide by the approach of the British system to helping drug misusers. These actions by the GMC have been viewed as arbitrary and unpredictable by respected medical experts. Many doctors are afraid to accept drug misusers as patients because they worry about being irrationally persecuted by the GMC.

The planned extension of the licensing system to all controlled drugs would be an illness masquerading as a cure. Stricter controls signal the death knell for a humanitarian and efficacious system of addiction prevention and treatment. The GMC has a duty to keep that tragedy from happening. Yet it almost seems intent on creating it.
Antidepressants may double risk of suicide and aggression in children, study finds
Authors: Jacqui Wise
Journal: BMJ (2016)

Doctors should avoid prescribing antidepressants to children and teenagers wherever possible because they are associated with a doubling in the risk of aggression and suicide, Danish researchers have concluded in The BMJ .1 They recommend considering alternative treatments such as exercise or psychotherapy.

The researchers carried out a systematic review and meta-analysis of 70 trials with 18 526 patients. The trials examined the use of five of the most commonly prescribed antidepressants: duloxetine; fluoxetine; paroxetine; sertraline, and venlafaxine.

They included in their study only double blind placebo …
Phase II study of neoadjuvant biochemotherapy (BCT) for stage III malignant melanoma (MM): Results of long-term follow-up (LTFU)
Authors: K. D. Lewis, A. Lane, C. Anderson, N. Pearlman, M. Becker, C. Zeng, A. Baron, R. Gonzalez
Journal: Journal of Clinical Oncology (2006)

8035 Background: Patients (pts) with MM metastatic to regional lymph nodes (LNs) (stage 3) are at high-risk of developing systemic disease and subsequent death. High-dose adjuvant alpha interferon (IFN) has proven in randomized studies to result in significant improvement in relapse-free survival (RFS), but the benefit on overall survival (OS) is less clear. BCT (cytotoxic chemotherapy with interleukin-2 (IL-2) and IFN) has shown high response rates in pts with metastatic MM. It is, therefore, hypothesized that using BCT in earlier stage disease may result in an improvement in OS for this high-risk population. Methods: This was a pilot phase 2 study of neoadjuvant BCT in pts with stage 3 MM with a planned accrual of 50 pts. Earlier results have previously been reported (Cancer 2002;94:470–6). LTFU is now obtained and reported here. Eligibility required biopsy confirmed MM to regional LNs without previous therapeutic lymphadenectomy. Two cycles of BCT were administered prior to and after lymphadenectomy. BCT was: cisplatin 20 mg/m 2 days (D) 1–4, vinblastine 1.6 mg/m 2 D 1–4, dacarbazine 800 mg/m 2 D 1, IFN 5 MIU/m 2 D 1–5, IL-2 9 MIU/m 2 continuous infusion D 1–4. The primary endpoints were RFS and OS. Results: Fifty-one pts were enrolled from 4–96 to 5–99. Three pts had stage 4 MM and are not included in this analysis. Of the remainder, 87.5% (42/48) had clinically detectable disease, while 12.5% (6/48) were sentinel lymph node positive. Twenty-five percent (12/48) had received prior IFN therapy. At a median follow-up of 75 months (mo), 54% are disease-free (26/48) and 65% are alive (31/48). The 5-year OS and RFS are 66% [95% confidence interval (CI) 50 - 78) and 56% (95% CI 41 - 69), respectively. Median survival has yet to be reached. After the 24-month time point there have been 3 relapses and 4 deaths. Toxicity was manageable. Conclusions: Neoadjuvant BCT may be an effective regimen for stage 3 MM. The LTFU of the current study shows favorable results in terms of RFS and OS when compared to historical controls. A subsequent larger, multicenter phase 2 study of neoadjuvant BCT has been completed. In addition, a cooperative group phase 3 study comparing adjuvant BCT to IFN is currently enrolling pts. [Table: see text]
Current Status and Perspective of Chemotherapy for Unresectable Pancreatic Neuroendocrine Carcinoma
Authors: Masafumi Ikeda, Hiroyuki Okuyama, Hideaki Takahashi, Izumi Ohno, Satoshi Shimizu, Shuichi Mitsunaga, Chigusa Morizane, Takuji Okusaka
Journal: Annals of Oncology (2014)
A study of a non-myeloablative conditioning regimen followed by allogeneic stem cell transplant (NMT) for patients with hematological malignancies using campath as part of a graft versus host disease (GVHD) strategy
Authors: T. Shore, M. W. Schuster, G. Roboz, J. P. Leonard, R. Silver, M. Coleman, E. Feldman
Journal: Journal of Clinical Oncology (2004)

6625 Background: NMT have been reported to have less toxicity than standard allografts, although they still pose a substantial risk of GVHD. We used Campath –1H (C1H) in an attempt to reduce this risk. Methods: Patients (pts) received fludarabine 120 mg/m2, one fraction of total body irradiation 200cGy and a total dose of C1H 100 mg. After progressive loss of chimerism in 5/6 patients (with 3/5 having simultaneous disease progression), the protocol was amended to decrease the C1H dose to 50 mg. Pts received cyclosporine post transplant. Leukemia pts were required to have <10% marrow blasts. Results: We evaluated 13 pts with hematologic malignancies (6 acute myeloid leukemia, 3 myelodysplasia, 1 chronic myeloid leukemia, 1 nonHodgkin's lymphoma, and 2 Hodgkin's.) Median age was 57 yrs (34 –71). Median time to engraftment (neutrophil count 500/ul., platelet count 20,000/ul.) was 19 days (9 - 30.) After protocol amendment, pts achieved chimerism with 90–100 % donor cells by day 100. 4 pts had active disease (1MDS, 1AML,1HD,1NHL) at transplant and progressed post transplant. 3 pts relapsed (2 AML, 1CML) but 1 subsequently achieved a complete remission with a donor lymphocyte infusion (DLI). 6 pts achieved a sustained remission post transplant. 5 pts had DLI; 2 to treat active disease and 3 because of loss of donor chimerism . GVHD occurred in 4 pts; Gr 1–1; Gr 2–3; Gr 3–1. 1 post transplant lymphoproliferative EBV positive plasma cell dyscrasia and 1 EBV viremia occurred. Both also had disease progression and died. Six of 12 pts had CMV viremia that cleared with antiviral therapy. Eight of 12 pts are alive with a median followup of 161 days (47–528). Conclusions: Nonmyeloablative transplantation using C1H at a total dose of 50 mg. is well tolerated and favors donor engraftment. No grade 4 GVHD occurred. DLI helped to convert mixed to full chimerism and to treat relapsed disease. CMV shedding occured in 50% of these transplants but was easily treated with pre–emptive strategies.This approach for the management of hematologic malignancies warrants further evaluation. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen