tbuckley/cabot-search huggingface dataset:
Phase I and pharmacologic studies of pyrazoloacridine, a novel DNA intercalating agent, on single-dosing and multiple-dosing schedules.
Authors: E K Rowinsky, D A Noe, L B Grochow, S E Sartorious, M K Bowling, T L Chen, B G Lubejko, S H Kaufmann, R C Donehower
Journal: Journal of Clinical Oncology (1995)

PURPOSE To determine the maximum-tolerated doses (MTDs), principal toxicities, and pharmacologic behavior of pyrazoloacridine (PZA), a novel DNA intercalator with a unique mechanism of action, on single- and multiple-dosing schedules. PATIENTS AND METHODS PZA was administered on a single-dosing schedule as a 1- to 3-hour infusion and on a multiple-dosing schedule as a 1-hour infusion daily for 5 days to cancer patients at doses ranging from 400 to 935 mg/m2 and 40 to 180 mg/m2/d every 3 weeks, respectively. RESULTS On the single-dosing 1-hour schedule, CNS toxicity, characterized by neuropsychiatric and neuromotor effects, prompted prolongation of the infusion duration to 3 hours and led to a study of PZA on a multiple-dosing schedule. Both measures resulted in lower incidence of CNS toxicity. Neutropenia was the principal toxicity and precluded dose escalation to levels greater than 750 mg/m2 on the single-dosing (3-hour) schedule and 150 mg/m2/d x 5 (total dose, 750 mg/m2) on the multiple-dosing schedule. Thrombocytopenia, anemia, and nonhematologic effects occurred less frequently. Responses were observed in several patients with platinum- and taxane-refractory ovarian carcinoma; antitumor activity was also noted in patients with cervical and colorectal carcinomas. Significant intraindividual variability characterized by the presence of multiple drug peaks and troughs was observed in the pharmacologic studies. The maximal PZA concentrations achieved in both studies exceeded drug concentrations associated with significant cytotoxicity in preclinical studies and correlated with the occurrence of CNS toxicity. CONCLUSION Neutropenia is the dose-limiting toxicity on both schedules and 750 mg/m2 and 150 mg/m2/d are the recommended starting doses of PZA on single- and multiple-dosing schedules, respectively, for minimally pretreated patients in phase II studies; slightly lower doses are recommended for more heavily pretreated subjects. The favorable toxicity profile of PZA and its antitumor activity in several refractory tumors warrant broad phase II evaluations of this agent.
Immune profiling of breast cancer patients: relationship between tumour antigen T cell responses with suppressor and effector leukocyte populations
Authors: Nicole Janssen, Graham Pawelec, Lisa Speigl, Sotirios P Fortis, Christoforos Haritos, Sonia A Perez, Constantin N Baxevanis, Jithendra Bailur, Christopher Shipp
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts It is becoming increasingly clear that the immune profile of breast cancer patients is informative for patient prognosis. Specifically, immune cells with suppressor or effector function have been shown to be valuable in the prediction of patient course on an individual basis. Our
The United Kingdom (Uk) National Cancer Research Network (Ncrn) Chemotherapy and Pharmacy Advisory Service (Cpas): Service Development and Quality Control Experience of Pharmacy Aspects in Clinical Research Protocols
Authors: P.R. Debruyne, P. Johnson, L. Pottel, S. Daniels, R. Greer, E. Hodgkinson, S. Kelly, M. Lycke, J. Samol, J. Simpson, D. Kimber, E. Loucaides, M.K. Parmar, S. Harvey
Journal: Annals of Oncology (2014)
CNS Anticancer Drug Discovery and Development Conference White Paper
Authors: Victor A Levin, Peter J Tonge, James M Gallo, Marc R Birtwistle, Arvin C Dar, Antonio Iavarone, Patrick J Paddison, Timothy P Heffron, William F Elmquist, Jean E Lachowicz, Ted W Johnson, Forest M White, Joohee Sul, Quentin R Smith, Wang Shen, Jann N Sarkaria, Ramakrishna Samala, Patrick Y Wen, Donald A Berry, Russell C Petter
Journal: Neuro-Oncology (2015)

Following the first CNS Anticancer Drug Discovery and Development Conference, the speakers from the first 4 sessions and organizers of the conference created this White Paper hoping to stimulate more and better CNS anticancer drug discovery and development. The first part of the White Paper reviews, comments, and, in some cases, expands on the 4 session areas critical to new drug development: pharmacological challenges, recent drug approaches, drug targets and discovery, and clinical paths. Following this concise review of the science and clinical aspects of new CNS anticancer drug discovery and development, we discuss, under the rubric "Accelerating Drug Discovery and Development for Brain Tumors," further reasons why the pharmaceutical industry and academia have failed to develop new anticancer drugs for CNS malignancies and what it will take to change the current status quo and develop the drugs so desperately needed by our patients with malignant CNS tumors. While this White Paper is not a formal roadmap to that end, it should be an educational guide to clinicians and scientists to help move a stagnant field forward.
CQC’s inspection of private hospitals is inadequate, report says
Authors: Gareth Iacobucci
Journal: BMJ (2015)

An analysis has identified “significant patient safety risks” at private hospitals treating NHS patients in England.

The Centre for Health and the Public Interest (CHPI) analysed data from the first 15 private hospitals to have been inspected under the Care Quality Commission’s (CQC) new regime and assessed the level of risk at each institution.1

Among the risks identified were two hospitals where consultant surgeons either had no indemnity insurance or failed to show that they had any despite it being a legal requirement. The report also found seven hospitals where clinical outcomes …
GmHs1-1, encoding a calcineurin-like protein, controls hard-seededness in soybean
Authors: Lianjun Sun, Zhenyan Miao, Chunmei Cai, Dajian Zhang, Meixia Zhao, Yanyan Wu, Xueling Zhang, Stephen A Swarm, Liwen Zhou, Zhanyuan J Zhang, Randall L Nelson, Jianxin Ma
Journal: Nature Genetics (2015)
Phase I trial of gemcitabine and CPT-11 given weekly for four weeks every six weeks
Authors: S.R. Alberts, C. Erlichman, J. Sloan, S.H. Okuno, P.A. Burch, J. Rubin, H.C. Pitot, R.M. Goldberg, A.A. Adjei, P.J. Atherton, S.H. Kaufmann
Journal: Annals of Oncology (2001)
Prehospital treatment with levetiracetam plus clonazepam or placebo plus clonazepam in status epilepticus (SAMUKeppra): a randomised, double-blind, phase 3 trial
Authors: Vincent Navarro, Christelle Dagron, Caroline Elie, Lionel Lamhaut, Sophie Demeret, Saïk Urien, Kim An, Francis Bolgert, Jean-Marc Tréluyer, Michel Baulac, Pierre Carli
Journal: The Lancet Neurology (2015)
Chemotherapy in pancreatic cancer.
Authors: Yong Tae Kim
Journal: BMJ (1981)

Chemotherapy is expected to play an important role in the treatment of pancreatic cancer because most of pancreatic cancers are being discovered at locally advanced or metastatic stages and recurrence rate is high even after the curative resection. Gemcitabine is a key agent for the first-line therapy of advanced pancreatic cancer. It can enhance the quality of life and prolong the survival of patients. Combination of erlotinib or capecitabine with gemcitabine showed a marginal survival benefit over single-agent gemcitabine. If patient's performance state is good, gemcitabine-based platinum combination therapy showed overall survival benefit compared with gemcitabine monothrapy. If the first-line palliative chemotherapy fails, 5-FU, capcitabine, or tegafur with or without combination can be used as the second-line agents. Adjuvant chemotherapy using 5-FU or gemcitabine after curative resection has overall survival benefit. However, neoadjuvant chemotherapy has not been proven to be effective in the treatment of pancreatic cancer.
Multifunctional Nanostructures for Tumor‐Targeted Molecular Imaging and Photodynamic Therapy
Authors: Hao Wu, Huihui Wang, Han Liao, Yan Lv, Xiaojie Song, Xiaojun Ma, Mingqian Tan
Journal: Advanced Healthcare Materials (2015)

A multifunctional ICG-FA-PPD nanostructure is constructed by a facile self-assembly method through the negatively charged indocyanine green (ICG)- and positively charged folic acid-modified PEI-PEG-gadoteric acid (FA-PPD). The resulting ICG-FA-PPD is not only able to be used for targeting tumors, magnetic resonance imaging (MRI), and near-infrared imaging, but, more importantly, it enables photodynamic therapy for tumor.
Abstract 14741: Genetic Defects in Protein Glycosylation as a Cause of Dyslipidemia
Authors: M A van den Boogert, Sacha D Kuil, G. K Hovingh, M. M Motazacker, G. Dallinga-Thie, J. A Kuivenhoven, R. Wevers, E. S Stroes, D. J Lefeber, A. G Holleboom
Journal: Circulation (2013)

Aim: In most of our patients, we cannot reach adequate risk reduction with current treatments for dyslipidemia. This stresses the need for a more accurate understanding of lipid metabolism in order...
Mitomycin-C and vernal conjunctivitis11The following letter addresses an article in the February issue of the Journal: Akpek EK, Hasiripi H, Christen WG, Kalayci D. A randomized trial of low-dose, topical mitomycin-C in the treatment of severe vernal keratoconjunctivitis. (Ophthalmology 2000;107:263–9)
Authors: J.D.Alexander MacLeod
Journal: Ophthalmology (2000)
Second-line chemotherapy in advanced pancreatic cancer: A retrospective, single-center analysis
Authors: T. Herrmann, D. Jaeger, W. Stremmel, C. Herrmann
Journal: Journal of Clinical Oncology (2007)

15187 Background: Patients with advanced pancreatic cancer profit from palliative chemotherapy. The role of second-line chemotherapy is not yet established. Methods: We performed a retrospective analysis in 98 patients who were treated at our department from 1/2004–6/2006 due to locally advanced or metastatic adenocarcinoma of the pancreas. Results: At the time of analysis 67 patients had died (median overall survival 9 months), 31 patients are still alive (median follow up 9 months). 12 patients were initially treated with radiochemotherapy. 86 patients received systemic chemotherapy; 43 of these patients were treated with second-line chemotherapy after disease progression. OS was significantly longer in patients who received second-line chemotherapy (10 months versus 5.0 months, p=0.023). Response to second-line chemotherapy was partial remission in 2 patients (4.6 %), stable disease in 18 patients (44.8 %), and progressive disease in 19 patients (44.2 %), in 3 patients the treatment was stopped due to toxicity (6.9 %). 12 patients received second-line treatment after early disease progression under first-line chemotherapy. 9 of these patients did not respond to second-line treatment, 2 achieved stable disease and 1 patient had partial remission. Elevated LDH and CA19.9 serum levels at the time of diagnosis were identified as negative prognostic factors. Conclusions: Prognosis of patients with advanced pancreatic cancer is still poor. Selected patients may benefit from salvage chemotherapy after failure of first-line chemotherapy. No significant financial relationships to disclose.
Prognostic factors related to dendritic cell vaccines on patients with advanced non-small cell lung cancers: a multicenter analysis
Authors: Hidenori Takahashi, Shigetaka Shimodaira, Masahiro Ogasawara, Masanori Kobayashi, Hirofumi Abe, Kazuhiro Nagai, Sunichi Tsujitani, Masato Okamoto, Yuji Morita, Yoshikazu Yonemitsu
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Dendritic cell (DC)-based cancer vaccines may have a significant benefit to patients with advanced non-small cell lung cancers (NSCLCs). However, variations among clinical studies make it difficult to compare clinical outcomes. J-SICT DC vaccine study group is composed of the
Evaluate the autonomic nervous system during the shuttle test (TS) in asthma difficult to control
Authors: Ivan Peres Costa, Jessyca Caroline dos Reis Pereira, Audrey Borghi-Silva, Dirceu Costa, Luis Vicente Franco Oliveira, Roberto Stirbulov, Luciana Maria Malosá Sampaio
Journal: European Respiratory Journal (2012)

Introduction: The autonomic nervous system (ANS) is a primary role in controlling airway caliber and its dysfunction may contribute to the pathogenesis of respiratory diseases. Objective: To evaluate the autonomic nervous system during the Shuttle Test (TS) in asthma difficult to control. Method: Twenty patients with asthma (30-52 years) and fifteen healthy subjects (30-52 years) were studied. We conducted the following procedures: controlled walk test (shuttle test) andheart rate variability. Were recorded for 360 seconds during the Shuttle Test. HRV was analyzed in the time domain (TD) (RMSSD index, ie, the root mean square of squares of differences between successive R-Ri records, and the SDNN index, ie the standard deviation of Ri- R ms in normal and in the frequency domain (FD) from the low frequency (LF) and high frequency (HF) in normalized units (NU) and LF / HF ratio. Results: In DT, the asthma group (GA) had significantly higher values for SDNN and RMSSD) during the Shuttle test, when compared with the control group (CG). In DF, the GC showed significantly higher values of the components of HF and LF and HF components. Conclusion: It can be concluded that patients with difficult to control asthma showed a reduced HRV compared with healthy during the Shuttle Walk Test with an increase in vagal activity simpatic. Thus, it can be suggested that in future studies, HRV can become a useful tool for parameters in cardiovascular risk stratification in this population, and in the evaluation of different physical therapy interventions to treat these patients.
Doctors oppose IMA meeting scheduled for Thai resort
Authors: Cheryl Travasso
Journal: BMJ (2015)

The Indian Medical Association (IMA) has postponed its upcoming meeting in the coastal town of Pattaya in Thailand, saying it will be rescheduled at a later date.

Marthanda Pillai, president of the IMA, told The BMJ that the national executive meeting, which was due to take place in November, had been postponed for logistical and internal reasons. 

On 22 November doctors from the Punjab Medical Council protested about the decision to hold the meeting in Thailand, saying that it would have been more appropriate to …
Vertebrate Neuroethology: Definitions and Paradigms
Authors: D Ingle
Journal: Annual Review of Neuroscience (1985)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Intracytoplasmic sperm injection (ICSI) in 2006: Evidence and Evolution
Journal: Human Reproduction Update (2007)

The introduction of intracytoplasmic sperm injection (ICSI) in 1992 has dramatically changed the management of severe male infertility. In severe male infertility, live birth rates with ICSI are superior to those with other non-donor treatments. In non-male infertility, however, pregnancy rates are not better with ICSI than with in vitro fertilization (IVF). With obstructive or non-obstructive azoospermia, reasonable pregnancy rates are now possible with ICSI after recovery of sperm from the testes followed by ICSI. Genetic counselling is indicated for severe male infertility, whether or not ICSI is considered. ICSI is indicated in preimplantation genetic diagnosis (PGD) to avoid contamination by extraneous DNA in the case of PCR-based testing and to increase the number of embryos available for testing. In turn, PGD may be indicated in pregnancies that are at high risk of aneuploidy because of genetic factors associated with azoospermia. As with IVF, not all couples succeed, but 2% of couples with failed ICSI cycles will conceive without treatment. ICSI outcome studies indicate that there is a significant increase in prematurity, low birthweight, and perinatal mortality associated with single and multiple births, similar to the outcomes of conventional IVF. However, as evidenced in long-term follow-up studies, the higher rates of urogenital abnormalities and increased use of healthcare may be associated with paternal characteristics.
First general outbreak of Verocytotoxin-producing Escherichia coli O157 in Denmark
Authors: C Jensen, S Ethelberg, A Gervelmeyer, E M Nielsen, K EP Olsen, K Mølbak
Journal: Eurosurveillance (2006)

This report describes the first general outbreak of verocytotoxin-producing E. coli (VTEC) in Denmark. Twenty five patients, 18 children and seven adults, with culture-confirmed VTEC O157:H- infection and indistinguishable pulsed-field gel electrophoresis DNA profiles, were identified during a six month period from September 2003 to March 2004. The outbreak strain possessed the virulence genes: eae, vtx1 and vtx2c. All patients but one presented with diarrhoea; none developed haemolytic uraemic syndrome. The outbreak was restricted to Copenhagen and surrounding areas. A case-control study including 11 cases and 55 matched controls revealed an association between VTEC O157:H- infection and shopping in a specific supermarket chain in Copenhagen and surrounding area, matched odds ratio (OR): 8.7 (95% confidence interval (CI): 1.1-71). After exclusion of three assumed secondary cases, only consumption of a particular kind of organic milk from a small dairy was associated with disease OR: 8.7 (95% CI 1.6-48). Environmental and microbiological investigations at the suspected dairy did not confirm the presence of the outbreak strain, but the outbreak stopped once the dairy was closed and thoroughly cleaned.
Coping with Problems: Attitudes Toward Children Who Set Fires
Authors: CAROLYN N. WINGET, ROY M. WHITMAN
Journal: American Journal of Psychiatry (1973)

As part of an environmental health survey, 300 urban adults were asked how they would deal with a child who set fires. Respondents who were young, of upper socioeconomic status, and with numerous interpersonal relationships and low degrees of alienation most frequently gave positive-constructive responses indicating the use of outside resources. However, only about one-third specified mental health professionals. The authors discuss the implications of these findings in terms of improved orientation of representatives of the official community as well as in decentralized and more easily accessible mental health centers.
Could be sponsored by drug companies
Authors: D. Berger
Journal: BMJ (1995)

EDITOR,—The prospect that the BMJ is even considering abandoning obituaries is too much.1 I am certain that a vast number of readers turn to the obituaries before reading anything else in the journal; this is definitely true among my friends and contemporaries (I graduated in 1991). The obituaries are truly fascinating, and, paradoxically, it is not those of the great and the good that are most interesting but …
The role of a cinema seminar in psychiatric education
Authors: G K Fritz, R O Poe
Journal: American Journal of Psychiatry (1979)

As the goals of psychiatric education are evaluated and innovative teaching methods are sought, the current cinema represents an untapped resource. Thoughtful viewing of contemporary films with serious discussion of them in a film discussion group as part of the residency training program is a useful and enjoyable teaching format that helps bridge the gap between the art and science of psychiatry.
TG20, a Transgenically-Derived Anti-CD20 Monoclonal Antibody, Exhibits Enhanced Cytotoxicity Against Cells with Low Levels of CD20
Authors: Yann Echelard, Daniel P. Pollock, Catherine De Coupade, Aurélie Groseil Olivier, Frédérique Brune, LiHow Chen, Nicholas C. Masiello, Jennifer L. Williams, William G. Gavin, Sami Chtourou, Harry M. Meade
Journal: Blood (2011)
Clinical Activity Of Idelalisib (GS-1101), a Selective Inhibitor Of PI3Kδ, In Phase 1 and 2 Trials In Chronic Lymphocytic Leukemia (CLL): Effect Of Del(17p)/TP53 Mutation, Del(11q), IGHV Mutation, and NOTCH1 Mutation
Authors: Steven E. Coutre, John P. Leonard, Jacqueline C. Barrientos, Sven De Vos, Ian Flinn, Richard R. Furman, Jennifer R Brown, Nina Wagner-Johnston, Don M. Benson, Marshall T. Schreeder, Jeff P. Sharman, Thomas Boyd, Stephen Spurgeon, Andrew D. Zelenetz, Nicole Lamanna, Thomas J. Kipps, Brad S. Kahl, Celeste M. Bello, Jan A. Burger, Kanti R. Rai, Roger Dansey, Yeonhee Kim, Leanne M. Holes, Mirella Lazarov, Ronald L. Dubowy, Susan M. O'Brien
Journal: Blood (2013)
Pentacyclic triterpenes grafted on CD cores to interfere with influenza virus entry: A dramatic multivalent effect
Authors: Sulong Xiao, Longlong Si, Zhenyu Tian, Pingxuan Jiao, Zibo Fan, Kun Meng, Xiaoshu Zhou, Han Wang, Renyang Xu, Xu Han, Ge Fu, Yongmin Zhang, Lihe Zhang, Demin Zhou
Journal: Biomaterials (2015)
Early and Late Outcomes of Surgical Treatment in Carcinoid Heart Disease
Authors: Heidi M. Connolly, Hartzell V. Schaff, Martin D. Abel, Joseph Rubin, J. Wells Askew, Zhuo Li, Jacob J. Inda, Sushil A. Luis, Rick A. Nishimura, Patricia A. Pellikka
Journal: Journal of the American College of Cardiology (2015)
Non-fibrillar collagenous proteins synthesized by rat mesangial cells.
Authors: N D Rosenblum, M J Karnovsky, B R Olsen
Journal: Journal of the American Society of Nephrology (1990)

Recent studies have shown that nonrenal extracellular matrices are composed of collagenous proteins with properties that are different from those of fibrillar collagens and type IV collagen. The structures of these newly described collagens suggest that they may provide connections between specific matrix molecules and, in so doing, partially determine the three-dimensional structure of the matrix. The molecular composition and organization of normal and diseased mesangial matrix are incompletely understood. As a means to further understand the structure of the mesangial matrix, we have further defined the collagenous proteins synthesized by rat mesangial cells. By using monospecific antibodies, we have shown that these cells secrete types III and IV collagen. Metabolic labeling and electrophoretic analysis of proteins isolated from the culture medium revealed that mesangial cells also synthesize and secrete short-chain collagenous proteins of 80, 75, and 69 kDa which differ in their binding to concanavalin A. Cell-free translation of mesangial mRNA demonstrated the presence of two additional collagenase sensitive proteins, 40 and 35 kDa in size, which were not detected in the culture medium. These results demonstrate that mesangial cells synthesize several short-chain collagenous proteins which may be similar to short-chain collagens isolated from nonrenal tissues. Further definition of these proteins will lead to a greater understanding of the extracellular matrix elaborated by mesangial cells.
ESEN : a comparison of vaccination programmes Part one: diphtheria
Authors: D Lévy-Bruhl, R G Pebody, I Veldhuijzen, M Valenciano, K Osborne
Journal: Eurosurveillance (1998)

The aim of the European Sero-Epidemiology Network (ESEN) is to coordinate and harmonise the serological surveillance of immunity to vaccine preventable diseases in eight countries in Europe (Denmark, England, France, Germany, Italy, the Netherlands, Finla