tbuckley/cabot-search huggingface dataset:
Utility of cetuximab-cross reactive IgE as a predictive biomarker for cetuximab associated severe infusion reactions
Authors: Douglas Robinson, David Mauro, Christine Chung, Floyd Fox, Maria Lundberg, Hans Oman, Trixia Camacho, Mary Storms
Journal: Clinical Cancer Research (2008)

B24    Background : Cetuximab, a chimeric IgG1 monoclonal antibody, is approved for use in colorectal and head and neck cancers. Severe infusion reactions (SIR) occur in approximately 3% of patients receiving cetuximab; approximately 90% of reactions occur during initial infusion (ERBITUX, US Package Insert. November 2007). Higher infusion-reaction rates have been noted in the southeast regions of the United States (O’Neil B, et al.  J Clin Oncol,  2007). Existing evidence indicates that most SIRs are mediated by pre-existing IgE antibodies that cross-react to cetuximab (Chung CH, et al.  N Egl J Med,  2008)   Objective:  The primary objective of this study is to evaluate the association between the presence of pretreatment IgE antibodies cross-reactive to cetuximab and the occurrence of SIRs in subjects receiving their initial infusion of cetuximab.   Methods  :  This retrospective study was a pooled analysis of 559 banked serum or plasma samples (106 samples from case-controlled subjects, and 453 from non-case controlled subjects) to assess the presence of pretreatment IgE antibodies and their association with SIRs. Samples were taken from subjects identified as participants in either a cetuximab clinical trial protocol or as part of physician-prescribed therapy, irrespective of tumor type. Cetuximab-cross reactive IgE was detected using an ImmunoCAP ®  Allergen Test. The criteria for SIR included: 1) signs and symptoms that are described as: “hypotension,” “hypoxia,” “angioedema,” “unarousable,” or “unresponsive;” 2) onset of severe infusion-related symptoms  within 1 hour  of the cetuximab infusion; 3) need for parenteral medications to treat reaction, and 4) physician decision to discontinue the subject from further cetuximab treatment.   Results :   For the subjects in the case-control subset, pre-treatment IgE antibodies cross reactive to cetuximab are significantly associated (p Conclusion:  Although the presence of cetuximab-cross reactive IgE cannot completely account for all cases of cetuximab-related infusion reactions, these findings suggest a close association between the presence of pretreatment IgE antibodies cross-reactive to cetuximab and the occurrence of severe hypersensitivity reactions in subjects receiving their initial infusion of cetuximab.
Lesson of the week: Horse allergy in children
Authors: G. Roberts
Journal: BMJ (2000)

Horse dander may be the “hidden” allergen responsible for a child's asthma 

Allergy to pets, such as cats and dogs, causes significant morbidity in children.1 Apart from immediate symptoms of hypersensitivity, allergens from pets are associated with chronic childhood asthma.1 2 Clinicians are less familiar with horse allergy. Our clinical experience suggests that it is an important problem, even in an urban environment. Despite a lack of obvious exposure to horse dander this allergen may be responsible for a child's asthma. We present three of the 28 cases of horse allergy seen recently in our clinic.



Peak expiratory flow in nine year old boy exposed to horse dander from his sister's riding gear. Lung function deteriorated each weekend apart from one his sister spent away. Once his sister gave up riding, variability in peak flow disappeared, with no dips below 200/min



Case 1 —Within minutes of riding a pony at a fete, an eight year old boy developed angio-oedema and respiratory distress. On initial assessment in the accident and emergency department, he was tachypnoeic with a saturation of 90% in air. He improved after treatment with oxygen, nebulised salbutamol, intravenous hydrocortisone, and intravenous chlorpheniramine. Skin prick testing produced a 6 mm weal to horse dander and a 3 mm weal to house dust mite (positive histamine control, 3 mm). He was advised to avoid horses, to carry chlorpheniramine in case of accidental exposure, and to use inhaled salbutamol and intramuscular adrenaline in the event of respiratory symptoms.

Case …
Investigation of the Involvement of <i>Echium plantagineum</i> (Paterson's Curse) in Seasonal Allergy
Authors: C. Katelaris, B. A. Baldo, M. E. H. Howden, P. A. Matthews, R. S. Walls
Journal: Allergy (1982)

The possible allergenicity of an insect pollinated weed, Echium plantagineum, was investigated in a rural area of Australia. Sixty-one subjects with respiratory allergy were studies. Positive skin test reactions to defatted ammonium bicarbonate extract of pollen were found in over 60% of subjects, and positive RAST tests in a similar number. The question of crossreactivity between weed pollens is discussed. The pollen of E. plantagineum was shown to reach the atmosphere in significant amounts about 1 month before the peak grass pollinating period. Evidence that the pollen of E. plantagineum becomes airborne and elicits an IgE response suggests that further attention should be directed to weed pollens as potential allergens.
Women with gene mutation may respond to chemotherapy differently
Authors: Deborah Josefson
Journal: BMJ (2001)

Women who harbour mutations in BRCA1, a gene implicated in some types of hereditary breast cancer, may respond differently to chemotherapy from those lacking such mutations, a new study has found.

Researchers from Thomas Jefferson University Medical Center in Philadelphia, Pennsylvania, and the Burnham Institute in LaJolla, California, presented these findings recently at the annual meeting of the American Association for Cancer Research in New Orleans, Louisiana.

The work highlights the heterogeneity of cancers and the emergence of pharmacogenomics, foretelling a time when chemotherapeutic regimens will be tailor made according to the individual genetic profiles of patients and …
The Conundrum of Functional Mitral Regurgitation in Chronic Heart Failure⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Maurice Enriquez-Sarano, Didier F. Loulmet, Daniel Burkhoff
Journal: Journal of the American College of Cardiology (2008)
Expression of the Neural Cell Adhesion Molecule CD56 Is Associated With Short Remission Duration and Survival in Acute Myeloid Leukemia With t(8; 21)(q22; q22)
Authors: Maria R. Baer, Carleton C. Stewart, David Lawrence, Diane C. Arthur, John C. Byrd, Frederick R. Davey, Charles A. Schiffer, Clara D. Bloomfield
Journal: Blood (1997)
641. Tetracycline-Inducible Human GDNF Expression Mediated by a Single AAV Vector
Authors: Abdelwahed Chtarto, Catherine Melas, David Blum, Jean-Marie Jaspar, Thierry Velu, Jacques Brotchi, Marc Levivier, Liliane Tenenbaum
Journal: Molecular Therapy (2004)

Neuroprotective gene therapy for Parkinson's disease, consisting in GDNF gene transfer into the striatum has been proposed using various viral vectors (Bilang-Bleuel et al., 1997; Kirik et al., 2000; Kordower et al., 2000; Georgievska et al., 2002). Undesirable effects of inapropriate expression of GDNF have been described in some of these studies. Therefore, precise control of transgene expression is a prerequisite for the design of optimal and safe clinical protocols. The use of regulatable promoters may provide the control of gene expression required for optimal dosage and period of expression of the therapeutic gene.
Abstract 57: Substrates of protein kinase C drive cell rac1-dependent motility
Authors: Susan A. Rotenberg, Xin Zhao, Shatarupa De
Journal: Cancer Research (2015)

Abstract This laboratory has identified and/or characterized substrates of PKC that upon phosphorylation give rise to motility, an aspect of metastasis. By use of the traceable kinase method, we discovered that alpha-tubulin and Cdc42 effector protein-4 (CEP4) are PKC substrates. Phosphorylation of alpha-tubulin stimulates its incorporation into microtubules (MTs), consequently increasing the stability and prolonged growth of MTs and leading to the activation of the small GTPase Rac1. CEP4 undergoes phosphorylation by PKC that results in its release from Cdc42, whereupon CEP4 binds a guanine nucleotide exchange factor (GEF) that in turn activates Rac1 GTPase. These results imply that Rac1 acts as a node in pathways driven by phosphorylated PKC substrates. Since translocation of IQGAP to the membrane is known to be promoted by Rac1, a role is explored in non-transformed human MCF-10A cells that express a specific phospho-mimetic mutant substrate. In addition, the phospho-mimetic mutant for each substrate expressed in human metastatic MDA-MB-231 cells produces different morphologies in 3-D growth assays. This research is being supported by NIH CA125632. Citation Format: Susan A. Rotenberg, Xin Zhao, Shatarupa De. Substrates of protein kinase C drive cell rac1-dependent motility. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 57. doi:10.1158/1538-7445.AM2015-57
Abstract 11826: Device Detected Atrial Fibrillation Poses Significant Risk of Heart Failure Related Hospitalization
Authors: George H Crossley, Andrew Boyle, R Hardwin Mead, Tracy Bergeman
Journal: Circulation (2014)

Background: Implantable cardioverter-defibrillators (ICDs) collect advanced diagnostics on the progression of the patient’s heart disease. Arrhythmia detection algorithms continuously identify atrial arrhythmias. Methods: The CONNECT (Clinical Evaluation of Remote Notification to Reduce Time to Clinical Decision) study was a multicenter, prospective, randomized evaluation involving 1980 randomized patients from 136 clinical sites who underwent an ICD implant and followed for 15 months. Health care utilization data included all CV-related hospitalizations, emergency department visits, and clinic office visits. The analysis here focuses on heart failure (HF) related hospitalizations. Device-detected atrial arrhythmias were collected throughout follow-up. A non-parametric estimate of the nonlinear relationship between average atrial tachycardia / atrial fibrillation (AT/AF) burden per day and hazard of HF-related hospitalization or death was modeled via a third-order P-spline. The number of AT/AF episodes greater than 12 hours long was tested as a time-dependent covariate in a Cox model. Results: Information was available on arrhythmia detection in 1939 of 1980 randomized patients. There were 1540 patients with at least one device-detected AT/AF episode. Estimation of average AT/AF burden per day and risk of HF-related hospitalization or death indicated that the risk of an event increased with increasing AT/AF burden and that the risk was consistently higher with AT/AF episodes ≥ 12 hours per day. The incremental hazard ratio of HF-related hospitalization or death associated with a 12 hour AT/AF episode was 2.58 (CI: 1.57--4.24; p = 0.0002). The risk remains after adjustment for other clinical variables of interest. Conclusions: Device-detected AT/AF episodes of at least 12 hours in duration pose significant and increased risk for HF-related hospitalizations.
Abstract 3755: Restoring sensitivity to cisplatin or TRAIL by targeting drug resistance master regulators in endometrial cancer
Authors: Xiangbing Meng, Shujie Yang, Xinjun Wang, Yichen Jia, Yuping Zhang, Kimberly K. Leslie
Journal: Cancer Research (2014)

Abstract Understanding the molecular mechanisms of drug resistance is vital to enhance the efficacy of current therapeutic regimens. In particular, metadherin (MTDH) and FOXM1 overexpression has been independently demonstrated to have a critical role in chemoresistance. Overexpression of MTDH correlates with poor clinical outcome in many cancers, including endometrial cancer. Our previous study showed that endometrial cancer cells are sensitive to the combination treatment of tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL) with histone deacetylase (HDAC) inhibitor LBH589, an effect that could be enhanced by depletion of MTDH. In this study, we focused on the therapeutic strategies to restore sensitivity to chemotherapeutic agent cisplatin or apoptosis-inducing TRAIL by disrupting drug resistance genes FOXM1 or MTDH. CUDC907 is a novel investigational dual inhibitor designed to target PI3K and HDACs. The high frequency of PI3K /PTEN/AKT pathway dysregulation in endometrial cancer suggests that CUDC907 will also be effective in this disease. Indeed, CUDC907 potently induced apoptosis when combined with TRAIL in MTDH-depleted endometrial cancer cells. Cisplatin is a frontline treatment for advanced endometrial cancers. However, drug resistance causes treatment failure. Although the detailed mechanisms of drug resistance are still elusive, gradual induction of FOXM1 and its downstream target gene network may be involved in the development of resistance to cisplatin. We found that co-treatment with cisplatin and the Nedd8 conjugation system inhibitor MLN4924 restored sensitivity to cisplatin by down-regulating drug resistant gene FOXM1. These findings imply that simultaneously depleting drug resistant master genes, such as MTDH and FOXM1, is a potentially novel avenue for reversing therapeutic resistance to current chemotherapy and targeted therapies in patients with endometrial cancer. Citation Format: Xiangbing Meng, Shujie Yang, Xinjun Wang, Yichen Jia, Yuping Zhang, Kimberly K. Leslie. Restoring sensitivity to cisplatin or TRAIL by targeting drug resistance master regulators in endometrial cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3755. doi:10.1158/1538-7445.AM2014-3755
Fortnightly Review: Pulse oximetry: a practical review
Authors: C D Hanning, J M Alexander-Williams
Journal: BMJ (1995)

Pulse oximetry is arguably the greatest advance in patient monitoring since electrocardiography.It enables oxygenation, an important physiological variable that is poorly detected by clinical means, to be monitored continuously, simply, and non- invasively.Hypoxaemia is commonly found in all aspects of medical practice and is a major cause of organ dysfunction and death.Pulse oximetry should be widely available and used routinely in clinical practice both in primary care and in hospital.
Abstract 11462: Neurocognitive Function and Silent Cerebral Thromboemboli Following Atrial Fibrillation Catheter Ablation
Authors: Mohammed Qintar, Muhammad Hammadah, Peter Hanna, Melanie Panko, Kurt Niebaur, Richard Naugle, Mina Chung
Journal: Circulation (2014)

Introduction: Silent cerebral thromboemboli following pulmonary vein isolation (PVI) catheter ablation for atrial fibrillation (AF) have been reported, but their clinical impact on neurocognitive dysfunction or longer term persistence remains unclear. Hypothesis: There is no difference in neurocognitive function tested 3-6 months after AF ablation in patients with silent cerebral thromboemboli. Methods: In a prospective pilot study, patients presenting for PVI were approached for inclusion. Consenting patients underwent a battery of 8 neurocognitive tests (see Table) and diffusion-weighted MRI (dMRI) within 3 days before procedure. A follow up dMRI was done within 3 days post procedure. The neurocognitive battery was repeated at 3-6 months after ablation. Results: Of 20 patients included, 6 patients (30%) had a new silent cerebral lesion on the follow up dMRI. A third MRI was done in 2 patients and their dMRI was back to normal. Radiofrequency ablation was done in 18 patients (90%) and Cryo ablation for t...
Circulating endothelial progenitor cells and residual in vivo thromboxane biosynthesis in low-dose aspirin-treated polycythemia vera patients
Authors: Francesca Santilli, Mario Romano, Antonio Recchiuti, Alfredo Dragani, Angela Falco, Gianfranco Lessiani, Francesca Fioritoni, Stefano Lattanzio, Domenico Mattoscio, Raimondo De Cristofaro, Bianca Rocca, Giovanni Davì
Journal: Blood (2008)
Organ failures on admission in patients with Ebola virus disease
Authors: Julien Bordes, Frédéric Janvier, Marc Aletti, Thierry de Greslan, Nicolas Gagnon, Jean Cotte, Claire Rousseau, Magali Billhot, Jean Marie Cournac, Ludovic Karkowski, Sophie Moroge, Sandrine Duron, Thierry Carmoi, Gilles Cellarier
Journal: Intensive Care Medicine (2015)
Transient stress response protects against cisplatin nephrotoxicity
Authors: Guiyan Xu, Marie Helen Hanigan
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

5877 

Hydration with saline and administration of mannitol are used clinically to reduce the nephrotoxicity of cisplatin. To identify the mechanism of this protective effect we used a renal proximal tubule cell line. Increasing the salt concentration in the media, thereby raising the osmolarity from 230 mOsm/l to 310 mOsm/l, reduced the toxicity of cisplatin. We have shown previously that this protective effect, which is within the physiologic range of serum osmolarity, is not due to altered uptake of cisplatin. In this study we found that altering the extracellular salt concentration induced a transient stress response in the cell that protected against cisplatin toxicity. We pretreated sets of cell with medium containing varying levels of sodium chloride, then changed the medium on all cells to the same medium, exposed the cells to cisplatin for 3hr and measured viability at 72hr. The pretreatment caused the cells to equilibrate in various osmotic environments. Pre-equilibrating the cells in a low salt medium then increasing the salt concentration induced the protective stress response against cisplatin toxicity. The degree of protection increased with the time of pretreatment from 10 min to a maximum effect with 2h of pretreatment. We also analyzed the duration of the stress response after increasing the osmolarity of the extracellular medium. The response was maintained for at least 4h, but was gone at 24h. Changing the osmolarity of the external medium induced measurable changes in cell volume. Reducing the osmolarity from 350 mOsm/l to 230 mOsm/l resulted in cells swelling to their largest volume within 1min, the cells then underwent a regulatory volume decrease returning to their normal volume within 20min. The change in sensitivity to cisplatin was not a direct consequence of a change in cell volume as the effect on the cell was maintained beyond the time at which the cells re-equilibrated to their normal volume. Cisplatin kills the cells through a caspase-3 dependent apoptotic pathway. Caspase 3 activity is significantly lower in cells protected from cisplatin toxicity by the elevated salt. These data demonstrate that the change in osmolarity signals a transient stress response. These data indicate that in patients serum osmolarity prior to cisplatin administration can significantly affect nephrotoxicity of the drug. Studies to identify the molecular pathways involved in this response are on going.
Drug company lobbyist joins Oxfam's cheap drugs campaign
Authors: Roger Dobson
Journal: BMJ (2001)

A senior lobbyist in the pharmaceutical industry is leaving his job to help to spearhead the battle for cheaper drugs to be made available in the developing world. David Earnshaw, director of European government affairs for SmithKline Beecham, will next month join Oxfam and lead its campaign on access to medicines.

Oxfam has been at the forefront of the growing confrontation over the costs of drugs to the developing world, especially AIDS and HIV treatment, and Mr Earnshaw is highly critical …
Therapeutic Marijuana Use Supported While Thorough Proposed Study Done
Authors: M Mitka
Journal: JAMA (1999)

ADVOCATES FOR THE MEDICAL USE ofmarijuanareceivedsupportrecently fromInstituteofMedicine (IOM), recommendations that clinical trialsanddrugdevelopmentshouldproceed. But its acceptance into the general population of prescribed drugs appears to be years away—if it happens at all. The coinvestigators of the report, Marijuana and Medicine: Assessing the Science Base, said advances in cannabinoid science over the last 16 years offer opportunities for the development of medical marijuana. The report summarizes and analyzes what is known about the medical use of marijuana, emphasizing evidence-based medicine. The investigators said the data suggest marijuana may help with pain relief, nausea, and appetite stimulation. Still, there are downsides to marijuana, said John A. Benson, Jr, MD, coprincipal investigator of the report and dean and professor of medicine emeritus at Oregon Health Sciences University School of Medicine in Portland. “Marijuana’s potential as medicine is seriously undermined by the fact that people smoke it, thereby increasing their chance of cancer, lung damage, and problems with pregnancies, including low birth weight,” Benson said. “For that reason, we do not recommend smoking marijuana for long-term medical use. While we see a future in the development of chemically defined cannabinoid drugs, we see little future in smoked marijuana as a medicine.” Cannabinoids are the group of compounds related to -tetrahydrocannabinol (THC), the primary psychoactive ingredient in marijuana. TWO POINTS OF VIEW Quick to pick up on the smoking comments was the White House Office of National Drug Control Policy (ONDCP), whose director, Gen Barry R. McCaffrey, has been critical of legalizing marijuana for medical use. In
Estrone-induced Mammary Tumors in the Rat II. Effect of Alterations in the Hormonal Environment on Tumor Induction, Behavior, and Growth
Authors: J. Harry Cutts
Journal: Cancer Research (1964)

Female rats were given implants of estrone pellets to study mammary tumor development and growth.  In the latter half of the induction period but before mammary tumors had developed additional hormones (estrogen testosterone growth hormone or progesterone) were administered.  In other groups hormonal treatment was not instituted until the tumors were well developed.  Oophorectomy was performed at the time of the initial implantation of the estrone pellet or later during the induction period (200 days).  Adrenalectomies were done 200 days after pellet administration and hypophysectomies were performed at 125 days.  Administration of additional estrogen reduced the latent period for mammary tumor induction following the implantation but did not alter the course of established tumors.  Testosterone growth hormone or progesterone increased the latent period and caused temporary regression of the established tumors.  Ovariectomy and adrenalectomy prolonged the time required for tumor induction.  Tumors failed to develop in hypophysectomized animals.