tbuckley/cabot-search huggingface dataset:
Abstract P6-15-07: A Dose-Escalation Study with a Special Drug Delivery System (SDS) of BEZ235, a Novel Dual PI3K/mTOR Inhibitor, in Patients with Metastatic/Advanced Solid Tumors
Authors: J Rodon, J Infante, H Burris, J Tabernero, MR Ranson, N Rouyrre, V Duval, A Silva, W Hackl, J. Baselga
Journal: Cancer Research (2010)

Abstract Background: The PI3K pathway plays a major role in cancer cell growth and survival and is the most frequently altered pathway in cancer. BEZ235 is a potent and highly specific oral PI3K/mTOR inhibitor. Administered as hard-gelatine capsule, BEZ235 was well tolerated with a favorable safety profile. Available data showed that BEZ235 led to PRs (1 patient (pt) with NSCLC [PTENnull], 1 pt with ER+ breast cancer [mutation unknown]) and prolonged disease stabilization (4 to &amp;gt;24 months) in pts with PI3K pathway dysregulated tumors (N=9/51), 5/9 with ER+, 1/9 with HER2+ breast cancer. Here, we present data from patients (pts) receiving treatment with a special drug delivery system of BEZ235 (SDS) with improved PK properties (Cao SABCS 2010). Results: 22 pts have been treated with BEZ235 SDS capsule at 3 dose levels (qd): 400 mg (5); 800 mg (6), 1000 mg (11). Median age was 56 years. The most common tumor types among pts enrolled were: breast cancer (4), CRC (4) and NSCLC (3). 2/22 pts were treated for &amp;gt;3 cycles, 16/22 pts progressed within the first three cycles of treatment. The maximum tolerated dose (MTD) is 1000 mg/d. Dose-limiting toxicities (DLTs) included: 2 Grade (G)3 fatigue (800 mg and 1000 mg) and 1 G3 skin rash (at 1000 mg). The most common treatment-related AEs included: fatigue, diarrhea, nausea, vomiting (G1-3). Preliminary PK data showed a slow absorption rate, Cmax at ∼6 h post-dose (range 2-8 h). The elimination halflife is ∼6 h across doses and visits. Steady state was reached after 8 days of treatment; the mean (SD) exposures at steady state (AUC, rss) for the dose of 400, 800, and 1000 mg/d were 8864 (12210), 19060 (19860), 46010 (36150) ng*h/mL, respectively. The exposure across dose levels (AUC0- 24, SS) was above the exposure required for tumor stasis in PI3K pathway dysregulated tumors, estimated based on CT measurements in patients(Bottino SABCS 2010). Currently, the efficacy of BEZ235 SDS, alone and in combination with trastuzumab, in patients with PIK3CA mutated breast cancer is investigated. As of today 1 clinical PR was observed with BEZ235+trastuzumab in a patient with breast cancer (HER2+, PIK3CA mutated, trastuzumab refractory) with brain and peripheral metastases. Conclusions: BEZ235 SDS treatment is well tolerated. The MTD is 1000 mg/d. Available PD and efficacy data show that BEZ235 is active in breast cancer (especially PI3K pathway dysregulated tumors). Phase II studies in breast cancer combining BEZ235 SDS with other agents will start soon. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-15-07.
Australian health insurance to include preventive measures
Authors: Christopher Zinn
Journal: BMJ (2006)

The federal government has expanded Australia's private health insurance regime to encourage more coverage of preventive medicine—such as fitness programmes approved by doctors. The wide reaching changes mean that insurance companies will be able to pay for smoking cessation programmes and health plans to manage conditions such as diabetes, instead of charging for costly extra cover.

The moves were announced to soften the blow of the government's decision to sell Medibank Private, the largest of the country's 38 funds, for an estimated $A1bn (£400m; 荤600m; $800m). …
Cannabis, pneumothorax and lung bullae
Authors: A. Gill
Journal: Journal of the Royal Society of Medicine (2006)

In a recent review (February 2006 JRSM1), the relationship between pneumothorax and cannabis was questioned (or at least not highlighted). There are too many reports describing pneumothorax, pneumediastinum and even pneumoarachis associated with cannabis for this to be a coincidence particularly as many reports describe the onset of symptoms whilst actually smoking drugs. In one series 13 of 15 consecutive patients with `spontaneous' pneumomediastinum or subcutaneous emphysema admitted to `using marijuana extensively before coming to hospital' and the remaining two performed the Valsalva manoeuvre during heroin injection.2 The link between cannabis and pneumothorax/pneumomediastinum may or may not be due to barotrauma but it is quite definite. It is recognized by users and frequently discussed on their Internet message boards.

The authors of the review were in error to use a mucosal biopsy study of drug smokers which does not mention bullae as evidence against a causative link with this disease.3 Mucosal biopsies do not include alveolar lung tissue and cannot assess bullous disease. When I studied lung pathology in cannabis smokers I examined wedge resections of lung with blebs and bullae performed for recurrent pneumothorax.4 Ten of 108 patients of all ages undergoing this procedure had definite regular cannabis use recorded in their medical records. However, most patients' records did not record whether or not drugs were used and many patients whose smoking status was unrecorded showed histopathological features suggestive of cannabis use. In fact, controls for this study had to be recruited prospectively with repeated reassurance of confidentiality.

Given that patients under-report drug use, this indicates that the number of patients with bullous lung disease who smoke cannabis regularly is probably much higher than 10% (the number of regular users in this population).5
Hydrocortisone Upregulates Th2-type Cytokine and Chemokine Receptor mRNA on Human B-lymphocytes.
Authors: S. Al-Tamemi, H. Zuzan, A. Norris, A. Saenz, A. Ponton, J. Guay, O. Hajoui, T. Hudson, B. Mazer
Journal: Journal of Allergy and Clinical Immunology (2006)
Complete Molecular Remission in Chronic Myelogenous Leukemia after Imatinib Therapy
Authors: Gisela Barbany, Martin Höglund, Bengt Simonsson
Journal: New England Journal of Medicine (2002)

To the Editor: The observations of Albert et al. (April 11 issue) 1 on the protective effects of long-chain n-3 fatty acids (largely available in fish) with regard to sudden death may have profound clinical implications.These findings confirm previous observations that suggest that dietary patterns may reduce sudden death without an effect on myocardial infarction. [2]3][4] A major underlying cause of sudden death is myocardial ischemia and infarction, as suggested by the authors' definition of sudden death: "death within one hour after the onset of symptoms."These symptoms may include chest pain, and therefore some patients who die suddenly have had an ischemic event, most probably an acute myocardial infarction.In the current study, the selection criteria for enrollment in the control group excluded patients with signs or symptoms of coronary artery disease at follow-up.Therefore, we believe that the authors' conclusions, based on comparison with a population selected for the absence of signs of coronary artery disease, may be appropriate but give only a partial answer to the following question: Do these long-chain n-3 fatty acids protect against sudden death when coronary artery disease is present?The Methods section of the article suggests that the investigators could have selected an additional group of controls who had survived a documented myocardial infarction at the time that they became controls, with an approximately equal follow-up.This comparison would have greatly enhanced the importance of the presented observations.
Bacterial Flora of the Human Small Intestine
Authors: George H. Bornside
Journal: JAMA (1966)

The literature regarding the normal bacterial flora of the human gastrointestinal tract has recently been reviewed by Rosebury<sup>1</sup>and Donaldson,<sup>2</sup>and can be summarized as follows: the stomach or upper small intestine may be sterile or contain a sparse bacterial population; those bacteria found in the upper portion of the gastrointestinal tract are considered to be contaminants from the mouth and respiratory tract, and seldom exceed counts of 10<sup>5</sup>bacteria per milliliter of intestinal content; although bacteria in the terminal ileum are often of the fecal type, about 50% of specimens are sterile; an entirely different situation prevails in the colon which is more stagnant and supports a large and varied bacterial population. <h3>Intestinal Bacteria</h3> Our interest in human small intestinal flora arose from research into the lethal role of intestinal bacteria and their products during intestinal strangulation obstruction.<sup>3,4</sup>These studies have been concerned with normal
Lies to a Patient
Authors: Abha Agrawal
Journal: Annals of Internal Medicine (2008)

On Being a Doctor6 May 2008Lies to a PatientAbha Agrawal, MDAbha Agrawal, MDFrom Kings County Hospital Center, Brooklyn, NY 11203.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-148-9-200805060-00012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail It was another routine afternoon in my office practice. My next patient was a 51-year-old woman, Mrs. K., presenting for an annual physical examination and a Pap smear.Mrs. K. and I exchanged the usual greetings and pleasantries. Noting my appearance and accent, she asked me where I was born and raised. I told her about my country of birth, India, and she mentioned how eager she was to visit that beautiful country someday.During the course of taking a social history, I found out that she was a nurse, was born in Massachusetts, was married, and had 2 grown ... Author, Article, and Disclosure InformationAffiliations: From Kings County Hospital Center, Brooklyn, NY 11203.Corresponding Author: Abha Agrawal, MD, Kings County Hospital Center, 451 Clarkson Avenue, Suite 1147, Brooklyn, NY 11203; e-mail, agrawal.[email protected]com. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoTruthfulness and Personal Disclosure in the Physician–Patient Relationship David Lewis Truthfulness and Personal Disclosure in the Physician–Patient Relationship Dean Blakeley Truthfulness and Personal Disclosure in the Physician–Patient Relationship David R. Fulp Truthfulness and Personal Disclosure in the Physician–Patient Relationship Abha Agrawal Metrics Cited byLGBTQ+ Identity and Ophthalmologist BurnoutPilot Survey of Physician Assistants Regarding Lesbian, Gay, Bisexual, and Transgender Providers Suggests Role for Workplace Nondiscrimination PoliciesTruthfulness and Personal Disclosure in the Physician–Patient RelationshipDavid Lewis, BMedSc(Hon), MBBSTruthfulness and Personal Disclosure in the Physician–Patient RelationshipDean Blakeley, MDTruthfulness and Personal Disclosure in the Physician–Patient RelationshipDavid R. Fulp, MD 6 May 2008Volume 148, Issue 9Page: 707KeywordsAdolescentsBirthChildrenDeceptionGenital anatomyHuman sexual behaviorNursesSpecimen preparation and treatment ePublished: 6 May 2008 Issue Published: 6 May 2008 Copyright & PermissionsCopyright © 2008 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Insulin-induced lipoatrophy: evidence for an immune pathogenesis.
Authors: W G Reeves, B R Allen, R B Tattersall
Journal: BMJ (1980)

Skin biopsy samples from 14 diabetic patients with lipoatrophy at injection sites and from five insulin-treated diabetic patients without such lipoatrophy (controls) were examined by immunofluorescence for the deposition of immunological components. Also sera from 13 of the patients with lipoatrophy and from all of the controls were assayed for insulin-binding capacity. Biopsy samples from the edge of lipoatrophic areas (eight cases) invariably showed abnormal deposition of immunological components in dermal vessel walls, whereas no such deposition was seen in the control samples. Mean serum insulin-binding capacity was 33.1 microgram/l in the patients with lipoatrophy compared with only 4.6 microgram/l in the controls. These findings suggest that insulin-induced lipoatrophy results from the local formation of immune complexes, complement fixation, and release of inflammatory mediators from the cellular infiltrate.
Multicenter Trial of EC145 in Advanced, Folate-Receptor Positive Adenocarcinoma of the Lung
Authors: Martin J. Edelman, Wael A. Harb, Sridhar E. Pal, Ralph V. Boccia, Michael J. Kraut, Philip Bonomi, Barbara A. Conley, John S. Rogers, Richard A. Messmann, Edward B. Garon
Journal: Journal of Thoracic Oncology (2012)

EC145 is a novel folate-receptor targeted agent consisting of a folate molecule linked to a vinca alkaloid. EC20 is a technetium-labeled folate that assesses the presence of folate receptors (FR) in vivo. The objective of this study was to determine the activity of EC145 in patients with chemotherapy refractory lung adenocarcinoma, whose tumors expressed the FR as determined by EC20 imaging.Patients with advanced adenocarcinoma of the lung, Eastern Cooperative Oncology Group performance status 0 to 2, normal organ function, those who had progressed after at least two prior cytotoxic regimens, and with EC 20 uptake in at least one index lesion were eligible. The primary objective of the study was the ability to receive four or more cycles of therapy.Sixty patients were screened and 43 patients were enrolled. Eleven patients (26%) received more than four cycles (95% confidence interval [CI] 14%, 41%), and one patient had partial response (response rate (RR) = 2.3%, 95% CI 0%, 12%). Patients in whom all target tumor lesions expressed FR by EC 20 scans had a trend toward superior results in terms of clinical benefit response (50% versus 14.3 %; p = 0.10) and survival (47.2 weeks versus 14.9 weeks [HR = 0.539, p = 0.101]) compared with those in whom at least one but not all target lesions were positive for FR (FR+).EC145 demonstrated clinical activity with a good toxicity profile in this population. Uniform uptake of EC20 may predict activity of EC145 and be useful for prospective selection of patients in future trials.
Effects of long-term Irbesartan in reducing portal pressure in cirrhotic patients: comparison with propranolol in a randomised controlled study
Authors: Wilma Debernardi Venon, Monica Baronio, Nicola Leone, Elio Rolfo, Maurizio Fadda, Claudio Barletti, Luca Todros, Giorgio Saracco, Mario Rizzetto
Journal: Journal of Hepatology (2003)
Indirect Costs and the Budget for the National Institutes of Health
Authors: William H. Danforth
Journal: New England Journal of Medicine (1982)

This paper discusses the proposal that the National Institutes of Health reduce by 10 per cent the amount that universities are reimbursed for indirect costs associated with its extramural grants. This proposal represents an important policy change and must be seen as part of the total NIH budget, which includes decreased amounts for new research grants, for competing renewals, and for training grants.On the surface a reduction in reimbursement for expenditures for indirect costs may seem desirable, since it gives the appearance of benefiting the overall national research effort by increasing funds for individual research grants. However, such a . . .
Review: Graduated compression stockings reduce deep venous thrombosis in hospitalized patients
Authors: Sara Vazquez, Matthew T. Rondina
Journal: Annals of Internal Medicine (2010)

ACP Journal Club21 December 2010Review: Graduated compression stockings reduce deep venous thrombosis in hospitalized patientsSara Vazquez, PharmD, Matthew T. Rondina, MDSara Vazquez, PharmDUniversity of Utah, Salt Lake City, Utah, USA (S.V., M.T.R.)Search for more papers by this author, Matthew T. Rondina, MDUniversity of Utah, Salt Lake City, Utah, USA (S.V., M.T.R.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-153-12-201012210-02006 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationSachdeva A, Dalton M, Amaragiri SV, Lees T. Elastic compression stockings for prevention of deep vein thrombosis. Cochrane Database Syst Rev. 2010;(7):CD001484. https://pubmed.ncbi.nlm.nih.gov/20614425Clinical Impact RatingsGIM/FP/GP: Hospitalists: Hematology: Critical Care: Reference1 Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. 8th ed. Chest. 2008;133:381S-453S. [PMID: 18574271] Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Utah, Salt Lake City, Utah, USA (S.V., M.T.R.)This article was published at Annals.org on 7 December 2010. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 21 December 2010Volume 153, Issue 12Page: JC6-6KeywordsDeep vein thrombosisHemorrhageProphylaxisScientistsStrokeSurgerySystematic reviewsVascular surgeryVenous thromboembolism ePublished: 21 December 2010 Issue Published: 21 December 2010 CopyrightCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Polyvalent immunoglobulins in neonates after perinatal exposure to measles
Authors: Caroline Charlier, Sophie Hourrier, Marianne Leruez-Ville, Jean Ralph Zahar, Daniel Floret, Laurent J. Salomon, Julie Toubiana, Marc Lecuit, Alexandre Lapillonne, Olivier Lortholary, Elsa Kermorvant-Duchemin
Journal: Journal of Infection (2015)
Muscle Atrophy and Hypertrophy Signaling in Patients with Chronic Obstructive Pulmonary Disease
Authors: Mariève Doucet, Aaron P. Russell, Bertrand Léger, Richard Debigaré, Denis R. Joanisse, Marc-André Caron, Pierre LeBlanc, François Maltais
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

The molecular mechanisms of muscle atrophy in chronic obstructive pulmonary disease (COPD) are poorly understood. In wasted animals, muscle mass is regulated by several AKT-related signaling pathways.To measure the protein expression of AKT, forkhead box class O (FoxO)-1 and -3, atrogin-1, the phosphophrylated form of AKT, p70(S6K) glycogen synthase kinase-3beta (GSK-3beta), eukaryotic translation initiation factor 4E binding protein-1 (4E-BP1), and the mRNA expression of atrogin-1, muscle ring finger (MuRF) protein 1, and FoxO-1 and -3 in the quadriceps of 12 patients with COPD with muscle atrophy and 10 healthy control subjects. Five patients with COPD with preserved muscle mass were subsequently recruited and were compared with six patients with low muscle mass.Protein contents and mRNA expression were measured by Western blot and quantitative polymerase chain reaction, respectively.The levels of atrogin-1 and MuRF1 mRNA, and of phosphorylated AKT and 4E-BP1 and FoxO-1 proteins, were increased in patients with COPD with muscle atrophy compared with healthy control subjects, whereas atrogin-1, p70(S6K), GSK-3beta, and FoxO-3 protein levels were similar. Patients with COPD with muscle atrophy showed an increased expression of p70(S6K), GSK-3beta, and 4E-BP1 compared with patients with COPD with preserved muscle mass.An increase in atrogin-1 and MuRF1 mRNA and FoxO-1 protein content was observed in the quadriceps of patients with COPD. The transcriptional regulation of atrogin-1 and MuRF1 may occur via FoxO-1, but independently of AKT. The overexpression of the muscle hypertrophic signaling pathways found in patients with COPD with muscle atrophy could represent an attempt to restore muscle mass.
The Synergistic Toxicity of Pesticide Mixtures: Implications for Risk Assessment and the Conservation of Endangered Pacific Salmon
Authors: Cathy A. Laetz, David H. Baldwin, Tracy K. Collier, Vincent Hebert, John D. Stark, Nathaniel L. Scholz
Journal: Environmental Health Perspectives (2008)

BackgroundMixtures of organophosphate and carbamate pesticides are commonly detected in freshwater habitats that support threatened and endangered species of Pacific salmon (Oncorhynchus sp.). These pesticides inhibit the activity of acetylcholinesterase (AChE) and thus have potential to interfere with behaviors that may be essential for salmon survival. Although the effects of individual anticholin-esterase insecticides on aquatic species have been studied for decades, the neurotoxicity of mixtures is still poorly understood.ObjectivesWe assessed whether chemicals in a mixture act in isolation (resulting in additive AChE inhibition) or whether components interact to produce either antagonistic or synergistic toxicity.MethodsWe measured brain AChE inhibition in juvenile coho salmon (Oncorhynchus kisutch) exposed to sublethal concentrations of the organophosphates diazinon, malathion, and chlorpyrifos, as well as the carbamates carbaryl and carbofuran. Concentrations of individual chemicals were normalized to their respective median effective concentrations (EC50) and collectively fit to a nonlinear regression. We used this curve to determine whether toxicologic responses to binary mixtures were additive, antagonistic, or synergistic.ResultsWe observed addition and synergism, with a greater degree of synergism at higher exposure concentrations. Several combinations of organophosphates were lethal at concentrations that were sublethal in single-chemical trials.ConclusionSingle-chemical risk assessments are likely to underestimate the impacts of these insecticides on salmon in river systems where mixtures occur. Moreover, mixtures of pesticides that have been commonly reported in salmon habitats may pose a more important challenge for species recovery than previously anticipated.
Methionine intolerance: A possible risk factor for coronary artery disease
Authors: Douglas R. Murphy-Chutorian, Mark P. Wexman, Anthony J. Grieco, James A. Heininger, Ephraim Glassman, Gerald E. Gaull, Steven K.C. Ng, Frederick Feit, Karen Wexman, Arthur C. Fox
Journal: Journal of the American College of Cardiology (1985)
An Autoimmune Disease-Associated CTLA-4 Splice Variant Lacking the B7 Binding Domain Signals Negatively in T Cells
Authors: Lalitha Vijayakrishnan, Jacqueline M Slavik, Zsolt Illés, Rebecca J Greenwald, Dan Rainbow, Bernhard Greve, Laurence B Peterson, David A Hafler, Gordon J Freeman, Arlene H Sharpe, Linda S Wicker, Vijay K Kuchroo
Journal: Immunity (2004)