tbuckley/cabot-search huggingface dataset:
The Consult Guys - Strokes and Surgery: What and When Are the Risks?
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2015)

Web Exclusives20 October 2015The Consult Guys - Strokes and Surgery: What and When Are the Risks?FREEGeno J. Merli, MD and Howard H. Weitz, MDGeno J. Merli, MDSearch for more papers by this author and Howard H. Weitz, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W15-0009 SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The Consult Guys bring a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations.For more videos from and information on The Consult Guys, visit www.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Yehia Y. Mishriki, MD, FACPLehigh Valley Health Network10 November 2015 One issue not addressed This was probably the best "Consult Guys" presentation to date. Very informative with regards the nuances of perioperative assessment. I would have been interested in hearing whether or not the consultants favored "bridging" the patient's anticoagulation versus withholding for a few days before surgery and resuming the day after surgery. As you well know, a recent study suggested that bridging leads to more complications that not bridging. Would that apply to the patient presented? Author, Article, and Disclosure InformationAffiliations: Disclosures: Geno J. Merli, MD, reports the following: Research grants/contracts: Bristol-Myers Squibb, Janssen, Portola; Consultancies: Bristol-Myers Squibb, Janssen. Howard H. Weitz, MD, reports that he has no financial relationships or interests to disclose.Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 20 October 2015Volume 163, Issue 8Page: CG1KeywordsDisclosureResearch grantsResearch reporting guidelinesStrokeSurgery ePublished: 20 October 2015 Issue Published: 20 October 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.Loading ...
Dendritic cells revisited in human allergic rhinitis and asthma
Authors: A. Froidure, C. Shen, C. Pilette
Journal: Allergy (2015)

The role of dendritic cells (DCs) in airway allergy has been studied for 15 years; recent data has highlighted the cross talk with airway epithelial cells and environmental factors (allergens, virus) during the inception and exacerbation of allergic asthma. Although murine models have provided key information, it remains uncertain to what extent these basic mechanisms take place in human allergic disease, notably with regard to different clinical phenotypes. In the present review, we discuss new evidence regarding mechanisms of DC regulation in the mouse which could be important in human asthma. Finally, after discussing the effects of current therapies on DC biology, we focus on pathways that could represent targets for future therapies.
Abstract 824: Optimal Definition of Left Ventricular Lead Position in Cardiac Resynchronization Therapy by Myocardial Deformation Imaging
Authors: Michael Becker, Dirk Frechen, Christian Meyer, Patrick Schauerte, Karl-Christian Koch, Malte Kelm, Rainer Hoffmann
Journal: Circulation (2008)

Objective. Left ventricular (LV) lead position has crucial impact on cardiac resynchronization therapy (CRT) success. This study compared fluoroscopy and myocardial deformation imaging for optimal definition of LV lead position. Methods. In 56 heart failure patients (53±5 years, 34 men) undergoing CRT implantation myocardial deformation imaging based on tracking of acoustic markers within 2D echo images (GE Ultrasound) was performed before CRT and directly postoperative on biventricular and LV pacing mode. In a 16 segment model circumferential strain was used to determine the segment with latest peak systolic circumferential strain prior to CRT, considered as the optimal LV lead target. LV lead was defined by (1) fluoroscopy, (2) the maximal temporal difference of peak circumferential strain before-to-on CRT and (3) the earliest peak systolic circumferential strain during LV pacing. For all 3 modalities optimal LV lead position was defined as concordance or immediate neighbouring of the segment with defin...
English paediatrician to be reinstated
Authors: Annabel Ferriman
Journal: BMJ (2001)

One of the doctors who was suspended from work at North Staffordshire Hospital, Stoke on Trent, because of complaints by parents over the diagnosis of child abuse, is to be reinstated, it was announced last week.

Dr Martin Samuels, a consultant paediatrician, who was suspended in November 1999, because of complaints by parents of harassment and victimisation, has been cleared of “professional misconduct …
The potential interaction of MARCKS-related peptide and diltiazem on acrolin-induced airway mucus hypersecretion in rats
Authors: Peng Chen, Zhiping Deng, Yongchun Shen, Tao Wang, Lei Chen, Jiqiong Li, Yulin Feng, Shangfu Zhang, Yunyie Nin, Fuqiang Wen
Journal: European Respiratory Journal (2013)

Airway mucus hypersecretion is a pathophysiological feature of airway inflammatory diseases. Ca2+ entry and myristoylated alanine-rich C kinase substrate(MARCKS) translocation are important factors involved. To investigate the interaction of MARCKS-related peptide and diltiazem on mucus hypersecretion,rat model was established by inhalation of acrolein fog.MARCKS-related peptide,diltiazem or combination was administered intratracheally respectively.Rats were given pilocarpine to stimulate mucus release before sacrifices. Mucin5AC expression in BALF was measured by ELISA. Intracellular Muc5ac was detected by immunohistochemical staining/western-blot.Muc5ac mRNA was analyzed by RT-PCR.Results:MARCKS-related peptide attenuated the release of Muc5ac in BALF induced by acrolein.Diltiazem alone had no effect.However,release of Muc5ac in BALF was further reduced when challenged with simultaneous instillation with MARCKS-related peptide and diltiazem.  Moreover, the intracellular level of Muc5ac was further increased when treated with MARCKS-related peptide plus diltiazem (p
Part II: Role of Maintenance Therapy in Transplant-Ineligible Patients
Authors: Antonio Palumbo, Roberto Mina
Journal: Journal of the National Comprehensive Cancer Network (2013)

Many advances were made in the treatment of multiple myeloma since the introduction of the immunomodulatory drugs thalidomide and lenalidomide and the proteasome inhibitor bortezomib. An increasing number of clinical trials have examined consolidation/maintenance therapy as part of a sequential approach after induction therapy and demonstrated benefit in patients eligible and ineligible for transplantation. This outcome improvement reported with consolidation/maintenance therapy should be balanced against the toxicity profile, and prompt management of adverse events is necessary. This article provides an overview of the main trials including consolidation/maintenance therapy after induction for transplant-ineligible patients. Recommendations on how to manage treatment-related toxicities are also provided.
Philippe Pinel's "Memoir on Madness" of December 11, 1794: a fundamental text of modern psychiatry
Authors: D B Weiner
Journal: American Journal of Psychiatry (1992)

Philippe Pinel's "Memoir on Madness" can now be precisely dated. It was read to the Society for Natural History in Paris on Dec. 11, 1794, soon after the fall of the Jacobin dictatorship. It is thus a political document, an appeal to the Revolutionary government to build asylums where the mentally ill could be decently treated. It is translated here for the first time. Philippe Pinel (1745-1826) served as "physician of the infirmaries" at Bicêtre, the public hospice for men near Paris, from 1793 to 1795. In the "Memoir on Madness" he explains his "psychologic treatment," the principles of the humane method that made him the founder of psychiatry in France. Pinel states that mental illness is often curable. To arrive at a diagnosis, the physician must carefully observe a patient's behavior, interview him, listen carefully, and take notes. He must understand the natural history of the disease and the precipitating event and write an accurate case history. Diagnosis and prognosis can then be made. Periodic patterns of mental illness can be helpful for therapy. Usually only one faculty is affected. Patients with delusions may be malicious or murderous. They may have to be restrained; it was Pinel's assistant, Jean Baptiste Pussin, who removed the chains from the insane men at Bicêtre Hospice in 1797 and replaced them with strait-jackets. Pinel followed suit at the Salpêtrière, the public hospice for women, 3 years later. Pinel here states that one must "dominate agitated madmen while respecting human rights."
Bivalirudin Versus Heparin With or Without Glycoprotein IIb/IIIa Inhibitors in Patients With STEMI Undergoing Primary Percutaneous Coronary Intervention
Authors: Gregg W. Stone, Roxana Mehran, Patrick Goldstein, Bernhard Witzenbichler, Arnoud van’t Hof, Giulio Guagliumi, Christian W. Hamm, Philippe Généreux, Peter Clemmensen, Stuart J. Pocock, Bernard J. Gersh, Debra Bernstein, Efthymios N. Deliargyris, Philippe Gabriel Steg
Journal: Journal of the American College of Cardiology (2015)
Assessment of primary care doctor's diagnosed bronchial asthma in schoolchildren
Authors: Ole D. Wolthers
Journal: European Respiratory Journal (2011)

Rationale:  In primary care settings the clinical diagnosis of paediatric asthma is mainly based on symptoms.   Objective:  To assess diagnostic outcome in schoolchildren referred to a secondary paediatric referral centre with a suspected or established primary care doctor9s diagnosis of bronchial asthma.   Methods:  Children with a suspected or established primary care doctor9s diagnosis of bronchial asthma were included in the survey. At referral and during a 6 months evaluation period patient characteristics, history, symptoms, signs and results of type 1 allergy tests, spirometry, post bronchial beta-2 agonist dilation tests, 4-weeks daily measurement of peak flow rates, corticosteroid reversibility trials and exercise challenge tests were entered into a pre-defined electronic form. The secondary centre diagnosis of asthma was based on these data.   Results:  665 consecutively referred children aged 5-15 (mean 8.1) years, 233 girls (35%) and 432 boys (65%), were included in the study. 183 (27.5%) children had a referral diagnosis of suspected asthma, 482 (72.5%) an established referral diagnosis of asthma. In the latter group 316 children (65.5%) were on inhaled steroids at the time of referral, 166 ((34.5%) were not. In the groups of suspected and established asthma the diagnosis was confirmed in 82 (44.8%) and 200 (41.5%), respectively.   Conclusions:  In more than half of schoolchildren with a suspected or established primary care doctor9s diagnosis of asthma referred to a secondary paediatric referral centre the diagnosis may not be confirmed. Sensitivity and specificity of the diagnosis of asthma in schoolchildren established in primary care settings need further improvement.
Enhancement of epidermal regeneration by biosynthetic epidermal growth factor.
Authors: G L Brown, L Curtsinger, J R Brightwell, D M Ackerman, G R Tobin, H C Polk, C George-Nascimento, P Valenzuela, G S Schultz
Journal: The Journal of Experimental Medicine (1986)

Epidermal regeneration depends on mitosis and migration of keratinocytes. Epidermal growth factor is known to stimulate growth of keratinocytes in vitro, thus it might be expected to promote wound healing. The results of this study show that topical application of biosynthetic human epidermal growth factor accelerates epidermal regeneration in split-thickness wounds and partial-thickness burns. The significant enhancement of epidermal regeneration suggests the potential for clinical use of epidermal growth factor for accelerating healing of burns, wounds from trauma, diabetic ulcers, skin graft donor sites, and others.
Incidence and characterization of secondary myelodysplastic syndrome and acute myelogenous leukemia following high-dose chemoradiotherapy and autologous stem-cell transplantation for lymphoid malignancies.
Authors: D L Darrington, J M Vose, J R Anderson, P J Bierman, M R Bishop, W C Chan, M E Morris, E C Reed, W G Sanger, S R Tarantolo
Journal: Journal of Clinical Oncology (1994)

To analyze the risk of developing myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) following autologous bone marrow transplantation (ABMT) or peripheral stem-cell transplantation (PSCT) and to determine the impact on failure-free survival (FFS).Patients underwent ABMT or PSCT for the treatment of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) at the University of Nebraska Medical Center. For those patients who went on to develop MDS/AML, controls were selected and a case-control-within-a-cohort study undertaken.Twelve patients developed MDS or AML a median of 44 months following ABMT/PSCT. The cumulative incidence (P = .42) and the conditional probability (P = .32) of MDS/AML were not statistically different between HD and NHL patients. Age greater than 40 years at the time of transplant (P = .05) and receipt of a total-body irradiation (TBI)-containing regimen (P = .06) were predictive for developing MDS/AML in patients with NHL.There is an increased risk of MDS/AML following ABMT/PSCT for lymphoid malignancies. NHL patients age > or = 40 years at the time of transplant and who received TBI are at greatest risk.
Haemoglobin, Smoking and Peripheral Vascular Disease
Authors: W M Castleden, Kingsley Faulkner, A K House, Alan Watt
Journal: Journal of the Royal Society of Medicine (1981)

One hundred and four patients with peripheral vascular disease requiring operation were reviewed retrospectively with respect to age, sex, preoperative haemoglobin, smoking habits and diabetic status. The preoperative haemoglobin levels and smoking status in 63 non-diabetic male patients with peripheral vascular disease were compared with a matched group of individuals treated for inguinal hernia. For all patients there was a significant correlation between smoking habits, preoperative haemoglobin level and the presence of peripheral vascular disease. The mechanisms by which smoking may damage the vascular tree are reviewed.
Mycolic acids, a promising mycobacterial ligand for targeting of nanoencapsulated drugs in tuberculosis
Authors: Yolandy Lemmer, Lonji Kalombo, Ray-Dean Pietersen, Arwyn T. Jones, Boitumelo Semete-Makokotlela, Sandra Van Wyngaardt, Bathabile Ramalapa, Anton C. Stoltz, Bienyameen Baker, Jan A. Verschoor, Hulda S. Swai, Chantal de Chastellier
Journal: Journal of Controlled Release (2015)

The appearance of drug-resistant strains of Mycobacterium tuberculosis (Mtb) poses a great challenge to the development of novel treatment programmes to combat tuberculosis. Since innovative nanotechnologies might alleviate the limitations of current therapies, we have designed a new nanoformulation for use as an anti-TB drug delivery system. It consists of incorporating mycobacterial cell wall mycolic acids (MA) as targeting ligands into a drug-encapsulating Poly dl-lactic-co-glycolic acid polymer (PLGA), via a double emulsion solvent evaporation technique. Bone marrow-derived mouse macrophages, either uninfected or infected with different mycobacterial strains (Mycobacterium avium, Mycobacterium bovis BCG or Mtb), were exposed to encapsulated isoniazid-PLGA nanoparticles (NPs) using MA as a targeting ligand. The fate of the NPs was monitored by electron microscopy. Our study showed that i) the inclusion of MA in the nanoformulations resulted in their expression on the outer surface and a significant increase in phagocytic uptake of the NPs; ii) nanoparticle-containing phagosomes were rapidly processed into phagolysosomes, whether MA had been included or not; and iii) nanoparticle-containing phagolysosomes did not fuse with non-matured mycobacterium-containing phagosomes, but fusion events with mycobacterium-containing phagolysosomes were clearly observed.
Bronchial response to nebulized antibiotics in children with cystic fibrosis
Authors: HL Chua, GG Collis, PN Le Souef
Journal: European Respiratory Journal (1990)

Nebulized antibiotics are being used increasingly in children with cystic fibrosis. We assessed the effect of nebulized antibiotic solutions of varying tonicity on lung function in 12 children aged 5-15 yrs with cystic fibrosis. Baseline forced expiratory volume in one second and (FEV1) was measured, followed by a single nebulization of normal saline (272 mosmol.kg-1), tobramycin (248 mosmol.kg-1), or ticarcillin (3,080 mosmol.kg-1). All children received each of these, administered randomly, one per day. FEV1 was remeasured 5, 15 and 30 min after completion of the nebulization. Ticarcillin (mean fall 10.7% (SD 8.9)) caused a larger fall in FEV1 than normal saline (4.8% (4.3), p less than 0.05). The fall in FEV1 for ticarcillin was greater than for tobramycin (1.2% (2.0), p less than 0.05). Normal saline did not result in a significantly larger fall in FEV1 than tobramycin (p greater than 0.05). Bronchoconstriction to ticarcillin persisted at 30 min. We conclude that nebulized antibiotics can affect lung function in children with cystic fibrosis if the solutions are hypertonic.
Clinical usefulness of end-tidal CO2 profiles during rapidly-incremental exercise in patients with idiopathic and chronic thromboembolic pulmonary hypertension
Authors: Roberta Ramos, Eloara Ferreira, Arakaki-Ota Jaquelina, Erika Treptow, Luiz Nery, J. Alberto Neder
Journal: European Respiratory Journal (2013)

Rationale : Low CO 2  set-point and inequalities in ventilation/perfusion distribution can lead to reduced end-tidal partial pressure for CO 2  during incremental exercise in pulmonary arterial hypertension (PAH). Whether progressive or sudden decreases in exercise PETCO 2  could be helpful in indicating more severe disease remains unclear.  Methods : 43 patients with chronic thromboembolic pulmonary hypertension (CTEPH) (50 ± 13 yrs, mPAP 53 ± 11 mmHg) and 18 with idiopathic PAH (39 ± 14 yrs, mPAP 63 ± 17 mmHg) performed a ramp-incremental exercise test. According to PETCO 2 , they were separated into: 1) Group A with a normal response; 2) Group B, showing an abrupt decrease and other signs of exercise-induced right-to-left shunt (EIS); and 3) Group C, showing a progressive decrease but without EIS.  Results : In CTEPH, Group B (n = 21/43, 48%) had worse haemodynamics (cardiac index= 1.9±0.6 vs 2.3±0.6 L/min/m 2 ), more impaired exercise performance (peak O 2  uptake= 12±2 vs 14±2 mL/kg/min) and higher ventilatory response (ΔV9E/VCO 2 = 70±22 vs 47±8, p Conclusion : Abnormal decrease in PETCO 2  during exercise is more commonly found in CTEPH than PAH and regardless its association with right-to-left shunt.should be clinically valued as a non-invasive marker of disease severity in both diseases.
Premature Senescence Is a Primary Fail-safe Mechanism of ERBB2-Driven Tumorigenesis in Breast Carcinoma Cells
Authors: Tatjana M. Trost, Ekkehart U. Lausch, Stephan A. Fees, Steffen Schmitt, Thorsten Enklaar, Dirk Reutzel, Lili R. Brixel, Peter Schmidtke, Marko Maringer, Ilka B. Schiffer, Carolin K. Heimerdinger, Jan G. Hengstler, Gerhard Fritz, Ernst O. Bockamp, Dirk Prawitt, Bernhard U. Zabel, Christian Spangenberg
Journal: Cancer Research (2005)

Abstract The receptor tyrosine kinase ERBB2 plays a central role in the development of breast cancer and other epithelial malignancies. Elevated ERBB2 activity is believed to transform cells by transmitting mitogenic and antiapoptotic signals. Here we show that tightly regulated overexpression of oncogenic ERBB2 in human breast carcinoma cells does not stimulate proliferation but provokes premature senescence, accompanied by up-regulation of the cyclin-dependent kinase inhibitor P21WAF1/CIP1. A similar effect was caused by retrovirus-mediated overexpression of oncogenic ERBB2 in low-passage murine embryonic fibroblasts. In contrast to previous observations based on constitutively overexpressing cell lines, P21 induced by tetracycline-regulated ERBB2 localizes to the nucleus in arrested cells. P21 up-regulation seems to be independent of the P53 tumor suppressor protein, and senescence-associated phenotypic alterations are reversed by specific inhibition of P38 mitogen-activated protein kinases. Functional inactivation of P21 by antisense oligonucleotides is sufficient to prevent cell cycle arrest as well as the senescent phenotype, thereby identifying the P21 protein as the key mediator of hypermitogenic cell cycle arrest and premature senescence in breast carcinoma cells. Our results may thus indicate that premature senescence represents an inherent anticarcinogenic program during ERBB2-driven mammary tumorigenesis. We propose a multistep model for the process of malignant transformation by ERBB2 wherein secondary lesions either target P21 or downstream effectors of senescence to bypass this primary fail-safe mechanism.
A Score to Guide the Decision for Retreatment After 2 Lines of Systemic Palliative Therapy for Solid Tumors. a Prospective Study
Authors: B. Chanez, M. Gilabert, A. Madroszyk, F. Rousseau, D. Perrot, F. Bertucci, P. Viens, J. Raoul
Journal: Annals of Oncology (2014)
Noninvasive Imaging of Tumor PD-L1 Expression Using Radiolabeled Anti–PD-L1 Antibodies
Authors: Sandra Heskamp, Willemijn Hobo, Janneke D.M. Molkenboer-Kuenen, Daniel Olive, Wim J.G. Oyen, Harry Dolstra, Otto C. Boerman
Journal: Cancer Research (2015)

Abstract Antibodies that block the interaction between programmed death ligand 1 (PD-L1) and PD-1 have shown impressive antitumor activity. Patients with tumors expressing PD-L1 are most likely to respond to this treatment. The aim of our study was to develop a noninvasive imaging technique to determine tumor PD-L1 expression in vivo. This could allow selection of patients that are most likely to benefit from anti–PD-1/PD-L1 treatment and to monitor PD-L1 expression during therapy. The monoclonal antibody PD-L1.3.1 was radiolabeled with Indium-111 (111In) and characterized using PD-L1–expressing MDA-MB-231 cells. Subsequently, the optimal antibody dose and time point for imaging was determined in mice with MDA-MB-231 xenografts. Finally, SPECT/CT imaging was performed in xenograft models with different PD-L1 expression levels and tumor sections were analyzed for PD-L1 expression using IHC. The optimal antibody dose of 111In-PD-L1.3.1 (Kd = 1 nmol/L) for SPECT/CT imaging was ≤1 μg. Highest tumor-to-normal tissue contrast was obtained at days 3 and 7 after injection. 111In-PD-L1.3.1 SPECT/CT showed efficient accumulation in high PD-L1–expressing tumors (MDA-MB-231 and SK-Br-3), whereas no specific uptake was observed in tumors with low or no detectable levels of PD-L1 (SUM149, BT474, and MCF-7). SPECT/CT and autoradiography showed a very heterogeneous distribution of 111In-PD-L1.3.1 within the tumor. In conclusion, this is the first study showing the feasibility of noninvasive in vivo imaging of PD-L1 expression in tumors. 111In-PD-L1.3.1 showed efficient and specific uptake in PD-L1 expressing xenografts. This technique may enable patient selection for PD-1 and PD-L1–targeted therapy. Cancer Res; 75(14); 2928–36. ©2015 AACR.