tbuckley/cabot-search huggingface dataset:
820. Highly Efficient Exon-Skipping and Sustained Correction of Muscular Dystrophy Using an Adeno-Associated Viral Vector
Authors: Aurelie Goyenvalle, Adeline Vulin, Jean Claude Kaplan, Olivier Danos, Luis Garcia
Journal: Molecular Therapy (2005)

Top of pageAbstract
In Duchenne Muscular Dystrophy (DMD), the lack of Dystrophin results in a series of catastrophic events that lead to muscle fiber death and muscle wasting. Dystrophin is a modular protein with a central rod domain composed of 24 spectrin-like repeats and truncated proteins missing some of these repeats can be fully functional or at least partly deficient as seen in patients with mild (Becker) forms of DMD. In a majority of severe DMD patients that presents out of frame alterations of the dystrophin transcript, a translational open reading frame would be restored by eliminating selected exon(s) from the pre mRNA. Exon skipping naturally occurs during dystrophin mRNA processing giving rise to rare revertant fibers that contain shortened proteins. It can be forced using antisense sequences delivered as synthetic oligonucleotides, or attached to a small nuclear (sn) RNA, notably U7. A |[ldquo]|double-target|[rdquo]| U7SmOPT containing antisense sequences from introns 22 and 23 (U7-SD23/BP22 ) was introduced in an AAV vector and packaged as an AAV2/1 pseudotype. Adult mdx mice were injected into the Tibialis Anterior, or submitted to whole limb arterial perfusion, and analysed between 2 and 13 weeks. Dystrophin transcripts missing exon 23 were detected by RT-PCR, representing 15% of the amplified material at two weeks and becoming the major species (60 to 70%) at one month. The Dystrophin protein was readily detected both by Western blot on muscle extracts and by immunofluorescence on tissue sections were restoration of the Dystrophin Associated Complex was also documented. The levels of rescued dystrophin was 3 % of normal at 2 weeks and 50 to 80% thereafter. The treated muscles were shown to recover normal contractile and mechanical properties by measuring resistance to eccentric contractions. Fiber resistance to exercise-induced damage was also restored, as seen using Evans Blue exclusion. The level and stability of U7-induced exon skipping that we observe in vivo in the context of an AAV vector is unparalleled, and provides a strong rational for the development of this approach in the clinic.
Analysis of the role of von Willebrand factor, platelet glycoprotein VI-, and α2β1-mediated collagen binding in thrombus formation
Authors: Yasuaki Shida, Natalia Rydz, David Stegner, Christine Brown, Jeffrey Mewburn, Kate Sponagle, Ozge Danisment, Bredon Crawford, Barbara Vidal, Carol A. Hegadorn, Cynthia M. Pruss, Bernhard Nieswandt, David Lillicrap
Journal: Blood (2014)
Medicine in Cambodian Refugee Camps
Authors: Allen D. Soffer, Henry Wilde
Journal: Annals of Internal Medicine (1986)

Abroad1 October 1986Medicine in Cambodian Refugee CampsALLEN D. SOFFER, M.D., HENRY WILDE, M.D.ALLEN D. SOFFER, M.D., HENRY WILDE, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-105-4-618 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAn estimated 10 to 20 million persons today are refugees, having been forced from their countries of birth by war, famine, or political or religious persecution. Whereas satisfactory long-term political solutions to their problems are often extraordinarily difficult to procure, basic needs such as food, shelter, and medical care must be fulfilled immediately if these people are to survive. Acute medical problems of refugees typically include malnutrition, infectious disease, and, in some situations, war-related trauma, each of which requires a rapid and sustained response from the international medical community. Relief workers are faced with an unusually challenging task: to provide...References1. SHAWCROSS W. The Quality of Mercy. New York: Simon & Schuster; 1984. Google Scholar2. High Commissioner's press conference on his return from Thailand and Viet Nam. Refugees. 1984;11(Nov):12. Google Scholar3. The northernmost camp. Refugees. 1986;29(May):16. Google Scholar4. . The CCSDPT Handbook. Paris: duMaurier Associates International: 1982. Google Scholar5. Situation in Cambodia. Dep State (US) Bull. 1986;86(Mar):58. Google Scholar6. Leadership squabbles sap KPNLF's strength. Bangkok Post. 1985; Oct 5. Google Scholar7. MASTRO T. UNBRO Medical Coordinators Report. CCSDPT Med Subcommittee Minutes. 1985; Aug 8: 15. (Available from CCSDPT, 2948-B Soi Somprasong 3, Petchburi Road; Bangkok, Thailand). Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ALLEN D. SOFFER, M.D.; HENRY WILDE, M.D.Affiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byTrauma Care for Forced MigrantsResiliency with Forced Migrants: A Qualitative Study of Providers and Forced Migrants through a Resilience PerspectiveThe Cradle of the New Humanitarian System? International Work and European Volunteers at the Cambodian Border Camps, 1979–1993More on Medicine in Refugee CampsTHOMAS C. JONES, M.D.Medicine in Cambodian Refugee CampsRUDI CONINXMedicine in Cambodian Refugee CampsCHRISTOPHER ELIAS, M.D., VINCENT IACOPINO, M.D., Ph.D.Health Care in Cambodian Refugee CampsTIMOTHY D. MASTRO, M.D. 1 October 1986Volume 105, Issue 4Page: 618-621KeywordsBirthCyclic adenosine monophosphateFoodHospital medicineInfectious diseasesMalnutritionStarvation ePublished: 1 December 2008 Issue Published: 1 October 1986 Copyright & Permissions©1986 American College of PhysiciansPDF downloadLoading ...
P100 Successful eradication of respiratory tract MRSA in cystic fibrosis: a retrospective study
Authors: H Green, R Gadhok, K Alshafi, D Bilton, NJ Simmonds
Journal: Thorax (2013)

<h3>Introduction</h3> The prevalence of pulmonary MRSA infection in cystic fibrosis (CF) has been increasing and is associated with accelerated pulmonary function decline and higher mortality rates. Eradication is generally recommended but there is no consensus of the optimal regimen. The current prevalence at our centre is low (3%, n = 20). <h3>Method</h3> Retrospective review of adult patients with newly acquired MRSA infection (2007–2012) confirmed by ≥1 positive sputum culture. Data were retrieved from clinical records. “New” infection was confirmed by ≥3 consecutive preceding negative MRSA cultures over ≥12 months. Reflective of changing practice towards MRSA eradication at our centre, antibiotic therapy was categorised as either “conventional” (pre-2008) - a single oral agent, or “contemporary” (2008 + ) using dual oral therapy (based on sputum susceptibilities). Our primary outcome was successful MRSA eradication from sputum at 3 months. <h3>Results</h3> 32 infection episodes (n = 25) were identified. 19 patients had a single episode of infection, 5 had 2 and 1 patient had 3, each separated by an MRSA-free period of ≥12 months. 13 episodes were treated by conventional approaches (n = 13), and 13 by contemporary means (n = 12). Eradication was not attempted for 6 episodes. Eradication at 3 months was confirmed by negative sputum cultures after treatment by conventional or contemporary regimens in 45% and 80% episodes, respectively (p = NS). Combined Rifampicin/Fusidic acid (Rif/Fus) and single agent tetracyclines were the most widely used regimens (treatment duration, median 2 weeks (range 1.4–4)). Rif/Fus was used for 8 infection episodes (n = 8), achieving eradication rates at 3 months of 100% (6/6 patients). Negative MRSA sputum cultures were maintained in 75% (6/8) patients at 6 months and 37.5% (3/8) at 12 months. Tetracyclines were used for 9 infection episodes (n = 9), achieving eradication rates of 42.9% at 3 months (3/7), 33.3% at 6 months (3/9) and 33.3% at 12 months (3/9). Rif/Fus was more likely to achieve eradication at 3 months compared with tetracyclines (p = 0.03), but this did not maintain statistical significance at 6 or 12 months. <h3>Conclusion</h3> Our findings demonstrate contemporary treatment with an antibiotic combination, particularly Rif/Fus, to be an effective MRSA eradication strategy. This requires validation with a prospective controlled trial.
Prediction of the incidence, recurrence, and persistence of atopic dermatitis in adolescence: A prospective cohort study
Authors: Astrid S. Peters, Jessica Kellberger, Christian Vogelberg, Holger Dressel, Doris Windstetter, Gudrun Weinmayr, Jon Genuneit, Dennis Nowak, Erika von Mutius, Katja Radon
Journal: Journal of Allergy and Clinical Immunology (2010)
A NEW BOTTLE HOLDER ELIMINATING CORKS
Authors: W. Barclay Stephens
Journal: JAMA (1927)

The device here pictured and described is the materialization of an idea that had been "floating" around in my mind for some time. So well has it filled the need for which it was created that I feel impelled to pass the idea on to my fellows. It serves both as a holder and as corks for the bottles. A material saving of time and temper is effected by reason of the fact that the bottles are always in their same relative position and therefore quickly located, and with a fillip of the thumb or finger instantly opened and as easily closed. Thus is avoided the annoyance of having to look for the needed bottle, the use of both hands to remove the cork, which often sticks, and the overturning of the bottles with the consequent staining of of the stand. For six months it has been in daily
Time-resolved characterization of cAMP/PKA-dependent signaling reveals that platelet inhibition is a concerted process involving multiple signaling pathways
Authors: Florian Beck, Jörg Geiger, Stepan Gambaryan, Johannes Veit, Marc Vaudel, Peter Nollau, Oliver Kohlbacher, Lennart Martens, Ulrich Walter, Albert Sickmann, René P. Zahedi
Journal: Blood (2013)
Darbepoetin decreased transfusions and fatigue, but increased adverse effects in patients with chronic kidney disease, diabetes, and anemia
Authors: Tejas V. Patel
Journal: Annals of Internal Medicine (2010)

ACP Journal Club16 March 2010Darbepoetin decreased transfusions and fatigue, but increased adverse effects in patients with chronic kidney disease, diabetes, and anemiaTejas V. Patel, MD, MPH, FACP, FASNTejas V. Patel, MD, MPH, FACP, FASNBrigham and Women’s Hospital, Boston, Massachusetts, USA (T.V.P.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-152-6-201003160-02009 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationPfeffer MA, Burdmann EA, Chen CY, et al. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med. 2009;361:2019−32. https://pubmed.ncbi.nlm.nih.gov/19880844Clinical Impact RatingsEndocrinology: Hematology: Nephrology: References1 Canadian Erythropoietin Study Group. Association between recombinant human erythropoietin and quality of life and exercise capacity of patients receiving haemodialysis. BMJ. 1990;300:573-8. [PMID: 2108751] Google Scholar2 Besarab A, Bolton WK, Browne JK, et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med. 1998;339:584-90. [PMID: 9718377] Google Scholar3 Singh AK, Szczech L, Tang KL, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med. 2006;355:2085-98. [PMID: 17108343] Google Scholar4 Drüeke TB, Locatelli F, Clyne N, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med. 2006;355:2071-84. [PMID: 17108342] Google Scholar Author, Article, and Disclosure InformationAffiliations: Brigham and Women’s Hospital, Boston, Massachusetts, USA (T.V.P.)This article was published at Annals.org on 2 March 2010. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 16 March 2010Volume 152, Issue 6Page: JC3-9KeywordsAnemiaChronic kidney diseaseFatigueHeart failureMedical dialysisMyocardial infarctionRenal failureStrokeType 2 diabetes ePublished: 16 March 2010 Issue Published: 16 March 2010 CopyrightCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
HPA-1a phenotype–genotype discrepancy reveals a naturally occurring Arg93Gln substitution in the platelet β3 integrin that disrupts the HPA-1a epitope
Authors: Nicholas A. Watkins, Elisabeth Schaffner-Reckinger, David L. Allen, Graham J. Howkins, Nicolaas H. C. Brons, Graham A. Smith, Paul Metcalfe, Michael F. Murphy, Nelly Kieffer, Willem H. Ouwehand
Journal: Blood (2002)
Lewis A. Conner
Authors: Jeffrey Fisher
Journal: Circulation (2000)

Abstract —Lewis A. Conner, MD (1867 to 1950), was a pioneer in public health cardiology, cardiac rehabilitation, and cardiac psychology. He helped establish the Burke Rehabilitation Hospital and was the founding president of the New York and American Heart Associations (AHA). Dr Conner was the founder of the American Heart Journal , America’s first medical subspecialty journal, and the official publication of the American Heart Association until 1950, when Circulation was created. Conner spent more than a half-century on the staff of the New York Hospital and Cornell University Medical College and was Chairman of Medicine from 1916 to 1932. During this time, he created the innovative Cornell Pay Clinic and united the “old” New York Hospital with the new and scientifically-oriented Cornell University Medical College on a modern and inspiring urban campus. An extraordinary clinician and a humanist with great equanimity, Conner devoted his career to the Oslerian tradition of scholarship, leadership, and organization in the quest for improved patient care. This article contains newly discovered biographic material on Dr Conner and explores his professional and personal connection to Sir William Osler.
Isotretinoin and Risk for Inflammatory Bowel Disease
Authors: Mahyar Etminan, Steven T. Bird, Joseph A. Delaney, Brian Bressler, James M. Brophy
Journal: JAMA Dermatology (2013)

<h3>Objective</h3>To examine the association between isotretinoin and the risk for inflammatory bowel disease (IBD) among women of reproductive age.<h3>Design</h3>Nested case-control study and meta-analysis.<h3>Setting</h3>A US health claims database.<h3>Participants</h3>We formed a cohort of women aged 18 to 46 years who had received at least 1 oral contraceptive prescription from May 1, 2001, through December 31, 2009. The IBD cases were required to have 3 health care contacts with documentation of IBD or a single health care contact followed by use of a drug to treat IBD. Twenty controls were selected for each case using incidence-density sampling, matched on age and date of diagnosis.<h3>Main Outcome Measures</h3>Risk ratios (RRs) were formed for incident cases of IBD associated with the use of isotretinoin. A subgroup analysis examined the risk for IBD among those diagnosed as having Crohn disease (CD) and ulcerative colitis (UC). A meta-analysis of published and unpublished studies assessing isotretinoin and IBD used a random-effects model to estimate a pooled RR.<h3>Results</h3>In the case-control study, we identified 2159 IBD cases (1056 with UC and 1103 with CD) and matched them with 43 180 controls. Only 10 cases (0.46%) and 191 controls (0.44%) were exposed to isotretinoin. The adjusted RR for IBD was 0.99 (95% CI, 0.52-1.90). The RRs for UC and CD were 1.10 (95% CI, 0.44-2.70) and 0.91 (0.37-2.25), respectively. For the meta-analysis, the pooled RR for IBD for the 5 studies was 0.94 (95% CI, 0.65-1.36).<h3>Conclusions</h3>The results of this study do not suggest an increase in the risk for IBD, including UC or CD, with use of isotretinoin. Because inflammatory acne in children and adolescents carries a high psychological burden, clinicians should not be discouraged from prescribing this drug owing to a putative association with IBD.
Focal Therapy: Patients, Interventions, and Outcomes—A Report from a Consensus Meeting
Authors: Ian A. Donaldson, Roberto Alonzi, Dean Barratt, Eric Barret, Viktor Berge, Simon Bott, David Bottomley, Scott Eggener, Behfar Ehdaie, Mark Emberton, Richard Hindley, Tom Leslie, Alec Miners, Neil McCartan, Caroline M. Moore, Peter Pinto, Thomas J. Polascik, Lucy Simmons, Jan van der Meulen, Arnauld Villers, Sarah Willis, Hashim U. Ahmed
Journal: European Urology (2014)

Focal therapy as a treatment option for localized prostate cancer (PCa) is an increasingly popular and rapidly evolving field.
Inhibition of platelet-aggregating activity in thrombotic thrombocytopenic purpura plasma by normal adult immunoglobulin G.
Authors: E C Lian, P T Mui, F A Siddiqui, A Y Chiu, L L Chiu
Journal: Journal of Clinical Investigation (1984)

Plasma from patients with thrombotic thrombocytopenic purpura (TTP) caused the aggregation of autologous and homologous platelets, and effect which was inhibited by normal plasma. IgG purified from seven normal adults at a concentration of 0.7 mg/ml completely inhibited the platelet aggregation induced by plasma obtained from two TTP patients with active disease. The inhibition of platelet aggregation by human adult IgG was concentration dependent, and the inhibitory activity of human IgG was neutralized by rabbit antihuman IgG. Fab fragments inhibited the TTP plasma-induced platelet aggregation as well as intact IgG, whereas Fc fragments had no effect. Platelet aggregation caused by ADP, collagen, epinephrine, or thrombin was not affected by purified human IgG. The prior incubation of IgG with TTP plasma caused a significantly greater reduction of platelet aggregation by TTP plasma than that of IgG and platelet suspension, suggesting that the IgG inhibits TTP plasma-induced platelet aggregation through direct interaction with platelet aggregating factor in TTP plasma. IgG obtained initially from five infants and young children under the age of 4 yr did not possess any inhibitory activity. When one of the children reached 3 yr of age, his IgG inhibited the aggregation induced by one TTP plasma, but not that caused by another plasma. The IgG procured from the same boy at 4 yr of age inhibited the aggregation induced by both TTP plasmas. The IgG purified from the TTP plasma during active disease failed to inhibit the aggregation caused by the same plasma. After recovery, however, the IgG effectively inhibited aggregation. These observations suggest that platelet-aggregating factors present in the TTP plasma are heterogeneous in nature and that the IgG present in the normal adult plasma, which inhibits the TTP plasma-induced platelet aggregation, may be partially responsible for the success of plasma infusion therapy in TTP.
Intravascular lymphomatosis presenting as adult respiratory distress syndrome
Authors: E. Peter Gabor, Thomas Sherwood, Karen E. Mercola
Journal: American Journal of Hematology (1997)

An unusual case of intravascular lymphomatosis caused by small noncleaved, non-Burkitt's lymphoma, which presented with adult respiratory distress syndrome, is described. Extensive invasion of the small- and medium-size blood vessels of the lung, liver, spleen, kidneys, heart, esophagus, stomach, small and large intestines, bladder, and brain—but not the bone marrow or peripheral blood—is documented. The possible mechanism and the unusual features of this case are discussed in comparison with previously reported cases. The pertinent literature is reviewed. The problem of diagnosing this pathological entity is emphasized. Am. J. Hematol. 56:155–160, 1997. © 1997 Wiley-Liss, Inc.
Childhood obesity and consumption of fizzy drinks: Play outside to reduce childhood obesity
Authors: Alan Sutton
Journal: BMJ (2004)

Editor—Preventing childhood obesity by reducing the consumption of carbonated drinks was studied by James et al.1 The rise in childhood obesity is paralleled by the rise in parental fears of the risks to children of being unaccompanied outdoors. I find it strange that the simple solution, to let children play outside more, is dismissed …
Erlotinib and Bevacizumab Have Synergistic Activity against Melanoma
Authors: Nikolaus Schicher, Verena Paulitschke, Alexander Swoboda, Rainer Kunstfeld, Robert Loewe, Peter Pilarski, Hubert Pehamberger, Christoph Hoeller
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Melanoma is one of the most aggressive types of cancer with currently no chance of cure once the disease has spread to distant sites. Therapeutic options for advanced stage III and IV are very limited, mainly palliative, and show response in only ∼20% of all cases. The presented preclinical study was done to investigate the influence of a combined treatment of the epidermal growth factor receptor inhibitor erlotinib and the vascular endothelial growth factor monoclonal antibody bevacizumab in melanoma. Experimental Design and Results: The epidermal growth factor receptor was expressed in all cell lines tested, and treatment with erlotinib did inhibit the activation of the MEK/extracellular signal-regulated kinase and AKT signaling pathways. Whereas in vitro no influence on tumor cell proliferation was seen with erlotinib or bevacizumab monotherapy, a decreased invasive potential on erlotinib treatment in a three-dimensional Matrigel assay was observed. Furthermore, both drugs inhibited proliferation and sprouting of endothelial cells. In vivo, in a severe combined immunodeficient mouse xenotransplantation model, reduction in tumor volume under combined treatment with erlotinib and bevacizumab was superior to the additive effect of both single agents. This was associated with reduced cell proliferation, increased apoptosis, and a reduction in tumor angiogenesis compared with control or single treatment groups. Likewise, the reduction in the extent of lymph node and lung metastasis was most pronounced in animals treated with both drugs. Conclusion: The presented data strongly support the use of a combination of erlotinib and bevacizumab as a novel treatment regimen for metastatic melanoma.
A randomized controlled trial of interferon alfa-2b as therapy for chronic non-A, non-B hepatitis
Authors: G. Saracco, F. Rosina, M.R.Torrani Cerenzia, V. Lattore, L. Chiandussi, V. Gallo, R. Petrino, A.G. De Micheli, E. Donegani, A. Solinas, A. Deplano, A. Tocco, P. Cossu, C. Pintus, E. David, G. Mazzucco, G. Verme, M. Rizzetto
Journal: Journal of Hepatology (1990)
Prevention of Impairment Among Residents in Training
Authors: Barry Blackwell
Journal: JAMA (1986)

The rigors of residency training and the rites of passage endured between graduation and practice have been cataloged over the years in a variety of biographical and anecdotal formats, including books that range from scholarly surveys<sup>1</sup>to best-selling novels.<sup>2</sup>Norman Cousins'<sup>3</sup>earlier editorial on this topic identified internship as "the weakest link in the entire chain of physician training" and provoked a lively debate in the correspondence columns ofThe Journalregarding the degree to which the experience provided legitimate preparation for practice or was a hazardous form of hazing. The national survey by Smith and co-workers4 published in this issue ofThe Journalprovides a much needed source of information with which to temper the debate. Their major finding is that 0.9% of internal medicine residents take a leave of absence because of emotional impairment during their training, declining from a peak of 1.4% during internship to