tbuckley/cabot-search huggingface dataset:
Exploring the Frontiers of Therapeutic Exon Skipping for Duchenne Muscular Dystrophy by Double Targeting within One or Multiple Exons
Authors: Annemieke Aartsma-Rus, Wendy E. Kaman, Rudie Weij, Johan T. den Dunnen, Gert-Jan. B. van Ommen, Judith C.T. van Deutekom
Journal: Molecular Therapy (2006)

Through antisense-induced single-, double-, and multiexon skipping, we have previously demonstrated restoration of dystrophin expression in Duchenne muscular dystrophy (DMD) patient-derived muscle cells in vitro. In this study we further explored the frontiers of this strategy by using specific combinations of 2′-O-methyl phosphorothioate antisense oligonucleotides (AONs) targeting either one or multiple exons. We show that skipping efficiencies may indeed be improved by targeting two putative splicing regulatory sequences within one exon. In particular, such double targeting was effective for the thus far "unskippable" exons 47 and 57. We previously reported the feasibility of multiexon skipping spanning exon 45 to exon 51, using a combination of AONs targeting both outer exons (45 and 51). This would be applicable to 13% of all DMD patients. We here explored the frontiers of multiexon skipping both to increase the number of patients that can be treated with the same set of AONs and to mimic large deletions found in relatively mildly affected BMD patients. We aimed at inducing larger multiexon-skipping stretches, such as exons 17–51, exons 42–55, and exons 45–59. However, this appeared complicated and may be dependent on cotranscriptional splicing and the size of the flanking introns.
Hepatic venous outflow obstruction in patients with polycystic liver disease: pathogenesis and treatment.
Authors: W Uddin, J K Ramage, B Portmann, P Wilson, I Benjamin, K C Tan, R Williams
Journal: Gut (1995)

Polycystic liver disease is commonly asymptomatic but may present with hepatomegaly, abdominal distension, and dull abdominal pain. Transudative ascites is a rare manifestation in these patients but may occur when portal hypertension is present resulting from associated hepatic fibrosis or after deroofing procedure of a cyst. Exudative ascites might suggest hepatic venous outflow obstruction. Four cases are described where hepatic venous outflow obstruction occurred in patients with polycystic liver disease. Three patients had orthotopic liver transplantation and one had a mesocaval shunt. Of the two patients that survived orthotopic liver transplantation both have shown considerable improvement in their symptoms. None of the patients had any confirmed procoagulant disorder. The mechanism of hepatic venous outflow obstruction in these patients seems to be mechanical compression of hepatic veins by the cysts and associated formation of thrombi in small hepatic vein tributaries. Patients with severe polycystic kidney/liver disease are at risk of hepatic venous outflow obstruction and the onset of this complication is heralded by tender hepatomegaly and presence of exudative ascites.
CHEMOTHERAPY OF TRYPANOSOME AND SPIROCHETE INFECTIONS
Authors: Wade H. Brown, Louise Pearce
Journal: The Journal of Experimental Medicine (1919)

To summarize the results obtained from these experiments, one may say that N-phenylglycineamide-p-arsonic acid is capable of exercising a very definite effect upon the course of infections produced by spirochetes of the recurrens group and by Treponema pallidum. It is more difficult to say, however, just how these effects should be interpreted. In the case of the blood spirochetes, the infection is ameliorated, and even though the spirochetes are not immediately destroyed, the infection is frequently brought to a termination which leaves the animal in a condition not unlike that produced by more powerful spirocheticidal agents. That is, the infecting organisms are either affected in such a way that they eventually die off or are destroyed by the host in such a way that no lasting immunity is developed in consequence of their destruction. Apparently much the same type of reaction occurs in the treatment of rabbits infected with Treponema pallidum. It is possible that when very large doses of the drug are used, these organisms may be completely destroyed, but it is certain that in other cases, where complete healing of the lesions is accomplished as a result of treatment, the organisms are not destroyed. Moreover, it appears that such a result can be accomplished in the presence of numerous actively motile spirochetes, and once the effect of the drug has reached this point, either the capacity of the spirochetes for stimulating reaction on the part of the tissues is lowered or else the reactivity of the tissues is reduced. At any rate., living spirochetes may remain in the tissues for considerable periods of time without giving rise to the usual tissue reaction which characterizes these infections. With either group of organisms, therefore, N-phenylglycineamide-p-arsonic acid appears to act in a manner somewhat different from that of the usual spirocheticidal agents. While it does possess a considerable degree of spirocheticidal action, its chief effect is seen in the peculiar manner in which it modifies or controls the course of these infections. Further than this, we shall not attempt to go at present. As set forth in the literature, the facts and principles upon which such experiments depend are so few as to offer almost no basis for an interpretation of these experiments. When we have had an opportunity of reporting our own experience in dealing with these infections, we may return to a consideration of the facts here reported.
Identification of novel microRNA signatures linked to human lupus disease activity and pathogenesis: miR-21 regulates aberrant T cell responses through regulation of PDCD4 expression
Authors: E. Stagakis, G. Bertsias, P. Verginis, M. Nakou, M. Hatziapostolou, H. Kritikos, D. Iliopoulos, D. T. Boumpas
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> MicroRNAs (miRNAs) regulate the expression of genes involved in immune activation. A study was undertaken to characterise the miRNA signature and identify novel genes involved in the regulation of immune responses in systemic lupus erythematosus (SLE). <h3>Methods</h3> The expression of 365 miRNAs in peripheral blood mononuclear cells of patients with SLE and healthy controls was analysed using TaqMan Low Density Arrays. The results were validated by quantitative real-time PCR and potential target genes were identified using prediction analysis software. The effect of miR-21 on T cell function was assessed by transfection with antago-miR-21 or pre-miR-21. <h3>Results</h3> A 27-miRNA signature was identified in patients with SLE; 19 miRNAs correlated with disease activity. Eight miRNAs were deregulated specifically in T cells and four miRNAs in B cells. miR-21 was upregulated and strongly correlated with SLE disease activity (r<sup>2</sup>=0.92). Compared with controls, CD4 T lymphocytes from patients with SLE had higher basal and activation-induced miR-21 expression. Silencing of miR-21 reversed the activated phenotype of T cells from patients with SLE—namely, enhanced proliferation, interleukin 10 production, CD40L expression and their capacity to drive B cell maturation into Ig-secreting CD19+CD38<sup>hi</sup>IgD−(plasma cells. Overexpression of mMiR-21 in normal T cells led to acquisition of an activated phenotype. Investigation of putative gene- targets showed that PDCD4 (a selective protein translation inhibitor) was suppressed by miR-21 and its expression was decreased in active SLE. <h3>Conclusions</h3> miRNAs represent potential biomarkers in SLE as their expression reflects underlying pathogenic processes and correlates with disease activity. Upregulated miR-21 affects PDCD4 expression and regulates aberrant T cell responses in human SLE.
Control of Portal Hypertension by Selective Mesenteric Arterial Drug Infusion.
Authors: Moreye Nusbaum
Journal: Annals of Internal Medicine (1970)

Meeting Abstracts1 May 1970Control of Portal Hypertension by Selective Mesenteric Arterial Drug Infusion.Moreye Nusbaum, M.D., Stanley Baum, M.D., William S. Blakemore, M.D.Moreye Nusbaum, M.D.Search for more papers by this author, Stanley Baum, M.D.Search for more papers by this author, William S. Blakemore, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-794_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptExperience with the selective infusion of small dosages of vasopressin directly through a catheter placed percutaneously in the superior mesenteric artery has resulted in the control of portal hypertension and hemorrhage in 10 of 11 patients. Variceal hemorrhage and portal hypertension was controlled promptly after the onset of the direct infusion of vasopressin, utilizing a continuous infusion pump. The infusions were maintained for 24 hr to 2 weeks without any complications at the catheter site with stabilization of liver function and hemodynamic status. Criteria for the establishment of the proper dosage and the monitoring of the portal pressure and splanchnic... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Moreye Nusbaum, M.D.; Stanley Baum, M.D.; William S. Blakemore, M.D.Affiliations: Philadelphia, Pa. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1970Volume 72, Issue 5 Page: 794-794 Keywords Catheters Drug regulation Drugs Hemodynamics Hemorrhage Liver Mesenteric arteries Portal hypertension Vasopressin ePublished: 1 December 2008 Issue Published: 1 May 1970 PDF downloadLoading ...
Operating room safety: 10 point plan to safe flinging
Authors: R. L. Hutchison, M. A. Hirthler
Journal: BMJ (2013)

Working in a hospital operating room is stressful, and stress can lead to adverse events.1 Several factors contribute to a surgeon’s stress, especially equipment malfunction.2 The traditional way for surgeons to deal with flawed surgical instruments is to fling them across the operating suite. This action is expedient, acts to alleviate …
SPINAL ANESTHESIA BY MAGNESIUM SULPHATE.A REPORT OF SEVEN OPERATIONS PERFORMED UNDER ITS INFLUENCE.
Authors: H. A. HAUBOLD
Journal: JAMA (1906)

<h3>EXPERIMENTS ON ANIMALS.</h3> In several series of experiments on animals<sup>1</sup>it was established that magnesium salts have very distinct anesthetic properties. Among other things it was established that by local application of solutions of magnesium sulphate on nerve trunks the conductivity and excitability of motor and sensory nerves can be temporarily abolished; that by subcutaneous injection of certain quantities of magnesium salts general anesthesia with complete recovery could be produced in several species of animals, and, finally, that by intraspinal injections into animals of comparatively small doses of a solution of magnesium sulphate a complete anesthesia and paralysis of the posterior part of these animals could be produced. These latter experiments interest us here particularly and we shall dwell on them a little longer. The experiments on dogs, cats and rabbits have demonstrated that by application of solutions of magnesium sulphate to the spinal cord, either through an opening made
A NEW ROUTINE IN HISTOPATHOLOGY
Authors: Guy Heyden, Tore Arwill, Maria Hogberg
Journal: British Journal of Dermatology (1974)

Journal Article A NEW ROUTINE IN HISTOPATHOLOGY Get access Guy Heyden, Guy Heyden Department of Oral Histopathology, Faculty of Odontology, University of Göteborg, Fack, S‐400 33 Göteborg 33, Sweden Search for other works by this author on: Oxford Academic Google Scholar Tore Arwill, Tore Arwill Department of Oral Histopathology, Faculty of Odontology, University of Göteborg, Fack, S‐400 33 Göteborg 33, Sweden Search for other works by this author on: Oxford Academic Google Scholar Maria Högberg Maria Högberg Department of Oral Histopathology, Faculty of Odontology, University of Göteborg, Fack, S‐400 33 Göteborg 33, Sweden Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 90, Issue 5, 1 May 1974, Pages 579–582, https://doi.org/10.1111/j.1365-2133.1974.tb06457.x Published: 01 May 1974
GPs approve simpler complaints and disciplinary procedure Health care in remote areas must be flexible Government endorses strategic review of pathology services European Commission reports on Europe's health
Authors: L. Beecham
Journal: BMJ (1995)

# GPs approve simpler complaints and disciplinary procedure {#article-title-2}

The General Medical Services Committee has approved the outline of new complaints and disciplinary procedures which would be simpler, quicker, and fairer for general practitioners and patients. In future the complaints and disciplinary procedures will be separated.

The complaints procedure is based on recommendations in the Department of Health's report Acting on Complaints, which was its response to the Wilson report, Being Heard. They are due to come into effect in April 1996, are investigative rather than punitive, and aim to resolve most complaints at an informal practice level. GPs would be obliged under their terms of service to operate a practice based complaints system and cooperate with a stage two procedure, which would operate if the practice based procedure did not resolve the complaint, and the new disciplinary arrangements.

Doctors would no longer be in breach of their terms of service in relation to complaints but would under the disciplinary procedure. The system of medical service committees would be abolished.

The GMSC has urged the government to reduce the time limit of one year for making a complaint and the health minister was due to announce a decision this week.

Under the stage one practice based procedure an initial response to a complaint should normally be made within two days and an explanation normally provided within two weeks.

If the stage two procedure had to be invoked health authorities would set up panels to hold informal hearings into complaints. They would have to make their report available to the authority, the complainant, and …
Pervasive Axonal Transport Deficits in Multiple Sclerosis Models
Authors: Catherine Diamante Sorbara, Naomi Elizabeth Wagner, Anne Ladwig, Ivana Nikić, Doron Merkler, Tatjana Kleele, Petar Marinković, Ronald Naumann, Leanne Godinho, Florence Martine Bareyre, Derron Bishop, Thomas Misgeld, Martin Kerschensteiner
Journal: Neuron (2014)
Rotator Cuff Disease
Authors: Samuel Whittle, Rachelle Buchbinder
Journal: Annals of Internal Medicine (2015)

Shoulder pain is a common musculoskeletal disorder and has a substantial negative effect on quality of life. Its monthly prevalence in the general population is reported to be between 18% and 31%, whereas lifetime prevalence ranges between 6.7% and 66.7%. Shoulder pain is the third most frequent musculoskeletal reason to present to primary care and accounts for up to 10% of all referrals to physical therapists. Although the natural history of shoulder pain varies and is often self-limiting,up to half of persons who present for care, particularly the elderly, might continue to have pain and/or functional disturbance for up to 2 years after presentation.
Ultraviolet radiation and immunosuppression
Authors: G.M. Murphy
Journal: British Journal of Dermatology (2009)

Journal Article Ultraviolet radiation and immunosuppression Get access G.M. Murphy G.M. Murphy Department of Dermatology, Beaumont & Mater Misericordiae Hospital, Dublin, Ireland Gillian M. Murphy. E‐mail:gmurphyoffice@eircom.net Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 161, Issue s3, 1 November 2009, Pages 90–95, https://doi.org/10.1111/j.1365-2133.2009.09455.x Published: 01 November 2009
Independent expression of fibril-forming collagens I, II, and III in chondrocytes of human osteoarthritic cartilage.
Authors: T Aigner, W Bertling, H Stöss, G Weseloh, K von der Mark
Journal: Journal of Clinical Investigation (1993)

Normal and osteoarthritic human articular cartilage was investigated by in situ hybridization for expression patterns of the fibrillar collagens type I, II, and III to evaluate phenotypic changes of articular chondrocytes related to the disease. In 11 out of 20 samples, a defined subset of chondrocytes in the superficial and upper middle zone of osteoarthritic cartilage showed significant levels of cytoplasmic alpha 1 (III) mRNA, whereas strong signals of alpha 1 (II) mRNA were found in the upper and lower middle zone, partially overlapping with the zone of alpha 1 (III) mRNA-expressing cells. The extent of type II and III collagen expression depended on the integrity of the extracellular matrix surrounding the chondrocytes, and the location within the articular cartilage. No alpha 1 (I) mRNA was detectable in osteoarthritic original articular cartilage. The alpha 1 (I) probe did, however, reveal signals in pannus-like tissue, osteophytes, and bone cells. In normal articular cartilage, no detectable levels of cytoplasmic mRNA for alpha 1(I), alpha 2 (I), or alpha 1 (III) were seen. Using specific mono- and polyclonal antibodies, we found deposition of type III collagen but hardly any of type I collagen in the superficial zone of osteoarthritic cartilage that is consistent with the in situ hybridization results. These results indicate a phenotypic alteration in a defined subset of chondrocytes in conditions of diseased cartilage, expressing and synthesizing collagen type III independently from type I collagen, but in part simultaneously with type II collagen.
6-month versus 36-month isoniazid preventive treatment for tuberculosis in adults with HIV infection in Botswana: a randomised, double-blind, placebo-controlled trial
Authors: Taraz Samandari, Tefera B Agizew, Samba Nyirenda, Zegabriel Tedla, Thabisa Sibanda, Nong Shang, Barudi Mosimaneotsile, Oaitse I Motsamai, Lorna Bozeman, Margarett K Davis, Elizabeth A Talbot, Themba L Moeti, Howard J Moffat, Peter H Kilmarx, Kenneth G Castro, Charles D Wells
Journal: The Lancet (2011)
End-of-Life Discussions and Preferences Among Persons With HIV
Authors: Neil S. Wenger
Journal: JAMA (2001)

Deficits in advance care planning leave many patients and their physicians unprepared for decisions about end-of-life care. Even though the prognosis has improved for many persons with human immunodeficiency virus (HIV) infection, a need for planning remains.To evaluate prevalence of end-of-life discussions, use of advance directives, and preferences concerning end-of-life care and their relationship with patient demographics, clinical status, psychosocial variables, and practitioner characteristics among HIV-infected persons.Cross-sectional survey of a US probability sample of 2864, which represents 231 400 adults receiving care for HIV, conducted from January 1996 to April 1997.Communication with physician regarding end-of-life issues, completion of an advance directive, preference for aggressiveness of care, and willingness to tolerate future permanent adverse health states.A total of 1432 patients (50%) discussed some aspect of end-of-life care with their practitioner and 1088 (38%) completed an advance directive. Patients were more likely to complete an advance directive after a physician discussion (odds ratio [OR], 5.82; 95% confidence interval [CI], 4.50-7.52). Practitioners discussed end-of-life care less with blacks (OR, 0.57; 95% CI, 0.39-0.83) and Latinos (OR, 0.74; 95% CI, 0.55-0.98) than with whites. Women (OR, 1.39; 95% CI, 1.05-1.84) and patients with children in the household (OR, 1.53; 95% CI, 1.12-2.10) communicated the most with practitioners about end-of-life issues. Patients infected with HIV via injection drug use (OR, 0.64; 95% CI, 0.45-0.89) and those with less education communicated the least with physicians about end-of-life issues. Less denial, greater trust in one's practitioner, and longer patient-practitioner relationship were associated with more advance care planning.Half of all persons infected with HIV are at risk of making end-of-life decisions without prior discussions with their health care practitioners. Blacks, Latinos, intravenous drug users, and less educated individuals need advance care planning interventions in clinical HIV programs.
CLINICAL OUTCOMES IN REAL-WORLD PATIENTS RECEIVING THE XIENCE V® EVEROLIMUS-ELUTING STENT PRESENTING WITH CHRONIC KIDNEY DISEASE: ONE-YEAR RESULTS FROM THE XIENCE V USA STUDY
Authors: Luis Gruberg, Allen Jeremias, David R. Rutledge, Vivian W. Mao, Weiying Zhao, Alena V. Pechonkina, Jin Wang, Olivia Wilburn, Krishnankutty Sudhir, Mitchell W. Krucoff, James B. Hermiller
Journal: Journal of the American College of Cardiology (2011)
Multimodality Management for Barcelona Clinic Liver Cancer Stage C Hepatocellular Carcinoma
Authors: Chihwan Choi, Gi Hong Choi, Tae Hyun Kim, Masatoshi Tanaka, Mao-Bin Meng, Jinsil Seong
Journal: Liver Cancer (2014)

This review summarizes the contents of a workshop on multimodality management for Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) held on July 6, 2013, under the auspices of the 4th Asia-Pacific Primary Liver Cancer Expert Meeting Scientific Advisory Committee. BCLC stage C HCC represents a varied disease spectrum and, therefore, further stratification of BCLC stage C should be explored. Although sorafenib is currently the standard treatment for BCLC stage C HCC, the survival benefits are modest and new treatment strategies are still needed. Based on the opinions of Asian experts, there are numerous alternative options aside from sorafenib for the treatment of BCLC stage C HCC, including surgical resection, hepatic arterial infusion chemotherapy, transarterial chemoembolization, and external radiotherapy. Moreover, there are several studies on the multimodality management of BCLC stage C HCC, mainly in the form of retrospective studies and a few phase I and II trials. Multimodality management with combinations of various locoregional therapies or locoregional therapies with systemic targeted therapy using sorafenib needs to be actively investigated. The Asia-Pacific clinical practice guidelines on multimodality management for BCLC stage C HCC need recommendations based on the level of evidence, the strength of the data, and the strength of recommendations of previously reported systems.
SMILE A WHILE
Authors: None Percyevsky
Journal: JAMA (1966)

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