tbuckley/cabot-search huggingface dataset:
Biodistribution Analysis of Oncolytic Adenoviruses in Patient Autopsy Samples Reveals Vascular Transduction of Noninjected Tumors and Tissues
Authors: Anniina Koski, Simona Bramante, Anja Kipar, Minna Oksanen, Juuso Juhila, Lotta Vassilev, Timo Joensuu, Anna Kanerva, Akseli Hemminki
Journal: Molecular Therapy (2015)

In clinical trials with oncolytic adenoviruses, there has been no mortality associated with treatment vectors. Likewise, in the Advanced Therapy Access Program (ATAP), where 290 patients were treated with 10 different viruses, no vector-related mortality was observed. However, as the patient population who received adenovirus treatments in ATAP represented heavily pretreated patients, often with very advanced disease, some patients died relatively soon after receiving their virus treatment mandating autopsy to investigate cause of death. Eleven such autopsies were performed and confirmed disease progression as the cause of death in each case. The regulatory requirement for investigating the safety of advanced therapy medical products presented a unique opportunity to study tissue samples collected as a routine part of the autopsies. Oncolytic adenoviral DNA was recovered in a wide range of tissues, including injected and noninjected tumors and various normal tissues, demonstrating the ability of the vector to disseminate through the vascular route. Furthermore, we recovered and cultured viable virus from samples of noninjected brain metastases of an intravenously treated patient, confirming that oncolytic adenovirus can reach tumors through the intravascular route. Data presented here give mechanistic insight into mode of action and biodistribution of oncolytic adenoviruses in cancer patients. In clinical trials with oncolytic adenoviruses, there has been no mortality associated with treatment vectors. Likewise, in the Advanced Therapy Access Program (ATAP), where 290 patients were treated with 10 different viruses, no vector-related mortality was observed. However, as the patient population who received adenovirus treatments in ATAP represented heavily pretreated patients, often with very advanced disease, some patients died relatively soon after receiving their virus treatment mandating autopsy to investigate cause of death. Eleven such autopsies were performed and confirmed disease progression as the cause of death in each case. The regulatory requirement for investigating the safety of advanced therapy medical products presented a unique opportunity to study tissue samples collected as a routine part of the autopsies. Oncolytic adenoviral DNA was recovered in a wide range of tissues, including injected and noninjected tumors and various normal tissues, demonstrating the ability of the vector to disseminate through the vascular route. Furthermore, we recovered and cultured viable virus from samples of noninjected brain metastases of an intravenously treated patient, confirming that oncolytic adenovirus can reach tumors through the intravascular route. Data presented here give mechanistic insight into mode of action and biodistribution of oncolytic adenoviruses in cancer patients.
<b>Addressing Depression and Suicide Among Physician Trainees—Reply</b>
Authors: Matthew L. Goldman, Ravi N. Shah, Carol A. Bernstein
Journal: JAMA Psychiatry (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
John M Templeton Jr
Authors: N. Stafford
Journal: BMJ (2015)

Paediatric surgeon, philanthropist, and head of the John Templeton Foundation



In the latter part of 1957, John M Templeton Jr received some bad news—he would have to undergo surgery to repair his left knee. Templeton, the son of mutual funds pioneer, billionaire, and philanthropist John Templeton Sr, had received the injury playing American football, when he was crunched hard simultaneously by three opposing players.

Templeton’s doctor, Frank Stinchfield, head of orthopaedic surgery at Columbia University in New York City, explained to the 17 year old boy that to allow his knee to heal properly, the crushed ligament and cartilage would have to be removed. Rather than being worried that his knee would be sliced open, Templeton, known throughout his life by the nickname Jack, became fascinated with the idea of surgery.

“I wanted to participate in my own case,” Templeton wrote 50 years later in his autobiography, John M Templeton Jr: Physician, Philanthropist, Seeker .1 “I asked the anaesthetist to give me a spinal, which would allow me to be awake during the operation. I even hoped that they would put up some mirrors so that I could watch the operation, but they flatly refused.” …
Abstract 13714: Coronary Artery Plaque in Elite Women Marathon Runners Compared with Sedentary Controls: Coronary CTA Analysis
Authors: Kelly Wickstrom, Ross F Garberich, Sue Duval, Denise Windenburg, Stephen C Oesterle, William Roberts, John R Lesser, Kevin M Harris, Robert S Schwartz
Journal: Circulation (2011)

Background: Recent coronary artery studies suggest that elite male marathon runners may paradoxically have increased plaque formation. However, little is known about elite women athletes, since com...
A Layman Considers Migraine
Authors: Walter B. Sheppard
Journal: Annals of Internal Medicine (1932)

Article1 June 1932A Layman Considers MigraineWALTER B. SHEPPARDWALTER B. SHEPPARDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-5-12-1532 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA layman, who has been subject to migraine for forty-seven years; who is quite familiar with its voluminous literature, and who is fairly well versed in what little is known about the human metabolism, may possibly have made some observations worthy of notice by the medical fraternity.ETIOLOGYMigraine is not an ache, but an acute pain, typically localized above and posterior to the supra-orbital process; but it may rarely be parietal or occipital, and it may switch its site in different attacks or in the same attack. It is a distinct pathological entity, always inherited, though in transmission it... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Denver, Colorado*Received for publication, February 19, 1932. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1932Volume 5, Issue 12Page: 1532-1539KeywordsMigrainePain ePublished: 1 December 2008 Issue Published: 1 June 1932 PDF downloadLoading ...
Development of target-specific liposomes for delivering small molecule drugs after reperfused myocardial infarction
Authors: Siva Sai Krishna Dasa, Ryo Suzuki, Michael Gutknecht, Lindsey T Brinton, Yikui Tian, Erik Michaelsson, Lennart Lindfors, Alexander L Klibanov, Brent A French, Kimberly A Kelly
Journal: Journal of Controlled Release (2015)
New epigenetic drug targets
Authors: William Nelson
Journal: Clinical Cancer Research (2008)

FO01-03  The progressive acquisition of genomic alterations is a defining feature of all human cancers: cancer cells are known to carry a variety of genetic defects, including gene mutations, deletions, translocations, and amplifications, that endow the cells with new capabilities for dysregulated proliferation, inappropriate survival, tissue invasion and destruction, immune system evasion, and metastasis. More recently, it has become apparent that cancer cells also carry epigenetic defects, including changes in cytosine methylation patterns and in chromatin structure and organization, which are equivalent to genetic changes in effecting and maintaining neoplastic and malignant phenotypes. For many human cancers, evidence has accumulated to suggest that somatic epigenetic alterations may appear earlier during cancer development than genetic changes, as well as more commonly and consistently. As a consequence, the study of somatic epigenetic changes has provided new insights into the mechanism(s) of carcinogenesis, new molecular biomarkers to aid in prostate cancer detection and diagnosis, and new opportunities for prostate cancer prevention and treatment. One epigenetic change, CpG island hypermethylation, leads to the epigenetic silencing of critical genes by recruiting 5-methyl-CpG-binding domain (MBD) family proteins capable of mediating transcriptional repression via effects on chromatin structure. As part of an effort to discovery and develop small molecule drugs targeting MBD repression pathways for the therapeutic reactivation of epigenetically silenced genes in prostate cancer cells, “high-throughput” chemical screening has yielded a number of lead compounds capable of activating transcription from hypermethylated GSTP1 promoters, a gene epigenetically silenced in nearly all prostate cancers, and most breast and liver cancers. Several compounds identified in this way were found to directly interfere with transcriptional trans-repression mediated by MBDs via antagonizing the binding of MBDs to methyl-CpG-containing DNA. These MBD antagonists reactivated epigenetically silenced genes in cancer cells, and synergistically increased silenced gene expression the presence of DNA methyltransferase inhibitors.
THE FOURTH GENERAL ASSEMBLY OF THE WORLD MEDICAL ASSOCIATION, OCTOBER 16 TO 20, 1950; REPORT OF THE OBSERVER FROM THE AMERICAN COLLEGE OF PHYSICIANS
Authors: Alex. M. Burgess
Journal: Annals of Internal Medicine (1950)

Editorial1 December 1950THE FOURTH GENERAL ASSEMBLY OF THE WORLD MEDICAL ASSOCIATION, OCTOBER 16 TO 20, 1950; REPORT OF THE OBSERVER FROM THE AMERICAN COLLEGE OF PHYSICIANSALEX. M. BURGESS, M.D.ALEX. M. BURGESS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-33-6-1499 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe World Medical Association, organized in 1946, has completed its fourth annual General Assembly, held this year in New York City. It is made up of representatives of the national medical associations of a large proportion of the nations of the world, not including those under the direct influence of the Soviet Union.*Because it is a non-political, non-governmental and independent agency, it is able to accomplish by private means many things which purely governmental agencies cannot do. Coöperation with such organizations is, however, part of its policy. The objectives of the Association, as stated in Article 3 of the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *The National Associations of Poland and Hungary were members but have been dropped because of non-payment of dues and failure to answer any correspondence. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1950Volume 33, Issue 6Page: 1499-1503 Issue Published: 1 December 1950 PDF downloadLoading ...
Comorbid Tourette's disorder and bipolar disorder: an etiologic perspective
Authors: J Kerbeshian, L Burd, M G Klug
Journal: American Journal of Psychiatry (1995)

Using an epidemiologic approach, the authors attempt to elucidate relationships between Tourette's disorder and bipolar disorder.Of 205 patients with Tourette's disorder in the North Dakota Longitudinal Tourette Syndrome Surveillance Project, 15 had comorbid bipolar disorder. A subset of the patients with Tourette's disorder had been included in earlier population-based prevalence studies of Tourette's disorder in children, adolescents, and adults. Minimal risk ratios were calculated for the patients with Tourette's disorder plus bipolar disorder by age group (children/adolescents and adults). This information was used to estimate genetic risk indicators for comorbid Tourette's disorder and bipolar disorder.The estimated risk of developing bipolar disorder among the study group of children, adolescents, and adults with Tourette's disorder was more than four times higher than the level expected by chance, but this finding did not reach statistical significance. It was indicative of trends, however.Comorbidity between Tourette's disorder and bipolar disorder does not appear to be due to chance co-occurrence of the two disorders. Although a genetic mechanism may play a causal role, in the absence of family studies an explanatory model involving the concept of canalization of basal-ganglia-mediated dysfunctions is offered. In such a construct, Tourette's disorder would be a likely accompaniment to other conditions, including bipolar disorder, whose pathogenic determinants might channel through neural pathways involving the basal ganglia. The presence of significant developmental disabilities may further enhance factors culminating in comorbid Tourette's disorder and bipolar disorder.
Abstract 12497: Timing of ST Elevation MI is Related to Patient Baseline Characteristics
Authors: Owen N Mogabgab, Stephen D Wiviott, Elliot M Antman, Joanne M Foody, Tracy Y Wang, Marc S Sabatine, Christopher P Cannon, Satishkumar Mohanavelu, Shuang Li, Robert P Giugliano
Journal: Circulation (2010)

Background: The presence of a morning peak in the onset of ST-Elevation Myocardial infarction (STEMI) has been observed. We investigated the relationships between patient baseline characteristics a...
Addison's Disease and Its Relation to Experimental Adrenal Insufficiency
Authors: George A. Harrop
Journal: Annals of Internal Medicine (1933)

Article1 June 1933Addison's Disease and Its Relation to Experimental Adrenal InsufficiencyGEORGE A. HARROP, M.D., F.A.C.P.GEORGE A. HARROP, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-6-12-1579 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAlthough the first accurate description of the adrenal glands is usually accredited to Eustachius, in 1563, very little further progress was made in the study of their structure or physiological significance for nearly three centuries and practically all of the further additions to our knowledge have been made within the past eighty years. Modern interest in the adrenals dates from Addison, who published in 1855 the clinical observations on the disease which bears his name.In all mammals, including man, the adrenal glands are paired organs, each composed of two distinct parts. The outer layer, or cortex, forms roughly two-thirds...References1 CLEGHORN RA: Observations on extracts of beef adrenal cortex and elasmobranch interrenal body, Jr. Physiol., 1932, lxxv, 413. CrossrefGoogle Scholar2 DUFFBERNSTEIN GLC: Five cases of Addison's disease with so-called atrophy of the adrenal cortex, Bull. Johns Hopkins Hosp., 1933, lii, 67. Google Scholar3 ALBRIGHTBAIRD FPC: Treatment of Addison's disease with cortin, Arch. Int. Med., 1932, l, 394. Google Scholar4 LOEB RF: Chemical changes in the blood in Addison's disease, Science, 1932, lxxvi, 420. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Baltimore, Maryland*Read before the Medical Section, New York Academy of Medicine, January 19, 1933.†From the Chemical Division of the Medical Clinic, the Johns Hopkins Hospital and University, Baltimore. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byUntersuchungen über den Muskelstoffwechsel des HerzensSix Cases of Addison's Disease 1 June 1933Volume 6, Issue 12Page: 1579-1590KeywordsAdrenal glands ePublished: 1 December 2008 Issue Published: 1 June 1933 PDF downloadLoading ...
Phase I study of the humanized epidermal growth factor receptor (EGFR) antibody EMD 72000 (matuzumab) in combination with ECX (epirubicin, cisplatin and capecitabine) as first line treatment for advanced oesophagogastric (OG) adenocarcinoma
Authors: S. Rao, N. Starling, M. Benson, A. Massey, A. Wotherspoon, G. Brown, N. Anstice, J. Tillner, D. Weber, D. Cunningham
Journal: Journal of Clinical Oncology (2005)

4028 Background: ECF (epirubicin, cisplatin and 5FU) is widely used for the treatment of advanced OG cancer. ECX, where capecitabine is substituted for 5FU has demonstrated comparable toxicity and efficacy to ECF. EGFR expression is commonly observed in OG cancer and thus ECX combined with matuzumab could improve these results. This phase I trial evaluated the safety, tolerability pharmacokinetics (PK) and efficacy of matuzumab combined with ECX as first-line treatment for advanced OG cancer. Methods: Eligible patients were required to have EGFR positive tumours. Patients were entered in phase A (6 weeks) to receive escalating doses 400 or 800 mg matuzumab weekly or 1200 mg 3 weekly (IV) with ECX (epirubicin [50 mg/m2] and cisplatin [60 mg/m2] day 1 every 3 weeks, and oral capecitabine [500 mg/m2] bd on days 1–21). Non-progressing patients were eligible to receive 6 more cycles in phase B. Anti-tumour activity was assessed by CT and endoscopy at baseline and after cycles 2 and 4, and CT alone on completion. Blood was sampled weekly in phase A and B. Results: 24/37 (64%) screened subjects were EGFR-positive. 17 (12/5 M/F) patients, median age 60 (range 51–76) years and median KPS 90, received 400 mg (7), 800 mg (6) or 1200 mg (4) matuzumab and ECX therapy. The 1200 mg cohort is ongoing. Sites of disease: stomach (n = 6), OG junction (7), lower oesophagus (4). Stage: IIIB (1), IV (16). Grade 3–4 toxicities were: hand-and-foot syndrome (3), fatigue/lethargy (5), neutropenia (10), thrombocytopenia (2), nausea (1), elevated amylase (1) and neutropenic sepsis (1). 2/13 subjects did not enter phase B due to an adverse event (400mg) or disease progression (800 mg). Best overall response was, 4 PR, 2 SD at 400 mg (57%) and 3 PR, 2 SD, 2 PD at 800 mg (43%). PK analysis will be available for presentation. Conclusions: The protocol specified maximal dose has been reached but the MTD has not yet been defined. Matuzumab and ECX appears to be reasonably tolerated, and preliminary efficacy data suggest anti-tumour activity in previously untreated patients with advanced OG cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck KGaA Merck KGaA Merck KGaA Merck KGaA
The Coronary Problem
Authors: Arthur R. Elliott
Journal: Annals of Internal Medicine (1929)

Article1 September 1929The Coronary ProblemARTHUR R. ELLIOTTARTHUR R. ELLIOTTSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-3-3-252 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptCoronary arterial disease presents a varied clinical picture. The abundant literature which has accumulated since Herrick's forceful and illuminating description of coronary occlusion in 1912 seems to be mainly devoted to certain of the more dramatic aspects of coronary disease, notably angina pectoris and coronary thrombosis with its consequences. This brief discussion will be concerned with coronary manifestations that are less frank and typical than the major developments referred to, in short with what has been termed because of this obscurity, "occult coronary diseases."Outspoken sensory complaints, such as angina pectoris, may not develop from disease of the coronaries, for...1 MorawitzHochrein : Munch. Med. Wchnschr., 1928, 5. 17. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Chicago, Illinois*Presented to the American College of Physicians at the Annual Clinical Session, Boston, April 9, 1929. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1929Volume 3, Issue 3Page: 252-258KeywordsAnginaStable coronary artery diseaseThrombosis Issue Published: 1 September 1929 PDF downloadLoading ...
Emerging tobacco hazards in China
Authors: T H Lam, S Y Ho, Y. Lhatoo, R. Peto, Z.-M. Chen, J. Boreham
Journal: BMJ (1999)

Surgical techniques should be fully evaluatedEditor-The editorial by Nicholson and Bradley on renal transplantation from living donors rightly pointed out that the United Kingdom has a lower rate of transplantations which use kidneys from living donors than the United States or Norway. 1 The recent report by the Royal College of Surgeons on organ transplantation in the United Kingdom recommended that steps should be taken to increase the use of kidneys from living donors in the United Kingdom to offset the shortage of cadaveric kidneys as well as to improve outcome. 2 In the United Kingdom in 1998, 38% more transplantations were performed using organs from living donors than in 1997.However, there is still some way to go if a level similar to that of the United States or Scandinavia (25-30%) is to be achieved.Nicholson and Bradley identify the risks associated with donor nephrectomy and state that much of the morbidity that occurs after open nephrectomy is related to the wound.For this reason they believe that the use of laparoscopically assisted donor nephrectomy needs to be examined in the light of the experience of, for example, the Johns Hopkins Hospital in Baltimore, Maryland.However, there have been no randomised prospective trials of this procedure, which takes longer than open nephrectomy.Furthermore, all of the non-randomised comparisons have been of open nephrectomy performed through a loin incision, with or without removal of a rib.If an anterior