tbuckley/cabot-search huggingface dataset:
Psychiatric diagnosis, drug development, and ethics
Authors: Harold Alan Pincus
Journal: BMJ (2003)

Accurate assessment and proper prescription 

From BMJ USA 2003;September:468 

Shorter and Tyrer in their Education and Debate article “Separation of anxiety and depressive disorders: blind alley in psychopharmacology and classification of disease” ( BMJ USA p 511) correctly point out that psychiatric diagnosis is stuck in a rut. Unfortunately, their analysis is flawed and their prescription is too narrow. They conflate three separate (though somewhat related) issues, each with its own pathophysiology, diagnosis and treatment: 1) drug development incentives and disincentives, 2) the influence of the pharmaceutical industry on clinical practice and research, and 3) fundamental tensions in psychiatric classification.

The data regarding the relationship between new drug development and the number of Diagnostic and Statistical Manual of Mental Disorders (DSM) categories and assumptions regarding the “slowdown in drug discovery” are …
Atrophy of the skin.
Authors: I.B. SNEDDON
Journal: British Journal of Dermatology (1976)

Journal Article Atrophy of the skin: THE CLINICAL PROBLEMS Get access I.B. SNEDDON I.B. SNEDDON Rupert Hallam Department of Dermatology, Sheffield Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 94, Issue s12, 1 March 1976, Pages 121–123, https://doi.org/10.1111/j.1365-2133.1976.tb02280.x Published: 01 March 1976
The Surgeon General Moves On
Authors: David Satcher
Journal: JAMA (2002)

AS SURGEON GENERAL OF THE United States, David Satcher, MD, PhD, opened millions of eyes to such often-neglected health problems as obesity, mental illness, and suicide. Since leaving his high-profile post in February, he’s been tackling another tough topic: trying to convince people that they can make a difference by working in government. In the fall, Satcher becomes director of the National Center for Primary Care at Morehouse School of Medicine in Atlanta. Until then, his work as a senior fellow with the Kaiser Family Foundation is focused on writing an account of his years in government as surgeon general of the United States, director of the Centers for Disease Control and Prevention (CDC), and assistant secretary for health with the US Department of Health and Human Services. “The bottom line really is to encourage people to spend time in government if they get the chance,” he says. “Very seldom is it easy, but it’s worth it. When you are successful, it has an impact on so many people.” In between writing about his government service and planning a move from Washington, DC, to Atlanta, Satcher reflected on his achievements as the nation’s physician and a public servant. JAMA: What influenced you early on to choose a career in medicine? Dr Satcher: At the age of 2 years I became very ill with whooping cough and pneumonia. The physician, Dr Jackson, warned my parents that he didn’t expect me to live through the week. They had lost two children very early because they didn’t have access to health care. My mother had nine pregnancies and never went to a hospital with any of them. They lived at a time and in a place where it was not unusual for children to die. My mother told me that story almost every day, that the doctor said I wasn’t going to live. By the time I was 6 I was saying when I grow up I want to be a doctor like Dr Jackson. I didn’t know what I was talking about, but I
215. Dimerizer-Regulated AADC Expression with Two AAV Vectors in 6-OHDA Lesioned Rats
Authors: Laura M. Sanftner, Victor M. Rivera, Lan Feng, Lori Berk, John R. Forsayeth, Tim Clackson, Janet Cunningham
Journal: Molecular Therapy (2004)

Recombinant AAV vectors containing the dimerizer-inducible system of transcriptional activation provide a promising strategy for regulated control of therapeutic gene expression in the CNS. To test the feasibility of applying this approach to our current treatment for Parkinson's disease, we explored regulation of expression of the enzyme Aromatic L-Amino Acid Decarboxylase (AADC) in rat striatum by means of a regulated AAV vector system. Expression of the AADC transgene was made dependent on reconstitution of a functional transcription factor (TF) by the dimerizer rapamycin. Two vectors were constructed: 1) AAV-CMV-TF and 2) AAV-Z12-hAADC. We evaluated them in vivo in a rodent model of Parkinson's disease. A 1:1 combination (3 × 1010 vg of each vector) was infused ipsilaterally into unilaterally 6-OHDA-lesioned rats. Induction of transgene expression was achieved via intraperitoneal administration of rapamycin at designated time points. Since increased expression of AADC in the lesioned striatum correlates with increased conversion of L-dopa to dopamine, we would expect to see altered behavioral rotational response to 5mg/kg L-dopa. This parameter was evaluated six times during the course of the experiment. The rotational response to L-dopa in the vector-infused (+) rapamycin group was significantly increased (P<0.003, one-way ANOVA) above both control groups (vector-infused (–) rapamycin and excipient-infused animals). There was no significant difference between the two control groups, suggesting that expression of AADC in the absence of induction was not high enough to elicit behavioral response. Seven weeks following intrastriatal infusion rats were sacrificed and tissue was processed for immunostaining. Serial sections of fixed brain tissue were stained for AADC. We quantitated the spread volume and positive cell number for AADC transgene-derived immunostaining by stereology for each animal. The vector-infused (+) rapamycin group had the greatest number of AADC positive cells (75,825+/−30,506 cells), followed by a lower number of positive cells (31,000+/−25,812 cells) in the vector-infused (–) rapamycin group (P<0.01, one-way ANOVA), and no detectable expression in the excipient-infused control group. Intensity of staining appeared much lower in the non-induced vector-treated rats compared to those that received rapamycin. In summary, this study demonstrated robust behavioral response of parkinsonian rats to AAV-mediated AADC treatment that could be regulated using the rapamycin system. A low level of AADC transgene expression was observed in the absence of rapamycin, however, it was not significant enough to elicit behavioral response. Recombinant AAV vectors controlled by rapamycin or rapamycin analogs show promise as candidates for CNS therapies in which regulation of the transgene may be important.
Researchers Wrestle With Spread and Control of Emerging Infections
Authors: Joan Stephenson
Journal: JAMA (2002)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract # 17051: Genome-wide Copy Number Analysis Identifies New Candidate Genes for Thoracic Aortic Aneurysms and Dissections
Authors: Siddharth Prakash, Dong-Chuan Guo, Ludivine Russell, Ellen Regalado, Molly Bray, Scott LeMaire, Dianna Milewicz, John Belmont
Journal: Circulation (2010)

Purpose: Aortic aneurysms and dissections are the nineteenth leading cause of death in the United States. The spectrum of thoracic aortic aneurysms and dissections (TAAD) ranges from congenital dis...
Abstract 5283: Perfluorocarbon Microcapsules for X-ray Visualization of Mesenchymal Stem Cell Delivery and Engraftment
Authors: Yingli Fu, Dorota Kedziorek, Veronica Crisostomo, Wesley Gilson, Nicole Azene, Aravind Arepally, Christine Lorenz, Jeff Bulte, Dara Kraitchman
Journal: Circulation (2008)

Mesenchymal stem cell (MSC) transplantation offers an alternative strategy for therapeutic angiogenesis for the management of ischemic cardiovascular disease. However, the poor survival of transplanted cells and lack of sustained engraftment severely limits therapeutic efficacy. We propose a novel cell microencapsulation method utilizing perfluoro-octyl-bromide (PFOB) impregnated alginate-poly-L-lysine-alginate microcapsules (PFOB Caps) that enable noninvasive cell delivery and tracking using conventional clinical X-ray fluoroscopy. Microen-capsulation of rabbit MSCs (1x10 6 cells/ml) combined with PFOB-loaded alginate was performed with an electrostatic droplet generator. Control capsules lacked PFOB. MSC viability post-encapsulation was determined using a microfluorometric assay. X-ray fluoroscopy was performed during direct intramuscular/intramyocardial injection of 2300 capsules/injection in a rabbit peripheral arterial disease (PAD) model (n=2) and a swine reperfused myocardial infarction (MI) model (n=3). Fluoroscopy and angiographic computed tomography (DynaCT) were performed to assess the ability to monitor microcapsule delivery and tracking with X-ray. As compared to control capsules, PFOB Caps showed similar swelling, when subjected to 55 mM sodium citrate incubation (mean diameter increased 5.4% for PFOB vs. 4.5% for control, P=NS), and mechanical strength (broken capsules from osmotic pressure tests: 2/591 for PFOB and 2/603 for control). The PFOB Caps showed a small viability decrease immediately after encapsulation (90±3%) with no significant further viability loss up to 4 weeks in vitro (79±5%). In both PAD and MI animals, successful injection of PFOB Caps could be demonstrated with DynaCT but not with real-time fluoroscopic images. Control capsules were never detected. CT tracking of PFOB Caps was possible up to 5 weeks post-injection. PFOB microcapsules provide an ideal microenvironment for maintaining MSC viability in vitro . In addition, PFOB proves to be a non-toxic, radiopaque agent suitable for cell tracking using conventional fluoroscopy in vivo . PFOB microencapsulation of MSCs may be a novel approach for X-ray tracking therapeutic angiogenesis.
First-in-human phase I trial of the dual mTORC1 and mTORC2 inhibitor AZD2014 in solid tumors.
Authors: Udai Banerji, Emma Jane Dean, Michael Gonzalez, Alastair P Greystoke, Bristi Basu, Matthew Krebs, Martina Puglisi, Lynda Grinsted, Elisabeth Oelmann, Wendy Burke, Elizabeth Harrington, Stephen Green, Malcolm Ranson
Journal: Journal of Clinical Oncology (2012)

3004 Background: AZD2014 is a potent, dual mTORC1/mTORC2 inhibitor with clear activity in in vivo and in vitro experimental models. Methods: This 2-part study consisted of "rolling six" dose escalation (Part A) and expansion (Part B) phases. Part A: 3–6 pts per cohort received an oral solution of AZD2014 BD starting at 50 mg. A further 6 pts were treated in Part A below the MTD to study changes in pharmacodynamic (PD) biomarkers. Part B: additional pts were dosed at the MTD, including a group of ER+/PR+ or HER2+ patients with breast cancer. Primary endpoint: safety and tolerability; secondary endpoints: pharmacokinetics (PK), PD and efficacy. Biomarkers assessed: mTORC1: pS6 (S235/236) and p4EBP1 (T37/46); mTORC2: pAKT (S473). Results: 50 pts have been enroled in this ongoing study and interim data are reported: Part A, n=23 (25 mg, n=6; 50 mg, n=8; 70 mg, n=5; 100 mg, n=4; all BD); Part B, n=27. The MTD was 50 mg BD. DLTs were seen at both 100 mg (Gr 2 and 3 lethargy/fatigue, n=4/4) and 70 mg (Gr 3 mucositis, Gr 2 lethargy, n=2/4); no DLTs were seen at 25 mg or 50 mg. The most common AEs in order of incidence were fatigue, stomatitis, decreased appetite, nausea and diarrhea. Seven SAEs (nausea, vomiting, lethargy, abdominal pain, mucositis) reported by 3 pts were considered ‘possibly related’ to the study drug by investigators. AZD2014 is rapidly absorbed following single and BD multiple doses with a short t 1/2 of ~3 h. At 50 mg (n=32), preliminary data show geometric mean AUC ss =7.4 µg.h/ml and C max ss =1.7 µg/ml. One pt with acinar pancreatic cancer had a RECIST partial response. pAKT and p4EBP1 reductions were observed between 2–8 h in platelet-rich plasma and peripheral blood mononuclear cells respectively. Target modulation in paired tumor biopsies was seen at the MTD. Reduction in the phosphorylation of S6 and 4EBP1 was evident in 8/10 and 3/9 paired biopsies respectively. pAKT was reduced in 3/6 evaluable paired biopsies. As opposed to rapalogs, pAKT was not upregulated in any of the evaluable post-treatment biopsies. Conclusions: The MTD for AZD2014 is 50 mg BD. Further clinical evaluation of AZD2014 is now warranted based on the safety, PK and proof-of-mechanism PD data, as well as its preliminary clinical activity. Updated results will be presented.
VON GIERKE'S GLYCOGEN DISEASE
Authors: Lionel M. Lindsay, Alan Ross, F. W. Wigglesworth
Journal: Annals of Internal Medicine (1935)

Article1 September 1935VON GIERKE'S GLYCOGEN DISEASELIONEL M. LINDSAY, M.D., ALAN ROSS, M.D., F. W. WIGGLESWORTH, M.D.LIONEL M. LINDSAY, M.D.Search for more papers by this author, ALAN ROSS, M.D.Search for more papers by this author, F. W. WIGGLESWORTH, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-9-3-274 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSince 1929, when von Gierke first reported two cases of the syndrome which now bears his name, a great interest has been shown in this disturbance of glycogen metabolism. Now that attention has been called to the disorder numerous cases have been reported from Europe, Australia and America; and a search into medical literature reveals the fact that several undoubted cases were reported under various names prior to 1929.The disease may be defined as a disturbance of glycogen metabolism which appears in early infancy and is characterized by an abnormal deposit of glycogen in the liver, kidneys, heart and...References1. BISCHOFF G: Zum klinischen Bild der Glykogen-Speicherungskrankheit, Ztschr. f. Kinderheilk., 1932, lii, 722-726. PUTSCHAR, W.: Über angeborene Glykogenspeicherkrankheit der Herzens, Beitr. z. path. Anat. u. z. allg. Path., 1932, xc, 222-232. CrossrefGoogle Scholar2. VAN CREVELD S: Investigations on glycogen disease, Arch. Dis. Child., 1934, ix, 9-26. CrossrefGoogle Scholar3. RAUHZELSON LC: Disturbance in glycogen metabolism with hepatomegaly, Am. Jr. Dis. Child., 1934, xlvii, 808-820. CrossrefGoogle Scholar4. HUMPHREYSKATO EMK: Glycogen storage disease, Am. Jr. Path., 1934, x, 589-614. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Montreal, Quebec,*Read at the Philadelphia meeting of the American College of Physicians, May 1, 1935. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byA Case of Glycogenic Cardiomegaly in a DogCardiac hypertrophy caused by glycogen storage disease in a fifteen-year-old boyIdiopathic lipemia with secondary xanthomatosis, hepatosplenomegaly, and lipemic retinalisEinblicke in den Kohlehydratstoffwechsel durch das Studium der GlykogenoseVon gierke's glycogen storage diseaseDie Speicherkrankheiten (Thesaurismosen) 1 September 1935Volume 9, Issue 3Page: 274-281KeywordsCardiovascular therapyGlycogensHeart diseasesKidneysLiverLiver diseases ePublished: 1 December 2008 Issue Published: 1 September 1935 PDF downloadLoading ...
Potentiation of the Cytocidal Effect of Human Immune Interferon by Different Synthetic Double-Stranded RNAs in the Refractory Human Colon Carcinoma Cell Line BE
Authors: Mrunal S. Chapekar, Robert I. Glazer
Journal: Cancer Research (1986)

A human cell line BE, derived from an undifferentiated carcinoma of the colon, was studied for its response to the cytocidal effects of human immune interferon (IFN-gamma) alone and in combination with various double-standard RNAs (dsRNAs). BE cells were moderately refractory to 3-day treatment with IFN-gamma (10 to 300 units/ml) where only 5 to 30% reduction in colony formation occurred. A similar exposure interval to polyriboinosinic.polyribocytidylic acid [poly(I).poly(C)] (100 micrograms/ml) had no detectable effect on colony formation. In contrast, the lethal effect of the combination of IFN-gamma and poly(I).poly(C) was synergistic and this regimen produced a 40 to 80% reduction in colony formation. The cytocidal effects of the combination of IFN-gamma with varying concentrations of the dsRNAs poly(I).poly(C), polyriboadenylic.polyribouridylic acid [poly(A).poly(U)], polyriboinosinic.polyribocytidylic acid stabilized with poly-L-lysine in carboxymethylcellulose [poly(ICLC)], and mismatched dsRNA [rIn.r(C13,U)n] were also examined. The concentration of the dsRNAs producing a 50% decrease in cell viability in combination with IFN-gamma (100 units/ml) was 6 micrograms/ml for poly(I).poly(C), 1 microgram/ml for poly(A).poly(U), 3 ng/ml for poly(ICLC), and 16 micrograms/ml for rIn.r(C13,U)n. DNA, RNA, and protein synthesis in IFN-gamma and poly(I).poly(C)-treated cells were reduced in a dose-dependent manner. However, there were no changes in either (2',5')oligoadenylate concentrations or in ribosomal RNA transcription following treatment with IFN-gamma and poly(I).poly(C). Thus, the synergism resulting from the combination of IFN-gamma and dsRNA appears to be mediated via another, as yet unknown, mechanism.
Abstract PR03: Delineating the roles of lysine 27 methylation-associated epigenetic modulators in T cell leukemia.
Authors: Panagiotis Ntziachristos, Grant Welstead, Thomas Trimarchi, Sofia Bakogianni, Luyao Xu, Pieter Van Vlierberghe, Rab Prinjha, Adolfo Ferrando, Rudolf Jaenisch, Charles Mullighan, Aifantis Iannis
Journal: Clinical Cancer Research (2015)

Abstract The cure rate for childhood acute lymphoblastic leukemia (ALL) has dramatically improved, yet up to 25% of patients experience disease recurrence. T cell ALL (T-ALL) represents 15% of pediatric and 25% of adult ALL and it is classified as a high-risk type of ALL. The aim of the hitherto studies is to specifically block the effects of cancer inducing oncogenes. Recently, we identified inactivating mutations of the polycomb repressive complex 2 (PRC2), the “writer” of Histone 3 lysine 27 methylation, in primary samples from human patients revealing a tumor suppressor role for the complex in T-ALL. Extending our work on the H3K27me3 mark, we now show the oncogenic role for the Jumonji d3 (JMJD3) demethylase. Functionally, genomic ablation of the JMJD3 modulator as well as targeting with a specific inhibitor, GSKJ4, leads to apoptosis and cell cycle arrest of T-ALL lines and primary cells. Genetic ablation of JMJD3 leads to slower initiation of the disease with significantly improved survival rates of the mice. Surprisingly, UTX acts as a tumor suppressor in the context of the same disease, as part of different transcriptional complexes, and we found that it is genetically inactivated in T-ALL patients. Importantly, in light of recent developments on novel epigenetic inhibitors against JMJD3, these findings pave the way to specific pharmacological targeting of T cell leukemia. Citation Format: Panagiotis Ntziachristos, Grant Welstead, Thomas Trimarchi, Sofia Bakogianni, Luyao Xu, Pieter Van Vlierberghe, Rab Prinjha, Adolfo Ferrando, Rudolf Jaenisch, Charles Mullighan, Aifantis Iannis. Delineating the roles of lysine 27 methylation-associated epigenetic modulators in T cell leukemia. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr PR03.
THE "PRECORDIAL CATCH," A SYNDROME OF ANTERIOR CHEST PAIN
Authors: A J MILLER, T A TEXIDOR
Journal: Annals of Internal Medicine (1959)

Article1 September 1959THE "PRECORDIAL CATCH," A SYNDROME OF ANTERIOR CHEST PAINALBERT J. MILLER, M.D., F.A.C.P., TEODORO A. TEXIDOR, M.D., F.A.C.P.ALBERT J. MILLER, M.D., F.A.C.P., TEODORO A. TEXIDOR, M.D., F.A.C.P.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-51-3-461 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn 1955 the authors called attention to a common syndrome of anterior chest pain.1, 2 A description of the typical pain syndrome, then based on a study of 10 patients, is as follows:The pain is sharp, sudden in onset and severe, and is localized at or near the cardiac apex. It occurs at rest or during mild activity, and is often associated with a "bent over" or "slouched" posture. The immediate reaction to the pain is a suspension of breathing in midrespiration or expiration. Subsequently, breathing usually is confined to shallow chest excursions. This eases the pain; attempts to...Bibliography1. MillerTexidor AJTA: "Precordial catch," a neglected syndrome of precordial pain, J. A. M. A. 159: 1364, 1955. CrossrefMedlineGoogle Scholar2. Wehrmacher WH: The painful anterior chest wall syndromes, M. Clin. North America 42: 111 (Jan.) 1958. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Chicago, Illinois*Received for publication November 26, 1958.From the Cardiovascular Department, Medical Research Institute, and the Department of Medicine, Michael Reese Hospital, Chicago, Illinois.Requests for reprints should be addressed to Albert J. Miller, M.D., Department of Cardiovascular Research, Michael Reese Hospital, Twenty-ninth Street and Ellis Avenue, Chicago 16, Illinois. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPrecordial Catch Syndrome in Elite Swimmers With AsthmaChest wall syndrome among primary care patients: a cohort studyChest PainChest PainAngina pectoris with coexisting skeletal chest painENZYME THERAPY AND ALLERGYPRECORDIAL CATCH (TEXIDOR'S TWINGE)MEDICAL EDUCATION OF THE PUBLICPRECORDIAL CATCHNEW WORDS REQUIREDPRECORDIAL CATCH (TEXIDOR'S TWINGE) 1 September 1959Volume 51, Issue 3Page: 461-467KeywordsBreathingCardiology and cardiovascular diseasesHospital medicineIschemiaPostural controlRespirationThorax Issue Published: 1 September 1959 PDF downloadLoading ...
Prognostic Implications of Left Ventricular Mass and Geometry Following Myocardial Infarction
Authors: Anil Verma, Alessandra Meris, Hicham Skali, Jalal K. Ghali, J. Malcolm O. Arnold, Mikhail Bourgoun, Eric J. Velazquez, John J.V. McMurray, Lars Kober, Marc A. Pfeffer, Robert M. Califf, Scott D. Solomon
Journal: JACC. Cardiovascular imaging (2008)