tbuckley/cabot-search huggingface dataset:
Case report of tricyclic-induced delirium at a therapeutic drug concentration
Authors: C D Godwin
Journal: American Journal of Psychiatry (1983)

A patient receiving a standard dose of imipramine developed a drug-induced delirium. Her plasma antidepressant level was in the low therapeutic range. Thus, tricyclic-induced delirium may in some cases be an idiosyncratic phenomenon unrelated to plasma drug concentration.
Abstract B20: Targeting Olig2 co-regulators for malignant glioma therapy
Authors: Robert Kupp, Costanza Lo Cascio, Femina Rauf, Dimphna Meijer, Charles D. Stiles, Nader Sanai, Joshua LaBaer, Shwetal V. Mehta
Journal: Cancer Research (2015)

Abstract The transcription factor OLIG2 is expressed within the highly tumorigenic sub-population of stem-like cells in malignant glioma and required for tumor formation in orthotopic grafts of human glioma as well as genetically defined murine glioma models. Our work (recently confirmed and extended by Suva et al., 2014) suggests that small molecule OLIG2 antagonist could serve as targeted therapy for high grade gliomas – either as a mono therapeutic or as an adjuvant to conventional radiotherapy or cytotoxic drugs. However, transcription factors in general are considered to be unattractive targets for drug development because their interactions with DNA and co-regulatory proteins involve large and complex surface area contacts. Our recent data suggests that OLIG2 interacts with distinct partner proteins based on its phosphorylation state, which in turn regulates its pro-mitogenic functions. Here we employed two independent proteomics screens (mass spectrometry and Nucleic Acid Programmable Protein Arrays, NAPPA) to identify OLIG2 co-regulators as possible surrogate targets to suppress OLIG2 function. These screens led to identification of two novel OLIG2 partner proteins: HDAC1 and proto-oncogene FYN kinase. OLIG2 is known to be a negative regulator of gene expression and histone deacetylation is required for suppression of gene expression. We demonstrate that OLIG2 functions as an HDAC1 carrier, delivering this enzyme to specific target genes (e.g., p21) and non-histone proteins like p53. HDACs are ubiquitously expressed and are known to be redundant, but we show that ablation of HDAC1 alone (using shRNA) significantly decreases the proliferation of glioma initiating cells with minimal impact on normal neural stem cells. In addition, we show that FYN kinase interacts with OLIG2 and phosphorylates it at tyrosine residues. Ablation of FYN decreases phosphorylation of OLIG2 at tyrosine residues and affects OLIG2-mediated expression of oncogenic target genes like EGFR and WNT5a. This work provides two potential co-regulators of OLIG2 which could serve as druggable surrogate targets to block OLIG2 function in malignant glioma. Further work will evaluate the efficacy of HDAC1 and FYN-specific inhibitor as single agents or as adjuvant therapy to radiation and temozolomide in orthotopic patient-derived xenograft models. Targeting factors regulating OLIG2-mediated tumor growth will have practical overtones for targeted therapies for malignant gliomas. Citation Format: Robert Kupp, Costanza Lo Cascio, Femina Rauf, Dimphna Meijer, Charles D. Stiles, Nader Sanai, Joshua LaBaer, Shwetal V. Mehta. Targeting Olig2 co-regulators for malignant glioma therapy. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr B20.
Genomic testing may offer therapeutic opportunity in salivary gland cancers.
Authors: Ashish V. Chintakuntlawar, Scott H. Okuno, Katharine Andress Rowe Price
Journal: Journal of Clinical Oncology (2015)

e17053 Background: Cytotoxic chemotherapy is not reliably effective for treating patients (pts) with recurrent/metastatic salivary gland cancers (SGC). Genomic testing in routine clinical practice is increasingly utilized, but the benefit is unknown. Methods: We retrospectively reviewed medical records of pts with SGC who had genetic testing for mutations by Foundation Medicine (Cambridge, MA) from July 2013-Dec 2014. Mutations that could be targeted with FDA-approved therapies were considered targetable. Results: Twenty-three pts (14 male) were tested. Median age at diagnosis was 55 yrs (22-78). Median follow up from date of diagnosis was 3.3 yrs (0.7-25). Thirteen pts had adenoid cystic carcinoma (ACC), 3 salivary duct carcinoma (SDC), 2 carcinoma ex-pleomorphic adenoma, and 1 each of myoepithelial, epithelial-myoepithelial, mucoepidermoid, adenocarcinoma-NOS and acinic cell carcinoma. Thirteen pts (56%) had mutations that were targetable, 7 non-targetable and 3 had none. There were 41 unique genes demonstrating either mutation or amplification. Most common were - p53 (n = 5), CDKN2A/B (n = 5), and NOTCH1 or NOTCH2 (n = 5). Targetable mutations included NRAS, HRAS, ALK, c-KIT, TSC, PI3KCA, PTEN, NF1, and amplification of KDR, Her2, PDGFR and AKT3. To date, 4 pts were treated with targeted drugs based on the test results. Two pts with ACC were treated with temsirolimus. One chemotherapy-naïve pt with ACC had AKT3 amplification and had a partial response (PR) with a response duration of 4 months. The second heavily pre-treated ACC pt has a PI3KCA (N282*) mutation and is receiving temsirolimus but is not yet evaluable for response. One pt with SDC with a NF1 (A2644*) mutation who failed androgen deprivation is being treated with everolimus with a PR (ongoing treatment, 5 months). One pt with epithelial-myoepithelial carcinoma who had received chemotherapy only as a radiation sensitizer was treated with trametinib for HRAS (Q61R) mutation with PR duration of 5 months. The remaining pts with targetable mutations have not been treated based on mutational profile. Conclusions: Genetic analysis detects a significant number of targetable mutations for SGC, and responses can be seen. Further study and follow up is needed to determine overall benefit.
A Meta‐Analysis to Estimate the Placebo Effect in Randomized Controlled Trials in Juvenile Idiopathic Arthritis
Authors: Erkan Demirkaya, Stefano Lanni, Francesca Bovis, Roberta Galasso, Angelo Ravelli, Elena Palmisani, Alessandro Consolaro, Silvia Pederzoli, Denise Marafon, Stefan Simianer, Alberto Martini, Nicolino Ruperto, Angela Pistorio
Journal: Arthritis & Rheumatology (2016)

To estimate the placebo effect in juvenile idiopathic arthritis (JIA) through a meta-analysis of phase III clinical trials with placebo comparator.A systematic literature search was carried out up to December 2014. For parallel design studies the outcome was evaluated as a single 1-dimensional (1-D) variable or as a composite score; outcomes of withdrawal studies were evaluated only as composite scores.We included 26 of 224 trials (12%). In trials with parallel study design and a 1-D outcome, the placebo effect was 0.35 (95% confidence interval [95% CI] 0.27-0.43). Among trials with parallel study design and a composite score outcome, the placebo rate response was higher in trials that included patients with nonsystemic JIA (0.35 [95% CI 0.29-0.42]) than in trials that included only patients with systemic JIA (0.17 [95% CI 0.10-0.30]). In the withdrawal design trials, the percentages of patients receiving placebo who had disease flares during the double-blind phase were lower in trials that included patients with nonsystemic JIA (0.55 [95% CI 0.47-0.64]) than in trials that included only patients with systemic JIA (0.68 [95% CI 0.33-0.90]).In trials with a parallel study design a sizable number of patients seem to benefit from a placebo effect, although this effect is smaller in patients with systemic JIA. In trials with a withdrawal design the inverse placebo effect is similar among the different JIA categories. This placebo effect should be considered when evaluating the effectiveness of proposed interventions and for future calculations of sample size.
Role of granulocyte-macrophage colony-stimulating factor in chemotherapy-induced oral mucositis.
Authors: A M Wardley, J H Scarffe
Journal: Journal of Clinical Oncology (1996)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1996.14.5.1741 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8622096 Role of granulocyte-macrophage colony-stimulating factor in chemotherapy-induced oral mucositis. A M WardleyxA M WardleySearch for articles by this author , J H ScarffexJ H ScarffeSearch for articles by this author https://doi.org/10.1200/JCO.1996.14.5.1741 PDF "Role of granulocyte-macrophage colony-stimulating factor in chemotherapy-induced oral mucositis.." Journal of Clinical Oncology, 14(5), pp. 1741–1743© 1996 by American Society of Clinical Oncology
Neutrophilic Leukemia
Authors: EDWARD B. SILBERSTEIN
Journal: Annals of Internal Medicine (1974)

Letters1 January 1974Neutrophilic LeukemiaEDWARD B. SILBERSTEIN, M.D., F.A.C.P., DAVID C. ZELLNER, M.D., F.A.C.P., BAVIKATTE N. SHIVAKUMAR, M.D., LEONARD A. BURGIN, M.D.EDWARD B. SILBERSTEIN, M.D., F.A.C.P.Search for more papers by this author, DAVID C. ZELLNER, M.D., F.A.C.P.Search for more papers by this author, BAVIKATTE N. SHIVAKUMAR, M.D.Search for more papers by this author, LEONARD A. BURGIN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-80-1-110 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Marked peripheral blood leukocytosis without immature forms in the peripheral blood leads the clinician to search for occult infection or other causes of a "leukemoid" reaction. We report here the clinical and pathologic data on such a patient, who proved to have "pure" neutrophilic leukemia. This is only the third such case, with bone-marrow chromosome study results, to be reported.The patient, a 75-year-old white woman, was hospitalized in January 1971 for splenomegaly and painful compression fractures of the D 12, L 1 and L 2 vertebrae. The leukocyte count was 45 000/mm3(88% were mature polymorphonuclear...References1. DAMESHEKGUNZ WF: Leukemia. New York, Grane & Stratton, Inc., 1964, p. 4 Google Scholar2. RETIEF F: Leuco-erythroblastosis in the adult. Lancet 1:639-642, 1964 CrossrefMedlineGoogle Scholar3. RUBIN H: Chronic neutrophilic leukemia. Ann Intern Med 65:93-100, 1966 LinkGoogle Scholar4. JACKSONCLARK IR: A case of neutrophilic leukemia. Am J Med Sci 249:72-74, 1965 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Departments of Medicine and Radiology Daniel Drake Memorial Hospital The University of Cincinnati Medical Center Cincinnati, Ohio PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByChronic Myeloid LeukaemiasChronic neutrophilic leukaemia and plasma cell-related neutrophilic leukaemoid reactionsChronic Myeloid LeukaemiasKnochenmark und myelogene NeoplasienSuccessful alpha-2b-interferon therapy for chronic neutrophilic leukemiaElevated neutrophil function in chronic neutrophilic leukemiaChronic Myeloproliferative Disorders in Bone Marrow BiopsiesChronic neutrophilic leukemia associated with polycythemia veraNeutrophilic leukemia accompanied by hemorrhagic diathesis: Report of two casesCoexistent chronic myeloid leukemia and IgA monoclonal gammopathy: report of a case and review of the literatureNeutrophilic Leukemia and Blastic CrisisTETSURO SHINDO, M.D., CHIKARA SAKAI, M.D., AKIRA SHIBATA, M.D. 1 January 1974Volume 80, Issue 1Page: 110-111KeywordsBloodChromosomesLeukemoidLeukocytosisSplenomegalyVertebrae Issue Published: 1 January 1974 PDF DownloadLoading ...
AIR POLLUTION AND COMMUNITY HEALTH
Authors: R E Waller
Journal: JAMA (1964)

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
Enhancement of Hepatocarcinogenesis by Sorbitan Fatty Acid Ester, a Liver Pyruvate Kinase Activity-Reducing Substance
Authors: S Yanagi, M Sakamoto, S Takahashi, A Hasuike, Y Konishi, K Kumazawa, T Nakano
Journal: JNCI Journal of the National Cancer Institute (1985)

Effect on hepatocarcinogenesis of dietary sorbitan fatty acid ester (SorFAE), which had been known to cause decrease in pyruvate kinase (PK) activity, was studied in rats fed a diet containing 0.06% 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) for 6 weeks. The incidence of hyperplastic nodules and/or hepatocellular carcinomas in the rats fed the 3'-Me-DAB diet alone was 45.0% at the end of 51 weeks, whereas the incidence in the rats fed 3'-Me-DAB diet followed by 5 or 10% SorFAE or 0.1% phenobarbital (PB) diet were 76.2, 90.5, and 95.0%, respectively. These incidences were significantly higher compared with the group fed 3'-Me-DAB diet alone (P less than .05). No tumors were observed in rats fed 10% SorFAE diet alone. The results show that SorFAE has an enhancing effect on hepatocarcinogenesis, although the effect was weak compared to that of the effective PB dose. The results seem to confirm our assumption that a chemical that causes decrease in PK activity in rat liver might promote hepatocarcinogenesis.
Soundings: Unauthorised practices
Authors: George Dunea
Journal: BMJ (2006)

The spouse who borrowed her husband's pills to treat her blood pressure was clearly taking a risk. But when many patients cannot afford a drug bill of over $500 (£271; €397) a month and may depend on drug samples, issues such as using drugs beyond their official expiry date become increasingly relevant. Though strictly speaking unauthorised, it has long been a common practice among doctors, as shown by the daughter of a southern practitioner who declared she was “brought up on grits and expired medicines.”

Hard data on this subject are difficult to come by. Insulin and nitroglycerin need to be fresh, as do most liquid preparations; and outdated tetracycline was notorious for causing a Fanconi syndrome. But for other drugs a study conducted some years ago by the Food and Drug Administration at the request of the US army, which had large stores of unused expensive medications, found that most of them were safe and effective, some even after 15 years. Other studies have found that some drugs may lose 10% of their efficacy, which is mostly clinically inconsequential.

Also controversial is the issue of splitting pills, an economy practice arising largely from the fact that for several medications all dosage forms cost the same. Studies by the Veterans Administration and by Stanford University have confirmed the safety of pill splitting, and several health plans now offer discounts to members who agree to split their pills. More recently several government agencies as well as Kaiser Permanente have mandated splitting certain expensive pills, to the displeasure of drug makers, pharmacy associations, and a trial lawyers' organisation.

To split pills most patients use a knife or a pill splitter, but some break them by hand or even use their teeth. Clearly patients with dementia, visual impairment, or tremors should not attempt this delicate operation; nor can delayed release pills be bisected without disrupting their mechanism. Other pills, such as the phosphodiesterase inhibitors, cannot be easily split evenly without their fragments occasionally hitting the dining room walls. Yet many patients oppressed by rising costs would rather accept this occasional mishap than pay $14 for a few minutes' exaltation.
Rapid Emergence of Acquired <i>cis</i>-Diamminedichloroplatinum(II) Resistance in an In Vivo Model of Human Ovarian Carcinoma
Authors: P A Andrews, J A Jones, N M Varki, S B Howell
Journal: Cancer Communications (1990)

We have characterized the acquisition of resistance to cisplatin (DDP) in an in vivo solid tumor model. Human ovarian carcinoma cells (2008 cell line) were grown s.c. as xenografts in athymic mice. Tumors were selected with 3.0 mg/kg of DDP i.p. given once per week for four weeks. One week after the last dose of DDP, cell lines were generated from the tumors. Cells from these lines were then re-inoculated into athymic mice, and the DDP selection process was repeated. This procedure was continued for a total of four passages (16 doses). Although this chemotherapy did not affect the tumors' growth, cell lines derived from these tumors after the first passage displayed low-level resistance to DDP as determined by the concentration causing 50% inhibition of colony formation in a clonogenic assay. The mean resistance (+/- SD) of cell lines derived from tumors treated with four doses of DDP was 1.6 +/- 0.06 (n = 5). A minimum of only two doses of DDP was required to generate significant resistance (1.5 fold). The DDP resistance slowly increased with further selections so that after four passages with chemotherapy, the cells were 3.0-fold resistant. The DDP resistance was not stable; after three passages, resistance slowly declined over 104 days from 2.2- to 1.4-fold. Resistant cells obtained after both three and four passages did not have elevated glutathione as determined by flow cytometry of monochlorobimane-stained cells. After three passages, DDP-resistant cells were not resistant to CdCl2, suggesting that metallothioneins were also not elevated. A key biochemical change found in these cells was a decrease in DDP accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of Treated Polygalacturonic Acid on Blood Volume Loss in the Rat Following Traumatic Injury
Authors: CHARLES E. BRAMBEL, DAVID MURPHY
Journal: Circulation Research (1958)

Evidence is presented that a polygalacturonic acid derivative (Stypturon) when administered intravenously to rats in an optimal dosage results in concomitant diminution of blood loss from experimental injury to the tail. Mortality rate associated with hemorrhagic shock was significantly reduced. Blood coagulation was inhibited at the site of injury by immersion of the traumatized tail in an anticoagulant solution at 37 C. for the duration of the experiment. The data for the enhancement of the normal hemostyptic mechanism by a polymeric substance without the apparent mediation of the blood coagulation system is discussed.
Evaluation of the Persistence, Remission, and Emergence of Attention-Deficit/Hyperactivity Disorder in Young Adulthood
Authors: Jessica C. Agnew-Blais, Guilherme V. Polanczyk, Andrea Danese, Jasmin Wertz, Terrie E. Moffitt, Louise Arseneault
Journal: JAMA Psychiatry (2016)

Attention-deficit/hyperactivity disorder (ADHD) is now recognized to occur in adulthood and is associated with a range of negative outcomes. However, less is known about the prospective course of ADHD into adulthood, the risk factors for its persistence, and the possibility of its emergence in young adulthood in nonclinical populations.
Abstract B38: Cancer-related circulating long noncoding RNAs in serous extracellular vesicles: Their characterization and potential application
Authors: Dong Lei, Lin Wanrun, Qi Peng, Xu Midie, Du Xiang
Journal: Cancer Research (2016)

Abstract Background: Circulating nucleic acids (CNAs) are extracellular nucleic acids found in cell-free sera, plasma and other bodily fluids of healthy subjects and cancer patients. We have previously demonstrated that human serum or plasma contains microRNAs (miRNAs) and long non-coding RNA (lncRNAs) that are significantly up-regulated or down-regulated in various types of cancer and are of good diagnostic value for screening. The mechanisms underlying the stability of serum RNAs are unclear; lncRNAs may be protected by extracellular vesicles (EV) including apoptotic body (AB), microvesicle (MV) and exosome (EXO), as for circulating miRNAs. In order to find optimal method to evaluate the potential utility of circulating lncRNAs for cancer diagnosis or prognosis, more exploration should be undertook for the distribution of circulating lncRNAs. Results: The shapes and sizes of three subgroups of extracellular vesicles, including AB, MV and EXO, were evaluated. NanoSight particle tracking analysis and transmission electron microscopy (TEM) showed the MVs, pelleted at 12, 000×g, were with the size range of 75-465 nm; and EXOs, pelleted at 120,000×g, with the size range of 45-205 nm. In serous vesicles of both colorectal cancer and healthy subjects, 17 of the 39 cancer-related lncRNAs were detected, including TDRG1, MEG3, DSCAM-AS1, 7SK, MIR31HG, CBR3-AS1, TUG1, BCAR4, EPB41L4A, PCA3, FAS-AS1, SUMO1P3, uc338, PRNCR1, PTENP1 and CUDR. The amount of most lncRNAs were higher in EXO than those in AB and MV. In addition, AB contains higher amount of most lncRNAs than MV. Results: The shapes and sizes of three subgroups of extracellular vesicles, including AB, MV and EXO, were evaluated. NanoSight particle tracking analysis and transmission electron microscopy (TEM) showed the MVs, pelleted at 12, 000×g, were with the size range of 75-465 nm; and EXOs, pelleted at 120,000×g, with the size range of 45-205 nm. In sera of both colorectal cancer and healthy subjects, 16 out of the 39 cancer-related lncRNAs were detected. The amount of most lncRNAs were higher in EXO than those in AB and MV. In addition, AB contains higher amount of most lncRNAs than MV. Conclusions: Among three types of vesicles in sera, EXOs were the richest reservoir for almost all measured lncRNAs, while the MVs contained the least amount of lncRNAs. EXOs, as their intercellular origin, have reasons to contain higher amount of lncRNAs among serous vesicles and seem to be the most promising research materials in the field of circulating lncRNA. Citation Format: Dong Lei, Lin Wanrun, Qi Peng, Xu Midie, Du Xiang. Cancer-related circulating long noncoding RNAs in serous extracellular vesicles: Their characterization and potential application. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr B38.
The acute administration ward as a therapeutic community
Authors: H Steiner, C V Haldipur, L C Stack
Journal: American Journal of Psychiatry (1982)

The authors evaluated six acute short-stay admission wards in a community mental health center using the sociometric Ward Atmosphere Scale. There was an attempt to run three of the six wards as therapeutic communities. No differences were found on Ward Atmosphere Scale dimensions between the therapeutic communities and other types of programs, nor did the therapeutic communities conform to an empirically derived therapeutic community program dimension profile. Possible reasons for this failure and its implications for community mental health centers are discussed.