tbuckley/cabot-search huggingface dataset:
Genotypic analysis of respiratory mucous sulfation defects in cystic fibrosis.
Authors: Y Zhang, B Doranz, J R Yankaskas, J F Engelhardt
Journal: Journal of Clinical Investigation (1995)

Intracellular dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) has been proposed to alter endosomal acidification. The most widely studied consequence of this defect has been alterations in the biochemical properties of cystic fibrosis (CF) respiratory mucus glycoproteins. However, studies confirming the existence of mucous processing defects in CF have been hindered by the lack of in vivo animal models by which to test these hypotheses in the absence of secondary effects of chronic bacterial infection. The human bronchial xenograft model has been useful in evaluating the pathophysiologic differences between CF and non-CF airway epithelium, in the absence of secondary disease effects such as goblet cell hyperplasia. In this study we sought to compare the extent of sulfation within secreted mucus glycoproteins from CF and non-CF human bronchial xenografts. Cumulative results of xenografts generated from 13 independent CF tissue samples demonstrated a statistically significant higher level of sulfation (1.7 +/- 0.18, P < 0.026) as compared to non-CF paired controls. Such findings add to the growing body of knowledge that primary defects in sulfation exist in CF respiratory mucin. Correlation of genotype with the extent of mucus sulfation revealed two categories of CF tissues with statistically different mucus sulfation profiles. Results from these studies demonstrated a 2.0 +/- 0.15-fold higher level of mucus sulfation produced from xenografts of five defined CF genotypes as compared to non-CF controls (P < 0.004, n= 10). Interestingly, three CF samples for which one mutant allele remained undefined (deltaoff8/unknown or G551D/unknown) demonstrated no statistical difference in the level of sulfation as compared with matched non-CF controls (n= 3). This as yet unknown allele was not identified within a screen for the 26 most common CF mutations. These results provide preliminary evidence for allelic variation within the CF population which may begin to elucidate the structure-function of CFTR with regards to intracellular mucus processing defects.
Dovitinib demonstrates antitumor and antimetastatic activities in xenograft models of hepatocellular carcinoma
Authors: Hung Huynh, Pierce Kah Hoe Chow, Wai Ming Tai, Su Pin Choo, Alexander Yaw Fui Chung, Hock Soo Ong, Khee Chee Soo, Richard Ong, Ronald Linnartz, Michael Ming Shi
Journal: Journal of Hepatology (2011)
Prescribing strong opioids for pain in adult palliative care: summary of NICE guidance
Authors: M. I. Bennett, J. Graham, M. Schmidt-Hansen, M. Prettyjohns, S. Arnold
Journal: BMJ (2012)

Pain is common in advanced cancer but also in the late stages of other incurable non-malignant diseases, such as heart failure and neurological conditions.1 2 Almost half of patients with advanced cancer are undertreated for their pain, largely because clinicians are reluctant to use strong opioids for effective analgesia.3 4 Strong opioids such as morphine are indicated for moderate to severe pain and should be prescribed only after a full assessment of the analgesic needs of the patient. This article summarises the most recent recommendations from the National Institute for Health and Clinical Excellence (NICE) on the care of people with advanced and progressive disease who require strong opioids for pain control.5 These patients are defined as those in moderate to severe pain who may never have used strong opioids, or those whose pain has been inadequately controlled by weak opioids such as codeine or tramadol. The guideline does not cover all aspects of pain management (including second line approaches) or pain control during the last days of life (for example, for patients who are being managed by the Liverpool care pathway, a care pathway that integrates the best aspects of care for dying patients that can be used in any clinical setting). NICE recommendations are based on systematic reviews of the best available evidence. When minimal evidence is available, recommendations are based on the Guideline Development Group's experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Communication and provision of information When offering strong opioids as pain treatment to a patient with advanced and progressive disease:
IOM Panel Exonerates Researchers in FIAU Deaths
Authors: Charles Marwick
Journal: JAMA (1995)

ISSUING its report on the deaths of five patients treated with fialuradine (FIAU), an experimental drug, in a study aimed at eliminating the carrier state of hepatitis B, the Institute of Medicine (IOM) has exonerated the scientists involved. There was no "evidence of negligence or carelessness," the fatalities could not have been foreseen, the report concludes. This conclusion was similar to an earlier report prepared at the request of the director of the National Institutes of Health. But it is at some variance with a probe of the incident by the Food and Drug Administration (FDA), which concluded in its report that the investigators had failed to analyze the data regarding adverse events in a way that might have tipped them off to the toxicity of FIAU (<i>JAMA</i>. 1994;272:9-11). The latest report was prepared by an eight-member committee chaired by Morton Swartz, MD, professor of medicine, Harvard Medical School, Boston,
Why America Needs a Strong FDA
Authors: Howard Markel
Journal: JAMA (2005)

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
CRITICAL APPRAISAL OF THE REVISED MARFAN NOSOLOGY IN CARDIOLOGICAL PRACTICE
Authors: Piet De Witte, Teodora Radonic, Maarten Groenink, Rianne A. de Bruin -Bon, Janneke Timmermans, Arthur J. Scholte, Maarten P. van den Berg, Marieke J. Baars, Peter J. van Tintelen, Marlies Kempers, Aeilko H. Zwinderman, Barbara J. Mulder
Journal: Journal of the American College of Cardiology (2011)
Diltiazem and Generalized Lymphadenopathy
Authors: BARBARA SCOLNICK
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 April 1985Diltiazem and Generalized LymphadenopathyBARBARA SCOLNICK, M.D., DON BRINBERG, M.D.BARBARA SCOLNICK, M.D., DON BRINBERG, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-102-4-558_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We report the case of a patient being treated with diltiazem who developed a severe hypersensitivity reaction that presented clinically as a generalized lymphadenopathy and skin rash; the reaction resolved after withdrawal of the drug.A 50-year-old patient with known coronary artery disease, hypertension, hyperlipidemia, and chronic vertigo was maintained on isosorbide dinitrate, 20 mg four times a day; nadolol, 40 mg once a day; hydrochlorthiazide, 50 mg once a day; nitroglycerin, 10 mg once a day; meclizine, 25 mg three times a day; and probucol, 500 mg twice a day. On 19 May 1984 he was...References1. MCGRAW B. Diltiazem hydrochloride. Drug Intell Clin Pharm. 1982;16:366-8. CrossrefMedlineGoogle Scholar2. MCGRAWWALKERHEMBERGERGITOMERNAKAMA BSJSM. Clinical experience with diltiazem in Japan. Pharmacotherapy. 1982;2:156-61. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Brockton/West Roxbury Veterans Medical Center West Roxbury, MA 02132 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe spectrum of nephrocutaneous diseases and associationsCalcium channel blockersDiltiazem☆Drug ReactionsAdverse immunological effects of drugs other than anticance drugs and drugs used in immunologyDrugs Used to Treat Hypertension, Heart Failure, and Angina PectorisCalcium channel blockersThe spectrum of cutaneous reactions associated with diltiazem: Three cases and a review of the literatureDrug-induced pseudolymphoma and drug hypersensitivity syndrome (drug rash with eosinophilia and systemic symptoms: DRESS)SKIN REACTIONS TO DILTIAZEMProbleme bei der Behandlung mit KalziumantagonistenReports of Erythematous Macular Skin Eruptions Associated with Diltiazem TherapySide Effects — Overdosage — Contraindications — Drug InteractionsAngioedema from calcium channel blockersNebenwirkungen — Überdosierung (Vergiftung) — Kontraindikationen — ArzneimittelinteraktionenKalziumantagonistenAntianginal and β-adrenoceptor antagonistsAntianginal and β-adrenoceptor blocking drugs 1 April 1985Volume 102, Issue 4Page: 558-558KeywordsDrugsHyperlipidemiaHypersensitivityHypertensionRashesStable coronary artery diseaseVertigo Issue Published: 1 April 1985 PDF downloadLoading ...
Recessive missense mutations in LAMB2 expand the clinical spectrum of LAMB2-associated disorders
Authors: K. Hasselbacher, R.C. Wiggins, V. Matejas, B.G. Hinkes, B. Mucha, B.E. Hoskins, F. Ozaltin, G. Nürnberg, C. Becker, D. Hangan, M. Pohl, E. Kuwertz-Bröking, M. Griebel, V. Schumacher, B. Royer-Pokora, A. Bakkaloglu, P. Nürnberg, M. Zenker, F. Hildebrandt
Journal: Kidney International (2006)
FACTORS ASSOCIATED WITH IMPROVEMENT IN GUIDELINE-BASED USE OF IMPLANTABLE CARDIOVERTER DEFIBRILLATORS IN ELIGIBLE HEART FAILURE PATIENTS BY IMPLEMENTING A PRACTICE-BASED PERFORMANCE IMPROVEMENT INTERVENTION: RESULTS FROM IMPROVE HF
Authors: Mandeep R. Mehra, Nancy M. Albert, Anne B. Curtis, Mihai Gheorghiade, J. Thomas Heywood, Patches Johnson Inge, Mark L. McBride, Christopher M. O'Connor, Dwight Reynolds, Mary Norine Walsh, Clyde W. Yancy, Gregg C. Fonarow
Journal: Journal of the American College of Cardiology (2011)
Comprehensive Textbook of Psychiatry/VI
Authors: Carl C. Bell
Journal: JAMA (1996)

This two-volume text covers nearly every aspect of modern psychiatry. Because the last edition was published in 1989, the advent of the<i>Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)</i>called for major changes in the 30th anniversary edition of the Kaplan and Sadock text. Thus, it is nearly 25% larger than the previous edition. The volumes contain 53 chapters, 27 of which focus on the diagnostic approach taken in<i>DSM-IV</i>, and accordingly, diagnostic categories are highlighted with a critical commentary on the criteria and a case example. A new useful addition are the color pictures of all the drugs currently used in psychiatry in the United States. Another serviceable feature is that contributors were asked to note with an asterisk the five most important references in their long bibliographies. The preface has a succinct and pithy explication of the crisis in US health care and is well
High-Resolution Renal SPECT In Eight Minutes Using a Multi-Detector Gamma Camera
Authors: JOHN R. BUSCOMBE, CAROLINE E. TOWNSEND, KYPROS KOURIS, GILL CLARKE, SHAHID MAHMOOD, PETER H. JARRITT, PETER J. ELL
Journal: Clinical Nuclear Medicine (1995)

Planar renal scintigraphy with Tc-99m DMSA has become established as a standard diagnostic test to determine if a kidney has been scarred by infection. It has been suggested that high resolution SPECT may improve the sensitivity of detection of renal scars. To determine if it is possible to produce good quality renal SPECT with a short acquisition time, 10 adults were examined with a new multi-detector gamma camera using 8 minute, 16 minute, and 32 minute acquisitions. The number of defects seen (N = 16) with an 8 minute acquisition was not significantly different from the defects (N = 15) seen using a 16 minute and a 32 minute acquisition. In adults when Imaging with a multi-detector gamma camera there was no clinical advantage in using an acquisition of longer than 8 minutes.
Influence of age on the metabolism of plasma low density lipoproteins in healthy males.
Authors: S Ericsson, M Eriksson, S Vitols, K Einarsson, L Berglund, B Angelin
Journal: Journal of Clinical Investigation (1991)

The plasma concentration of the atherogenic low density lipoproteins (LDL) increases with age. To clarify the mechanism of this change, we studied the kinetics of autologous 125I-LDL apolipoprotein B (apo B) in 41 normolipidemic, nonobese healthy males. For comparison, they were divided into three age groups: young, 21-39 yr (n = 18), middle-aged, 40-59 yr (n = 11), and old, 60-80 yr (n = 12). The levels of plasma LDL cholesterol and LDL apo B increased from respectively 3.4 +/- 0.1 (SEM) mmol/liter and 86 +/- 2 mg/dl in the young to 4.1 +/- 0.1 mmol/liter and 95 +/- 3 mg/dl in the old (P less than 0.01), and this increase was linked to a progressively decreased (r = -0.38, P less than 0.02) fractional catabolic rate of LDL apo B (0.348 +/- 0.010 pools per day in the young vs. 0.296 +/- 0.009 pools per day in the old, P less than 0.01). The production rate of LDL apo B did not differ significantly between the groups. The reduced fractional catabolic rate of LDL apo B in the old was not associated with a decrease in binding affinity of the LDL particle to its receptor, as judged from its ability to compete for 125I-LDL fibroblast binding. When hepatic LDL receptor expression was stimulated by cholestyramine treatment in six old males, their LDL apo B fractional catabolic rate increased to the levels observed in the young subjects. We conclude that the increase in LDL which normally occurs with age is explained by a reduced capacity for its removal, and hypothesize that this is mediated via a reduced hepatic LDL receptor expression.
TUBELIKE INFILTRATIVE MUCINOUS CARCINOMA OF RECTUM IN A NINETEEN YEAR OLD PATIENT
Authors: Charles S. Higley
Journal: JAMA (1933)

This case is reported because of the unusual type of the tumor, which converted the rectum into a rigid firm tube as disclosed by clinical and pathologic examination. Karsner and Clark<sup>1</sup>in their review of the literature found only one direct reference to this form of tumor, that of Bensaude, Cain and Orléan.<sup>2</sup>They reported three cases, without information as to age, sex or special microscopic features, and stated that the condition was simply referred to by Bard. In their first case the lesion extended for 7 cm. at the rectosigmoid junction. In the second there was a vegetating cancer in the ampulla of the rectum which extended in tubelike form for 18 cm. above, involving posterior and lateral walls. The symptoms of the third case began as an acute dysentery and the lesion extended for 20 cm. in the rectosigmoid region. They used the descriptive phrase "un
COMBINED DRUG SCREENING AND PHOSPHOPROTEOMICS IDENTIFIES CANDIDATE BRAIN TUMOR THERAPEUTICS AND NOVEL TARGETS IN PRIMARY HUMAN BRAIN TUMOR-INITIATING CELLS
Authors: D. Kaplan, N. Grinshtein, C. Rioseco, A. Luchman, A. Datti, A. Aman, D. Uehling, M. Prakesch, J. Wrana, G. Cairncross, Y. Shen, S. Jones, M. Marra, D. Senger, S. Robbins, R. Al-Awar, M. Moran, S. Weiss
Journal: Neuro-Oncology (2014)

BACKGROUND: “Therapeutic Targeting of Glioblastoma” is a new pan-Canadian research team of the Terry Fox Research Institute and the Canadian Stem Cell Network funded to discover efficacious therapeutics for GBM. The team's goals are also to discover novel signaling pathways regulating GBM cell survival and genetic alterations that mediate drug resistance. As a platform, we use our collection of over 100 primary GBM tumor-initiating lines (BTIC) that are subjected to drug screening by over 1400 compounds, and to genetic and phosphoproteomic analysis. METHODS: We performed drug screening of 21 BTIC lines that represent the molecular heterogeneity of GBM patients, with a library of 110 clinically-relevant kinase inhibitors at three concentrations. We have also completed a phosphotyrosine characterization of 14 BTIC lines using phosphoproteomics. RESULTS: Multiple compounds that exhibit nanomolar cytotoxicity towards all of the lines were prioritized based upon their potency, novelty for GBM, ability to accumulate to relevant concentrations in brain, clinical status and cytotoxicity towards normal cells. Of the several hit compounds that fulfilled all of these criteria, the CDK inhibitor dinaciclib was chosen as our lead compound. We are currently investigating its mechanism of action using phosphoproteomics and RNAi as well as testing its efficacy in vivo in an orthotopic xenograft model as a single agent and in combination with TMZ. Furthermore, we have identified several compounds that exhibit selective cytotoxicity towards only a specific set of BTIC lines, suggesting that genetic differences between the lines account for differential sensitivities. The sensitivity of BTICs to one such compound, EMD-1214063, a selective MET inhibitor, may correlate with Met amplification status. Finally, phosphoproteomics results show activation of RTKs (EGFR, FGFR, PDGFRA, Eph receptor family) and non-receptor kinases (FYN, FAK1, GSK3b, MAPK, CDKs, DYRK) in the majority of BTIC lines, and of adaptor/scaffold proteins and proteins important in adhesion and migration. We are now (1) determining whether drugs that inhibit the activity of identified phosphoproteins suppress BTIC survival in culture and in orthotopic models, (2) validating the importance of those phosphoproteins in GBM survival, and (3) asking whether the prioritized drug hits from our drug screens suppress the phosphorylation of the identified phosphoproteins. CONCLUSIONS: We anticipate that our drug screening approach will generate several clinical candidates that will enable us to proceed to the clinic in the next several years. We also believe that our phosphoproteomics results will lead to identification of novel therapeutic targets for GBM. SECONDARY CATEGORY: Preclinical Experimental Therapeutics.
Obscure splenomegaly in the tropics that is not the tropical splenomegaly syndrome.
Authors: K M DeCock, S B Lucas, P H Rees, A N Hodgen, R A Jupp, B Slavin
Journal: BMJ (1983)

From the age of 18 this had become gradually more severe, and he had observed progressive coarsening of his features.At referral he was noted to have severe facial acne and acromegalic features.Acromegaly was confirmed by basal growth hormone concentrations of 16-7-20 mU/l, which failed to decrease after oral glucose.Serum concentrations of luteinising hormone (4 U/1) and follicle stimulating hormone (3 U/1) rose to 12 U/I and 14 U/l respectively in response to gonadotrophin releasing hormone.Serum concentrations of testosterone (21-6 nmol/l (6-2 ng/ml)) and prolactin (295 mU/1) were normal.Attempted surgical removal of a suprasellar pituitary adenoma only partially suppressed secretion of growth hormone (to 13-6-14-6 mU/I); because medical treatment also failed to give adequate control external radiotherapy (4000 rads) was given.Meanwhile his acne remained active, the acromegaly became more gross, and he developed hidradenitis suppurativa of the left axilla and perineum.
Radioimmunotherapy-based conditioning for hematopoietic cell transplantation in children with malignant and nonmalignant diseases
Authors: Ansgar S. Schulz, Gerhard Glatting, Manfred Hoenig, Catharina Schuetz, Susanne A. Gatz, Simon Grewendorf, Monika Sparber-Sauer, Rainer Muche, Norbert Blumstein, Gabriele Kropshofer, Meinolf Suttorp, Donald Bunjes, Klaus-Michael Debatin, Sven N. Reske, Wilhelm Friedrich
Journal: Blood (2011)
Indian prison doctors are promised more help to fight abuse of prisoners
Authors: Vivienne Nathanson
Journal: BMJ (2007)

The Indian Medical Association has vowed to secure better resources for prison doctors and to provide protection for those doctors who speak out against abuse. It has also publicly stated that it opposes interrogational torture—an illegal but widely used practice in the country.

Delegates at a conference in Delhi last week on medical ethics in places of detention described how many prisoners and detainees are subject to torture or to cruel, inhumane, and …
Continuous subcutaneous insulin infusion: an approach to achieving normoglycaemia.
Authors: J C Pickup, H Keen, J A Parsons, K G Alberti
Journal: BMJ (1978)

A study was performed to examine the feasibility of achieving long periods of near-normoglycaemia in patients with diabetes mellitus by giving a continuous subcutaneous infusion of insulin solution from a miniature, battery-driven, syringe pump. Twelve insulin-dependent diabetics had their insulin pumped through a subcutaneously implanted, fine nylon cannula; the basal infusion rate was electronically stepped up eightfold before meals. The blood glucose profile of these patients was closely monitored during the 24 hours of the subcutaneous infusion and compared with the profile on a control day, when the patients were managed with their usual subcutaneous insulin. Diet and exercise were standardised on both days. In five out of 14 studies the subcutaneous insulin infusion significantly lowered the mean blood glucose concentration without producing hypoglycaemic symptoms; in another six patients the mean blood glucose concentration was maintained. As assessed by the M value the level of control was statistically improved in six out of 14 studies by the infusion method and maintained in six other patients. To assess the effects of blood glucose control on diabetic microvascular disease it will be necessary to achieve long-term normoglycaemia in selected diabetics. The results of this preliminary study suggest that a continuous subcutaneous insulin infusion may be a means of maining physiological glucose concentrations in diabetics. Though several problems remain--for example, in determining the rate of infusion--longer-term studies with the miniature infusion pumps are now needed.
Extrapancreatic action of truncated glucagon-like peptide-I in otsuka long-evans tokushima fatty rats, an animal model for non—insulin-dependent diabetes mellitus
Authors: Akira Mizuno, Masamichi Kuwajima, Kaori Ishida, Yoshihiko Noma, Takashi Murakami, Kayoko Tateishi, Izumi Sato, Kenji Shima
Journal: Metabolism (1997)