tbuckley/cabot-search huggingface dataset:
Save the FDA
Authors: Alexander S D Spiers
Journal: BMJ (2005)

Save the FDAEditor-Abbasi asks whether drug regulation is failing. 1 The US Food and Drug Administration (FDA) performs a thankless task.Patients want new drugs available immediately and agitate to accomplish this.Patients also wish medicines to be guaranteed safe, and blame the FDA when toxicity leads to a drug's withdrawal.Clinical scientists complain that the FDA obstructs their investigations.Pharmaceutical companies see the FDA as an adversary, not a protector.Practising in the USA for 20 years, I encountered many FDA agents.A few revered regulations for their own sake.Such people are irksome, but without strict oversight valueless and toxic agents would be marketed.A prime example is Laetrile (laevo-mandelonitrile-beta-glucuronoside), a useless and poisonous drug promoted for cancer treatment.The FDA, supported by the National Cancer Institute, successfully resisted extreme public pressure to allow its marketing, saving many lives and a multimillion dollar fraud.The FDA faces serious accusations.Attempting to suppress David Graham's whistleblowing on rofecoxib assaults scientific honesty. 2 3 The FDA's refusal to allow non-prescription sales of emergency contraception indicates unacceptable political pressure from the religious right.Unduly close relations between the FDA and pharmaceutical companies may lead to premature marketing approvals.How should the FDA be saved?Firstly, officials ordering withdrawal of a drug should be independent of those who approve marketing.Secondly, making the FDA a quango would protect from political pressures.Thirdly, conflicts of interest involving FDA employees and consultants must be rigorously scrutinised, even more severely than editors scrutinise the interests of contributors.The UK's Medicines and Healthcare products Regulatory Agency is accused of proindustry bias.Housecleaning there and at the FDA will benefit patients, doctors, and the pharmaceutical industry itself.
Fibroblast growth factor signaling in liver carcinogenesis
Authors: Dalbir S. Sandhu, Esha Baichoo, Lewis R. Roberts
Journal: Hepatology (2013)

Fibroblast growth factors, or FGFs, are a large family of polypeptide cytokines exhibiting a pleiotropy of functions, from cell growth to angiogenesis, wound healing, and tissue repair. This review broadly covers the genetics and protein expression of the FGF family members and the signaling pathways involved in FGF-mediated growth regulation. We emphasize the role of FGFs in the pathogenesis of hepatocellular carcinoma (HCC), including their effects on regulation of the tumor microenvironment and angiogenesis. Finally, we present current views on FGF's potential role as a prognostic marker in clinical practice, as well as its potential as a therapeutic target in HCC. (Hepatology 2014;59:1166–1173)
Sleep: A Comprehensive Handbook
Authors: Raman K. Malhotra, Alon Y. Avidan
Journal: JAMA (2007)

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 4924: Gene-specific hyper and hypomethylation in follicular lymphoma progression
Authors: Matilde Saggese, Venkata Thodima, Adriana Heguy, Timothy A. Chan, Raju S. K. Chaganti
Journal: Cancer Research (2010)

Abstract Epigenetic mechanisms involved in the origin and transformation of indolent lymphomas to aggressive forms are poorly understood. Based on the comparison of methylation states of follicular lymphoma (FL) pre and post- transformation, it has been suggested that DNA methylation changes occur during the early stages of lymphomagenesis. To obtain a more complete understanding of methylation aberrations responsible for progression and transformation of FL, we analyzed 20 untreated FL biopsies (10 low grade, 10 high grade), 5 diffuse large B cell lymphoma (DLBCL) biopsies, and 5 benign reactive lymph node (RLN) biopsies by using methyl-DNA immunoprecipitation coupled with analysis with Agilent 244K human promoter ChIP-on-chip microarrays. Our analysis revealed statistically significant differences in methylation status for 120 genes between FL samples and RLN samples and for 23 genes between low and high grade FL samples. To investigate the biological significance of these findings, we used DAVID functional annotation clustering algorithms and Gominer software. We found that the most methylation-enriched functional groups were comprised of genes with roles in cell cycle control, adhesion and motility, transcription regulation, homeobox, and developmental genes. In order to validate the DNA methylation differences of the significant gene regions, we utilized the MassARRAY EpiTYPER assay. Our data identified 13 genes (CYP26B1, GRM7, HS3ST2, DOCK5, GRB10, SST, TAC1, PALM2-AKAP, FLJ40125, ST6GAL2, WDR35, NCAM1, SATB2) with increased levels of DNA methylation in FL samples compared to controls; 3 of these genes (ST6GAL2, WDR35, NCAM1) exhibited increased methylation in high grades FLs and 1 gene (SATB2) in low grades FLs. We are currently investigating gene specific DNA hypomethylation in low versus high grade FL and FL versus DLBCL. Our data are the first to characterize the global changes in methylation that occur in FL progression. Our findings suggest that high grade FL are associated with hypermethylation of a specific subset of genes compared to low grade subtypes. Ongoing efforts include investigating the functional relevance of these methylation changes by treating, in vitro, FL cell lines with demethylating agents to evaluate changes in gene expression levels and correlating with phenotype alterations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4924.
ABC of colorectal diseases. Intestinal stomas.
Authors: M. H. Irving, O. Hulme
Journal: BMJ (1992)

A stoma is a surgically created opening of the bowel or urinary tract on to the body surface.The commonest procedures for producing intestinal stomas are ileostomy, colostomy, and urostomy.End stoma. Types of stomaThere are several different types of stoma.End stomas are the simplest to create.The divided bowel is brought through the abdominal wall and anastomosed to the skin.Loop stomas are created when a mobile loop of bowel-of necessity either the small bowel or the mobile parts of the colon (transverse or sigmoid)-is brought through the abdominal wall and the margins sewn to the skin.Loop stomas are usually temporary, being used to protect anastomoses distal to the stoma or divert bowel contents away from diseased segments Loop stoma.further down the bowel such as an obstructing lesion or multiple perineal fistulas.Such stomas are prone to complications and because of their bulk are difficult to manage.Continent stomas are those in which surgical techniques are used to create a valve-like mechanism in the bowel proximal to the cutaneous opening which will allow discharge of faecal contents only when intubated.When successful such a valve avoids the need for a patient to wear an appliance.Other ways of creating openings on the abdominal wall include caecostomy, by which the caecum is intubated with a Foley catheter, which is commonly inserted through the stump of the removed appendix.Flatus and liquid faeces can escape through the lumen of the catheter.-1Z' 'The distal end of a divided se gent of bowel can be closed and returned to the abdomen as in the Hartmann's procedure, but it is often brought to the abdominal surface and sutured to the skin and is then termed a mucus fistula.Continent stoma with catheter in pouch. Stoma care nurses tStoma care coursesAlthough the patient's doctor will be the first to suggest that a stoma will Stoma care courses be necessary, preoperative explanation and counselling will usually be * Hope Hospital, Salford undertaken by a stoma care nurse, who is specially trained in the * North Tees General Hospital, Stockton management of patients with all types of stomas.Courses leading to the
Activation of chemicals into mutagens by green plants: a preliminary discussion.
Authors: M J Plewa
Journal: Environmental Health Perspectives (1978)

This paper is a review of recent studies that demonstrate the activation of chemicals (especially pesticides into mutagens by green plants. Such activation of pesticides may be hazardous to the public health because of their widespread use in agriculture and the current lack of information that exists about such processes. The mutagenic properties of the s-triazine herbicides (atrazine, simazine, and cyanazine) as exhibited in various assay systems are discussed. In vivo, in vitro, and in situ plant assays are presented, and the maize wx locus assay is discussed.
Diagnostic Decision
Authors: ANTHONY L. SUCHMAN
Journal: Annals of Internal Medicine (1986)

The activated partial thromboplastin time (APTT) and prothrombin time (PT) have three principal uses. In screening for coagulation disorders (or increased risk of postoperative hemorrhage), the tests add no information to the preoperative care of patients without clinical findings indicative of increased bleeding risk. Furthermore, the prevalence of asymptomatic congenital coagulopathies is so low that false-positive test results greatly outnumber true-positive results. Thus, clinicians may use clinical assessment to screen and should reserve coagulation tests to investigate patients with abnormal findings. In evaluating abnormal bleeding, these tests are sufficiently sensitive that if both are negative, further investigation of the coagulation system is obviated. If one or both tests are positive, the pattern of results directs further attention to limited segments of the coagulation sequence. In monitoring anticoagulation therapy, the APTT and PT tests appear to contribute to the safety and effectiveness of heparin and warfarin therapies, respectively.
Effects of short-term and long-term treatment with inhaled corticosteroids on bone metabolism in patients with airways obstruction. Dutch CNSLD Study Group.
Authors: H A Kerstjens, D S Postma, J J van Doormaal, A K van Zanten, P L Brand, P N Dekhuijzen, G H Koeter
Journal: Thorax (1994)

BACKGROUND--Recent reports have suggested short-term changes in serum parameters of bone metabolism with inhaled corticosteroids. The relevance of these findings to the balance between bone formation and resorption during years of corticosteroid treatment remains uncertain. METHODS--Two novel markers of bone turnover were first compared with conventional markers in a pilot study and subsequently measured in a long-term double blind study of inhaled corticosteroids. In study I 15 patients were newly started on at least 800 micrograms inhaled corticosteroids daily. At entry and after four weeks serum levels of alkaline phosphatase, osteocalcin, and PICP (procollagen type I carboxy terminal propeptide; a procollagen splice product) were measured as markers of bone formation, as well as the urinary hydroxyproline/creatinine ratio and serum levels of ICTP (type I collagen carboxy terminal telopeptide; a collagen degradation product) as markers of bone resorption. In study II 70 patients with airways obstruction received 800 micrograms beclomethasone daily in addition to terbutaline and 85 received bronchodilators only in a double blind fashion. Serum levels of PICP and ICTP were measured before and after 2.5 years of treatment. RESULTS--In study I a decrease in osteocalcin levels was accompanied by an increase in levels of PICP and a small and non-significant rise in alkaline phosphatase. There were no changes in hydroxyproline or ICTP. In study II no differences were found in serum levels of PICP between the treatment groups; an increase in serum ICTP was found in the group treated without inhaled corticosteroids compared with the group treated with inhaled corticosteroids. CONCLUSIONS--No detrimental long-term effect of inhaled corticosteroids was found with three conventional and two novel parameters of bone metabolism. The results indicate that long-term changes in bone turnover during treatment with inhaled corticosteroids should not be deduced from short-term studies with single serum parameters of bone metabolism, but well designed long-term studies of, for example, bone densitometry should be awaited before quoting detrimental effects of inhaled corticosteroids on bone metabolism.
Health-Manpower Needs
Authors: Alexander Leaf
Journal: New England Journal of Medicine (1978)

Congress has temporarily settled the health-manpower controversy with its compromised, but still controversial, legislation. As a condition for federal capitation support of medical schools, the new law requires a 5 per cent increase in third-year medical-school classes from defined new pools of potential applicants. Although some may claim that the current legislation is largely the result of political pressures rather than a perception that a great need exists for more physicians in this country, the continued expansionist policies of Congress in increasing the number of physicians deserves examination.Even when the figure of a 50,000-physician shortage suddenly sprang on the . . .
Spatiotemporal Characteristics of Junctional and Nonjunctional Focal Ca <sup>2+</sup> Release in Rat Atrial Myocytes
Authors: Sun-Hee Woo, Lars Cleemann, Martin Morad
Journal: Circulation Research (2003)

Atrial myocytes have two functionally separate Ca 2+ release sites: those in peripheral sarcoplasmic reticulum (SR) adjacent to the Ca 2+ channels of surface membrane and those in central SR not associated with Ca 2+ channels. Recently, we have reported on the gating of these two different Ca 2+ release sites by Ca 2+ current. In the present study, we report on the spatiotemporal properties of focal Ca 2+ releases (sparks) occurring spontaneously in central and peripheral sites of voltage-clamped rat atrial myocytes, using rapid 2-dimensional (2-D) confocal Ca 2+ imaging. Peripheral and central sparks were similar in size and release time (≈300 000 Ca 2+ ions for ≅12 ms), but significantly larger and longer than ventricular sparks. Both sites were resistant to Cd 2+ and inhibited by ryanodine. Peripheral sparks were brighter and flattened against surface membrane, had ≈5-fold higher frequency, ≈2 times faster diffusion coefficient, and dissipated abruptly. Central sparks, in contrast, occurred less frequently, were elongated along the cellular longitudinal axis, and dissipated slowly. Compound sparks (composed of 2 to 5 unitary focal releases) aligned longitudinally and occurred more frequently at the center. The diversity of peripheral and central sparks with respect to shape, frequency, and speed of spatial development and decay is consistent with regional ultrastructural heterogeneity of SR. The retarded dissipation of central atrial sparks, and high prevalence of compound sparks in cell center may be critical in facilitating the propagation of Ca 2+ waves in atrial myocytes lacking t-tubular system and provide the atrial myocytes with functional Ca 2+ signaling diversity. The full text of this article is available at http://www.circresaha.org.
Encephalopathy assessment in children with extra-hepatic portal vein obstruction with MR, psychometry and critical flicker frequency
Authors: Santosh K. Yadav, Anshu Srivastava, Arti Srivastava, Michael A. Thomas, Jaya Agarwal, Chandra M. Pandey, Richa Lal, Surender K. Yachha, Vivek A. Saraswat, Rakesh K. Gupta
Journal: Journal of Hepatology (2010)
MIXTURES OF THE UNITED STATES PHARMACOPEIA
Authors: OLIVER T. OSBORNE
Journal: JAMA (1913)

This paper is to complete the series of three which I have recently written on the subject of a better, more limited Pharmacopeia.<sup>1</sup> I seriously question the advisability of including the following mixtures in the next Pharmacopeia, on the ground that many of the ingredients are needless and useless, and, in fact, that these multiple mixtures are unscientific. The preparations in questions are: Elixir adjuvans. Elixir ferri, quininae et strychninae phosphatum. Extractum colocynthidis compositum. Infusum sennae compositum (black draught). Liquor ferri et ammonii acetatis (Basham's mixture). Liquor sodii phosphatis compositus. Massa hydrargyri. Mistura glycyrrhizae composita (brown mixture). Mistura rhei et sodae. Pilulae catharticae compositae. Pulvis aromaticus. Pulvis cretae compositus. Syrupus hypophosphitum compositus. Syrupus sarsaparillae compositus. Syrupus scillae compositus. Tinctura benzoini composita. Tincture lavandulae composita. This is the age in which we are analyzing and criticizing everything in the therapeutic line, and why should we accept as gospel, and as above
Serum interleukin-10 in plasma-cell dyscrasias
Authors: Roberto Stasi, Maurizio Brunetti, Stefano Bussa, Adalberto Pagano
Journal: American Journal of Hematology (1997)

Serum levels of interleukin-10 (IL-10) were measured by enzyme-linked immunosorbent assay in 115 patients with multiple myeloma (MM) in various phases of the disease (68 at diagnosis, 22 in plateau phase, 22 in relapse), in 71 individuals with monoclonal gammopathy of undetermined significance (MGUS), and in 53 normal volunteers. Detectable levels of serum IL-10 were found in 24 myelomas (20.9%), in 7 cases of MGUS (9.9%), and in 4 normal subjects (7.5%) (P = NS, χ2 test). In patients with MM, cytokine was detected with a comparable frequency in all pathologic stages and phases of the disease: 4/19 in stage I, 6/26 in stage II, 5/23 in stage III, 4/22 in plateau phase, and 5/25 in progressing or relapsed disease. IL-10 concentrations did not differ significantly between controls and patients with plasma-cell dyscrasia, between patients with MGUS and those with MM, between early vs. advanced MM, or between patients in different phases of the disease. In 36 patients with MM in whom IL-10 was measured serially, no significant changes were observed over the course of the disease. Also, when comparing the outcomes of individuals with detectable or undetectable IL-10 in single stages or in the whole myeloma group, no differences were revealed. Our results do not support an apparent involvement of IL-10 in the pathogenesis of MM in vivo. However, further studies are required to define the exact role of this cytokine within the complex cytokine network of this neoplastic disorder. Am. J. Hematol. 54:335–337, 1997. © 1997 Wiley-Liss, Inc.
Borrelia in Boston
Authors: Robert L. Goodman
Journal: JAMA (1969)

A 26-year-old, intermittently febrile woman returned from the West to Boston, where a diagnosis of relapsing fever was established. The infection should be considered in travelers from the western states who manifest recurrent fever and weakness, often with splenomegaly and rash. The diagnosis is most directly established by demonstrating spirochetes in properly stained blood smears during the febrile periods.
Intramural Virtual Electrodes in Ventricular Wall
Authors: Oleg F. Sharifov, Vladimir G. Fast
Journal: Circulation (2004)

Intramural virtual electrodes (IVEs) are believed to play an important role in defibrillation, but their existence in intact myocardium remains unproven. Here, IVEs were detected by use of optical recordings of shock-induced transmembrane potential (V(m)) changes (DeltaV(m)) measured from the intact epicardial heart surface.To detect IVEs, isolated porcine left ventricles were sequentially stained with a V(m)-sensitive dye by 2 methods: (1) surface staining (SS) and (2) global staining (GS) via coronary perfusion. Shocks (2 to 50 V/cm) were applied across the ventricular wall in an epicardial-to-endocardial direction during the action potential plateau via transparent mesh electrodes, and shock-induced DeltaV(m) were measured optically from the same epicardial locations after SS and GS. Optical recordings revealed significant differences between DeltaV(m) of 2 types that became more prominent with increasing shock strength: (1) for weak shocks, SS-DeltaV(m) were larger and faster than GS-DeltaV(m); (2) for intermediate shocks, cathodal GS-DeltaV(m) became multiphasic, whereas SS-DeltaV(m) remained monophasic; and (3) for strong shocks, cathodal GS-DeltaV(m) became uniformly negative, whereas SS-DeltaV(m) typically remained positive. The radical differences in the shape and polarity of SS and GS polarizations can be explained by the contribution of subepicardial IVEs to optical signals. Histological examination revealed a dense network of collagen septa in the subepicardium, which could form the IVE substrate.Intramural virtual electrodes are reflected in optical measurements of shock-induced DeltaV(m) on the intact epicardial surface. These IVEs could be a result of microscopic resistive discontinuities formed by collagen septa.
Oral Contraceptives and Reduced Risk of Benign Breast Diseases
Authors: Howard Ory, Philip Cole, Brian MacMahon, Robert Hoover
Journal: New England Journal of Medicine (1976)

In 1970 a questionnaire on oral-contraceptive use was mailed to 97,254 married women 25 to 49 years of age in Greater Boston. Sixty-nine per cent responded. During the subsequent 30 months, 1072 of the women were hospitalized for breast diseases. Hospitalization rates for fibrocystic disease were similar for non-users of oral contraceptives and users of one to 12 months' duration. However, users for 13 months to 24 months and 25 or more months had rates only 70 and 35 per cent, respectively, of those of non-users. Detailed analysis of these results, and their similarity to findings in previous studies, suggest that the association is causal — use of oral contraceptives appears to lower risk of fibrocystic breast disease. A similar association was seen for fibroadenoma. Rates of breast cancer were lower for users than for non-users, but this finding was neither related to duration of use nor statistically significant. (N Engl J Med 294:419–422, 1976)
The Verdict From ALLHAT—Thiazide Diuretics Are the Preferred Initial Therapy for Hypertension
Authors: Lawrence J. Appel
Journal: JAMA (2002)

Quite simply, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is one of the most important trials of antihypertensive therapy. For decades, experts have passionately debated which class of drugs should be initial therapy for hypertension. Resolution of this issue, which has enormous clinical, public health, and economic implications, comes at a time of intense pressure to reduce health care costs while improving clinical outcomes. In this setting, the ALLHAT results, reported in this issue of THE JOURNAL, are particularly noteworthy, because there is no cost-quality tradeoff; the most effective therapy was also the least expensive.