tbuckley/cabot-search huggingface dataset:
Intrahepatic cholangiectases and large-duct obliteration in primary sclerosing cholangitis
Authors: Jurgen Ludwig, Robert L. Maccarty, Nicholas F. Larusso, Ruud A. F. Krom, Russell H. Wiesner
Journal: Hepatology (1986)

We studied intrahepatic bile ducts of five patients with chronic ulcerative colitis and primary sclerosing cholangitis. The livers had been obtained at the time of orthotopic liver transplantation. After specimen cholangiography and perfusion fixation, sequential blocks and sections from portal tracts were studied, combining light microscopy with scanning electron microscopy. In vivo cholangiograms were studied also. The specimens revealed: absence of normal bile ducts; presence of thin-walled tubular or saccular cholangiectases with semicircular and annular fibrous crests, without evidence of superinfection; cholangiectases with secondary acute or chronic-cellular cholangitis, with or without cholangitic abscesses; fibrous cholangitis without ductal dilatation; transformation of bile ducts into fibrous cords which were either solid or contained remnants of bile duct epithelium, and complete loss of bile ducts. The shape and distribution of the cholangiectases suggested that these lesions were manifestations of the disease process and not passively dilated normal ducts. Fibrous-obliterative cholangitis with formation of fibrous cords was found not only at the level of interlobular and adjacent septal bile ducts but also at the level of segmental bile ducts that normally would have been demonstrable in cholangiograms. The "pruned-tree" appearance in cholangiograms appears to result from the transition between patent and often cholangiectatic ducts, and duct obliteration. At present, intrahepatic cholangiectases in association with duct obliteration can be considered pathognomonic morphologic features of primary sclerosing cholangitis.
A <i>C. elegans</i> Screening Platform for the Rapid Assessment of Chemical Disruption of Germline Function
Authors: Patrick Allard, Nicole C. Kleinstreuer, Thomas B. Knudsen, Monica P. Colaiácovo
Journal: Environmental Health Perspectives (2013)

Background: Despite the developmental impact of chromosome segregation errors, we lack the tools to assess environmental effects on the integrity of the germline in animals.Objectives: We developed an assay in Caenorhabditis elegans that fluorescently marks aneuploid embryos after chemical exposure.Methods: We qualified the predictive value of the assay against chemotherapeutic agents as well as environmental compounds from the ToxCast Phase I library by comparing results from the C. elegans assay with the comprehensive mammalian in vivo end point data from the ToxRef database.Results: The assay was highly predictive of mammalian reproductive toxicities, with a 69% maximum balanced accuracy. We confirmed the effect of select compounds on germline integrity by monitoring germline apoptosis and meiotic progression.Conclusions: This C. elegans assay provides a comprehensive strategy for assessing environmental effects on germline function.
Hormonal contraception and risk of venous thromboembolism: national follow-up study
Authors: O. Lidegaard, E. Lokkegaard, A. L. Svendsen, C. Agger
Journal: BMJ (2009)

<b>Objective</b> To assess the risk of venous thrombosis in current users of different types of hormonal contraception, focusing on regimen, oestrogen dose, type of progestogen, and route of administration. <b>Design</b> National cohort study. <b>Setting</b> Denmark, 1995-2005. <b>Participants</b> Danish women aged 15-49 with no history of cardiovascular or malignant disease. <b>Main outcome measures</b> Adjusted rate ratios for all first time deep venous thrombosis, portal thrombosis, thrombosis of caval vein, thrombosis of renal vein, unspecified deep vein thrombosis, and pulmonary embolism during the study period. <b>Results</b> 10.4 million woman years were recorded, 3.3 million woman years in receipt of oral contraceptives. In total, 4213 venous thrombotic events were observed, 2045 in current users of oral contraceptives. The overall absolute risk of venous thrombosis per 10 000 woman years in non-users of oral contraceptives was 3.01 and in current users was 6.29. Compared with non-users of combined oral contraceptives the rate ratio of venous thrombembolism in current users decreased with duration of use (&lt;1 year 4.17, 95% confidence interval 3.73 to 4.66, 1-4 years 2.98, 2.73 to 3.26, and &gt;4 years 2.76, 2.53 to 3.02; P&lt;0.001) and with decreasing dose of oestrogen. Compared with oral contraceptives containing levonorgestrel and with the same dose of oestrogen and length of use, the rate ratio for oral contraceptives with norethisterone was 0.98 (0.71 to 1.37), with norgestimate 1.19 (0.96 to 1.47), with desogestrel 1.82 (1.49 to 2.22), with gestodene 1.86 (1.59 to 2.18), with drospirenone 1.64 (1.27 to 2.10), and with cyproterone 1.88 (1.47 to 2.42). Compared with non-users of oral contraceptives, the rate ratio for venous thromboembolism in users of progestogen only oral contraceptives with levonorgestrel or norethisterone was 0.59 (0.33 to 1.03) or with 75 μg desogestrel was 1.12 (0.36 to 3.49), and for hormone releasing intrauterine devices was 0.90 (0.64 to 1.26). <b>Conclusion</b> The risk of venous thrombosis in current users of combined oral contraceptives decreases with duration of use and decreasing oestrogen dose. For the same dose of oestrogen and the same length of use, oral contraceptives with desogestrel, gestodene, or drospirenone were associated with a significantly higher risk of venous thrombosis than oral contraceptives with levonorgestrel. Progestogen only pills and hormone releasing intrauterine devices were not associated with any increased risk of venous thrombosis.
Mortality and VD
Authors: THOMAS M. ELDER
Journal: Annals of Internal Medicine (1972)

Letters, Comments, and Corrections1 March 1972Mortality and VDTHOMAS M. ELDERTHOMAS M. ELDERSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-3-513 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: My congratulations to Dr. Kampmeier on his cogent, timely discussion of the current epidemic in veneral disease (Ann Intern Med 75:793-794, 1971). As a medical student I thought his emphasis on the inadequacy of undergraduate medical education especially relevant. But I should like to call attention to a point I found lacking.Although he observes that "efforts at education based on 'morals' and 'right or wrong' are not 'in' and are to be avoided at all cost," parts of his editorial display an element of righteous indignation at what he may see as the moral turpitude of...Reference1. KAMPMEIER R: Physical Examination in Health and Disease., 4th ed. Philadelphia, F. A. Davis Co., 1970, p. 12 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: UCLA School of Medicine Los Angeles, Calif. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1972Volume 76, Issue 3Page: 513-514KeywordsMedical educationMortality Issue Published: 1 March 1972 PDF DownloadLoading ...
On Defective Lactation, its Causes, and How Far it may be Influenced by Drugs
Authors: T. M. Dolan
Journal: BMJ (1884)

IN some papers published 'in the Pvactitioner in 1881, I attempted to throw some light on the influence exercised by drugs on the milk of mothers and nurses, taking, it the same time, ageneral survey of the whole question of lactation.It would be impossible, in a short paper, to enter into details of my experiments, I must, therefore, be content to lay before ypu the conclusions at which I arrived.This I da in the bope that ,they may be corrected, if they be proved wrong; and that the riper experiegce of others may throw additional light upon a subject which I deem to be even of national importance.I shall formulate a number of general principles, as you will thus be in a better position to discups my views.1.All therapeutical agents, inteaded to act on the mammary gland must first enter the blood, or be capable of seimn,ting the blood-supply in the mammary apparatis..This principlq folowsfrom what we know of the processes involved in the making, of, milk, and depends on the general principle that nutrition is dependent on blood-supply.2. All the drugs deriveed from the families Liliaceai, Cruciferwa' Solanaceve, Umbelliferae, etc., enter the blood and impreg,nate the milk, so that poisons in any of these classes must be adaj.nisteiedwith caution to the mother or nurse, lest the nursling may.be in- jured.I have,furnished instances, as dill, aniseed, and: conium,.to prove this..3. There is no true galaptagogue in the sense in which itis u.nder- stood.The nearest approach to, this is to be found in jahorandi * but this drug is not persistent in ita.action, as'it only temporarily afects the mammary secretion.4.There is an antigalactagogqb,.lelladonna.5. In inaction of the m4naiux, the milk may be increased and in- fluenced by medicines.6.The salts of milk, may,be ,mproved by the adm;inistration of 7. Various physiological actions-,purgative, alterative,'.diuretip,etc.-may,be produced in the child by the administration of drugs to the mother.. If we are to expect any improvement in, mill;-secreting,'power, both as to quantity and quality, we must look to diet and,hygiene for the attainment of that object.I shall next briefly suirise some of ihp causes why lactation is defective.
Fish Oil Supplementation and Plasma Cholesterol: The Power of a Clinical Trial
Authors: Ted P. Szatrowski
Journal: Annals of Internal Medicine (1990)

Letters and Corrections15 April 1990Fish Oil Supplementation and Plasma Cholesterol: The Power of a Clinical TrialTed P. Szatrowski, MDTed P. Szatrowski, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-112-8-633 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: Recently, Wilt and colleagues (1) concluded that fish oil supplementation fails to lower plasma cholesterol in hypercholesterolemic men. In a crossover study of 19 patients, no statistically significant (α = 0.10) difference in cholesterol levels was found in 38 treated subjects and 38 placebo controls. The authors implied that the study had greater than 99.9% power to detect a 5% drop (compared with placebo) in cholesterol level, suggesting a false-negative rate of less than 0.1%. The notion of type II error, or false-negative rate, in the setting of clinical trials has been reviewed (2).However, power calculations...References1. WiltLofgrenNichol TRK. Fish oil supplementation does not lower plasma cholesterol in men with hypercholesterolemia. Results of a randomized, placebo-controlled crossover study. Ann Intern Med. 1989;111:900-5. LinkGoogle Scholar2. FreimanChalmersSmithKuebler JTHR. The importance of beta, the type II error and sample size in the design and interpretation of the randomized control trial. Survey of 71 "negative" trials. N Engl J Med. 1978;299:690-4. CrossrefMedlineGoogle Scholar3. Lachin J. Introduction to sample size determination and power analysis for clinical trials. Controlled Clinical Trials. 1981;2:93-113. CrossrefMedlineGoogle Scholar4. Fleiss J. The Design and Analysis of Clinical Experiments. New York: John Wiley & Sons; 1986. Google Scholar5. WoodsWilliamsTavel JJM. The two-period crossover design in medical research. Ann Intern Med. 1989;110:560-6. LinkGoogle Scholar1. WiltLofgrenNichol TRK. Fish oil supplementation does not lower plasma cholesterol in men with hypercholesterolemia. Ann Intern Med. 1989;111:900-5. LinkGoogle Scholar2. . The Expert Panel. Arch Intern Med. 1988;148:36-69. CrossrefMedlineGoogle Scholar3. Fleiss J. The Design and Analysis of Clinical Experiments. New York: John Wiley & Sons; 1986:369-71. Google Scholar4. GardnerHeady MJ. Some effects of within-person variability in epidemiological studies. J Chron Dis. 1973;26:781-95. CrossrefGoogle Scholar5. Rosner B. Fundamentals of Biostatistics. Boston: PWS Publishers; 1986:264. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Cornell University Medical College New York, NY 10021 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 April 1990Volume 112, Issue 8Page: 633-634KeywordsBlood plasmaCholesterolClinical trialsOils Issue Published: 15 April 1990 PDF downloadLoading ...
Service commitment and the training of surgeons.
Authors: J J Shipman, K W Giles, R H Armour
Journal: BMJ (1979)

develop ways in which health and safety performance can be improved.The HMSO's sectional list 18 (Health and Safety Executive forms and publications) lists many publications, parts of which are now applicable to hospitals and associated areas.Sectional list 18 (Department of Health and Social Security) enumerates many codes, etc.
An Unusual Inflammatory Rash
Authors: Robert M. Gathings, John M. Abide, Robert T. Brodell
Journal: JAMA Pediatrics (2014)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Prevention of Dystrophic Pathology in Severely Affected Dystrophin/Utrophin-deficient Mice by Morpholino-oligomer-mediated Exon-skipping
Authors: Aurélie Goyenvalle, Arran Babbs, Dave Powell, Ryszard Kole, Sue Fletcher, Steve D Wilton, Kay E Davies
Journal: Molecular Therapy (2009)

Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder caused by mutations in the dystrophin gene that result in the absence of functional protein. Antisense-mediated exon-skipping is one of the most promising approaches for the treatment of DMD because of its capacity to correct the reading frame and restore dystrophin expression, which has been demonstrated in vitro and in vivo. In particular, peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) have recently been shown to induce widespread high levels of dystrophin expression in the mdx mouse model. Here, we report the efficiency of the PPMO-mediated exon-skipping approach in the utrophin/dystrophin double-knockout mouse (dKO) mouse, which is a much more severe and progressive mouse model of DMD. Repeated intraperitoneal (i.p.) injections of a PPMO targeted to exon 23 of dystrophin pre-mRNA in dKO mice induce a near-normal level of dystrophin expression in all muscles examined, except for the cardiac muscle, resulting in a considerable improvement of their muscle function and dystrophic pathology. These findings suggest great potential for PPMOs in systemic treatment of the DMD phenotype. Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder caused by mutations in the dystrophin gene that result in the absence of functional protein. Antisense-mediated exon-skipping is one of the most promising approaches for the treatment of DMD because of its capacity to correct the reading frame and restore dystrophin expression, which has been demonstrated in vitro and in vivo. In particular, peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) have recently been shown to induce widespread high levels of dystrophin expression in the mdx mouse model. Here, we report the efficiency of the PPMO-mediated exon-skipping approach in the utrophin/dystrophin double-knockout mouse (dKO) mouse, which is a much more severe and progressive mouse model of DMD. Repeated intraperitoneal (i.p.) injections of a PPMO targeted to exon 23 of dystrophin pre-mRNA in dKO mice induce a near-normal level of dystrophin expression in all muscles examined, except for the cardiac muscle, resulting in a considerable improvement of their muscle function and dystrophic pathology. These findings suggest great potential for PPMOs in systemic treatment of the DMD phenotype.
Genetic prediction and family structure in Huntington's chorea.
Authors: P S Harper, M Sarfarazi
Journal: BMJ (1985)

A deoxyribonucleic acid marker linked to the locus for Huntington9s chorea exists, but its possible use in the prediction of this disorder depends on the pedigree structure of individual families. Analysis of data from a population register for Huntington9s chorea in south Wales showed that only a minority of subjects at risk had the appropriate members of their family living to allow the presence or absence of the gene to be definitively predicted. However, the structure of the family allowed a degree of prediction (in particular, exclusion of the disorder) to be made for the fetus during pregnancies of these subjects in almost 90% of cases. Such a prediction need not alter the risk state for the parent at risk. The structure of the family will remain crucial for prediction even when current limitations of the linked marker have been overcome.
Endogenous benzodiazepine receptor ligands in idiopathic recurring stupor
Authors: J.D. Rothstein, A. Guidotti, P. Tinuper, P. Cortelli, P. Avoni, G. Plazzi, E. Lugaresi, P. Montagna, P. Schoch
Journal: The Lancet (1992)

"Endozepines" are endogenous ligands for the benzodiazepine recognition sites on gamma-aminobutyric acid A receptors in the nervous system. Idiopathic recurring stupor (IRS) is a syndrome of spontaneous stupor or coma that is not associated with known metabolic, toxic, or structural abnormalities but can be reversed by flumazenil, a pure benzodiazepine antagonist. We measured endozepine-2 and endozepine-4 by high-performance liquid chromatography and radioreceptor assay in serum and cerebrospinal fluid from three patients with IRS. During episodes of stupor there was a large (up to 300-fold compared with control patients) increase of endozepine-4 content in cerebrospinal fluid and serum, but a return to normal concentrations between attacks. Endozepine-4 may contribute to, or be the cause of, IRS. The reasons for abnormal concentrations of endozepine in blood and brain are unknown.
Enhanced survival in Sandhoff disease mice receiving a combination of substrate deprivation therapy and bone marrow transplantation
Authors: Mylvaganam Jeyakumar, Francine Norflus, Cynthia J. Tifft, Mario Cortina-Borja, Terry D. Butters, Richard L. Proia, V. Hugh Perry, Raymond A. Dwek, Frances M. Platt
Journal: Blood (2001)
Bepridil and cetiedil. Vasodilators which inhibit Ca2+-dependent calmodulin interactions with erythrocyte membranes.
Authors: P Agre, D Virshup, V Bennett
Journal: Journal of Clinical Investigation (1984)

Two new vascular smooth muscle relaxants, bepridil and cetiedil, were found to possess specific CaM-inhibitory properties which resembled those of trifluoperazine. Trifluoperazine, bepridil, and cetiedil inhibited Ca2+-dependent 125I-CaM binding to erythrocyte membranes and CaM activation of membrane Ca2+-ATPase with IC50 values of approximately 12, approximately 17, and approximately 40 microM, respectively. This does not appear to be the result of a nonspecific hydrophobic interaction since inhibition was not observed with micromolar concentrations of many other hydrophobic agents. The predominant inhibition of binding and Ca2+-ATPase activation was competitive with respect to CaM. Bepridil and cetiedil bind directly to CaM since these drugs displaced [3H]trifluoperazine from sites on CaM. Inhibition of Ca2+-ATPase and binding by the drugs was not due to interference with the catalytic activity of this enzyme since: (a) neither inhibition of CaM-independent basal Ca2+-ATPase activity nor inhibition of proteolytically-activated Ca2+-ATPase activities were produced by these agents, and (b) no drug-induced inhibition of CaM binding was detected when membranes were preincubated with these agents but washed prior to addition of 125I-CaM. Thus, bepridil and cetiedil competitively inhibit Ca2+-dependent interactions of CaM with erythrocyte membranes, most likely by a direct interaction between these drugs and CaM. The principal clinical actions of these drugs may be explained by their interactions with CaM or CaM-related proteins leading to reduced activation of Ca2+-regulated enzymes in certain other tissues, such as myosin light chain kinase in vascular smooth muscle.
MPs call for greater transparency after "climategate" scandal
Authors: J. Hayes
Journal: BMJ (2010)

MPs have called for an end to the secrecy surrounding data collection by climate change scientists after emails between one group of researchers caused uproar after they were leaked last November

The cross party Science and Technology Committee condemned the culture of withholding information by scientists at the climate research unit at the University of East Anglia. The committee, however, said that the university was at fault for failing to support scientists when they received a requests for data under the Freedom of Information Act.

Phil Jones, director of …
Nevus anemicus in neurofibromatosis type 1: A potential new diagnostic criterion
Authors: Myriam Marque, Agathe Roubertie, Audrey Jaussent, Maryline Carneiro, Laurent Meunier, Bernard Guillot, Lucile Pinson, Stéphane Pinson, Didier Bessis
Journal: Journal of the American Academy of Dermatology (2013)
New Staging System: How Does It Affect Our Practice?
Authors: Peter Goldstraw
Journal: Journal of Clinical Oncology (2013)

The anatomic extent of disease, as described by the TNM classification, remains the most powerful prognostic indicator for lung cancer. It is used daily by specialists in all branches of lung cancer care and research. Any new edition of the TNM classification is therefore an important event in the thoracic oncology community and one greeted with mixed feelings. The changes introduced in the seventh edition were the first for 13 years and arguably the most profound since the first data-driven revision more than 40 years earlier. Inevitably there will be concerns that any change in the T, N, or M descriptors and resultant stage groupings will have implications for previous treatment pathways. In this article, the changes to the classification are described, and their possible impacts on clinical care and research are discussed.