tbuckley/cabot-search huggingface dataset:
Prevalence and determinants of primary sclerosing cholangitis in patients with ulcerative colitis and colorectal carcinoma or dysplasia and normal liver function tests
Authors: E. L. Culver, H. K. Bungay, F. J. Cummings, R. W. Chapman
Journal: Gut (2011)

<h3>Introduction</h3> Approximately 2.4–7.5% of patients with ulcerative colitis (UC) may also be diagnosed with primary sclerosing cholangitis (PSC). The risk of colorectal carcinoma (CRC) or dysplasia (CRD) has been reported to be fourfold higher in patients with PSC and UC compared to UC alone. The objective of this study is to determine the prevalence of undiagnosed PSC in UC patients with CRC or CRD. <h3>Methods</h3> 19 patients with histologically confirmed UC and CRC or CRD, with normal liver function and no prior imaging suggestive of PSC were identified. Patients had a magnetic resonance cholangiogram (MRC) and blood tests taken for pANCA, ANA, IgG and subclasses and HLA typing. Medical case notes, laboratory data and endoscopic records were reviewed retrospectively. MRCs were obtained from 21 healthy volunteers and 22 patients with established PSC to act as negative and positive controls, respectively. The Student9s t test and χ<sup>2</sup> test were used for analysis where appropriate. <h3>Results</h3> 26 patients met the inclusion criteria, of which 19 patients were recruited. The median age was 67 years (range 52–87) with a male predominance (74%). 15 patients (79%) had extensive and 4 (21%) left-sided colitis. Two patients (10%) had CRC, 6 (32%) high-grade and 11 (58%) low-grade CRD. 17 patients (89%) had CRC or CRD in the left colon. Two out of 19 patients (10%) had biliary abnormalities consistent with PSC on MRC. All 21 healthy volunteers had no evidence of PSC on MRC. All 22 PSC patients had characteristics of PSC on MRC. Both patients with evidence of PSC had a quiescent pancolitis and a mild disease course, with no acute admissions, immunosuppressive or biological therapy for colitis. One patient had high-grade CRD and the other CRC in the left colon. Neither patient had a positive pANCA or ANA. One had HLA haplotypes known to be associated with PSC as well as a raised IgG and IgG4. There was no difference between the median ages, duration of IBD, family history or presence of extra-intestinal manifestations of the two groups. No patient has had a liver biopsy. <h3>Conclusion</h3> This small study of patients with UC and CRC or CRD and normal liver function has demonstrated unsuspected biliary abnormalities consistent with PSC on MRC, in 2 of 19 patients. Previous work in our group has suggested a comparable prevalence of PSC in patients with extensive UC and normal LFTs.1 Larger studies are required to explore the relationship between possible undiagnosed PSC and the development of CRC/CRD in IBD patients. This may help to stratify screening strategies in the future.
Injuries in professional footballers.
Authors: D. S. Muckle
Journal: British Journal of Sports Medicine (1981)

The incidence of injuries in footballers is described. Nearly half of footballer's injuries involve the knee, with vertical tearing of the meniscus being common; surgical intervention may be required. Approximately one third of injuries involve the ankle, and will often require immobilisation. Other injuries include muscle damage, spondylosis of L4 or L5, concussion, and dislocations. The importance of prompt and correct treatment of injuries is emphasised.
ON EARLY TAPPING IN CASES OF ASCITES.
Authors: AUSTIN FLINT
Journal: JAMA (1883)

[Read at the meeting the of Section on Medicine of the British Medical Association, in Liverpool, August 2, 1883.] Mr. President and Gentlemen: The subject which I have selected for a short paper cannot, perhaps, be said to belong in the higher regions of pathology and practice, but it is one which, as it seems to me, has considerable material importance. Most writers on practical medicine at the present time, as in the past, recommend tapping, in cases of ascites, as a last resort, to be employed only when the dropsical accumulation has occasioned an alarming interference with respiration, and after other measures of treatment have proved ineffectual. The practice of most physicians now, as hitherto, I suppose to be in accordance with this recommendation. Many years ago I was led by reasoning and by clinical observation to advocate tapping early in cases of that affection. In 1863 I communicated
Carbonic anhydrase IX: A new druggable target for the design of antitumor agents
Authors: Jean‐Yves Winum, Marouan Rami, Andrea Scozzafava, Jean‐Louis Montero, Claudiu Supuran
Journal: Medicinal Research Reviews (2007)

Abstract Carbonic anhydrases (CAs, EC 4.2.1.1) are a family of enzymes widespread in all life kingdoms. In mammals, isozyme CA IX is highly overexpressed in many cancer types being present in few normal tissues. Its expression is strongly induced by hypoxia present in many tumors, being regulated by the HIF transcription factor and correlated with a poor response to classical chemo‐ and radiotherapies. CA IX was recently shown to contribute to acidification of the tumor environment, by efficiently catalyzing the hydration of carbon dioxide to bicarbonate and protons with its extracellularly situated active site, leading both to the acquisition of metastasic phenotypes and to chemoresistance with weakly basic anticancer drugs. Inhibition of this enzymatic activity by specific and potent inhibitors was shown to revert these acidification processes, establishing a clear‐cut role of CA IX in tumorigenesis. The development of a wide range of potent and selective CA IX inhibitors belonging to diverse chemical classes, such as membrane‐impermeant, fluorescent or metal‐containing such agents, could thus provide useful tools for highlighting the exact role of CA IX in hypoxic cancers, to control the pH (im)balance of tumor cells, and to develop novel diagnostic or therapeutic applications for the management of tumors. Indeed, both fluorescent inhibitors or positively charged, membrane impermeant sulfonamides have been recently developed as potent CA IX inhibitors and used as proof‐of‐concept tools for demonstrating that CA IX constitutes a novel and interesting target for the anticancer drug development. © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 3, 445–463, 2008
Adriamycin-induced alterations of the action potential in rat papillary muscle
Authors: M L LAZARUS, K L ROSSNER, K M ANDERSON
Journal: Cardiovascular Research (1980)

The present study investigates the effects of adriamycin on the electrophysiological properties of the myocardium as monitored by intracellular recordings of the cardiac action potential. ADR was administered to rats at a dose of 20 mg·kg−1 given as a single intravenous injection or in four daily doses of 5 mg·kg−1 each. Twenty-four hours following the last injection, papillary muscles were removed and intracellular recordings of the action potential were sampled from the tissue. In another set of experiments, papillary muscles were removed from non-injected, control animals and superfused in vitro with adriamycin at a concentration of 200 (μmol·litre−1. Several parameters of the action potential were measured and compared with control values in both in vivo and in vitro experiments. In all studies, the major effect of adriamycin on the cardiac action potential was shown to be a prolongation of the duration at 20%, 50% and 95% repolarisation. Adriamycin did not appear to exert its effect by depression of cell metabolism, as supervision with NaCN or dinitrophenol reduced the action potential duration. The upstroke velocity, which is proportional to the sodium conductance, was unaltered by ADR; it appears that ADR alters conductance of calcium and /or potassium across the myocardial membrane by an as yet unknown mechanism.
Chromosome 17q12 Variants Contribute to Risk of Early-Onset Prostate Cancer
Authors: Albert M. Levin, Mitchell J. Machiela, Kimberly A. Zuhlke, Anna M. Ray, Kathleen A. Cooney, Julie A. Douglas
Journal: Cancer Research (2008)

In a recent genome-wide association study by Gudmundsson and colleagues, two prostate cancer susceptibility loci were identified on chromosome 17q. The first locus, at 17q12, was distinguished by two intronic single-nucleotide polymorphisms (SNPs) in the TCF2 gene (rs4430796 and rs7501939). The second locus was in a gene-poor region of 17q24, where the strongest evidence of association was for SNP rs1859962. To determine if these loci were also associated with hereditary prostate cancer, we genotyped them in a family-based association sample of 403 non-Hispanic white families, including 1,015 men with and without prostate cancer. SNPs rs4430796 and rs7501939, which were in strong linkage disequilibrium (r(2) = 0.68), showed the strongest evidence of prostate cancer association. Using a family-based association test, the A allele of SNP rs4430796 was overtransmitted to affected men (P = 0.006), with an odds ratio of 1.40 (95% confidence interval, 1.09-1.81) under an additive genetic model. Notably, rs4430796 was significantly associated with prostate cancer among men diagnosed at an early (<50 years) but not later age (P = 0.006 versus P = 0.118). Our results confirm the prostate cancer association with SNPs on chromosome 17q12 initially reported by Gudmundsson and colleagues. In addition, our results suggest that the increased risk associated with these SNPs is approximately doubled in individuals predisposed to develop early-onset disease. Importantly, these SNPs do not account for a significant portion of our prior prostate cancer linkage evidence on chromosome 17. Thus, there likely exist one or more additional independent prostate cancer susceptibility loci in this region.
THE IMPORTANCE OF BEING HISTORICALLY MINDED
Authors: WILLIAM ALLEN PUSEY
Journal: JAMA (1927)

James Harvey Robinson ends his book  Ordeal of Civilization, in which he undertakes to show, by giving an outline of the history of medieval and modern times, how we have arrived at our present position in civilization, with a chapter on the importance of being historically minded. By this he means the possession of an intelligent appreciation of the history and of the evolution of civilization into its present state; to put it in the vernacular, an understanding of how we have gotten this way. It is undoubtedly an important quality of mind in seeing one's period in proper perspective. The same quality, but dealing with a different set of facts, is equally important in seeing ourselves in proper proportions in, and in proper relations to, our own period. It is, indeed, probably impossible for any group to appraise itself accurately in either respect. Distance, whether of space or
Valproic Acid at Therapeutic Plasma Levels May Increase 5-Azacytidine Efficacy in Higher Risk Myelodysplastic Syndromes
Authors: Maria Teresa Voso, Valeria Santini, Carlo Finelli, Pellegrino Musto, Enrico Pogliani, Emanuele Angelucci, Giuseppe Fioritoni, Giuliana Alimena, Luca Maurillo, Agostino Cortelezzi, Francesco Buccisano, Marco Gobbi, Lorenza Borin, Anna Di Tucci, Gina Zini, Maria Concetta Petti, Giovanni Martinelli, Emiliano Fabiani, Paola Fazi, Marco Vignetti, Alfonso Piciocchi, Vincenzo Liso, Sergio Amadori, Giuseppe Leone
Journal: Clinical Cancer Research (2009)

Epigenetic changes play a role and cooperate with genetic alterations in the pathogenesis of myelodysplastic syndromes (MDS). We conducted a phase II multicenter study on the combination of the DNA-methyltransferase inhibitor 5-azacytidine (5-AZA) and the histone deacetylase inhibitor valproic acid (VPA) in patients with higher risk MDS.We enrolled 62 patients with MDS (refractory anemia with excess blasts, 39 patients; refractory anemia with excess blasts in transformation, 19 patients; and chronic myelomanocytic leukemia (CMML), 4 patients) and an International Prognostic Scoring System (IPSS) rating of Intermediate-2 (42 patients) or high (20 patients). VPA was given to reach a plasma concentration of >50 microg/mL, then 5-AZA was added s.c. at 75 mg/m(2) for 7 days in eight monthly cycles.The median overall survival was 14.4 months. At a median follow-up of 12 months (range, 0.7-21.0), the disease progressed in 20 patients, with 21% cumulative incidence of progression. Of 26 patients who completed eight cycles, 30.7% obtained complete or partial remission, 15.4% had a major hematologic improvement, whereas 38.5% showed stable disease. Drug-related toxicity was mild. Favorable prognostic factors for survival were IPSS Intermediate-2 and plasma VPA of > or =50 microg/mL (log rank = 0.013 and 0.007, respectively). Analysis of polymorphisms important for the metabolism of the drugs used in the trial showed that carriers of the CYP2C19*2 variant of cytochrome P450 required higher VPA doses to achieve the target VPA plasma concentration of 50 microg/mL on day 1 of 5-AZA treatment (P = 0.0021).Our data show that the 5-AZA/VPA combination is active and safe in patients with MDS with a poor prognosis. Achievement of VPA therapeutic levels may indeed increase 5-AZA efficacy.
Aortic-Valve Atresia
Authors: David G. Watson
Journal: JAMA (1962)

Few chroniclers of heart disease have stressed the importance of aortic-valve atresia as a congential defect. However, at the Hospital for Sick Children, Toronto, this lesion is the most frequent cause of congestive heart failure and death in the neonatal period. In the cases presented, the average survival was 4 1/2 days, with a maximum survival of 7 1/2 months. The chief clinical features were cyanosis, dyspnea, rapidly progressive heart failure with hepatomegally, and often a gallop rhythm. Pulmonary ejection murmurs and weak peripheral pulses were both frequently noted. The x-rays showed cardiomegally with pulmonary congestion. The electrocardiogram indicated right atrial and right ventricular hypertrophy. The prognosis is at present hopeless, but it is desirable to differentiate this condition from the more easily remediable causes of neonatal distress.
Enhanced aortic atherosclerosis in transgenic Watanabe heritable hyperlipidemic rabbits expressing lipoprotein lipase
Authors: T KOIKE, J LIANG, X WANG, T ICHIKAWA, M SHIOMI, H SUN, T WATANABE, G LIU, J FAN
Journal: Cardiovascular Research (2004)

Objective: This study was designed to address the effects of increased lipoprotein lipase (LPL) activity on atherosclerosis in the setting of LDL receptor deficiency.
INVESTIGATIONS ON CASTOR OIL PLANT ALLERGY IN A RURAL COLLECTIVITY
Authors: N. GH. LUPU, G.T. DINISCHIOTU, I. GR. POPESCU, R. PĂUN, L. FOTESCU, M. ZAMFIRESCU‐GHEORGHIU, CORNELIA OLARU, C. G. IOTA, B. MOSCOVICI, C. MOLNER, N. URSEA
Journal: Allergy (1962)
Pharmacologic inhibition of hepcidin expression reverses anemia of chronic inflammation in rats
Authors: Igor Theurl, Andrea Schroll, Thomas Sonnweber, Manfred Nairz, Milan Theurl, Wolfgang Willenbacher, Kathrin Eller, Dominik Wolf, Markus Seifert, Chia Chi Sun, Jodie L. Babitt, Charles C. Hong, Tracey Menhall, Patrick Gearing, Herbert Y. Lin, Guenter Weiss
Journal: Blood (2011)
THE SURGICAL TREATMENT OF ACUTE SUPPURATIVE PARANASAL SINUSITIS
Authors: JOHN J. SHEA
Journal: JAMA (1926)

ABSTRACT The surgical treatment of acute suppurative paranasal sinusitis is of the emergency type and as such is accomplished with as little trauma as possible. No radical surgical intervention should be instituted, but only such measures attempted as will produce sufficient drainage and ventilation. The general surgeon has appreciated the folly of extensive manipulations whenever he encounters an acute suppurative condition in the abdomen, and from him we can learn a lesson. It is one thing to obtain drainage of an abscess and another to maintain this drainage. Here, again, we may imitate the general surgeon and use rubber tubing for drainage and not gauze wicks.This paper presumes that routine medical and local procedures have failed to arrest the condition or that the disease has advanced to such a degree as to indicate immediate surgical intervention. The paranasal sinuses have an indulgence to cope with infections without serious symptoms and
Alexithymia and Somatization
Authors: Stuart Shipko
Journal: Psychotherapy and Psychosomatics (1982)

Although alexithymia was originally described in patients with classical psychosomatic illnesses, attempts to specifically correlate these illnesses with alexithymia have not been successful. Despite the prominent role of somatization in the clinical description of alexithymia, a specific correlation between alexithymia and somatization has not been established. Data are presented which suggest that alexithymia is significantly more prevalent in somatizers than in healthy subjects, or subjects with classical psychosomatic illness in the absence of somatization. Other findings suggest that alexithymia may be a widespread phenomenon not necessarily associated with somatization or other illness. In the absence of debilitating somatization alexithymia may be useful in facilitating task-oriented behavior over prolonged periods of time without distraction.
Cancer of the GI tract: colon, rectum, anus. Introduction
Authors: P. Rubin
Journal: JAMA (1975)

CANCER of the lower intestinal tract is the second greatest reaper in the annual death harvest from cancer. The figures have remained essentially unchanged during the past four decades; 75% of all intestinal cancers arise in the colon, rectum, or anus. The incidence among sexes is equally distributed, and the majority (two thirds) of all patients are more than 50 years of age. The demographic distribution is worldwide, but like other alimentary tract cancers, its incidence varies from one country to another. Although the prevalence is high in the United States, it is low in Japan and Finland; the disease is relatively uncommon in Puerto Rico and Africa.<sup>1</sup>According to Bacon and Giambalva,<sup>2</sup>this disease is infrequent in blacks; the authors found only a 3.5% incidence among 640 black patients studied. It is difficult to find a common etiologic factor from these epidemiologic facts, although diet is immediately
Measles Immune Globulin
Authors: Robert J. Warren
Journal: JAMA (1968)

Serologic responses and reactions to live attenuated measles virus vaccine given with measles immune globulin in two different dosages were compared in children in Catawba County, North Carolina. The two dosages used were (1) approximately 0.01 cc/lb of body weight, and (2) 0.3 cc regardless of the child's weight. Although low-grade fevers were more common in larger children (50 to 70 lb [22.7 to 31.8 kg]) given the proposed standard 0.3 cc dose, both dosages produced similar antibody responses, incidence of high temperature, and school absenteeism.
Long-term outcome in patients with acute myocardial infarction undergoing primary percutaneous intervention: a pooled analysis of the primary angioplasty in myocardial infarction trials
Authors: C.Samuel Ledford, Cindy L. Grines, Gregg W. Stone, David Cox, Bruce Brodie, Lorelei Grines, Judith Boura, William W. O'Neill
Journal: Journal of the American College of Cardiology (2002)
CDDO induces granulocytic differentiation of myeloid leukemic blasts through translational up-regulation of p42 CCAAT enhancer–binding protein alpha
Authors: Steffen Koschmieder, Francesco D'Alò, Hanna Radomska, Christine Schöneich, Ji Suk Chang, Marina Konopleva, Susumu Kobayashi, Elena Levantini, Nanjoo Suh, Annalisa Di Ruscio, Maria Teresa Voso, Julie C. Watt, Ramasamy Santhanam, Bülent Sargin, Hagop Kantarjian, Michael Andreeff, Michael B. Sporn, Danilo Perrotti, Wolfgang E. Berdel, Carsten Müller-Tidow, Hubert Serve, Daniel G. Tenen
Journal: Blood (2007)
POST-DISCHARGE MORTALITY AND READMISSION IN HEART FAILURE PATIENTS WITH PRESERVED, BORDERLINE, AND REDUCED LEFT VENTRICULAR EJECTION FRACTION
Authors: Richard Kar-Hang Cheng, Margueritte Cox, Megan Neely, Paul Heidenreich, Deepak Bhatt, Zubin Eapen, Adrian Hernandez, Javed Butler, Clyde Yancy, Gregg Fonarow
Journal: Journal of the American College of Cardiology (2014)
AN EYE SPECULUM FOR CATARACT OPERATIONS
Authors: M. M. Cullom
Journal: JAMA (1933)

<h3>To the Editor:</h3> —My attention has been called to a communication inThe Journal, Dec. 3, 1932, from Dr. Walter B. Lancaster commenting on an eye speculum for cataract extraction which I described and illustrated inThe Journal. Oct. 8, 1932, page 1252. Dr. Lancaster says that the eye speculum is a good illustration of how far one can go afield if one starts from an erroneous premise. I started from the premise that a patient with a cataract incision and an unsupported speculum in the eye can expel vitreous by a contraction of the orbicularis muscle. If that premise is erroneous, I have indeed gone far afield. I agree fully with Dr. Lancaster when he says, "Expulsion of vitreous during cataract operations may come from either or both of two causes: pressure on the eyeball by the surgeon, or pressure on the eyeball by the patient through muscular action."
Population-Based <i>in Vitro</i> Hazard and Concentration–Response Assessment of Chemicals: The 1000 Genomes High-Throughput Screening Study
Authors: Nour Abdo, Menghang Xia, Chad C. Brown, Oksana Kosyk, Ruili Huang, Srilatha Sakamuru, Yi-Hui Zhou, John R. Jack, Paul Gallins, Kai Xia, Yun Li, Weihsueh A. Chiu, Alison A. Motsinger-Reif, Christopher P. Austin, Raymond R. Tice, Ivan Rusyn, Fred A. Wright
Journal: Environmental Health Perspectives (2015)

Understanding of human variation in toxicity to environmental chemicals remains limited, so human health risk assessments still largely rely on a generic 10-fold factor (10½ each for toxicokinetics and toxicodynamics) to account for sensitive individuals or subpopulations.We tested a hypothesis that population-wide in vitro cytotoxicity screening can rapidly inform both the magnitude of and molecular causes for interindividual toxicodynamic variability.We used 1,086 lymphoblastoid cell lines from the 1000 Genomes Project, representing nine populations from five continents, to assess variation in cytotoxic response to 179 chemicals. Analysis included assessments of population variation and heritability, and genome-wide association mapping, with attention to phenotypic relevance to human exposures.For about half the tested compounds, cytotoxic response in the 1% most "sensitive" individual occurred at concentrations within a factor of 10½ (i.e., approximately 3) of that in the median individual; however, for some compounds, this factor was > 10. Genetic mapping suggested important roles for variation in membrane and transmembrane genes, with a number of chemicals showing association with SNP rs13120371 in the solute carrier SLC7A11, previously implicated in chemoresistance.This experimental approach fills critical gaps unaddressed by recent large-scale toxicity testing programs, providing quantitative, experimentally based estimates of human toxicodynamic variability, and also testable hypotheses about mechanisms contributing to interindividual variation.
Rosiglitazone and Outcomes for Patients With Diabetes Mellitus and Coronary Artery Disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial
Authors: Richard G. Bach, Maria Mori Brooks, Manuel Lombardero, Saul Genuth, Thomas W. Donner, Alan Garber, Laurence Kennedy, E. Scott Monrad, Rodica Pop-Busui, Sheryl F. Kelsey, Robert L. Frye
Journal: Circulation (2013)

Rosiglitazone improves glycemic control for patients with type 2 diabetes mellitus, but there remains controversy regarding an observed association with cardiovascular hazard. The cardiovascular effects of rosiglitazone for patients with coronary artery disease remain unknown.