tbuckley/cabot-search huggingface dataset:
Ronald Stanley Thorpe
Authors: N. Cardoe, N A. Green
Journal: BMJ (2008)

The son of a general practitioner/radiologist, Ronald Stanley Thorpe (“Ron”) entered military service with the Royal Army Medical Corps. His inventive skills led to a research project on escape mechanisms in floating tanks used in the D Day landings in the second world war, his regiment, the 79th armoured division, taking part on the actual day. He had been stationed near Fritton Lake in Norfolk, and this began his lifelong love of the county. He was later posted …
Abnormalities of Platelet Function in the Myeloproliferative Disorders
Authors: Joseph M. Cardamone, J. Roger Edson, James R. McArthur, Harry S. Jacob
Journal: JAMA (1972)

Despite extensive investigation of all aspects of the coagulation system, the mechanisms underlying the hemorrhagic and thrombotic complications seen in the "myeloproliferative disorders" have not been satisfactorily elucidated. In an attempt to define the abnormality underlying the hemorrhagic diathesis, the platelet function of 21 consecutive patients admitted to the University of Minnesota Hospitals with various myeloproliferative disorders (polycythemia vera, myelogenous leukemia, agnogenic myeloid metaplasia, and erythroleukemia) was evaluated by the use of both the older, less sensitive methods, and those more sensitive and reliable techniques which have recently become available. All 21 patients demonstrated some degree of platelet function abnormality, which was more severe in those patients with clinically apparent bleeding diatheses. Two illustrative cases point out the therapeutic approaches which are currently available to control the hemorrhagic problems occurring in these patients as a consequence of their abnormal platelet functions.
Quantitative polymerase chain reaction for transforming growth factor-beta applied to a field study of fish health in Chesapeake Bay tributaries.
Authors: C A Harms, C A Ottinger, V S Blazer, C L Densmore, L H Pieper, S Kennedy-Stoskopf
Journal: Environmental Health Perspectives (2000)

Fish morbidity and mortality events in Chesapeake Bay tributaries have aroused concern over the health of this important aquatic ecosystem. We applied a recently described method for quantifying mRNA of an immunosuppressive cytokine, transforming growth factor-beta (TGF-beta), by reverse transcription quantitative-competitive polymerase chain reaction to a field study of fish health in the Chesapeake Basin, and compared the results to those of a traditional cellular immunoassay macrophage bactericidal activity. We selected the white perch (Morone americana) as the sentinel fish species because of its abundance at all of the collection sites. White perch were sampled from Chesapeake Bay tributaries in June, August, and October 1998. Splenic mononuclear cell TGF-beta mRNA levels increased and anterior kidney macrophage bactericidal activity decreased, particularly in eastern shore tributaries, from June to August and October. The results of the two assays correlated inversely (Kendall's [Tau] b = -0.600; p = 0.0102). The results indicated both temporal and spatial modulation of white perch immune systems in the Chesapeake Basin, and demonstrated the utility of quantitative PCR for TGF-beta as a molecular biomarker for field assessment of teleost fish immune status.
Risks of Isoniazid Therapy
Authors: ARNOLD BROWN
Journal: Annals of Internal Medicine (1976)

Comments1 December 1976Risks of Isoniazid TherapyARNOLD BROWN, M.D.ARNOLD BROWN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-85-6-828 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Recent reports (1-4) suggest that liver injury with isoniazid (INH) therapy is due to a metabolite of INH, not hypersensitivity, and occurs more often in rapid acetylators. Studies in volunteers (3) show that INH is converted to the toxic acetylhydrazine and that the rate of conversion depends on the rate of INH acetylation. It is suggested that clinical data support this hypothesis (Orientals, who are more likely to be rapid acetylators, are more susceptible to INH hepatic injury [1]) and that 86% (18 of 21) of the patients in whom INH hepatotoxicity was evident were found to...References1. BLACKMITCHELLZIMMERMAN MJH: Isoniazid-associated hepatitis in 114 patients. Gastroenterology 69:289-302, 1975 CrossrefMedlineGoogle Scholar2. MITCHELLLONGTHORGEIRSSON JMU: Acetylation rates and monthly liver function tests during one year of isoniazid preventive therapy. Chest 68:181-190, August 1975 CrossrefMedlineGoogle Scholar3. MITCHELLTHORGEIRSSONBLACK JUM: Increased incidence of isoniazid hepatitis in rapid acetylators: possible relation to hydrazine metabolites. Clin Pharmacol Ther 18:70-79, 1975 CrossrefMedlineGoogle Scholar4. MITCHELLZIMMERMANISHAK JHK: Isoniazid liver injury: clinical spectrum, pathology, and probable pathogenesis. Ann Intern Med 84:181-192, 1976 LinkGoogle Scholar5. MADDREYBOITNOTT WJ: Isoniazid hepatitis. Ann Intern Med 79:1-12, 1973 LinkGoogle Scholar6. SMITHTYRELLGOW JWA: Hepatotoxicity in rifampin-isoniazid treated patients related to their rate of isoniazid inactivation. Chest 61:587-588, June 1972 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Veterans Administration Hospital University Drive C Pittsburgh, PA 15240 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited BySynthesis and Stereochemistry of Some 1,3-Oxazolidine Systems Based on TRIS (α,α,α-Trimethylolaminomethane) and Related Aminopolyols Skeleton. Part 1: (Di)spiro-1,3-oxazolidinesOther Antibacterial DrugsHäufigkeit und pathophysiologische Aspekte der INH-Hepatitis bei tuberkulostatischer Kombinationsbehandlung 1 December 1976Volume 85, Issue 6Page: 828-829KeywordsHypersensitivityIsoniazidLiverMetabolitesRisk management Issue Published: 1 December 1976 PDF DownloadLoading ...
Pulmonary Amyloidosis. The Mayo Clinic Experience from 1980 to 1993
Authors: James P. Utz
Journal: Annals of Internal Medicine (1996)

To define the prognosis for and radiographic presentation of patients with pulmonary amyloidosis.Retrospective review of the Mayo Clinic experience with biopsy-proven pulmonary amyloidosis from 1980 to 1993.Tertiary care center.Patients with pulmonary biopsy specimens showing amyloid deposition.Medical records were reviewed, and pertinent information was recorded, including demographic data, type of pulmonary biopsy, results of biopsies of nonpulmonary sites and of immunoelectrophoresis, and other clinical, radiographic, and laboratory information necessary for distinguishing localized pulmonary amyloidosis, primary systemic amyloidosis, secondary amyloidosis, and familial amyloidosis.35 of 55 patients with pulmonary amyloidosis had primary systemic amyloidosis that presented radiographically as an interstitial or reticulonodular pattern with or without pleural effusion. The median survival after diagnosis was 16 months. Nodular pulmonary "amyloidomas" (nodular amyloid lesions) were not associated with systemic disease and were associated with a benign prognosis. Three of 4 patients with localized tracheobronchial amyloidosis required Nd:YAG (neodymium:yttrium-aluminum-garnet) laser therapy for obstructive symptoms. "Senile" amyloid deposition was an incidental finding in some patients at autopsy.Localized amyloidomas are characterized by a benign course and are not associated with systemic amyloidosis. Despite its localized nature, tracheobronchial amyloid deposition may be asymptomatic or may result in significant morbidity due to obstructive phenomena. Pulmonary amyloidosis associated with primary systemic amyloidosis generally presents as a diffuse interstitial pattern with or without pleural effusion. Complete survival data indicate that long-term outcome is poor after diagnosis. We describe the largest series of patients diagnosed by bronchoscopic lung biopsy. Despite reports to the contrary, we have found bronchoscopic lung biopsy to be a safe and effective diagnostic technique.
Families demand reform of India's medical negligence system
Authors: M. Chaudhuri
Journal: BMJ (2014)

<h3>Abstract</h3> Methods for inferring population structure from genetic information traditionally assume samples are contemporary. Yet, the increasing availability of ancient DNA sequences begs revision of this paradigm. We present Dystruct (Dynamic Structure), a framework and toolbox for inference of shared ancestry from data that include ancient DNA. By explicitly modeling population history and genetic drift as a time-series, Dystruct more accurately and realistically discovers shared ancestry from ancient and contemporary samples. Formally, we use a normal approximation of drift, which allows a novel, efficient algorithm for optimizing model parameters using stochastic variational inference. We show that Dystruct outperforms the state of the art when individuals are sampled over time, as is common in ancient DNA datasets. We further demonstrate the utility of our method on a dataset of 92 ancient samples alongside 1941 modern ones genotyped at 222755 loci. Our model tends to present modern samples as the mixtures of ancestral populations they really are, rather than the artifactual converse of presenting ancestral samples as mixtures of contemporary groups. <h3>Availability</h3> Dystruct is implemented in C++, open-source, and available at https://github.com/tyjo/dystruct.
A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis
Authors: Shoji Ichikawa, Erik A. Imel, Mary L. Kreiter, Xijie Yu, Donald S. Mackenzie, Andrea H. Sorenson, Regina Goetz, Moosa Mohammadi, Kenneth E. White, Michael J. Econs
Journal: Journal of Clinical Investigation (2007)

Familial tumoral calcinosis is characterized by ectopic calcifications and hyperphosphatemia due to inactivating mutations in FGF23 or UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3). Herein we report a homozygous missense mutation (H193R) in the KLOTHO (KL) gene of a 13-year-old girl who presented with severe tumoral calcinosis with dural and carotid artery calcifications. This patient exhibited defects in mineral ion homeostasis with marked hyperphosphatemia and hypercalcemia as well as elevated serum levels of parathyroid hormone and FGF23. Mapping of H193R mutation onto the crystal structure of myrosinase, a plant homolog of KL, revealed that this histidine residue was at the base of the deep catalytic cleft and mutation of this histidine to arginine should destabilize the putative glycosidase domain (KL1) of KL, thereby attenuating production of membrane-bound and secreted KL. Indeed, compared with wild-type KL, expression and secretion of H193R KL were markedly reduced in vitro, resulting in diminished ability of FGF23 to signal via its cognate FGF receptors. Taken together, our findings provide what we believe to be the first evidence that loss-of-function mutations in human KL impair FGF23 bioactivity, underscoring the essential role of KL in FGF23-mediated phosphate and vitamin D homeostasis in humans.
Obesity in children in England continues to rise
Authors: Susan Mayor
Journal: BMJ (2005)

Obesity in children in England continues to rise 334 More than one in four children in England are overweight or obese, said a government report published last week which showed that obesity in young people is continuing to rise.The report said that the prevalence of obesity in children aged 2 to 10 increased from 9.9% in 1995 to 13.7% in 2003.The total number of overweight and obese children rose from 22.7% to 27.7% in this period.Obesity increased most in older children aged 8 to 10, rising from 11.2% in 1995 to 16.5% in 2003.Levels of obesity were similar for both sexes, increasing from 9.6% in 1995 to 14.9% in 2003 for boys and from 10.3% to 12.5% for girls.Children living in households with the lowest incomes had higher rates of obesity than those from households with the highest incomes (15.8% v 13.3%).
Hypertension and Renal Disease
Authors: Howard Rubinoff
Journal: JAMA (1976)

<h3>To the Editor.—</h3> In his review of the management of hypertension (233:990, 1975), Dr Maronde implies that hypertension should not be treated vigorously in patients with advanced renal disease. This is contrary to several recent articles in the literature.<sup>1-6</sup>There seems to be a general consensus that hypertension in those with advanced renal disease should be treated vigorously, most authors maintaining that the pressure should be normalized. This may result in some temporary decrease in renal function, but the end result is that the renal function stabilizes and often improves. I would like to know why Dr Maronde advises continued conservatism in the management of hypertension of advanced renal disease.
A10.24 Switching Infliximab for New Alternatives: A Correspondence Analysis of Biologics, Reasons to Stop, and Time Periods
Authors: Julia Uceda, Loreto Carmona, Alejandro Muñoz, Jose L Marenco
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The reason to stop the first biologic may vary from agent to agent and also from the earlier times to the more recent ones. Issues like the availability of newer alternatives or a better knowledge of the effectiveness and safety profile of individual biologics may influence treatment decisions, including the discontinuation of the biologic. <h3>Objective</h3> To visually assess the relationship between the reason for stopping the first biologic and the period of time when the biologic was started. <h3>Methods</h3> All patients with rheumatoid arthritis undergoing treatment with a biologic are registered in the clinical database of a single centre with seven treating rheumatologists. The biologic used, as well as the reason to stop it is recorded, as well as all dates regarding the start and the last dose. We performed a multiple correspondence analysis with the Burt method of adjusted inertias and standard normalisation with the variables: first biologic, time period (1998–2001, 2002–2005, 2006–2009), and reason to stop (adverse event, inefficacy, others). Correspondence analysis provides a means of displaying or summarising a set of data with categorical variables in two-dimensional graphical form. <h3>Results</h3> The total inertia of the exploratory analysis was 0.10. The first two dimensions added to 57% of the inertia, so that all dimensions were accounted for. The major drives of the relationship between the three variables were “infliximab” and the time period “1998–2001” (% inertia 0.146 and 0.177, respectively). The distance between other categories of the three variables was not relevant enough to make any suggestions of an association. The figure shows the correspondence map of the relationship. <h3>Conclusions</h3> If to any biologic at all, time has affected the decision to start infliximab, with more treatments started in the earlier times than in the later ones. The reason to stop any first biologic does not clearly relate to the time neither to the biologic itself in this single centre dataset.
Improving Health and Health Care for Persons With Serious Mental Illness
Authors: Benjamin G. Druss
Journal: JAMA (2010)

IN 1928, BENJAMIN MALZBERG, A YOUNG EPIDEMIOLOgist in New York State’s Division of Mental Hygiene, began a groundbreaking study examining causes of mortality in New York State’s mental hospitals. During the ensuing 3 years, Malzberg reviewed every death that occurred throughout the state’s psychiatric hospital system; his findings were both surprising and troubling. Patients in these hospitals died an average of 15 years younger than the general population of New York State. Malzberg speculated that these excess deaths were likely due to a complex combination of factors:
NOR-EPINEPHRINE (ARTERENOL,® SYMPATHIN N) AS A PRESSOR DRUG
Authors: MARCEL GOLDENBERG
Journal: JAMA (1949)

Epinephrine and the corresponding primary amine l-nor-epinephrine (nor-adrenaline, arterenol®) normally exist in the mammalian body. Nor-epinephrine was first shown to be present in significant amounts in postganglionic, adrenergic nerves of cattle by pharmacologic methods.<sup>1</sup>Recently its presence has been demonstrated in the adrenal medulla of cattle by paper chromatography<sup>2</sup>and in tumors of chromaffin tissue (pheochromocytomas) of human beings by pharmacologic and chemical methods.<sup>3</sup>l-Nor-epinephrine is believed to function as excitor sympathin in most of the investigated areas of the cardiovascular system withthe exception of cardiac muscle and the vessels of the skin. In these areas epinephrine appears to be the mediator of excitor functions.<sup>4</sup>(Sympathin N [norepinephrine] and sympathin A [epinephrine], as suggested by von Euler, should be used rather than the term sympathin E, since at least two excitor sympathins seem to exist.<sup>5</sup>) Recent investigations of the hemodynamics of epinephrine and nor-epinephrine
General Internists’ Preferences and Knowledge About the Care of Adult Survivors of Childhood Cancer
Authors: Eugene Suh, Christopher K. Daugherty, Kristen Wroblewski, Hannah Lee, Mackenzie L. Kigin, Kenneth A. Rasinski, Jennifer S. Ford, Emily S. Tonorezos, Paul C. Nathan, Kevin C. Oeffinger, Tara O. Henderson
Journal: Annals of Internal Medicine (2014)

Adult childhood cancer survivors (CCSs) are at high risk for illness and premature death. Little is known about the physicians who provide their routine medical care.To determine general internists' self-reported attitudes and knowledge about the care of CCSs.Cross-sectional survey.Mailed survey delivered between September 2011 and August 2012.Random sample of 2000 U.S. general internists.Care preferences, comfort levels with caring for CCSs (7-point Likert scale: 1 = very uncomfortable, 7 = very comfortable), familiarity with available surveillance guidelines (7-point Likert scale: 1 = very unfamiliar, 7 = very familiar), and concordance with Children's Oncology Group Long-Term Follow-Up Guidelines in response to a clinical vignette.The response rate was 61.6% (1110 of 1801). More than half the internists (51.1%) reported caring for at least 1 CCS; 72.0% of these internists never received a treatment summary. On average, internists were "somewhat uncomfortable" caring for survivors of Hodgkin lymphoma, acute lymphoblastic leukemia, and osteosarcoma. Internists reported being "somewhat unfamiliar" with available surveillance guidelines. In response to a clinical vignette about a young adult survivor of Hodgkin lymphoma, 90.6% of respondents did not appropriately recommend yearly breast cancer surveillance, 85.1% did not appropriately recommended cardiac surveillance, and 23.6% did not appropriately recommend yearly thyroid surveillance. Access to surveillance guidelines and treatment summaries were identified as the most useful resources for caring for CCSs.Findings, based on self-report, may not reflect actual clinical practice.Although most general internists report involvement in the care of CCSs, many seem unfamiliar with available surveillance guidelines and would prefer to follow patients in collaboration with a cancer center.National Cancer Institute.
A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis
Authors: Mourad Matmati, Peggy Jacques, Jonathan Maelfait, Eveline Verheugen, Mirjam Kool, Mozes Sze, Lies Geboes, Els Louagie, Conor Mc Guire, Lars Vereecke, Yuanyuan Chu, Louis Boon, Steven Staelens, Patrick Matthys, Bart N Lambrecht, Marc Schmidt-Supprian, Manolis Pasparakis, Dirk Elewaut, Rudi Beyaert, Geert van Loo
Journal: Nature Genetics (2011)
122. Enhanced Expression of Glutamate Decarboxylase 65 Significantly Improves Rat Parkinsonian Symptom
Authors: Boyoung Lee, Young Ran Nam, Sung Jin Kim, Jin Hwan Oh, Yoon Hee Choi, Jin Woo Chang, Heuiran Lee
Journal: Molecular Therapy (2005)

Glutamate decarboxylase (GAD) is the rate-limiting enzyme in GABA production, which has been intensively investigated as a mean to increase inhibitory synaptic activity. By expressing GAD65 encoded in a recombinant adeno-associated virus 2 (rAAV2) with a modified CMV promoter (JDK) in the subthalamic nucleus (STN), we investigated the degree of the amelioration of parkinsonian symptoms in a rat Parkinson's disease (PD) model. Behavioral improvement was evaluated by apomorphine-induced rotational and forepaw-adjusting tests. Additionally, the alteration of neuronal activities was investigated by monitoring electrophysiological changes.
Incessant Ventricular Tachycardia in an Infant Treated With Transmural Radiofrequency Ablation
Authors: Aravinda Thiagalingam, David Winlaw, Aarti Hejmadi, Shingo Kasahara, Sandra Biankin, Susan Arbuckle, David Ross, K.C. Lau, Graham Nunn
Journal: Circulation (2002)
Pentazocine-lnduced Fibrous Myopathy
Authors: Shin Joong Oh
Journal: JAMA (1975)

Fibrous myopathy was found in three patients who had taken pentazocine intramuscularly for years. Fibrotic induration in the quadriceps and deltoid muscles,<i>the considerable limitation of motion due to the fibrotic muscle contracture, and the minimal weakness of involved muscles</i>are the most characteristic findings in this condition. Results of animal experiments support the close relationship between myopathy and pentazocine. This serious complication emphasizes more judicious use of pentazocine. (<i>JAMA</i>231:271-273, 1975)
Low density lipoprotein enhances the thrombin-induced growth of vascular smooth muscle cells
Authors: Stefan Seewald, Georg Nickenig, Yon Ko, Hans Vetter, Agapios Sachinidis
Journal: Cardiovascular Research (1997)

Objective: In the present study we investigated whether low density lipoprotein is able to enhance the growth promoting effects of thrombin in vascular smooth muscle cells. Methods: DNA synthesis was examined by measurement of the [3H]thymidine incorporation into the cell DNA. Cell count was measured with a Neubauer cell box. Thrombin receptor mRNA was determined by Northern blotting. Ca2+ was measured by the fura 2-method. Results: Thrombin (5 nmol/l), thrombin receptor activating protein (3 μmol/l) and low density lipoprotein (33 nmol/l) induce a 652±80%, 593±80% and a 316±60% increase in [3H]thymidine incorporation into DNA (mean±SD, n = 3), respectively. A coincubation of thrombin or thrombin receptor activating protein with low density lipoprotein led to a 1245±160% or 1200±40% increase of DNA synthesis (mean±SD, n = 3). Thus, coincubation of low density lipoprotein and thrombin causes a synergistic rather than an additive mitogenic effect on smooth muscle cells. Thrombin and low density lipoprotein induced a 22±8,4% and a 29%±6% increase in cell number, respectively. Simultaneous treatment of vascular smooth muscle cells with thrombin and low density lipoprotein caused a 63±14% increase in cell number (mean±SD, n = 3). To further elucidate the underlying mechanism, we studied the effect of low density lipoprotein on the expression of thrombin receptor mRNA. Low density lipoprotein caused a 2.5-fold increase of thrombin receptor mRNA within 24 h, as assessed by Northern analysis. Preincubation of cells for 24 h with 33 nmol/l low density lipoprotein resulted in an elevation of the thrombin-induced increase in cytosolic free Ca2+ concentration from 538±54 to 923±75 nmol/l (mean±SD, n = 4). Conclusion: In summary, low density lipoprotein may enhance the mitogenic effect of thrombin probably by an up-regulation of thrombin receptor gene expression in vascular smooth muscle cells or by an elevation of the thrombin-induced increase in cytosolic free Ca2+ concentration.
283 HCV PROTEASE INHIBITOR RESTORES INSULIN SENSITIVITY IN GENOTYPE 1 CHRONIC HEPATITIS C PATIENTS
Authors: R. Moucari, N. Forestier, D. Larrey, D. Guyader, P. Couzigou, Y. Benhamou, H. Voitot, M. Vidaud, S. Seiwert, B. Bradford, S. Zeuzem, P. Marcellin
Journal: Journal of Hepatology (2010)