tbuckley/cabot-search huggingface dataset:
Dispensable role of Drosophila ortholog of LRRK2 kinase activity in survival of dopaminergic neurons
Authors: Danling Wang, Beisha Tang, Guohua Zhao, Qian Pan, Kun Xia, Rolf Bodmer, Zhuohua Zhang
Journal: Molecular Neurodegeneration (2008)

Abstract Background Parkinson's disease (PD) is the most prevalent incurable neurodegenerative movement disorder. Mutations in LRRK2 are associated with both autosomal dominant familial and sporadic forms of PD. LRRK2 encodes a large putative serine/threonine kinase with GTPase activity. Increased LRRK2 kinase activity plays a critical role in pathogenic LRRK2 mutant-induced neurodegeneration in vitro . Little is known about the physiological function of LRRK2. Results We have recently identified a Drosophila line with a P-element insertion in an ortholog gene of human LRRK2 ( dLRRK ). The insertion results in a truncated Drosophila LRRK variant with N-terminal 1290 amino acids but lacking C-terminal kinase domain. The homozygous mutant fly develops normally with normal life span as well as unchanged number and pattern of dopaminergic neurons. However, dLRRK mutant flies were selectively sensitive to hydrogen peroxide induced stress but not to paraquat, rotenone and β-mercaptoethanol induced stresses. Conclusion Our results indicate that inactivation of d LRRK kinase activity is not essential for fly development and suggest that inhibition of LRRK activity may serve as a potential treatment of PD. However, d LRRK kinase activity likely plays a role in protecting against oxidative stress.
Update in Geriatrics: Evidence Published in 2013
Authors: William J. Hall
Journal: Annals of Internal Medicine (2014)

Updates17 June 2014Update in Geriatrics: Evidence Published in 2013William J. Hall, MDWilliam J. Hall, MDFrom University of Rochester School of Medicine, Rochester, New York.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M14-0301 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The 8 articles selected for this update reflect the continuing maturation of the geriatrics literature. An aging population so familiar to internists is presenting new clinical challenges, increased utilization of ever more costly therapy, and more demands about justification of services and hospitalization. This update discusses how evidence-based principles can facilitate more cost-effective geriatrics care by internists in the ambulatory and hospital environments. Topics include cognitive impairment and dementia, hospital readmissions, adverse drug events, and falls.Cognitive ImpairmentBrief Screening Instruments Can Detect Dementia ...References1. Larson EB, Yaffe K, Langa KM. New insights into the dementia epidemic. N Engl J Med. 2013;369:2275-7. [PMID: 24283198] CrossrefMedlineGoogle Scholar2. Lipska KJ, Montori VM. Glucose control in older adults with diabetes mellitus—more harm than good? JAMA Intern Med. 2013;173:1306-7. [PMID: 23753259] CrossrefMedlineGoogle Scholar3. Joynt KE, Gawande AA, Orav EJ, Jha AK. Contribution of preventable acute care spending to total spending for high-cost Medicare patients. JAMA. 2013;309:2572-8. [PMID: 23797716] CrossrefMedlineGoogle Scholar4. Robinovitch SN, Feldman F, Yang Y, Schonnop R, Leung PM, Sarraf T, et al. Video capture of the circumstances of falls in elderly people residing in long-term care: an observational study. Lancet. 2013;381:47-54. [PMID: 23083889] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAuthors: William J. Hall, MDAffiliations: From University of Rochester School of Medicine, Rochester, New York.Disclosures: None disclosed. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-0301.Corresponding Author: William J. Hall, MD, University of Rochester School of Medicine, Highland Hospital, 1000 South Avenue, Box 58, Rochester, NY 14620; e-mail, william_hall@urmc.rochester.edu.Author Contributions: Analysis and interpretation of the data: W.J. Hall.Drafting of the article: W.J. Hall.Final approval of the article: W.J. Hall.Collection and assembly of data: W.J. Hall.This article was published online first at www.annals.org on 10 April 2014. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 17 June 2014Volume 160, Issue 12 Page: 842-846 Keywords Angiotensin converting enzyme Cataract surgery Dementia Drugs Elderly Falls Glucose Hip fractures Hospitalizations Medicare ePublished: 17 June 2014 Issue Published: 17 June 2014 Copyright & PermissionsCopyright © 2014 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Diffuse Extravasation of Urine After Renal Transplant
Authors: DOV FRONT, ORA ISRAEL, IRIT WEISSMANN, ORI BETTER
Journal: Clinical Nuclear Medicine (1981)

This authoritative journal provides up-to-date information on nuclear medicine that can be readily applied to clinical situations. Written for both generalists and specialists in nuclear medicine, Clinical Nuclear Medicine ensures timely dissemination of data on current developments that affect all aspects of the specialty. The most practice-oriented journal in the field of nuclear imaging, its numerous illustrations show physicians how to apply vital information immediately in their everyday practice.
Eyestrain as a Cause of Headache and Other Nervous Symptoms—A Question of Precedence.
Authors: A. L. Ranney
Journal: JAMA (1904)

New York City, March 3, 1904. <h3>To the Editor:</h3> —In your issues of Jan. 16 and Jan. 23, 1904, Dr. George M. Gould publishes an interesting article concerning the dependence of "Migraine" on eyestrain. In this article he goes extensively into the history of the literature relating to this distressing and extremely common malady. In this connection he makes the most remarkable statement regarding a contribution of a French oculist to this field. He says (italics are my own): In 1888 Dr. G. Martin (<i>Ann. d'Oc</i>.), a French oculist, published an article which some time will be recognized as truly epoch-making. But two writers, as far as I have noticed, have even mentioned Martin's magnificent and daring attempt to bring the medical world to its senses. A compiler should certainly have shown more care than Dr. Gould appears to have shown in reviewing medical literature, before he ignores the work
Is there a difference in the cost-effectiveness of erythropoietic therapies for the treatment of anemia in patients receiving HCV combination therapy?
Authors: Wenchen Kenneth Wu, Mei Sheng Duh, Patrick Lefebvre
Journal: Hepatology (2007)

We read with interest the cost-effectiveness analysis by Del Rio et al.,1 which compared epoetin alpha and darbepoetin alfa therapy for anemia in patients receiving pegylated interferon and ribavirin combination therapy for HCV. The authors concluded that use of darbepoetin alfa is cost-effective because the cost of darbepoetin per additional quality-adjusted life-year (QALY) was below a cost per QALY threshold of $50,000, whereas epoetin alfa was above the threshold value. We believe this conclusion was incorrect because of a major calculation error in the costs of erythropoietic treatments made by the authors. The authors report calculating the weekly drug costs for epoetin ($596.50) and darbepoetin ($278.44) based on the average wholesale prices (AWP) published in the 2005 Red Book for the base case analysis (table 4 in Del Rio et al.). However, a correct calculation would have nearly doubled the darbepoetin weekly costs and resulted in comparable weekly drug costs between epoetin and darbepoetin, drastically changing the authors' conclusions. The doses of growth factors used in the model were 40,000 Units epoetin once a week and 3.0 μg/kg body weight darbepoetin once every 2 weeks (∼200 μg for a 70-kg patient, or about 100 μg weekly; see page 1600 in Del Rio et al.1). The published Red Book AWP prices in 20052 are $572.64 per one 40,000 Unit vial for epoetin alfa, and $1025.28 per one 200 μg vial for darbepoetin alfa. Therefore, weekly doses of 40,000 Units epoetin and 100 μg darbepoetin valued at the 2005 AWP translate into weekly drug costs of $572.64 and $512.64, respectively. The weekly costs for these selected regimens are actually much more comparable than the 2-fold difference reported by the authors. Using the correct weekly darbepoetin alfa cost in the base case of the authors' model, the incremental cost-effectiveness ratios for darbepoetin and epoetin should become very similar, and may both be above the $50,000 threshold. Wenchen Kenneth Wu MBA, Ph.D.*, Mei Sheng Duh M.P.H., Sc.D. , Patrick Lefebvre M.A. , * College of Pharmacy and Allied Health Professions, St. Johns University, Jamaica, NY, Analysis Group Inc., Boston, MA.
THE EFFECT OF CUSHING'S SYNDROME UPON SERUM ALBUMIN METABOLISM *
Authors: Kenneth Sterling
Journal: Journal of Clinical Investigation (1960)

The present investigation of albumin metabolism in Cushing's syndrome employing the I'3'- labeled albumin turnover method (1) was undertaken in view of clinical and experimental evi- dence of significant effects of steroid hormones upon protein metabolism.Previous reports have described acute effects of large doses of glucocorticoids in human subjects (2-4).The effects of chronic hyperadrenalism were examined in the present work. MATERIAL AND M ETHODS Clinical inaterialThe following four categories of subjects were studied: 1) normal volunteers, 2) physically healthy hospitalized schizophrenic patients, 3) cases of Cushing's syndrome due to adrenal cortical hyperplasia; and 4) a patient with Cushing's syndrome due to exogenous steroids.1) Normiial volunteers.Thirteen subjects, 10 male, 3 female with ages ranging from 19 to 40 years.2) Physically healthy hospitalied schizophrcnic pa- tients.Ten subjects, 5 male, 5 female with ages ranging from 17 to 39 years.3) Cushing's syndromiie.Albumin turnover studies were carried out on 4 women during the active stage of clinically typical Cushing's syndrome attributed to bilateral adrenal hyperplasia.Three of the 4 were studied again after therapy and remission.The diagnoses were supported by elevated urinary ketogenic steroids or corticoids (Porter-Silber chromogens).In MWI.W., adminis- tration of prednisone was followed by suppression of uri- nary 17-ketosteroid levels.In the other 3 subjects, in- travenous ACTH was followed by an exaggerated rise in plasma corticoids, considered indicative of hyperplasia rather than tumor (5).None of the women exhibited appreciable virilization.All had amenorrhea; the 3 of pre-menopausal age resumed menstruation after therapy.M.W., aged 36, had severe Cushing's syndrome with osteoporosis and collapsed lumbar vertebrae, hypertension, intermittent hypokalemic alkalosis, and increased
Margaret McCartney: Who's measuring the harm caused by the new benefits system?
Authors: M. McCartney
Journal: BMJ (2015)

The Disability Living Allowance benefit started to become Personal Independence Payments (PIPs) in 2013. These payments, which are not means tested, go to people with long term disabilities who need help to cook, eat, travel, wash, or dress, for example.

The UK government’s stated aim was to reassess each person receiving Disability Living Allowance to reduce “caseload and expenditure” by 20%.1 After a “spending to save” philosophy the government gave two private companies, Atos and Capita, contracts worth about £500m2 and £140m3 to administer the assessments and, supposedly, to save us £3bn. The rationale was a need for objective functional assessments and continual reassessment.

Many in the media have focused on “benefit cheats.” Anxiety is a common, unintended outcome of health and social …
Genetic Basis of Morphological Variation: An Evaluation and Application of the Twin Study Method
Authors: C. N. Herndon
Journal: JAMA (1960)

This monograph presents a brief review of the methodology of twin studies and the results of applying some of these methods to a series of measurements on a group of monozygotic and dizygotic twins. In addition to containing variance analyses for detecting genetic components in 62 classical anthropometric measures, the book includes analyses based on Sheldon's somatotyping scale and on a masculine-feminine body-build scale devised by the authors. Unlike many previous twin studies, the authors have wisely included the variances of measurement errors (based on the differences between two measurements of the same dimension on a single person). Both the foreword (by Theodosius Dobzhansky) and the text emphasize the importance of learning more about polygenic inheritance in man and the fact that twins provide an excellent resource, not only for this purpose, but also for the equally important task of assaying the role of environmental factors in man, both in
Leukocytosis as an important risk factor for arterial thrombosis in WHO‐defined early/prefibrotic myelofibrosis: An international study of 264 patients
Authors: Veronika Buxhofer‐Ausch, Heinz Gisslinger, Jürgen Thiele, Bettina Gisslinger, Hans‐Michael Kvasnicka, Leonhard Müllauer, Sophie Frantal, Alessandra Carobbio, Francesco Passamonti, Elisa Rumi, Marco Ruggeri, Francesco Rodeghiero, Maria L. Randi, Irene Bertozzi, Alessandro M. Vannucchi, Elisabetta Antonioli, Guido Finazzi, Naseema Gangat, Ayalew Tefferi, Tiziano Barbui
Journal: American Journal of Hematology (2012)

We aimed to determine risk factors for thrombotic events in early/prefibrotic myelofibrosis diagnosed according to the World Health Organization criteria. Multivariate Cox regression analysis was calculated on a total number of 264 patients derived from an international database. After a median follow-up of 6.28 years, 42 (15.9%) patients experienced arterial (n = 31) or venous thrombosis (n = 11). A higher leukocyte count correlated with an increased risk for total thrombosis and in particular, with an increased risk for arterial thrombosis (P = 0.005, HR 1.15 and P = 0.047, HR 1.12, respectively). A platelet count above 870 × 10⁹/L was associated with a lower risk for total thrombosis and also for venous thrombosis (P = 0.022, HR 0.44 and P = 0.027, HR 0.19). Moreover, a lower hemoglobin level was associated with an increased risk for venous thrombosis (P = 0.007, HR 0.59). Our data indicate that leukocytosis is a prominent risk factor for thrombosis in early/prefibrotic MF.
A highly sensitive and specific method for quantitation of O-alkylated DNA adducts and its application to the analysis of human tissue DNA.
Authors: H Kang, C Konishi, T Kuroki, N Huh
Journal: Environmental Health Perspectives (1993)

Formation and accumulation of O6-alkylguanine and O4-alkylthymine in human tissues is possibly the most relevant marker for cancer risk. Because humans are chronically exposed to diverse kinds of chemicals and eventual DNA structural modifications are supposed to be a complex mixture of adducts at very low levels, it is essential to use an assay with extremely high sensitivity and specificity. We have established a quantitation method, called PREPI, for O6-methylguanine, O4-methylthymine, and O4-ethylthymine by the combination of prefractionation by HPLC, 32P-postlabeling, and immunoprecipitation. The detection limit was about 1 fmole for all three adducts, enabling us to analyze about 1 x 10(-8) levels as a molar ratio to normal counterpart using 100 micrograms of DNA. In a pilot experiment, we analyzed 11 peripheral blood samples from healthy volunteers. O6-Methylguanine was detected in all the cases with a mean value of 2.0 +/- 1.3 x 10(-8) (range, 0.78-4.6 x 10(-8)). Neither O4-methylthymine nor O4-ethylthymine was above the detection limit of 0.8 x 10(-8) as a ratio to thymine.
Epithelial cells in bone marrow: do they matter?
Authors: W A Marsman
Journal: Gut (2005)

Pitfalls in diagnosing acute pancreatitisWe thank Jolobe for his letter (Gut 2005;54:1207-8) which mentions the difficulty of establishing the diagnosis of acute pancreatitis in patients with diabetic ketoacidosis.We did not address diagnostic tests and medical intensive care treatment of acute pancreatitis in our article, 1 but reviewed the interventional and surgical treatment strategies in acute pancreatitis.There is no doubt that treatment of acute pancreatitis, including organ failure in its early phase, is solely supportive. 2 Due to improvements in inten- sive care medicine, mortality of severe disease has decreased dramatically over the past decades.However, to treat patient adequately, the correct diagnosis has to be made.Therefore, the first step in the diagnostic process of acute pancreatitis is to think of this disease.According to the latest classification from Atlanta, 3 acute pancreatitis is an acute inflammatory process of the pancreas with variable involvement of other regional tissues or remote organ systems.From a clinical point of view, acute upper abdominal pain and elevated pancreatic enzyme levels are needed to diagnose acute pancreatitis.As pointed out by Jolobe in his letter, acute pancreatitis is still underdiagnosed under certain clinical conditions, including diabetic ketoacidosis, but also in other clinical situations, such as shock of unknown origin, patients under intensive care treatment, as well as rare causes of the disease.As acute pancreatitis can be associated with diabetic ketoacidosis and the association between these two is a two way cause-and-effect relationship, early imaging of the pancreas is recommended in these patients to establish the correct diagnosis.Our article focused on the surgical and interventional treatment of severe acute pancreatitis.
A kinase in the life of the β cell
Authors: Domenico Accili
Journal: Journal of Clinical Investigation (2001)

Pancreatic β cells synthesize, store, and secrete insulin in response to appropriate environmental cues. The classic paradigm, as originally proposed by Matschinsky (1), holds that the products of glucose metabolism in β cells control insulin production and release. In recent years, this view has been broadened to include signaling by receptor tyrosine kinases as part of the β cell sensing mechanism, impinging on such diverse functions as insulin release and cellular proliferation (2).
Orthopedic Roentgen Atlas
Authors: H. Andrew Wissinger
Journal: JAMA (1970)

A roentgen atlas, to be valuable, should provide the reader with illustrations of acceptable technique and scope, that will cover the subject of the authors' intent. It also should provide clear explanations of the subject matter, so that the reader is aware of the visual information being offered. This book satisfies these requirements in some portions but in others has obvious shortcomings.  The early sections on the normal skeleton and variations of normal are excellent. They provide the reader with a complete set of illustrations and accurate information pertaining thereto. The authors' reasons for including these sections in the book are also sound.  Unfortunately when the reader progresses into the sections dealing with pathology, the book deteriorates for a number of reasons. In many chapters the authors deviate into treatment. This in our opinion is not within the province of an atlas. In other sections, eg, on aseptic necroses of
PITYRIASIS ROSEA-A VIROLOGICAL STUDY
Authors: L. GARCIA e SILVA, P. S. GARDNER
Journal: British Journal of Dermatology (1968)

SUMMARY. Virological studies were carried out on 11 patients with pityriasis rosea. The techniques employed were capable of demonstrating a wider variety of viruses than those employed by previous investigators, but the possibility that pityriasis rosea is caused by a virus has not been finally excluded.
Neutropenia due to beta lactamine antibodies.
Authors: B Rouveix, K Lassoued, D Vittecoq, B Regnier
Journal: BMJ (1983)

Neutropenia developed in 13 patients during treatment with beta lactamines. The time of onset ranged from eight to 27 days after beginning treatment and occurred with doses as low as 40 mg/24 hours. Concomitant symptoms were eosinophilia, rashes, and fever. Leucoagglutinins were detected in eight out of nine patients by the microleucoagglutination technique. Clinical and serological findings suggested that neutrophils become sensitised as a result of absorption on the cell membrane of drug-antibody immune complexes. An immune mediated pathogenesis for neutropenia induced by beta lactamine seems highly probable.
GlaxoSmithKline grants researchers access to clinical trial data
Authors: R. Coombes
Journal: BMJ (2012)

GlaxoSmithKline has taken steps to open up more clinical data behind its drug trials, just months after the company was fined a record amount for ethical breaches.

From January all anonymised patient level data that sit hidden behind the results of clinical trials of its approved and failed drugs will be available without charge through a secure website once access has been approved.

Andrew Witty, GSK’s chief executive, said that the move sprang from a desire to dismiss the perception that drug companies are always “hiding something.” 

“People have to really believe they are looking at the whole picture,” he …
Gender is more important than advancing age as a predictor of preserved systolic function in older persons hospitalized with heart failure
Authors: Frederick A. Masoudi, Grace L. Smith, Edward P. Havranek, Ronald H. Fish, Pam Wolfe, Beth R. Stevens, Diana L. Ordin, Harlan M. Krumholz, JoAnne Foody
Journal: Journal of the American College of Cardiology (2002)
Review clears Brompton surgeons
Authors: G. Yamey
Journal: BMJ (1999)

A review of the surgical outcomes at the Royal Brompton Hospital has cleared the hospital over allegations of excessive mortality in children undergoing cardiac surgery.

The independent review of paediatric surgery, comprising paediatric consultant cardiologists Dr Stewart Hunter and Dr Michael Godman and consultant cardiac surgeon Mr James Monro, studied operative data from 1987 to 1999 and found that “the Brompton results are similar to, and in most cases better than, the results from the UK register.”

The data, sent by an anonymous whistleblower to Private Eye magazine, were “incomprehensible, incomplete, and misleading.” Private Eye, which did not publish the allegations, passed the data, in confidence, to Mark Taylor, chief executive of the Brompton …
Association Between an Angiotensinogen Microsatellite Marker in Children and Coronary Events in Their Grandparents
Authors: Renee F. Badenhop, Xing Li Wang, David E.L. Wilcken
Journal: Circulation (1996)

Background Recently we found that the deletion (D) allele of the insertion/deletion (I/D) polymorphism of the ACE gene in 404 children was associated with a history of coronary artery disease (CAD) in their grandparents. This led us to explore polymorphisms in other genes of the renin-angiotensin system in this same population. Methods and Results We determined the genotypes for three microsatellite markers located near or in the angiotensinogen, angiotensin II (type-1) receptor, and renin genes in the children and related the allele frequencies to grandparental CAD. We found a significant association between the angiotensinogen marker in children and grandparental CAD (χ 2 =42.2, P =.00001) with these children having an excess of the 125-bp and 129-bp alleles (odds ratio, 2.5; 95% confidence interval, 1.7 to 3.7). Greatest grandparental risk was when their grandchildren had the 125-bp/125-bp, 129-bp/129-bp, or 125-bp/129-bp genotypes (odds ratio, 7.75; 95% confidence interval, 2.2 to 27). There was no association between the microsatellites at either the angiotensin II (type-1) receptor ( P =.8) or renin ( P =.2) genes in children and grandparental CAD and none between the angiotensinogen and ACE polymorphisms in relation to CAD family history. Conclusions This study identifies a significant association between an angiotensinogen marker in children and grandparental CAD. There was no association between the microsatellites at either the angiotensin II (type-1) receptor or renin genes and CAD in this population. We conclude that the angiotensinogen polymorphism as well as the ACE polymorphism may explain a part of the risk related to a family history of CAD.