tbuckley/cabot-search huggingface dataset:
Aging and the Anticoagulant Response to Warfarin Therapy
Authors: Jerry H. Gurwitz, Jerry Avorn, Dennis Ross-Degnan, Igor Choodnovskiy, Jack Ansell
Journal: Annals of Internal Medicine (1992)

Objective: To assess the effect of aging on the anticoagulant response to warfarin. Design: Retrospective cohort study. Setting: A university hospital outpatient anticoagulation clinic. Patients: All patients (n = 530) monitored in the anticoagulation clinic over a 10-year period (1980 to 1990). The 530 study patients had a mean age of 61.5 (± 14.7) years (age range, 12 to 90 years). The patients were stratified into four age groups: younger than 50 years (n = 97); 50 to 59 years (n = 107); 60 to 69 years (n = 149); and 70 years or older (n = 177). Measurements: For each patient, a dose-adjusted mean prothrombin time ratio was calculated by dividing the mean prothrombin time ratio by the mean daily warfarin dose. Results: Older patients were more likely to be female (P < 0.001), to have more medical problems (P < 0.001), to be taking more medications (P < 0.001), and to weigh less than younger patients (P < 0.001). Across age groups, there were no significant differences in the use of medications that potentiated or inhibited the anticoagulant effects of warfarin. The prothrombin time ratio, when adjusted for dose, was significantly increased in older patients (P < 0.001). The increased anticoagulant response to warfarin seen with increasing patient age persisted even after simultaneously controlling for relevant demographic and clinical variables in a multivariate model. Other factors significantly associated with an increased sensitivity to warfarin included use of a medication with a potentiating interactive effect with warfarin, female gender, and overall medication use. Increased body weight and duration of warfarin use exceeding 6 months were found to be inversely related to anticoagulant response. Conclusion: The anticoagulant response to warfarin is exaggerated with advancing age. This finding emphasizes the need for close monitoring of older patients treated with warfarin therapy.
Sri Lankan government knowingly shelled hospitals, says UN report
Authors: N. Siva
Journal: BMJ (2011)

Hospitals within the no fire zone in the north of Sri Lanka were continually shelled by the Sri Lankan army during the final months of the civil war in 2009, says a United Nations report.

The report from a panel of experts commissioned by Ban Ki-moon, the UN secretary general, looked specifically at the Sri Lankan government’s accountability during the last stages of the civil war. It concluded that that there was evidence of war crimes being committed by the government and by the Liberation Tigers of Tamil Eelam (Tamil Tigers).

In May 2009 President Mahinda Rajapaksa made a victory speech congratulating his army on crushing the rebels and ending a war that spanned nearly three decades. However, since then …
839 TWELVE WEEKS OF TREATMENT IS INSUFFICIENT FOR HCV GENOTYPE 2 AND 3 INFECTED PATIENTS WITH STEATOSIS
Authors: J. Westin, M. Lagging, C. Pedersen, M. Rauning Buhl, M. Farkkila, N. Langeland, K. Morch, A. Alsio, G. Norkrans
Journal: Journal of Hepatology (2008)
The Effect of Tolerance to Noninherited Maternal HLA Antigens on the Survival of Renal Transplants from Sibling Donors
Authors: William J. Burlingham, Alan P. Grailer, Dennis M. Heisey, Frans H.J. Claas, Douglas Norman, Thalachallour Mohanakumar, Daniel C. Brennan, Hans de Fijter, Teun van Gelder, John D. Pirsch, Hans W. Sollinger, Michael A. Bean
Journal: New England Journal of Medicine (1998)

During pregnancy and nursing, a baby's developing immune system is intimately exposed to the mother's antigens. To determine whether this exposure is of clinical benefit to patients who later receive an allograft as an adult, we analyzed the outcome of primary renal transplantations from sibling donors.We retrospectively studied graft survival and rejection episodes in 205 patients who had received renal transplants at nine centers between 1966 and 1996 from sibling donors bearing maternal or paternal HLA antigens not inherited by the recipient. The sibling donors were categorized by analysis of family HLA-typing data.In the multicenter analysis, graft survival was higher at 5 years and at 10 years after transplantation in recipients of kidneys from siblings expressing maternal HLA antigens not inherited by the recipient than in recipients of kidneys from siblings expressing paternal HLA antigens not inherited by the recipient (86 percent vs. 67 percent at 5 years and 77 percent vs. 49 percent at 10 years, P=0.006 for both). Paradoxically, there was a higher incidence of early rejection in the former group, suggesting that fetal and neonatal exposure to maternal antigens results in immunologic priming. Pretransplantation transfusions of donor blood reduced the incidence of acute rejection while preserving the beneficial effect of tolerance to noninherited maternal antigens on graft survival. Since 1986, new immunosuppressive drugs have lessened the short-term, but not the long-term, survival advantage of grafts expressing maternal HLA antigens not inherited by the recipient.In the transplantation of a kidney from a sibling donor who is mismatched with the recipient for one HLA haplotype, graft survival is higher when the donor has maternal HLA antigens not inherited by the recipient than when the donor has paternal HLA antigens not inherited by the recipient.
483. Targeted Receptor Trafficking Affects the Efficiency of Retrovirus Transduction
Authors: Delfi Krishna, Julia Raykin, Joseph Le Doux
Journal: Molecular Therapy (2005)

We describe the development of an experimental system to test the hypothesis that the efficiency of retrovirus transduction is dependent on the pathway of virus entry into the host cell and the intracellular trafficking itinerary of the cellular receptor with which it interacts. The experimental system consists of three model target cell lines, derived from HeLa cells, that stably express one of three interleukin-2 receptor alpha chain (CD25) chimeras |[ndash]| TAC, TAC-CD16, and TAC-DKQTLL- that have identical extracellular domains but different intracellular trafficking itineraries, and a targeted amphotropic murine leukemia retrovirus whose envelope proteins were modified to include a binding site for TAC at their N-termini. We found that the efficiency of retrovirus transduction was affected by the distribution and trafficking itinerary of the TAC receptors. Transduction of cells that expressed TAC-DKQTLL was nearly 4-fold lower than transduction of control cells that did not express any of the TAC receptors. In contrast, transduction of cells that expressed TAC was 1.6 fold higher than transduction of control cells, whereas transduction was not significantly affected by the expression of TAC-CD16. Our results suggest that in the course of designing a targeted retrovirus it may be prudent to target only those receptors that internalize retroviruses via pathways that most efficiently support post-binding steps of infection.
OBESITY AS A RISK FOR LEFT VENTRICULAR DIASTOLIC DYSFUNCTION INDEPENDENT OF CARDIOVASCULAR RISK FACTORS AND LEFT VENTRICULAR MASS
Authors: Yoko Miyasaka, Satoshi Tsujimoto, Yoshinobu Suwa, Fumio Yuasa, Hirofumi Maeba, Toshiji Iwasaka
Journal: Journal of the American College of Cardiology (2012)
Factors affecting the response of lung clearance systems to acid aerosols: role of exposure concentration, exposure time, and relative acidity.
Authors: R B Schlesinger
Journal: Environmental Health Perspectives (1989)

The ability of the lungs to clear deposited material is essential for maintenance of lung homeostasis. Acid aerosols have been shown to alter the efficiency of this process. This paper assesses the role of acid aerosol exposure concentration (C), exposure time (T), and relative acidity in producing changes in clearance from both the tracheobronchial tree and respiratory region of the lungs of rabbits. The response was found to be due to total exposure, i.e., some combination form of C x T, and was also related to relative acidity.
ENVIRONMENT AND SKIN DISEASE.*
Authors: F. F. Hellier
Journal: British Journal of Dermatology (1940)

Journal Article ENVIRONMENT AND SKIN DISEASE. Get access F. F. Hellier, M. A., M.D., M.R.C.P. F. F. Hellier, M. A., M.D., M.R.C.P. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 52, Issue 4, 1 April 1940, Pages 107–123, https://doi.org/10.1111/j.1365-2133.1940.tb10847.x Published: 01 April 1940
Terodiline with bladder retraining for treating detrusor instability in elderly people.
Authors: P A Wiseman, J Malone-Lee, G S Rai
Journal: BMJ (1991)

To compare terodiline with bladder retraining against placebo with bladder retraining in the treatment of detrusor instability in frail elderly patients.Randomised, double blind, parallel group study. Treatment lasted for six weeks. Frequency of micturition and episodes of incontinence recorded on diary chart by patients.Incontinence clinic and a geriatric day hospital at two teaching hospitals.37 frail but ambulant patients, mean (range) age 80.4 (70-89) years with urinary frequency and urge incontinence, due to detrusor instability. Two patients withdrew before the first assessment (one in each group) and one could not complete the diary chart (placebo group).19 patients received bladder retraining and terodiline 25 mg daily and 18 bladder retraining and placebo.Change in urinary frequency and number of episodes of incontinence after six weeks' treatment. Patient's subjective evaluation of symptoms.Little difference was found in the results of treatment with terodiline and placebo. The change in episodes of incontinence per 24 hours was no different in the two groups (95% confidence interval -0.6 to 1.2; p = 0.75) and the difference between treatments in the change in frequency of micturition per 24 hours (-0.2) was not significant (-1.1 to 1.2; p = 0.76). Ten patients taking terodiline thought they had improved compared with seven receiving placebo; this difference was not significant.Although the number of patients in each group was small and may have been insufficient to detect a drug effect, the possible benefit of terodiline is likely to be small.
Six international research bodies form alliance to target chronic diseases
Authors: H. MacDonald
Journal: BMJ (2009)

Six of the world’s biggest research bodies have come together to channel funding into the fight against chronic diseases. The Global Alliance on Chronic Disease “will give big funders a neutral platform to meet, talk, and share,” said Stig Pramming, who is charged with developing the alliance. “It will provide an effective way of making decisions and facilitating donations.”

Professor Pramming, who is head of the Oxford Health Alliance, a UK based group of international experts, activists, and corporate …
Autoimmune lymphoproliferative syndrome–like disease with somatic KRAS mutation
Authors: Masatoshi Takagi, Kunihiro Shinoda, Jinhua Piao, Noriko Mitsuiki, Mari Takagi, Kazuyuki Matsuda, Hideki Muramatsu, Sayoko Doisaki, Masayuki Nagasawa, Tomohiro Morio, Yoshihito Kasahara, Kenichi Koike, Seiji Kojima, Akira Takao, Shuki Mizutani
Journal: Blood (2010)
Hypotensive and Renal Effects of Diazoxide, a Sodium-Retaining Benzothiadiazine Compound
Authors: C. BARTORELLI, N. GARGANO, G. LEONETTI, A. ZANCHETTI
Journal: Circulation (1963)

Diazoxide, a new compound of the benzo-thiadiazine group, has been shown to decrease both systolic and diastolic arterial pressure in mild or moderate hypertensive patients, even though it lacks the saluretic properties characteristic of the other known compounds of the group. Instead of promoting sodium excretion, diazoxide appears to be a powerful sodium- and chloride-retaining agent, its prolonged use leading to important increases in plasma volume and body weight, and probably to some redistribution between extracellular and intracellular fluid. Glomerular filtration rate and renal plasma flow are often increased during treatment with the drug. Although diazoxide was in several respects a useful hypotensive agent, at least in hypertensive patients without heart failure, it may share with other benzothiadiazine compounds some pancreatic toxicity, a side effect that should be carefully considered during benzothiadiazine treatment.
Acknowledgements for THSNA Meeting Proceedings
Authors: Elizabeth M. Van Cott
Journal: American Journal of Hematology (2012)

THSNA extends our deepest gratitude to all the individuals listed below for their expertise and help in making the inaugural THSNA meeting possible. David Garcia, Chair Peter Kouides, Vice-Chair Mark Crowther Jorge DiPaola Eric Grabowski Christine Guelcher Catherine Hayward Scott Kaatz Barbara Konkle Stephan Moll Lynn Oertel Leonard Valentino Ann Wittkowsky James Zehnder. Elizabeth Van Cott, Editor, THSNA Meeting Proceedings Dorothy Adcock-Funk Jack Ansell Deborah Brown Carlo Brugnara Spero Cataland Jorge DiPaola David Garcia James George Joan Gill Kathryn Hassell Peter Kouides Marlies Ledford-Kraemer Michael Makris Karen Moffat Stephan Moll Anne Neff Edith Nutescu Rajiv Pruthi Leslie Raffini Michael Tarantino Leonard Valentino Daniel Witt James Zehnder. Eric Grabowski, Chair James Bussell Marc Carrier Anthony Chan Jorge DiPaola Nancy Dower Charlie Francis David Garcia Christine Guelcher John Heit Susan Hunter Shannon Jackson Paula James Craig Kessler Marion Koerper Peter Kouides Richard Marlar Patricia Massicotte Diane Nugent Lynn Oertel Thomas Ortel Michael Paidas David Paje Elizabeth Plumhoff Rajiv Pruthi Margaret Ragni Fred Rickles Jeff Weitz. Elizabeth Goldstein as Program Director of THSNA, Lori Jacobson-Tews and Laura Mott for outstanding administrative support, All the THSNA meeting exhibitors and sponsors, without whose support educational meetings like this one would not be possible, The American Journal of Hematology and its staff for publishing the THSNA Meeting Proceedings, including Anna Wesley for all the assistance she provided to the authors, reviewers, and editors, and Carlo Brugnara, Editor-in-Chief at American Journal of Hematology, for his expert guidance throughout the entire process of producing this journal supplement, The meeting faculty and poster authors for sharing with THSNA their expertise in their presentations, and manuscripts and abstracts in this supplement, All the THSNA attendees for their shared interest in thrombosis and hemostasis. Together, the combined efforts from all are what make THSNA a success. Thank you! At press time, unrestricted educational grants and/or sponsorship were kindly received from the following: This activity is supported by an educational donation provided by Amgen Baxter The activity is supported, in part, by an educational grant from Bayer Healthcare Pharmaceuticals, Inc. Bristol-Myers Squibb and Pfizer, Inc. This activity is supported by an educational grant from Daiichi Sankyo, Inc, and Lilly USA, LLC Grifols Supported by an educational grant from Janssen Pharmaceuticals, Inc., administered by Janssen Scientific Affairs, LLC Novo Nordisk Pfizer Canada Sponsorships Gold Level Support Biogen Idec Hemophilia Boehringer Ingelheim Pharmaceuticals, Inc. CSL Behring, LLC Silver Level Support: Alexion Pharmaceuticals Grifols Janssen Pharmaceuticals, Inc. Octapharma USA, Inc. Pfizer, Inc. Other Centers for Disease Control and Prevention, Division of Blood Disorders.
S150 Smad-dependent and Smad-independent induction of Id1 by prostacyclin analogues inhibits proliferation of pulmonary artery smooth muscle cells in vitro and in vivo
Authors: J. Yang, X. Li, R. S. Al-Lamki, M. Southwood, J. Zhao, A. M. Lever, F. Grimminger, R. T. Schermuly, N. W. Morrell
Journal: Thorax (2010)

<h3>Introduction and Objectives</h3> Mutations in the bone morphogenetic protein type II receptor (BMPR-II) are responsible for the majority of cases of heritable pulmonary arterial hypertension (PAH). Mutations lead to reduced Smad1/5-driven expression of inhibitor of DNA binding protein 1 (Id1) and loss of the growth suppressive effects of BMPs. The impact of existing PAH therapies on BMP signalling is lacking. Because prostacyclin analogues are effective treatments for clinical PAH, we hypothesised that these agents enhance Smad1/Id1 signalling. <h3>Methods</h3> Iloprost alone induced Id1 expression in human pulmonary artery smooth muscle cells (PASMCs), an effect that was independent of Smad1/5 activation but dependent on a cAMP-responsive element in the Id1 promoter. In addition, iloprost and treprostinil enhanced BMP-induced phosphorylation of Smad1/5 and Id1 expression in a cAMP-dependent manner. The mechanism involved suppression of inhibitory Smad, Smad6. Furthermore, iloprost rescued the deficit in Smad1/5 phosphorylation and Id gene expression in PASMCs harbouring mutations in BMPR-II and restored growth suppression to BMP4 in mutant PASMCs. <h3>Results</h3> We confirmed a critical role for Id1 in PASMC proliferation. Reduced expression of Id1 was observed in concentric intimal lesions of heritable PAH cases. In the monocrotaline rat model of PAH, associated with reduced BMPR-II expression, we confirmed that treprostinil inhibited smooth muscle cell proliferation and prevented progression of PAH while enhancing Smad1/5 phosphorylation and Id1 gene expression. <h3>Conclusions</h3> Prostacyclin analogues enhance Id1 expression in vitro and in vivo and restore deficient BMP signalling in BMPR-II mutant PASMCs.
BMA continues to oppose assisted suicide and euthanasia
Authors: Kathryn Godfrey
Journal: BMJ (2004)

The BMA continues to oppose legislation to allow assisted suicide for patients, despite other bodies that represent doctors now taking a neutral stance.

During questioning last week by a House of Lords select committee on Lord Joffe's Assisted Dying for the Terminally Ill Bill, representatives from the BMA said that the results of “consistent and regular” debates with members meant that the position of the association, which represents 80% of British doctors, remained unchanged.

Giving evidence to the same committee the previous week the Royal College of Physicians and the Royal College of General Practitioners …
Brominated flame retardants: cause for concern?
Authors: Linda S Birnbaum, Daniele F Staskal
Journal: Environmental Health Perspectives (2003)

Brominated flame retardants (BFRs) have routinely been added to consumer products for several decades in a successful effort to reduce fire-related injury and property damage. Recently, concern for this emerging class of chemicals has risen because of the occurrence of several classes of BFRs in the environment and in human biota. The widespread production and use of BFRs; strong evidence of increasing contamination of the environment, wildlife, and people; and limited knowledge of potential effects heighten the importance of identifying emerging issues associated with the use of BFRs. In this article, we briefly review scientific issues associated with the use of tetrabromobisphenol A, hexabromocyclododecane, and three commercial mixtures of polybrominated diphenyl ethers and discuss data gaps. Overall, the toxicology database is very limited; the current literature is incomplete and often conflicting. Available data, however, raise concern over the use of certain classes of brominated flame retardants.
Active Immunization with Lipopolysaccharide Pseudomonas Antigen for Chronic Pseudomonas Bronchopneumonia in Guinea Pigs
Authors: James E. Pennington, William F. Hickey, Linda L. Blackwood, M. Amin Arnaut
Journal: Journal of Clinical Investigation (1981)

Chronic respiratory infection with Pseudomonas aeruginosa is a leading clinical problem among patients with cystic fibrosis. Because antimicrobial agents are usually ineffective in eradicating these infections, additional therapeutic or prophylactic measures should be considered. In this study, an experimental guinea pig model of chronic Pseudomonas aeruginosa bronchopneumonia was utilized to determine whether active immunization with lipopolysaccharide (LPS) P. aeruginosa antigen may favorably influence the course of this infection. Experimental pneumonia was established by tracheobronchial instillation of suspensions of microscopic agar beads, which were impregnated with viable P. aeruginosa. After 4 wk of infection, the geometric mean (reciprocal) passive hemagglutinating Pseudomonas antibody titer was 185±1.3, and lungs contained 16.8±4 × 103 colony-forming units Pseudomonas/ml of lung homogenate. Pseudomonas immunization, given prior to a 4-wk infection, resulted in significantly higher passive hemagglutinating titers (474±1.4; P < 0.05), lower numbers of viable Pseudomonas in lung tissues (2.4±0.6 × 103; P < 0.01), and reduced histopathology in lungs. In contrast, providing Pseudomonas immunization to animals 2 wk after pulmonary infection was established, offered no apparent benefit. Likewise, no protection was afforded by prophylactic immunization with a non-Pseudomonas LPS antigen (Escherichia coli J5 vaccine). Using a Raji cell assay, modified to detect circulating immune complexes in vaccinated and infected guinea pig sera, there was no evidence that active immunization increased the frequency of circulating immune complexes in infected guinea pigs.It is concluded that prophylactic immunization with Pseudomonas LPS antigen may confer protection from subsequent Pseudomonas bronchopneumonia, but that immunization during established infection is not beneficial.
The NASA Syndrome
Authors: Bruce Spurlock
Journal: JAMA (1992)

To the Editor.  —I was asked to see a patient recently who had received a diagnosis I did  understand. The patient, a 50-year-old man with abdominal pain, had been evaluated thoroughly by an emergency department physician and had also been seen by a surgeon. The diagnosis given by the resident surgeon was not a surgical abdomen and an internal medicine consultation was recommended.  What is meant by not a surgical abdomen? Because I had seen this diagnosis before, signed by both resident and staff surgeons, I thought it appropriate to investigate what seemed to me to be a new disease. After consulting major surgical textbooks with no success, I conducted a computerized search of the biomedical literature with the aid of a medical librarian. I couldn't find any reports of this diagnosis, nor could I find a diagnosis related group or International Classification of Diseases, Ninth Revision code for