tbuckley/cabot-search huggingface dataset:
Abuse of Amitriptyline
Authors: Murry J. Cohen
Journal: JAMA (1978)

Amitriptyline hydrocholride (Elavil) is frequently used in treating mild to moderate depressive states. A survey of 346 persons enrolled in a methadone maintenance program showed that 86 (25%) had admitted taking amitriptyline with the purpose of achieving euphoria. Thin-layer chromatography of random urine specimens over five months showed that 34% of the patients had a positive result for amitriptyline at least once during this time. These results suggest that misuse of amitriptyline is not uncommon and should be carefully considered prior to prescribing this agent to narcotic dependent persons.
The White Blood Cell Count as a Risk Factor
Authors: Richard Todd Light
Journal: JAMA (1986)

To the Editor.—  The recent report by Grimm and co-workers 1 of the prognostic importance of white blood cell (WBC) count as an independent predictor of future coronary heart disease raises many interesting questions about the role WBCs, particularly granulocytes, could play in the etiology of atherosclerosis. In addition to the generation of toxic oxidation metabolites injuring endothelial cells as cited by the authors, the possible role of granulocyte proteinases warrants consideration.  Granulocytes contain abundant proteolytic enzymes including an elastase, a collagenase, and cathepsin G, a proteinase with chymotrypsinlike substrate specificity. Under normal circumstances these enzymes, when released, are rapidly and irreversibly inhibited by a group of plasma proteins that circulate in large-molar excess over enzyme concentrations. For example, α 1 -proteinase inhibitor, formerly called α 1 -antitrypsin, is present in plasma at concentrations of 20μM or more. 2 However, α 1 -proteinase inhibitor, the principal inhibitor of granulocyte elastase,
Spontaneous reversal of acquired autoimmune dysfibrinogenemia probably due to an antiidiotypic antibody directed to an interspecies cross-reactive idiotype expressed on antifibrinogen antibodies.
Authors: A Ruiz-Arguelles
Journal: Journal of Clinical Investigation (1988)

A young man with a long history of abnormal bleeding was seen in January 1985. Coagulation tests showed dysfibrinogenemia and an antifibrinogen autoantibody was demonstrable in his serum. This antibody, when purified, was capable of inhibiting the polymerization of normal fibrin monomers, apparently through binding to the alpha fibrinogen chain. 6 mo later the patient was asymptomatic, coagulation tests were normal, and the antifibrinogen autoantibody was barely detectable. At this time, affinity-purified autologous and rabbit antifibrinogen antibodies were capable of absorbing an IgG kappa antibody from the patient's serum, which reacted indistinctly with both autologous and xenogeneic antifibrinogen antibodies in enzyme immunoassays. It has been concluded that the patient's dysfibrinogenemia was the result of an antifibrinogen autoantibody, and that later on an anti-idiotype antibody, which binds an interspecies cross-reactive idiotype expressed on anti-human fibrinogen antibodies, inhibited the production of the antifibrinogen autoantibody which led to the remission of the disorder.
Effect of aspirin on coronary collateral blood flow.
Authors: J D Altman, D Dulas, T Pavek, R J Bache
Journal: Circulation (1993)

BACKGROUND Although aspirin exerts beneficial antiplatelet activity in patients with coronary artery disease, cyclooxygenase blockade produced by aspirin causes a potentially deleterious effect by interrupting endothelial production of prostacyclin. Collateral vessels that develop in response to coronary occlusion display prominent endothelial cell proliferation and undergo vasoconstriction in response to indomethacin. This study was performed to test the hypothesis that cyclooxygenase blockade with aspirin would cause constriction of coronary collateral vessels and that such vasoconstriction would be reversed with nitroglycerin. METHODS AND RESULTS Collateral vessel growth was induced by embolic occlusion of the left anterior descending coronary artery in dogs. Four to 6 months later, coronary collateral flow was measured as retrograde flow from the cannulated collateral-dependent artery. Aspirin (1 mg/kg i.v.) caused 70 +/- 8% blockade of the increase in coronary blood flow produced by intra-arterial arachidonic acid and decreased retrograde flow from 37 +/- 7 to 28 +/- 7 ml/min (p &lt; 0.03). Increasing the dose of aspirin to 15 mg/kg i.v. caused 91 +/- 3% blockade of the response to arachidonic acid and further decreased retrograde flow to 21 +/- 4 ml/min (p &lt; 0.01). After aspirin administration, nitroglycerin (150 micrograms/min i.c.) reversed the collateral constriction and increased retrograde flow to 37 +/- 10 ml/min (p &lt; 0.01). CONCLUSIONS These data suggest that products of cyclooxygenase metabolism cause tonic vasodilation of well-developed coronary collateral vessels. Blockade of cyclooxygenase with even low-dose aspirin caused collateral vessel constriction with a decrease in collateral blood flow. However, nitroglycerin was able to fully reverse aspirin-induced collateral vasoconstriction and restore flow to the control level.
Ventricular Defibrillation — A Comparative Trial Using 175-J and 320-J Shocks
Authors: W. Douglas Weaver, Leonard A. Cobb, Michael K. Copass, Alfred P. Hallstrom
Journal: New England Journal of Medicine (1982)

We compared the effects of initial electrical shocks using 175 and 320 J (joules) in 249 patients with ventricular fibrillation. Survival was unrelated to the energy level used for defibrillation. Reversion to an organized rhythm occurred in a similar proportion of both treatment groups after one or two shocks. The rhythm identified after the first shock was related to outcome (the survival rate was 42 per cent in patients with supraventricular rhythm, 30 per cent in persistent ventricular fibrillation, 26 per cent in idioventricular rhythm, and 14 per cent in asystole; P less than 0.02). Fibrillation recurred in 68 per cent of patients who had been initially defibrillated to an organized rhythm. Repeated shocks at the higher energy level resulted in a higher incidence of atrioventricular block after defibrillation (24 per cent of patients receiving 320 J and 9 per cent of those receiving shocks of lower energy; P less than 0.005). Patients who survived required fewer shocks than patients who later died in the hospital (2.6 shocks as compared with 3.6; P less than 0.005). We conclude that initial defibrillatory shocks using 175 J are as safe and effective as shocks of nearly twice that energy level.
AB0610 No changes in sirtuin-1 (hdac 3) activity from pbmc of patients with osteoporosis
Authors: D. Wendling, M. Godfrin-Valnet, K. Khan, X. Guillot, W. Abbas, L. Baud, E. Toussirot, J.-P. Cedoz, C. Prati, G. Herbein
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Sirtuin 1 (Sirt1) is a nuclear enzyme from the class 3 histone deacetylases (HDACs) modulating gene expression, involved in the regulation of diverse biological processes ( cell survival, apoptosis, gluconeogenesis, adipogenesis, lipolysis), local and systemic inflammation, as well as in bone and cartilage remodeling. <h3>Objectives</h3> The main objective of the study was to evaluate Sirt1 activity in PBMC by venous blood aspiration in patients with osteoporosis (OP), compared to those of control patients, and to analyze the relationship between Sirt1 activity and production of mediators of inflammation and cytokines (TNFalpha, IL-6, IL-8) by the cells after ex vivo treatment with a Sirtuin activator, resveratrol, the most potent natural compound able to activate Sirt1. <h3>Methods</h3> A prospective and comparative monocentric study was performed in order to compare the activity of Sirt1 in patients with OP and controls. OP was defined by low BMD and at least one vertebral fracture. Secondary causes of osteoporosis were ruled out. PBMC were isolated from venous blood, and Sirt1 activity was evaluated from cytoplasmic and nuclear compartments using a fluorometric assay (SIRT1 fluorometric kit, BML-AK-555, Enzo Life Sciences, Villeurbanne, France) at the 15 minutes point. Culture supernatant levels of TNF alpha, IL-6, IL-8 were quantified before and after resveratrol ( 1 µmol and 5 µmol) ex vivo treatment, with commercial kits (Quantikine Kits, R&amp;D Systems, Minneapolis, MN). Bone remodeling markers (Ca, P, Vitamin D, sCTX I), and inflammation (CRP, ESR) were evaluated at the same time. Statistical analysis used Wilcoxon and t tests; significance : p less than 0.05. <h3>Results</h3> Eighteen patients with symptomatic OP (age 68 ± 9 years) and 18 controls (age 54 ± 13 years) were included. No differences were found in cytoplasmic or nuclear Sirt1 activity between patients and controls. Cytoplasmic and nuclear Sirt1 activity were significantly correlated in patients and controls. Sirt1 activity did not correlate with bone biologic remodeling biomarkers or biologic markers of inflammation (CRP). After resveratrol treatment, no changes in TNF alpha, IL-6 or IL-8 levels were found, compared to pre treatment values, or between patients and controls. <h3>Conclusions</h3> Sirt1 activity (cytoplasmic and nuclear) from PBMC was not different between OP patients and controls. These results suggest that there is no implication of Sirt regulation of pro inflammatory cytokines or chemokines in PBMC from patients with osteoporosis. <h3>Disclosure of Interest</h3> None Declared
Methylene Ether as an Anaesthetic
Authors: L. Tait
Journal: BMJ (1873)

The three drachms daily were continuied up to Mlay 6th, when she com- menced takinig half an ouince daily, which was persevered with until she left the hospital.For five or six weeks she also hadl a warm bath twice a week.At no time did she complain of any rheumatic or other pain during her time of treatment ; and dulring her sojourn in the hos- pitLal no change of symptoms occurred, anid no fresh one, such as cough, albumen in the urine, etc., came on.The temperature was registered night andl morning, as before said, for several days, andl as may be seen by the appended table.After a time the gluten-bread became very distasteful, even when tried in every possible mode, and its use had to be discontinued.In spite of treatment and diet, the patient (thoughi from time to time she varied in weight and strength), on the 8th of Mlay, began decidedly to lose strength and spirits, and, at her own request, left the hospital eventually.The following table contains the registration of thae dail-y amount and specific gravity of the urine, and the occasional weight and tem- prtr.Urinle.
The Proteomic Constraint and Its Role in Molecular Evolution
Authors: S. E. Massey
Journal: Molecular Biology and Evolution (2008)

Recently, the concept of a "Proteomic Constraint" was introduced to explain the frequency of genetic code deviations in mitochondrial genomes. The Proteomic Constraint was proposed to be proportional to the size of the mitochondrially encoded proteome, hence small proteomes are expected to experience smaller total numbers of errors resulting from genetic code deviations, leading to less likelihood of causing lethality. The concept is now extended to encompass several other aspects of the genetic information system. When the Proteomic Constraint is small, it is proposed that there is little selective pressure to evolve or maintain error correction mechanisms, as a result of the smaller total number of errors that accumulate. Conversely, a large Proteomic Constraint is proposed to result in a correspondingly large selective pressure to evolve or maintain error correction mechanisms. Differences in the size of the Proteomic Constraint can help to explain differences in replicational, transcriptional, and translational fidelities between genomes. A key piece of evidence is the existence of negative power law relationships between proteome size and error rates; these are demonstrated to be diagnostic of the action of the Proteomic Constraint. The Proteomic Constraint is argued to be a major factor determining mutation rates in a diverse range of DNA genomes, implying that mutation rates are clock like. A small Proteomic Constraint partly explains why RNA viruses possess high mutation rates. A reduced Proteomic Constraint in intracellular pathogenic bacteria predicts a drift upwards in mutation rates. Differences in the Proteomic Constraint also appear to be linked to differences in recombination rates between eukaryotes. In addition, a reduced Proteomic Constraint may explain features of resident genomes, such as loss of DNA repair pathways, increased substitution rates, and AT biases, in addition to the occurrence of genetic code deviations. Thus, it is argued that the Proteomic Constraint is a universal factor that influences a wide range of properties of the genetic information system.
Abstract 2478: Novel tyrosine derivatives of temozolomide active against breast cancer cell lines.
Authors: Jordan Kiefer O'Sullivan, Taylor R. Helphrey, Johnny Laim, Maggie C. Louie, Maria Graciela Carranza
Journal: Cancer Research (2013)

Abstract A series of L- and D-tyrosine derivatives of temozolomide (TMZ) was synthesized and evaluated as potentially improved anticancer agents against breast cancer cell lines. TMZ is a well tolerated, broad spectrum oral alkylating agent that crosses the blood–brain barrier. It has demonstrated activity against glioma and melanoma, as well as preclinical activity against breast cancer. Recent studies have shown the effectiveness of combining alkylating agents with the amino acid tyrosine, yielding analogs with significantly improved in vitro anticancer activity when compared with the parent compound. Following from this, we seek to improve the efficacy of TMZ by chemically modifying the C-8 position of the imidazotetrazine to include L- and D-tyrosine adducts attached either directly or via a linker of varying size. The novel TMZ derivatives were synthesized in good yields through efficient peptide synthesis methods. The anticancer efficacy of the derivatives was evaluated over several hormone-dependent and hormone-independent (ER+ and ER-) breast cancer cell lines. Preliminary results show that at a concentration of 2 x 10−5 M the novel derivatives display at least a 20% greater in vitro growth inhibitory activity when compared to TMZ, particularly in hormone-dependent MCF-7 breast cancer cell line. Structure–activity relationship (SAR) analysis suggests the influence of both the length of the linker and the stereochemistry of the tyrosine adduct on the anticancer activity of the derivatives. Further investigation will reveal if interaction with hormone-related receptors is involved in the mechanism of action of the newly synthesized derivatives. Citation Format: Jordan Kiefer O'Sullivan, Taylor R. Helphrey, Johnny Laim, Maggie C. Louie, Maria Graciela Carranza. Novel tyrosine derivatives of temozolomide active against breast cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2478. doi:10.1158/1538-7445.AM2013-2478
John A J Macleod
Authors: J. D M Douglas
Journal: BMJ (2009)

Rural doctor and world expert on island health care

Dr John Macleod and his father before him served the Hebridean island community of North Uist for 77 years. His death marks the ending of an iconic style of UK rural general practice. He had an international reputation as the world’s expert on island health care.

Sir John Dewar MP chaired the Highlands and Islands Medical Service report that was the world’s first government inquiry into rural health care delivery, published in 1912. His recommendations to constitute an essential general practice service to tackle rural deprivation were not implemented until 1932, when John’s parents arrived on North Uist with some certainty of income despite the island’s poverty. The Highlands and Islands Medical Service became the template for the establishment of NHS general practice by the postwar government in 1948.

John was born three years after his parents moved to North Uist and went to Lochmaddy Primary School before secondary school in Stornoway and Keil School, Glasgow. He studied medicine at the University of Glasgow and enjoyed the newfound freedoms, social life, and rugby in the city. He graduated in 1963, with national service with the Royal Navy minesweepers as intercalated life experience. House jobs in Glasgow were followed by teaching hospitals in London, where he gained a perspective in tertiary care.

The doctor’s wee boy returned to his island with his wife Lorna after 10 years of hospital experience, as Dr John. His father had gone by the nickname Zadok Macleod (after Zadok …
Potent toxicity of 2-chlorodeoxyadenosine toward human monocytes in vitro and in vivo. A novel approach to immunosuppressive therapy.
Authors: C J Carrera, C Terai, M Lotz, J G Curd, L D Piro, E Beutler, D A Carson
Journal: Journal of Clinical Investigation (1990)

Lymphoid cells were thought to be uniquely susceptible to excess 2'-deoxyadenosine (dAdo), when exposed to inhibitors of adenosine deaminase (ADA). However, we now find that human monocytes are as sensitive as lymphocytes to dAdo or to the ADA-resistant congener 2-chloro-2'-deoxyadenosine (CldAdo). Monocytes exposed in vitro to CldAdo, or to dAdo plus deoxycoformycin rapidly developed DNA strand breaks. Both the DNA damage and the toxicity of CldAdo or dAdo toward monocytes were blocked by deoxycytidine, but not by inhibitors of poly(ADP-ribose) polymerase. A partial decrease in RNA synthesis and a gradual decline of cellular NAD were early biochemical events associated with monocyte DNA damage. Low CldAdo concentrations (5-20 nM) inhibited monocyte phagocytosis and reduced the release of interleukin 6. Higher CldAdo concentrations led to a dose- and time-dependent loss of monocyte viability. Circulating monocytes disappeared within 1 wk in patients with cutaneous T cell lymphoma or with rheumatoid arthritis during continuous CldAdo infusion. The marked sensitivity of human monocyte function and survival to CldAdo in vitro, together with the monocyte depletion in patients receiving CldAdo chemotherapy, suggests that CldAdo or other dAdo analogues offer a novel therapeutic strategy for chronic inflammatory and autoimmune diseases characterized by inappropriate monocyte deployment or function.
INTRATESTICULAR IMPLANTATION OF THE FLEXNER-JOBLING RAT CARCINOMA
Authors: William H. Woglom
Journal: The Journal of Experimental Medicine (1916)

The Flexner-Jobling adenocarcinoma of the rat is easily transplantable into the testis of this animal. The resulting growths in the intact testis do not often attain the size of subcutaneous tumors. The smaller size of intratesticular nodules can not be explained solely by the pressure to which they are subjected during their growth; other factors, which cannot be determined, appear to be concerned.
Systemic Lupus Erythematosus During Penicillamine Therapy for Rheumatoid Arthritis
Authors: ANDREW CHALMERS
Journal: Annals of Internal Medicine (1982)

Six patients with rheumatoid arthritis developed a syndrome resembling lupus erythematosus while being treated with penicillamine. All patients had previous mucocutaneous reactions to chrysotherapy. Manifestations included pleurisy in five of six patients, rashes in three, nephritis in two, and neurologic disturbances in two; lupus erythematosus cells were found in five patients, antinuclear antibodies in all six, antideoxyribonucleic acid in three, positive Coombs' test results for three patients, and low C4 complement in five of the six. Symptoms were slow to resolve after penicillamine treatment was discontinued, and four of the patients needed corticosteroid therapy. A higher frequency than expected of HLA A 11 in three patients and B 15 in five patients was seen.
Lied aus der Ferne (Song From Afar)
Authors: Janet M. Torpy
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Primary Love and Psycho-analytic Technique
Authors: D. W. Kay
Journal: BMJ (1965)

MD:IcBtioURNAL non-specifically toxic.If tanned red cells were treated with extract of kidney antigen from the donor then they were agglutinated specifically by lymphocytes.This pheno- menon was heat-labile and was not enhanced by recipient serum.This volume is a highly specialized mono- graph written in French, and contains some important contributions to an understanding of transplantation phenomena.It will be of value to all those interested in tissue trans- plantation.R. Y. CALNE.
A Conserved Role for Phosphatidylinositol 3-Kinase but Not Akt Signaling in Mitochondrial Adaptations that Accompany Physiological Cardiac Hypertrophy
Authors: Brian T. O'Neill, Jaetaek Kim, Adam R. Wende, Heather A. Theobald, Joseph Tuinei, Jonathan Buchanan, Aili Guo, Vlad G. Zaha, Don K. Davis, John C. Schell, Sihem Boudina, Benjamin Wayment, Sheldon E. Litwin, Tetsuo Shioi, Seigo Izumo, Morris J. Birnbaum, E. Dale Abel
Journal: Cell Metabolism (2007)
The patient safety story
Authors: Glyn Elwyn, Janet M Corrigan
Journal: BMJ (2005)

Investigating and improving patient safety in health care is now an international phenomenon. The establishment of the National Patient Safety Agency in the United Kingdom1 and of the Center for Quality Improvement and Patient Safety in the United States2 are prime examples of the prominence given to safety within the wider concept of healthcare quality. No longer can there be any doubt that the most fundamental ethical principle in medicine—first, do no harm—is being taken seriously by a wide constituency. The next step is to embed safe practice into everyday clinical behaviour.

Why is there so much interest in patient safety? Why now? Data have been available on error rates in medicine for at least a decade. Although there had been earlier work in the 1970s, the landmark Harvard Medical Practice study of hospital inpatients was published in 1991.3 Additional studies followed from Australia and other contexts.4 This research points to an adverse event rate in secondary care close to 10%. The error rate in primary care is less well studied.