tbuckley/cabot-search huggingface dataset:
Impact of age on clinical outcome and postlytic management strategies in patients treated with intravenous thrombolytic therapy. Results from the TIMI II Study. TIMI II Investigators.
Authors: F V Aguirre, R P McMahon, H Mueller, N S Kleiman, M J Kern, P Desvigne-Nickens, W P Hamilton, B R Chaitman
Journal: Circulation (1994)

BACKGROUND Few thrombolytic studies have assessed whether patient age is an indication for routine postlytic cardiac catheterization and revascularization or evaluated the impact of age on 1-year outcome differences after acute myocardial infarction. METHODS AND RESULTS A secondary analysis of 3339 patients enrolled in the TIMI II trial was performed to identify differences in clinical and coronary angiographic findings and 1-year cardiac event rates among 841 patients &lt; 50 years old, 1639 patients 50 to 64 years old, and 859 patients 65 to 75 years old. Differences in 1-year clinical outcome were assessed among patients randomly assigned to an invasive or a conservative postlytic strategy within each age group. The percentages of patients with a prior history of myocardial infarction, angina, congestive heart failure, hypertension, or diabetes mellitus or an infarction complicated at the time of study entry by shock, pulmonary edema, hypotension, rales more than one third of lung fields, or atrial fibrillation as well as the percentage of female patients (all P &lt; .001) increased with age. Fewer older patients (65 to 75 years) received early (ie, &lt; or = within 2 hours after symptom onset) treatment with recombinant tissue-type plasminogen activator (rTPA), and fewer were eligible for random assignment to immediate or deferred beta-blocker therapy (P = .01). The location of the infarct-related artery and the percentage of patients with patent (ie, TIMI flow grade 2 or 3) or "complete" (ie, TIMI flow grade 3) infarct-related artery flow did not vary with age. The percentage of patients with multivessel disease was greatest in the older patients (P = .001). Cumulative 1-year mortality was low in the youngest patients (2.8%; 99% confidence interval [CI], 1.6% to 4.7%) regardless of whether the infarct location was anterior (3.7%) or nonanterior (1.6%). The highest 1-year mortality occurred in the older patients (13.6%; 99% CI, 10.9% to 16.9%), particularly when the infarct location was anterior (18%). The 42-day rates of reinfarction (P = .85), death (P = .95), or death or reinfarction (P = .99) were similar in patients assigned to the invasive or conservative postlytic treatment strategy, regardless of age group. CONCLUSIONS Among patients with acute myocardial infarction treated with intravenous rTPA, heparin, and aspirin, there were age-related differences in time to treatment with thrombolytic therapy, use of beta-blockers, extent of coronary artery disease, and 1-year cardiac event rates. Routine use of cardiac catheterization and coronary revascularization does not improve immediate or 1-year outcome in terms of mortality or reinfarction compared with a more conservative strategy in young, middle-aged, or elderly patients similar to those enrolled in TIMI II.
Albumin gene expression is down-regulated by albumin or macromolecule infusion in the rat.
Authors: A Pietrangelo, A Panduro, J R Chowdhury, D A Shafritz
Journal: Journal of Clinical Investigation (1992)

A novel feedback regulatory mechanism operating on transcription of the albumin gene is described in the rat. In 1946, it was proposed that circulating colloids, including serum albumin, may affect the synthesis and/or secretion of albumin in the liver. The molecular basis for this proposed regulation has now been investigated by adding oncotically active macromolecules to the circulation of normal or genetically albumin-deficient Nagase analbuminemic rats (NAR) and analyzing the hepatic expression of genes, including albumin after 24 h. The transcription rate of the albumin gene was higher in NAR than in normal rats and was dramatically reduced by raising serum albumin to 1.6 g/dl. Intravenous infusion of albumin into normal rats also decreased transcriptional activity of the albumin gene by 50-60%, and this decrease correlated with changes in serum colloid osmotic pressure after albumin infusion. Inhibition of albumin gene transcription was also observed upon intravenous infusion of other protein or nonprotein macromolecules, such as gamma-globulin and dextran. This down-regulation appears to control the steady-state level of albumin mRNA in the liver. Aside from a concomitant decrease in apo E gene transcription after albumin or macromolecule infusion, there was no change in the transcription rate of other genes, including those exhibiting liver-preferred or -specific expression (e.g., tyrosine amino-transferase, cytochrome P-450, alpha 1-antitrypsin, apolipoproteins A-I and B, and transferrin) or general cellular expression (e.g., alpha-tubulin, pro alpha 2 collagen, and beta-actin). Feedback regulation of albumin gene expression by serum colloids may serve as a specific homeostatic mechanism to maintain the steady-state level of total protein in the circulation.
Desensitization of the insulin receptor by antireceptor antibodies in vivo is blocked by treatment of mice with beta-adrenergic agonists.
Authors: D Elias, M Rapoport, I R Cohen, Y Shechter
Journal: Journal of Clinical Investigation (1988)

In previous studies we reported that immunization of mice with ungulate insulins induced the development of antiinsulin antibodies, which include an idiotype that appeared to recognize the part of the insulin molecule recognized by the hormone receptor. The antiinsulin antibodies of this idiotype were replaced spontaneously by antiidiotypic antibodies. The antiidiotypic antibodies, which persisted for about 14 d, mimicked insulin and functioned as antibodies to the insulin receptor. They induced down regulation, desensitization and refractoriness of the insulin receptor and disturbances in glucose homeostasis in vivo (Shechter, Y., D. Elias, R. Maron, and I.R. Cohen., 1984; Elias, D., R. Maron, I.R. Cohen, and Y. Shechter. 1984, J. Biol. Chem. 259: 6411-6419). We now report that effects of the antiidiotypic antibodies on the insulin receptor effector system can be modified pharmacologically. Administration of the beta-adrenergic agonist isoproterenol during the period of insulin resistance (days 26-40 after primary immunization), largely restored fat cell responsiveness to insulin, and eliminated the appearance of fasting hyperglycemia. This restoration appeared to be caused by inhibition of both insulin receptor desensitization and refractoriness. In contrast, down regulation of insulin receptors was not reversed by isoproterenol treatment in vivo. The effects of treatment with isoproterenol persisted for 2-4 d after termination of treatment. The beta-antagonist, propranolol and more so, the beta 1a-antagonist metoprolol, specifically blocked the effect of isoproterenol at a molar ratio of 3-10:1. Oral administration of the cAMP phosphodiesterase inhibitor, aminophylline, was also effective in inhibiting the development of desensitization in fat cells. These results indicate that treatment with beta 1-adrenergic agonists in vivo, or other agents that elevate cellular cAMP levels, can inhibit the development of the "postbinding" defects induced by insulin-mimicking, antireceptor antibodies. These observations have both basic and clinical implications.
Acyclovir Exposure and Birth Defects
Authors: James L. Mills, Tonia C. Carter
Journal: JAMA (2010)

Twenty-two percent of pregnant women are seropositive for herpes simplex virus 1 and 2% of susceptible pregnant women acquire a primary herpes simplex virus infection. 2Data on the use of acyclovir and valacyclovir to treat infected women are extremely scarce.The Slone Epidemiology Center, Boston, Massachusetts, statistics on normal pregnancies indicate that approximately 2 per 1000 pregnancies are exposed to each drug during organogenesis (A.Mitchell and C. Louik, Slone Epidemiology Center at Boston University, written communication, July 14, 2010).Thus, each year in the United States approximately 15 000 conceptuses are potentially exposed to these drugs, yet little information is available on their teratogenicity.4][5][6] Although these studies generally showed no teratogenic effects, they were underpowered to answer the question definitively.
Ulcerative colitis and Crohn's disease
Authors: A Ferguson
Journal: BMJ (1994)

In the past four years three excellent and comprehensive books on inflammatory bowel disease have been published.*RF 1-3* In a total of 1812 pages 156 contributors provide detailed accounts of the recent striking rise in the incidence of Crohn's disease but not ulcerative colitis in most developed countries; patients' genetic disposition (the dis-eases are apparently not HLA related); and clinical features, immunology, pathology, complications, and management options. Can there be much left to find out? Regrettably for the 120 000 or so patients with inflammatory bowel disease in Britain, from toddlers to octogenarians, the answer is yes. And despite inflam-matory bowel disease being unfashionable and attracting little research funding, there is a wealth of research going on.

Theories of the cause of inflammatory bowel disease abound. Current front runners include a range of types of immune dysregulation, such as abnormally vigorous stimulation of the gut immune system by products of the commensal flora, inappropriate activation of a single component among the many gut immune cells and mediators, or failure of an inhibitory signal that normally switches off a protective local inflammatory reaction. …
Mixed Cryoglobulinemia in HIV-1 Infection: The Role of HIV-1
Authors: Antonios N. Dimitrakopoulos
Journal: Annals of Internal Medicine (1999)

Background: Cryoglobulins are associated with chronic infections. Objective: To investigate the prevalence of mixed cryoglobulinemia in patients with HIV-1 infection, the clinical spectrum of cryoglobulinemia in these patients, and the possible role of HIV-1 in cryoglobulin formation. Design: Prospective cohort study. Setting: Laiko Hospital, Athens, Greece. Patients: 89 patients with HIV-1 infection. Measurements: Serum and cryoglobulins were evaluated for antibodies to HIV and hepatitis C virus (HCV), HIV-1, and HCV viral load. Results: Mixed cryoglobulins were detected in 24 patients with HIV-1 infection (27% [95% CI, 18% to 36%]). The HIV-1 viral load was higher in cryoglobulin-positive patients (median, 38.25 × 103 copies/mL [25th, 75th percentiles: 13.8 × 103 copies/mL, 78.55 × 103 copies/mL]) than in cryoglobulin-negative patients (median, 5.3 × 103 copies/mL [25th, 75th percentiles: 0.7 × 103 copies/mL, 27.2 × 103 copies/mL]) (P = 0.001). Antibodies to HIV were detected in all cryoprecipitates, and HIV-1 RNA sequences were identified in 22 of the 23 cryoprecipitates examined. Nine cryoglobulin-positive patients (38% [CI, 19% to 54%]) had clinical manifestations compatible with cryoglobulinemia. Conclusions: Mixed cryoglobulinemia is common in patients with HIV-1 infection.
THE RELATION OF THE LEUCOCYTIC BACTERIOLYSIN TO BODY FLUIDS
Authors: Wilfred H. Manwaring
Journal: The Journal of Experimental Medicine (1913)

1. An extract of horse leucocytes is strongly bactericidal when dissolved in distilled water; it has considerable bactericidal power when dissolved in physiological saline; but it loses its bactericidal properties when mixed with blood serum or with normal or pathological tissue fluids. 2. About half the antibactericidal action of blood serum is due to the serum colloids, about a quarter to the neutral serum crystalloids, and a quarter to the diffusible alkalies. Diffusible acids have no antibactericidal action. 3. The addition of boric acid to an inactive mixture of leucocytic extract and serum or other body fluid occasionally restores part of the original bactericidal power, but never more than a small fraction of that power.
The Serologic Marker CA 19-9 and Pancreatic Cancer
Authors: David A. Nardone
Journal: Annals of Internal Medicine (1989)

Letters and Corrections15 July 1989The Serologic Marker CA 19-9 and Pancreatic CancerDavid A. Nardone, MDDavid A. Nardone, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-111-2-184 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: The serologic marker for pancreatic cancer, CA 19-9, is more useful than presented in the study by Pleskow and colleagues (1). Its value is not shown by comparing CA 19-9 to carcinoembryonic antigen at a cutoff of 70 U/mL (P< 0.0001) but by doing calculations for true-positive rates (sensitivity), false-positive rates (1 — specificity), and for likelihood ratio-positive at different cutoff points: for 10 000 U/ mL: true-positive rate, 0.19; false-positive rate, 0.01; likelihood ratio-positive, 19; for 1000 U/mL: true-positive rate, 0.39; false-positive rate, 0.01; likelihood ratio-positive, 39; for 100 U/mL: true-positive rate, 0.63; false-positive rate, 0.10; likelihood ratio-positive, 6.3; and for 70 U/mL: true-positive rate, 0.70; false-positive rate,...References1. PleskowBergerGyvesAllenMcLeanPodolsky DHJEAD. Evaluation of a serologic marker, CA 19-9, in the diagnosis of pancreatic cancer. Ann Intern Med. 1989;110:704-9. LinkGoogle Scholar2. Measuring the accuracy of clinical data. In: Sox HC Jr., Blatt MA, Higgins MC, Marton KI, eds. Medical Decision Making. Boston: Butterworths; 1988:123-4. Google Scholar3. Centor R. A Visicalc program for estimating the area under a receiver operating characteristic (ROC) curve. Med Decis Making. 1985;5:139-48. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Veterans Administration Medical Center Portland, OR 97225 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDiagnosing cancer of the pancreas. 15 July 1989Volume 111, Issue 2Page: 184-185KeywordsCarcinoembryonic antigenPancreatic cancerSpecificity Issue Published: 15 July 1989 PDF downloadLoading ...
The future for medical education
Authors: Tiago Villanueva
Journal: BMJ (2005)

Academic medicine has a key role in health systems, and the definition of the International Campaign to Revitalise Academic Medicine (ICRAM) captures the issues well. 1 In the United Kingdom, the number of clinical academics continues to fall, particularly at the clinical lecturer grade (42% lower in 2004 than in 2000). 2 At the same time, the numbers of students and young doctors are rising, creating an unstable situation.NHS staff already do most of the training for both postgraduates and undergraduates, and this is increasingly occurring outside university centres, including in primary care.The NHS funds some 40% of the academic posts.
Speed/accuracy relations: The kinetic–kinematic link and predictions for rapid timing tasks
Authors: Les G. Carlton, Yeou-Teh Liu
Journal: Behavioral and Brain Sciences (1997)

Recent accounts of the speed/accuracy relation for motor tasks have focused on the concept of motor output variability. We outline the advantages of this approach and the limitation of Plamondon's model in explaining movement error. We also examine and present complimentary data for rapid timing tasks. While these tasks do not meet the presented assumptions, the data still fit the model predictions.
THE IN VITRO METABOLISM OF 7α-3H DEHYDROEPIANDRO-STERONE BY HUMAN SKIN
Authors: J. CHAKRABORTY, J. THOMSON, M.P. MacSWEEN, A.V. MUIR, K.C. CALMAN, J.K. GRANT, J.A. MILNE
Journal: British Journal of Dermatology (1970)

SUMMARY.— Slices of skin from human subjects have been shown to transform 3H-dehydroepiandrosterone predominantly to 4-androstene-3,17-dione and 5-androstene-3β,17β-diol. Testosterone, testosterone sulphate and dehydro-epiandrosterone sulphate were not formed in detectable amounts under the conditions of the investigation. Skin from the shoulder appeared significantly more active than that from the thigh or axilla in metabolizing the dehydro-epiandrosterone.
878 Hepatic overexpression of TGF-beta 1 during liver injury leads to massively increased IL-6 levels and high mortality rates
Authors: F THIERINGER, J GARCIALAZARO, P CZOCHRA, D FRIEBE, E MEYER, S LUTH, M SCHUCHMANN, P GALLE, A LOHSE, S KANZLER
Journal: Hepatology (2003)
Calories Count
Authors: Linda Van Horn
Journal: JAMA (2011)

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
Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production
Authors: Zhou Zhu, Robert J. Homer, Zhonde Wang, Qingsheng Chen, Gregory P. Geba, Jingming Wang, Yong Zhang, Jack A. Elias
Journal: Journal of Clinical Investigation (1999)

Interleukin (IL)-13 is a pleiotropic cytokine produced in large quantities by activated CD4(+) Th2 lymphocytes. To define further its potential in vivo effector functions, the Clara cell 10-kDa protein promoter was used to express IL-13 selectively in the lung, and the phenotype of the resulting transgenic mice was characterized. In contrast to transgene-negative littermates, the lungs of transgene-positive mice contained an inflammatory response around small and large airways and in the surrounding parenchyma. It was mononuclear in nature and contained significant numbers of eosinophils and enlarged and occasionally multinucleated macrophages. Airway epithelial cell hypertrophy, mucus cell metaplasia, the hyperproduction of neutral and acidic mucus, the deposition of Charcot-Leyden-like crystals, and subepithelial airway fibrosis were also prominently noted. Eotaxin protein and mRNA were also present in large quantities in the lungs of the transgene-positive, but not the transgene-negative, mice. IL-4, IL-5, granulocyte-macrophage colony-stimulating factor, and monocyte chemoattractant protein-5 were not similarly detected. Physiological evaluations revealed significant increases in baseline airways resistance and airways hyperresponsiveness (AHR) to methacholine in transgene-positive animals. Thus, the targeted pulmonary expression of IL-13 causes a mononuclear and eosinophilic inflammatory response, mucus cell metaplasia, the deposition of Charcot-Leyden-like crystals, airway fibrosis, eotaxin production, airways obstruction, and nonspecific AHR. IL-13 may play an important role in the pathogenesis of similar responses in asthma or other Th2-polarized tissue responses.
S110 Experience with suspected cancer referrals from the UK lung screen trial
Authors: G Jones, D Komrower, M Murthy, N Hunt, J Holemans, J Field, M Ledson, M Walshaw
Journal: Thorax (2013)

<h3>Introduction</h3> Early diagnosis of lung cancer improves survival and strategies to facilitate this include screening high risk populations. The ongoing UK Lung Screen Trial (UKLS) is investigating this with low-dose CT scans, and positive screens are referred to clinical services for further investigation and treatment. We report the outcome for such cases referred to our large lung cancer unit. <h3>Methods</h3> The UKLS reporting radiologists code scans according to their abnormality: local patients with features suspicious for malignancy (category 4) are referred to our MDT, where following counselling they undergo appropriate investigation. <h3>Results</h3> We have received 37 referrals (mean age68 [range 61–75], median performance status 1, mean FEV1 78% predicted [33–107], 27 male) during the first 14 months of the trial. In 23 cases (62%) subsequent investigation confirmed malignancy (11 adenocarcinoma, 8 squamous cell carcinoma, 3 small cell carcinoma, 1 mesothelioma). In 14 cases where malignancy was not confirmed all had been referred for additional investigations (including 3 PET-CT scans, 5 bronchoscopies and 8 CT scans):1 patient underwent wedge resection of a PET positive lesion (granulomatous process) and 13 remain under follow-up for nodule surveillance. Twenty of those with malignancy (87%) were potentially operable (median stage 1A, mean age 68 [range 61–74], median performance status 1, mean FEV1 80% predicted [33–107], 13 male), including 2 with limited stage small cell carcinoma. Overall, 19 patients were treated by lobectomy with curative intent. The remaining 4 cases all received oncological management. <h3>Discussion</h3> The UKLS is the first large randomised controlled trial to assess a CT-based screening protocol for lung cancer in the United Kingdom. We have shown that the majority of referrals from this programme were confirmed as cases of lung cancer of which nearly all were operable. Such screening programmes will help us improve the prognosis in this previously late-diagnosed and often incurable disease.
Thyroid Dysfunction in the Ailing, Aging, and Aberrant
Authors: Martin L. Nusynowitz
Journal: JAMA (1979)

The unusually high sensitivity and specificity of the serum free thyroxine (FT<sub>4</sub>) index—the product of the total thyroxine (T<sub>4</sub>) and triiodothyronine (T<sub>3</sub>) uptake—makes this readily obtainable laboratory measurement a superb discriminator of thyroid dysfunction, even where the clinical findings of hypothyroidism or thyrotoxicosis are minimal or lacking. In thyrotoxicosis, elevation of the FT<sub>4</sub>index is an almost universal finding, occurring even before symptoms and signs are evident. In the unusual case of T<sub>3</sub>thyrotoxicosis (T<sub>3</sub>toxicosis), the FT<sub>4</sub>index may not reflect the thyrotoxic state, but determination of the T<sub>3</sub>concentration and calculation of the free T<sub>3</sub>FT<sub>3</sub>index enable the diagnosis to be made readily. The T<sub>3</sub>concentration and FT<sub>3</sub>index are not good tests for hypothyroidism, since the results are normal in 30% to 50% of proved cases; but in the absence of pituitary disease, elevation of the thyroid-stimulating hormone (TSH) will presage the disorder,