tbuckley/cabot-search huggingface dataset:
Methotrexate-mediated activation of an AMPK-CREB-dependent pathway: a novel mechanism for vascular protection in chronic systemic inflammation
Authors: C C Thornton, F Al-Rashed, D Calay, G M Birdsey, A Bauer, H Mylroie, B J Morley, A M Randi, D O Haskard, J J Boyle, J C Mason
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Aims</h3> Premature cardiovascular events complicate chronic inflammatory conditions. Low-dose weekly methotrexate (MTX), the most widely used disease-modifying drug for rheumatoid arthritis (RA), reduces disease-associated cardiovascular mortality. MTX increases intracellular accumulation of adenosine monophosphate (AMP) and 5-aminoimidazole-4-carboxamide ribonucleotide which activates AMP-activated protein kinase (AMPK). We hypothesised that MTX specifically protects the vascular endothelium against inflammatory injury via induction of AMPK-regulated protective genes. <h3>Methods/results</h3> In the (NZW×BXSB)F<sub>1</sub> murine model of inflammatory vasculopathy, MTX 1 mg/kg/week significantly reduced intramyocardial vasculopathy and attenuated end-organ damage. Studies of human umbilical vein endothelial cells (HUVEC) and arterial endothelial cells (HAEC) showed that therapeutically relevant concentrations of MTX phosphorylate AMPKα<sup>Thr172</sup>, and induce cytoprotective genes including manganese superoxide dismutase (MnSOD) and haem oxygenase-1 (HO-1). These responses were preserved when HUVECs were pretreated with tumour necrosis factor-α to mimic dysfunctional endothelium. Furthermore, MTX protected against glucose deprivation-induced endothelial apoptosis. Mechanistically, MTX treatment led to cyclic AMP response element-binding protein (CREB)<sup>Ser133</sup> phosphorylation, while AMPK depletion attenuated this response and the induction of MnSOD and HO-1. CREB siRNA inhibited upregulation of both cytoprotective genes by MTX, while chromatin immunoprecipitation demonstrated CREB binding to the MnSOD promoter in MTX-treated EC. Likewise, treatment of (NZW×BXSB)F<sub>1</sub> mice with MTX enhanced AMPKα<sup>Thr172</sup> phosphorylation and MnSOD, and reduced aortic intercellular adhesion molecule-1 expression. <h3>Conclusions</h3> These data suggest that MTX therapeutically conditions vascular endothelium via activation of AMPK-CREB. We propose that this mechanism contributes to the protection against cardiovascular events seen in patients with RA treated with MTX.
Hemolytic anemia following intravenous immunoglobulin administration
Authors: Fang Yin, John A. Nesbitt, Aaron A.R. Tobian, Peter A. Holt, Jamal Mikdashi
Journal: American Journal of Hematology (2008)

RAD51 and XRCC3 polymorphism frequency and risk of myelodysplastic syndromes P value for w 2 or Fisher's exact test for allele frequency where appropriate.
Effect of dobutamine on oxygen consumption and gastric mucosal pH in septic patients.
Authors: G Gutierrez, C Clark, S D Brown, K Price, L Ortiz, C Nelson
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Decreases in gastric mucosal pH (pHi) are associated with splanchnic hypoxia in animals and with increased mortality in patients. In the present study we measured changes in gastric pHi with a tonometer in septic patients after a short-term infusion of dobutamine. These changes were compared with concurrent alterations in systemic O2 consumption (VO2) and arterial lactate. Twenty-one patients admitted sequentially to a medical intensive care unit with sepsis and gastric pHi < 7.32 were prospectively separated into a normal lactate group (< or = 2.2 mM; n = 10) and an elevated lactate group (> 2.2 mM; n = 11). Dobutamine HCl was infused intravenously at 5 micrograms/kg/min for approximately 3 h and then increased to 10 micrograms/kg/min. Measurements were obtained after each increase in the dose of dobutamine. Dobutamine infused at 10 micrograms/kg/min produced increases in O2 transport in both groups (p < 0.05) whereas systemic O2 consumption remained unchanged. These changes were accompanied by decreases in the arterial lactate concentration of the elevated lactate group (p < 0.01). Arterial lactate remained constant in the normal lactate group. Gastric pHi increased in both groups when dobutamine was infused at 5 micrograms/kg/min (p < 0.01), and then again at 10 micrograms/kg/min (p < 0.05). These results imply that regional tissue hypoxia, as characterized by a low gastric pHi, may be present in septic patients with normal arterial lactate concentration. Moreover, a rise in gastric pHi in response to increases in systemic O2 transport may be a better indicator of regional hypoxia in septic patients than related increases in systemic VO2.
Live Attenuated Rubella Virus Vaccine Given in an Orphanage Just Prior to a Rubella Epidemic
Authors: Roger Detels
Journal: JAMA (1969)

Rubella virus vaccine (attenuated strain HPV-77) caused no reactions and showed no communicability when given to 14 Chinese orphans 2 to 6 years of age. Although the proportion of children demonstrating hemagglutination inhibition antibody by 39 days after immunization was low (7 of 12), protection from infection was demonstrated when a rubella epidemic swept the orphanage. Rubella developed in only 1 of 14 children 2 1/2 months after immunization while there were 20 cases of rash among 55 nonimmunized children of the same age. Results of this study suggest that the vaccine does not alter the disease in persons already in the incubation period of natural rubella.
Chekhov's Doctors: A Collection of Chekhov's Medical Tales
Authors: Michael A. LaCombe
Journal: Annals of Internal Medicine (2004)

Medical Writings: Book Notes20 January 2004Chekhov's Doctors: A Collection of Chekhov's Medical TalesMichael A. LaCombe, MDMichael A. LaCombe, MDFrom Maine General Medical Center, Augusta, Maine.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-140-2-200401200-00036 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Chekhov AP. Coulehan J, ed. 232 pages. Kent, OH: Kent State Univ Pr; 2003. $18.00. ISBN 0873387805. Order phone 330-672-8098.Field of medicine: All.Format: Softcover.Audience: All physicians, medical students, doctors' spouses, and patients.Purpose: To remind us of our humanity.Content: The book is a collection of short stories by Chekhov that have a physician as the central character, who may show courage and altruism or arrogance and incompetence. The foreword, by Robert Coles, and the introduction, by the book's editor, Jack Coulehan, provide both a brief, fascinating biography of the Russian physician, who lived 100 years ago, ... Author, Article, and Disclosure InformationAffiliations: From Maine General Medical Center, Augusta, Maine. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 20 January 2004Volume 140, Issue 2Page: 152KeywordsMedical ethics, humanities, and educationSoftware toolsTaste ePublished: 20 January 2004 Issue Published: 20 January 2004 Copyright & PermissionsCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Medical-Legal Aspects of Curbside Consultation
Authors: Barry C. Fox
Journal: JAMA (1996)

<h3>To the Editor.</h3> —The Commentary by Drs Manian and Janssen<sup>1</sup>provided a useful framework for considerations of curbside consultations. The reasons for curbside consultation, advantages, disadvantages, and recommendations are adeptly discussed. However, further elaboration is necessary regarding concerns of recording the consultant's name in the patient medical record as a potential subject for litigation without the patient's having been seen formally. At the time, the authors were "not aware of any successful lawsuits brought against a curbside consultant for having given incorrect advice. The possibility of being named in such litigation, however frivolous and groundless, is still a matter of concern."<sup>1</sup> With health care in the United States trending toward increased use of managed care, the legal issues borne out by informal communication in the case of<i>Hand v Tavera</i><sup>2</sup>deserve further consideration. In this case, a physician-patient relationship (and, hence, legal liability) was found to exist when
THE TALLEST AMERICAN BOYS
Authors: HORACE GRAY
Journal: JAMA (1927)

Brailsford Robertson, 1 who has given so much attention to growth, says: To compare groups of children in regard to physical welfare we should compare their average statures and the variabilities thereof.  In a recent paper 2 offering to those who work with boarding and country day school boys averages compiled from observations on that special class of individual, the statement was made that the average exceed in stature the gifted children reported by Baldwin 3 as being above the best standards for American born children in physical growth status. Owing to the interest and importance attached to height, our statement is worth further evidence.  In table 1, accordingly, are shown statistical constants reduced from our raw data, including the mean stature for each age as published in the paper just cited. For comparison we have translated Baldwin's means into  metric equivalents and have computed the probable errors of those
Cranial Computed Tomography: A Comprehensive Text
Authors: Michael S. Huckman
Journal: JAMA (1987)

This is not only a fine introductory text on cranial computed tomography, but also an excellent reference text, even for those with considerable experience in this field. Several things about this volume are particularly impressive. The quality of the photographs is superb, the labeling is unobstrusive, and the markings are easily readable. The illustrations are large and roughly the size one might encounter in actually reading a scan. Each photograph gives excellent history, and the legends are brief and informative. The book is approximately 85% illustrations, and in most instances the illustrations lie in close proximity to the text that describes them. The lists of references for each chapter are lengthy and extend up to 1983, with a few references appended on the acquired immunodeficiency syndrome that are dated 1984. The book deals briefly with the technical aspects of scanning, including a collection of scanning artifacts and explanations of why
High Prevalence of Hepatitis C Virus Infection in Diabetic Patients
Authors: Rafael Simó, Cristina Hernández, Joan Genescà, Rossend Jardí, Jordi Mesa
Journal: Diabetes Care (1996)

To evaluate the prevalence of hepatitis C virus (HCV) infection in diabetic patients and to investigate the influence of several epidemiological and clinical factors on HCV infection.A total of 176 consecutive diabetic patients were compared with 6,172 blood donors, matched by recognized risk factors to acquire HCV infection. Serologic testing for anti-HCV was done using a second-generation commercial enzyme-linked immunosorbent assay (ELISA) and an immunoblot assay was performed in anti-HCV positive samples to confirm HCV specificity. Diabetic patients were divided in two groups according to their HCV antibody status and analyzed for the following variables: age, sex, type of diabetes, duration of disease, mode of therapy, late diabetic complications, previous blood transfusions, intravenous drug addiction, hospital admissions, major surgical procedures, and liver function tests (LFTs).A higher prevalence of HCV infection was observed in diabetic patients in comparison with blood donors (11.5 vs. 2.5%; P < 0.001; odds ratio 4.39; 95% Cl2.61-7.24). We did not detect any particular epidemiological factor for HCV infection in anti-HCV positive diabetic patients. In these patients, abnormal LFTs were observed in 72.3%, compared with only 24.7% of anti-HCV negative diabetic patients (P < 0.001).A high prevalence of HCV infection was detected in diabetic patients, and most of anti-HCV positive patients presented with abnormal LFTs. Therefore, testing for HCV infection of diabetic patients with an abnormal LFT is mandatory. The lack of any particular epidemiological factor for HCV infection in our diabetic population suggests that HCV may have a direct role in the development of diabetes.
Targeted inhibition of mTORC1 and mTORC2 by active-site mTOR inhibitors has cytotoxic effects in T-cell acute lymphoblastic leukemia
Authors: C Evangelisti, F Ricci, P Tazzari, G Tabellini, M Battistelli, E Falcieri, F Chiarini, R Bortul, F Melchionda, P Pagliaro, A Pession, J A McCubrey, A M Martelli
Journal: Leukemia (2011)
Staphylococcic Endocarditis
Authors: Edward L. Quinn
Journal: JAMA (1966)

The sixfold increased incidence of staphylococcic endocarditis since 1953 was due to cases caused by penicillin-G-resistant strains. On the basis of this change in the staphylococcus and other clinical and laboratory findings, the patients were classified into three groups: acute bacterial endocarditis, due to coagulase-positive staphylococci which were usually resistant to penicillin; subacute bacterial endocarditis, due to coagulase-negative organisms sensitive to penicillin; and, postcardiotomy endocarditis, usually due to coagulase-negative strains that were resistant to penicillin. Treatment with the new semisynthetic penicillins gave much more favorable results than with the older antibiotics. Administration of large amounts of the antibiotic for at least six weeks was essential.
Neuroprotective Effect of Reduced Glutathione on Oxaliplatin-Based Chemotherapy in Advanced Colorectal Cancer: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Stefano Cascinu, Vincenzo Catalano, Luigi Cordella, Roberto Labianca, Paolo Giordani, Anna Maria Baldelli, Giordano D. Beretta, Emilio Ubiali, Giuseppina Catalano
Journal: Journal of Clinical Oncology (2002)

PURPOSE: We performed a randomized, double-blind, placebo-controlled trial to assess the efficacy of glutathione (GSH) in the prevention of oxaliplatin-induced neurotoxicity. PATIENTS AND METHODS: Fifty-two patients treated with a bimonthly oxaliplatin-based regimen were randomized to receive GSH (1,500 mg/m 2 over a 15-minute infusion period before oxaliplatin) or normal saline solution. Clinical neurologic evaluation and electrophysiologic investigations were performed at baseline and after four (oxaliplatin dose, 400 mg/m 2 ), eight (oxaliplatin dose, 800 mg/m 2 ), and 12 (oxaliplatin dose, 1,200 mg/m 2 ) cycles of treatment. RESULTS: At the fourth cycle, seven patients showed clinically evident neuropathy in the GSH arm, whereas 11 patients in the placebo arm did. After the eighth cycle, nine of 21 assessable patients in the GSH arm suffered from neurotoxicity compared with 15 of 19 in the placebo arm. With regard to grade 2 to 4 National Cancer Institute common toxicity criteria, 11 patients experienced neuropathy in the placebo arm compared with only two patients in the GSH arm (P = .003). After 12 cycles, grade 2 to 4 neurotoxicity was observed in three patients in the GSH arm and in eight patients in the placebo arm (P = .004). The neurophysiologic investigations (sural sensory nerve conduction) showed a statistically significant reduction of the values in the placebo arm but not in the GSH arm. The response rate was 26.9% in the GSH arm and 23.1% in the placebo arm, showing no reduction in activity of oxaliplatin. CONCLUSION: This study provides evidence that GSH is a promising drug for the prevention of oxaliplatin-induced neuropathy, and that it does not reduce the clinical activity of oxaliplatin.
DELIRIUM TREMENS TREATED WITH INTRAVENOUSLY ADMINISTERED CORTICOTROPIN (ACTH)
Authors: Karl Fischbach
Journal: JAMA (1952)

The treatment of delirium tremens, as advocated until recently, 1 consisted mainly of sedation and supportive measures. With the availability of corticotropin (ACTH) we now have a potent therapeutic agent that can effect a remission in an amazingly short time. Good results with divided intramuscular doses have been reported, 2 but the large total dose required has raised an objection to its use. Gordon 3 has reported that the action of corticotropin is enhanced as much as 20 times by its intravenous administration. The favorable use of small doses of corticotropin by this route has been shown by Mandel and others. 4 With this in mind, we recently had the opportunity to contrast the two methods of therapy.  REPORT OF CASES  Case 1.—  A 42-year-old white man was admitted to Fordham Hospital on Sept. 17, 1951, in a hyperactive state, with a marked alcoholic odor to his breath. He gave
Withholding versus withdrawal of life support: is there an ethical difference?
Authors: S. Glick
Journal: BMJ (2011)

<h3>Objectives</h3> To understand the impact of emergency department (ED) reconfiguration on the number of patients waiting for hospital beds on trolleys in the remaining EDs in four geographical regions in Ireland using time-series analysis. <h3>Setting</h3> EDs in four Irish regions; the West, North-East, South and Mid-West from 2005 to 2015. <h3>Participants</h3> All patients counted as waiting on trolleys in an ED for a hospital bed in the study hospitals from 2005 to 2015. <h3>Intervention</h3> The system intervention was the reconfiguration of ED services, as determined by the Department of Health and Health Service Executive. The timing of these interventions varied depending on the hospital and region in question. <h3>Results</h3> Three of the four regions studied experienced a significant change in ED trolley numbers in the 12-month post-ED reconfiguration. The trend ratio before and after the intervention for these regions was as follows: North-East incidence rate ratio (IRR) 2.85 (95% CI 2.04 to 3.99, p&lt;0.001), South IRR 0.68 (95% CI 0.51 to 0.89, p=0.006) and the Mid-West IRR 0.03 (95% 1.03 to 2.03, p=0.03). Two of these regions, the South and the Mid-West, displayed a convergence between the observed and expected trolley numbers in the 12-month post-reconfiguration. The North-East showed a much steeper increase, one that extended beyond the 12-month period post-ED reconfiguration. <h3>Conclusions</h3> Findings suggest that the impacts of ED reconfiguration on regional level ED trolley trends were either non-significant or caused a short-term shock which converged on the pre-reconfiguration trend over the following 12 months. However, the North-East is identified as an exception due to increased pressures in one regional hospital, which caused a change in trend beyond the 12-month post reconfiguration.
Monotherapy with Tadalafil or Tamsulosin Similarly Improved Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia in an International, Randomised, Parallel, Placebo-Controlled Clinical Trial
Authors: Matthias Oelke, François Giuliano, Vincenzo Mirone, Lei Xu, David Cox, Lars Viktrup
Journal: European Urology (2012)
The Complications of Diabetes Mellitus
Authors: Albert I. Winegrad, Douglas A. Greene
Journal: New England Journal of Medicine (1978)

The common perception of the complications of diabetes mellitus has been distorted by the heated controversy over two mutually exclusive unifying theories of their pathogenesis. The complications are a very heterogeneous group of clinical syndromes that are associated with both ketosis-prone juvenile diabetes and maturity-onset diabetes; they include myocardial infarction, uremia, visual impairment resulting from proliferative retinopathy and polyneuropathy. (In populations in which myocardial infarction is uncommon its association with diabetes is not demonstrable.) At present the development of any of these syndromes in any given diabetic patient is quite unpredictable, and there are numerous series of 20-year to 40-year . . .
Psychological screening before interferon therapy
Authors: Astrid Scalori, Paolo Apale, Luigi Roffi
Journal: Hepatology (2001)

3][4] Moreover, it is not always possible to single out patients who on clinical grounds are likely to develop psychiatric side effects.We therefore believe that it is important to have a method, easy to carry out, reproducible, self-administered, and inexpensive, to screen all patients.The authors suggest using the Beck Depression Inventory, the Zung Self-Rating Depression Scale, or the Center for Epidemiologic Studies Depressed Mood Scale.Since 1995, we have used the computerized version of the MMPI (Minnesota Multiphasic Personality Inventory) to screen all patients before interferon therapy, with psychiatric evaluation of those patients whose score is pathological.The computerized version of the MMPI is a selfevaluating test, composed of 566 items covering an extensive range of behaviors and attitudes.Patients must answer "true," "false," or "don't know."To assess the compliance, some items are repeated in a slightly different way throughout the test.The computer then determines a psychologic profile of the patient, dividing it into 13 scales representing different personality aspects, each expressed by a numerical score.For this scale, a score of 60 of 100 is considered the cut-off of normality.According to our experience, 5 all patients who need psychopharmacologic therapy during interferon treatment are among those with a pathologic MMPI score before the beginning of therapy and who the psychiatrist consequently monitored.We are therefore able to identify these neuropsychiatric side effects at an early stage and, so far, none of our patients has had to stop interferon therapy for psychiatric disorders, even if some of them required antidepressant therapy.
Coronary Artery Wounds Treated With Saphenous Vein Bypass Grafts
Authors: Alfred J. Tector
Journal: JAMA (1973)

Two patients with penetrating wounds to the left anterior descending coronary artery were treated with emergency aortocoronary saphenous vein bypass grafts. On follow-up angiography, the first patient's bypass graft to the distal anterior descending coronary artery was not patent. The second patient's graft to the proximal anterior descending vessel was patent with bidirectional flow. Both patients had other associated intracardiac injuries, the first having an aortic-right ventricular fistula requiring reoperation. It is desirable, and often necessary, to reestablish coronary artery continuity of flow following injury. We propose a protocol to detect other associated intracardiac defects prior to emergency cardiopulmonary bypass so that these lesions might be repaired, obviating excess postoperative morbidity, mortality, and subsequent reoperation.
The Normal and Abnormal Unipolar Electrocardiogram in Infants and Children: An Analysis of the Normal QRS Complex Morphology and Ventricular Activation Times
Authors: Irving L. Rosen
Journal: JAMA (1964)

This monograph has two parts. In the first, Wasserburger presents a survey of electrocardiograms of normal infants and children based on 259,915 individual measurements of the QRS complexes of 1150 persons. The text is profusely illustrated with electrocardiograms demonstrating the variety of normal records seen in various age groups. In addition, there is a large number of charts of mean and maximum activation time and minimum and maximum amplitude of the Q, R, and S waves in leads AVR and precordial leads V<sub>3</sub>R through V<sub>6</sub>. In the second section the author uses the normal data to suggest criteria for distinguishing abnormal from normal electrocardiograms. A large number of electrocardiograms typical of each abnormality are shown, as well as tracings which present problems in interpretation. The author points out that measurements of a single deflection in a single lead often result in interpretation difficulties, and emphasizes the necessity