tbuckley/cabot-search huggingface dataset:
Tofacitinib versus Methotrexate in Rheumatoid Arthritis
Authors: Eun Bong Lee, Roy Fleischmann, Stephen Hall, Bethanie Wilkinson, John D. Bradley, David Gruben, Tamas Koncz, Sriram Krishnaswami, Gene V. Wallenstein, Chuanbo Zang, Samuel H. Zwillich, Ronald F. van Vollenhoven
Journal: New England Journal of Medicine (2014)

Methotrexate is the most frequently used first-line antirheumatic drug. We report the findings of a phase 3 study of monotherapy with tofacitinib, an oral Janus kinase inhibitor, as compared with methotrexate monotherapy in patients with rheumatoid arthritis who had not previously received methotrexate or therapeutic doses of methotrexate.We randomly assigned 958 patients to receive 5 mg or 10 mg of tofacitinib twice daily or methotrexate at a dose that was incrementally increased to 20 mg per week over 8 weeks; 956 patients received a study drug. The coprimary end points at month 6 were the mean change from baseline in the van der Heijde modified total Sharp score (which ranges from 0 to 448, with higher scores indicating greater structural joint damage) and the proportion of patients with an American College of Rheumatology (ACR) 70 response (≥70% reduction in the number of both tender and swollen joints and ≥70% improvement in three of five other criteria: the patient's assessment of pain, level of disability, C-reactive protein level or erythrocyte sedimentation rate, global assessment of disease by the patient, and global assessment of disease by the physician).Mean changes in the modified total Sharp score from baseline to month 6 were significantly smaller in the tofacitinib groups than in the methotrexate group, but changes were modest in all three groups (0.2 points in the 5-mg tofacitinib group and <0.1 point in the 10-mg tofacitinib group, as compared with 0.8 points in the methotrexate group [P<0.001 for both comparisons]). Among the patients receiving tofacitinib, 25.5% in the 5-mg group and 37.7% in the 10-mg group had an ACR 70 response at month 6, as compared with 12.0% of patients in the methotrexate group (P<0.001 for both comparisons). Herpes zoster developed in 31 of 770 patients who received tofacitinib (4.0%) and in 2 of 186 patients who received methotrexate (1.1%). Confirmed cases of cancer (including three cases of lymphoma) developed in 5 patients who received tofacitinib and in 1 patient who received methotrexate. Tofacitinib was associated with increases in creatinine levels and in low-density and high-density lipoprotein cholesterol levels.In patients who had not previously received methotrexate or therapeutic doses of methotrexate, tofacitinib monotherapy was superior to methotrexate in reducing signs and symptoms of rheumatoid arthritis and inhibiting the progression of structural joint damage. The benefits of tofacitinib need to be considered in the context of the risks of adverse events. (Funded by Pfizer; ORAL Start ClinicalTrials.gov number, NCT01039688.).
Determinants of direct costs in Dutch rheumatoid arthritis patients
Authors: S M M Verstappen
Journal: Annals of the Rheumatic Diseases (2004)

To estimate annual direct costs in four distinct disease duration groups (0 to < or =2, 2 to < or =6, 6 to < or =10, and >10 years) of patients with rheumatoid arthritis (RA), to determine predictors of high costs and to describe characteristics of patients with high and with low costs.A questionnaire assessing RA related care and resource utilisation rates and costs was completed by 615 RA patients. Predictive variables for incurred costs, as observed during the first year after disease onset, were determined in a subgroup of patients (n = 347).Mean (median) annual direct costs for the four groups with increasing disease duration were respectively: 5235 (2923) Euros, 3930 (1968) Euros, 4664 (1952)Euros, and 8243 (3778) Euros, (p < 0.05). During the first 2 years of the disease total direct costs comprised mainly of consultations with healthcare workers (28%). After 10 years, devices and adaptations were the main contributors (40%) to total costs. Positive rheumatoid factor results at the time of diagnosis and deterioration of functional disability in the first year of disease were predictors of high costs later on in the course of the disease.Annual direct costs among patients with a disease duration of less than 2 years tend to be lower among patients with a disease duration of between 2 and 10 years than among patients with a disease duration of more than 10 years. In addition, the proportional distribution of different cost categories to total costs increases with with increasing disease duration.
Use of propranolol to reduce the rebleeding rate during injection sclerotherapy prior to variceal obliteration
Authors: David Westaby, Walter Melia, John Hegarty, Alexander E. S. Gimson, Anthony J. Stellon, Roger Williams
Journal: Hepatology (1986)

In a prospective, randomized controlled trial, 53 patients with variceal hemorrhage from portal hypertension, including 44 with cirrhosis, were allocated, after initial control of the bleeding, to treatment by sclerotherapy alone, or by this together with oral propranolol in a dose sufficient to reduce resting pulse rate by 25% during the period up to the time when varices were obliterated. Eight of the 27 patients undergoing sclerotherapy alone rebled during this period as compared to 7 of the 26 patients in the additional propranolol group (p &gt; 0.80), two patients from each group dying from uncontrollable variceal hemorrhage. Propranolol precipitated encephalopathy in one patient and complicated resuscitation following bleeding in a second, and as there was no evidence in this study that use of the drug reduced the frequency or severity of the variceal bleeding, its administration cannot be recommended during the period prior to obliteration of varices by sclerotherapy.
THE RELATION OF ASCITES TO DISEASES OF THE KIDNEYS, AND PARACENTESIS ABDOMINALIS AS A REMEDY.
Authors: W. F. McNUTT
Journal: JAMA (1896)

The accumulation of fluid in the abdominal cavity with or without dropsy was recognized by the earliest medical writers. Hippocrates was, from his many references to the subject, evidently familiar with dropsy and the accumulation of fluid into the serous sacs. Erasistratus's master, Chrysippus, must have been a contemporary of Hippocrates. According to Galen this famous physician, Erasistratus wrote a work on dropsy and taught that all varieties depended upon obstruction of the liver. Galen himself taught that diseases of other organs might also be responsible for dropsical effusions, and that they not infrequently had their origin in the morbid state of the blood. Asclepiades, who seems to have been a voluminous writer, according to what can be gathered of his views from Celsus and Galen, divided all dropsies into acute and chronic, not designating the particular viscera whose disease caused the dropsy. Probably Avicenna in his "Canon Medicinæ," is
Cabozantinib—Getting Under the Skin of Cutaneous Toxicity
Authors: Anuradha Jayaram, Zafeiris Zafeiriou, Johann S. de Bono
Journal: JAMA Oncology (2015)

Tyrosine kinases (TKs) are a family of proteins that play a key role in themost fundamental cellular processes including the cell cycle, proliferation, differentiation, cell death and survival and are crucial inoncogenesis. Tyrosinekinase inhibitors (TKIs) actby inhibiting the catalytic subunit of TKs. Clinical trials in several cancer types have established the role of these drugs in cancer therapeutics. Although TKIs are “targeted therapeutics,”many inhibit a range of kinase receptorswithvariedpotencyand selectivity. Targeted receptors include vascular endothelial growth factor receptor (VEGFR), platelet-derivedgrowthfactor receptors (PDGFRs), fibroblastgrowth factor receptor (FGFR), epidermal growth factor receptor (EGFR), c-KIT, FLT-3, c-MET, MEK, BRAF, and insulin-like growth factor receptor (IGFR).1 Tyrosinekinase inhibitors causeaspectrumofdermatologic adverse events that has been described as a “class effect.” These adverse effects include rash, hand-foot-skin reaction (HFSR), alopecia, depigmentation, pruritus, xerosis, acneiform rashes, scrotal lesions, andmucositis. The distinctmultikinase inhibition profile of TKIs produces a different constellation of these cutaneous adverse events (CEs).2 Despite this spectrum,many phase 3 trials involving TKIs reportedCEscollectivelyas “skin toxicity.”There isclearlyaneed forgreaterdetail anddescriptionsof therangeofCEsrelatedtothese agents. In support of this, one meta-analysis2 focusing on CEs reportedonlyonHFSR, andpruritus. Toelucidate the full potential diversity of CEs, 2 small prospective trials3,4 with sorafenib and sunitinib, respectively, were designed. Zuo et al report the incidence of CEs in patients treated with cabozantinib administered at a dose of 60 mg/d continuously in metastatic urothelial carcinomabymeans of dedicated history and physical examination.Adermatologist reviewedpatientsonlywhen signs and symptoms of skin toxicity were present. Cabozantinib is a potent, small-molecule, oral multi-TKI targeting VEGFR2, c-MET, RET, c-KIT, AXL, and FLT3. In 2012, the US Food andDrug Administrationapprovedcabozantinib for the treatmentofmetastaticmedJAMADERMATOLOGY
Cross-linking of Fas By Antibodies to a Peculiar Domain of gp120 V3 Loop Can Enhance T Cell Apoptosis in HIV-1–infected Patients
Authors: Franco Silvestris, Shigekazu Nagata, Paola Cafforio, Nicola Silvestris, Franco Dammacco
Journal: The Journal of Experimental Medicine (1996)

Previous studies have demonstrated that T cell–reactive antibodies in HIV-1 infection contribute to lymphocyte depletion by cytotoxicity that involves differential membrane targets, such as the 43.5-kD receptor on CEM cells. Here, we show that these antibodies bind Fas as result of a molecular mimicry of the gp120. Both flow cytometry and immunoblotting using the human Fas-transfected mouse WC8 lymphoma revealed positive binding of immunoglobulin G from several patients to a 43.8-kD membrane receptor that also reacts with the CH11 anti-Fas monoclonal antibody. Specificity to Fas was further confirmed to chimeric recombinant human Fas-Fc by ELISA, whereas overlapping peptide mapping of a Fas domain (VEINCTR–N) shared by gp120 V3 loop demonstrated a predominant affinity to the full-length 10-mer peptide. Four anti-Fas affinity preparations greatly increased the subdiploid DNA peak of CEM cells similar to agonist ligands of Fas. In addition, anti-Fas immunoglobulin G strongly inhibited the [3H]thymidine uptake of CEM cells in proliferative assays, inducing a suppression as high as provoked by both CH11 mAb and recombinant human Fas ligand. Since anti-Fas were reactive to gp120, it is conceivable that antibodies binding that domain within the V3 region are effective cross-linkers of Fas and increase apoptosis in peripheral T cells. These results suggest that autologous stimulation of the Fas pathway, rather than of lymphocytotoxic antibodies, may aggravate lymphopenia in a number of HIV-1+ subjects.
Responsibilities beyond the patient
Authors: J. Wise, R. Coombes
Journal: BMJ (2010)

Do family and hospital doctors have a duty to the health of their local community, or just to the individual patient in front of them? <b>Jacqui Wise</b> and <b>Rebecca Coombes</b> report on a discussion hosted last week by the<i> BMJ</i> and the King’s Fund
French Maritime Pine Bark Extract Pycnogenol Dose-Dependently Lowers Glucose in Type 2 Diabetic Patients
Authors: Ximing Liu, Ha-Jun Zhou, Peter Rohdewald
Journal: Diabetes Care (2004)

Pycnogenol, a standardized extract from the bark of the French maritime pine, consists of phenolic compounds including catechin, taxifolin, procyanidins, and phenolic acids (1).

We investigated whether Pycnogenol has a glucose-lowering effect because of personal verbal communication from patients reporting no need for insulin following supplementation with Pycnogenol.

The study was designed as an open, controlled, dose-finding study and was approved by the ethical committee of Guangnamen Hospital. Patients gave written informed consent. We recruited 18 men and 12 women among outpatients of the Guangnamen Hospital and Municipal Dental Hospital. Patients were 28–64 years of age and had a BMI 22–34 kg/m2. Patients with type 2 diabetes were included with fasting plasma glucose between 7 and …
Effect of chronic potassium depletion on digitalis-induced inotropy and arrhythmias
Authors: R. J HALL, A. GELBART, M. BILLINGHAM, G. SNIDOW, R. H GOLDMAN
Journal: Cardiovascular Research (1981)

The arrhythmogenic and inotropic effects of digoxin were studied in normokalemic controls, chronically hypokalaemic, and potassium-repleted dogs instrumented to maintain heart rate, mean aortic pressure, mean left atrial pressure and autonomic tone constant. The duration of digoxin infusion needed to produce ventricular tachycardia (VT) was 56.7 ± 3.6 min in depleted dogs, 69.0 ± 2.7 min in controls (P < 0.005 compared with depleted dogs), and 60.5 ± 3.0 min in repleted dogs. Baseline left ventricular dP/dt (LV dP/dt) was similar in all groups. After digoxin, LV dP/dt increased more in controls and repleted dogs than in chronically hypokalaemic dogs; eg, after 45 min of digoxin infusion LV dP/dt increased 12.7 ± 4.4% in hypokalaemic dogs, 43.8 ± 3.3% in controls (P < 0.025) and 39.3 ± 8.5% in repleted dogs (P < 0.025). The inotropic response to iso-prenaline was also attenuated in the chronically hypokalaemic dogs. Plasma digoxin was similar in all groups. LV digoxin was also similar in control and depleted dogs. Although inhibition of Na +, K+−ATPase and the initial velocity of 3[H]-ouabain specific binding was less in depleted dogs at VT than in controls (P < 0.05), the magnitude of this difference was not sufficient to explain the attenuated inotropic response. No histological abnormalities were seen on light or electron microscopy in any of the groups. Therefore chronic hypokalemia has two deleterous effects. It increases sensitivity to the arrhythmogenic effects of digoxin and impairs the inotropic response to digoxin, and isoprenaline.
Oomycete pathogens encode RNA silencing suppressors
Authors: Yongli Qiao, Lin Liu, Qin Xiong, Cristina Flores, James Wong, Jinxia Shi, Xianbing Wang, Xigang Liu, Qijun Xiang, Shushu Jiang, Fuchun Zhang, Yuanchao Wang, Howard S Judelson, Xuemei Chen, Wenbo Ma
Journal: Nature Genetics (2013)
Medical Practice in Colorado.
Authors: J. N. Hall
Journal: JAMA (1893)

Denver, Col., July 24, 1893. <h3>To the Editor:</h3> —I should be glad to have you publish the following regarding our present Colorado law: Hereafter the Colorado State Board of Medical Examiners will recognize only diplomas from three year schools as entitling their holders to license. The courses of lectures must have been of at least twenty weeks each, and given in three separate years, and a preliminary examination must have been required. Instruction must have been given in anatomy, chemistry, physiology, pathology, materia medica and therapeutics, obstetrics and gynecology, surgery, medical jurisprudence, theory, and practice of medicine and hygiene. In default of such a diploma the candidate for license must pass an examination in anatomy, chemistry, physiology, pathology, surgery, obstetrics and gynecology, and theory and practice of medicine. Yours very truly,
The nature of parasitism; the relationship of some metazoan parasites to their hosts.
Authors: J. Walter Beck
Journal: JAMA (1963)

As stated by the author, the chief purpose of this book is to arouse interest in the many problems which must be solved before we can begin to understand the basic features of the host-parasite relationship and the nature of parasitism. The book is divided into four parts. Part one is entitled, "Speculations on the Host-Parasite Relationship." Recognizing the present day concepts of pathology and immunology, and the role they have played in understanding parasitism, the author proceeds to place emphasis upon an understanding of "infectiousness," which he defines as the capacity of the organism to infect the host and live as a parasite. This must come about, he believes, through a better understanding of the needs, if the parasite and its defense mechanisms are available. Emphasis is also placed upon the variations that must occur, as both parasite and host age and change. Part two deals with "The Problem
DO NOT EAT THE MAHIMAHI!
Authors: HARRY L. ARNOLD
Journal: Annals of Internal Medicine (1966)

Letters and Comments1 May 1966DO NOT EAT THE MAHIMAHI!HARRY L. ARNOLD JR., M.D.HARRY L. ARNOLD JR., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-64-5-1150 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor:The admirable tabulation of sources of acute food poisoning furnished by Drs. Rose and Rieders (ANNALS, February, 1966), should have included the pompano or mahimahi under the fishes capable of poisoning people with histamine, the so-called scombroid fish poisoning.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: HARRY L. ARNOLDJR., M.D.Affiliations: Straub Clinic Honolulu, Hawaii PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1966Volume 64, Issue 5Page: 1150-1150KeywordsFood poisoningHistamine ePublished: 1 December 2008 Issue Published: 1 May 1966 PDF downloadLoading ...
The new health authorites: moving forward, moving back?
Authors: J. Boyce, T. Lamont
Journal: BMJ (1998)

There is much to celebrate in the new white paper. The emphasis on quality and partnership both within and outside the health service is welcome. Longer term agreements will replace the stop-start demands of the annual contracting round, and the need for strategic coherence is recognised: indeed, this government is not afraid of the word “planning.” But perhaps the most radical aspect of the white paper is its commitment to keep primary care “in the driving seat in shaping local health services.” This will attract the most attention-not least because the “problem” of general practitioner fundholding was one of the main triggers for a review of the NHS. But it begs many questions:
THE SOUL OF THE CLINIC
Authors: FRANCIS W. PEABODY
Journal: JAMA (1928)

[Note.  —During the latter weeks and, indeed, days of his life, Dr. Francis W. Peabody set down on paper in a letter to a friend his conception of the relationship and responsibilities of the Medical Chief to his Clinic. Though he felt that it was not entirely complete in certain details, he finished the first draft and wrote the last sentence the day before his death. The letter has been read by many of Dr. Peabody's friends, who have been deeply affected by his broad and clear vision of this complex problem and have been profoundly impressed by his beautiful exposition of what must be called the soul of the clinic. His friends feel that the letter is too valuable to remain as a private possession and should be made available to the medical profession. The document is being published, therefore, as it was written, a letter to an intimate
Australia Antigen and Acute Viral Hepatitis
Authors: W. THOMAS LONDON
Journal: Annals of Internal Medicine (1969)

Australia antigen (Au(1)) was found in the sera of 20% of 125 patients with acute viral hepatitis. It was not present in the sera of 138 patients with other diseases affecting the liver (Laennec's cirrhosis, infectious mononucleosis, hepatoma, and so on). These data indicate that the antigen is selectively associated with viral hepatitis and is not a nonspecific manifestation of liver damage. Previously we have reported the association of Au(1) with leukemia, lepromatous leprosy, and Down's syndrome, and in 1 to 20% of some tropical populations. In these groups the antigen occurs more frequently in young males; once present, it tends to persist for long periods (years). In the acute hepatitis patients there was no significant difference in distribution between the sexes; the antigen was not found in any patient less than 19 years old, and with two exceptions it was present in the sera for short intervals (days and weeks). Host factors related to immunologic competence may be responsible for these differences.
823. Dissecting Overlapping Functions of Transcriptional Enhancer and Polyadenylation in the Lentiviral U3
Authors: Qing Yang, Wayne Chou, Lung-Ji Chang
Journal: Molecular Therapy (2005)

The transcriptional readthrough activity of the 3' long terminal repeat (LTR) of lentiviral vectors is critical to the safety profile of this vector system in future clinical applications. We have previously reported that the 3' polyadenylation (polyA) readthrough activity of the murine leukemia virus long terminal repeat (LTR) is much higher than that of the human immunodeficiency virus type 1 (HIV-1) LTR; however, deletion of the U3 or HIV-1 LTR to generate a self-inactivating (SIN) lentiviral vector results in a high transcriptional readthrough activity (J. Virol. 76: 7209-7219, 2002). This strongly suggests that other transcriptional termination signals (TS) besides the polyA signal (AAUAAA) in the R region are present in the U3 region. By serially inserting back different lengths of the U3 sequence, we demonstrated that the readthrough activity of the HIV-1 3' LTR was inversely correlated with the length of the U3, suggesting that the termination signals span across the entire U3 region. However, the transcriptional control region, co ntaining 124 nt of the U3 sequence, preserves |[sim]| 70-80% of the wild type TS function. Furthermore, deletion of the Sp1 and NF-kB binding sites abolished most of the TS function. Knocking down NF-kB expression by siRNA down-regulated the TS function. The introduction of foreign TS elements including human T cell leukemia virus type I (HTLV-I) polyA signal, human growth hormone gene intron, a tRNA tertiary structure, or a tetracycline responsive element (TRE) with a TRE-binding factor did not restore the TS function. Therefore, the lentiviral U3 contains an overlapping transcriptional enhancer and termination function which is difficult to be separated. Further improving the transcriptional termination but not the enhancer/promoter function of the 3' LTR will be critical to safety improvement of this vector system.
The Economics of Health Equity
Authors: Karunesh Tuli
Journal: JAMA (2008)

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