tbuckley/cabot-search huggingface dataset:
EFFECT OF PHENYLBUTAZONE (3,5 DIOXO-1,2-DIPHENYL-4-n-BUTYLPYRAZOLIDINE) ON RENAL CLEARANCE OF URATE AND OTHER DISCRETE RENAL FUNCTIONS IN GOUTY SUBJECTS 1
Authors: Tsai Fan Yü, Jonas H. Sirota, Alexander B. Gutman
Journal: Journal of Clinical Investigation (1953)

Phenylbutazone is a potent analgesic agent cur- rently employed in the treatment of various arth- ritic disorders (1) including acute gouty arthritis (1,2).It is generally agreed that administration of the drug to gouty subjects effects a sharp lower- ing of the serum urate level (1, 2).The mecha- nism by which this is accomplished is still obscure.Evidence that phenylbutazone is a uricosuric drug which depresses tubular reabsorption of urate has been presented elsewhere (2, 3).Further data are recorded here.These deal in greater detail with a) the acute and protracted effects of in- travenous and oral phenylbutazone administration upon the renal clearance of urate and upon serum urate concentration; b) the effects of intravenously administered phenylbutazone upon the renal clear- ances of inulin, endogenous creatinine and PAH, the urinary excretion of sodium, potassium, chlo- ride and inorganic phosphate, and upon TmpAH; and c) the effects of simultaneous administration of phenylbutazone and probenecid (Benemid) upon urinary urate excretion. METHODSThe acute effects of intravenously administered phenylbutazone on the simultaneous renal clearances of urate, inulin, endogenous creatinine and p-aminohippurate, using techniques previously described (4), were studied in ten gouty subjects in the intercritical phase of the disease.All abstained from meat and purine-rich food for three days prior to the study, which was started in the morning during the post-absorptive state.Liberal quantities of water were administered orally to maintain urine flows higher than 3 cc.per min.throughout the course of the acute clearance determinations.Following three 10 to 15 minute control urine collection periods, 1 or 2 Gm. of
Intra-articular hyaluronan treatment for osteoarthritis
Authors: E GEORGE
Journal: Annals of the Rheumatic Diseases (1998)

In 1934 Meyer and Palmer isolated a polysaccharide from bovine vitreous humour and named it hyaluronic acid.1 The name derives from the Greek word “hyalos” (that is, glass like). In 1986 Balazs et al 2 proposed the name hyaluronan as an alternative to hyaluronic acid. “Hyaluronic acid”, “sodium hyaluronate”, and “HA” are terms used in the literature and frequently interchangeably with “hyaluronan”, but the latter has become the preferred name.

In osteoarthritis (OA) the synovial fluid (SF) is more abundant and less viscous,3 the concentration of hyaluronan is decreased as is its chain length and therefore molecular weight.4 These changes severely decrease the physiological and protective functions of the SF5; shock absorption, traumatic energy dissipation and storage, lubrication and protective coating of the articular cartilage surface and of the inner lining of the synovial membrane, as well as control of the “traffic” between the synovial vessels and cartilage by an exclusion effect on migrating cells and large molecules.

The concept of viscosupplementation, first proposed by Balazs,6 is based on the hypothesis that intra-articular injection of hyaluronan into OA joints could restore the rheological properties of the SF, promote the endogenous synthesis of a higher molecular weight and possibly more functional hyaluronan, thereby improving mobility, articular function, and decreasing pain. This mechanism is suggested by the finding of hyaluronan with a molecular weight larger than that of the injected solution and within the range of normal SF hyaluronan in humans7 and animals.8 

Hyaluronan used for medical uses has to be extracted from umbilical cord, rooster comb or bacterial cultures then purified and separated from any pyrogenic, inflammatory, immunogenic or chemotactic fractions. The first therapeutic injections of hyaluronan in animal joints were performed on track horses for traumatic arthritis, the treatment proved effective and …
Probenecid, nephrotic syndrome, and renal failure.
Authors: J T Scott, P K O'Brien
Journal: Annals of the Rheumatic Diseases (1968)

This report describes two patients in whom oedema and proteinuria occurred during treatment with the uricosuric agent probenecid.In one of them these features were accompanied by hypoalbuminaemia and hypercholesterolaemia, recovery following with- drawal of the drug.In the other there was renal failure from which the patient died.Case 1, an electrical engineer, had had recurrent gouty arthritis since the age of 14 years.A paternal uncle had also suffered with gout.From the age of 50 onwards numerous tophi appeared on the hands, feet, elbows, and ears.At one time or another he had been given various drugs, including corticosteroid hormones, phenylbutazone, salicylates, and probenecid.These drugs had produced no harmful effects, but he had not taken any of them for more than a few days or weeks.,There was no history of exposure to any other chemicals.He was first admitted to Hammersmith Hospital in November, 1962, when he was 60 years of age.Examination.-He was rather obese, weighing 94 kg.There were changes of chronic gouty arthritis with multiple tophi, some of them discharging.The heart was slightly enlarged but examination showed no other abnormalities.There was no oedema.The blood pressure was 130/80.The serum uric acid lay between 9-2 and 12-5 mg./100 ml. and impairment of renal function was indicated by a blood urea of between 82 and 116 mg./100 ml., phenosulphthalein excretion of 24 per cent. in one hour (normal 40-60 per cent.), and maximum urine concentration of 1016.The urine contained no protein, or a trace only, there were no abnormal deposits, and culture was sterile.Erythrocyte sedimentation rate 7 mm./hr., Hb 16-6 g. per cent.; white cells 7,000; serum albumin 3.9 g./100 ml.Chest x ray showed a slightly enlarged left ventricle.Intravenous pyelogram was normal.Treatment.-He was given probenecid 1-0 g., colchicine 1X0 mg., and sodium bicarbonate 6-0 g. daily.
Respiratory Tract Disease from Thermosetting Resins
Authors: GUlLLERMO A. doPICO
Journal: Annals of Internal Medicine (1975)

An outbreak of upper and lower respiratory tract inflammatory disease and conjunctivitis among synthetic rubber tire workers occurred. The outbreak began after the introduction of a new thermosetting resin, containing resorcinol and a trimere of methylene aminoacetronitrile, into the rubber tire carcass stock formulation. Two hundred ten workers were affected. Characteristically, symptoms improved during periods of sick leave or vacation, recurring upon the workers' return to the plant. Chest radiograms disclosed pneumonic infiltrates in about one fourth of the cases. Pulmonary function studies detected abnormal airways dynamics as well as abnormal diffusing capacity in more than one third of the workers tested. Lung biopsy showed evidence of focal interstitial fibrosis and peribronchiolar and perivascular chronic inflammatory reaction. The illness was ascribed to volatile products released during the manufacture of synthetic rubber tires. The exact chemical nature of these products is unknown.
A Failure to Adapt
Authors: Gordon F. Tomaselli
Journal: Circulation (2007)

he development of serious, potentially lethal cardiac arrhythmias is determined by a complex integration of factors, including, but not limited to, common and rare genetic variants that determine the responses to gene-gene and gene-environment interactions.Even the rare "simple" channelopathies that cause long-QT syndrome (LQTS) and a host of other potentially lethal arrhythmias exhibit a complex set of phenotypes of varying severity and overlapping features.Ankyrins are a family of adapter proteins, first identified in the erythrocyte membrane, that mediate the localization of a diverse group of cellular proteins.Three genes in the mammalian genome encode ankyrins that share a similar global architecture but exhibit distinct expression patterns and functions: ANK1 encodes ankyrin-R, which exhibits a more restricted expression; ANK2 (chromosome 4q25-27) encodes the more broadly distributed ankyrin-B; and ANK3 encodes the ankyrin-G for general or global.Ankyrins bind a number of ion motive proteins essential to normal cardiac electrophysiology, including the Na ϩ -Ca 2ϩ exchanger; inositol 1,4,5-triphosphate receptor; Na ϩ -K ϩ ATPase; and the voltage-dependent sodium channel (Na V 1.5)By the very nature of the role of ankyrins in excitation and contraction in cardiac myocytes, it is understandable that variants in ankyrin-B originally described in a family with congenital LQTS 1 would exhibit protean electrical phenotypes.Indeed, in the original LQTS cohort, sinus node dysfunction and atrial fibrillation have been described, 1,2 and other electrophysiological abnormalities such as conduction block, idiopathic ventricular fibrillation, and catecholaminergic ventricular tachycardia have been included under the rubric of ankyrin-B syndrome. 3A mutation in the ankyrin binding domain of Na V 1.5 has been associated with defective ankyrin-G binding and Brugada syndrome.
Hedgehog signaling regulates epithelial-mesenchymal transition during biliary fibrosis in rodents and humans
Authors: Alessia Omenetti, Alessandro Porrello, Youngmi Jung, Liu Yang, Yury Popov, Steve S. Choi, Rafal P. Witek, Gianfranco Alpini, Juliet Venter, Hendrika M. Vandongen, Wing-Kin Syn, Gianluca Svegliati Baroni, Antonio Benedetti, Detlef Schuppan, Anna Mae Diehl
Journal: Journal of Clinical Investigation (2008)

Epithelial-mesenchymal transitions (EMTs) play an important role in tissue construction during embryogenesis, and evidence suggests that this process may also help to remodel some adult tissues after injury. Activation of the hedgehog (Hh) signaling pathway regulates EMT during development. This pathway is also induced by chronic biliary injury, a condition in which EMT has been suggested to have a role. We evaluated the hypothesis that Hh signaling promotes EMT in adult bile ductular cells (cholangiocytes). In liver sections from patients with chronic biliary injury and in primary cholangiocytes isolated from rats that had undergone bile duct ligation (BDL), an experimental model of biliary fibrosis, EMT was localized to cholangiocytes with Hh pathway activity. Relief of ductal obstruction in BDL rats reduced Hh pathway activity, EMT, and biliary fibrosis. In mouse cholangiocytes, coculture with myofibroblastic hepatic stellate cells, a source of soluble Hh ligands, promoted EMT and cell migration. Addition of Hh-neutralizing antibodies to cocultures blocked these effects. Finally, we found that EMT responses to BDL were enhanced in patched-deficient mice, which display excessive activation of the Hh pathway. Together, these data suggest that activation of Hh signaling promotes EMT and contributes to the evolution of biliary fibrosis during chronic cholestasis.
Hormone trial for disease prevention stopped early
Authors: J. Hopkins Tanne
Journal: BMJ (2002)

A US randomised, placebo controlled, double blind trial to evaluate oestrogen and progestogen in postmenopausal women was stopped early by the Women's Health Initiative because health risks exceeded health benefits by a small margin.

It is the first trial to examine whether continuous oestrogen plus progestogen has a favourable or unfavourable effect on coronary heart disease and overall risks and benefits in healthy women.

JAMA has already posted the article on its website (http://www.jama.com/issues/v288/n3/abs/joc21036.html). The article will then be …
THE IMPACT OF CONCUSSION ON CARDIAC AUTONOMIC FUNCTION: A SYSTEMATIC REVIEW OF EVIDENCE FOR RECOVERY AND PREVENTION
Authors: T Blake, C McKay, WH Meeuwisse, C Emery
Journal: British Journal of Sports Medicine (2014)

Background Concussions can negatively impact cognitive, behavioural, and physiological function. The current standard of care does not account for the physiological impact of concussion. Cardiac autonomic function (CAF) is responsive to changes in physical and cognitive exertion in healthy populations. The influence of concussion on CAF is not well understood. Objective To evaluate the evidence regarding the effect of concussion on cardiac autonomic function. Design Systematic Review. Setting Databases [Medline, SportDiscus, HealthSTAR, PsycINFO, Web of Science, CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, PubMed and ProQuest, Web of Science and Google Scholar] were systematically searched using keywords and MeSH terms. Sample Inclusion criteria: original research, available in English, included participants with concussion or mild traumatic brain injury (mTBI) and had a comparison group. Studies of humans (greater than 6 years old) and animals were included. Ten articles were identified for critical appraisal (six cohort studies, four cross-sectional). Independent variable Diagnosis of a concussion or mTBI. Main outcome measurements Heart rate (HR) and/or heart rate variability (HRV). Critical appraisal was conducted using the Downs and Black criteria. Results There is conflicting evidence regarding CAF at rest following concussion/mTBI. There is evidence of elevated HR and reduced HRV with low intensity, steady-state exercise up to 10 days following concussion. No significant difference in HRV was found during isometric handgrip testing following concussion. The validity of current literature is limited by small sample sizes, lack of female or pediatric participants, varying methodologies and lack of follow-up. No studies evaluating CAF during cognitive exertion following concussion were found. Conclusions There is evidence to suggest that CAF is altered during physical activity following concussion. The limitations in available literature highlight the need further research. Understanding the effect of concussion on CAF will contribute to the development of more comprehensive concussion management and prevention strategies.
Alterations in Mucosal Immunity Identified in the Colon of Patients With Irritable Bowel Syndrome
Authors: Jeroen Aerssens, Michael Camilleri, Willem Talloen, Leen Thielemans, Hinrich W.H. Göhlmann, Ilse Van den Wyngaert, Theo Thielemans, Ronald De Hoogt, Christopher N. Andrews, Adil E. Bharucha, Paula J. Carlson, Irene Busciglio, Duane D. Burton, Thomas Smyrk, Raul Urrutia, Bernard Coulie
Journal: Clinical Gastroenterology and Hepatology (2008)
Long-term experience of mycophenolate mofetil for treatment of diffuse cutaneous systemic sclerosis
Authors: Elizabeth N Le, Fredrick M Wigley, Ami A Shah, Francesco Boin, Laura K Hummers
Journal: Annals of the Rheumatic Diseases (2011)

Background Immunosuppressive therapy may potentially alter the natural disease course of scleroderma. There have been reports of using mycophenolate mofetil (MMF) for the treatment of scleroderma skin disease. Objective To analyse the experience of using MMF for the treatment of active diffuse cutaneous scleroderma. Methods The authors compared the change in mean modified Rodnan skin scores (mRSS) in an MMF cohort at baseline with scores at 3, 6, 9 and 12 months and with those of historical controls from a pooled analysis of three multicentre randomised clinical trials of recombinant human relaxin, d-penicillamine and oral bovine type I collagen. Results Improvement in mRSS after treatment with MMF compared with baseline was seen as early as 3 months and continued through the 12-month follow-up. The mRSS of the MMF cohort was not different from that of the historical controls at 6 months (MMF −3.05±7.4 vs relaxin −4.83±6.99, p=0.059), but was significantly lower at 12 months (MMF −7.59±10.1 vs d-penicillamine −2.47±8.6, p&lt;0.001; collagen −3.4±7.12, p=0.002). General and muscle severity scores and quality of life measures also improved compared with baseline. Pulmonary function remained stable. Conclusions MMF may benefit skin disease in patients with diffuse scleroderma, but prospective studies are required to determine its role.
Improved Survival for Children and Adolescents With Acute Lymphoblastic Leukemia Between 1990 and 2005: A Report From the Children's Oncology Group
Authors: Stephen P. Hunger, Xiaomin Lu, Meenakshi Devidas, Bruce M. Camitta, Paul S. Gaynon, Naomi J. Winick, Gregory H. Reaman, William L. Carroll
Journal: Journal of Clinical Oncology (2012)

Purpose To examine population-based improvements in survival and the impact of clinical covariates on outcome among children and adolescents with acute lymphoblastic leukemia (ALL) enrolled onto Children's Oncology Group (COG) clinical trials between 1990 and 2005. Patients and Methods In total, 21,626 persons age 0 to 22 years were enrolled onto COG ALL clinical trials from 1990 to 2005, representing 55.8% of ALL cases estimated to occur among US persons younger than age 20 years during this period. This period was divided into three eras (1990-1994, 1995-1999, and 2000-2005) that included similar patient numbers to examine changes in 5- and 10-year survival over time and the relationship of those changes in survival to clinical covariates, with additional analyses of cause of death. Results Five-year survival rates increased from 83.7% in 1990-1994 to 90.4% in 2000-2005 (P &lt; .001). Survival improved significantly in all subgroups (except for infants age ≤ 1 year), including males and females; those age 1 to 9 years, 10+ years, or 15+ years; in whites, blacks, and other races; in Hispanics, non-Hispanics, and patients of unknown ethnicity; in those with B-cell or T-cell immunophenotype; and in those with National Cancer Institute (NCI) standard- or high-risk clinical features. Survival rates for infants changed little, but death following relapse/disease progression decreased and death related to toxicity increased. Conclusion This study documents ongoing survival improvements for children and adolescents with ALL. Thirty-six percent of deaths occurred among children with NCI standard-risk features emphasizing that efforts to further improve survival must be directed at both high-risk subsets and at those children predicted to have an excellent chance for cure.
Toward a clinical model of psychotherapy for depression, I: Systematic comparison of three psychotherapies
Authors: T B Karasu
Journal: American Journal of Psychiatry (1990)

In a two-part series, the author explores the current status of psychotherapy for depression. In part I, three predominant approaches to the psychological treatment of depressive disorders today--psychodynamic, cognitive, and interpersonal--are described and contrasted schematically. They are depicted as conceptually different but potentially complementary with regard to 1) basic characteristics, including theoretical orientation, major strategies, goals, and mechanisms of change, and 2) respective advantages and limitations. This clinical comparison forms the foundation of an integrative and selective model for the treatment of depression.
ETIOLOGY OF YELLOW FEVER
Authors: Hideyo Noguchi
Journal: The Journal of Experimental Medicine (1922)

Analysis of the records of instances in which non-immune persons contracted yellow fever notwithstanding vaccination shows that the onset of disease occurs soon after vaccination, the longest period being 13 days. Since the average incubation period in yellow fever is 6 days, it seems that infection must have taken place in some instances during the period while protection was developing. These instances led to a study of the possibility of immediate protection by means of the anti-icteroides serum. It had already been shown that the immune serum protects at once against experimental Leptospira icteroides infection, but it remained to determine how long the protection would last. Guinea pigs were given different quantities of the immune serum and subsequently injected, at various intervals, with a virulent strain of Leptospira icteroides. Complete protection enduring 5 days was obtained with as minute a quantity of serum as 0.002 cc. per 1,000 gm. of body weight. After 5 days, however, the immune substance rapidly diminished, and to keep the animal protected for as long as 10 days it was necessary to give 100 times as much, or 0.2 cc. For a man weighing 80 kilos, 0.16 cc. (0.002 x 80) would theoretically be sufficient to protect for at least 5 days, 1.6 cc. for 7 days, and 16 cc. for 10 days. This temporary protection may be a valuable antecedent to that furnished by vaccination, since the final effect of the latter cannot be expected until at least 9 to 10 days have passed.
A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS)
Authors: N.I. Cherny, R. Sullivan, U. Dafni, J.M. Kerst, A. Sobrero, C. Zielinski, E.G.E. de Vries, M.J. Piccart
Journal: Annals of Oncology (2015)
The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial
Authors: Colin Baigent, Martin J Landray, Christina Reith, Jonathan Emberson, David C Wheeler, Charles Tomson, Christoph Wanner, Vera Krane, Alan Cass, Jonathan Craig, Bruce Neal, Lixin Jiang, Lai Seong Hooi, Adeera Levin, Lawrence Agodoa, Mike Gaziano, Bertram Kasiske, Robert Walker, Ziad A Massy, Bo Feldt-Rasmussen, Udom Krairittichai, Vuddidhej Ophascharoensuk, Bengt Fellström, Hallvard Holdaas, Vladimir Tesar, Andrzej Wiecek, Diederick Grobbee, Dick de Zeeuw, Carola Grönhagen-Riska, Tanaji Dasgupta, David Lewis, William Herrington, Marion Mafham, William Majoni, Karl Wallendszus, Richard Grimm, Terje Pedersen, Jonathan Tobert, Jane Armitage, Alex Baxter, Christopher Bray, Yiping Chen, Zhengming Chen, Michael Hill, Carol Knott, Sarah Parish, David Simpson, Peter Sleight, Alan Young, Rory Collins
Journal: The Lancet (2011)
MRI equilibrium signal mapping is a quantitative and reproducible alternative to CT for the estimation of lung density in COPD
Authors: Weijuan Zhang, Penny Hubbard, Eva Bondesson, Lars Wigström, Simon Young, David Singh, Josephine Naish, Geoffrey Parker
Journal: European Respiratory Journal (2012)

In MRI, the equilibrium tissue magnetisation is proportional to tissue water density. This study aimed to explore the feasibility and reproducibility of mapping the signal (S 0 ) associated with the equilibrium magnetisation in the assessment of structural abnormalities in COPD.  MR images were acquired in 12 COPD subjects twice within 1 week for T 1  and S 0  mapping. Lung S 0  was normalized by dividing by muscle S 0  to obtain a quantitative S 0  (qS 0 ). Matched CT slices were selected to calculate PD 15  and RA -950 .  Lung qS 0  maps were reproducible with reduced values seen in regions comparable to CT detected emphysema regions. The mean and 15 th , 50 th , 75 th  percentile qS 0  showed strong correlations with PD 15  and RA -950 .  Equilibrium signal maps of MRI correlate strongly with CT density estimates, indicating that qS 0  may be a reproducible, non-invasive/-ionising measure for quantifying lung density changes in COPD.