tbuckley/cabot-search huggingface dataset:
Relative potencies of several non-steroidal anti-inflammatory drugs against soya bean 15-lipoxygenase
Authors: P. Verrando, B. Shroot, J.P. Ortonne, C.N. Hensby
Journal: British Journal of Dermatology (2006)

The 15-lipoxygenase from soya bean has been claimed to represent a rapid assay procedure for drugs and chemical agents that inhibit other lipoxygenase products (Kingston, 1981). Although the exact role of products derived from skin lipoxygenase enzymes is not well established, many of these products, e.g. leukotriene B4, have inflammatory characteristics that warrant further examination (Camp, 1982). We have therefore started to evaluate anti-inflammatory drugs in vitro for their ability to inhibit soya bean 15-lipoxygenase, before appraising their effects in vivo in animal and human skin.
Hypoxia induces differential acute and chronic adaptations in regulation of skeletal muscle protein turnover
Authors: C.C. de Theije, R.J.C. Langen, A.M.W.J. Schols, W.H. Lamers, S.E. Köhler
Journal: European Respiratory Journal (2011)

Hypoxia may be a trigger of skeletal muscle atrophy in acute and chronic respiratory disease. To test this hypothesis, short- and long-term regulation of muscle mass in response to normobaric hypoxia was investigated in mice.  During 48h, O 2 – levels were reduced stepwise to 8%, which was maintained for 21 days. Food intake was monitored daily and mice were sacrificed at days 4 and 21. mRNA and protein expression levels were determined in gastrocnemius muscle.  Food intake was affected during short- (day (d) 4: -50%) and long-term (d21: -20%) hypoxia. Compared to normoxia, gastrocnemius muscle weight decreased (d4: -7.5% and d21: -11.9%). The reduced food intake was partially responsible for this effect. Hypoxia increased expression of  Atf4  (d4: +52%, d21: +31%) and  Gadd34  (d4: +148%, d21: +73%) indicative for acute and chronic ER stress signaling. Protein synthesis regulation was differentially affected by short- and long-term hypoxia (p-eIF2α d4: -29% and d21: -23%, p-4EBP1 d4: not significant (ns) and d21: +36%).  Atrogin-1  as proteasomal protein degradation marker was activated during acute and chronic hypoxia (d4: +128%, d21: +60%), whereas  MuRF1  only at day 4 (d4: +102%, d21: ns) and was explained by reduced food intake. short- and long-term hypoxia induced markers of lysosomal protein degradation  Bnip3  (d4: +95%, d21: +74%) and  Lc3  (d4: +18%, d21: +26%) which could be attributed in part to the reduced food intake.  In conclusion, these data suggest that acute adaptation of muscle mass to hypoxia reflects an increased protein degradation, whereas chronic adaptation may involve increased protein turnover.  Supported by the Dutch Top Institute Pharma (project # T1-201).
Surgeon length of service and risk-adjusted outcomes: linked observational analysis of the UK National Adult Cardiac Surgery Audit Registry and General Medical Council Register
Authors: Graeme L Hickey, Stuart W Grant, Nick Freemantle, David Cunningham, Christopher M Munsch, Steven A Livesey, James Roxburgh, Iain Buchan, Ben Bridgewater
Journal: Journal of the Royal Society of Medicine (2014)

Summary Objectives To explore the relationship between in-hospital mortality following adult cardiac surgery and the time since primary clinical qualification for the responsible consultant cardiac surgeon (a proxy for experience). Design Retrospective analysis of prospectively collected national registry data over a 10-year period using mixed-effects multiple logistic regression modelling. Surgeon experience was defined as the time between the date of surgery and award of primary clinical qualification. Setting UK National Health Service hospitals performing cardiac surgery between January 2003 and December 2012. Participants All patients undergoing coronary artery bypass grafts and/or valve surgery under the care of a consultant cardiac surgeon. Main outcome measures All-cause in-hospital mortality. Results A total of 292,973 operations performed by 273 consultant surgeons (with lengths of service from 11.2 to 42.0 years) were included. Crude mortality increased approximately linearly until 33 years service, before decreasing. After adjusting for case-mix and year of surgery, there remained a statistically significant ( p = 0.002) association between length of service and in-hospital mortality (odds ratio 1.013; 95% CI 1.005–1.021 for each year of ‘experience’). Conclusions Consultant cardiac surgeons take on increasingly complex surgery as they gain experience. With this progression, the incidence of adverse outcomes is expected to increase, as is demonstrated in this study. After adjusting for case-mix using the EuroSCORE, we observed an increased risk of mortality in patients operated on by longer serving surgeons. This finding may reflect under-adjustment for risk, unmeasured confounding or a real association. Further research into outcomes over the time course of surgeon's careers is required.
Housing, health, and illness.
Authors: J A Gray
Journal: BMJ (1978)

Cases referred to a community physician in his role as medical adviser to a housing authority were reviewed. A new system of classifying health problems was devised because conventional diagnostic classification was found to be inappropriate. The effectiveness of medical intervention was apparently low, since only 29 out of 612 (4.7%) applications for rehousing on medical grounds were successful. The effectiveness of the community physician's role was limited by the available resources and the number of cases he could take before the housing committee. It is proposed that the use of medical resources for intervention in such cases is acceptably efficient, though this proposal is based on value judgement rather than on economic grounds. Doctors should be concerned in improving housing conditions, which are still unacceptably poor in many parts of Britain, in the interests of improving general standards of public health.
Chemotherapeutic induced fascial oedema
Authors: I Lim
Journal: Annals of the Rheumatic Diseases (2004)

No patient had a history of a male twin or a solid organ transplant at the time of biopsy.SLE, systemic lupus erythematosus; CLE, cutaneous lupus erythematosus; DM, dermatomyositis; MF, mycosis fungoides.
Aluminum Citrate Prevents Renal Injury from Calcium Oxalate Crystal Deposition
Authors: Lauren M. Besenhofer, Marie C. Cain, Cody Dunning, Kenneth E. McMartin
Journal: Journal of the American Society of Nephrology (2012)

Calcium oxalate monohydrate crystals are responsible for the kidney injury associated with exposure to ethylene glycol or severe hyperoxaluria. Current treatment strategies target the formation of calcium oxalate but not its interaction with kidney tissue. Because aluminum citrate blocks calcium oxalate binding and toxicity in human kidney cells, it may provide a different therapeutic approach to calcium oxalate-induced injury. Here, we tested the effects of aluminum citrate and sodium citrate in a Wistar rat model of acute high-dose ethylene glycol exposure. Aluminum citrate, but not sodium citrate, attenuated increases in urea nitrogen, creatinine, and the ratio of kidney to body weight in ethylene glycol–treated rats. Compared with ethylene glycol alone, the addition of aluminum citrate significantly increased the urinary excretion of both crystalline calcium and crystalline oxalate and decreased the deposition of crystals in renal tissue. In vitro, aluminum citrate interacted directly with oxalate crystals to inhibit their uptake by proximal tubule cells. These results suggest that treating with aluminum citrate attenuates renal injury in rats with severe ethylene glycol toxicity, apparently by inhibiting calcium oxalate's interaction with, and retention by, the kidney epithelium.
Normal Myocardial Function and Energetics in Volume-Overload Hypertrophy in the Cat
Authors: GEORGE COOPER, FRANCISCO J. PUGA, KAREN J. ZUJKO, CARLOS E. HARRISON, HENRY NEAL COLEMAN
Journal: Circulation Research (1973)

Depressed contractility with a paradoxically increased myocardial oxygen consumption has been associated with pressure-overload hypertrophy. The present experiments investigated myocardial hypertrophy induced by volume overload. Right ventricular volume overload was produced in 19 cats by surgically creating atrial septal defects (ASD); these cats were compared with 10 sham-operated control cats. The ASD cats showed an increase in the ratio of pulmonary blood flow to systemic blood flow from 1.04 ± 0.01 ( SE ) (control) to 3.30 ± 0.28 (ASD) ( P &lt; 0.001). Hypertrophy was evidenced by a ratio of right ventricular weight to body weight of 0.59 ± 0.03 g/kg for control cats and 0.97 ± 0.03 for ASD cats ( P &lt; 0.001). A polarographic muscle bath was used to study papillary muscles from 8 control and 8 ASD cats. ASD muscles demonstrated normal force-velocity curves, with maximal measured preload velocities of 1.32 ± 0.05 muscle lengths/sec: control velocities were 1.33 ± 0.05 muscle lengths/sec ( P &gt; 0.9). The myocardial oxygen consumption of isotonic contractions was normal for ASD muscles. The length-tension curves were comparable, with developed tensions at Lmax of 6.20 ± 0.31 g/mm 2 for ASD muscles and 6.34 ± 0.23 g/mm 2 for control muscles ( P &gt; 0.7). Myocardial oxygen consumption pergram of tension development at Lmax was 0.66 ± 0.06 µliters/mg beat -1 x 10 -3 in the ASD muscles and 0.65 ± 0.05 µliters/mg beat -1 x 10 -3 in the control muscles ( P &gt; 0.8). The mitochondrial oxidative indexes from control and hypertrophied right ventricles were similar, with respiratory control indexes of 14.3 ± 0.8 for ASD hearts and 12.8 ± 1.6 for control hearts ( P &gt; 0.1). These data demonstrate that contractility and energetics are normal in volume-overload hypertrophy, although these same factors are abnormal in pressure-overload hypertrophy. Thus, hypertrophy alone is not a common denominator for abnormal myocardial function and energetics.
(R)-Albuterol for Asthma: Pro [a.k.a. (S)-Albuterol for Asthma: Con]
Authors: Bill T. Ameredes, William J. Calhoun
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Is there scientific evidence to support the replacement of the beta-agonist racemic albuterol with levalbuterol--that is, (R)-albuterol? The argument presented further refines the question as "Do we wish to continue to treat asthma with a mixture of albuterol, of which half is an agent with no known benefit--that is, (S)-albuterol--and which may exacerbate the disease?"
Does physical activity ameliorate the health hazards of obesity?
Authors: D C Lee, X Sui, S N Blair
Journal: British Journal of Sports Medicine (2008)

Obesity is an established risk factor for chronic disease and premature death, but losing weight and keeping it off is difficult. Therefore, although obese individuals may know that they are at higher risk of disease and early death, they still may not be able to lose weight and maintain weight loss. Perhaps health professionals should focus less on weight and more on how to enhance and maintain health for people of all sizes and shapes.
Nature of anaemia in rheumatoid arthritis. XI. Changes in iron metabolism induced by the administration of corticotrophin.
Authors: A.G Mowat, T.E Hothersall, W.R Aitchison
Journal: Annals of the Rheumatic Diseases (1969)

Moderate anaemia of a hypochromic, normocytic type is a common feature of rheumatoid arthritis and disturbance of iron metabolism is a prominent feature of this anaemia.Several previous reports in this series have described abnormalities in the metabolism of iron in this disease (Roy, Alexander, and
Communicative intentions can modulate the linguistic perception-action link
Authors: Yoshihisa Kashima, Harold Bekkering, Emiko S. Kashima
Journal: Behavioral and Brain Sciences (2013)

Abstract Although applauding Pickering &amp; Garrod's (P&amp;G's) attempt to ground language use in the ideomotor perception-action link, which provides an “infrastructure” of embodied social interaction, we suggest that it needs to be complemented by an additional control mechanism that modulates its operation in the service of the language users' communicative intentions. Implications for intergroup relationships and intercultural communication are discussed.
Phase II Study of Tirapazamine, Cisplatin, and Etoposide and Concurrent Thoracic Radiotherapy for Limited-Stage Small-Cell Lung Cancer: SWOG 0222
Authors: Quynh-Thu X. Le, James Moon, Mary Redman, Stephen K. Williamson, Primo N. Lara, Zelanna Goldberg, Laurie E. Gaspar, John J. Crowley, Dennis F. Moore, David R. Gandara
Journal: Journal of Clinical Oncology (2009)

A SWOG pilot study (S0004) showed that tirapazamine (TPZ) when combined with concurrent chemoradiotherapy yielded a promising median survival of 22 months in limited-stage small-cell lung cancer (LSCLC). We report results of the phase II study designed to confirm this result.The concurrent phase consisted of two cycles of cisplatin, etoposide, and once-daily radiation to 61 Gy. TPZ was given at 260 mg/m(2) on days 1, 29, and at 160 mg/m(2) on days 8, 10, 12, 36, 38, and 40. Consolidation consisted of two cycles of cisplatin and etoposide. Complete responders received prophylactic cranial irradiation. Results were considered promising if the median survival time was at least 21 months and of no further interest if < or = 14 months.S0222 was closed early due to a report of excess toxicity for TPZ in a head and neck cancer trial elsewhere. Of planned 85 patients, 69 were accrued. In 68 assessable patients, 17 (25%) had grade 3 to 4 esophagitis and eight (12%) had grade 3 febrile neutropenia during the concurrent phase. There were three possible treatment-related deaths, two in concurrent phase (one progressive disease not otherwise specified within 30 days, one pericardial effusion) and one in consolidation phase (esophageal hemorrhage). At a median follow-up of 35 months, median progression-free survival was 11 months (95% CI, 10 to 13 months) and median overall survival was 21 months (95% CI, 17 to 33 months).S0222 showed acceptable levels of toxicity and similar promising median survival as S0004. Further study of hypoxia-targeted therapy is warranted in LSCLC.
Acute Sprue in Britain
Authors: M. B. Drummond, R. D. Montgomery
Journal: BMJ (1970)

ME BRILJSNadmitted more than eight weeks after injury and the danger period was considered to be passed; one suffered multiple trauma (head injury plus compound fractures of three limbs); one had such a transient and subjective neurological distur- bance that it was thought that the dangers of therapy out- weighed the advantages; and one who had a severe head injury with a pulsating exophthalmos together with a C3 frac- ture and amputation of one limb died after a week before therapy could be instituted.We used phenindione as we had most experience with this drug and did not think it necessary to begin anticoagulants rapidly by using heparin.Owing to the fact that all patients with spinal injuries are admitted to another hospital after injury, there is an unavoidable delay in starting therapy, in contradistinction to Sevitt and Gallagher (1959), who worked in a receiving hospital; they showed that up to 50% of these patients de- veloped deep venous thrombosis within a week of injury, and we realize that we may have been instituting therapy at a later stage than was ideal.We controlled the therapy by the thrombotest reagent, as this was in use in the laboratory.We kept the level between 7 and 40%.We realize that the upper limit is slightly higher than recommended.If the level fell below 10% we had fre- quent bleeds, particularly from the bladder; however, it did not interfere with treatment in any way.Fifteen patient were in fact circumcized while under treatment (normal practice to reduce urinary infection and to facilitate the wearing of a urinal), nor did we find any ascent of the spinal lesion due to bleeding into or around the cord.One patient (an asthmatic) was sensitive to both phenindione and warfarin and developed bleeding from the bladder and mouth, so the treatment was discontinued.Of greater theoretical interest is the observation that there appears to be a greater incidence of ectopic ossifi- cation around the hips in.patients on treatment (Silver, 1969), possibly owing to bleeding into the adductor muscles.The regimen of general management has not substantially changed over the past four years, and, while we realize the pitfalls of retrospective comparisons, the fact that no patient has had pulmonary embolus since the institution of this pro- phylactic regimen in contrast to the pjrevious period quoted, would indicate that this treatment is effective.The observa- tion that four of the six patients who developed pulmonary emboli had thoracic lesions is of great interest since Walsh and Tribe (1965) and Watson (1968) observed the highest incidence in this group of patients (17-1% and 7% respec- tively).
Therapeutic Decisions in Multiple Sclerosis
Authors: Wolfgang Brück, Ralf Gold, Brett T. Lund, Celia Oreja-Guevara, Alexandre Prat, Collin M. Spencer, Lawrence Steinman, Mar Tintoré, Timothy L. Vollmer, Martin S. Weber, Leslie P. Weiner, Tjalf Ziemssen, Scott S. Zamvil
Journal: JAMA Neurology (2013)

Importance-Several innovative disease-modifying treatments (DMTs) for relapsing remitting multiple sclerosis (RRMS) have been licensed recently, or are in late-stage development.The molecular targets of several of these DMTs are well defined.All affect at least one of four properties: (1) immune cell trafficking, (2) cell depletion, (3) immune cell function, or (4) cell replication.In contrast to β-interferons and glatiramer acetate, the first generation DMTs, several newer therapies are imbued with safety issues.In addition to efficacy, understanding the relationship between the mechanism of action (MOA) of the DMTs and their safety profile is essential for decision-making in patient care.Objective-In this article, we relate safety issues of newer DMTs to their pharmacological characteristics, including molecular targets, MOA, chemical structure, and metabolism.Some newer DMTs also represent repurposing or modifications of previous treatments used in other diseases.Here, we describe how identification and understanding of adverse events (AEs) observed with these established drugs within the same class, provide clues regarding safety and toxicities of newer MS therapeutics.Conclusions and relevance-While understanding mechanisms underlying DMT toxicities is incomplete, it is important to further develop this knowledge to minimize risk to patients, and to ensure future therapies have the most advantageous risk-benefit profiles.Recognizing the individual classes of DMTs described here may be beneficial when considering use of such agents sequentially and possibly in combination.
Concomitant Boost Radiation Plus Concurrent Cisplatin for Advanced Head and Neck Carcinomas: Radiation Therapy Oncology Group Phase II Trial 99-14
Authors: K. Kian Ang, Jonathan Harris, Adam S. Garden, Andy Trotti, Christopher U. Jones, Luis Carrascosa, Jonathan D. Cheng, Sharon S. Spencer, Arlene Forastiere, Randal S. Weber
Journal: Journal of Clinical Oncology (2005)

Purpose To investigate the feasibility of combining concomitant boost accelerated radiation regimen (AFX-C) with cisplatin and to assess its toxicity and the relapse pattern and survival in patients with advanced head and neck carcinoma (HNC). Patients and Methods Between April and November of 2000, 84 patients with stage III to IV HNC who met the eligibility criteria were enrolled; 76 of these patients were analyzable. Radiation consisted of 72 Gy in 42 fractions over 6 weeks (daily for 3.5 weeks, then twice a day for 2.5 weeks). Cisplatin dose was 100 mg/m 2 on days 1 and 22. Tumor and clinical status were assessed, and acute late toxicities were graded. Results Sixty-five patients (86%) received both radiation and chemotherapy per protocol or with minor variations. The estimated 2-year locoregional relapse and distant metastasis rates were 34.7% and 16.1%, respectively. The estimated 2-year overall survival and disease-free survival rates were 71.6% and 53.5%, respectively. Three patients (4%) died of complications, 19 patients (25%) had acute grade 4 toxicity, and 49 patients (64%) had acute grade 3 toxicity. The 2-year cumulative incidence of late grade 3 to 5 toxicities was 51.3%. Conclusion These data showed that it was feasible to combine AFX-C with cisplatin. The compliance to therapy was high, and the locoregional control and survival rates achieved compared favorably with AFX-C alone or other concurrent chemoradiation regimens tested by the Radiation Therapy Oncology Group. A phase III trial comparing AFX-C plus cisplatin against standard radiation plus cisplatin is ongoing to determine whether the use of AFX-C in the concurrent chemoradiation setting further improves outcome.
Pharmacological chaperones rescue cell-surface expression and function of misfolded V2 vasopressin receptor mutants
Authors: Jean-Pierre Morello, Ali Salahpour, André Laperrière, Virginie Bernier, Marie-Françoise Arthus, Michèle Lonergan, Ulla Petäjä-Repo, Stéphane Angers, Denis Morin, Daniel G. Bichet, Michel Bouvier
Journal: Journal of Clinical Investigation (2000)

Over 150 mutations within the coding sequence of the V2 vasopressin receptor (V2R) gene are known to cause nephrogenic diabetes insipidus (NDI). A large number of these mutant receptors fail to fold properly and therefore are not routed to the cell surface. Here we show that selective, nonpeptidic V2R antagonists dramatically increase cell-surface expression and rescue the function of 8 mutant NDI-V2Rs by promoting their proper folding and maturation. A cell-impermeant V2R antagonist could not mimic these effects and was unable to block the rescue mediated by a permeant agent, indicating that the nonpeptidic antagonists act intracellularly, presumably by binding to and stabilizing partially folded mutants. In addition to opening new therapeutic avenues for NDI patients, these data demonstrate that by binding to newly synthesized mutant receptors, small ligands can act as pharmacological chaperones, promoting the proper folding and maturation of receptors and their targeting to the cell surface.
Alkylphosphocholine Analogs for Broad-Spectrum Cancer Imaging and Therapy
Authors: Jamey P. Weichert, Paul A. Clark, Irawati K. Kandela, Abram M. Vaccaro, William Clarke, Marc A. Longino, Anatoly N. Pinchuk, Mohammed Farhoud, Kyle I. Swanson, John M. Floberg, Joseph Grudzinski, Benjamin Titz, Anne M. Traynor, Hong-En Chen, Lance T. Hall, Christopher J. Pazoles, Perry J. Pickhardt, John S. Kuo
Journal: Science Translational Medicine (2014)

Many solid tumors contain an overabundance of phospholipid ethers relative to normal cells. Capitalizing on this difference, we created cancer-targeted alkylphosphocholine (APC) analogs through structure-activity analyses. Depending on the iodine isotope used, radioiodinated APC analog CLR1404 was used as either a positron emission tomography (PET) imaging ((124)I) or molecular radiotherapeutic ((131)I) agent. CLR1404 analogs displayed prolonged tumor-selective retention in 55 in vivo rodent and human cancer and cancer stem cell models. (131)I-CLR1404 also displayed efficacy (tumor growth suppression and survival extension) in a wide range of human tumor xenograft models. Human PET/CT (computed tomography) and SPECT (single-photon emission computed tomography)/CT imaging in advanced-cancer patients with (124)I-CLR1404 or (131)I-CLR1404, respectively, demonstrated selective uptake and prolonged retention in both primary and metastatic malignant tumors. Combined application of these chemically identical APC-based radioisosteres will enable personalized dual modality cancer therapy of using molecular (124)I-CLR1404 tumor imaging for planning (131)I-CLR1404 therapy.