tbuckley/cabot-search huggingface dataset:
Cinacalcet, Fibroblast Growth Factor-23, and Cardiovascular Disease in Hemodialysis
Authors: Sharon M. Moe, Glenn M. Chertow, Patrick S. Parfrey, Yumi Kubo, Geoffrey A. Block, Ricardo Correa-Rotter, Tilman B. Drüeke, Charles A. Herzog, Gerard M. London, Kenneth W. Mahaffey, David C. Wheeler, Maria Stolina, Bastian Dehmel, William G. Goodman, Jürgen Floege
Journal: Circulation (2015)

Patients with kidney disease have disordered bone and mineral metabolism, including elevated serum concentrations of fibroblast growth factor-23 (FGF23). These elevated concentrations are associated with cardiovascular and all-cause mortality. The objective was to determine the effects of the calcimimetic cinacalcet (versus placebo) on reducing serum FGF23 and whether changes in FGF23 are associated with death and cardiovascular events.This was a secondary analysis of a randomized clinical trial comparing cinacalcet to placebo in addition to conventional therapy (phosphate binders/vitamin D) in patients receiving hemodialysis with secondary hyperparathyroidism (intact parathyroid hormone ≥300 pg/mL). The primary study end point was time to death or a first nonfatal cardiovascular event (myocardial infarction, hospitalization for angina, heart failure, or a peripheral vascular event). This analysis included 2985 patients (77% of randomized) with serum samples at baseline and 2602 patients (67%) with samples at both baseline and week 20. The results demonstrated that a significantly larger proportion of patients randomized to cinacalcet had ≥30% (68% versus 28%) reductions in FGF23. Among patients randomized to cinacalcet, a ≥30% reduction in FGF23 between baseline and week 20 was associated with a nominally significant reduction in the primary composite end point (relative hazard, 0.82; 95% confidence interval, 0.69-0.98), cardiovascular mortality (relative hazard, 0.66; 95% confidence interval, 0.50-0.87), sudden cardiac death (relative hazard, 0.57; 95% confidence interval, 0.37-0.86), and heart failure (relative hazard, 0.69; 95% confidence interval, 0.48-0.99).Treatment with cinacalcet significantly lowers serum FGF23. Treatment-induced reductions in serum FGF23 are associated with lower rates of cardiovascular death and major cardiovascular events.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00345839.
Microsatellite Instability, Immunohistochemistry, and Additional PMS2 Staining in Suspected Hereditary Nonpolyposis Colorectal Cancer
Authors: Andrea E. de Jong, Marjo van Puijenbroek, Yvonne Hendriks, Carli Tops, Juul Wijnen, Margreet G. E. M. Ausems, Hanne Meijers-Heijboer, Anja Wagner, Theo A. M. van Os, Annette H. J. T. Bröcker-Vriends, Hans F. A. Vasen, Hans Morreau
Journal: Clinical Cancer Research (2004)

Immunohistochemistry (IHC) and microsatellite instability (MSI) analysis can be used to identify patients with a possible DNA mismatch repair defect [hereditary nonpolyposis colorectal carcinoma (HNPCC)]. The Bethesda criteria have been proposed to select families for determination of MSI. The aims of this study were to assess the yield of MSI analysis in families suspected for HNPCC, to compare the results of immunohistochemical staining and MSI analysis, and to assess the additional value of PMS2 staining.Clinical data and tumors were collected from 725 individuals from 631 families with suspected HNPCC. MSI analysis was performed using eight markers including the 5 National Cancer Institute markers. Four immunohistochemical staining antibodies were used (MLH1, MSH2, MSH6 and PMS2).A MSI-H (tumors with instability for >30% of the markers) phenotype in colorectal cancers (CRCs) was observed in 21-49% of families that met the various Bethesda criteria. In families with three cases of CRC diagnosed at age > 50 years, families with a solitary case of CRC diagnosed between ages 45 and 50 years, and families with one CRC case and a first-degree relative with a HNPCC-related cancer, one diagnosed between ages 45 and 50 years (all Bethesda-negative families), the yield of MSI-H was 10-26%. Immunohistochemical staining confirmed the MSI results in 93% of the cases. With IHC, adding PMS2 staining led to the identification of an additional 23% of subjects with an hMLH1 germ-line mutation (35 carriers were tested).The Bethesda guidelines for MSI analysis should include families with three or more cases of CRC diagnosed at age > 50 years. The age at diagnosis of CRC in the original guidelines should be raised to 50 years. Routine IHC diagnostics for HNPCC should include PMS2 staining.
Systemic Gene-Directed Enzyme Prodrug Therapy of Hepatocellular Carcinoma Using a Targeted Adenovirus Armed with Carboxypeptidase G2
Authors: Silke Schepelmann, Paul Hallenbeck, Lesley M. Ogilvie, Douglas Hedley, Frank Friedlos, Janet Martin, Ian Scanlon, Carl Hay, Lynda K. Hawkins, Richard Marais, Caroline J. Springer
Journal: Cancer Research (2005)

Abstract Hepatocellular carcinoma is the fifth most common cancer worldwide, and there is no effective therapy for unresectable disease. We have developed a targeted systemic therapy for hepatocellular carcinoma. The gene for a foreign enzyme is selectively expressed in the tumor cells and a nontoxic prodrug is then given, which is activated to a potent cytotoxic drug by the tumor-localized enzyme. This approach is termed gene-directed enzyme prodrug therapy (GDEPT). Adenoviruses have been used to target cancer cells, have an intrinsic tropism for liver, and are efficient gene vectors. Oncolytic adenoviruses produce clinical benefits, particularly in combination with conventional anticancer agents and are well tolerated. We rationalized that such adenoviruses, if their expression were restricted to telomerase-positive cancer cells, would make excellent gene vectors for GDEPT therapy of hepatocellular carcinoma. Here we use an oncolytic adenovirus to deliver the prodrug-activating enzyme carboxypeptidase G2 (CPG2) to tumors in a single systemic administration. The adenovirus replicated and produced high levels of CPG2 in two different hepatocellular carcinoma xenografts (Hep3B and HepG2) but not other tissues. GDEPT enhanced the adenovirus-alone therapy to elicit tumor regressions in the hepatocellular carcinoma models. This is the first time that CPG2 has been targeted and expressed intracellularly to effect significant therapy, showing that the combined approach holds enormous potential as a tumor-selective therapy for the systemic treatment of hepatocellular carcinoma.
Effects of Long-Term Postoperative Interferon-α Therapy on Intrahepatic Recurrence after Resection of Hepatitis C Virus–Related Hepatocellular Carcinoma
Authors: Shoji Kubo, Shuhei Nishiguchi, Kazuhiro Hirohashi, Hiromu Tanaka, Taichi Shuto, Osamu Yamazaki, Susumu Shiomi, Akihiro Tamori, Hiroko Oka, Sumito Igawa, Tetsuo Kuroki, Hiroaki Kinoshita
Journal: Annals of Internal Medicine (2001)

Background: Interferon therapy decreases the incidence of hepatocellular carcinoma in patients with chronic hepatitis C. Objective: To evaluate effects of interferon-α on recurrence after resection of hepatitis C virus–related hepatocellular carcinoma. Design: Randomized, controlled trial. Setting: University hospital, medical center, and affiliated hospital in Osaka, Japan. Patients: 30 men were randomly allocated after resection to the interferon-α group (n = 15) or the control group (n = 15). Intervention: Patients in the interferon-α group received interferon-α, 6 MIU intramuscularly daily for 2 weeks, then three times weekly for 14 weeks, and finally twice weekly for 88 weeks. Measurements: Recurrence rates after resection. Results: Recurrent tumors were detected in 5 patients in the interferon-α group and in 12 control patients. The recurrence rate was significantly lower in the interferon-α group than in the control group (P = 0.037). Conclusion: Postoperative interferon-α therapy appears to decrease recurrence after resection of hepatitis C virus–related hepatocellular carcinoma.
Extracellular Superoxide Dismutase Attenuates Lung Injury after Hemorrhage
Authors: RUSSELL P. BOWLER, JOHN ARCAROLI, JAMES D. CRAPO, ARON ROSS, JAN W. SLOT, EDWARD ABRAHAM
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Reperfusion of the lung after hemorrhage generates free radicals such as superoxide (O2 ·) that may injure the lung; however, the relative importance of intracellular versus extracellular free radicals is unclear. The superoxide dismutases (SOD) are the primary enzymatic method to reduce superoxide. We examined whether lung-specific overexpression of extracellular superoxide dismutase (EC-SOD) would attenuate hemorrhage-induced lung injury. Wild-type mice and mice overexpressing the human EC-SOD gene with a lung-specific promoter were hemorrhaged by removing 30% of blood volume. After hemorrhage, the lung wet to dry weight ratios increased from 5.4 ± 0.11 in unmanipulated control mice to 6.3 ± 0.16 in wild-type mice, but to only 5.60 ± 0.17 in the EC-SOD transgenic mice (p < 0.05 compared with hemorrhaged wild-type). Hemorrhage-induced lipid peroxidation, as assessed by lung F2 isoprostanes, was lower in the EC-SOD transgenic mice (3.4 ± 0.3 μ g/lung) compared with wild-type mice (1.9 ± 0.2 μ g/lung; p < 0.05). Compared with wild-type, EC-SOD transgenic mice had attenuated the hemorrhage-induced increase in both pulmonary nuclear factor kappa B (NK- κ B) activation (relative absorbance 1.1 ± 0.2 for EC-SOD transgenic versus 2.5 ± 0.1 for wild-type; p < 0.05) and myeloperoxidase activity (5.1 ± 0.87 units/g for EC-SOD transgenic versus 11.3 ± 1.8 units/g for wild-type; p < 0.01). Thus, overexpression of pulmonary EC-SOD in the mouse lung attenuates lung injury after hemorrhage.Keywords: hemorrhage; extracellular superoxide dismutase; NF-κB; myeloperoxidase
Empowering African genomics for infectious disease control
Authors: Onikepe A Folarin, Anise N Happi, Christian T Happi
Journal: Genome biology (2014)

Abstract At present, African scientists can only participate minimally in the genomics revolution that is transforming the understanding, surveillance and clinical treatment of infectious diseases. We discuss new initiatives to equip African scientists with knowledge of cutting-edge genomics tools, and build a sustainable critical mass of well-trained African infectious diseases genomics scientists.
A British Medical Association Lecture ON SOME COMMON, BUT OFTEN UNRECOGNIZED, OBSTETRICAL DIFFICULTIES
Authors: W. B. Bell
Journal: BMJ (1921)

WHEN you kindly invited me to give you a lecture on some obstetrical subject of interest to the general practitioner, I felt at once that you bad allowed me a wide choice, for obstetrical practice in this country is, as it should be, very largely in the hands of the familv medical attendant.This being so, it follows, as I feel certain you will agree, that since so much is at stake-the lives cf a mother and a member of 'the next generation-tllose who are responsible for a safe issue must be alert in the anticipation and diagnosis of complications in everv aspect of this highly important and now scientific art.The obstetrical difficulties to which I wish specially to call your attention are those wlhich are common and recognizable, but wlhich, owina to imperfect investiaation of the patient are, unfortuniately, often not discovered until too late, or are missed altogether.
The electrical and motor actions of gastrointestinal hormones on the duodenum in man
Authors: W. E. Waterfall, H. L. Duthie, B. H. Brown
Journal: Gut (1973)

The electrical and motor activity was recorded from the duodenum in 16 conscious human subjects in resting conditions.The main electrical wave form variously known as the pace- setter potential or slow wave was constantly present and periodically accompanied by a second electrical trace consisting of rapid bursts of fast waves or action potentials which were related to motor waves.Secretin and the synthetic analogue of gastrin, pentagastrin, were given in separate tests and their complementary actions on myoelectrical activity are reported.In general, secretin (in six subjects) depressed and pentagastrin (in eight subjects) enhanced motor activity and bursts of action potentials.
Increased ischemia-reperfusion injury to the heart associated with short-term, diet-induced hypercholesterolemia in rabbits.
Authors: R G Tilton, P A Cole, J D Zions, A Daugherty, K B Larson, S P Sutera, C Kilo, J R Williamson
Journal: Circulation Research (1987)

The effects of increased dietary cholesterol content on coronary vascular hemodynamics and endothelial cell transport function were assessed in isolated rabbit hearts during 3.5 hours of reperfusion after 30 minutes of global, no-flow ischemia. In control hearts from rabbits fed normal chow, perfusion pressure, left ventricular end-diastolic pressure, maximum +dP/dt, and the rate of intravascular clearance of radiolabelled albumin remained constant during 5 hours of continuous perfusion, while the mean transit time of radiolabelled albumin increased 1.6 X baseline. In ischemic hearts from rabbits fed normal chow, perfusion pressure increased 59% during reperfusion while left ventricular end-diastolic pressure and maximum +dP/dt returned toward control levels. The rate of intravascular clearance of radiolabelled albumin decreased 36%, and the mean transit time of albumin increased approximately 3 X baseline. Ischemia-reperfusion injury to the cardiac vasculature and musculature was markedly increased in hearts of rabbits fed chow supplemented with 2% cholesterol for 2-3 weeks compared to rabbits fed the same diet for a longer duration (5-16 weeks) or rabbits fed normal chow. Prior to ischemia, permeation of the coronary vasculature by albumin was increased twofold in rabbits fed cholesterol for 2-3 weeks while myocyte contractile function was normal relative to chow-fed controls or the group fed cholesterol for 5-16 weeks. These effects of acute cholesterol feeding precede occlusive atherosclerotic coronary artery disease and occur at plasma cholesterol concentrations one third of those in rabbits fed cholesterol for the longer duration.(ABSTRACT TRUNCATED AT 250 WORDS)
The Circulatory Effects of Roniacol
Authors: G. S. ROBACK, A. C. IVY
Journal: Circulation (1952)

The vasodilatory effects of nicotinic alcohol tartrate (Roniacol) were tested on 12 normal adult males, utilizing digital venous occlusion plethysmography, brachial and digital artery oscillometry and flicker photometry. Orally administered Roniacol in single doses up to 200 mg. has no significant effect on the auscultatory blood pressure, pulse rate, or peripheral arterial circulation of normal individuals.
Government makes up hospital bailout policies "on the hoof," say MPs
Authors: A. O'Dowd
Journal: BMJ (2012)

The government is not sufficiently prepared to deal with any NHS trust in England that is facing serious financial problems such as bankruptcy and is making up rules and processes “on the hoof,” MPs have said.

MPs on the parliamentary Public Accounts Committee have published a highly critical report on the financial sustainability of the NHS, which they say is more precarious than would at first appear.1

The report says that the public will have confidence in NHS services only if assurances are given of a viable financial future for healthcare providers. Such assurances, however, were missing, the committee said, because critical details were not yet known of how the new system for the NHS introduced by the government would work so that services remained available to patients …
Comparative Effectiveness of New Oral Anticoagulants and Standard Thromboprophylaxis in Patients Having Total Hip or Knee Replacement
Authors: Soheir S. Adam, Jennifer R. McDuffie, Paul F. Lachiewicz, Thomas L. Ortel, John W. Williams
Journal: Annals of Internal Medicine (2013)

Pharmacologic thromboprophylaxis reduces the risk for venous thromboembolism after total hip replacement (THR) or total knee replacement (TKR). New oral anticoagulants (NOACs), including direct thrombin inhibitors and factor Xa inhibitors, are emerging options for thromboprophylaxis after these procedures.To compare the benefits and risks of NOACs versus standard thromboprophylaxis for adults having THR or TKR.MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from January 2009 through March 2013.English-language systematic reviews.Two independent reviewers abstracted data and rated study quality and strength of evidence.Six good-quality systematic reviews compared NOACs with low-molecular-weight heparin (LMWH) for thromboprophylaxis after THR or TKR. Risk for symptomatic deep venous thrombosis, but not risk for death or nonfatal pulmonary embolism, was reduced with factor Xa inhibitors compared with LMWH (4 fewer events per 1000 patients). Conversely, the risk for major bleeding increased (2 more events per 1000 patients). Outcomes of dabigatran did not significantly differ from those of LMWH. Indirect evaluation of NOACs by common comparison with LMWH showed nonsignificantly reduced risks for venous thromboembolism with rivaroxaban compared with dabigatran (risk ratio [RR], 0.68 [95% CI, 0.21 to 2.23]) and apixaban (RR, 0.59 [CI, 0.26 to 1.33]) but increased major bleeding. New oral anticoagulants have not been compared with warfarin, aspirin, or unfractionated heparin.Head-to-head comparisons among NOACs were not available. Efficacy is uncertain in routine clinical practice.New oral anticoagulants are effective for thromboprophylaxis after THR and TKR. Their clinical benefits over LMWH are marginal and offset by increased risk for major bleeding.U.S. Department of Veterans Affairs.
Differential role of actin in lung endothelial and epithelial barrier properties in perfused rabbit lungs
Authors: L Ermert, R Rossig, T Hansen, H Schutte, K Aktories, W Seeger
Journal: European Respiratory Journal (1996)

Lung fluid balance is critically dependent on capillary endothelial and alveolar epithelial barrier properties, and cytoskeletal components have been implicated in these barrier functions. In an earlier study, we perfused Clostridium botulinum C2 toxin, which effects selective loss of non-muscle F-actin, through isolated rabbit lungs: a severalfold increase in the capillary filtration coefficient (Kfc) was noted, together with attenuations and disruptions of endothelial cells upon electron microscopic examination. In this model we have investigated the influence of the C2 toxin on alveolar epithelial barrier properties. Epithelial permeability was assessed by continuous monitoring of the transepithelial passage of technetium-labelled diethylenetriamine penta-acetic acid (99mTc-DTPA), offered to the alveolar surface by aerosol technique. Intravascular administration of hydrogen peroxide, used as control agent, was shown to provoke a four- to fivefold increase in the clearance rate of 99mTc-DTPA under conditions of severe fluid leakage into the lung interstitial and alveolar space. Intravascular administration of C2 toxin caused a dose- and time-dependent increase in Kfc values (8-15 fold), but the Tc-DTPA clearance rate was entirely unaffected. Moreover, transbronchial application of C2 toxin again reproduced the manifold increase in Kfc data (about six fold), but the rate of transepithelial passage of the hydrophilic Tc-DTPA complex remained unchanged. We conclude that the barrier properties of the lung microvascular endothelial and epithelial layer are differentially regulated. It is suggested that the actin microfilament system plays a decisive role in the structural and functional integrity of the endothelial but not the epithelial barrier.
Phase II Study of Conformal Hypofractionated Radiotherapy With Concurrent Gemcitabine in Muscle-Invasive Bladder Cancer
Authors: Ananya Choudhury, Ric Swindell, John P. Logue, P. Anthony Elliott, Jacqueline E. Livsey, Marcus Wise, Paul Symonds, James P. Wylie, Vijay Ramani, Vijay Sangar, Jeanette Lyons, Ian Bottomley, Damian McCaul, Noel W. Clarke, Anne E. Kiltie, Richard A. Cowan
Journal: Journal of Clinical Oncology (2011)

The aim of this prospective, phase II trial was to determine the response of muscle-invasive bladder cancer (MIBC) to concurrent chemoradiotherapy of weekly gemcitabine with 4 weeks of radiotherapy (RT; GemX).
Long-term culture of pluripotent stem-cell-derived human neurons on diamond – A substrate for neurodegeneration research and therapy
Authors: Paul A. Nistor, Paul W. May, Francesco Tamagnini, Andrew D. Randall, Maeve A. Caldwell
Journal: Biomaterials (2015)

Brain Computer Interfaces (BCI) currently represent a field of intense research aimed both at understanding neural circuit physiology and at providing functional therapy for traumatic or degenerative neurological conditions. Due to its chemical inertness, biocompatibility and stability, diamond is currently being actively investigated as a potential substrate material for culturing cells and for use as the electrically active component of a neural sensor. Here we provide a protocol for the differentiation of mature, electrically active neurons on microcrystalline synthetic thin-film diamond substrates starting from undifferentiated pluripotent stem cells. Furthermore, we investigate the optimal characteristics of the diamond microstructure for long-term neuronal sustainability. We also analyze the effect of boron as a dopant for such a culture. We found that the diamond crystalline structure has a significant influence on the neuronal culture unlike the boron doping. Specifically, small diamond microcrystals promote higher neurite density formation. We find that boron incorporated into the diamond does not influence the neurite density and has no deleterious effect on cell survival.
A randomized trial of methotrexate versus azathioprine for severe atopic eczema
Authors: Mandy Elvira Schram, Evelien Roekevisch, Mariska Maria Geertruida Leeflang, Jan Dositheus Bos, Jochen Schmitt, Phyllis Ira Spuls
Journal: Journal of Allergy and Clinical Immunology (2011)
A postgraduate journal in a medical institute.
Authors: J R Heron
Journal: BMJ (1979)

and conclusionsThe opinions of 600 randomly selected doctors on what should be taught to undergraduates in clinical years were analysed.The respondents gave a high priority to general medicine, paediatrics, general surgery, casualty, and gynaecology, but a low priority to forensic medicine, plastic surgery, radiotherapy, anaesthetics, radiology, and rehabilitation medicine.Doctors thought that these should be taught to postgraduates.The two major groupings of doctors-general practitioners and consultants-gave essentially the same priorities.Undergraduate curricula cannot include all major specialties, so the results of this analysis may provide a useful basis for selecting the most suitable subjects.Criteria for including other specialties might be the ability and enthusiasm of the teachers and well-thoughtout and academically sound teaching programmes.