tbuckley/cabot-search huggingface dataset:
Indications for Marrow Transplantation
Authors: E D Thomas, R A Clift, R Storb
Journal: Annual Review of Medicine (1984)

Marrow grafting, originally considered only for end-stage patients after failure of all other treatment, is now the treatment of choice for a variety of malignant and nonmalignant diseases. Donor and recipient selection and the results of marrow transplantation for various diseases and stages of diseases are summarized.
Health concerns in UK Armed Forces personnel
Authors: Dominic Murphy, Neil Greenberg, Duncan Bland
Journal: Journal of the Royal Society of Medicine (2009)

As a result of the nature of their employment members of the UK Armed Forces may, on occasion, be exposed to physical danger. Although the nature of the occupational hazards they encounter may be predictable, such as enemy action or adverse climactic conditions, they are frequently far more uncertain. Most military professionals acknowledge that they may face danger as part of the job – that is the nature of the military contract. However it is probable that personnel view such danger as resulting from enemy action rather than being caused by their own side. Again the latter is inherent in the military contract – the former is not. In this paper we explore the occupational health concerns connected to the anthrax vaccination and depleted uranium ammunitions used by the UK Armed Forces and their coalition partners, both of which have been the cause of considerable controversy.
Carcinogenicity Test of Acetoxime in MRC-Wistar Rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Sidney S. Mirvish, Shahrokh Salmas, Richard G. Runge
Journal: JNCI Journal of the National Cancer Institute (1982)

Acetoxime was tested for carcinogenicity by chronic administration in the drinking water to male and female outbred MRC-Wistar rats. The dose of 1.0 g/liter was administered 5 days/week for 18 months (total dose, 6.2--7.0 g/rat). The test compound induced benign hepatocellular adenomas in 80% of the males but did not produce tumors in the females. This is the first report that oximes, which are fairly widely used in industry, are tumorigenic.
Airway Inflammation after Controlled Exposure to Diesel Exhaust Particulates
Authors: JULIA A. NIGHTINGALE, RICHARD MAGGS, PAUL CULLINAN, LOUISE E. DONNELLY, DUNCAN F. ROGERS, ROBERT KINNERSLEY, K. FAN CHUNG, PETER J. BARNES, MICHAEL ASHMORE, ANTHONY NEWMAN-TAYLOR
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Epidemiologic evidence suggests a link between morbidity and mortality and levels of particulate matter in the atmosphere. We studied the inflammatory response to inhalation of diesel exhaust particulates (DEP) in normal volunteers. DEP were collected from the exhaust of a stationary diesel engine and were resuspended in an exposure chamber. Ten nonsmoking healthy volunteers were exposed for 2 h at rest to a controlled concentration of DEP (monitored at 200 μ g/m3 particulate matter of less than 10 μ m aerodynamic diameter [PM10]) or air in a double-blind, randomized, crossover study. Exposures were followed by serial spirometry and measurement of pulse, blood pressure, exhaled carbon monoxide (CO), and methacholine reactivity, as well as sputum induction and venesection for up to 4 h after exposure, and a repeat of all these procedures at 24 h after exposure. There were no changes in cardiovascular parameters or lung function following exposure to DEP. Levels of exhaled CO were increased ater exposure to DEP, and were maximal at 1 h (air: 2.9 ± 0.2 ppm [mean ± SEM]; DEP: 4.4 ± 0.3 ppm; p < 0.001). There was an increase in sputum neutrophils and myeloperoxidase (MPO) at 4 h after DEP exposure as compared with 4 h after air exposure (neutrophils: 41 ± 4% versus 32 ± 4%; MPO: 151 ng/ml versus 115 ng/ml, p < 0.01), but no change in concentrations of inflammatory markers in peripheral blood. Exposure to DEPs at high ambient concentrations leads to an airway inflammatory response in normal volunteers.
ELECTROPHORETIC STUDIES ON PR8 INFLUENZA VIRUS
Authors: Gail Lorenz Miller, Max A. Lauffer, W. M. Stanley
Journal: The Journal of Experimental Medicine (1944)

Crude preparations of PR8 influenza virus, obtained by high-speed centrifugation, contain two electrophoretically distinct components. One of these, present to the extent of 10 to 20 per cent, was identified by electrophoresis, centrifuge, and activity tests, as an impurity similar to or identical with a high molecular weight acidic substance shown by Knight to be elaborated by normal uninfected embryos. The other component, present to the extent of 80 to 90 per cent, appeared to represent the active virus. The virus fraction was separated from the impurity by repeated fractional centrifugation. It then appeared homogeneous in the analytical centrifuge and in the Tiselius apparatus, and possessed an isoelectric point at pH 5.3 as measured by the micro-electrophoresis method.
Ultrathin Bronchoscopy with Multimodal Devices for Peripheral Pulmonary Lesions. A Randomized Trial
Authors: Masahide Oki, Hideo Saka, Masahiko Ando, Fumihiro Asano, Noriaki Kurimoto, Katsuhiko Morita, Chiyoe Kitagawa, Yoshihito Kogure, Teruomi Miyazawa
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

The combination of an ultrathin bronchoscope, navigational technology, and endobronchial ultrasound (EBUS) seems to combine the best of mutual abilities for evaluating peripheral pulmonary lesions, but ultrathin bronchoscopes that allow the use of EBUS have not been developed so far.To compare the diagnostic yield of transbronchial biopsy under EBUS, fluoroscopy, and virtual bronchoscopic navigation guidance using a novel ultrathin bronchoscope with that using a thin bronchoscope with a guide sheath for peripheral pulmonary lesions.In four centers, patients with suspected peripheral pulmonary lesions less than or equal to 30 mm in the longest diameter were included and randomized to undergo transbronchial biopsy with EBUS, fluoroscopy, and virtual bronchoscopic navigation guidance using a 3.0-mm ultrathin bronchoscope (UTB group) or a 4.0-mm thin bronchoscope with a guide sheath (TB-GS group).A total of 310 patients were enrolled and randomized, among whom 305 patients (150, UTB group; 155, TB-GS group) were analyzed. The ultrathin bronchoscope could reach more distal bronchi than the thin bronchoscope (median fifth- vs. fourth-generation bronchi; P < 0.001). Diagnostic histologic specimens were obtained in 74% (42% for benign and 81% for malignant lesions) of the UTB group and 59% (36% for benign and 70% for malignant lesions) of the TB-GS group (P = 0.044, Mantel-Haenszel test). Complications including pneumothorax, bleeding, chest pain, and pneumonia occurred in 3% and 5% in the respective groups.The diagnostic yield of the UTB method is higher than that of the TB-GS method. Clinical trial registered with www.umin.ac.jp/ctr/ (UMIN 000003177).
Obstruction of extrahepatic bile ducts by lymphocytes is regulated by IFN-γ in experimental biliary atresia
Authors: Pranavkumar Shivakumar, Kathleen M. Campbell, Gregg E. Sabla, Alexander Miethke, Greg Tiao, Monica M. McNeal, Richard L. Ward, Jorge A. Bezerra
Journal: Journal of Clinical Investigation (2004)

The etiology and pathogenesis of bile duct obstruction in children with biliary atresia are largely unknown. We have previously reported that, despite phenotypic heterogeneity, genomic signatures of livers from patients display a proinflammatory phenotype. Here, we address the hypothesis that production of IFN-gamma is a key pathogenic mechanism of disease using a mouse model of rotavirus-induced biliary atresia. We found that rotavirus infection of neonatal mice has a unique tropism to bile duct cells, and it triggers a hepatobiliary inflammation by IFN-gamma-producing CD4(+) and CD8(+) lymphocytes. The inflammation is tissue specific, resulting in progressive jaundice, growth failure, and greater than 90% mortality due to obstruction of extrahepatic bile ducts. In this model, the genetic loss of IFN-gamma did not alter the onset of jaundice, but it remarkably suppressed the tissue-specific targeting of T lymphocytes and completely prevented the inflammatory and fibrosing obstruction of extrahepatic bile ducts. As a consequence, jaundice resolved, and long-term survival improved to greater than 80%. Notably, administration of recombinant IFN-gamma led to recurrence of bile duct obstruction following rotavirus infection of IFN-gamma-deficient mice. Thus, IFN-gamma-driven obstruction of bile ducts is a key pathogenic mechanism of disease and may constitute a therapeutic target to block disease progression in patients with biliary atresia.
Use of Maternal GHb Concentration to Estimate the Risk of Congenital Anomalies in the Offspring of Women with Prepregnancy Diabetes
Authors: Andrea Guerin, Rosane Nisenbaum, Joel G. Ray
Journal: Diabetes Care (2007)

We sought to determine the absolute risk of having a congenital anomaly in relation to periconceptional GHb concentration among women with prepregnancy diabetes.Two reviewers independently retrieved all cohort studies through a systematic literature search between January 1985 and May 2006. For each study, the absolute risk of having a pregnancy affected by a major or minor structural anomaly (diagnosed either antenatally or up to 28 days after conception) was calculated according to the number of SDs of GHb above the mean for nondiabetic, nonpregnant control subjects. A multilevel logistic-normal model was used to pool the data, which were expressed in tabular and graphic formats.In seven cohort studies, there were 117 anomalies among 1,977 pregnancies. At a periconceptional GHb concentration 0 SD above normal, the absolute risk of a pregnancy affected by a congenital anomaly was approximately 2% (95% CI 0.0-4.4). At 2 SD above normal, the risk was 3% (0.4-6.1), and at 8 SD it was approximately 10% (2.3-17.8). For each 1-SD unit increase in GHb, the associated risk of a congenital malformation increased by an odds ratio of 1.2 (95% CI 1.1-1.4). The risk in relation to A1C followed the same pattern.Using data from a limited number of published studies, a practical aid was developed to optimize use of the GHb and A1C concentrations for estimating the absolute risk of a congenital anomaly in the offspring of women with prepregnancy diabetes.
Novel “Breath Figure”‐Based Synthetic PLGA Matrices for In Vitro Modeling of Mammary Morphogenesis and Assessing Chemotherapeutic Response
Authors: Thiruselvam Ponnusamy, Geetika Chakravarty, Debasis Mondal, Vijay T. John
Journal: Advanced Healthcare Materials (2013)

Biodegradable poly(lactic‐ co ‐glycolic acid) (PLGA) porous films are developed to support mammary cell growth and function. Such porous polymer matrices of PLGA are generated using the easily implemented water‐templating “breath‐figure” technique that allows water droplets to penetrate the nascent polymer films to create a rough porous polymer film. Such breath figure‐based micropatterned porous films show higher epithelial differentiation and growth than the corresponding flat 2D films, and represent the first instance of using them for tissue culture. Specifically, the breath figure morphology supports robust acinar growth with almost double the number of lobular–alveolar units compared to the 2D cultures. Gene profile analysis indicates that the cells grown on porous polymer films show enhanced expressions of mammary differentiation genes (GATA3, EMA, and INTEGB4) but lower the expression of mesenchymal gene (CALLA). Hormonal stimulation of these cultures dramatically increases expression of progenitor marker gene Notch1. Importantly, cells grown on porous PLGA films exhibit an enhanced resistance to doxorubicin treatment in comparison to 2D cultures. Breath‐figure PLGA films show promise in mimicking in vivo mammary functions and can potentially be used to screen chemotherapeutic drugs. The simplicity and ease of fabrication of these polymer films is especially appealing to the development of effective biomaterials to support cell culture and differentiation.
The largest mass gathering
Authors: T J Hodgetts, M W Cooke
Journal: BMJ (1999)

An organised mass gathering has predictable medical problems. Yet emergency care at these events has been criticised as haphazard at best and dangerous at worst, with a wide variation of medical care provision.1 On 31 December 1999 potentially the largest ever series of mass gatherings will occur. What lessons should we apply when planning the millennium celebrations?

No clear definition of a mass gathering exists. Large crowds are commonly associated with leisure events but may occur at religious festivals, parades, and demonstrations and during public disorder. A figure of 1000 has been suggested to constitute a mass gathering,1 and this is reflected in the recommendations for first aid support of one first aider per 1000 people.2 Casualty rates vary considerably with the type of event, category 1 events (short all seater events such as football matches or a concerts) having a lower rate than category 2 (spectators mobile within a defined area often over a long period, as in a fairground or golf tournament).3 At the Los Angeles Olympic Games in 1984, a predominantly all seater event, the casualty rate was 1.6 per 1000 spectators.4 …
“Super surgeries” threaten general practice
Authors: Adrian O'Dowd
Journal: BMJ (2005)

Super sized surgeries and a confusingly large number of ways of accessing NHS care are threats that could “shake general practice to its core,” GPs heard last week at an annual conference.

Doctors at the BMA's local medical committees conference in London voted overwhelmingly for a motion saying the government was misguided over the value it gave to the “super surgeries,” which would bring several services such as dentistry, health visitors, and a pharmacy as well as general practice under one roof, and that they would not improve quality of care.

Dr John Dracass of …
Morphologic and Functional Predictors of Eventual Circulation in the Fetus With Pulmonary Atresia or Critical Pulmonary Stenosis With Intact Septum
Authors: Helena M. Gardiner, Cristian Belmar, Gerald Tulzer, Anna Barlow, Lucia Pasquini, Julene S. Carvalho, Piers E.F. Daubeney, Michael L. Rigby, Fabiana Gordon, Elena Kulinskaya, Rodney C. Franklin
Journal: Journal of the American College of Cardiology (2008)
Higher Risk of Infections with PI3K–AKT–mTOR Pathway Inhibitors in Patients with Advanced Solid Tumors on Phase I Clinical Trials
Authors: Saeed Rafii, Desamparados Roda, Elena Geuna, Begona Jimenez, Karim Rihawi, Marta Capelan, Timothy A. Yap, L. Rhoda Molife, Stanley B. Kaye, Johann S. de Bono, Udai Banerji
Journal: Clinical Cancer Research (2015)

Novel antitumor therapies against the PI3K-AKT-mTOR pathway are increasingly used to treat cancer, either as single agents or in combination with chemotherapy or other targeted therapies. Although these agents are not known to be myelosuppressive, an increased risk of infection has been reported with rapamycin analogues. However, the risk of infection with new inhibitors of this pathway such as PI3K, AKT, mTORC 1/2, or multikinase inhibitors is unknown.
Simultaneous measurement of velocity, diameter, flow and pressure in the ascending aorta of cats. Evaluation of an extractable Doppler ultrasound probe for continuous monitoring of aortic blood flow
Authors: K. MATRE, L. SEGADAL
Journal: Cardiovascular Research (1988)

To evaluate an extractable Doppler ultrasound probe designed for monitoring postoperative aortic flow in infants, simultaneous measurements of velocity, diameter, electromagnetic flow estimates, and pressure in the ascending aorta were recorded in cats. Doppler flow calculators were designed to provide flow estimates based on preset constant or measured instantaneous aortic diameter. Doppler sample volume was extended to about 1.2 X 1.6 X 4.0 mm. By pharmacological interventions, a wide range of flow rates and pressures were obtained, some of which were outside physiological values. The prototype probe described here was well suited for implantation in aortas with outer diameter 8-12 mm. Correlation coefficients between Doppler and electromagnetic estimated flow for 140 samples were 0.908 and 0.959 for constant and instantaneous diameter, respectively. Mean difference between the two methods was calculated, as well as the 95% confidence limits (2SD) of the differences. Limits of agreement, in stable haemodynamic situations without drugs, were -20.0 and 22.4% of mean average flow for constant diameter Doppler flow estimates, and -14.5 and 15.1% of electromagnetic flow values for instantaneous diameter estimates. These limits increased when all samples were taken into account, but the limits for instantaneous diameter estimates were reduced from -33.1 and 32.4 to -23.9 and 19.3% after removal of data obtained during isoprenaline infusion, which introduced extreme high flow/low pressure situations. This Doppler method seems well suited for postoperative monitoring of aortic flow in infants. Errors observed in larger aortas with an asymmetric flow profile do not seem to be present in smaller vessels within normal values of flow and pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Variation in <i>TCF7L2</i> and Increased Risk of Colon Cancer
Authors: Aaron R. Folsom, James S. Pankow, James M. Peacock, Suzette J. Bielinski, Gerardo Heiss, Eric Boerwinkle
Journal: Diabetes Care (2008)

The purpose of this study was to determine whether a variation in the transcription factor 7-like 2 (TCF7L2) gene, which influences diabetes risk, is associated with incidence of cancers.
EFFICACY AND SAFETY OF THE CHOLESTERYL ESTER TRANSFER PROTEIN INHIBITOR ANACETRAPIB AS MONOTHERAPY AND COADMINISTERED WITH ATORVASTATIN IN JAPANESE PATIENTS WITH DYSLIPIDEMIA
Authors: Tamio Teramoto, Hirotaka Numaguchi, Masayoshi Shirakawa, Masashi Kikuchi, Mariko Nakagomi, Christine McCrary Sisk, Satoko Tamura
Journal: Journal of the American College of Cardiology (2012)
Additive antitumour response to the rabbit VX2 hepatoma by combined radio frequency ablation and toll like receptor 9 stimulation
Authors: Barbara Behm, Pietro Di Fazio, Patrick Michl, Daniel Neureiter, Ralf Kemmerling, Eckhart Georg Hahn, Deike Strobel, Thomas Gress, Detlef Schuppan, Thaddaeus Till Wissniowski
Journal: Gut (2014)

<h3>Introduction</h3> Radiofrequency ablation (RFA), a palliative therapeutic option for solid hepatic tumours, stimulates localised and systemic antitumour cytotoxic T cells. We studied how far addition of CpG B oligonucleotides, toll like receptor (TLR) 9 agonists, would increase the antitumoural T cell response of RFA in the highly aggressive VX2 hepatoma. <h3>Methods</h3> Rabbits were randomised to receive RFA, CpG B, their combination or no therapy. The antitumour efficacy of RFA alone or in combination with CpG B was further tested by rechallenging a separate group with intravenously injected VX2 tumour cells after 120 days. Animals were assessed for survival, tumour size and spread, and tumour and immune related histological markers after 120 days. Peripheral blood mononuclear cells were tested for tumour-specific T cell activation and cytotoxicity. Immune modulatory cytokines tumour necrosis factor α, interleukin (IL)-2/IL-8/IL-10/IL-12 and interferon γ, and vascular endothelial growth factor were measured in serum. <h3>Results</h3> Mean survival of untreated animals was 36 days, as compared with 97, 78 and 114 days for RFA, CpG and combination therapy, respectively. Compared with untreated controls, antitumour T cell stimulation/cytotoxicity increased 26/16-fold, 32/17-fold and 50/38-fold 2 weeks after RFA, CpG and combination treatments, respectively. The combination inhibited tumour spread to lungs and peritoneum significantly and prohibited new tumour growth in animals receiving a secondary systemic tumour cell injection. RFA alone induced a Th1 cytokine pattern, while IL-8 and IL-10 were only upregulated in CpG treated animals and controls. <h3>Conclusions</h3> The combination of TLR9 stimulation with RFA resulted in a potentiated antitumour T cell response and cytotoxicity in the VX2 tumour model. Only this combination prevented subsequent tumour spread and resulted in a significantly improved survival, justifying the need for further exploration of the combination of ablative therapies and TLR9 agonists in liver cancer.
<i>In vitro</i> and <i>In vivo</i> Activity of Novel Small-Molecule Inhibitors Targeting the Pleckstrin Homology Domain of Protein Kinase B/AKT
Authors: Sylvestor A. Moses, M. Ahad Ali, Song Zuohe, Lei Du-Cuny, Li Li Zhou, Robert Lemos, Nathan Ihle, A. Geoffrey Skillman, Shuxing Zhang, Eugene A. Mash, Garth Powis, Emmanuelle J. Meuillet
Journal: Cancer Research (2009)

Abstract The phosphatidylinositol 3-kinase/AKT signaling pathway plays a critical role in activating survival and antiapoptotic pathways within cancer cells. Several studies have shown that this pathway is constitutively activated in many different cancer types. The goal of this study was to discover novel compounds that bind to the pleckstrin homology (PH) domain of AKT, thereby inhibiting AKT activation. Using proprietary docking software, 22 potential PH domain inhibitors were identified. Surface plasmon resonance spectroscopy was used to measure the binding of the compounds to the expressed PH domain of AKT followed by an in vitro activity screen in Panc-1 and MiaPaCa-2 pancreatic cancer cell lines. We identified a novel chemical scaffold in several of the compounds that binds selectively to the PH domain of AKT, inducing a decrease in AKT activation and causing apoptosis at low micromolar concentrations. Structural modifications of the scaffold led to compounds with enhanced inhibitory activity in cells. One compound, 4-dodecyl-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide, inhibited AKT and its downstream targets in cells as well as in pancreatic cancer cell xenografts in immunocompromised mice; it also exhibited good antitumor activity. In summary, a pharmacophore for PH domain inhibitors targeting AKT function was developed. Computer-aided modeling, synthesis, and testing produced novel AKT PH domain inhibitors that exhibit promising preclinical properties. [Cancer Res 2009;69(12):5073–81]