tbuckley/cabot-search huggingface dataset:
Abstract 3739: TAK-733, an investigational, selective MEK1/2 inhibitor, in combination with alisertib (MLN8237), an investigational, selective Aurora A kinase inhibitor is tolerated and results in additive to synergistic antitumor activity: Results from In Vivo Studies
Authors: Robyn Fabrey, Shawn O'Connell, Andrew Stanton, Arijit Chakravarty, Esha Gangolli, Jeffery Ecsedy, Jodi Zarycki, Patrick Vincent
Journal: Cancer Research (2012)

Abstract MEK and Aurora A kinase inhibitors (AAK) have profound impacts on cell cycle progression. Inhibition of MEK leads to defects in cell-cycle progression followed by cell cycle arrest and/or apoptosis. These cell-cycle progression defects may in part be due to the role of MEK in the DNA replication or damage checkpoint responses through positive regulation of DNA repair mechanisms. AAK inhibition leads to chromosome congression and segregation defects leading to DNA damage followed by apoptosis or senesence. The overlapping biological effects of inhibition of AAK and MEK kinases in cell cycle progression and chromosomal integrity raise the possibility that inhibiting both targets would provide added benefit over the inhibition of either target alone. The in vivo antitumor activity of TAK-733, an investigational potent, selective, non-ATP-competitive allosteric inhibitor of MEK, in combination with alisertib, an investigational potent, selective, reversible, ATP-competitive inhibitor of Aurora A kinase, was examined in experimental human solid tumor xenograft models including NSCLC (NCI H23 [KRAS and LKB1 mutations]), CRC (SW620 [KRAS, APC, p53 mutations]), and pancreatic cancer (Panc 1 and Capan 1 [KRAS mutations] and BxPC-3 [No MAPK mutations]) models in immunocompromised mice. The previously established maximally efficacious doses for the single agents dosed once daily (QD) orally (PO) (10 mg/kg TAK-733 and 30-mg/kg alisertib) were examined. A lower dose of 20 mg/kg alisertib was also examined in the event the maximally efficacious dose of each agent was not tolerated in combination. The once daily (QD) concurrent oral administration of TAK-733 and alisertib resulted in additive to synergistic antitumor activity and in prolonged inhibition of tumor regrowth after terminating treatment compared to single agent treatment in all xenograft models examined. Concurrent administration of TAK-733 and alisertib daily for 21 days was well tolerated. Treatment with TAK-733 alone and in combination with alisertib clearly inhibited phosphorylated ERK and produced a slight increase in phosphorylated histone H3. The results from the nonclinical models examined demonstrate considerable improvement in nonclinical antitumor activity over either single agent alone and provide a biological rationale for clinical evaluation of a TAK-733/alisertib combination in patients with advanced malignancies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3739. doi:1538-7445.AM2012-3739
Continuous glucose monitoring in women with diabetes during pregnancy
Authors: M. R Festin
Journal: BMJ (2008)

Can improve outcomes alongside other standard interventions 

The diagnosis and management of diabetes that presents during pregnancy has always been difficult. Women are usually asymptomatic and are not aware that the condition may occur for the first time during pregnancy. The prevalence varies from 1.4% to 14% depending on the population.1 Women who are first found to have abnormal glucose concentrations during pregnancy form a heterogeneous group, which includes women with unrecognised pre-existing type 2 diabetes and small numbers of women with unrecognised type 1 diabetes.2 Once the diagnosis of diabetes is established in a pregnant woman, blood glucose concentrations should be controlled to decrease the risk of maternal and neonatal complications.

The linked randomised controlled trial by Murphy and colleagues (doi:10.1136/bmj.a1680) compares the effects of standard antenatal care with and without continuous glucose monitoring in 71 women with type 1 or type 2 diabetes. Continuous glucose monitoring was used as an educational tool to inform shared decision making and subsequent therapeutic changes at four to six week intervals during pregnancy.3

Most methods of monitoring glucose in pregnant women are the same as those used in non-pregnant patients with diabetes and …
Safe Use of Latex Rubber
Authors: Gordon L. Sussman
Journal: Annals of Internal Medicine (1995)

Letters1 August 1995Safe Use of Latex RubberGordon L. Sussman and Donald H. BeezholdGordon L. SussmanEmory Clinic; Atlanta, GA 30322The New York Hospital-Cornell Medical Center; New York, NY 10021Guthrie Foundation for Medical Research; Sayre, PA 18840. and Donald H. BeezholdEmory Clinic; Atlanta, GA 30322The New York Hospital-Cornell Medical Center; New York, NY 10021Guthrie Foundation for Medical Research; Sayre, PA 18840.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-3-199508010-00015 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Latex allergy is a significant occupational hazard affecting 5% to 10% of health care workers. Latex-related illness causes severe morbidity and potentially life-threatening anaphylactic shock [1]. A clear hospital policy is necessary to deal with this increasingly important problem.Nonallergenic natural rubber latex is not currently available. Because latex-allergic patients have reported severe clinical allergy to low-protein latex gloves, we cannot recommend their use in persons with a positive history, skin test result, or radioallergosorbent test result. Patients with clear histories of latex-induced contact urticaria, rhinitis, conjunctivitis, asthma, and anaphylaxis can safely use most nonlatex alternatives to prevent ...References1. Ownby DR, Tonlanovich M, Sammons N, McCullough J. Anaphylaxis associated with latex allergy during barium enema examinations. AJR Am J Roentgenol. 1991; 156:903-8. Google Scholar2. Korniewicz DM, Laughton BE, Cyr WH, et al. Leakage of virus through used vinyl and latex examination gloves. J Clin Microbiol. 1990; 28:787-8. Google Scholar3. Tarlo SM, Sussman GL, Contala A, Swanson MC. Control of airborne latex by use of powder-free latex gloves. J Allerg Clin Immunol. 1994; 93:985-9. Google Scholar4. Beck WC, Beezhold DH. Starch powder should follow talc into limbo (Editorial). J Am Coll Surg. 1994; 178:185-6. Google Scholar Author, Article, and Disclosure InformationAffiliations: Emory Clinic; Atlanta, GA 30322The New York Hospital-Cornell Medical Center; New York, NY 10021Guthrie Foundation for Medical Research; Sayre, PA 18840. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1995Volume 123, Issue 3Page: 234-235KeywordsAllergensAllergy and immunologyHealth care providersLatexRadioallergosorbent testRhinitisShockSkin testsSurgeryUrticaria Issue Published: 1 August 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Multiple vaccinations, health, and recall bias within UK armed forces deployed to Iraq: cohort study
Authors: D. Murphy, M. Hotopf, S. Wessely
Journal: BMJ (2008)

To assess the relation between self reported number of vaccinations received and health, and between numbers of vaccinations recorded from individuals' medical records and health.First phase of a cohort study.UK armed forces personnel.4882 randomly selected military personnel deployed to Iraq since 2003 and a subset of 378 whose vaccination records were accessed.Psychological distress, fatigue, symptoms of post-traumatic stress disorder, health perception, and multiple physical symptoms.Personnel who reported receiving two or more vaccinations on a single day were more likely to report symptoms of fatigue (adjusted risk ratio 1.17, 95% confidence interval 1.05 to 1.30), show caseness according to the general health questionnaire (1.31, 1.13 to 1.53), and have multiple physical symptoms (1.32, 1.08 to 1.60). These associations were no longer significant when number of vaccinations recorded in individuals' medical records was used as the independent variable.Multiple vaccinations given to personnel in the UK armed forces in preparation for deployment to Iraq are not associated with adverse health consequences when vaccinations are recorded objectively from medical records. Adverse health consequences associated with self reported multiple vaccinations could be explained by recall bias.
HLA-matched sibling bone marrow transplantation for β-thalassemia major
Authors: Mitchell Sabloff, Mammen Chandy, Zhiwei Wang, Brent R. Logan, Ardeshir Ghavamzadeh, Chi-Kong Li, Syed Mohammad Irfan, Christopher N. Bredeson, Morton J. Cowan, Robert Peter Gale, Gregory A. Hale, John Horan, Suradej Hongeng, Mary Eapen, Mark C. Walters
Journal: Blood (2010)
MALIGNANT DISEASE OF THE NASAL CAVITY SHOWING THE VALUE OF EARLY DIAGNOSIS.
Authors: J. H. SHORTER
Journal: JAMA (1896)

I will mention briefly a case of what proved to be malignant tumor of the interior of the nose, to show what differences of opinion as to diagnosis, there may be among competent men. It was the case of a gentleman, sent to me from Milledgeville, Ga., about a year ago. He complained of a lump on the side of his neck under the jaw, and a feeling of obstruction in the left nostril. I found a large polypoid growth in the upper part of the left nasal cavity, which I presume sprang from the ethmoid, and which I thought presented the appearance of malignancy. I removed a large piece, examined it, and also had it examined by a competent microscopist, who pronounced it a carcinoma. I informed the patient's family physician of the confirmation of my opinion, and recommended an immediate operation, as the only hope of relief, though
Force and velocity of sarcomere shortening in trabeculae from rat heart. Effects of temperature.
Authors: P P de Tombe, H E ter Keurs
Journal: Circulation Research (1990)

The effect of temperature on the force-sarcomere velocity relation (20 degrees, 25 degrees, and 30 degrees C) and maximum velocity of sarcomere shortening (Vo; range 15 degrees-35 degrees C) was studied in trabeculae from rat heart. Sarcomere length and Vo were measured by laser diffraction techniques. Sarcomere length and sarcomere velocity, determined from each of the first-order diffraction lines, differed by less than 4%. Slack sarcomere length in the trabeculae appeared to be 1.9 microns. Isovelocity release techniques were used to obtain sarcomere velocity and Vo directly. Sarcomere velocity was measured at SL = 1.9-2.0 microns for elimination of contributions of parallel elastic force and restoring force to the external load of the sarcomeres. Peak twitch force development (Fo) was maximal (Fo-max) at 25 degrees C at [Ca2+]o = 1.5 mM. Lowering of the temperature below 25 degrees C led to development of spontaneous sarcomere activity and depression of Fo; both responses could be prevented by the addition of 0.5 mM procaine. Increase of temperature above 25 degrees C reduced twitch duration and Fo. Hill's rectangular hyperbola fitted the force-velocity data if the load during shortening was less than 70% of Fo. Vo appeared to be independent of the level of activation at all temperatures when Fo was maintained above 90% of Fo-max, either by an increase of [Ca2+]o (to 3.0 mM) or by paired pulse stimulation. Vo increased with increasing temperature; the parameter a, calculated from force-velocity relations measured at 20 degrees, 25 degrees, and 30 degrees C, decreased with increasing temperature. The Arrhenius plot of Vo was studied in detail over a wider temperature range (15 degrees-35 degrees C) and in smaller temperature increments. The relation was linear between 18 degrees and 33 degrees C; the observed Q10, defined as the ratio of Vo measured at temperature (T) over Vo at T-10 degrees C, was 4.6 A Q10 of 4.6 for Vo is consistent with the reported temperature dependence of rat cardiac actin-activated myosin ATPase, which suggests that the same reaction step may limit the activity of the enzyme in vitro and during shortening of the cardiac sarcomeres at zero external load.
Experimental and observational methods of evaluation
Authors: N Black
Journal: BMJ (1994)

want to lose the benefits.It seems we are each unwittingly introducing a different bias by what we say.If randomised clinical trials in cancer are to be successful in recruiting patients, clinicians need more guidance on what is meant by informed consent and how to obtain it.An article by Tobias and Souhami2 and subsequent correspondence3 aired some of the issues but did not help with the practicalities.Perhaps the BMJ could commission a "How to do it" article-or is it too difficult?
Israeli transplant surgeon is arrested for suspected organ trafficking
Authors: Merav Sarig
Journal: BMJ (2007)

A leading kidney transplant surgeon from Israel has been arrested in Turkey on suspicion of involvement in an illegal organ transplantation ring that performed operations at a private hospital in Istanbul.

Zaki Shapira, former head of the transplant centre at Rabin Medical Center in Petah Tikva, to the north east of Tel Aviv, was arrested in the course of a gun battle between police and armed robbers at the hospital on 27 April. Turkish doctors and hospital staff were also arrested.

Turkish sources say that police officers who searched the hospital after the shooting discovered …
Comparison of recombinant timothy grass pollen allergens with natural extract for diagnosis of grass pollen allergy in different populations☆, ☆☆, ★
Authors: S LAFFER, S SPITZAUER, M SUSANI, H PAIRLEITNERA, C SCHWEIGER, H GRONLUNDD, G MENZ, G PAULI, T ISHII, H NOLTE
Journal: Journal of Allergy and Clinical Immunology (1996)
Oxidative stress fuels Trypanosoma cruzi infection in mice
Authors: Claudia N. Paiva, Daniel F. Feijó, Fabianno F. Dutra, Vitor C. Carneiro, Guilherme B. Freitas, Letícia S. Alves, Jacilene Mesquita, Guilherme B. Fortes, Rodrigo T. Figueiredo, Heitor S.P. Souza, Marcelo R. Fantappié, Joseli Lannes-Vieira, Marcelo T. Bozza
Journal: Journal of Clinical Investigation (2012)

Oxidative damage contributes to microbe elimination during macrophage respiratory burst. Nuclear factor, erythroid-derived 2, like 2 (NRF2) orchestrates antioxidant defenses, including the expression of heme-oxygenase-1 (HO-1). Unexpectedly, the activation of NRF2 and HO-1 reduces infection by a number of pathogens, although the mechanism responsible for this effect is largely unknown. We studied Trypanosoma cruzi infection in mice in which NRF2/HO-1 was induced with cobalt protoporphyrin (CoPP). CoPP reduced parasitemia and tissue parasitism, while an inhibitor of HO-1 activity increased T. cruzi parasitemia in blood. CoPP-induced effects did not depend on the adaptive immunity, nor were parasites directly targeted. We also found that CoPP reduced macrophage parasitism, which depended on NRF2 expression but not on classical mechanisms such as apoptosis of infected cells, induction of type I IFN, or NO. We found that exogenous expression of NRF2 or HO-1 also reduced macrophage parasitism. Several antioxidants, including NRF2 activators, reduced macrophage parasite burden, while pro-oxidants promoted it. Reducing the intracellular labile iron pool decreased parasitism, and antioxidants increased the expression of ferritin and ferroportin in infected macrophages. Ferrous sulfate reversed the CoPP-induced decrease in macrophage parasite burden and, given in vivo, reversed their protective effects. Our results indicate that oxidative stress contributes to parasite persistence in host tissues and open a new avenue for the development of anti-T. cruzi drugs.
Edmund Hey – a personal appreciation
Authors: Iain Chalmers
Journal: Journal of the Royal Society of Medicine (2010)

Edmund Hey was my friend and colleague for over 30 years, and a fellow campaigner for human rights during the decade before he died. With others, we worked together to expose untruths propagated about paediatricians and paediatric nurses in Stoke on Trent, and to draw attention to the resulting injustices they suffered. The series of articles in the JRSM provides a record of a cynically manufactured ‘non-scandal’, and the damage it has caused. The series begins and ends by emphasizing that allegations of research misconduct should be judged only after the facts have been ascertained by suitably qualified forensic investigators.
Epidemic Bronchiolitis in Infants
Authors: M. E. Disney, B. R. Sandiford, J. Cragg, J. Wolff
Journal: BMJ (1960)

Many good descriptions of epidemic bronchiolitis in infants (Hubble and Osborn, 1941; Garrow and Fawcett, 1953; Heycock and Noble, 1956) have appeared in recent years.Further articles on therapy by Morrison (1955) and by High (1957) have shown how the best modern treatment can decrease the mortality to 1%.However, its frequent very severe and sudden onset, especially in some of the younger infants, and its wide incidence still cause the death of many of these babies.In spite of advances so far made, it is true to say that we are still ignorant of the amount and frequency of secondary bacterial infection, the exact cause of death, and the cause of the condition itself.With these points in mind we decided to investigate two epidemics occurring in Birmingham in the winters of 1955-6 and 1956-7.In these, a total of 325 infants (under 2 years of age) were admitted to Dudley Road Hospital with acute epidemic bronchiolitis.The first epidemic started in late October, 1955, and continued until early March, 1956.Of the 147 patients admitted, 26.6% required oxygen therapy and 2.7% died.The second epidemic started in December, 1956, with a peak in February, 1957.A total of 178 patients were admitted, of whom 44.3% required oxygen therapy and 5% died (see Chart).Clinically the cases did not differ from those described by Hubble and Osborn (1941) and Heycock and Noble (1956).The majority presented as an upper respiratory 1*2?w'.
Costs of Temporary and Permanent Disability Induced by Diabetes
Authors: Ercilia M Olivera, Esteban Péerez Duhalde, Juan Jose Gagliardino
Journal: Diabetes Care (1991)

Objective To evaluate the indirect costs of diabetes and show their relationship to the chronic complications of diabetes. Research Design and Methods The cost of temporary and permanent disability for diabetic patients was studied in a group of La Plata University employees and in a second group at the government institutions of the Buenos Aires Province during 3 consecutive yr (1984–1986). Results Absences due to temporary disability were similar for the diabetic group without chronic complications and an age-and sex-matched nondiabetic control group. Conversely, diabetic patients with chronic complications had major increases in absences compared with the control subjects. Diabetes mellitus was the third leading cause of permanent disability mainly due to macrovascular and retinal lesions. This disability resulted in an average of 11 yr of work production loss per patient. Conclusions These results suggest that diabetic individuals without complications incur few additional costs compared with nondiabetic individuals. However, once complications appear, the indirect costs are very high, suggesting that secondary preventions of the diabetic complications might be an optimal approach for reducing the health-care burden of diabetes.
A theme issue by, for, and about Africa
Authors: Issiaka Sombie, Nicolas Meda, Odette Ky-Zerbo, Michèle Dramaix-Wilmet, Simon Cousens
Journal: BMJ (2005)

A theme issue by, for, and about Africa Results from Ugandan programme preventing maternal transmission of HIVEditor-Since the efficacy of antiretroviral drugs in preventing HIV transmission from mother to child was first shown, much effort has been devoted in many countries in Africa to implement sustainable regimens. [1]2][3][4] To identify potential reasons affecting uptake we evaluated the five year performance of a programme at St Francis Hospital Nsambya in Kampala, Uganda.The programme included voluntary counselling and confidential HIV testing for pregnant women and administration of antiretroviral prophylaxis in the peripartum period (zidovudine or nevirapine) for HIV positive women.Overall 24 133 women received counselling, 76% (18 384) agreed to be tested, and 2011 (10.9%) were HIV positive; 1341 (66.7% of the HIV positive women) were enrolled in the programme and received antiretroviral drugs.Acceptance of the test increased from 72.7% (9103/12 524) in 2000-2 to 79.9% (9281/11 609) in 2003-4, when a drug access programme became available in the hospital.Acceptance of the test and enrolment in the programme were lower in married or cohabitating women (test acceptance rate 72.9% (7735/10 605)) than single women (78% (860/1106)), indicating that the fear of being identified as HIV positive in the family is still a strong limiting factor and that men could have an important role.Acceptance of the test was lower in women belonging to the local tribe in Kampala (Baganda), probably because of fear of being recognised by hospital health workers.Higher education was associated with a lower prevalence of HIV and a higher enrolment in the programme, confirming that education can have a key role not only in protecting against HIV but also in allowing HIV positive people to benefit from existing measures against the spread of HIV.
Acute myocardial infarction occurring in versus out of the hospital: patient characteristics and clinical outcome
Authors: Ralf Zahn, Rudolf Schiele, Karlheinz Seidl, Thomas Kapp, Hans Georg Glunz, Edwin Jagodzinski, Thomas Voigtländer, Martin Gottwik, Gunther Berg, Helmut Thomas, Jochen Senges
Journal: Journal of the American College of Cardiology (2000)
902-1 Mechanisms of Acute Luminal Enlargement in PTCA and Stent: A Prospective Intravascular Ultrasound Study
Authors: Jean-François Tanguay, Stephen C. Culp, Kevin R. Kruse, Brian A. Armstrong, Marino Labinaz, Brigitta C. Brott, James P. Zidar, Harry R. Phillips, Richard S. Stack
Journal: Journal of the American College of Cardiology (1995)
Role of myocardial restoring forces in the determination of early diastolic peak velocity of fibre lengthening in the conscious dog
Authors: D. CAILLET, B. CROZATIER
Journal: Cardiovascular Research (1982)

Journal Article Role of myocardial restoring forces in the determination of early diastolic peak velocity of fibre lengthening in the conscious dog Get access DOMINIQUE CAILLET, DOMINIQUE CAILLET * From I.N.S.E.R.M. U2, Hôpital Léon Bernard, 94450 Limeil-Brévannes, France *Address for correspondence and reprint requests: D Caillet, MD, I.N.S.E.R.M. U2, Hôpital Léon Bernard, 94450 Limeil-Brevannes, France. Search for other works by this author on: Oxford Academic PubMed Google Scholar BERTRAND CROZATIER BERTRAND CROZATIER From I.N.S.E.R.M. U2, Hôpital Léon Bernard, 94450 Limeil-Brévannes, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 16, Issue 2, February 1982, Pages 107–112, https://doi.org/10.1093/cvr/16.2.107 Published: 01 February 1982
Renal tubular function in glycerol-induced acute renal failure
Authors: Christof Westenfelder, Gilberto J. Arevalo, Paul W. Crawford, Philip Zerwer, Robert L. Baranowski, Fredric M. Birch, Wayne R. Earnest, Ronald K. Hamburger, Richard D. Coleman, Neil A. Kurtzman
Journal: Kidney International (1980)