tbuckley/cabot-search huggingface dataset:
A randomized trial of metoclopramide and a combination of dexamethasone and lorazepam for prevention of chemotherapy-induced vomiting.
Authors: M Gagen, D Gochnour, D Young, T Gaginella, J Neidhart
Journal: Journal of Clinical Oncology (1984)

In a randomized, crossover design the antiemetic activity of one of the most active single agents, metoclopramide was compared with a combination of dexamethasone and lorazepam. Both regimens were effective, but dexamethasone-lorazepam was significantly better than metoclopramide in preventing (26% versus 13%) or limiting (44% versus 23%) vomiting. Although side effects were more frequent with lorazepam-dexamethasone, the patients generally judged them desirable and overall patient preference was strong (70% versus 12%) for the lorazepam-dexamethasone combination. Patients required supervision and assistance due to lorazepam-induced drowsiness.
Abstract SY07-04: The evolutionary landscape of CLL: Therapeutic implications
Authors: Catherine J. Wu
Journal: Cancer Research (2015)

Abstract Clonal evolution is a key feature of cancer progression and relapse. Recent studies across cancers have demonstrated the extensive degree of intratumoral heterogeneity present within individual cancers. We hypothesized that evolutionary dynamics contribute to the variations in disease tempo and response to therapy that are highly characteristic of chronic lymphocytic leukemia (CLL). We have recently investigated this phenomenon by developing a pipeline that estimates the fraction of cancer cells harboring each somatic mutation within a tumor through integration of whole-exome sequence (WES) and local copy number data (Landau et al., Cell 2013). By applying this analysis approach to 149 CLL cases, we discovered earlier and later cancer drivers, uncovered patterns of clonal evolution in CLL and linked the presence of subclones harboring driver mutations with adverse clinical outcome. Thus, our study, generated from a heterogeneous sample cohort, strongly supports the concept that CLL clonal evolution arises from mass extinction and therapeutic bottlenecks which lead to the emergence of highly fit (and treatment resistant) subclones. We further hypothesized that epigenetic heterogeneity also shapes CLL clonal evolution through interrelation with genetic heterogeneity. Indeed, in recent work, we have uncovered stochastic methylation disorder as the primary cause of methylation changes in CLL and cancer in general, and that this phenomena impacts gene transcription, genetic evolution and clinical outcome. Thus, integrated studies of genetic and epigenetic heterogeneity in CLL have revealed the complex and diverse evolutionary trajectories of these cancer cells. Immunotherapy is exquisitely suited for specifically and simultaneously targeting multiple lesions. We have developed an approach that leverages whole-exome sequencing to systematically identify personal tumor mutations with immunogenic potential, which can be incorporated as antigen targets in multi-epitope personalized therapeutic vaccines. We are pioneering this approach in an ongoing trial in melanoma and will now expand this concept to address diverse malignancies. Our expectation is that the choice of tumor neoantigens for a vaccine bypasses thymic tolerance and thus generates highly specific and potent high-affinity T cell responses to eliminate tumors in any cancer, including both ‘trunk’ and ‘branch’ lesions. Citation Format: Catherine J. Wu. The evolutionary landscape of CLL: Therapeutic implications. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY07-04. doi:10.1158/1538-7445.AM2015-SY07-04
Physicians and Insider Trading
Authors: Aaron S. Kesselheim, Michael S. Sinha, Steven Joffe
Journal: JAMA Internal Medicine (2015)

Although insider trading is illegal, recent high-profile cases have involved physicians and scientists who are part of corporate governance or who have access to information about clinical trials of investigational products. Insider trading occurs when a person in possession of information that might affect the share price of a company's stock uses that information to buy or sell securities--or supplies that information to others who buy or sell--when the person is expected to keep such information confidential. The input that physicians and scientists provide to business leaders can serve legitimate social functions, but insider trading threatens to undermine any positive outcomes of these relationships. We review insider-trading rules and consider approaches to securities fraud in the health care field. Given the magnitude of the potential financial rewards, the ease of concealing illegal conduct, and the absence of identifiable victims, the temptation for physicians and scientists to engage in insider trading will always be present. Minimizing the occurrence of insider trading will require robust education, strictly enforced contractual provisions, and selective prohibitions against high-risk conduct, such as participation in expert consulting networks and online physician forums, by those individuals with access to valuable inside information.
Efficacy of early COPD diagnosis and intervention system
Authors: Kenichiro Tanaka, Takako Tanaka, Yuichi Tawara, Masaharu Asai, Tsuyoshi Nishinakagawa, Masatoshi Itaki, Ryo Kozu, Hideaki Senjyu
Journal: European Respiratory Journal (2014)

Background 

Early detection and diagnosis of chronic obstructive pulmonary disease (COPD) is essential to maintain patients' physical function. We have established a novel COPD screening system for early diagnosis and treatment of 50- to 80-year-old local residents with an FEV1% of <70%.

Objective 

To verify the efficacy of this medical examination system according to changes in physical function during a 5-year intervention period.

Methods 

All participants (21 patients with COPD and 25 healthy subjects with an FEV1% of ≥70%) were inhabitants of Matsuura, Nagasaki Prefecture and underwent community medical examinations in 2006 and 2011. For 5 years, pulmonary function tests were performed once yearly, and patient education was implemented two to four times yearly. The evaluation items were age, body mass index, pulmonary function test results (VC, %VC, FVC, FEV1, %FEV1, and FEV1%), the variation of 1 year, and grip strength.

Results 

Patients with COPD were significantly older than healthy subjects, while all patients' pulmonary function was significantly lower than that of healthy subjects. The %VC decreased at a significantly lower rate in the patients. The FVC and FEV1 showed a similar tendency; however, the rate of grip strength decline was significantly higher in the patients.

Conclusions 

Pulmonary function and grip strength decreased with age in both the patients and healthy subjects. However, the COPD interventions effectively suppressed the decrease in pulmonary function in the patients to a greater degree than the normal age-associated decline. COPD examination is now optional in Japan, but we hope that local residents become obligated to undergo the examination to allow for early diagnosis and treatment of potential COPD.
Abstract 3652: Surface expression and shedding of NKG2D ligands by (metastasizing) tumor cells is altered by platelets leading to impaired NK cell immunosurveillance
Authors: Stefanie Raab, Korbinian Nepomuk Kropp, Alexander Steinle, Gerd Klein, Hans-Georg Kopp, Helmut R. Salih
Journal: Cancer Research (2014)

Abstract NK cells play an important role in anti-tumor immunity. The mechanisms leading to NK cell activation are described by the ‘missing-self’ and ‘induced-self' hypotheses, implying that cells with low or absent expression of MHC class I and stress-induced expression of ligands for activating receptors such as NKG2D (NKG2DL), are targeted by NK cells. Besides the direct interaction with their target cells, NK activity is also influenced by various other hematopoietic cells. In mouse models, thrombocytopenia impairs metastasis, and this is reversed by additional depletion of NK cells. Hence, the knowledge of the underlying molecular mechanisms by which platelets influence NK cells is still fragmentary. We already showed that release of TGF-β by platelets upon their interaction with (metastasizing) tumor cells downmodulates the activating receptor NKG2D on NK cells (Kopp et al, Cancer Res. 2009; Placke, J Innate Immun. 2011). Moreover, platelets transfer ´healthy´ MHC class I to the tumor cell surface. Thus, platelets may facilitate metastasis by interfering with both, ‘induced and missing self' NK cell recognition. Here we provide evidence for a yet unknown mechanism by which platelets further impair NKG2D-mediated immunosurveillance. Tumor cells were incubated with platelets from healthy donors resulting in coating of tumor cells and activation of the platelets, or treated with platelet-derived soluble factors (releasate) obtained either by tumor cell-induced platelet activation (TCIPA) or the platelet agonist thrombin. Presence of platelet derived factors derived either from coating of tumor cells or contained in platelet releasate substantially reduced surface expression of NKG2DL on tumor cells. This was paralleled by enhanced levels of soluble NKG2DL in culture supernatants, indicating that platelet-derived factors mediate NKG2DL shedding from the tumor cell surface. Diminished NKG2DL surface expression resulted in diminished NKG2D-dependent natural cytotoxicity of NK cells, as revealed by blocking experiments using NKG2D antibody and NKG2DL-specific F(ab)2 fragments targeting the specifically modulated NKG2DL. Our data thus identify induction of NKG2DL shedding as novel mechanism by which interaction of platelets with metastasizing tumor cells impairs NK cell immunosurveillance. Citation Format: Stefanie Raab, Korbinian Nepomuk Kropp, Alexander Steinle, Gerd Klein, Hans-Georg Kopp, Helmut R. Salih. Surface expression and shedding of NKG2D ligands by (metastasizing) tumor cells is altered by platelets leading to impaired NK cell immunosurveillance. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3652. doi:10.1158/1538-7445.AM2014-3652
Israel to allow women to donate their ova
Authors: Judy Siegel-Itzkovich
Journal: BMJ (2001)

A 15 year old Israeli law that has barred all women, other than those undergoing infertility treatment, from donating their ova will be replaced soon by a detailed law that actually encourages such donation.

The original law was instituted to prevent the sale of ova. Health officials and legislators thought that permitting donations only by those women whose ova were being removed for in vitro fertilisation would prevent the illegal sales of eggs. But the law had the effect of severely restricting the supply of donated eggs, with the result that about 2000 women in Israel are now waiting …
Risk of respiratory hospital admission in preterm children
Authors: Oleksandr Mazulov
Journal: European Respiratory Journal (2014)

BACKGROUND 

Prematurely born children have many health features including respiratory morbidity. We investigate a risk of emergency respiratory hospital admission children during first 3 years of life associated with gestational age at birth.

METHODS 

We analysed a population of 647 children born from 2006 to 2009 in Vinnitsa region in Ukraine who were prematurely born and were treated in Children's Regional Hospital due to different reasons. The main outcome measure was emergency respiratory hospital admission.

RESULTS 

Children with gestational age less than 40 weeks had an increased risk of emergency hospital admissions for respiratory conditions compared with infants born on time (adjusted hazard ratio 1.10; 95% CI 1.06-1.15). The rate of admission in the first year of life was from 38.5 per 100 child-years for infants born before 33 weeks of gestation to 7.4 per 100 child-years for infants born up to 40 weeks of gestation. The risk of any emergency respiratory admission up to 3 years increased as gestational age decreased to <40 weeks.

CONCLUSIONS 

The risk of emergency respiratory admission in premature children higher than in with normal gestational age up to age 3 years and it decreased with each next week in gestation up to 40 weeks.
Attitude of chest physicians working in provincial state hospitals, in Turkey toward continous medical education
Authors: Tarkan Ozdemir, Leyla Yilmaz Aydin
Journal: European Respiratory Journal (2011)

Introduction:  Continuing medical education is carried out primarily by medical associations. Bulletins are published on method.   Aim:  To investigate post-training status and trends regarding this issue of chest physicians working in provincial state hospitals   Methods:  Questionnaires, that consist of 18 questions about years of work, institution, participation in congresses and training activities, regular follow-up of publications and web sites, views about post- training; with permission of Ministry of Health; was sent to chest physicians. Participants, completed the questionnaire and sent back anonymously.   Results:  85 of 130 chest physicians in 36 provinces participated. Response rate was 65%. Average working years was 15.05±8.40. 44.7% were working in state hospitals and 54.1% were in chest disease hospitals. Participation to congresses on last 2 years was 3.59±1.62. 28.2% were attending education meetings regularly. 38.8% answered question of “Do you follow a publication regularly?” with “No”. Participants who do not follow the web sites was 34.1%. While years of work increased, follow-up of web sites decreased (p=0,00).  Question of “Do you feel yourself declined in terms of professional information and facilities sometimes?” replied “Yes” by 58.8%.  Question of “Do you want to go institutions providing education on a temporary working for educational purposes” replied “yes” by who feel themselves declined in terms of professional information (p=0,008).   Conclusion:  We found that our colleagues have been less interested in training activities.Training activities, independent of personal initiatives, will increase self-confidence and professional qualifications.
Measurement and analysis of the common food allergens specific IgE
Authors: Huimin Huang, Nili Wei, Wenting Luo, Peiyan Zheng, Baoqing Sun
Journal: European Respiratory Journal (2014)

Objective To discuss and analyse the correlation of the positive rate of common food allergen sIgE with suspected food allergy patients in our hospital. Methods Using fluorescence enzyme-linked immunosorbent assay to detect the serum sIgE antibody of the patients ,including 7 kinds of food allergens(milk, egg white, egg yolk, peanut, soybean, shrimp and crab) from July 2006 to January 2013. Results The positive rates of the 7 kinds of food allergen were 39.3%(283/720),36.3(216 /595),9.8%(28/285),21.2%(36/170),24.3%(17/70),14.8%(9/61)and10.0%(5/50). 528 patients were detected milk and egg white sIgE, the positive rate of milk sIgE was 35.2% , the positive rate of egg white was 33.7% , 26.9% were both positive (r s =0.758,  P  s  =0.973,  P  s =0.879,  P
Abstract P182: Usefulness of Mobile Telemedicine System in Real-time Transmission of Out-of-hospital 12-lead ECG
Authors: Hiroshi Nonogi, Hiroyuki Yokoyama, Yoritaka Otsuka, Yoichiro Kasahara, Yu Kataoka, Nobuaki Kokubu, Kazuhiro Sase
Journal: Circulation (2008)

[Purpose] AHA/ACC guidelines recommend routine use of 12-lead ECG and advance notification for patients with acute coronary syndrome. However, transmission of out-of-hospital 12-lead ECG to emergency department is still not spread and ECG interpretation on the prehospital and emergency department is not established. Therefore, we have developed and tested the clinical usefulness of the mobile telemedicine system to transmit 12-lead ECG between moving ambulances and physicians in cardiovascular emergency. [Method] We set up the mobile telemedicine using the third-generation digital mobile phone to promote communications between an ambulance and diverse hospital. Compatibility issue among device vendors was solved by the implementation of open-standard medical waveform encoding rule with motion noise-reduction system. Real time 12-lead ECG was transferred together with vital signs and live video during transfer the patient by an ambulance. The performance of the mobile telemedicine system in the field-test was checked to transfer 12-lead ECG in different scenarios such as transferred ECG from a volunteer moving hand or leg, coughing or twisting body in an ambulance driving on common road or highway. In the next step, we set up the mobile telemedicine on an ambulance to promote communications between moving 5 ambulances in Suita-city and National Cardiovascular Center since 2008 June 2. To establish the efficacy of real-time transmission of out-of-hospital 12-lead ECG, the time-line from the onset of acute myocardial infarction to reperfusion is analyzed. [Results] Totally 36 patters of 12-lead ECG were checked in the field test and all of them were comparable than those original one in the ambulance. Time-delay for transmission of 12 lead ECG was within 10seconds and for one-lead ECG monitoring and vital signs including BP, HR and oxygen saturation was 1 second without the difficulties for the interpretation. [Conclusion] Those results indicate the usefulness and reliability of transmission of 12-lead ECG using the mobile telemedicine system from the ambulance. Further investigation is on-going to determine the efficacy in clinical conditions to reduce the treatment delay for acute myocardial infarction.
Liposomal doxorubicin extravasation controlled by phenotype-specific transport properties of tumor microenvironment and vascular barrier
Authors: Kenji Yokoi, Diana Chan, Milos Kojic, Miljan Milosevic, David Engler, Rise Matsunami, Tomonori Tanei, Yuki Saito, Mauro Ferrari, Arturas Ziemys
Journal: Journal of Controlled Release (2015)
Bronchiectasis Is a Model for Chronic Bacterial Infection Inducing Autoimmunity in Rheumatoid Arthritis
Authors: Anne‐Marie Quirke, Elizabeth Perry, Alison Cartwright, Clive Kelly, Anthony De Soyza, Paul Eggleton, David Hutchinson, Patrick J. Venables
Journal: Arthritis & Rheumatology (2015)

To examine the potential of chronic severe bacterial infection to generate rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs), by studying patients with bronchiectasis (BR) alone and BR patients with rheumatoid arthritis (BR/RA).We studied 122 patients with BR alone, 50 patients with BR/RA, and 50 RA patients without lung disease, as well as 87 patients with asthma and 79 healthy subjects as controls. RF levels were measured using an automated analyzer, and cyclic citrullinated peptide 2 (CCP-2) was used to detect ACPAs. The fine specificities of citrullinated α-enolase peptide 1 (CEP-1), Cit-vimentin, and Cit-fibrinogen to their arginine-containing control peptides (arginine-containing α-enolase peptide 1 [REP-1], vimentin, and fibrinogen) were measured by enzyme-linked immunosorbent assay.Among the BR patients and control subjects, 39% and 42%, respectively, were ever-smokers. The frequency of RF positivity in serum was increased in BR patients compared with controls (25% versus 10%), as were the frequencies of antibodies to CCP-2 (5% versus 0%), CEP-1 (7% versus 4%), Cit-vimentin (7% versus 4%), and Cit-fibrinogen (12% versus 4%), although only the differences for RF and Cit-fibrinogen were significant (P < 0.05). We observed a corresponding increase in the frequency of antibodies to the arginine-containing control peptides in BR patients compared with controls (for REP-1, 19% versus 4% [P < 0.01]; for vimentin, 16% versus 4% [P < 0.05]), demonstrating that the ACPA response in patients with BR is not citrulline specific. The lack of citrulline specificity was further confirmed by absorption studies. In BR/RA patients, all ACPA responses were highly citrulline specific.Bronchiectasis is an unusual but potent model for the induction of autoimmunity in RA by bacterial infection in the lung. Our study suggests that the ACPA response is not citrulline specific during the early stages of tolerance breakdown but becomes more specific in patients with BR in whom BR/RA develops.
Acetylcysteine for Prevention of Renal Outcomes in Patients Undergoing Coronary and Peripheral Vascular Angiography
Journal: Circulation (2011)

It remains uncertain whether acetylcysteine prevents contrast-induced acute kidney injury.We randomly assigned 2308 patients undergoing an intravascular angiographic procedure with at least 1 risk factor for contrast-induced acute kidney injury (age >70 years, renal failure, diabetes mellitus, heart failure, or hypotension) to acetylcysteine 1200 mg or placebo. The study drugs were administered orally twice daily for 2 doses before and 2 doses after the procedure. The allocation was concealed (central Web-based randomization). All analysis followed the intention-to-treat principle. The incidence of contrast-induced acute kidney injury (primary end point) was 12.7% in the acetylcysteine group and 12.7% in the control group (relative risk, 1.00; 95% confidence interval, 0.81 to 1.25; P=0.97). A combined end point of mortality or need for dialysis at 30 days was also similar in both groups (2.2% and 2.3%, respectively; hazard ratio, 0.97; 95% confidence interval, 0.56 to 1.69; P=0.92). Consistent effects were observed in all subgroups analyzed, including those with renal impairment.In this large randomized trial, we found that acetylcysteine does not reduce the risk of contrast-induced acute kidney injury or other clinically relevant outcomes in at-risk patients undergoing coronary and peripheral vascular angiography.http://www.clinicaltrials.gov. Unique identifier: NCT00736866.
Hydrogen sulphide as a biomarker in COPD and asthma
Authors: Debraj Jash
Journal: European Respiratory Journal (2014)

Background:   Exhaled NO, H 2 S and CO was extensively studied as biomarkers in asthma and COPD. Recent studies proposed role of serum H 2 S as a biomarker in different obstructive airway diseases. Evaluation of the association of serum H 2 S level to COPD and asthma (both in stable state and during exacerbation) was done in our study.   Materials &Methods:   We measured serum levels of H 2 S, spirometry, ell differential counts in induced sputum in 25patients with acute exacerbation of COPD (AECOPD), 65 patients with stable COPD,32 patients with acute exacerbation of asthma,50 patients of controlled asthma and 60 healthy subjects. We studied the relation of serum H 2 S with age, sex, smoking, FEV 1 , sputum differential count.   Results:   There was no significant difference in serum H 2 S level between in relation to age and sex among normal population but there was significant difference among smokers and non-smokers. Serum H 2 S was significantly lower(p  2 S was lower in COPD than asthma but there was no significant difference between them. Serum H 2 S level was significantly higher in patients with stable COPD and controlled asthma than in patients with exacerbations of COPD and in acute exacerbations of asthma. Serum H 2 S level was correlated positively with FEV I  in patients with COPD (r=0.35) and asthma (r= 0.26). Serum H 2 S level was negatively correlated with proportion of neutrophils in sputum (r = - 0.45 in COPD and r = 0.34 in asthma) and positively correlated with proportion of lymphocytes (r = 0.39 in COPD and r = 0.32 in asthma).   Conclusion:   Serum H 2 S may serve as a biomarker in exacerbation of COPD and asthma but more studies are required to arrive at a definite conclusion.