tbuckley/cabot-search huggingface dataset:
Nicholas Mark Alma Oakman
Authors: Simon Harris
Journal: BMJ (2004)

was a renowned nuclear physicist.But what resonates for me, and for the BMJ-at a time when 3000 deaths every day on the world's roads is accepted as the necessary albeit regrettable cost of motorised transportation-is Marcel's contribution as a road safety activist and advocate for justice for those injured and killed.In 1988 Marcel's eldest daughter, Vlasta, died when her car was struck by a speeding driver, who survived, was prosecuted, and was required to pay compensation.Marcel and his family were expected to suffer in silence just like the thousands of other parents who have lost children to road traffic crashes.The state's response to road death is unlike any other form of violent death.There is rarely a proper police investigation, the judicial response is characteristically lackadaisical, and little effort is made to prevent a recurrence.Given the numbers killed and injured each year-over 50 000 deaths and 150 000 permanent disabilities in Europe alone-road death might be thought of as state sanctioned genocide.In many countries, Britain included, road deaths are called "accidents."No one is really responsible and no one is really to blame.Marcel, however, could not accept this.In their fight for justice, those injured on the roads had recruited a formidable ally.Marcel was a scientist, a statesman, and extraordinarily tenacious.He obtained a doctorate in physics at the University of Geneva in 1968.He worked for several years as a
Concurrent involved field radiation therapy and Temsirolimus in refractory mantle cell lymphoma (MCL)
Authors: Youlia M. Kirova, Cyrus Chargari, Malika Amessis, Jean‐Paul Vernant, Nathalie Dhedin
Journal: American Journal of Hematology (2010)

Temsirolimus, an inhibitor of mammalian target of rapamycin, has antitumor activity and improves progress-free survival in patients with relapsed or refractory mantle cell lymdhoma (MCL) [1, 2]. Helical tomotherapy (HT) is an irradiation modality, which combines accurate patient positioning and intensity-modulated fan-beam radiotherapy (RT) [3-5]. Because of highly conformal dose distribution, it improves sparing of critical organs. This is particularly relevant in heavily treated patients who are at risk for subsequent toxicities [3]. This work is reporting the first case in the literature of concurrent use of Temsirolimus and RT in patient before bone marrow transplantation (BMT). A 47-year-old male patient treated since 2003 for Stage IV refractory MCL with over expression of D1 gene and t(11; 14) translocation, was referred in our Department. The patient had been heavily previously treated and had received: six lines chemotherapy, two total body irradiations, one autologous stem cell transplantation, and one allogeneic cord blood transplantation. He experienced lymph node (inguinal and lombo-aortic iliac) and bone marrow relapse in January 2009 and was treated with VELCAD-ARACYTIN-DXM × three cycles, follow by R-CHOP and VELCADE, then REVLIMID with DXM with persistence of the lymph nodes in low mediastinum, lombo-aortic, iliac, and inguinal lymph nodes. New treatment protocol using Temsirolimus as previously reported [2] was offered to the patient and at the same time, he was addressed in our Department for debulking HT before new allogeneic cord blood transplant. The patient received 36 Gy in 18 fractions concurrently with Temsirolimus. The dose distribution is shown in Image 1. The patient was followed weekly clinically and biologically by his radiation oncologist. The clinical tolerance was perfect without any symptoms. The only observed toxicity was Grade III thrombopenia as reported in 59% of patients treated with this protocol of Temsirolimus [2]. Two months after the end of RT, the patient experienced very good response objectived by CT scan and positron emission tomography (PET). Currently, he is ECOG 0 and is prepared for his transplant. Dose distribution, the colors are corresponding to the dose distribution, the helical tomotherapy permitted to omit the organs of risk. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] This first report shows the efficacy and feasibility of concurrent Temsirolimus and HT as a therapeutic option in relapsed or refractory MCL. Prospective studies are needed to confirm this result.
Influence of Home Monitoring on the clinical status of heart failure patients: Design and rationale of the IN‐TIME study
Authors: Arash Arya, Michael Block, Josef Kautzner, Thorsten Lewalter, Heinrich Mörtel, Stefan Sack, Burghard Schumacher, Peter Søgaard, Milos Taborsky, Daniela Husser, Gerhard Hindricks
Journal: European Journal of Heart Failure (2008)
Gains in Life Expectancy from Medical Interventions — Standardizing Data on Outcomes
Authors: Janice C. Wright, Milton C. Weinstein
Journal: New England Journal of Medicine (1998)

The gain in life expectancy is an important measure of the effectiveness of medical interventions, but its interpretation requires that it be placed in context. The interpretation of gains in life expectancy is particularly problematic for preventive interventions, for which the gains are often just weeks or even days when averaged across the entire target population.
Chronic delta hepatitis: Detection of hepatitis delta virus antigen in serum by immunoblot and correlation with other markers of delta viral replication
Authors: Maria Buti, Rafael Esteban, Rosendo Jardi, Francisco Rodriguez-Frias, Jose Casacuberta, Juan Ignacio Esteban, Elena Allende, Jaime Guardia
Journal: Hepatology (1989)

To investigate the presence of serum hepatitis delta virus antigen by immunoblot and its correlation with other markers of active viral replication (intrahepatic hepatitis D antigen, IgM antibody to hepatitis D and serum hepatitis D virus RNA), we studied serum samples from 50 patients with chronic hepatitis D virus infection (38 with and 12 without intrahepatic hepatitis D antigen). Of the 38 patients with intrahepatic hepatitis D antigen, 27 (71%) had antigen detectable in seurm by immunoblot, whereas only two were reactive by conventional enzyme–linked immunosorbent assay. Thirty–one (82%) patients were also positive for serum hepatitis D virus RNA by spot hybridization and 33 (87%) were positive for IgM anti–hepatitis D virus. All markers were simultaneously present in 24 patients. Circulating hepatitis D antigen was detected in one (8%), IgM antihepatitis D in seven (58%) and hepatitis D virus RNA in two (17%) of the 12 patients who had anti–hepatitis D in serum but not detectable hepatitis D antigen in liver. Hepatitis D antigen was not detected in serum of any of the 15 control patients. The results suggest that serum hepatitis D antigen as detected by immunoblot and serum hepatitis D virus RNA are similar in sensitivity for detection of active hepatitis D virus replication during chronic infection and constitute useful, sensitive and noninvasive tests for the diagnosis and monitoring of chronic hepatitis D virus infection.
Heart disease, cancer, and stroke mortality trends and their interrelations. An international perspective.
Authors: T J Thom, F H Epstein
Journal: Circulation (1994)

Changes in mortality from heart disease, cancer, and stroke over recent decades in many countries have received much attention. However, comprehensive and concurrent analyses of these trends and their effect on total mortality have been lacking. Moreover, the extent to which the trends for one disease may relate to those for another disease is unknown. Concordance of trends for major diseases would suggest that they have common causes and thus may be responsive to the same preventive measures.Age-adjusted death rates for total mortality and mortality from heart disease, stroke, lung cancer, and cancer other than lung cancer were obtained for the years 1950 to 1987 in 27 countries by sex and ages 35 to 74 years from the World Health Organization statistical reports. Concordance of mortality trends was assessed for ages 35 to 74 between 1950 and 1983 through visual inspection and semiquantitative measurements of percentage change over time. The epidemic increase in heart disease mortality ended in the 1960s or 1970s in most industrialized countries; death rates often declined very steeply. Stroke mortality also changed from an increase to a decline or from a modest to a steep decline in the 1960s or 1970s. Lung cancer mortality slopes generally changed from a steep increase to either a modest increase, a flat trend, or a decline; the changes in slope are lagging behind those for heart disease and stroke. These improvements influenced trends for total mortality. Cancer other than lung cancer trends are less distinct than those for the three other causes of mortality. Yet, testing them for concordance with heart disease trends reveals that they are mostly concordant on a time-lag analysis that assumes that heart disease responds more rapidly to a change in lifestyle or environment than cancer. Trends for heart disease and lung cancer in men also tend to be concordant on time-lag analysis. Heart disease and stroke trends have become more concordant with time.Trends for mortality from heart disease, stroke, lung cancer, and, less distinctly, cancer other than lung cancer, tend to be similar in different countries, leading to a corresponding similarity in total mortality trends. An analysis of trends for pairs of diseases within countries indicates a tendency toward concordance of trends, suggesting the existence of common causes amenable to the same preventive measures. This analysis of international mortality trends is intended to stimulate further research along these lines, as a guide to preventive and therapeutic action.
Proportion of Adults With Sickle Cell Anemia and Pain Crises Receiving Hydroxyurea
Authors: Nicolas Stettler, Colleen M. McKiernan, Court Q. Melin, Oluwakayode O. Adejoro, Nancy B. Walczak
Journal: JAMA (2015)

The recommendation from the 2014 National Heart, Lung, and Blood Institute guidelines 1 to treat all adults with sickle cell anemia (SCA) and 3 or more moderate to severe pain crises within 1 year with hydroxyurea was rated as strong based on high-quality evidence reviewed in 2008. 2,3Despite benefits in reducing pain crises, hospitalizations, blood transfusions, and possibly mortality, it is thought that hydroxyurea is underused, although the extent of its use is unknown. 2 We sought to document the use of hydroxyurea when indicated for SCA in a large insurance claims database.Methods | Data were obtained from the deidentified Optum Normative Health Informatics database, a nationwide sample of commercial health and pharmacy claims from more than 36 million residents in all 50 states and Washington, DC. 4,5 Compared with the US population, the database has more patients aged 18 to 54 years, 1.3% fewer women, 2.3% fewer blacks, 6.4% fewer Latinos, and 6.8% more whites.Adults (aged ≥18 years) with 1 or more inpatient or outpatient claims between January 1, 2009, and June 30, 2013, for probable SCA were identified using International Classification of Diseases, Ninth Revision (ICD-9) codes 282.61 (HbSS disease without crisis) or 282.62 (HbSS disease with crisis) on at least 2 encounters.Patients were selected when they had 3 or more hospitalizations, emergency department (ED) visits, or both within 12 months that included 1 of the 5 most frequent diagnosis codes used for patients with SCA and pain crises (HbSS disease with crisis [282.62];acute chest syndrome [517.3];pain in limb [729.5];chest pain, unspecified [786.50];other chest pain [786.59]),independent of existing or continuing treatment with hydroxyurea.Treatment was defined as filling 1 or more hydroxyurea prescriptions during the 3, 6, or 12 months of continued enrollment following the third episode.The percentage of treated patients, 95% confidence intervals, and χ 2 for trend were calculated using SAS version 9.3 (SAS Institute Inc).A 2-sided P value of <.05 was considered statistically significant.This analysis was exempted from review by the Western Institutional Review Board.a Data are expressed as No. (%) [95% CI] unless otherwise indicated.
The distinct health risk analyses required for genotoxic carcinogens and promoting agents.
Authors: J H Weisburger, G M Williams
Journal: Environmental Health Perspectives (1983)

Health risk analysis needs to apply newer developments in the understanding of the underlying mechanisms of the carcinogenic process which has allowed for the classification of chemical carcinogens into those that damage genetic material directly (genotoxic carcinogens) and those that operate by indirect or epigenetic mechanisms. We propose a systematic decision point approach for detecting and evaluating substances for carcinogenic risk. This approach recognizes that genotoxic and epigenetic agents operate by different mechanisms and distinguishes between these two categories of carcinogens primarily on the basis of results in a battery of short-term tests that includes systems which reliably detect genotoxic carcinogens and others which may respond to epigenetic agents. Genotoxic carcinogens at very low dosages may have practical, effective threshold no-effect levels, but, nevertheless, because of their mechanism of action they are regarded as a qualitative hazard. The action of epigenetic agents of the promoter class is highly dose-dependent and reversible, and thus, a distinctively different health risk analysis is required for these agents to take account of their quantitatively lesser hazard.
The British Experience in Medical Malpractice: An Upward Trend
Authors: William J. Curran
Journal: New England Journal of Medicine (1973)

AMERICAN physicians generally believe that they are unique in the world in one onerous regard: malpractice suits. There seems to be a quite universal assumption that doctors are sued more often and for more money in the United States than anywhere else. The latest report of the British Medical Defence Union for 1972 casts some doubt on this view.1 The Defence Union represents some 70,000 physicians and dentists and provides them with defense and insurance indemnification in professional-liability suits. It is operated and administered by physicians and dentists on a nonprofit basis and works in close cooperation with the British . . .
The incidence and natural history of pericardial effusion after cardiac surgery--an echocardiographic study.
Authors: L B Weitzman, W P Tinker, I Kronzon, M L Cohen, E Glassman, F C Spencer
Journal: Circulation (1984)

One hundred twenty-two consecutive patients (104 men; 18 women) were studied to determine the incidence and natural history of pericardial effusion occurring 2, 5, 10, and 20 to 50 days after cardiac surgery. Three patients had pericardial effusions before and 103 patients (91 men; three women) had effusions after surgery. Effusions were first recorded on the second postoperative day in 72 patients, on the fifth postoperative day in 29 patients, and on the tenth postoperative day in two patients. In 96 of these patients, effusions reached their maximum size by postoperative day 10. Of the 103 patients with effusions, 66 (64%) were followed to complete resolution. A specific pattern was observed in most resolving effusions. The echo-free space diagnostic of pericardial effusion became progressively more echo-dense as the effusion diminished in size. As the effusion became echo-dense, the posterior pericardium, which had been motionless, resumed its normal systolic anterior motion. One patient developed cardiac tamponade on postoperative day 3. We conclude that pericardial effusion occurs frequently after cardiac surgery, but that associated complications are rare.
Trial Design and Patient Safety — The Debate Continues
Authors: Robert Steinbrook
Journal: New England Journal of Medicine (2003)

On July 3, 2003, nearly a year after it first became involved, the Office for Human Research Protections (OHRP) of the Department of Health and Human Services released its decision about two disputed multicenter clinical trials of treatment for the acute respiratory distress syndrome (ARDS).1,2 In a 15-page letter, the office seems to substantiate the ethical appropriateness and research design of both trials and to refute concern that participants were subjected to unnecessary risks. The OHRP does this by referring to the opinions of outside consultants whom it retained, without taking a position on the controversy itself. However, the . . .
Physiology and Pathology of the Leydig Cell
Authors: Howard L. Bleich, Mary Jean Moore, Mortimer B. Lipsett
Journal: New England Journal of Medicine (1980)

LEYDIG cells, the interstitial cells of the testes, lie between the seminiferous tubules and produce androgenic steroids. The secretion of testosterone in men has been thought to be regulated by a feedback system in which luteinizing hormone from the anterior pituitary stimulates the conversion of cholesterol to testosterone. Testosterone, or one of its metabolites, modulates the sensitivity of the pituitary to hypothalamic luteinizing-hormone-releasing hormone, which in turn regulates the blood level of luteinizing hormone.Until recently, it was assumed that Leydig cells were relatively resistant to systemic disease and that their function was governed by a simple regulatory mechanism. It . . .
Thalidomide Has 37-Year History
Authors: Teri Randall
Journal: JAMA (1990)

THALIDOMIDE, a glutamic acid derivative (α[<i>N</i>=Phthalimido] glutarimide), was first described in 1953 by the Swiss pharmaceutical firm Ciba. The company discontinued its research on the drug when no pharmacologic effects were apparent. Despite Ciba's decision, Chemie Grünenthal, a Federal Republic of (West) Germany pharmaceutical company, synthesized the drug in 1954 and undertook its development. This company first marketed thalidomide as an anticonvulsant for the treatment of epilepsy. The drug proved ineffective for this purpose, but it did cause sleep. Thereafter, it was marketed as a hypnotic, sedative, and tranquilizer. It had prompt action and provided a deep sleep with no hangover; moreover, large doses alone did not cause death, so it was an unlikely vehicle for suicide. Thalidomide soon became West Germany's most popular sleeping pill and was widely used in hospitals and mental institutions. By the end of the 1950s, 14 pharmaceutical companies were marketing thalidomide in
Abstract 1232: Overcoming resistance to EGFR-tyrosine kinase inhibitor therapy in non-small cell lung cancer
Authors: J Rafael Sierra, Anderson Chang, Jason Moffat, Benjamin G. Neel, Ming-Sound Tsao
Journal: Cancer Research (2012)

Abstract Lung cancer is the leading cause of cancer death in developed countries both for men and women; and the second most common type of cancer diagnosed, with less than 15% of patients surviving beyond 5 years. Since more than 60% of lung adenocarcinomas and more than 90% of lung squamous cell carcinomas express high levels of EGFR mRNA and protein, it has been the focus of efforts to develop new agents that target the EGFR pathway. Clinical trials have demonstrated that patient selection plays a major role for patient response. Patients that present amplification or activating mutations (L878R or exon 19 deletions) of EGFR, have higher response rates. Selection improved response rates from less than 10% to over 60-80%. Despite the promising results, all patients that receive TKI therapy develop resistance to treatment in less than one year. The mechanisms of resistance to EGFR TKi's described so far are those dependant on the overactivation/amplification of other receptor tyrosine kinases (RTK) capable to sustain anti-apoptotic signaling pathways. Our study proposes the use of genome-wide screenings using an 80,000 shRNA library on EGFR resistant cells can identify new genes that mediate the resistance to EGFR targeted therapy and provide the basis for designing new therapeutic approaches to avoid the emergence of resistance. So far, we have generated a shortlist of gene candidates that confer synergistic synthetic lethal interactions with EGFR targeted therapies and that are also highly expressed in resistant cells. We are currently overexpressing candidate genes in sensitive cells searching for those that can confer resistance to EGFR targeted therapies. Our study proposes target genes that can synergize with the current treatments to create new therapeutical strategies that can avoid the acquisition of resistance to targeted therapies. Overall, the information gained from this type of study can be applicable to tumors where ERBB receptor(s) play an important role and targeted therapies are currently used. 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 1232. doi:1538-7445.AM2012-1232
GW25-e4430 Ibuprofen Attenuates Cardiac Fibrosis via Restoring the Imbalance of ACE and ACE2 in Diabetic Rat
Authors: Qiao Weili, Wang Cheng, Zhang Fan, Liu Yaowu, Yan Changdong, Sun Hong, Yin Xiaoxing
Journal: Journal of the American College of Cardiology (2014)
Evidence for neutral transcellular NaCl transport and neutral basolateral chloride exit in the rabbit proximal convoluted tubule.
Authors: M Baum, C A Berry
Journal: Journal of Clinical Investigation (1984)

The electrical nature of active NaCl transport and the significance of a basolateral membrane chloride conductance were examined in isolated perfused rabbit proximal convoluted tubules (PCT). PCT were perfused with a high chloride solution that simulated late proximal tubular fluid and were bathed in an albumin solution that simulated rabbit serum in the control and recovery periods. The electrical nature of NaCl transport was examined by bathing the tubules in a high chloride albumin solution where there were no anion gradients. Volume reabsorption (Jv) during the control and recovery period was 0.56 and 0.51 nl/mm X min, respectively, and 0.45 nl/mm X min when the tubules were bathed in a high chloride bath. The transepithelial potential difference (PD) during the control and recovery periods averaged 2.3 mV, but decreased to 0.0 mV in the absence of anion gradients, which indicated that NaCl transport is electroneutral. Further evidence that NaCl transport is electroneutral was obtained by examining the effect of addition of 0.01 mM ouabain in PCT perfused and bathed with high chloride solutions. The Jv was 0.54 nl/mm X min in the control period and not statistically different from zero after inhibition of active transport. The PD was not different from zero in both periods. Two groups of studies examined the role of basolateral membrane Cl- conductance in NaCl transport. First, depolarizing the basolateral membrane with 2 mM bath Ba++ did not significantly affect Jv or PD. Second, the effect of the presumptive Cl- conductance inhibitor anthracene-9-CO2H was examined. Anthracene-9-CO2H did not significantly affect Jv or PD. In conclusion, these data show that NaCl transport in the PCT is electroneutral and transcellular and provide evidence against a significant role for basolateral membrane chloride conductance in the rabbit PCT.
Incremental Prognostic Value of Gated Rb-82 Positron Emission Tomography Myocardial Perfusion Imaging Over Clinical Variables and Rest LVEF
Authors: Sharmila Dorbala, Rory Hachamovitch, Zelmira Curillova, Deepak Thomas, Divya Vangala, Raymond Y. Kwong, Marcelo F. Di Carli
Journal: JACC. Cardiovascular imaging (2009)