tbuckley/cabot-search huggingface dataset:
Abstract 2822: Characterization of the effects of PLX4720 in the immunocompetent BRAF/PTEN mouse melanoma model
Authors: Alexander Marzuka, Marcus Bosenberg
Journal: Cancer Research (2012)

Abstract Vemurafenib is a BRAF inhibitor approved by the FDA for the treatment of BRAF V600E-positive metastatic melanoma after a phase III clinical trial demonstrated improved survival in patients taking vemurafenib compared to dacarbazine. As the first personalized treatment for metastatic melanoma to show a survival benefit, vemurafenib is a major breakthrough in the field. Although tumors in patients frequently shrink significantly within weeks of initiation of treatment, resistance eventually develops in many patients, with a median progression free survival of approximately 7 months. Evaluation of the biomarker and phenotypic correlates of response are difficult to determine as paired pre-treatment and on-treatment biopsies generally only represent one on-treatment time point when available. A better in vivo understanding of the effects of BRAF inhibitor-treatment of relevant mouse models may yield insights into the nature of the clinical response and subsequent relapse. The conditional BRAF/PTEN mouse model of melanoma that we co-developed is ideal to study this process. In this non-xenograft model, expression of BRAF V600E and loss of PTEN is under control of the Cre-Lox recombination system. Expression of the Cre recombinase is under control of the tyrosinase promoter, ensuring that recombination is limited to melanocytes. The Cre recombinase is fused to an estrogen receptor that inhibits the activity of the recombinase. Activation of the Cre recombinase requires topical application of 4-hydroxytamoxifen, allowing for induction of recombination at specific time points in the life span of the mouse. The use of this mouse model allows for more thorough evaluation of the time course and phenotype of BRAF-inhibitor response in melanoma in an immunocompetent host. Specific studies include evaluation of the effect of PLX4720 on the expression, localization, and activation of proteins involved with growth arrest, apoptosis, and glucose uptake. 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 2822. doi:1538-7445.AM2012-2822
Mouse Models of Prostate Adenocarcinoma with the Capacity to Monitor Spontaneous Carcinogenesis by Bioluminescence or Fluorescence
Authors: Chun-Peng Liao, Chen Zhong, Gohar Saribekyan, James Bading, Ryan Park, Peter S. Conti, Rex Moats, Anton Berns, Wei Shi, Zongxiang Zhou, Alexander Yu Nikitin, Pradip Roy-Burman
Journal: Cancer Research (2007)

The application of Cre/loxP technology has resulted in a new generation of conditional mouse models of prostate cancer. Here, we describe the improvement of the conditional Pten deletion model of prostate adenocarcinoma by combining it with either a conditional luciferase or enhanced green fluorescent protein reporter line. In these models, the recombination mechanism that inactivates the Pten alleles also activates the reporter gene. In the luciferase reporter model, the growth of the primary cancer can be followed noninvasively by bioluminescence imaging (BLI). Surgical castration of tumor-bearing animals leads to a reduced bioluminescence signal corresponding to tumor regression that is verified at necropsy. When castrated animals are maintained, the emergence of androgen depletion-independent cancer is detected using BLI at times varying from 7 to 28 weeks postcastration. The ability to monitor growth, regression, or relapse of the tumor with the use of BLI lead to the collection of tumors at different stages of development. By comparing the distribution of phenotypically distinct populations of epithelial cells in cancer tissues, we noted that the degree of hyperplasia of cells with neuroendocrine differentiation significantly increases in the recurrent cancer relative to the primary cancer, a characteristic which may parallel the appearance of a neuroendocrine phenotype in human androgen depletion-independent cancer. The enhanced green fluorescent protein model, at necropsy, can provide an opportunity to locate or assess tumor volume or to isolate enriched populations of cancer cells from tumor tissues via fluorescence-based technologies. These refined models should be useful in the elucidation of mechanisms of prostate cancer progression, and for the development of approaches to preclinical intervention.
A new dawn for antiretrovirals
Authors: Rebecca Kay Sutherland
Journal: BMJ (2005)

L ast year may be remembered as the year when antiretroviral drugs began to be available to people living in Africa. I worked in South Africa's KwaZulu-Natal region last year and was involved in setting up one of the first antiretroviral clinics.

KwaZulu-Natal, which stretches along the east coast of South Africa, is renowned for some of the most beautiful scenery in the country, but it also holds a much bleaker claim to fame. It has the highest prevalence of HIV-1 infection in South Africa, with 38% of people testing HIV positive at the end of 2003, according to health department statistics. On the medical wards in Ngwelezane Hospital the prevalence of AIDS was about 80%.

Every evening a stream of skeletal young people would arrive at the hospital doors. Doctors and nurses who have seen the HIV epidemic grow over the years often turned department was reserved for trauma, of which there was plenty in the form of gunshot wounds, stabbings, and injuries from traffic collisions. …
HEALTH IN RELATION TO CITIZENSHIP IN URBAN AND IN RURAL COMMUNITIES
Authors: JOHN A. FERRELL
Journal: JAMA (1925)

Among community interests none is more important than public health, and among community liabilities none more serious than preventable sickness. The community welfare is definitely dependent on man's productivity, and this in turn is invariably influenced by the state of his health. If the community is to prosper, maintain high social, economic and intellectual standards, and otherwise meet its opportunities and responsibilities, it must include among its major activities measures for the preservation of health and the prevention of disease. This principle has been accepted by the more progressive urban communities, and is rapidly gaining acceptance in rural communities. Experience, moreover, is teaching the wisdom of employing competent professionally trained personnel, of paying reasonable compensation, and of making tenure secure when it is merited. It is teaching also that an adequate expenditure in this field, wisely administered, will yield large returns.  SCOPE OF HEALTH WORK  Practically all community programs of
Super or Not-So-Super Selective Vagotomy?
Authors: William Silen
Journal: New England Journal of Medicine (1972)

Carefully controlled clinical trials have now demonstrated that the so-called "lesser operations" for duodenal ulcer such as truncal vagotomy with drainage produce unpleasant postoperative symptoms as frequently as resectional procedures.1 Selective gastric denervation was introduced independently by Franksson2 and Jackson3 in 1948 in an attempt to obviate some of these side effects through maintenance of vagal innervation to the liver, pancreas and small intestine. Two well controlled trials4 , 5 have now shown that at least one goal has been realized — namely, that diarrhea is considerably less common after selective than after truncal vagotomy. An interesting but unexpected by-product of selective . . .
Conversion of a self peptide sequence into a Kd-restricted neo-antigen by a Tyr substitution.
Authors: F Healy, C Drouet, P Romero, C Jaulin, J L Maryanski
Journal: The Journal of Experimental Medicine (1991)

We have previously found that a Tyr residue was critical for the interaction of peptides with the Kd molecule, and therefore may be acting as an anchor residue. In the present report we show that it is possible to convert a self peptide sequence into a Kd-restricted neo-antigen by a single Tyr substitution at position 2 of the peptide. This supports the idea that Tyr is a critical element in the binding motif of Kd-restricted peptides and is a finding that could also prove useful for vaccine development.
S91 Once-daily tiotropium Respimat(R) add-on to ICS + LABA improves symptom control and reduces exacerbations in patients with symptomatic asthma
Authors: D. Price, M. Engel, P. Moroni-Zentgraf, H. Schmidt, R. Dahl, P. Paggiaro, M. Vandewalker, H. Kerstjens, A. Kaplan
Journal: Thorax (2014)

<h3>Background</h3> We evaluated the effect of once-daily tiotropium Respimat<sup>®</sup> 5 µg on lung function, asthma exacerbation and asthma symptom control among patients with symptomatic asthma receiving inhaled corticosteroids (ICS; ≥800 μg/day budesonide or equivalent) + long-acting β<sub>2</sub>-agonist (LABA). <h3>Methods</h3> Data were pooled from two replicate, double-blind, placebo-controlled, 48-week, parallel-group studies of once-daily tiotropium 5 µg versus placebo, both delivered via the Respimat<sup>®</sup> SoftMist™ inhaler (PrimoTinA-asthma<sup>®</sup>: NCT00772538, NCT00776984). Eligible patients had: ≥5-year history of asthma diagnosed before the age of 40 years; seven-question Asthma Control Questionnaire (ACQ-7) score of ≥1.5; experienced ≥1 exacerbation during the previous year. Patients were either lifelong non-smokers, or ex-smokers (&lt;10 pack-years) who quit smoking ≥1 year before study enrolment. Exclusion criteria included diagnosis of chronic obstructive pulmonary disease. Co-primary end points in individual trials: peak forced expiratory volume in 1 second (FEV<sub>1</sub>) within 3 h post-dose (0–3 h) and trough FEV<sub>1</sub>. A co-primary end point in pooled data was time to first severe exacerbation; secondary end points included time to first episode of asthma worsening and ACQ-7 response. <i>Post hoc</i> efficacy analyses were performed. <h3>Results</h3> 912 patients were randomised to receive tiotropium Respimat<sup>®</sup> (n = 456) or placebo Respimat<sup>®</sup> (n = 456). At Week 48, tiotropium Respimat<sup>®</sup> was associated with statistically significant improvements versus placebo Respimat<sup>®</sup> in peak FEV<sub>1(0–3h)</sub> (adjusted mean difference 100 mL; 95% confidence interval: 52, 148; p &lt; 0.0001) and trough FEV<sub>1</sub> (adjusted mean difference 62 mL; 95% confidence interval: 18, 106; p = 0.006). Time to first severe asthma exacerbation was significantly longer with tiotropium Respimat<sup>®</sup> versus placebo Respimat<sup>®</sup> (282 vs 226 days, respectively; hazard ratio 0.79; p = 0.034), as was time to first episode of asthma worsening (315 vs 181 days, respectively; hazard ratio 0.69; p &lt; 0.0001). At Week 24, ACQ-7 responder rate was significantly higher with tiotropium Respimat<sup>®</sup> (53.9%) versus placebo Respimat<sup>®</sup> (46.9%; odds ratio 1.32; p = 0.0427). <h3>Conclusion</h3> Once-daily tiotropium Respimat<sup>®</sup> add-on to ICS + LABA improves lung function, reduces risk of severe asthma exacerbation and asthma worsening, and significantly improves asthma symptom control compared with placebo Respimat<sup>®</sup> in patients with symptomatic asthma.
Contrasting Efficacy of Dofetilide in Differing Experimental Models of Atrial Fibrillation
Authors: Danshi Li, Agnes Bénardeau, Stanley Nattel
Journal: Circulation (2000)

Background —Rapid atrial pacing (RAP) and congestive heart failure (CHF) produce different experimental substrates for atrial fibrillation (AF). We tested the hypothesis that AF maintained by different substrates responds differently to antiarrhythmic-drug therapy. Methods and Results —The class III antiarrhythmic agent dofetilide was given intravenously at doses of 10 (D10) and 80 (D80) μg/kg to dogs with AF induced either (1) after 7 days of RAP at 400 bpm or (2) in the presence of CHF induced by rapid ventricular pacing. Dofetilide terminated AF in all CHF dogs, but D10 failed to terminate AF in any RAP dog, and D80 terminated AF in only 1 of 5 RAP dogs (20%) ( P &lt;0.01 for efficacy in CHF versus RAP dogs). Dofetilide was highly effective in preventing AF induction by atrial burst pacing in dogs with CHF but was totally ineffective in dogs with RAP. Dofetilide increased atrial effective refractory period and AF cycle length to a greater extent in CHF dogs. Epicardial mapping with 248 bipolar electrodes showed that CHF-related AF was often due to macroreentry, with dofetilide terminating AF by causing block in reentry circuits. RAP-related AF was due to multiple–wave front reentry, with dofetilide slowing reentry and decreasing the number of simultaneous waves, but not sufficiently to stop AF. Conclusions —The mechanism underlying AF importantly influences dofetilide efficacy. The dependence of drug efficacy in AF on the underlying mechanism has potentially significant implications for antiarrhythmic drug use and development and may explain the well-known therapeutic resistance of longer-duration AF.
Do fat babies stay fat?
Authors: E M Poskitt, T J Cole
Journal: BMJ (1977)

A total of 203 children included in a study of feeding practices and weight in infancy were reviewed four to five years later. Although in infancy 28 (14%) of the children were obese and a further 52 (26%) overweight, in childhood most were of normal weight and fatness, with only 5 (2-5%) obese and 22 (11%) overweight, Three of the five obese children were also obese as infants, but only one in nine obese infants was obese at 5 years. Weight in infancy does not necessarily indicate later body size. Tall stature of the children was probably related to their socioeconomic environment.
Effects of high-normal and low-normal serum potassium levels on hepatic encephalopathy: Facts, half-facts or artifacts?
Authors: Harold O. Conn
Journal: Hepatology (1994)

An inverse relation is known to link blood potassium with renal synthesis and the release of ammonia. Given the liability of hyperammonemia for precipitating hepatic encephalopathy (HE), 28 patients affected by stage I HE were equally divided into two groups and maintained up to their death at the highest (5.4-5.5 mEq/l) or the lowest (3.5-3.6 mEq/l) normokalemia levels. When compared with the lowest normokalemia group, the highest one showed an early, albeit transient, improvement in the mental state (as assessed by both EEG and psychiatric investigations) and to a lesser extent in hepatic functions (as assessed by the variations in serum bilirubin, GPT, GGT and plasma prothrombin time). In the highest normokalemia group the survival was also prolonged. The cause of this improvement may be related to the induced decrease in blood pH, the consequent depression of renal ammoniagenesis and the rise in the arterial and urine NH + 4 /HN 3 ratios. These factors reduce the entry of ammonia into the cells and enhance the urinary excretion of this metabolite, respectively.
Perceived health and physical activity of the Empowering Health Learning for the Elderly project
Authors: J Tortosa-Martínez, L Vega-Ramirez, A Soler-Gomis, A Plaza-Salán
Journal: British Journal of Sports Medicine (2010)

The Empowering Health Learning for the Elderly project targeted the promotion of competences and abilities related to health education for professionals working with adults. The first step of the programme was to analyse the perceived health of 1200 adults and older adults of four different countries (Spain, Italy, France and Holland). The instrument used was a questionnaire with 64 multiple choice questions about healthy lifestyles such as physical exercise, eating, drinking and smoking, use of drugs, memory and emotional intelligence. Data were analysed using Excel dynamic tables and SPSS V.15. The data discussed here represent only physical activity related results of the Spanish sample (300). 86% of the subjects were between 55 and 74 years of age. The perceived health of the population is good and 95% of the sample reports to be independent. About 50% consider themselves as active with only 2% reporting being seated for most of the day. Daily physical activity is reduced with age (p&lt;0.01). Especially, people over 85 years old have reduced activity compared to younger ones (p=0.01). Around 45% of the men consider their physical fitness good compared to nearly 50% for women. There is a higher number of men doing physical activity five or more times a week than women (p&lt;0.017). There is a correlation between reporting a high frequency of physical exercise and having a good perceived physical condition (p=0.05). Overall, the perceived health of the sample is good. The levels of physical activity are also good. This is probably due to the characteristics of the sample, with a high socioeconomic status and a high educational level. The study relies on perceived analyses and not on objective measures. It would be appropriate to use both methods to compare results.
The Southern Medical College Association.
Authors: W. T. Briggs.
Journal: JAMA (1892)

<h3>To the Editor of the Journal of the American Medical Association:</h3> An editorial in your issue of December 10,1892, in reference to the two Medical College Associations, does great injustice to the action of the Convention of the Southern Medical Colleges, which was recently called to meet and did meet, in Louisville, Ky., for the<i>sole purpose</i>of raising the standard of medical education in the South. At a meeting of the Faculty of the Medical Departments of the University of Nashville, and Vanderbilt University, in August last, a committee was appointed to call a Convention of the Medical Colleges of the South for the purpose of raising the standard of medical education in the South. The call was made by circular letters mailed to the officers of every reputable Medical College in the South, and answers were received from all addressed (except one) warmly endorsing the movement and promising
American Medical Research Foundation Perinatal Study
Authors: Sydney H. Kane
Journal: JAMA (1961)

THE American Medical Research Foundation Perinatal Study announces that it will now accept many additional participating hospitals into the program. The Board of Trustees of the American Medical Research Foundation, after reviewing the successful experience gained in the operation of the pilot study, have authorized the continuation of the perinatal study on a larger scale. This enlarged scope of investigation will provide an opportunity for many additional hospitals to join in the perinatal study and thus extend the benefits of this investigative program more widely across the country. Hospitals will be admitted to the group on the basis of meeting certain criteria, geographical distribution, and the ability to carry on the program for a minimum of one year. The AMRF Perinatal Study is a nationwide data-collection program, which has as its primary aims: research, education, and service into the area of perinatal problems. It hopes to improve the quality of
Applications to restrict elderly people without mental capacity rose 70% in three years
Authors: A. Cole
Journal: BMJ (2014)

Care homes and hospitals in England and Wales are increasingly seeking authorisation to restrain or restrict the liberty of elderly people who are deemed to lack mental capacity, says a new report by the health and safety watchdog the Care and Quality Commission.1

The figures come from the commission’s latest report on the operation of deprivation of liberty safeguards, a key element of the Mental Capacity Act. The safeguards seek to ensure that people are deprived of their liberty and human rights only if it is in their best interests and no other treatment is available. They cover a range of restrictions, including keeping …
Demonstration of functional border zone with myocardial contrast echocardiography in human hearts. Simultaneous analysis of myocardial perfusion and wall motion abnormalities.
Authors: S Nanto, T Masuyama, Y J Lim, M Hori, K Kodama, T Kamada
Journal: Circulation (1993)

Although the presence of a functional border zone (FBZ), defined as the nonischemic but asynergic myocardium adjacent to the ischemic area, has been demonstrated in animal hearts, it is not known whether this zone exists in humans.Myocardial contrast echocardiography (MCE) was performed before and during balloon inflation in the area of coronary stenosis by injecting contrast medium through the guiding catheter in 13 patients with effort angina who underwent successful coronary angioplasty. The area showing MCE defect during balloon inflation was determined with reference to the preangioplasty MCE and was regarded as an ischemic area. The size of the FBZ was assessed by measuring the length of the endocardium that showed asynergy in the echo-enhanced (nonischemic) area. The FBZ measured was 13 +/- 4 mm in the short-axis view (n = 5) and 16 +/- 9 mm in the long-axis view (n = 8).Nonischemic contractile dysfunction exists even in human hearts. The presence of an FBZ may limit the use of wall motion analysis in assessing the risk or ischemic area in patients with myocardial infarction. MCE appears to be a unique technique for assessing the risk or ischemic area.
Primary Cerebral Angioimmunoblastic T-Cell Lymphoma
Authors: Florence Lachenal, Françoise Berger, Sébastien Cimarelli, Maité Formaglio, Hervé Ghesquières
Journal: Journal of Clinical Oncology (2013)

Case ReportA 71-year-old woman with a past medical history of chronic alcoholism and depression presented with a subacute confusional state and was admitted to the Department of Neurology (Ho ˆpital Pierre Wertheimer, Bron, France) in November 2008.At admission, the patient was somnolent, apathetic, and confused.Her spatiotemporal orientation and cognitive function were impaired.She suffered from a moderately painful headache but presented no meningeal syndrome.An initial neurologic examination was performed, which did not reveal any focal abnormality or cranial nerve palsy.A general examination of the patient was normal except for weight loss and a low-grade fever (38.3°C), which disappeared in time.No peripheral lymphadenopathy, splenomegaly hepatomegaly, and/or rash were noted.The patient had a WHO performance status of 3.All laboratory tests results, including C-reactive protein levels, lactate dehydrogenase levels, and CBC, were normal.HIV testing was negative.A diagnosis of metabolic alcohol-or drug-related disorders was rejected.Brain computed tomography (CT) revealed extensive hypodensity in the right temporal lobe.Brain magnetic resonance imaging (MRI) revealed hyperintense lesions in the right temporal lobe on T2-weighted fluid-attenuated inversion recovery sequences (Fig 1A) and diffusion-weighted sequences.After gadolinium injection, the signal was enhanced in the lesion periphery, which suggested the presence of mild edema (Fig 1B).MRI also