tbuckley/cabot-search huggingface dataset:
Growth of Human Breast Neoplasms in Cell Culture2
Authors: John F. Foley, Byron T. Aftonomos
Journal: JNCI Journal of the National Cancer Institute (1965)

A method is described to obtain epithelioid and fibroblast-like cells from primary biopsy specimens of human breast carcinoma. The specimens were digested with collagenase and the cells grown in a complex medium containing medium 199 and a mixture of human and fetal calf sera. Of 32 biopsy specimens, there was growth of cells in 31; epithelioid and fibroblast-like components were noted in 21 of 31 and 29 of the 31 successfully cultivated specimens, respectively. In no instance has an epithelioid cell line been established. The fibroblast-like cells were readily subcultured and provided an excellent source of such cells for other purposes.
Abstract 4415: Comparison of Subsequent Vascular Response in Diabetic Patients Following Coronary Stenting Between Sirolimus- and Paclitaxel-Eluting Stents: Optical Coherence Tomography Analysis
Authors: Kenya Nasu, Mitsuyasu Terashima, Etsuo Tsuchikane, Osamu Katoh, Takahiko Suzuki
Journal: Circulation (2009)

Background: Diabetes mellitus is one of the major predictors for target lesion revascularization even in drug-eluting stent era. The aim of this study is to evaluate the differences of chronic vasc...
Amyloidosis in Wild House Mice During Inbreeding and in Hybrids Derived From Inbred Strains and Wild Mice
Authors: Howard B. Andervont, Thelma B. Dunn
Journal: JNCI Journal of the National Cancer Institute (1970)

A colony of wild house mice (Mus musculus) was maintained for 23 generations by no brother × sister matings. Starting with the 24th-generation mice, brother × sister inbreeding continued for 8 generations and noninbreeding for 8 additional generations. Amyloid was detected in all 34 autopsied mice of the inbreeding lines and in 4 of 25 of the noninbred control line. High-amyloid strain A and low-amyloid strain BALB/c females were bred to a wild male from an inbreeding line or a wild male from the noninbreeding line. All 19 hybrids derived from strain A and the inbreeding male developed amyloidosis; all 23 derived from the noninbred male were free of amyloid. Of 22 hybrids derived from BALB/c and the inbreeding male, 9 developed amyloidosis; all of 23 derived from the noninbred male were free of amyloid. Heredity and inbreeding influenced strongly the occurrence of amyloidosis.
Evolution of depression symptoms in smokers during an intensive intervention to quit
Authors: Eryka Urdapilleta, Mayra Piña, Ramces Falfan, Roger Quintana, Perez Gloria, Raul Sansores
Journal: European Respiratory Journal (2014)

Background: It has been reported that previous and current symptoms of depression influence during the smoking cessation process. Current and former smokers are 80 % more likely to have depressive symptoms compared with non-smokers. The subjects that have a moderate to severe depression also present a high degree of nicotine addiction and consume more than 21 cigarettes per day . In Mexico, little is known about the influence of intensive treatments for smoking cessation on depressive symptoms. This information would be useful to develop treatments for those conditions and increase abstinence rates and reduce relapse rate. Objective: Assess symptoms of depression, in the short and medium term, of smokers who received intensive intervention for smoking cessation. Instrument: Hamilton´s Depression Scale (HAM- D). Method: Experimental and Longitudinal study of a single group of 40 chronic smokers that were admitted to an intensive smoking cessation intervention (10 group sessions plus 4 individual therapy) with a follow-up at 3 months and 6 months after treatment ends. Results: Symptoms of depression decreased significantly in the participants of the intensive intervention and follow-ups compared with its baseline (p = 0.027). Men and female were different as men decrease significative compared with female (p=0.013). Conclusions: The intensive intervention suggested to be effective in the management of depressive symptoms in the process of quitting smoking alternative.
Transporters and Renal Drug Elimination
Authors: Wooin Lee, Richard B. Kim
Journal: The Annual Review of Pharmacology and Toxicology (2004)

Carrier-mediated processes, often referred to as transporters, play key roles in the reabsorption and secretion of many endogenous and xenobiotic compounds by the kidney. The renal proximal tubule is the primary site of active transport for a wide variety of substrates, including organic anions/cations, peptides, and nucleosides. During the past decade, significant advances in molecular identification and characterization of transporter proteins have been made. Although it is generally noted that these transporters significantly contribute to renal drug handling and variability in drug disposition, the extent of our knowledge regarding the specific roles of such transporters in drug disposition and drug-drug interactions remains, for the most part, limited. In this review, we summarize recent progress in terms of molecular and functional characterization of renal transporters and their clinical relevance to drug therapy.
Prognostic significance of BCL-2 expression and bcl-2 major breakpoint region rearrangement in diffuse large cell non-Hodgkin's lymphoma: a British National Lymphoma Investigation Study
Authors: ME Hill, KA MacLennan, DC Cunningham, B Vaughan Hudson, M Burke, P Clarke, F Di Stefano, L Anderson, G Vaughan Hudson, D Mason, P Selby, DC Linch
Journal: Blood (1996)
Abstract 10916: Blocking MicroRNA-17 by Intravenous Injection of Antagomirs Improves Pulmonary Hemodynamics and Right Heart Function in Experimental Pulmonary Hypertension
Authors: Soni S Pullamsetti, Carmen Doebele, Ariane Fischer, Rajkumar Savai, Baktybek Kojonazarov, Friedrich Grimminger, Angelika Bonauer, Werner Seeger, Andreas M Zeiher, Stefanie Dimmeler, Ralph T Schermuly
Journal: Circulation (2010)

Pulmonary hypertension (PH) is a disorder of the lung vasculature caused by increased pulmonary vascular resistance due to vasoconstriction and vascular remodeling. MicroRNAs (miRs) have gained att...
Getting research findings into practice: Barriers and bridges to evidence based clinical practice
Authors: B. Haynes, A. Haines
Journal: BMJ (1998)

This is the fourth in a series of eight articles analysing the gap between research and practice

Series editors: Andrew Haines and Anna Donald

Clinicians and healthcare planners who want to improve the quality and efficiency of healthcare services will find help in research evidence. This evidence is increasingly accessible through information services that combine high quality evidence with information technology. However, there are several barriers to the successful application of research evidence to health care. We discuss both the prospects for harnessing evidence to improve health care and the problems that readers—clinicians, planners, and patients—will need to overcome to enjoy the benefits of research(box).

View this table:

Problems in implementing evidence based medicine and possible solutions



The aim of evidence based health care is to provide the means by which current best evidence from research can be judiciously and conscientiously applied in the prevention, detection, and care of health disorders.1 This aim is decidedly ambitious given how slowly important new treatments are disseminated into practice2–%4and how resistant practitioners are to withdrawing established treatments from practice even once their utility has been disproved.5

### Summary points

The barriers to the dissemination and timely application of research findings in the making of decisions about health care are complex and have been little studied. They include many factors beyond the control of the practitioner …
The effect of administration rate on cisplatin-induced emesis.
Authors: N S Jordan, P K Schauer, A Schauer, C Nightingale, G Golub, R S Martin, H M Williams
Journal: Journal of Clinical Oncology (1985)

In an attempt to determine the influence of administration time on cisplatin-induced emesis, 20 adults previously untreated with cisplatin were enrolled into this double-blind study. Twenty patients were randomly assigned to receive high-dose cisplatin (greater than 100 mg/m2) either by a one-hour infusion or by an eight-hour infusion. All patients received antiemetic therapy with metoclopramide 2 mg/kg intravenously one-half hour before cisplatin administration, and 1 1/2, 3 1/2, 5 1/2, and 8 1/2 hours after cisplatin administration. Patients in the eight-hour infusion group experienced significantly fewer emesis episodes than did patients in the one-hour infusion group. The median of emesis episodes in the eight-hour group was one (range, 0 to 2) and in the one-hour group was three (range, 0 to 8). In patients receiving high-dose cisplatin plus metoclopramide, increasing the administration time from one hour to eight hours resulted in a small but significant decrease in emesis episodes. The cisplatin infusion rate should be considered as a variable in cisplatin-antiemetic trials.
Managing demand: Managing demand at the interface between primary and secondary care
Authors: A. Coulter
Journal: BMJ (1998)

This is the fourth of five articles on ways of managing demand for health care

General practitioners have acted as official gatekeepers to the United Kingdom hospital service since the inception of the NHS in 1948, but the roots of the referral system can be traced to the conflict between physicians, surgeons, and apothecaries in the 15th and 16th centuries.1 Specialists and general practitioners had to compete for paying patients until the early 20th century, when the issue was resolved with the establishment of registered general practice lists, a salaried hospital service, and a formal system of referral from one to the other. The gatekeeping role (more recently called filtering) of general practitioners is arguably the most important mechanism for managing demand in the NHS. The British referral system undoubtedly contributes to the low cost of health care relative to other countries. Healthcare systems which allow patients direct access to specialists—America, Germany, France, and Sweden—tend to incur higher costs than those that channel demand via general practitioner referrals, such as Britain, Denmark, Finland, and the Netherlands.2 At its best the referral system ensures that most care is contained within general practice, and when specialist care is needed patients are directed to the most appropriate specialist. However, it is also a restrictive practice, initially introduced to protect the interests of doctors, which gives general practitioners a monopoly over primary medical care and restricts patients' freedom of choice. Despite this the system has survived relatively unscathed by public criticism, a tribute to the widespread public confidence in general practitioners and to the fact that the gatekeepers have been very willing to open the gates to secondary care in response to patient demand.

Evidence of wide variations in the rates at which general practitioners referred patients to specialist clinics began to …
The usefulness of antimycobacterial antibodies detection in TB diagnosis
Authors: Elena Cojocaru, Codrin Popa, Irina Luciana Dumitriu, Bogdan Gurzu, Cristian Cojocaru
Journal: European Respiratory Journal (2012)

Aim: Due to the high number of cases, it could be useful a rapid and cost effective test for early diagnosis of tuberculosis. We planned to evaluate if a test based on detection of anti-lipoarabinomannan antibodies in serum is suitable for diagnose the tuberculosis (TB).  Methods: The test used is based on detection of anti-lipoarabinomannan antibodies from the sample using plastic combs. The test is positive if a colored spot appears on plastic comb. We used a randomized lot of patients addressed to Clinic of Pulmonary Diseases, Iasi, Romania.  Results: We have tested 46 patients from June 2011 to January 2012 from Iasi County. The final bacteriological results are available for 27 patients in present (February 2012). All the data presented below are just for patients with final evaluations. The average age was 45 years. Based on bacteriological tests 10 cases (37%) were diagnosed with TB. From patients with TB, the rapid serum test was positive in 8 cases (80%), 2 cases were negative. The other 17 cases were culture negative for  M. tuberculosis . From negative cases 14 (82.4%) were also negative for rapid TB test, and 3 cases were positive. For all 3 cases negative in bacteriology but positive in rapid TB test were observed opacities in upper lobes. Tuberculin test was positive in one case and not performed in others two. The producer revealed that this test has a sensitivity of 70.2% in patients with pulmonary tuberculosis and a specificity of 95.1%.  Conclusion: In the study population, this rapid TB test seems to be interesting for a rapid TB screening. Adding the patients expected for final evaluation is necessary for a more apropiate evaluation of the utility of this rapid TB test.
Carriage and antibiotic resistance of respiratory pathogens and molecular epidemiology of antibiotic-resistant Streptococcus pneumoniae colonizing children in day-care centers in Lisbon: the Portuguese day-care center initiative
Authors: Herminia de Lencastre, Ilda Santos Sanches, António Brito-Avô, Raquel Sá-Leão, Joana Saldanha, Karl G. Kristinsson, Alexander Tomasz
Journal: Clinical Microbiology and Infection (1999)
Gene expression of EGFR, MINA53,MEN1 and MTOR in NSCLCs
Authors: Dora Marinova, Yanina Slavova, Darina Kachakova, Gergana Stancheva, Atanaska Mitkova, Radka Kaneva, Danail Petrov, Vanio Mitev
Journal: European Respiratory Journal (2014)

Aim:To study the gene expression of Epidermal growth factor receptor(EGFR),MYC-induced nuclear antigen 53kDa(MINA53),Multiple endocrine neoplasia type 1(MEN1) and Mechanistic target of rapamycin(MTOR) in non-small cell lung carcinomas(NSCLC),and their correlations and prognostic significance.

Methods:Surgically resected specimens from 57 NSCLC patients were studied:29 adenocarcinomas(AC) and 28 squamous cell carcinomas(SCC).Histological subtype,pTNM stage,survival and gene expression of EGFR,MINA53,MEN1 and MTOR were evaluated.

Results:Overexpression of EGFR was found in 46%(17 SCC&9 AC),MINA53–54%(14SCC&17 AC),MEN1–53%(16SCC&14AC) and MTOR–25%(5SCC&9AC).Decreased expression of EGFR was found in 11%(2SCC&4 AC),MINA53–1 SCC,MEN1-2 AC and MTOR–5%(1 SCC&2 AC).Co-overexression of the 4 genes was found in 11%(4 SCC&2 AC).AC were more often with normal/decreased expression of EGFR(69%), while SCC-more often with overexpression(61%)(p=0.03),confirmed by regression analysis(Odds ratio 3.43;p=0.03).

No prognostic significance of EGFR, MINA53,MEN1 or MTOR expression was found with Kaplain-Meier and Cox regression analysis (p>0.05).

In SCC statistically significant correlations between EGFR&MEN1(p<0.001),EGFR&MTOR(p=0.01),MINA53&MTOR(p=0.004) and MEN1&MTOR(p=0.02) were observed.In AC statistically significant correlations between MINA53&MTOR(p=0.02) and MEN1&MTOR(p=0.01) were observed. MEN1 overexpression correlates with early stage(p=0.02).

Conclusion:EGFR,MINA53,MEN1 and MTOR are often overexpressed in NSCLCs and there are positive correlations between their expression levels making them potential targets for combined therapy. They don't show a prognostic significance, although MEN1 overexpression correlate with early stage.
A survey of the perception of asthma by primary care physicians in Republic of Moldova
Authors: Alexandru Corlateanu, Victor Botnaru, Svetlana Cemirtan, Elizaveta Cornei
Journal: European Respiratory Journal (2014)

Background:   In Republic of Moldova primary care physicians provide all or at least major part of the health care for the general population with recognized and unrecognized asthma. For those with recognized asthma, current management is frequently incompatible with the recommended international guidelines (GINA 2011).  The  aim  of this study was to explore knowledge related to asthma diagnosis and asthma management from family physicians.   Methods:  The survey was taken by 81 primary care physicians. The questions on local epidemiology, management and treatment of asthma were included in the study.   Results:   Our study shows that in the mean 5.7±4.3 patients with asthma are registered in each distinct of primary care physician (average number of general population for each distinct is 1757.1±568.3). Each month 2.2±2.5 of them take medical care. Rate of asthmaexacerbations is 2.7±1.9 per year. Majority of physicians (98%) explained the pathology of asthma to at least some of their patients and tried to identify aggravating factors of the asthma (78%). Fewer physicians have observed the inhalation technique of their patients (67%) and prescribed a written asthma management plan (65%). Only 41% uses Asthma Control Test in daily practice. Also there have been shown a limited level of knowledge of asthma control criterias. The main controllers prescribed to patients with asthma were inhaled corticosteroids (27%), and combinations of an inhaled corticosteroid and a long-acting beta-2 agonist (37%).   Conclusion:   The primary care physicians from Republic of Moldova continue to report lack of awareness and use of asthma guidelines. There is a strong need for adequate and efficient use of knowledge.
Proteinase 3 and its potential role in emphysema
Authors: Nicola Sinden, Timothy Dafforn, Robert Stockley
Journal: European Respiratory Journal (2012)

Introduction  Proteinase 3 (PR3) is an elastin-degrading proteinase similar to neutrophil elastase (NE). PR3 is the most abundant serine proteinase in neutrophils, causes emphysema in animal models & induces mucus secretion in humans. Its main circulating inhibitors are alpha-1-antitrypsin (AAT) & alpha-2-macroglobulin (A2M). Its role in respiratory disease has not been studied in detail.  Aims  1) To determine how efficiently PR3 activity is inhibited by healthy (PiM), AAT deficient (PiZ) & AAT variant (PiFZ, PiIZ) sera.  2) To study partitioning of PR3 between its 2 serum inhibitors.  Methods  Serum from subjects with different AAT phenotypes (PiM, PiZ, PiFZ, PiIZ) was taken & AAT concentration measured. Increasing molar ratios of serum AAT to PR3 were incubated & residual PR3 activity measured. Experiments were reproduced using comparable mixtures of pure AAT & A2M. Association rate constants (Kass) of PR3 & NE with AAT variants were determined using methylamine-treated serum (A2M inactivated).  Results  Increasing the molar ratio of serum AAT to PR3 increasingly inhibited PR3 activity, however even in AAT excess some residual PR3 activity remained which was greater in PiZ serum compared to PiM serum. These results were reproduced using mixtures of pure AAT & A2M suggesting that PR3 bound to A2M remains catalytically active. The Kass values for AAT variants with PR3 & NE are shown in table 1.  Conclusion  When serine proteinases are released from neutrophils, NE is more likely to be inhibited by AAT than PR3 (due to the lower Kass values) & binding of PR3 to A2M retains its activity.
MPs will debate assisted dying bill in September
Authors: C. Dyer
Journal: BMJ (2015)

A bill to legalise physician assisted suicide for terminally ill people in England and Wales is due to go before the House of Commons after it was chosen by the MP who came first in the ballot for private members’ bills.

The Assisted Dying Bill, introduced in the House of Lords in the last parliament, was supported by a majority of peers but fell …
Abstract 50: Therapeutic Silencing of miRNA-652 Restores Cardiac Function and Attenuates Pathological Remodeling in a Mouse Model of Pressure Overload
Authors: Bianca C Bernardo, Sally S Nguyen, Catherine E Winbanks, Xiao-Ming Gao, Esther J Boey, Yow Keat Tham, Helen Kiriazis, Colleen J Thomas, Ruby C Lin, Xiao-Jun Du, Julie R McMullen
Journal: Circulation Research (2014)

Introduction: Targeting microRNAs differentially regulated in settings of stress and protection could represent a new approach for the treatment of heart failure. miR-652 expression increased in hearts of a cardiac stress mouse model and was downregulated in a model of cardiac protection. Aim: To assess the therapeutic potential of silencing miR-652 in a mouse model with established pathological hypertrophy and cardiac dysfunction due to pressure overload. Methods: Mice were subjected to a sham operation (n=10) or transverse aortic constriction (TAC, n=14) for 4 weeks to induce hypertrophy and cardiac dysfunction. Mice were subcutaneously administered a locked nucleic acid (LNA)-antimiR-652 or LNA-control. Cardiac function was assessed by echocardiography before and 8 weeks post treatment, followed by molecular and histological analyses. Results: Expression of miR-652 increased in hearts subjected to pressure overload compared to sham operated mice (2.9 fold, n=3-5, P&lt;0.05), but was silenced in hearts of mice administered LNA-antimiR-652 (95% decrease, n=3-7, P&lt;0.05). In mice subjected to pressure overload, inhibition of miR-652 improved cardiac function (29±1% at 4 weeks post TAC compared to 35±1% post treatment, n=7, P&lt;0.001) and attenuated cardiac hypertrophy. Functional and morphologic improvements in hearts of treated mice were associated with reduced cardiac fibrosis, apoptosis, cardiomyocyte size; decreased B-type natriuretic peptide gene expression; and preserved angiogenesis (all P&lt;0.05, n=4-7/group). Mechanistically, we identified Jagged1, a Notch1 ligand, as a direct target of miR-652 by luciferase assay. Jagged1 and Notch1 mRNA were upregulated in hearts of TAC treated mice (1.2-1.7 fold, n=7, P&lt;0.05). Importantly, chronic knockdown of miR-652 was not associated with any notable toxicity in other tissues. Conclusion: Therapeutic silencing of miR-652 protects the heart against pathological cardiac remodeling and improves heart function via mechanisms that are associated with preserved angiogenesis, decreased fibrosis and upregulation of a miR-652 target, Jagged1. These studies provide the first evidence that targeted inhibition of miR-652 could represent an attractive approach for the treatment of heart failure.
Left heart dysfunction in COPD- Ignored combination
Authors: Deepak Singh, Kailash Agarwal, Vinod Joshi, Gopal Purohit, Shital Patil
Journal: European Respiratory Journal (2013)

Cardiovascular alterations are among the most frequently observed and constitute majority of this morbidity and mortality.  Objectives-To look for left heart dysfunction in COPD cases as it is routinely missed in routine practice.  Methods- This study had 50 patients of COPD from the outpatient and indoor of KN chest Hospital, Jodhpur.These patients belonging in majority to moderate (II) and severe (III) GOLD(Global Initiative on obstructive Lung Disease) stages were analyzed by Blood profile, BMI, Resting oxygen saturation, CX Ray, Spirometry, ECG and Echocardiography. Main objective was to observe cardiovascular effects in these COPD patients.  The statistical analysis was done using Chi Square and Student ‘t’ test.  Results- Maximum patients had Emphysema predominant on CX ray, BMI was low, CRP was raised and were hypoxic, belonged to MMRC grade II and III with low Hemoglobin and Hematocrit. The chief cardiovascular alterations were LVDD (56%), Pulmonary hypertension (48%), Right Ventricular enlargement (46%) and Right atrial enlargement (32%) while LVSD (18%), LA enlargement (10%), LVH (10%) and Cor Pulmonale (18%).These changes were significantly associated with the stage of COPD and increasing MMRC grades of dyspnea.  Conclusions-  The cardiovascular alterations in COPD are far too common especially LVDD, which remains grossly unmanaged. Diastolic dysfunction should be sought actively in COPD besides the right sided changes and pulmonary hypertension. Both can give rise to clinical worsening and exacerbation in COPD. Most correctable factor is Hypoxia. Treatment of condition is rewarding. So all patients of COPD especially of Moderate and Severe stages should have thorough Cardiovascular check up and Holistic management.