tbuckley/cabot-search huggingface dataset:
Abstract 15740: Effects of an Integrated Self-Care Intervention on Frailty Risk in Persons With Heart Failure and Type 2 Diabetes Mellitus
Authors: Brittany Butts, Rebecca Gary, Carolyn M Reilly, Melinda K Higgins, Javed Butler, Sandra Dunbar
Journal: Circulation (2014)

Introduction:  Frailty is a common condition in the elderly and a powerful predictor of mortality in CVD. In heart failure (HF), frailty has been shown to predict falls, disability, hospitalization and to substantially lower health related quality of life. Persons with HF are 6-7 times more likely to be frail than their age matched counterparts; the risk of frailty increases with multiple chronic conditions. Although 30-47% of persons with HF have concomitant type 2 diabetes mellitus (DM), frailty in persons with HF and DM has not been reported. The purpose of this study is to examine the effects of an integrated intervention on risk of frailty in persons with HF and DM.   Methods:  A secondary analysis of a randomized, controlled, repeated measures 6-month intervention trial was performed. Persons with HF and DM (n=102), mean age 58.14 ± 10.3 years, 69% male, 66% African American, and mean LVEF 34.72 ± 17.5 were randomized into usual care (UC) or an integrated HF-DM self-care education/counseling (HF-DM-SC) group which provided HF-DM self-care education and skills, psychosocial counseling to increase HF and DM self-efficacy, enhanced physical activity through walking, and facilitated decision making. Baseline and 6-month data were examined. Frailty was defined as total distance    Results:  At baseline, 60% of participants were classified as frail. Mean age (59.82) was higher (t=-2.001, p=.05) in the frail group compared with those considered not frail (55.58). No group differences in frailty were found at baseline (p=.55); frailty was not associated with BMI, LVEF, NYHA class, or comorbidities. After the 6-month HF-DM-SC intervention, the percent considered frail in the intervention group decreased from 56% to 29% while frailty in the UC group increased from 63.5% to 65% (p=0.021). No differences in age between frail and non-frail remained at 6 months.   Discussion:  Frailty increases the risk of adverse outcome in persons with HF and is not limited to the elderly in persons with HF and HF-DM. An integrated self-care intervention which emphasizes increased walking and physical activity can improve frailty risk and outcomes in persons with HF-DM.
Influence of aerobic exercise training on respiratory muscle strength in obese Thai women
Authors: Wilaiwan Khrisanapant, Orapin Pasurivong, Tunda Suthitum, Jureeporn Namarmarth
Journal: European Respiratory Journal (2011)

Obesity is one of major risk factors for developing several respiratory diseases which is probably linked to respiratory muscle impairment. This study aimed to determine whether aerobic exercise training improves respiratory muscle strength (RMS) in obese women. Inspiratory pressure from residual volume (PImaxRV) or function residual capacity (PImaxFRC), sniff nasal inspiratory pressure (Pnsn) and maximal expiratory pressure (PEmax) were measured in 13 obese women pre- and post-aerobic exercise training programme performed at least 30 min per session; 3 sessions per week for 12 weeks. Results showed that aerobic exercise training significantly reduced body mass indices (BMI) (29.8±2.9 vs. 28.7±2.9 kg/m 2 , fat mass (27.1±3.8 vs. 23.9±3.76 kg) and body fat (37.3±2.5 vs. 34.2±2.5%} (p 2 O), PImaxFRC (119.8±26.4 vs. 105.8.1±1524.8 cmH 2 O), Pnsn (113.2±122.1 vs. 98.1±21.2 cmH 2 O) and PEmax (127.3±24.7 vs. 119.8±26.4 cmH 2 O). The data suggest that aerobic exercise training in obese women studied appears to increase the RMS which may be, partly, a consequence of decreased fat mass and body fat.
Retropubik (IVS- 2) ve Transobturator (IVS- 4) Orta Üretra Askılarının Klinik Etkinlikleri: Randomize Çalışma
Authors: Tomasz Rechberger, Konrad Futyma, Katarzyna Jankiewicz, Aneta Adamiak, Paweł Skorupski
Journal: European Urology (2009)
Abstract P4-05-07: Functional genomics of TP53 mutations and its impact in breast cancer progression
Authors: Anasuya Pal, Laura Gonzalez-Malerva, Seron Eaton, Mayra Guzman, Donald Chow, Hongwei Yin, Jin Park, Karen Anderson, Joshua LaBaer
Journal: Cancer Research (2015)

Abstract Somatic TP53 mutations are prevalent in basal-like breast cancer (BLBC) tumors. Patients with BLBC tumors have fewer treatment options and respond poorly to current therapies. The majority of TP53 point mutations occurs in the DNA binding domain and can be categorized as either DNA contact or structural mutations. TP53 mutation results in a dominant negative phenotype with neomorphic activity. We predicted that different p53 mutations may lead to different phenotypic characteristics. To investigate this, we generated MCF10A stable transduced cell lines over-expressing the ten most frequent TP53 point mutations associated with breast cancer located in the DNA binding domain of TP53. Ectopic expression of TP53 in these stable cells has been confirmed by qRT-PCR and immunoblot. To assess the impact of mutation on carcinogenesis, we developed a series of high-throughput quantitative assays that measure several hallmarks of cancer, including proliferation, escape from apoptosis, epithelial to mesenchymal transition (EMT), cell migration and invasion, anoikis and morphology in 3D. We observed that one DNA contact mutation with the substitution of a positively charged amino acid with hydrophobic side chains such as R248W, and two structural mutants Y234C and H179R are resistant to apoptosis in presence of doxorubicin, are the most invasive displaying a mesenchymal phenotype characterized by the presence of disrupted B-catenin and E-cadherin staining, with reported worst clinical outcome, suggesting that these are the most aggressive phenotypes. Interestingly, the DNA contact mutants (R248Q, R273H, R248W, and R273C) had a growth advantage in absence of growth factors while structural mutants (R175H, H179R, Y220C, Y234C and Y163C) were more resistant to apoptosis after the cells were challenged with doxorubicin. G245S is comparable to the MCF10Ap53wt and is less proliferative, sensitive to apoptosis, and neither migratory nor invasive. In comparison, R248W which is one of the most aggressive mutants, together with R273C, and H179R resist anoikis; but Y234C, requires matrix for attachment in order to be invasive. In conjunction, these results confirmed our hypothesis that different TP53 point mutants have distinct phenotypes and functional effects on hallmarks of cancer due to distinct underlying cellular programs. Citation Format: Anasuya Pal, Laura Gonzalez-Malerva, Seron Eaton, Mayra Guzman, Donald Chow, Hongwei Yin, Jin Park, Karen Anderson, Joshua LaBaer. Functional genomics of TP53 mutations and its impact in breast cancer progression [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-05-07.
Targeting PSMA on tumor cells using novel aptamer-gelonin conjugates
Authors: Andrew D. Ellington, John W. Marks, Ted Chitai Chu, Laura Lavery, Sarah Faulkner, Matthew Levy, Michael G. Rosenblum
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

6183 

PSMA is a transmembrane receptor whose expression increases on prostatic tumor cells during disease progression. This protein is also expressed on the endotheluim of tumor vasculature but not normal vasculature. Aptamers are small nucleic acids selected to bind proteins such as cell-surface tumor antigens with high affinity and specificity. Aptamers have the potential to serve as replacements for cell-targeting antibodies or other cell-targeting ligands. We utilized a modified RNA aptamer (designated PSMAA) known to bind the external domain of PSMA with high affinity (previously reported Ki = 2 nM). The 22 kDa PSMAA molecule was conjugated to recombinant gelonin(rGel) toxin using the heterobifunctional cross-linking agent SPDP. The PSMAA/rGel conjugate was then purified by ion exchange and gel permeation chromatography. The final product was uncontaminated by free aptamer or free rGel and migrated as a single species (∼50 kDa) by SDS-PAGE. Analysis of the construct demonstrated that the rGel component was enzymatically active compared to free rGel. In addition, the conjugate was found to bind specifically to PSMA-expressing LNCAP cells. Cytotoxicity studies of the PSMAA/rGel conjugate demonstrated an I.C.50 of 32 nM on antigen-positive LNCAP cells compared to an I.C.50 of 350,000 nM on PC3 cells, which contain much less antigen; a targeting index of approximately 10,000 fold. Internalization studies should reveal the details of toxin conjugate entry, and animal model studies are ongoing. These data suggest that aptamers can be used to successfully deliver protein molecules such as toxins to tumor cells and may provide a novel approach to development of targeted therapeutic agents. The fact that aptamers can be chemically synthesized and thereby site-specifically conjugated makes them especially interesting as targeting ligands. The PSMAA-rGel construct may prove useful to target PSMA on prostate cells and on tumor vasculature. Research conducted, in part, by the Clayton Foundation for Research.
Molecular epidemiology and prevalence of mutations conferring rifampicin and isoniazid resistance in Mycobacterium tuberculosis strains from the southern Ukraine
Authors: V.V. Nikolayevskyy, T.J. Brown, Y.I. Bazhora, A.A. Asmolov, Y.M. Balabanova, F.A. Drobniewski
Journal: Clinical Microbiology and Infection (2006)
Handgrip Increases Endothelin-1 Secretion in Normotensive Young Male Offspring of Hypertensive Parents 11This study was supported by Grant 5/15/02/003 from the Ministero Università e Ricerca Scientifica e Tecnologica-Italia, Rome.
Authors: Enrico Mangieri, Gaetano Tanzilli, Francesco Barillà, Massimo Ciavolella, Paolo E Puddu, Claudio De Angelis, Louis J Dell’Italia, Pietro P Campa
Journal: Journal of the American College of Cardiology (1998)
Donor Characteristics As Pretransplant Predictive Factors of Long-Term Outcomes After Allogeneic Peripheral Blood Stem Cell Transplantation From HLA-Matched Related and Unrelated Donors in Patients with Hematologic Malignancies
Authors: Sophie Servais, Raphaël Porcher, Marie Robin, Alienor Xhaard, Emeline Masson, Jerome Larghero, Patricia Ribaud, Sarah Abbes, Nathalie Dhedin, Gerard Socie, Regis Peffault de Latour
Journal: Blood (2012)
Uptake of HIV-1 Tat protein mediated by low-density lipoprotein receptor-related protein disrupts the neuronal metabolic balance of the receptor ligands
Authors: Ying Liu, Melina Jones, Cynthia M. Hingtgen, Guojun Bu, Nick Laribee, Rudolph E. Tanzi, Robert D. Moir, Avindra Nath, Johnny J. He
Journal: Nature Medicine (2000)
X-linked ichthyosis: relation between cholesterol sulphate, dehydroepiandrosterone sulphate and patient's age
Authors: None Delfino, None Procaccini, None Illiano, None Milone
Journal: British Journal of Dermatology (1998)

Steroid sulphatase deficiency is a feature of recessive X-linked ichthyosis (RXLI) that causes the accumulation of sulphated steroids (SS) in various organs and cells. In a previous study, we detected elevated cholesterol sulphate (CS) and dehydroepiandrosterone sulphate (DHEAS) serum levels in a group of 15 RXLI patients selected in a narrow age range. In the present study both CS and DHEAS serum levels were qualitatively and quantitatively determined using gas-chromatographic analysis in a group of 33 RXLI patients ranging in age from 3 to 70 years. The levels of CS and DHEAS were significantly increased in all patients. Variations in SS were related both to patients' ages and clinical course of the disease; Serum SS levels start to increase in early infancy, peak at puberty, remain elevated in adults and decrease slightly in the elderly.
Abstract MP16: Adherence to Healthy Lifestyle Factors is Associated With a Lower Risk of Death Among US Male Physicians With Type 2 Diabetes
Authors: Andrew B Petrone, J. Michael Gaziano, Luc Djousse
Journal: Circulation (2015)

Background: Previous studies have suggested that adherence to a healthy lifestyle is associated with reduced risk of type 2 diabetes, cardiovascular disease, and mortality. However, it is unknown whether a combination of healthy lifestyle after the diagnosis of diabetes is associated with reduced risk of all-cause mortality. Objective: To test the hypothesis that healthy modifiable lifestyle factors are associated with a lower risk of all-cause mortality in people diagnosed with type 2 diabetes. Methods: A prospective cohort study of 1,160 male physicians from the Physicians’ Health Study with prevalent type 2 diabetes. Smoking habits, body mass index, exercise frequency, and alcohol consumption were assessed via questionnaire, and diet was assessed via a food frequency questionnaire between 1999 and 2002. Death was ascertained by an endpoint committee. Healthy lifestyle factors were defined as: 1) never or past smoking, 2) body mass index &lt;25 kg/m 2 , 3) vigorous physical activity 1+ days/week, alcohol consumption of 1-2 drinks/day, and 5) being in the top two quintiles of the Alternative Healthy Eating Index score. We used Cox regression to estimate multivariable adjusted hazard ratios of death according to each lifestyle factor, and total number of healthy lifestyle factors met. Results: During a median follow-up of 9.2 years, there were 248 deaths. The mean age at baseline was 68.9 ± 8.2 years. Healthy diet score was associated with a 40% (95% CI: 20-55%) lower risk of mortality. Multivariable adjusted hazard ratios (95% CI) for mortality were: 1.0 (ref), 0.58 (0.42-0.80), 0.58 (0.41-0.81), and 0.55 (0.35-0.87) for meeting 0 or 1, 2, 3, and 4+ healthy lifestyle factors, respectively. Conclusions: Our data are consistent with an inverse association between the number of healthy lifestyle factors and risk of mortality in US male physicians with type 2 diabetes.
Short-term prednisolone followed by recombinant human α-interferon alone or combined with adenine-arabinoside in chronic hepatitis B
Authors: Pierre Brissot, Christian Jacquelinet, Hervé Jouanolle, Véronique David, Dominique Guyader, Monique Guéguen, Martine Blayau, Gérard Lescoat, Michel Messner, Yves Deugnier
Journal: Journal of Hepatology (1991)
Cytokine‐induced histamine release from basophils of AIDS patients
Authors: M. Pedersen, H. Permin, C. Bindslev‐Jensen, K. Bendtzen, S. Norn
Journal: Allergy (1991)

Basophil leukocytes obtained from AIDS patients, allergic patients and healthy control were stimulated in vitro with interleukin 4, lymphotoxin, tumour necrosis factor alpha and interferon gamma to examine the histamine releasing effect. The cytokines caused histamine release from the basophils of approximately half the AIDS patients and from 8–17% of the allergic patients. No response was obtained in the control group. Removal of cell surface immunoglobulins abolished the response to cytokines, indicating an Ig‐dependent mechanism. Passive sensitization with cell‐derived Ig, with Ig deprived of IgE, or with IgG, indicated that cell‐bound IgE was responsible for the cytokine‐induced histamine release in AIDS patients. This response may be mediated by cytokine‐selective IgE antibodies.
Narrative based medicine: Narrative based medicine in an evidence based world
Authors: T. Greenhalgh
Journal: BMJ (1999)

This is the last in a series of five articles on narrative based medicine

In a widely quoted riposte to critics who accused them of naive empiricism, Sackett and colleagues claimed that “the practice of evidence based medicine means integrating individual clinical expertise with the best available external clinical evidence By individual clinical expertise we mean the proficiency and judgment that individual clinicians acquire through clinical experience and clinical practice.”1 Sackett and colleagues were anxious to acknowledge that there is an art to medicine as well as an objective empirical science but they did not attempt to define or categorise the elusive quality of clinical competence. This article explores the dissonance between the “science” of objective measurement2 and the “art” of clinical proficiency and judgment,3–5 and attempts to integrate these different perspectives on clinical method.

### Summary points

Even “evidence based” clinicians uphold the importance of clinical expertise and judgment

Clinical method is an interpretive act which draws on narrative skills to integrate the overlapping stories told by patients, clinicians, and test results

The art of selecting the most appropriate medical maxim for a particular clinical decision is acquired largely through the accumulation of “case expertise” (the stories or “illness scripts” of patients and clinical anecdotes)

The dissonance we experience when trying to apply research findings to the clinical encounter often occurs when we abandon the narrative-interpretive paradigm and try to get by on “evidence” alone

Science is concerned with the formulation and attempted falsification of hypotheses using reproducible methods that allow the construction of generalisable statements about how the universe behaves. Conventional medical training teaches students to view medicine as a science and the doctor as an impartial investigator who builds differential diagnoses as if they were scientific theories and who excludes competing possibilities in a manner …
Phantoms in the brain
Authors: P. W Halligan, A. Zeman, A. Berger
Journal: BMJ (1999)

After amputation many people experience vivid sensations of the body part they have lost.1 These “sensory ghosts” can arise within hours of the loss of the limb and are often painful. Such phenomena have been a mysterious part of medical lore for over a century, but recent research suggests that phantoms can teach us substantial lessons about the organisation and plasticity of the brain.



Fig 1. 
How amputees perceive their phantoms

(Credit: ALEXA WRIGHT)



We stand to learn most from phantoms if we attend closely to patients' subjective reports. One innovative study, for example, has made use of digital photography to depict how amputees perceive their phantoms (fig 1) (A Wright et al, Wellcome Trust Sci Art Project, 1997). By remaining true to patients' own experiences, the researchers found it …
Abstract 2457: Left Ventricular Assist Device Therapy with the HeartMate II Continuous Flow Rotary Pump as a Bridge to Heart Transplantation
Authors: Francis D Pagani, Leslie W Miller, Stuart D Russell, Ranjit John, Keith D Aaronson, John V Conte, Yoshifumi Naka, Reynolds M Delgado, Thomas E MacGillivray, David J Farrar, O. H Frazier
Journal: Circulation (2007)

Background: The HeartMate (HM) II continuous flow rotary pump represents a new generation of implantable left ventricular assist device (LVAD) that has recently completed clinical evaluation in an FDA-approved study for bridge to transplantation (BTT). Through a continued access protocol (CAP), an additional cohort of patients has undergone implantation of the HMI II device. We report on a comparative analysis of outcomes from both the primary and CAP cohorts. Methods: In a prospective, multi-center study, 297 patients with refractory heart failure and on intravenous inotrope therapy underwent implantation of the HM II to evaluate safety and efficacy as a BTT (n=133 patients-primary study cohort; n=164 patients-CAP; 61 patients in the CAP cohort completed 6 mo followup). Results: Baseline demographics, hemodynamics, renal and hepatic function were not significant between groups (Table 1 ). Number of patients with positive outcomes at 6 mo (transplant, cardiac recovery, alive on LVAD) were similar between cohorts (79% vs 80%). HM II therapy improved 6 minute walk distance at 3 month followup (by 250±232 m vs 226±180 m), and quality of life (Minnesota Living with Heart Failure; by 37% vs. 41%) to similar degrees for each cohort. The incidence of significant adverse events (pump replacements, 5 vs. 1; postoperative bleeding requiring surgery, 31% vs 23%; ischemic and hemorrhagic stroke, 8.0% vs 9.8%; need for RVAD, 4% vs 8%) were not significant between groups. Conclusions: Outcomes from patients implanted with the HMII device during CAP were similar to outcomes of patients implanted in the primary cohort. These analyses validate the original findings regarding efficacy and risk profile of the HM II continuous flow LVAD in this patient population as a BTT. table 1
Advice given to patients with fractures
Authors: D. J Torgerson, P. Dolan, J. Compston
Journal: BMJ (1999)

Editor—We recently undertook a cost analysis of osteoporosis, which showed that the disease is probably more costly than earlier estimates quoted by Pal suggested.1 We estimated that the total annual cost of fractures in a United Kingdom population is around £940 million, with hip fractures costing roughly £12 000 each.2 More importantly, using data from the general practice research database, like Pal we found little evidence that patients who had sustained a fracture were being offered treatment.3 The table (taken from our paper) summarises our results. 

In terms of evidenced based medicine the only population of patients that has been widely studied for secondary prevention is those who have sustained a vertebral fracture. Most, if not all, widely available treatments for the prevention of fractures have been shown to be effective at preventing new vertebral fractures in patients who have had one previously. Despite this, over three fifths of patients with a vertebral fracture diagnosed in primary care were not prescribed any drugs that reduce the fracture rate to prevent new vertebral fractures. Such patients are also at high risk of non-vertebral fractures.4 The priority in preventing fractures would seem to be to offer drug treatments that reduce the fracture rate to patients with existing vertebral fractures.
Abstract 14336: Long-Term Risk of Bleeding and Impact of Non-Therapeutic INRs in Patients Discharged on Triple Antithrombotic Therapy After Hospitalization For Acute Coronary Syndrome
Authors: Thomas T Tsai, Thomas M Maddox, Steven M Bradley, Ina Gylys-Colwell, Kelly McDermott, Christian D Helfrich, Stephan D Fihn, Christopher L Bryson, John S Rumsfeld, P. Michael Ho
Journal: Circulation (2011)

Background: There are limited data on the use of triple antithrombotic therapy (aspirin, clopidogrel, and warfarin) after discharge for acute coronary syndromes or its association with control of I...