tbuckley/cabot-search huggingface dataset:
Fast track centres aim to cut waiting times
Authors: J. Wise
Journal: BMJ (2001)

Remains of hospitals in the earthquake ravaged areas of Gujarat in western India are being bulldozed in readiness for a huge rebuilding programme. Overall in Gujarat state, some 900 villages suffered serious damage in the earthquake of 26 January. The worst affected area is the Kutch district, in which maximum destruction is visible in Bhuj, Bhachau, Anjar, and Rapar.

Bhachau has been completely flattened. Operating theatre lights can be seen dangling out of the mass of rubble that remains of its 50-bed hospital. These and a destroyed ambulance are the only …
Drotrecogin alfa (activated) in the treatment of severe sepsis patients with multiple-organ dysfunction: data from the PROWESS trial
Authors: Jean-François Dhainaut, Pierre-François Laterre, Jonathan M. Janes, Gordon R. Bernard, Antonio Artigas, Jan Bakker, Hanno Riess, Bruce R. Basson, Julien Charpentier, Barbara G. Utterback, Jean-Louis Vincent
Journal: Intensive Care Medicine (2003)
Abstract 3757: Vacuolar ATPase ‘a’ subunit mediates platinum resistance in ovarian cancer
Authors: Arpita Kulshrestha, Gajendra K. Katara, Sahithi Pamarthy, Alice Gilman-Sachs, Kenneth D. Beaman
Journal: Cancer Research (2014)

Abstract Development of resistance to platinum compounds significantly hinders successful ovarian cancer treatment. Understanding the molecular alterations in chemo-resistance is important for developing therapeutic strategies for reversal of resistance. Vacuolar-H + −ATPases (V-ATPases) are multi-subunit proton pumps that play key roles in regulating cytosolic/extracellular pH and drug tolerance in tumor cells. The present study begins to decipher the role of V-ATPase `a’ subunit isoforms (major pH sensing unit) in cisplatin resistance. For this, cisplatin resistant human ovarian cancer cell lines A2780 and TOV112D were generated in lab by stepwise increase in drug pressure. Comparative expression profiling revealed that V-ATPase `a` subunit levels correlated with cisplatin resistance and each of the a1,a2 and a3 isoforms were significantly up regulated in the resistant lines. Isoform-specific shRNAs were employed to selectively and stably reduce mRNA levels for VATPase ‘a’ subunit in cisplatin resistant cell lines and determine their effect on cisplatin/carboplatin sensitivity, DNA damage and apoptosis. V-ATPase a2 or a3 isoform knocked down resistant lines exhibited sensitization to cisplatin and carboplatin. In vitro effects showed increased DNA damage by forming platinum DNA adducts which led to higher levels of apoptosis. In conclusion, inhibition of V-ATPase `a` subunit expression by monoclonal antibodies or V-ATPase inhibitors could serve as a therapeutic strategy to overcome cisplatin resistance and has a potential as a combination therapy along with platinum drugs for treatment of chemo-resistant ovarian carcinoma. Citation Format: Arpita Kulshrestha, Gajendra K. Katara, Sahithi Pamarthy, Alice Gilman-Sachs, Kenneth D. Beaman. Vacuolar ATPase ‘a’ subunit mediates platinum resistance in ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3757. doi:10.1158/1538-7445.AM2014-3757
Abstract MP27: Cellphone Intervention for You (CITY): A Randomized, Controlled Trial of Behavioral Weight Loss Intervention by Cellphone or Personal Coaching for Young Adults
Authors: Laura P Svetkey, Stephen S Intille, Bryan C Batch, Leonor Corsino, Crystal C Tyson, Gary G Bennett, Hayden B Bosworth, Corrine Voils, Steven Grambow, Catherine Loria, S S Arteaga, Pao-Hwa Lin
Journal: Circulation (2015)

Background: Obesity affects young adults, leading to future morbidity and mortality. Early behavioral intervention may promote long-term weight control. Mobile technology-based (mHealth) interventions may be particularly effective in young adults. We compared both an mHealth behavioral weight loss intervention and a personal coaching weight loss intervention to no intervention (and to each other) in overweight/obese young adults. Methods: We randomized 365 generally healthy adults age 18-35 years with BMI &gt; 25 kg/m2 (overweight or obese) to 24-months of intervention delivered primarily via investigator-designed cell phone (CP) or intervention delivered primarily via in-person (6 weekly) and by phone (23 monthly) coaching (PC), compared to usual care control group (Control). Primary outcome was weight change from baseline to 24 months. This study was conducted as part of the Early Adult Reduction of weight through LifestYle (EARLY) cooperative trials. Results: Randomized participants (N=365) had mean BMI 35 kg/m2, mean age 29yrs, were 70% women, 36% African American, 6% Latino. Final weight was obtained in 86%; missing weight was multiply imputed. At 24 months, weight loss was not different in either PC or CP vs Control (see Figure). Weight loss in PC was significantly greater than Control at 6 months. From baseline to 24 months, clinically significant weight loss (&gt; 3% per national guidelines) occurred in 40% of PC, 34% of CP, and 30% of Control. Conclusions: mHealth alone may not be sufficient for weight loss in young adults but mHealth-enhanced contact with an interventionist has a modest short-term effect. Future interventions should maximize the complementarity of mHealth and personal contact to achieve larger and more sustained effect.
Abstract 16797: Red Cell Distribution Width and Risk of Coronary Heart Disease Among Low Risk Healthy Representative US Adults
Authors: Sandip K Zalawadiya, Sidakpal S Panaich, Vikas Veeranna, Ashutosh Neeraj, Naga V Kommuri, Luis Afonso
Journal: Circulation (2011)

Objective: Evaluate the risk reclassification properties of red cell distribution width (RDW) in low risk healthy population free of prior cardiovascular disease (CVD) and diabetes. Background: Red cell distribution width (RDW) is an independent predictor of future CVD events. No prior study has evaluated whether addition of RDW to traditional cardiovascular risk factors (CVRF) (age, male sex, hypertension, dyslipidemia and smoking) improves risk reclassification, especially for those at intermediate risk of CVD events. Study Type: Prospective observational Methods: 15,460 participants aged ≥20 years of National Health and Nutrition Examination Survey (1988 to 1994) were evaluated. Adjusted Cox-proportional hazard analyses were performed to evaluate independent association between RDW and cardiovascular deaths (CVD and coronary heart disease (CHD)) beyond traditional CVRF, C-reactive protein, estimated glomerular filtration rate, hemoglobin, mean corpuscular volume and deficiency of nutritional factors like iron, folate and vitamin B 12 . Various calibrative and discriminatory methods were used to evaluate model with RDW and CVRF compared to model with CVRF alone. Newer reclassification index, category-less net reclassification improvement (NRI), was computed to analyze reclassification properties of RDW over traditional CVRF. Results: RDW independently predicted CVD (adjusted hazard ratio (aHR): 2.18, 95% Confidence interval (CI) - 1.70 to 2.82, p&lt;0.001) and CHD (aHR 2.15, 95% CI - 1.61 to 2.88, p&lt;0.001) mortality after adjustments. Statistically favored model including RDW and traditional CVRF reclassified 74% of overall population (95% CI - 65% to 85%, p&lt;0.001) based on category-less NRI. Nearly 35% of those classified to have intermediate risk by traditional CVRF were reclassified into higher or lower risk categories by addition of RDW. Conclusion: In this nationally representative adult US population, RDW significantly improves risk reclassification beyond traditional CVRF.
Paclitaxel treatment of ovarian tumor SKOV-3 cells at the sublethal dose in culture renders them more susceptible to lymphokine-activated killer cytolysis
Authors: Kim-Sheng Law, Shuen-Kuei Liao
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

628 

The standard treatment of epithelial ovarian cancer is tumor debulking by surgery, followed by six cycles of chemotherapy consisting of cisplastinum and Paclitaxel. A second look operation is usually scheduled to determine the effectiveness of the treatments. However, this therapy protocol is not satisfactory, since about 50% of patients with the so-called “pathologically negative findings” eventually experience tumor recurrence within a few years of follow-up. Thus, a more innovative treatment modality is urgently needed for patients with this malignancy. IL-2 has been demonstrated to augment the killing capability of lymphokine-activated killer (LAK) cells in vitro and in vivo against a variety of tumors. The major problem of this type of therapy has been the induction of severe toxicity in treated patients due to a high dose of IL-2 infused along with LAK cells. We hypothesized that pretreatment of human ovarian SKOV-3 cells at a sublethal low dose of Paclitaxel results in increased sensitivity to LAK cell killing. To determine the range of subthelal doses of Paclitaxel to SKOV-3 cells, total number of viable cells and % viability were examined every 24 h interval for 6 days. Results determined by trypan blue dye exclusion and MTT assays showed that the subthelal dose range was between 0.05 μM and 0.1 μM. LAK cells were prepared from peripheral blood mononuclear cells of healthy donors which were incubated with human recombinant IL-2 (R&D Systems) at 37°C for 72 h. Pretreatment of SKOV-3 cells with Paclitaxel at 0, 0.025, 0.05, 0,01 and 0.1 μM of a for 72 h repeatedly revealed enhanced LAK cell killing against SKOV-3 cells in a dose-dependent manner, as compared with the baseline killing with LAK cell alone. We concluded that this approach of may be useful for further development of an effective treatment mode for ovarian cancer.
The Kenny Method
Authors: A L Murphy
Journal: JAMA (1942)

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Reversal of multi drug resistance to taxanes by P-glycoprotein modulating chemopreventive phytochemicals
Authors: Sudha Kondraganti, Lihua Wang, Weiwu Jiang, Kathirvel Muthiah, Bhagavatula Moorthy
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

2278 

Breast cancer is a leading cause of cancer-related death among American women. The etiology of majority of breast cancers is multifactorial, of which 95% is environmental and hormonal. Polycyclic aromatic hydrocarbons (PAHs), commonly found in our environment are carcinogenic by genotoxic mechanisms. Some of the environmental chemicals mimic the properties of estrogen and may exert a hormonal influence on breast cancer. These chemicals share a common mode of action by activating the estrogen receptor (ER) and thereby elicit estrogenic responses. In addition to being estrogenic, xenoestrogens interact with xenobiotic- and drug-metabolizing CYP forms, including members of the CYP1A and CYP3A subfamilies.

The regulation of gene expression of various drug metabolizing enzymes (DMEs) has potential impact on drug interactions of many therapeutic agents. DMEs include phase I, phase II metabolizing enzymes as well as phase III transporters. P-glycoprotein (P-gp), Pregnane X receptor (PXR), and CYP3A4 are associated with multi drug resistance (MDR) in breast cancer chemotherapy. Taxanes are among the most unique, and successful chemotherapeutic agents used for the treatment of breast and ovarian cancer. Taxanes induce CYP3A by activating PXR-mediated transcription and enhance P-gp mediated drug clearance in human mammary tumor cells. The abundant and inexpensive chemopreventive dietary phytochemicals are being explored as P-gp modulators for the reversal of MDR to breast cancer chemotherapeutic drugs.

In the present study, we evaluated the effects of PAHs and chemopreventive dietary phytochemicals on the expression of liver and mammary CYP3A11, PXR, and P-gp activities. In wild type (C57BL/6J) female mice treated with 7,12-dimethylbenz(a)anthracene (DMBA), the apoprotein contents (Western blotting), and mRNA (Real time RT-PCR) expression of CYP3A11 and PXR genes were elevated in liver tissues of mice exposed to taxanes. The CYP3A11 and PXR gene expression was down regulated when the mice were treated with both taxanes and phytochemicals. The mammary P-gp expression was elevated in mice treated with taxanes compared to controls. Administration of phytochemicals along with taxanes inhibited the P-gp expression significantly showing a potential to reverse multi drug resistance. Induction of specific DNA adducts was observed in liver and mammary tissues of mice treated with PAHs and phytochemicals.

These studies show a potential for development of dietary phytochemical as a therapeutic drug to be used in combination chemotherapy for treating human breast cancer.
Mechanisms of Ventricular Fibrillation in Canine Models of Congestive Heart Failure and Ischemia Assessed by In Vivo Noncontact Mapping
Authors: Thomas H. Everett, Emily E. Wilson, Scott Foreman, Jeffrey E. Olgin
Journal: Circulation (2005)

Much of the research performed studying the mechanism of ventricular fibrillation (VF) has been in normal ventricles rather than under a pathological condition predisposing to VF. We hypothesized that different ventricular substrates would alter the mechanism and characteristics of VF.Three groups of dogs were studied: (1) control (n=8), (2) pacing-induced congestive heart failure (n=7), and (3) acute ischemia produced by 30 minutes of mid left anterior descending artery ligation (n=5). A noncontact mapping catheter (Ensite 3000, ESI) was placed via transseptal into the left ventricle (LV), along with an electrophysiology catheter. A multielectrode basket catheter (EP Technologies) was placed in the right ventricle, along with an electrophysiology catheter. Several episodes of VF were recorded in each animal. In addition to constructing isopotential and isochronal maps of the VF episodes, signals underwent frequency domain analysis as a fast Fourier transform was performed over a 2-second window every 1 second. From the fast Fourier transform, the dominant frequency was determined, and the organization was calculated. In control dogs, meandering, reentrant spiral wave activity was the main feature of the VF. The congestive heart failure group showed evidence of a stable rotor (n=3), evidence of a focal source (n=3), or no evidence of a driver in the LV (n=1). The ischemic group showed evidence of an initial focal mechanism that transitioned into reentry. In the control and ischemic groups, the LV always had higher dominant frequencies than the right ventricle.Different ventricular substrates produced by the different animal models altered the characteristics of VF. Thus, different mechanisms of VF may be present in the LV, depending on the animal model.
Abstract 16503: Comparison of Long-Term Results After Treatment of Ascending Aortic Aneurysms by Different Surgical Techniques
Authors: Klaus Kallenbach, Merve Oezsoez, Dubravka Kojic, Dominique Halmer, Thomas Bruckner, Carsten J Beller, Stany Sandrio, Arjang Ruhparwar, Matthias Karck
Journal: Circulation (2011)

Background: The proper treatment of aneurysm of the ascending aorta is still under debate. Here we compare the early and late outcome of patients undergoing composite replacement (CR), supracomissu...
Association between the mini nutritional assessment and the COPD assessment test
Authors: Ryuko Furutate, Takeo Ishii, Takashi Motegi, Kouichi Yamada, Kumiko Hattori, Yuji Kusunoki, Akihiko Gemma, Kozui Kida
Journal: European Respiratory Journal (2012)

Background:  The Mini Nutritional Assessment® (MNA) has not been studied extensively in COPD patients.   Objectives:  We evaluated whether COPD patients with impaired health status as determined by the COPD Assessment Test (CAT) have poor nutritional status according to the MNA.   Methods:  We recruited clinically stable male COPD outpatients (age, ≤65 years) for a cross-sectional study. We conducted the following examinations: pulmonary function tests, nutritional assessment using the MNA questionnaire (high scores indicate good nutritional status), the CAT, and dyspnoea evaluation. The patients were divided into 2 groups: (A) those with CAT scores ≥10 and (B) those with CAT scores    Results:  The study included 68 patients (mean age, 75.4 years). The total score was significantly correlated with FEV1% predicted, BMI, the modified Medical Research Council dyspnoea score, and the CAT score (Spearman9s rank correlation coefficient, ρ = 0.298, p = 0.013; ρ = 0.701, p  U -test).   Conclusions:  The nutritional status as determined by the MNA was associated with pulmonary function, dyspnoea, and the COPD-related health status. In addition, the nutritional status as determined by the MNA was significantly lower in COPD patients with CAT scores ≥10 than in those with CAT scores
Myocarditis as a Cause of Sudden Death
Authors: Guy Fontaine, Paul Fornes, Fabrice Fontaliran
Journal: Circulation (2001)

Myocarditis as a Cause of Sudden DeathTo the Editor:We appreciated the outstanding review by Drs Zipes and Wellens on sudden cardiac death. 1 However, the authors did not mention myocarditis as a cause of sudden death.In our experience at the Forensic Institute of Paris, myocarditis accounts for Ϸ5% of sudden, out-of-hospital cardiac deaths. 2 Two patterns are common.Acute myocarditis, the first type, occurs most frequently in children or young adults.The diagnosis is likely to be overlooked because of the frequent lack of symptoms.When present, symptoms are not specific; they suggest a bad cold in most instances.The heart is grossly normal.In particular, it is not enlarged.Myocyte necrosis and inflammatory infiltrates, predominantly composed of lymphocytes, are present, but they are most frequently patchy rather than diffuse (American Academy of Forensic Sciences, Orlando, Fla, personal communication, 1999).Therefore, multiple myocardial samples are required for the diagnosis.The second pattern is chronic myocarditis, which also involves young adults. 2The heart is again grossly normal.Histological examination of both ventricles shows patchy areas of fibrosis.In some sections, small clusters of lymphocytes may be present.These victims have no history of drug abuse, and toxicological analyses are negative.Viral infection is likely to be involved in most cases of both acute and chronic myocarditis.Idiopathic giant cell myocarditis, granulomatous myocarditis, and eosinophilic myocarditis are exceptional in our experience.Fibrosis is known to cause slow conduction in cardiomyocytes, resulting in arrhythmogenic substrate reentry circuits and subsequent ventricular desynchronization.Even more important is the possible role of acute inflammation of the myocardium, which could, by itself, promote ventricular arrhythmias or act as a trigger if this inflammation occurs in patients with heart disease who are prone to arrhythmia, such as those with concealed forms of cardiomyopathies. 3Hoffman et al 4 studied reperfusion arrhythmia and demonstrated, for the first time, the role played by the activation of neutrophils in producing early after-depolarization.These results demonstrate a direct link between acute inflammation and an electrophysiological phenomenon that is a possible trigger of arrhythmias.From a personal correspondence with Dr Brian Hoffman (October 1997), we learned that this mechanism is also likely to be involved in patients with advanced congestive heart failure in which tumor necrosis factor-␣ is present and that it is also an important cause of early after-depolarizations.
Abstract P301: Association of Toenail Cadmium Levels with Measures of Sub-Clinical Atherosclerosis: The Coronary Artery Risk Development in Young Adults (CARDIA) Trace Element Study
Authors: Pengcheng Xun, Kiang Liu, Steve Morris, Martha Daviglus, Catherine Loria, David Jacobs, David Goff, Ka He
Journal: Circulation (2012)

Background: Experimental studies have suggested that cadmium (Cd) exposure is a potential risk factor for early atherosclerosis and cardiovascular diseases as it can disrupt integrity of the endothelial cell layer. However, longitudinal data in humans relating Cd levels to sub-clinical atherosclerosis are lacking. Methods: 2589 participants from the CARDIA Study, aged 20-32 years in 1987 (baseline) with up to 18 years of follow-up were included in the analyses to examine prospectively the associations of toenail Cd concentrations with carotid intima-media thickness (CIMT) and coronary artery calcium score (CAC score). Toenail clippings were collected in 1987 and Cd was assessed by instrumental neutron-activation analysis. Common (c), bulb (b), and internal (i) CIMTs were measured in 2005 and CAC score in 2000 and 2005. CAC presence (score, &gt;0 Agatston units) and CAC progression (incident CAC in 2005 or increase in CAC score by ≥10 Agatston units) were defined based on CAC score. General linear regression or logistic regression was used as appropriate. Results: Median Cd levels were 0.003, 0.006, 0.012 and 0.039 μ g/g from 1 st - 4 th quartile. We observed a positive linear relation of Cd levels with cCIMT, but not bCIMT and iCIMT ( Table 1 ). Null associations between Cd levels and CAC progression [Q 4 vs . Q 1 : OR=1.11 (95% CI: 0.73, 1.68); P trend =0.14] or presence of CAC [Q 4 vs . Q 1 : OR=1.05 (0.73, 1.53); P trend =0.56] were documented. Conclusions: In this young adult cohort, toenail Cd levels were positively associated with cCIMT, but not bCIMT, iCIMT and CAC score. Further studies are needed to determine whether there is an atherosclerotic mechanism linking Cd exposure to the risk of cardiovascular disease. Table 1 Multivariable-adjusted carotid intima-media thickness (mm) by toenail cadmium levels No. of participants Quartile of toenail cadmium levels P trend Q1 Q2 Q3 Q4 cCIMT 2587 0.781 (0.773-0.790) 0.784 (0.776-0.793) 0.789 (0.781-0.798) 0.791 (0.781-0.798) 0.03 bCIMT 2527 1.010 (0.990-0.1.031) 1.002 (0.982-1.022) 0.981 (0.962-1.001) 1.001 (0.980-1.022) 0.17 iCIMT 2436 0.787 (0.772-0.802) 0.790 (0.776-0.804) 0.784 (0.770-0.798) 0.778 (0.763-0.793) 0.86 Data are geometric means (95%CIs) adjusted for age, gender, race, study center, body mass index, physical activity, education, smoking status, alcohol consumption, systolic blood pressure, LDL/HDL, HOMA, body mass index, long-chain omega-3 polyunsaturated fatty acids intake with toenail zinc, chromium, lead and mass weight. cCIMT : common carotid intima-media thickness; bCIMT : bulb carotid intima-media thickness; iCIMT : internal carotid intima-media thickness.