tbuckley/cabot-search huggingface dataset:
Respiratory involvement in Fabry disease
Authors: Paola Faverio, Marco Mantero, Stefano Aliberti, Federico Pieruzzi, Giacomo Torti, Antonella Di Giacomo, Alberto Pesci
Journal: European Respiratory Journal (2013)

Fabry disease is an inherited lysosomal storage disease affecting kidney, heart and nervous system. Respiratory involvement has been described, but complete evaluation of pulmonary functional tests (PFTs) has not been yet performed. Our aim is to evaluate the presence and severity of PFTs alteration in adult patients with Fabry disease.  A prospective observational study was performed in adults with Fabry disease referring to the Nephrology clinic of San Gerardo Hospital, Monza, Italy, from 2010 to 2012. Medical history and complete PFTs were recorded for each patient. Percentage of predicted for PFT values was considered. Results are expressed as median [IQR].  16 patients were enrolled (5 male; median age 48 yrs). Among those, 3 were previous and 1 active smoker (median pack/years 4), 3 had asthma, 6 received enzyme replacement therapy (ERT). 5 patients (31%) presented Forced Expiratory Volume in 1 second (FEV1) mildly decreased (2.1L [1.3-2.8], 81% [44-92]) and a FEV1/FVC ratio  In 10 subjects (63%), specific Airway Resistance (sRAW) and Residual Volume (RV) were increased (152% [133-171] and 140% [131-152], respectively), while Total Lung Capacity (TLC) was normal in all patients (107% [94-114]). Middle Expiratory Flow (MEF) at 75%, MEF50% and MEF25% were slightly decreased (86.5% [79-103], 78.5% [62-100] and 76.5% [57-96], respectively).  A minority of patients had airway obstruction, defined as FEV1/FVC
Analysis of the use and indications of different modalities of ambulatory oxigenotherapy
Authors: Leyre Serrano Fernandez, Amaia Urrutia Gajate, Jose Amilibia Alonso, Ruth Diez Arnesto, Alejandro Ruiz Idarraga, Lide Alaña Rodrigo, Mikel Latorre Guisasola, Valentin Cabriada Nuño
Journal: European Respiratory Journal (2014)

INTRODUCTION: ambulatory oxygenotherapy (AO) has been typically administrated as liquid oxygen (LO). Nowadays portable oxygen concentrators (POC) are available. We elaborated a protocol to choose the type of deceive depending on activity and mobility skills. Aims: analyze the actual use of both deceives, evaluate the activity and mobility skills of our patients, compare the actual use with the theoretical use by applying our protocol and contrast the satisfaction between the two devices

METHODS: Transversal observational study. We studied patients from our area treated with AO by February 2013. We carried out questionnaires about mobility and activity skills and satisfaction grade. We applied the protocol to patients with AO

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RESULTS: 56 (83.6%) LO and 11 POC. 47.7% had a mild activity, 31.3% moderate and 21% high. The mobility was mild in 41.7%, moderate in 18% and high in 40.3%. Applying our protocol, POC should be prescribed in 40 patients (59%) and LO in 27. 32 cases (48%) have the adequate modality and we proposed a change in 35 (32 LO to POC), 12 accepted the change (LO to POC). The indication was reevaluated in 18 (27%), removed in 4. At satisfaction questionnaire, POC were more satisfied

CONCLUSIONS: Low rate of POC prescriptions. 59% of our patients have moderate or high mobility; cording to our protocol, POC is more adequate for them. This protocol needs further validation. Higher satisfaction level with POC.

 [1]: pending:yes
Abstract 15960: Activation of TRAF2-NF-κB Signaling suppresses Mitochondrial Perturbations in Doxorubicin Cardiotoxicity
Authors: Rimpy Dhingra, Lorrie A Kirshenbaum
Journal: Circulation (2014)

Doxorubicin (dox) is a highly effective anti-tumour agent, however, its use is limited by its protracted and cardiotoxic effects that manifest as heart failure. The canonical NFκB signaling pathway has been suggested to play a critical survival role in cardiac myocytes. Herein, we demonstrate that, impaired TRAF2 signaling disrupts NFκB activation in hearts of mice treated with dox (20mg/kg) or ventricular myocytes treated with dox (10μM). This was accompanied by severe ultrastructural defects including vacuolization, mitochondrial perturbations including mPTP, loss of [[Unable to Display Character: ∆]]Ψm and ROS production. Further we investigated role of TRAF2 on IKKβ- NFκB signaling in ventricular myocytes. Interestingly, TRAF2 mediated K-63 poly-ubiquitination of Receptor Interacting Protein 1 (RIP1) which recruits Tak-1 complex and activates IKKβ -NF-κB signaling was impaired in cells treated with dox. This coincided with a marked increase in expression and mitochondrial targeting of the Bcl-2 death protein Bnip3. Interestingly, expression of wild type TRAF2 but not the ring finger domain mutant defective for ubiquitination, restored TAK1-IKKβ-NF-κB signaling and suppressed Bnip3 gene activation in cells treated with dox. Concordant with TRAF2’s ability to suppress Bnip3, was accompanied by reduction in dox induced mPTP, ROS and cell death. Hence, our findings reveal a novel signaling pathway that functionally couples TRAF2 mediated NF-κB signaling to mitochondrial function and survival of cardiac myocytes.
VITAMIN E IN HEART DISEASE
Authors: H LEVY, E P BOAS
Journal: Annals of Internal Medicine (1948)

Article1 June 1948VITAMIN E IN HEART DISEASEHYMAN LEVY, M.D., ERNST P. BOAS, M.D.HYMAN LEVY, M.D., ERNST P. BOAS, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-28-6-1117 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptEnthusiastic reports1, 2on the value of vitamin E (alpha-tocopherol) in the treatment of certain forms of heart disease warrant further trial with this substance. Cardiac failure has been reported in cattle fed with vitamin E-free rations.3Such animals exhibit progressive electrocardiographic abnormalities, are prone to sudden death, and sections of their heart muscle show microscopical evidences of atrophy and scarring of muscle fibers. In our small but carefully studied and controlled group of patients, we have been unable to reproduce the therapeutic improvement previously reported. In fact, in chronic angina pectoris due to coronary sclerosis, in heart failure secondary...Bibliography1. SHUTESHUTEVOGELSANG WEEVA: Vitamin E in heart disease. I. The anginal syndrome, Med. Rec., 1947, clx, 2. Google Scholar2. VOGELSANGSHUTESHUTE AEVWE: Vitamin E in heart disease. II. The rheumatic heart, Med. Rec., 1947, clx, 3. Google Scholar3. GULLIKSONCALVERLEY TWCE: Cardiac failure in cattle on vitamin E-free rations as revealed by electrocardiograms, Science, 1946, civ, 312. CrossrefGoogle Scholar4. EVANSHOYLE WC: Comparative value of drugs used in continuous treatment of angina pectoris, Quart. Jr. Med., 1933, ii, 311. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Received for publication September 10, 1947.From the medical service of Dr. George Baehr, Mount Sinai Hospital.†The vitamin E preparation used was "Ephynal" and was supplied through the generosity of the Hoffmann-LaRoche Company. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byNutzen und Gefahren hochdosierter Vitamin E‐PräparateVitamin E as a food additiveA double-blind trial of vitamin E in angina pectorisVitamin E and Its Relation to Heart DiseaseVitamin E and coronary heart diseaseDie Pathologie der Avitaminosen und HypervitaminosenBibliographyDie Coronarerkrankungen. Coronarinsuffizienz, Angina pectoris und HerzinfarktTreatment of Angina PectorisFailure of Alpha Tocopherol to Influence Chest Pain in Patients with Heart DiseaseVitamin Supplementation in Health and DiseaseCOMPARISON OF EFFECTS OF ALPHA-TOCOPHEROL AND A MATCHING PLACEBO ON CHEST PAIN IN PATIENTS WITH HEART DISEASECOMPARISON OF EFFECTS OF ALPHA-TOCOPHEROL AND A MATCHING PLACEBO ON CHEST PAIN IN PATIENTS WITH HEART DISEASE 1 June 1948Volume 28, Issue 6Page: 1117-1124KeywordsAnginaAtrophyCardiac musclesCardiovascular therapyElectrocardiographyElectron microscopyHeart failureMedical servicesMyocardiumVitamin E ePublished: 1 December 2008 Issue Published: 1 June 1948 PDF downloadLoading ...
Preliminary results of first year of application of cardiopulmonary exercise test (CPET) in resection lung surgery in Navarra (Spain)
Authors: Sonia Herrero, Vanessa López, Amparo Urrizburu, María Jesús Martínez, José Javier Lorza, Juan José Guelbenzu, Xenia López, Pilar Cebollero
Journal: European Respiratory Journal (2014)

AIM: analyse the clinical and functional results during the first year of application of the ERS/ESTS guidelines on fitness for radical therapy in lung cancer (LC) patients.  Methods: prospective analysis of data of those patients proposed to surgical treatment for LC. We analysed pre FEV1, DLCO, VO2%, VO2/kg/min , complications in the first 30 days, mortality at 6 months and six months postFEV1, DLCO, VO2%, VO2/kg/min when available.  Results: during 2013,103 patients were proposed to surgical treatment because of LC .All of them were evaluated with FEV1 and DLCO. Of them, 52 needed a CPET (ERS/ESTS guidelines: FEV1 or DLCO  8 complications were registered in first 30 days, three of them moderate. 2 deaths in six months not related to surgery were found.  In 12 patients we made a second CPET six months after surgery. Only VO2/kg/min showed a significant difference (p=0.02)  Conclusions:  -We could apply ERS/ESTS guideline to 100% of our patients  -The main cause of CPET indication was impaired DLCO  -Half of cases proposed for surgery needed CPET, much more than those if we use previous protocol  -we only found deterioration in VO2/k/min but our sample is still small.
Abstract ES9-3: Adjuvant and neoadjuvant therapy: Current practice and future approaches
Authors: Eric P. Winer
Journal: Cancer Research (2015)

Abstract Triple negative breast cancer (TNBC) is accounts for approximately 10-15% of all breast cancer and is associated with a higher risk of disease recurrence, particularly early recurrence, than the other breast cancer subtypes. From a genomic standpoint, TNBC is heterogeneous, though we do not know how to incorporate this heterogeneity in treatment decisions. At the present time, there are no targeted systemic therapies for TNBC, and standard/neoadjuvant treatment consists of chemotherapy. Most treatment regimens include both an anthracyline and a taxane and involve 6-8 cycles of therapy, though simpler regimens such as AC x 4, TC x 4, or CMF x 6 remain an option for patients with a stage I disease. Neoadjuvant chemotherapy is often administered to decrease the extent of breast or axillary surgery. Outside of a clinical trial, anthracycline/taxane-based regimens remain the standard of care in the neoadjuvant setting. The addition of the platinum salts to standard therapy increases the proportion of patients who achieve a pathologic complete response, but it is unclear if these agents extend disease-free or overall survival. It is also unknown which patients benefit from the platinum salts and whether these agents should be added to or substituted for some portion of the standard regimen. Other investigational regimens, such as those including the PARP inhibitors, are also being studied in the neoadjuvant setting. On an individual patient level, response to neoadjuvant therapy is closely tied to outcome. Patients with a pathologic complete response have a far better outcome than those with residual disease, particularly those with extensive residual disease. However, it is unknown if the achievement of a higher pathologic complete response within a comparative trial leads to an improvement in disease-free or overall survival. Similarly, it is unknown if the addition of agents such as the platinum salts or other investigational treatmens can reduce the risk of recurrence in patients with residual disease after standard therapy. Ultimately, improved outcomes will be achieved through carefully controlled adjuvant and neoadjuvant trials conducted in close collaboration with laboratory investigators. It is likely that our understanding of the underlying biology of triple negative disease as well as our treatment approaches will evolve significantly in the next decade. Citation Format: Eric P. Winer. Adjuvant and neoadjuvant therapy: Current practice and future approaches [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 ES9-3.
Interleukin-6 (IL-6) Prevents Activation-Induced Cell Death: IL-2–Independent Inhibition of Fas/fasL Expression and Cell Death
Authors: Emira Ayroldi, Ornella Zollo, Lorenza Cannarile, Francesca D’ Adamio, Ursula Grohmann, Domenico V. Delfino, Carlo Riccardi
Journal: Blood (1998)
Proteasome Inhibition Enhances AAV-Mediated Transgene Expression in Human Synoviocytes in Vitro and in Vivo
Authors: Kristi Jennings, Takako Miyamae, Russell Traister, Anthony Marinov, Shigeki Katakura, Dawn Sowders, Bruce Trapnell, James M. Wilson, Guangping Gao, Raphael Hirsch
Journal: Molecular Therapy (2004)

To explore the potential applicability of recombinant adeno-associated virus (rAAV) vectors in the treatment of rheumatoid arthritis (RA), primary human fibroblast-like synoviocytes (FLS) derived from patients with RA were infected with rAAV encoding mouse IL-10 under the control of the CMV promoter. Addition of the proteasome inhibitor carbobenzoxy-l-leucyl-l-leucyl-l-leucinal (zLLL) to the cultures dramatically enhanced expression of the IL-10 transgene, in a dose-dependent manner. The increased expression was transient, peaking at 3 days and returning to near baseline by 7 days. The enhancement was observed even when zLLL was added 13 days after infection with rAAV. The effect of zLLL was not specific to either the mIL-10 transgene or the CMV promoter, as similar findings were observed using an rAAV construct encoding alpha1-anti-trypsin under the control of the chick beta-actin promoter or GFP, driven by the CMV promoter. Transgene expression could be repeatedly induced by reexposure to zLLL. Transgene mRNA levels increased in parallel with protein levels. Transgene expression could also be repeatedly induced in vivo by administering zLLL to SCID mice previously injected with rAAV-infected FLS. These data demonstrate that proteasome inhibition can dramatically enhance transgene expression in human RA FLS following infection with rAAV and suggest a possible approach to regulating synovial transgene expression in vivo.
Failure of antibiotic therapy in Staphylococcus epidermidis infection of implantable venous access devices in patients with AIDS, as documented by molecular typing
Authors: Christophe Piketty, Annie Buu Hoï, Jacques Gilquin, Anne Casetta, Philippe Castiel, Sabine Vaupre, Laurent Gutmann, Michel D. Kazatchkine
Journal: Clinical Microbiology and Infection (1999)
Toward a Cancer Drug of Fungal Origin
Authors: Alexander Kornienko, Antonio Evidente, Maurizio Vurro, Véronique Mathieu, Alessio Cimmino, Marco Evidente, Willem A. L. van Otterlo, Ramesh Dasari, Florence Lefranc, Robert Kiss
Journal: Medicinal Research Reviews (2015)

Abstract Although fungi produce highly structurally diverse metabolites, many of which have served as excellent sources of pharmaceuticals, no fungi‐derived agent has been approved as a cancer drug so far. This is despite a tremendous amount of research being aimed at the identification of fungal metabolites with promising anticancer activities. This review discusses the results of clinical testing of fungal metabolites and their synthetic derivatives, with the goal to evaluate how far we are from an approved cancer drug of fungal origin. Also, because in vivo studies in animal models are predictive of the efficacy and toxicity of a given compound in a clinical situation, literature describing animal cancer testing of compounds of fungal origin is reviewed as well. Agents showing the potential to advance to clinical trials are also identified. Finally, the technological challenges involved in the exploitation of fungal biodiversity and procurement of sufficient quantities of clinical candidates are discussed, and potential solutions that could be pursued by researchers are highlighted.
Combined Inhibition of Tumor Necrosis Factor α and Interleukin‐17 As a Therapeutic Opportunity in Rheumatoid Arthritis: Development and Characterization of a Novel Bispecific Antibody
Authors: Jens A. A. Fischer, Axel J. Hueber, Stacy Wilson, Margarete Galm, Wolfgang Baum, Christopher Kitson, Johannes Auer, Stefan H. Lorenz, Jörg Moelleken, Martin Bader, Alain C. Tissot, Seng‐Lai Tan, Stefan Seeber, Georg Schett
Journal: Arthritis & Rheumatology (2014)

Rheumatoid arthritis therapies that are based on inhibition of a single cytokine, e.g., tumor necrosis factor α (TNFα) or interleukin-6 (IL-6), produce clinically meaningful responses in only about half of the treated patients. This study was undertaken to investigate whether combined inhibition of TNFα and IL-17 has additive or synergistic effects in the suppression of mesenchymal cell activation in vitro and inflammation and tissue destruction in arthritis in vivo.Cultures of human fibroblast-like synoviocytes (FLS) were stimulated with TNFα, IL-17, or a combination of both. Single/combined neutralizing antibodies against TNFα and IL-17 were used to examine in vitro cytokine responses and in vivo development of arthritis and bone and cartilage destruction in TNFα-transgenic mice. Bispecific anti-TNFα/IL-17 antibodies were designed, and their potential to block cytokine responses in human FLS was tested.TNFα and IL-17 had additive/synergistic effects in promoting production of IL-6, IL-8, and granulocyte colony-stimulating factor, as well as matrix metalloproteinases, in FLS. Bispecific anti-TNFα/IL-17 antibodies showed superior efficacy in blocking cytokine and chemokine responses in vitro. Furthermore, dual versus single inhibition of both cytokines using neutralizing antibodies was more effective in inhibiting the development of inflammation and bone and cartilage destruction in arthritic mice.Combined blockade of TNFα and IL-17 was more effective than single blockade in inhibiting cytokine, chemokine, and matrix enzyme responses from human mesenchymal cells and in blocking tissue destruction associated with arthritis, and additionally showed a positive impact on rebalance of bone homeostasis. Bispecific anti-TNFα/IL-17 antibodies may have superior efficacy in the treatment of arthritis and may overcome the limited therapeutic responses obtained with single cytokine neutralization.
Pregnancy and Crimean-Congo haemorrhagic fever
Authors: O. Ergonul, A. Celikbas, U. Yildirim, A. Zenciroglu, D. Erdogan, I. Ziraman, F. Saracoglu, N. Demirel, O. Cakmak, B. Dokuzoguz
Journal: Clinical Microbiology and Infection (2009)
Final overall survival (OS) and safety analyses of RIBBON-2, a randomized phase III trial of bevacizumab (BEV) versus placebo (PL) combined with second-line chemotherapy (CT) for HER2-negative BEV-naive metastatic breast cancer (MBC).
Authors: Adam M. Brufsky, Sara A. Hurvitz, Edith A. Perez, Hideharu Yamamoto, Vicente Valero, Vincent O'Neill, Hope S. Rugo
Journal: Journal of Clinical Oncology (2012)

100 Background: Combining BEV with CT significantly improved progression-free survival (primary endpoint) in the E2100, AVADO, and RIBBON-1 trials in the 1st-line setting and the RIBBON-2 trial in the 2nd-line setting. Primary efficacy and safety results from RIBBON-2 have been published; here we present final OS results. Methods: Eligible patients (pts) had MBC that had progressed on 1st-line CT without BEV. 2nd-line CT (taxane, gemcitabine, capecitabine, or vinorelbine) was chosen before 2:1 randomization to CT with either BEV (10 mg/kg q2w or 15 mg/kg q3w) or PL continued until progression. Stratification factors were 2nd-line CT, hormone receptor status, and time from MBC diagnosis to 1st progression. All pts could receive BEV at progression. The primary endpoint was PFS. Final analysis of OS, a secondary endpoint, in the intent-to-treat population was planned after 557 events and provided 80% power to detect a hazard ratio (HR) of 0.77 (median OS increased from 14.0 to 18.2 months) at α=0.04. Results: At the time of data cutoff (Oct. 31, 2011), 184 (82%) of 225 pts in the CT/PL arm and 376 (82%) of 459 pts in the CT/BEV arm had died. BEV was administered in subsequent treatment lines in 12% vs 6% of pts, respectively. There was no difference in OS between treatment arms: HR 1.013 (95% CI 0.845–1.215), log-rank p=0.8843. Median OS was 17.8 months with CT/PL vs 18.6 months with CT/BEV. The 1-year OS rates were 69% vs 71%, respectively. Subgroup analyses by CT cohort showed HRs ranging from 0.86 (95% CI 0.58–1.29) in the capecitabine cohort (n=144) to 1.44 (95% CI 0.82–2.53) in the vinorelbine cohort (n=76). HRs were close to 1 for the two largest CT cohorts (taxane and gemcitabine). Exploratory analysis in the subgroup of patients with triple-negative MBC showed a HR of 0.85 (95% CI 0.58–1.26). Updated safety results were similar to those previously reported from the primary analysis. There were fewer fatal adverse events in the CT/BEV arm (1.5%) than in the CT/PL arm (3.2%). Conclusions: Final OS results from RIBBON-2 reveal no difference between treatment arms. No new safety signals were observed.
Abstract 4120: Periodic fasting mimicking diet started late in life reduces and delays carcinogenesis
Authors: Sebastian Brandhorst, Min Wei, Gerrardo Navarre, Louis Dubeau, Peter Conti, Todd Morgan, Valter D. Longo
Journal: Cancer Research (2014)

Abstract Nutrition can have profound effects on aging and age-related pathologies including cancer. As such, studies of fasting (the complete withdrawal of food) and dietary restriction (DR, generally described as a 20- 40% reduction in calories) have greatly contributed to the understanding of the relationship between nutrients, cellular aging, cancerogenesis and cancer cell survival. Our findings in yeast indicated that starvation decreases age-dependent mutations whereas our mouse xenograft tumor models indicate that fasting alone can be as effective as chemotherapy drugs in delaying the progression of certain tumor types, in part through the reduction of extracellular glucose and IGF-1 concentration/signaling. Here, we developed a fasting mimicking/enhancing diet (FMD) and tested its effects on cancerogenesis. In a cohort of female C57Bl6 mice, bi-monthly 4 day FMD feeding cycles followed by normal food intake, significantly improved survival in mice without causing excessive weight loss. Mice in the FMD cohort had a significantly reduced lifelong cancer incidence rate. Lymphoma was the most common cause of morbidity/mortality and affected ∼67% in the ad lib fed control group but only ∼40% of the FMD fed mice. In both cohorts lymphomas contributed to the great majority of all neoplasms found. Neoplasms were found in animals in the ad lib fed cohort starting 5 months after onset of our study, whereas no tumors occurred in the first 8 months in the FMD cohort. Furthermore, the FMD caused a shift from the presence of tumors in multiple organs (≥3) to tumors being either absent or present in 2 or less sites, thus indicating a potential shift to the development of benign tumors in the FMD group. In summary, the periodic FMD cycles had a significant impact on the development of cancer while allowing the preservation of lean body mass and animal weight until old age and extending longevity. Citation Format: Sebastian Brandhorst, Min Wei, Gerrardo Navarre, Louis Dubeau, Peter Conti, Todd Morgan, Valter D. Longo. Periodic fasting mimicking diet started late in life reduces and delays carcinogenesis. [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 4120. doi:10.1158/1538-7445.AM2014-4120