tbuckley/cabot-search huggingface dataset:
Treatment of hepatic metastases by cryotherapy and regional cytotoxic perfusion.
Authors: D L Morris, M D Horton, A V Dilley, A Warlters, P R Clingan
Journal: Gut (1993)

Leading articleTreatment of hepatic metastases by cryotherapy and regional cytotoxic perfusion Cryotherapy was probably first used to treat tumours by Arnott' almost 150 years ago.Much scientific work was done more than 20 years ago, including findings on the effect of repeated freeze/thaw cycles in the liver.2Hepatic cryotherapy was done by direct application of liquid nitrogen at -196°C,
Erythropoietin Decreases Renal Fibrosis in Mice with Ureteral Obstruction
Authors: Sun-Hee Park, Min-Jeong Choi, In-Kyung Song, Soon-Youn Choi, Ju-Ock Nam, Chan-Duck Kim, Byung-Heon Lee, Rang-Woon Park, Kwon Moo Park, Yong-Jin Kim, In-San Kim, Tae-Hwan Kwon, Yong-Lim Kim
Journal: Journal of the American Society of Nephrology (2007)

The inhibitory effects of recombinant human erythropoietin (rhEPO) were examined against (1) the progression of renal fibrosis in mice with complete unilateral ureteral obstruction and (2) the TGF-beta1-induced epithelial-to-mesenchymal transition (EMT) in MDCK cells. Unilateral ureteral obstruction was induced in BALB/c mice and rhEPO (100 or 1000 U/kg, intraperitoneally, every other day) or vehicle was administered from day 3 to day 14. Immunoblotting and immunohistochemistry revealed increased expressions of TGF-beta1, alpha-smooth muscle actin (alpha-SMA), and fibronectin and decreased expression of E-cadherin in the obstructed kidneys. In contrast, rhEPO treatment significantly attenuated the upregulation of TGF-beta1 and alpha-SMA and the downregulation of E-cadherin. MDCK cells were treated with TGF-beta1 (5 ng/ml) for 48 h to induce EMT, and the cells were then co-treated with TGF-beta1 and rhEPO for another 48 h. Increased expressions of alpha-SMA and vimentin and decreased expressions of zona occludens-1 and E-cadherin were observed after TGF-beta1 treatment, and these changes were markedly attenuated by rhEPO co-treatment. TGF-beta1 increased phosphorylated Smad-2 expression in MDCK cells, which was decreased by rhEPO co-treatment. In conclusion, rhEPO treatment inhibits the progression of renal fibrosis in obstructed kidney and attenuates the TGF-beta1-induced EMT. It is suggested that the renoprotective effects of rhEPO could be mediated, at least partly, by inhibition of TGF-beta1-induced EMT.
Evaluation of Systems-Oriented Public Health Interventions: Alternative Research Designs
Authors: Robert W. Sanson-Fisher, Catherine A. D'Este, Mariko L. Carey, Natasha Noble, Christine L. Paul
Journal: Annual Review of Public Health (2014)

The need to provide sound evidence of the costs and benefits of real-world public health interventions has driven advances in the development and analysis of designs other than the controlled trial in which individuals are randomized to an experimental condition. Attention to methodological quality is of critical importance to ensure that any evaluation can accurately answer three fundamental questions: (a) Has a change occurred, (b) did the change occur as a result of the intervention, and (c) is the degree of change significant? A range of alternatives to the individual randomized controlled trial (RCT) can be used for evaluating such interventions, including the cluster RCT, stepped wedge design, interrupted time series, multiple baseline, and controlled prepost designs. The key features and complexities associated with each of these designs are explored.
Attention-Deficit/Hyperactivity Disorder and Risk of Substance Use Disorder: Developmental Considerations, Potential Pathways, and Opportunities for Research
Authors: Brooke S.G. Molina, William E. Pelham
Journal: Annual Review of Clinical Psychology (2014)

Many opportunities to explain attention-deficit/hyperactivity disorder (ADHD)-related risk of substance use disorder (SUD) remain available for study. We detail these opportunities by considering characteristics of children with ADHD and factors affecting their outcomes side by side with overlapping variables in the developmental literature on SUD etiology. Although serious conduct problems are a known contributor to ADHD-related risk of SUD, few studies have considered their emergence developmentally and in relation to other candidate mediators and moderators that could also explain risk and be intervention targets. Common ADHD-related impairments, such as school difficulties, are in need of research. Heterogeneous social impairments have the potential for predisposing, and buffering, influences. Research on neurocognitive domains should move beyond standard executive function batteries to measure deficits in the interface between cognitive control, reward, and motivation. Ultimately, maximizing prediction will depend, as it has in the SUD literature, on simultaneous consideration of multiple risk factors.
Application of a Macromolecular Contrast Agent for Detection of Alterations of Tumor Vessel Permeability Induced by Radiation
Authors: Hisataka Kobayashi, Koen Reijnders, Sean English, Alexander T. Yordanov, Diane E. Milenic, Anastasia L. Sowers, Deborah Citrin, Murali C. Krishna, Thomas A. Waldmann, James B. Mitchell, Martin W. Brechbiel
Journal: Clinical Cancer Research (2004)

Permeability of tumor vasculature can be a major barrier to successful drug delivery, particularly for high molecular weight agents such as monoclonal antibodies and their diagnostic or therapeutic conjugates. In this study, changes in permeability of SCCVII tumor vessels after radiation treatment were evaluated by dynamic magnetic resonance imaging as a function of time after irradiation using a generation-8 polyamidoamine dendrimer (G8-Gd-D)-based magnetic resonance imaging contrast agent shown previously to be confined to tumor blood vessels. Tumor irradiation consisted of either single doses (2-15 Gy) or various daily fractionated doses (5 days). A single radiation dose of 15 Gy resulted in significant transient image enhancement of the tumor tissue with a maximum occurring between 7 and 24 hours after radiation treatment. No observable enhancement was recorded for fractionated radiation doses. Use of dynamic magnetic resonance imaging coupled with G8-Gd-D provides an exquisite methodology capable of defining the timing of enhanced permeability of macromolecules in tumors after irradiation. Such information might be applied to optimize the efficacy of subsequent or concurrent therapies including radiolabeled antibodies or other anticancer agents in combination with external beam therapies.
Interferon-γ Regulates Idiopathic Pneumonia Syndrome, a Th17<sup>+</sup>CD4<sup>+</sup>T-Cell–mediated Graft-versus-Host Disease
Authors: Nora Mauermann, Julia Burian, Christophe von Garnier, Stefan Dirnhofer, Davide Germano, Christine Schuett, Michael Tamm, Roland Bingisser, Urs Eriksson, Lukas Hunziker
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: Pulmonary complications of hematopoietic stem cell transplantation include infections and graft-versus-host diseases, such as idiopathic pneumonia syndrome (IPS). Conflicting data exist regarding the role of the interferon (IFN)-γ–producing Th1 CD4+ T-cell subset and IL-17A in IPS.Objectives: To determine the role of IFN-γ and IL-17A in the establishment of pulmonary graft-versus-host disease.Methods: A semiallogeneic murine model based on C57BL/6 × BALB/c as recipients with transplantation of BALB/c RAG2−/− bone marrow and transfer of different genetic knockout T cells (T-bet−/−, IFN-γ−/−, IFN-γR−/−) on a BALB/c background. Lung tissue was examined for parenchymal changes and infiltrating cells by histology and fluorescence-activated cell sorter analysis.Measurements and Main Results: After transfer of semiallogeneic bone marrow together with donor CD4+ T cells lacking IFN-γ or T-bet—a T-box transcription factor controlling Th1 commitment—we found severe inflammation in the lungs, but no enhancement in other organs. In contrast, wild-type donor CD4+ T cells mediated minimal inflammation only, and donor CD8+ T cells were not required for IPS development. Mechanistically, the absence of IFN-γ or IFN-γ signaling in pulmonary parenchymal cells promoted expansion of IL-17A–producing CD4+ T cells and local IL-17A release. In vivo depletion of IL-17A reduced disease severity.Conclusions: One mechanism of IFN-γ protection against IPS is negative regulation of the expansion of pathogenic IL-17A–producing CD4+ T cells through interaction with the IFN-γ receptor on the pulmonary parenchymal cell population.
Idiopathic polydactylous longitudinal erythronychia: a newly described entity
Authors: R. Baran, R.P.R. Dawber, C. Perrin, J.L. Drape
Journal: British Journal of Dermatology (2006)

Journal Article Idiopathic polydactylous longitudinal erythronychia: a newly described entity Get access R. Baran, R. Baran Nail Disease Centre, 42 rue des Serbes, 06400 Cannes, France *Department of Dermatology, Churchill Hospital, Headington, Oxford OX3 7LJ, U.K. †Department of Pathology, Hopital Pasteur, 06000 Nice, France ‡Department of Radiology, Hopital Cochin, 75679 Paris cedex 14, France E‐mail: baran.r@club‐internet.fr; baran.r@wanadoo.fr Search for other works by this author on: Oxford Academic Google Scholar R.P.R. Dawber, R.P.R. Dawber Nail Disease Centre, 42 rue des Serbes, 06400 Cannes, France *Department of Dermatology, Churchill Hospital, Headington, Oxford OX3 7LJ, U.K. †Department of Pathology, Hopital Pasteur, 06000 Nice, France ‡Department of Radiology, Hopital Cochin, 75679 Paris cedex 14, France E‐mail: baran.r@club‐internet.fr; baran.r@wanadoo.fr Search for other works by this author on: Oxford Academic Google Scholar C. Perrin, C. Perrin Nail Disease Centre, 42 rue des Serbes, 06400 Cannes, France *Department of Dermatology, Churchill Hospital, Headington, Oxford OX3 7LJ, U.K. †Department of Pathology, Hopital Pasteur, 06000 Nice, France ‡Department of Radiology, Hopital Cochin, 75679 Paris cedex 14, France E‐mail: baran.r@club‐internet.fr; baran.r@wanadoo.fr Search for other works by this author on: Oxford Academic Google Scholar J.L. Drape J.L. Drape Nail Disease Centre, 42 rue des Serbes, 06400 Cannes, France *Department of Dermatology, Churchill Hospital, Headington, Oxford OX3 7LJ, U.K. †Department of Pathology, Hopital Pasteur, 06000 Nice, France ‡Department of Radiology, Hopital Cochin, 75679 Paris cedex 14, France E‐mail: baran.r@club‐internet.fr; baran.r@wanadoo.fr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 155, Issue 1, 1 July 2006, Pages 219–221, https://doi.org/10.1111/j.1365-2133.2006.07311.x Published: 01 July 2006
Induced sputum substance P in children with difficult-to-treat bronchial asthma and gastroesophageal reflux: Effect of esomeprazole therapy
Authors: Adel Salah Bediwy, Mohamed Gamal Elkholy, Mohamed Al-Biltagi, Hesham G. Amer, Eman Farid
Journal: European Respiratory Journal (2012)

Objectives. To assess the induced sputum substance P (ISSP) levels in children having difficult-to-treat asthma (DA) with and without gastroesophageal reflux (GER). We aimed also to evaluate the association of GER with childhood DA, relationship of GER severity with childhood asthma control test (C-ACT), FEV1, peak expiratory flow (PEF) variability, and ISSP. Finally, we tried to evaluate esomeprazole treatment effect on C-ACT and FEV1 in children with DA.  Methods. Spirometry, C-ACT, upper gastrointestinal endoscopy, and ISSP measurement were done for children with DA compared to healthy controls.  Results. ISSP was high in DA with higher levels in the group having associated GER. In the latter group, ISSP and C-ACT improved significantly after esomeprazole treatment while FEV1 and PEF variability did not improve. Reflux severity was positively correlated with ISSP and negatively correlated with FEV1.  Conclusions. GER was found in 49% of our patients with childhood DA. Very high ISSP levels in children with DA may be used as a marker for presence of GERD. Esomeprazole therapy improved asthma symptoms but did not improve lung function.
Targeted Therapy for Brain Metastases: Improving the Therapeutic Ratio
Authors: Rakesh R. Patel, Minesh P. Mehta
Journal: Clinical Cancer Research (2007)

Abstract Brain metastasis is the most common intracranial malignancy in adults. Improvements in modern imaging techniques are detecting previously occult brain metastases, and more effective therapies are extending the survival of patients with invasive cancer who have historically died from extracranial disease before developing brain metastasis. This combination of factors along with increased life expectancy has led to the increased diagnosis of brain metastases. Conventional treatment has been whole brain radiotherapy, which can improve symptoms, but potentially results in neurocognitive deficits. Several strategies to improve the therapeutic ratio are currently under investigation to either enhance the radiation effect, thereby preventing tumor recurrence or progression as well as reducing collateral treatment-related brain injury. In this review article, we discuss new directions in the management of brain metastases, including the role of chemical modifiers, novel systemic agents, and the management and prevention of neurocognitive deficits.
Repeated Circulatory Arrest under Hypothermia
Authors: V. O. Bjork, S. Hogstrom
Journal: Thorax (1963)

Incasesofpulmonary valvular stenosis without infundibular constriction andincasesofatrial septal defect withorwithout abnormal venous return wecontinue touseinflow occlusion under hypothermia (29to310C.)inpreference toextracorporeal circulation. Thereason forthisisthat a smallbutsignificant mortality ratemustbe ascribed totheperfusion technique perse,whereas inourexperience thesamerisk doesnotfollow a well-conducted hypothermia (Bjork, Holmdahl, and Petersson, 1960). Ifasecond period ofinflow occlusion isneeded tocomplete theintracardiac partoftheoperation itisgenerally recommended thatthecirculation is restored foraperiod oftwice thelength ofcirculatoryarrest before a secondarrest ispermitted (Zindler, 1957). Theaimofthis paperistoexplain whynosuch ruleofthumbcanberecommended. Itisnecessary tofollow theacid-base balance continuously and towaituntil anormal oralkalotic state hasagain beenreached. Thismaytakelonger thananticipatedandsometimes theaddition ofsodium bicarbonate mayprovevaluable. Twocases, one withpulmonary valvular stenosis andatrial septal defect andonewithatrial septal defect combined withan abnormal pulmonary venousreturn, illustrate thevalue ofthese principles.
Impact of lapatinib plus trastuzumab versus single-agent lapatinib on quality of life of patients with trastuzumab-refractory HER2+ metastatic breast cancer
Authors: Y. Wu, M.M. Amonkar, B.H. Sherrill, J. O’Shaughnessy, C. Ellis, J. Baselga, K.L. Blackwell, H.J. Burstein
Journal: Annals of Oncology (2011)
Novel Role of Prostate-Specific Membrane Antigen in Suppressing Prostate Cancer Invasiveness
Authors: Arundhati Ghosh, Xinning Wang, Eric Klein, Warren D.W. Heston
Journal: Cancer Research (2005)

Abstract Prostate-specific membrane antigen (PSMA), a type II transmembrane glycoprotein, is overexpressed in prostate cancer. PSMA is a unique cell surface marker, negatively regulated by androgen and extensively used for imaging of hormone refractory carcinomas and metastatic foci. PSMA is a carboxypeptidase with two important enzymatic functions, namely, folate hydrolase and NAALADase. PSMA also exhibits an endocytic function, in which it spontaneously recycles through endocytic vesicles. PSMA is overexpressed at various stages of prostate cancer, including androgen-sensitive and -independent disease, increased in expression with early relapse after therapy. We have used in vitro invasion assays to explore the possible role of PSMA in the metastasis of prostate cancer cells. Androgen-dependent prostate cancer lines, which express PSMA endogenously (e.g., LNCaP, MDA PCa2b, and CWR22Rv1) are less invasive compared with androgen-independent PC3 or DU145 cells, neither of which expresses PSMA. Ectopic expression of PSMA in PC3 cells reduced the invasiveness of these cells, suggesting that this reduction in the invasion capability of PSMA-expressing cells is due to PSMA expression and not to intrinsic properties of different prostate cancer cell lines. Furthermore, knockdown of PSMA expression increased invasiveness of LNCaP cells by 5-fold. Finally, expression of PSMA mutants lacking carboxypeptidase activity reduced the impact of PSMA expression on invasiveness. Thus, it seems that the enzymatic activity is associated with the effect of PSMA on invasiveness.
Moving Away From the “One Shoe Fits All” Strategy: The Key to Future Progress in Chemotherapy
Authors: Martine J. Piccart-Gebhart
Journal: Journal of Clinical Oncology (2005)

Chemotherapy has long been considered our most efficient weapon in the fight against breast cancer, particularly in the United States, where its most enthusiastic supporters explored very high doses of cytotoxic agents in the hope of eradicating metastatic disease. This dream, unfortunately, did not materialize. In Europe, faith in our second most powerful weapon against the disease— namely endocrine therapy—grew more rapidly and reached important milestones with the demonstration that tamoxifen and, more recently, the aromatase inhibitors, have a significant impact on the course of early endocrineresponsive breast cancer. Today, divergent opinions between the continents remain, but they are much less pronounced than a decade ago. This is well exemplified by the fact that one of the Review Articles in the chapter on chemotherapy in this issue of the Journal of Clinical Oncology was co-authored by an American-Australian medical oncology team! The comprehensive review by Hamilton and Hortobagyi nicely summarizes the incremental progress made through the incorporation into the clinic of a number of new, useful cytotoxic agents that demonstrate either partial non-cross resistance with older drugs or improved toxicity profiles. It is, however, obvious that the major emphasis of the last 5 years has been on the development of new drugs, with less attention paid to four other important dimensions in the use of chemotherapy: (1) optimal drug schedule; (2) optimal timing of drug administration; (3) potential gains from a ‘‘wedding’’ of chemotherapy and newer endocrine agents; and (4) improved understanding of heterogeneity in the magnitude of treatment benefit. Let us briefly examine these four challenges one by one and understand why we need to address them better in the next 5 years. OPTIMAL DRUG SCHEDULE
EGFR Activation Increases Parathyroid Hyperplasia and Calcitriol Resistance in Kidney Disease
Authors: Maria Vittoria Arcidiacono, Tetsuhiko Sato, Daniel Alvarez-Hernandez, Jing Yang, Masanori Tokumoto, Ignacio Gonzalez-Suarez, Yan Lu, Yoshihiro Tominaga, Jorge Cannata-Andia, Eduardo Slatopolsky, Adriana S. Dusso
Journal: Journal of the American Society of Nephrology (2008)

Calcitriol, acting through vitamin D receptors (VDR) in the parathyroid, suppresses parathyroid hormone synthesis and cell proliferation. In secondary hyperparathyroidism (SH), VDR content is reduced as hyperplasia becomes more severe, limiting the efficacy of calcitriol. In a rat model of SH, activation of the EGF receptor (EGFR) by TGF-alpha is required for the development of parathyroid hyperplasia, but the relationship between EGFR activation and reduced VDR content is unknown. With the use of the same rat model, it was found that pharmacologic inhibition of EGFR activation with erlotinib prevented the upregulation of parathyroid TGF-alpha, the progression of growth, and the reduction of VDR. Increased TGF-alpha/EGFR activation induced the synthesis of liver-enriched inhibitory protein, a potent mitogen and the dominant negative isoform of the transcription factor CCAAT enhancer binding protein-beta, in human hyperplastic parathyroid glands and in the human epidermoid carcinoma cell line A431, which mimics hyperplastic parathyroid cells. Increases in liver-enriched inhibitory protein directly correlated with proliferating activity and, in A431 cells, reduced VDR expression by antagonizing CCAAT enhancer binding protein-beta transactivation of the VDR gene. Similarly, in nodular hyperplasia, which is the most severe form of SH and the most resistant to calcitriol therapy, higher TGF-alpha activation of the EGFR was associated with an 80% reduction in VDR mRNA levels. Thus, in SH, EGFR activation is the cause of both hyperplastic growth and VDR reduction and therefore influences the efficacy of therapy with calcitriol.
Cure pulmonary arterial hypertension associated with HIV (PAH-HIV)? ... Toward an answer
Authors: Colas Tcherakian, Elisabeth Rivaud, Anne-Cécile Metivier, Emilie Catherinot, David Zucman, Louis-Jean Couderc
Journal: European Respiratory Journal (2011)

PAH-HIV is a severe condition associated with HIV infection. Guidelines propose to associate a specific PAH treatment with a highly active anti-retroviral therapy (HAART).  Recent studies report some excellent response to Bosentan treatment, with hemodynamic normalisation and long term benefit of this treatment. But, there is no data upon specific treatment discontinuation  We report here two patients with persistent remission after Bosentan cessation.  Patients were women, IV drugs users, one of African origin 36-years old, the other Caucasian of 46-years old. Diagnosis of PH was performed respectively one year and twenty years after diagnosis of HIV infection. Both patients received HAART and Bosentan.  Because of persistent normalization of hemodynamic and functional parameters, bosentan was withdrawn respectively 5 and 1 years after beginning. Both patients remain asymptomatic with normal hemodynamic results respectively at 42 and 12 months after bosentan discontinuation.  Data are illustrated on figure for both patients.   Conclusion:  We propose herein to go one step further in PAH treatment with these two cases of cured PAH-HIV, despite more than three years of Bosentan discontinuation. But we recommended not stopping treatment without complete clinical, hemodynamic and immunological persistent normalisation during at least one year.
Effect of Aerobic Exercise on Plasma Adiponectin Levels and Insulin Resistance in Type 2 Diabetes
Authors: Hisayo Yokoyama, Masanori Emoto, Takahiro Araki, Shigehiko Fujiwara, Koka Motoyama, Tomoaki Morioka, Hidenori Koyama, Tetsuo Shoji, Yasuhisa Okuno, Yoshiki Nishizawa
Journal: Diabetes Care (2004)

Aerobic exercise is a generally accepted therapeutic strategy for type 2 diabetes because it has beneficial effects not only on glycemic profile, but also on reducing metabolic risk factors for cardiovascular diseases including insulin resistance. Previous studies (1,2) have showed the effects of moderate-intensity exercise on the improvement of insulin sensitivity.

Adiponectin, a protein secreted by adipose tissue, presents lower plasma levels in subjects with obesity or type 2 diabetes and is closely correlated with the degree of insulin resistance assessed by the glucose clamp technique (3). Adiponectin also plays a protective role against the development of atherosclerosis by suppressing inflammatory processes on the vascular endothelium (4,5). Therefore, adiponectin is a candidate link between insulin resistance and the high risk of cardiovascular diseases in type 2 diabetes.

To date, however, little is known about whether the improvement in insulin resistance induced by short-term aerobic exercise is associated with changes in plasma adiponectin in type 2 diabetes. Only a few reports (6,7) have examined the acute or chronic effect of high-intensity exercise on plasma adiponectin, mainly in healthy subjects using surrogate insulin resistance indexes. The aim of this study was to assess the effect of aerobic exercise on plasma adiponectin in relation to the improvement …