tbuckley/cabot-search huggingface dataset:
Use of 5-α-Reductase Inhibitors for Prostate Cancer Chemoprevention: American Society of Clinical Oncology/American Urological Association 2008 Clinical Practice Guideline
Authors: Barnett S. Kramer, Karen L. Hagerty, Stewart Justman, Mark R. Somerfield, Peter C. Albertsen, William J. Blot, H. Ballentine Carter, Joseph P. Costantino, Jonathan I. Epstein, Paul A. Godley, Russell P. Harris, Timothy J. Wilt, Janet Wittes, Robin Zon, Paul Schellhammer
Journal: Journal of Clinical Oncology (2009)

PURPOSE To develop an evidence-based guideline on the use of 5-alpha-reductase inhibitors (5-ARIs) for prostate cancer chemoprevention. METHODS The American Society of Clinical Oncology (ASCO) Health Services Committee (HSC), ASCO Cancer Prevention Committee, and the American Urological Association Practice Guidelines Committee jointly convened a Panel of experts, who used the results from a systematic review of the literature to develop evidence-based recommendations on the use of 5-ARIs for prostate cancer chemoprevention. Results The systematic review completed for this guideline identified 15 randomized clinical trials that met the inclusion criteria, nine of which reported prostate cancer period prevalence. CONCLUSION Asymptomatic men with a prostate-specific antigen (PSA) <or= 3.0 ng/mL who are regularly screened with PSA or are anticipating undergoing annual PSA screening for early detection of prostate cancer may benefit from a discussion of both the benefits of 5-ARIs for 7 years for the prevention of prostate cancer and the potential risks (including the possibility of high-grade prostate cancer). Men who are taking 5-ARIs for benign conditions such as lower urinary tract [obstructive] symptoms (LUTS) may benefit from a similar discussion, understanding that the improvement of LUTS relief should be weighed with the potential risks of high-grade prostate cancer from 5-ARIs (although the majority of the Panel members judged the latter risk to be unlikely). A reduction of approximately 50% in PSA by 12 months is expected in men taking a 5-ARI; however, because these changes in PSA may vary across men, and within individual men over time, the Panel cannot recommend a specific cut point to trigger a biopsy for men taking a 5-ARI. No specific cut point or change in PSA has been prospectively validated in men taking a 5-ARI.
Joseph Sung: marking the tenth anniversary of SARS
Authors: David Holmes
Journal: The Lancet (2013)

The timing is uncanny. As WHO closely monitors the emergence of a new deadly coronavirus, it is almost 10 years to the day on March 12, 2003, that the agency issued its first global health alert in more than a decade in an effort to combat the spread of severe acute respiratory syndrome (SARS). Most of the thousands who became infected and the almost 800 people who died from SARS during the outbreak were from China, Hong Kong, and southeast Asia, and the legacy of that trauma is still very much in evidence today.
Aflibercept in Pediatric Solid Tumors: Moving Beyond the Trap
Authors: Cindy H. Chau, William D. Figg
Journal: Clinical Cancer Research (2012)

Abstract Angiogenesis plays a pivotal role in the growth and metastasis of adult and pediatric solid tumors. Clinical investigation of angiogenesis inhibitors is currently under way for childhood cancers. While the pediatric study of aflibercept provides a proof-of-principle, challenges remain in developing clinical endpoints and biomarkers of angiogenesis for pediatric trials. Clin Cancer Res; 18(18); 4868–71. ©2012 AACR.
Mechanisms of arrhythmogenic delayed and early afterdepolarizations in ferret ventricular muscle.
Authors: E Marban, S W Robinson, W G Wier
Journal: Journal of Clinical Investigation (1986)

Drug-induced triggered arrhythmias in heart muscle involve oscillations of membrane potential known as delayed or early afterdepolarizations (DADs or EADs). We examined the mechanism of DADs and EADs in ferret ventricular muscle. Membrane potential, tension and aequorin luminescence were measured during exposure to elevated [Ca2+]0, strophanthidin and/or isoproterenol (to induce DADs), or cesium chloride (to induce EADs). Ryanodine (10(-9)-10(-6) M), an inhibitor of Ca2+ release from the sarcoplasmic reticulum, rapidly suppressed DADs and triggered arrhythmias. When cytoplasmic Ca2+-buffering capacity was enhanced by loading cells with the Ca2+ chelators BAPTA or quin2, DADs were similarly inhibited, as were contractile force and aequorin luminescence. In contrast to DADs, EADs induced by Cs were not suppressed by ryanodine or by loading with intracellular Ca2+ chelators. The possibility that transsarcolemmal Ca2+ entry might produce EADs was evaluated with highly specific dihydropyridine Ca channel agonists and antagonists. Bay K8644 (100-300 nM) potentiated EADs, whereas nitrendipine (3-20 microM) abolished EADs. We conclude that DADs and DAD-related triggered arrhythmias are activated by an increase in intracellular free Ca2+ concentration, whereas EADs do not require elevated [Ca2+]i but rather arise as a direct consequence of Ca2+ entry through sarcolemmal slow Ca channels.
Symptoms experienced by COPD patients during exacerbations and their association with healthcare utilization – EXACO study
Authors: Isabelle Tillie Leblond, Frédéric Masure, Bruno Housset, Nicolas Roche, Thierry Perez, Isabelle Boucot, François Denis, Aida Myftiu, Juliette Ostinelli, Isabelle Pithois-Merli, Céline Pribil, Stephane Schück
Journal: European Respiratory Journal (2011)

Background:  Definitions of COPD exacerbations are symptom-based while severity assessment often relies on the level of healthcare utilization.   Objectives:  To assess symptoms associated with COPD exacerbations and their association with patients9 decision to seek healthcare.   Methods:  Patients with GOLD stage ≥ II COPD participating in an observational study, reported symptoms and healthcare use associated with exacerbations by telephone interviews.   Results:  835 patients reported 3 527 exacerbations. The most common symptom was increased breathlessness. 82.2% of led to a medical consultation, visit to a hospital. Fever was the symptom most strongly associated with the decision to seek healthcare.   Conclusions:  Breathlessness was by far the dominant symptom of exacerbations while fever was the strongest predictor of health care utilization.
INTRAVENOUS SCLEROSING SOLUTIONS
Authors: T. H. T. Barber
Journal: BMJ (1930)

Late Loeal Ef#ects.-Theseconisist prinicipally of ecehy- moses anid gangrene of the vein, and ulcer;, of these, the n-ot coelni_ a by far is t!e '' in jection ulcer,'' which is due ill illost cases to the lel)osition of tlhe solttioni in the tissues r,oun1d.tile veini.It is serious and painful, anrd four to six mlolnthis elapse before a c-ure is effected.No
Is OT interval prolongation a strong or a weak predictor for cardiac death?
Authors: J M Dekker, E G Schouten, A Algra, J Pool
Journal: Circulation (1993)

Is QT Interval Prolongation a Strong or a Weak Predictor for Cardiac Death?In Ahnve's Editorial Comment in Circulation, ' based in part on our own papers,23 he discusses the prognostic value of QT, prolongation.We agree with his conclusion that QT, duration of >440 msec is associated with increased risk for cardiac death.However, we would like to draw attention to the observed difference between men and women.Among women, the prevalence of QT, prolongation is two to three times higher than among men.2-6However, we found that
SOME REMARKS ON THE BACTERICIDAL PROPERTIES OF ZINC OXIDE
Authors: H. HAXTHAUSEN, C. Rasch
Journal: British Journal of Dermatology (1928)

Journal Article SOME REMARKS ON THE BACTERICIDAL PROPERTIES OF ZINC OXIDE Get access H. HAXTHAUSEN, M.D., H. HAXTHAUSEN, M.D. From the Skin‐Department of the Rigshospital, Copenhagen Search for other works by this author on: Oxford Academic Google Scholar C. Rasch C. Rasch From the Skin‐Department of the Rigshospital, Copenhagen Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 40, Issue 12, 1 December 1928, Pages 497–501, https://doi.org/10.1111/j.1365-2133.1928.tb13640.x Published: 01 December 1928
Feedback regulation of angiotensin converting enzyme activity and mRNA levels by angiotensin II.
Authors: H Schunkert, J R Ingelfinger, A T Hirsch, Y Pinto, W J Remme, H Jacob, V J Dzau
Journal: Circulation Research (1993)

Although renin and angiotensinogen are known to be subject to feedback regulation, the effects of angiotensin II (Ang II) on the regulation of angiotensin converting enzyme (ACE) gene expression and enzymatic activity have not yet been studied. Therefore, the effects of exogenous Ang II infusion and ACE inhibition on ACE mRNA expression were examined. Ang II was infused intravenously in male Sprague-Dawley rats for 3 days at 100 (low dose), 300 (medium dose), or 1,000 (high dose) ng/kg per minute (n = 8 for each group). Compared with control (vehicle infusion, n = 8), Ang II infusion increased plasma Ang II concentration (62, 101, 126 [p &lt; 0.05], and 187 [p &lt; 0.05] fmol/ml) and mean arterial blood pressure (106, 119 [p &lt; 0.05], 134 [p &lt; 0.05], and 125 mm Hg for control, low, medium, and high doses, respectively). Ang II infusion decreased ACE mRNA levels in the lung (57%, 52%, and 51%; p &lt; 0.05 for each) and testis (49%, 63%, and 53% of control for low, medium, and high doses, respectively; p &lt; 0.05 for each), two major sites of ACE synthesis. There was, albeit less pronounced, a parallel decrease in pulmonary ACE activity (4.38, 3.92, 3.07 [p &lt; 0.05], and 3.48 [p &lt; 0.05] nM/mg per minute for control, medium, and high doses, respectively). In contrast, serum (54, 50, 48, and 38 [p &lt; 0.05] nM/ml per minute) and testicular (2.63, 2.08 [p &lt; 0.05], 2.24, and 2.18 nM/mg per minute for control, low, medium, and high doses, respectively) ACE activities displayed only minimal change in animals infused with Ang II.(ABSTRACT TRUNCATED AT 250 WORDS)
Small-Molecule Screening Identifies Modulators of Aquaporin-2 Trafficking
Authors: Jana Bogum, Dörte Faust, Kerstin Zühlke, Jenny Eichhorst, Marie C. Moutty, Jens Furkert, Adeeb Eldahshan, Martin Neuenschwander, Jens Peter von Kries, Burkhard Wiesner, Christiane Trimpert, Peter M.T. Deen, Giovanna Valenti, Walter Rosenthal, Enno Klussmann
Journal: Journal of the American Society of Nephrology (2013)

In the principal cells of the renal collecting duct, arginine vasopressin (AVP) stimulates the synthesis of cAMP, leading to signaling events that culminate in the phosphorylation of aquaporin-2 water channels and their redistribution from intracellular domains to the plasma membrane via vesicular trafficking. The molecular mechanisms that control aquaporin-2 trafficking and the consequent water reabsorption, however, are not completely understood. Here, we used a cell-based assay and automated immunofluorescence microscopy to screen 17,700 small molecules for inhibitors of the cAMP-dependent redistribution of aquaporin-2. This approach identified 17 inhibitors, including 4-acetyldiphyllin, a selective blocker of vacuolar H(+)-ATPase that increases the pH of intracellular vesicles and causes accumulation of aquaporin-2 in the Golgi compartment. Although 4-acetyldiphyllin did not inhibit forskolin-induced increases in cAMP formation and downstream activation of protein kinase A (PKA), it did prevent cAMP/PKA-dependent phosphorylation at serine 256 of aquaporin-2, which triggers the redistribution to the plasma membrane. It did not, however, prevent cAMP-induced changes to the phosphorylation status at serines 261 or 269. Last, we identified the fungicide fluconazole as an inhibitor of cAMP-mediated redistribution of aquaporin-2, but its target in this pathway remains unknown. In conclusion, our screening approach provides a method to begin dissecting molecular mechanisms underlying AVP-mediated water reabsorption, evidenced by our identification of 4-acetyldiphyllin as a modulator of aquaporin-2 trafficking.
A multicentre study of capecitabine, oxaliplatin plus bevacizumab as perioperative treatment of patients with poor-risk colorectal liver-only metastases not selected for upfront resection
Authors: R Wong, D Cunningham, Y Barbachano, C Saffery, J Valle, T Hickish, S Mudan, G Brown, A Khan, A Wotherspoon, A S Strimpakos, J Thomas, S Compton, Y J Chua, I Chau
Journal: Annals of Oncology (2011)
Total and cause specific mortality among Swedish women with cosmetic breast implants: prospective study
Authors: V C M Koot
Journal: BMJ (2003)

The potential health hazards of breast implants have been heavily debated for the past decade, yet only one study has reported on long term mortality among women with such implants, and around one fifth of the participants were lost to follow up. 1 2 We assessed total and cause specific mortality among Swedish women who underwent augmentation mammoplasty between 1965 and 1993. As a desire for cosmetic surgery represents underlying psychopathology in some patients, we hypothesised that deaths due to suicide may be over-represented.3

Details about accrual of the cohort have been given elsewhere.4 We obtained records from the Swedish Inpatient Register of all 15–69 year old women who had had breast implants (n=7585) in 1965-93. We identified records with erroneous registration numbers or where emigration or death occurred before surgery through linkages with registers held by Statistics Sweden, using the unique national registration numbers. We excluded such records and records where surgery occurred …
Surfactant protein C G100S mutation causes familial pulmonary fibrosis in Japanese kindred
Authors: S. Ono, T. Tanaka, M. Ishida, A. Kinoshita, J. Fukuoka, M. Takaki, N. Sakamoto, Y. Ishimatsu, S. Kohno, T. Hayashi, M. Senba, M. Yasunami, Y. Kubo, L. M. Yoshida, H. Kubo, K. Ariyoshi, K. Yoshiura, K. Morimoto
Journal: European Respiratory Journal (2011)

Several mutations in the surfactant protein C (SP-C) gene (<i>SFTPC</i>) have been reported as causing familial pulmonary fibrosis (FPF). However, the genetic background and clinical features of FPF are still not fully understood. We identified one Japanese kindred, in which at least six individuals over three generations were diagnosed with pulmonary fibrosis. We examined the patients radiologically and histopathologically and sequenced their <i>SFTPC</i> and <i>ABCA3</i> genes. We also established a cell line stably expressing the mutant gene. All the patients had similar radiological and histopathological characteristics. Their histopathological pattern was that of usual interstitial pneumonia, showing numerous fibroblastic foci even in areas without abnormal radiological findings on chest high-resolution computed tomography. No child had respiratory symptoms in the kindred. Sequencing of <i>SFTPC</i> showed a novel heterozygous mutation, c.298G&gt;A (G100S), in the BRICHOS domain of proSP-C, which co-segregated with the disease. However, in the <i>ABCA3</i> gene, no mutation was found. <i>In vitro</i> expression of the mutant gene revealed that several endoplasmic reticulum stress-related proteins were strongly expressed. The mutation increases endoplasmic reticulum stress and induces apoptotic cell death compared with wild-type SP-C in alveolar type II cells, supporting the significance of this mutation in the pathogenesis of pulmonary fibrosis.
Nicotinamide reduces photodynamic therapy-induced immunosuppression in humans
Authors: S.M. Thanos, G.M. Halliday, D.L. Damian
Journal: British Journal of Dermatology (2012)

The immune suppressive effects of topical photodynamic therapy (PDT) are potential contributors to treatment failure after PDT for nonmelanoma skin cancer. Nicotinamide (vitamin B(3) ) prevents immune suppression by ultraviolet radiation, but its effects on PDT-induced immunosuppression are unknown.To determine the effects of topical and oral nicotinamide on PDT-induced immunosuppression in humans.Twenty healthy Mantoux-positive volunteers received 5% nicotinamide lotion or vehicle to either side of the back daily for 3 days. Another group of 30 volunteers received 500 mg oral nicotinamide or placebo twice daily for 1 week in a randomized, double-blinded, crossover design. In each study, methylaminolaevulinate cream was applied to discrete areas on the back, followed by narrowband red light irradiation (37 J cm(-2) ) delivered at high (75 mW cm(-2) ) or low (15 mW cm(-2) ) irradiance rates. Adjacent, nonirradiated sites served as controls. Delayed-type hypersensitivity (Mantoux) reactions were assessed at treatment and control sites to determine immunosuppression.High irradiance rate PDT with vehicle or with placebo caused significant immunosuppression (equivalent to 48% and 50% immunosuppression, respectively; both P < 0·0001); topical and oral nicotinamide reduced this immunosuppression by 59% and 66%, respectively (both P < 0·0001). Low irradiance rate PDT was not significantly immunosuppressive in the topical nicotinamide study (15% immunosuppression, not significant), but caused 22% immunosuppression in the oral study (placebo arm; P = 0·006); nicotinamide reduced this immunosuppression by 69% (P = 0·045).While the clinical relevance of these findings is currently unknown, nicotinamide may provide an inexpensive means of preventing PDT-induced immune suppression and enhancing PDT cure rates.
Biological Role of Estrogen Receptor β in Salivary Gland Adenocarcinoma Cells
Authors: Kazufumi Ohshiro, Suresh K. Rayala, Michelle D. Williams, Rakesh Kumar, Adel K. El-Naggar
Journal: Clinical Cancer Research (2006)

Abstract Purpose: This study is intended to investigate the biological role of estrogen receptor (ER) nongenomic signaling in salivary gland adenocarcinoma cells that predominantly express ERβ. Experimental Design: Salivary gland adenocarcinoma cell lines HSG and HSY were used to study the effect of diarylpropionitrile and estrogen on the nongenomic signaling of ERβ, cytoskeletal remodeling, and cell motility. Results: We found that diarylpropionitrile and estrogen triggered rapid activation of the extracellular signal-regulated kinase 1/2 (ERK), Src, and focal adhesion kinase signaling pathways. Estrogen stimulation also induced long cytoplasmic extensions, filopodia formation, and abnormal outgrowths in both HSG and HSY cells. We further observed that ligand-induced migration of these cells was blocked by the pure antiestrogen ICI 182780 and the mitogen-activated protein/ERK kinase inhibitor PD98059, indicating that estrogen-induced cell migration is mediated by the activation of ERβ nongenomic signaling. Conclusion: These results clearly showed that ERβ nongenomic signaling is active in salivary gland cells and has a biological role in migration, presumably via the stimulation of ERK1/2. In future, the findings of this study might have clinical importance as several ERβ-selective agonists are currently being available, and these could potentially be used for therapeutic targeting of ERβ-positive salivary tumors.
Sudden cardiac death: mandatory exclusion of athletes at risk is a step too far
Authors: Lynley Anderson, Dan Exeter, Lynne Bowyer
Journal: British Journal of Sports Medicine (2011)

Sudden cardiac death (SCD) in young athletes is a distressing event and it is not surprising that some physicians working with sports people are proposing that preventive action should be taken. There is a push for a system similar to that established in some countries, which involves screening and mandatory exclusion of those at risk. We argue that while screening can provide useful information to at-risk athletes making decisions about their future athletic careers, mandatory exclusion of athletes is paternalistic and such decisions are not rightfully within the domain of medicine.
Allometric Scaling Law Questions the Traditional Mechanical Model for Axillary Lymph Node Involvement in Breast Cancer
Authors: Romano Demicheli, Elia Biganzoli, Patrizia Boracchi, Marco Greco, William J.M. Hrushesky, Michael W. Retsky
Journal: Journal of Clinical Oncology (2006)

Purpose To find a quantitative relationship between tumor size and frequency of axillary lymph node involvement. Patients and Methods The frequency of axillary node involvement versus primary tumor volume was analyzed in 10 selected series of patients incorporating a total of 57,244 women with resectable breast cancer. The average number of events per unit volume resulting in tumor spread to axillary lymph nodes before tumor surgical removal Θ(V)/V, was estimated under simple probabilistic assumptions. Results The allometric scaling law Θ(V)/V = 0.0586V −0.7457 was estimated on the data, fitting the proportion of lymph node involvement on tumor volume V (in microliters). The estimate 0.7457 (95% CI, 0.7200 to 0.7713) suggests that the true scaling exponent, under the assumed model, may be the fractional value, which characterizes scaling relationships for a wide variety of biologic variables at both the whole organism level and organ level. Conclusion Results suggest that the phenomenon should be related to some internal structural trait of the tumor. The vascular network seems to be the best candidate. This result does not support a mere mechanical model of lymphatic tumor spread. A more complex biology-based model of lymphohematogenous spread is suggested, in which the axillary nodes draining the lymph from the primary tumor may become activated by factors produced by both tumor cells and tumor stroma, thus favoring cell-selective homing of otherwise circulating tumor cells. The success of fractal features related to the internal architecture brings additional support to the consideration of primary breast cancer as an organ-like structure.
Protein phosphatase subunit G5PR is needed for inhibition of B cell receptor–induced apoptosis
Authors: Yan Xing, Hideya Igarashi, Xiaodan Wang, Nobuo Sakaguchi
Journal: The Journal of Experimental Medicine (2005)

B cell receptor (BCR) cross-linking induces B cell proliferation and sustains survival through the phosphorylation-dependent signals. We report that a loss of the protein phosphatase component G5PR increased the activation-induced cell death (AICD) and thus impaired B cell survival. G5PR associates with GANP, whose expression is up-regulated in mature B cells of the peripheral lymphoid organs. To study G5PR function, the G5pr gene was conditionally targeted with the CD19-Cre combination (G5pr−/− mice). The G5pr−/− mice had a decreased number of splenic B cells (60% of the controls). G5pr−/− B cells showed a normal proliferative response to lipopolysaccharide or anti-CD40 antibody stimulation but not to BCR cross-linking with or without IL-4 in vitro. G5pr−/− B cells did not show abnormalities in the BCR-mediated activation of Erks and NF-κB, cyclin D2 induction, or Akt activation. However, G5pr−/− B cells were sensitive to AICD caused by BCR cross-linking. This was associated with an increased depolarization of the mitochondrial membrane and the enhanced activation of c-Jun NH2-terminal protein kinase and Bim. These results suggest that G5PR is required for the BCR-mediated proliferation associated with the prevention of AICD in mature B cells.
Novel CD20 monoclonal antibodies for lymphoma therapy
Authors: Shundong Cang, Nikhil Mukhi, Kemeng Wang, Delong Liu
Journal: Journal of Hematology & Oncology (2012)

Abstract Rituximab (RTX), a monoclonal antibody (mAb) against CD20, has been widely used for lymphoma therapy. RTX in combination with cyclophosphamide /doxorubicin /vincristine /prednisone (R-CHOP) remains the standard frontline regimen for diffuse large B-cell lymphoma. However, suboptimal response and /or resistance to rituximab have remained a challenge in the therapy of B-cell non-Hodgkin’s lymphoma (NHL). Novel agents are under active clinical trials. This review will summarize the latest development in new mAbs against CD20, which include second-generation mAbs, ofatumumab, veltuzumab (IMMU-106), ocrelizumab (PRO70769), and third-generation mAbs, AME-133v (ocaratuzumab), PRO131921 and GA101 (obinutumumab).