tbuckley/cabot-search huggingface dataset:
High dose nicotinamide in the treatment of necrobiosis lipoidica
Authors: SUSAN HANDFIELD-JONES, S. JONES, R. PEACHEY
Journal: British Journal of Dermatology (1988)

Journal Article High dose nicotinamide in the treatment of necrobiosis lipoidica Get access SUSAN HANDFIELD‐JONES, SUSAN HANDFIELD‐JONES Department of Dermatology, Bristol Royal Infirmary, Bristol BS2 8HW, U.K. Dr S. Jones. Search for other works by this author on: Oxford Academic Google Scholar S. JONES, S. JONES Department of Dermatology, Bristol Royal Infirmary, Bristol BS2 8HW, U.K. Search for other works by this author on: Oxford Academic Google Scholar R. PEACHEY R. PEACHEY Department of Dermatology, Bristol Royal Infirmary, Bristol BS2 8HW, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 118, Issue 5, 1 May 1988, Pages 693–696, https://doi.org/10.1111/j.1365-2133.1988.tb02572.x Published: 01 May 1988
UK government may consider minimum price for alcohol
Authors: A. O'Dowd
Journal: BMJ (2009)

The UK government is considering several options on pricing of alcohol and has not ruled out a minimum price per unit, MPs were told at the parliamentary health select committee’s inquiry into alcohol held last week.

MPs on the committee asked Gillian Merron, public health minister, whether she supported the chief medical officer Liam Donaldson’s call for minimum pricing on alcohol in his annual report published in March, a call that was rejected at the time. Ms Merron replied, “We work very closely with the chief medical officer. We are not ruling this out. I am interested in exploring various pricing options.

“It’s a big decision should a government decide to interfere in any way in …
Opportunistic Screening for Diabetes in Routine Clinical Practice
Authors: Mark W. Ealovega, Bahman P. Tabaei, Michael Brandle, Ray Burke, William H. Herman
Journal: Diabetes Care (2004)

Since 1997, the American Diabetes Association has recommended that nondiabetic individuals >/=45 years of age be screened for diabetes at least every 3 years. We sought to characterize the frequency, methods, and results of diabetes screening in routine clinical practice.We studied opportunistic screening in nondiabetic members of a health maintenance organization >/=45 years of age who were assigned to a large, integrated, academic health care delivery system. Screening was defined as the first glucose, HbA(1c), or oral glucose tolerance test (OGTT) performed between 1 January 1998 and 31 December 2000. Chart review was performed to determine the prevalence of diabetes risk factors and to describe follow-up.Of 8,286 nondiabetic patients >/=45 years of age, 69% (n = 5,752) were screened. The frequency of screening was greater in patients with one or more primary care visits and increased with age. Women were more likely to be screened than men, and patients with at least one diabetes risk factor were more likely to be screened than those without risk factors. Random plasma glucose was the most common screening test (95%). Four percent (n = 202) of those screened had abnormal results. Only 38% (n = 77) of those with abnormal results received appropriate follow-up, and 17% (n = 35) were diagnosed with diabetes within 6 months of screening. The yield of screening was very low (0.6%, 35 of 5,752).Despite frequent screening and appropriate targeting of high-risk patients, follow-up of patients with abnormal results is uncommon and the yield of screening is low. Interventions are needed to help physicians recognize and provide appropriate follow-up for patients with potentially abnormal random glucose levels.
Randomized Phase III Trial of High–Dose-Intensity Methotrexate, Vinblastine, Doxorubicin, and Cisplatin (MVAC) Chemotherapy and Recombinant Human Granulocyte Colony-Stimulating Factor Versus Classic MVAC in Advanced Urothelial Tract Tumors: European Organization for Research and Treatment of Cancer Protocol No. 30924
Authors: C. N. Sternberg, P. H.M. de Mulder, J. H. Schornagel, C. Théodore, S. D. Fossa, A. T. van Oosterom, F. Witjes, M. Spina, C. J. van Groeningen, C. de Balincourt, L. Collette
Journal: Journal of Clinical Oncology (2001)

PURPOSE: This randomized trial evaluated antitumor activity of and survival asociated with high–dose-intensity chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) plus granulocyte colony-stimulating factor (HD-MVAC) versus MVAC in patients with advanced transitional-cell carcinoma (TCC). PATIENTS AND METHODS: A total of 263 patients with metastatic or advanced TCC who had no prior chemotherapy were randomized to HD-MVAC (2-week cycles) or MVAC (4-week cycles). RESULTS: Using an intent-to-treat analysis, at a median follow-up of 38 months, on the HD-MVAC arm there were 28 complete responses (CRs) (21%) and 55 partial responses (PRs) (41%), for an overall response of 62% (95% confidence interval [CI], 54% to 70%). On the MVAC arm, there were 12 CRs (9%) and 53 PRs (41%), for an overall response of 50% (95% CI, 42% to 59%). The P value for the difference in CR rate was .009; and for the overall response, it was .06. There was no statistically significant difference in survival (P = .122) or time to progression (P = .114). Progression-free survival was significantly better with HD-MVAC (P=.037; hazard ratio .75; 95% CI .58 to .98). The median progression-free survival time was 9.1 months on the HD-MVAC arm versus 8.2 months on the MVAC arm. The 2-year progression-free survival rate was 24.7% for HD-MVAC (95% CI, 17.1% to 32.3%) versus 11.6% for MVAC (95% CI, 5.9% to 17.4%). CONCLUSION: With HD-MVAC, it was possible to deliver twice the doses of cisplatin and doxorubicin in half the time, with fewer dose delays and less toxicity. Although a 50% difference in median overall survival was not detected, a benefit was observed in progression-free survival, CR rates, and overall response rates with HD-MVAC.
Melanesian and Asian Origins of Polynesians: mtDNA and Y Chromosome Gradients Across the Pacific
Authors: Manfred Kayser, Silke Brauer, Richard Cordaux, Amanda Casto, Oscar Lao, Lev A. Zhivotovsky, Claire Moyse-Faurie, Robb B. Rutledge, Wulf Schiefenhoevel, David Gil, Alice A. Lin, Peter A. Underhill, Peter J. Oefner, Ronald J. Trent, Mark Stoneking
Journal: Molecular Biology and Evolution (2006)

The human settlement of the Pacific Islands represents one of the most recent major migration events of mankind. Polynesians originated in Asia according to linguistic evidence or in Melanesia according to archaeological evidence. To shed light on the genetic origins of Polynesians, we investigated over 400 Polynesians from 8 island groups, in comparison with over 900 individuals from potential parental populations of Melanesia, Southeast and East Asia, and Australia, by means of Y chromosome (NRY) and mitochondrial DNA (mtDNA) markers. Overall, we classified 94.1% of Polynesian Y chromosomes and 99.8% of Polynesian mtDNAs as of either Melanesian (NRY-DNA: 65.8%, mtDNA: 6%) or Asian (NRY-DNA: 28.3%, mtDNA: 93.8%) origin, suggesting a dual genetic origin of Polynesians in agreement with the “Slow Boat” hypothesis. Our data suggest a pronounced admixture bias in Polynesians toward more Melanesian men than women, perhaps as a result of matrilocal residence in the ancestral Polynesian society. Although dating methods are consistent with somewhat similar entries of NRY/mtDNA haplogroups into Polynesia, haplotype sharing suggests an earlier appearance of Melanesian haplogroups than those from Asia. Surprisingly, we identified gradients in the frequency distribution of some NRY/mtDNA haplogroups across Polynesia and a gradual west-to-east decrease of overall NRY/mtDNA diversity, not only providing evidence for a west-to-east direction of Polynesian settlements but also suggesting that Pacific voyaging was regular rather than haphazard. We also demonstrate that Fiji played a pivotal role in the history of Polynesia: humans probably first migrated to Fiji, and subsequent settlement of Polynesia probably came from Fiji.
Biologically Different Subgroups of Invasive Ductal Carcinoma of the Pancreas
Authors: Hidenori Takahashi, Tatsuya Oda, Takahiro Hasebe, Yasuyuki Aoyagi, Taira Kinoshita, Masaru Konishi, Toshio Nakagohri, Kazuto Inoue, Shinichiro Takahashi, Hiroshi Kawahira, Morito Monden, Atsushi Ochiai
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Among invasive ductal carcinomas of the pancreas (IDCP), there is a morphologically characteristic subgroup accompanied by abundant intraductal carcinoma components (ICCs). With the aim of determining whether ICC-rich IDCP are biologically different from ICC-poor IDCP, the expression status of Dpc4 protein was analyzed. Experimental Design: A total of 43 IDCP was subdivided into two groups: (a) ICC-rich IDCP (ICCs area occupies ≥10% of the entire tumorous area); and (b) ICC-poor IDCP (with &amp;lt;10% of ICCs area). A total of 10 invasive carcinomas derived from intraductal papillary-mucinous neoplasms (ICs from IPMNs) were also analyzed. Each invasive and intraductal carcinoma area was then evaluated for Dpc4 protein status by immunohistochemistry. Results: In a total of 43 IDCP, there were 23 ICC-rich IDCP and 20 ICC-poor IDCP. Dpc4-positive immunostaining was observed in the invasive carcinoma component of ICC-rich IDCP, ICC-poor IDCP, and ICs from IPMN in 18 of 23 (78%), 4 of 20 (20%), and 7 of 10 (70%) cases, respectively. In the intraductal component, positive staining for Dpc4 was found in 20 of 23 (87%), 3 of 7 (41%), and 8 of 10 (80%) cases, respectively. Dpc4 expression was found in both the invasive and ICC components of ICC-rich IDCP, similar to that found in IC derived from IPMN, whereas the expression of Dpc4 was largely diminished in ICC-poor IDCP. Conclusions: Morphologically distinct subgroups of invasive ductal carcinomas of the pancreas, namely ICC-rich IDCP and ICC-poor IDCP, are also biologically distinguishable as revealed by the differential expression of Dpc4.
TCT-904 Catheter Laboratory Predictors Of Post Procedure Paraprosthetic Aortic Regurgitation Following Self-expanding Medtronic CoreValve Implantation: A Multicentre Registry Analysis
Authors: Omar Ali, Carl Schultz, Andrew Jabbour, Michael Rubens, Mohamed Amrani, Carlo Di Mario, Neil Moat, Peter De Jaegere, Miles Dalby
Journal: Journal of the American College of Cardiology (2012)
Randomized Comparison of GR-II Stent and Palmaz-Schatz Stent for Elective Treatment of Coronary Stenoses
Authors: Alexandra J. Lansky, Gary S. Roubin, Charles D. O’Shaughnessy, Paul B. Moore, Larry S. Dean, Albert E. Raizner, Robert D. Safian, James P. Zidar, Jennifer L. Kerr, Jeffrey J. Popma, Roxana Mehran, Richard E. Kuntz, Martin B. Leon
Journal: Circulation (2000)

This prospective multicenter randomized clinical trial was designed to evaluate the long-term angiographic and clinical outcomes of elective treatment with the GR-II stent compared with the Palmaz-Schatz (PS) stent in patients with coronary stenoses.Seven hundred fifty-five patients with myocardial ischemia and de novo native coronary stenoses in 3- to 4-mm vessels were randomly assigned to the PS (375 patients) or the GR-II stent (380 patients). The primary end point was 12-month target lesion revascularization (TLR)-free survival. Angiography was performed at baseline and at follow-up in the first 300 consecutive patients to assess the frequency of angiographic restenosis. Procedure success was 98.5% for the GR-II stent and 99.4% for the PS stent (P:=0.19). At 30 days, patients assigned to the GR-II stent had a higher stent thrombosis rate (3.9% versus 0.3% for PS stent, P:<0.001) and TLR rate (3.9% versus 0.5% for PS stent, P:<0.001). The GR-II group had a higher follow-up restenosis frequency (47.3% versus 20.6% for the PS group, P:<0.001) and a lower 12-month TLR-free survival rate (71.7% versus 83.9% for the PS group, P:<0. 001). Multivariate logistic regression analysis identified a smaller final stent minimal lumen diameter (odds ratio [OR] 2.49, 95% CI 1. 56 to 3.98; P:<0.001), diabetes mellitus (OR 2.14, 95% CI 1.42 to 3. 22; P:<0.001), and use of the GR-II stent (OR 1.78, 95% CI 1.20 to 2. 64; P:<0.01) as independent determinants of 12-month TLR.On the basis of these long-term follow-up data, we conclude that use of the GR-II stent should be limited to the acute treatment of abrupt or threatened closure after failed conventional balloon angioplasty procedures.
The Growing Impact of Globalization for Health and Public Health Practice
Authors: Ronald Labonté, Katia Mohindra, Ted Schrecker
Journal: Annual Review of Public Health (2011)

In recent decades, public health policy and practice have been increasingly challenged by globalization, even as global financing for health has increased dramatically. This article discusses globalization and its health challenges from a vantage of political science, emphasizing increased global flows (of pathogens, information, trade, finance, and people) as driving, and driven by, global market integration. This integration requires a shift in public health thinking from a singular focus on international health (the higher disease burden in poor countries) to a more nuanced analysis of global health (in which health risks in both poor and rich countries are seen as having inherently global causes and consequences). Several globalization-related pathways to health exist, two key ones of which are described: globalized diseases and economic vulnerabilities. The article concludes with a call for national governments, especially those of wealthier nations, to take greater account of global health and its social determinants in all their foreign policies.
The ABL Switch Control Inhibitor DCC-2036 Is Active against the Chronic Myeloid Leukemia Mutant BCR-ABLT315I and Exhibits a Narrow Resistance Profile
Authors: Christopher A. Eide, Lauren T. Adrian, Jeffrey W. Tyner, Mary Mac Partlin, David J. Anderson, Scott C. Wise, Bryan D. Smith, Peter A. Petillo, Daniel L. Flynn, Michael W.N. Deininger, Thomas O'Hare, Brian J. Druker
Journal: Cancer Research (2011)

Abstract Acquired point mutations within the BCR-ABL kinase domain represent a common mechanism of resistance to ABL inhibitor therapy in patients with chronic myeloid leukemia (CML). The BCR-ABLT315I mutant is highly resistant to imatinib, nilotinib, and dasatinib, and is frequently detected in relapsed patients. This critical gap in resistance coverage drove development of DCC-2036, an ABL inhibitor that binds the switch control pocket involved in conformational regulation of the kinase domain. We evaluated the efficacy of DCC-2036 against BCR-ABLT315I and other mutants in cellular and biochemical assays and conducted cell-based mutagenesis screens. DCC-2036 inhibited autophosphorylation of ABL and ABLT315I enzymes, and this activity was consistent with selective efficacy against Ba/F3 cells expressing BCR-ABL (IC50: 19 nmol/L), BCR-ABLT315I (IC50: 63 nmol/L), and most kinase domain mutants. Ex vivo exposure of CML cells from patients harboring BCR-ABL or BCR-ABLT315I to DCC-2036 revealed marked inhibition of colony formation and reduced phosphorylation of the direct BCR-ABL target CrkL. Cell-based mutagenesis screens identified a resistance profile for DCC-2036 centered around select P-loop mutations (G250E, Q252H, Y253H, E255K/V), although a concentration of 750 nmol/L DCC-2036 suppressed the emergence of all resistant clones. A decreased concentration of DCC-2036 (160 nmol/L) in dual combination with either nilotinib or dasatinib achieved the same zero outgrowth result. Further screens for resistance due to BCR-ABL compound mutations (two mutations in the same clone) identified BCR-ABLE255V / T315I as the most resistant mutant. Taken together, these findings support continued evaluation of DCC-2036 as an important new agent for treatment-refractory CML. Cancer Res; 71(9); 3189–95. ©2011 AACR.
Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II)
Authors: Werner Hacke, Markku Kaste, Cesare Fieschi, Rüdiger von Kummer, Antoni Davalos, Dieter Meier, Vincent Larrue, Erich Bluhmki, Stephen Davis, Geoffrey Donnan, Dietmar Schneider, Exuperio Diez-Tejedor, Paul Trouillas
Journal: The Lancet (1998)
Systemic Stromal Effects of Estrogen Promote the Growth of Estrogen Receptor–Negative Cancers
Authors: Piyush B. Gupta, David Proia, Oya Cingoz, Janusz Weremowicz, Stephen P. Naber, Robert A. Weinberg, Charlotte Kuperwasser
Journal: Cancer Research (2007)

Abstract Numerous hormonal factors contribute to the lifetime risk of breast cancer development. These include inherited genetic mutations, age of menarche, age of menopause, and parity. Inexplicably, there is evidence indicating that ovariectomy prevents the formation of both estrogen receptor (ER)–positive and ER-negative breast cancers, suggesting that ER-negative breast cancers are dependent on ovarian hormones for their formation. To examine the mechanism(s) by which this may be occurring, we investigated the hypothesis that steroid hormones promote the outgrowth of ER-negative cancers by influencing host cell types distinct from the mammary epithelial cells. We used a novel xenograft mouse model of parturition-induced breast carcinoma formation, in which the tumors that arise following pregnancy lack the expression of nuclear hormone receptors, thereby recapitulating many clinical cases of this disease. Despite lacking ER expression, the tumors arising following pregnancy in this model require circulating estrogens for their formation. Moreover, increasing the levels of circulating estrogens sufficed to promote the formation and progression of ER-negative cancers, which was accompanied by a systemic increase in host angiogenesis and was attendant with the recruitment of bone marrow–derived stromal cells. Furthermore, bone marrow cells from estrogen-treated mice were sufficient to promote tumor growth. These results reveal a novel mechanism by which estrogens promote the growth of ER-negative cancers. [Cancer Res 2007;67(5):2062–71]
Zonal down-regulation and redistribution of the multidrug resistance protein 2 during bile duct ligation in rat liver
Authors: Coen C. Paulusma, M. J. Kothe, Conny T. Bakker, Piter J. Bosma, Irene van Bokhoven, Jan van Marle, Ulrich Bolder, Guido N. Tytgat, Ronald P. Elferink
Journal: Hepatology (2000)

We have studied regulation of the multidrug resistance protein 2 (mrp2) during bile duct ligation (BDL) in the rat. In hepatocytes isolated after 16, 48, and 72 hours of BDL, mrp2-mediated dinitrophenyl-glutathione (DNP-GS) transport was decreased to 65%, 33%, and 33% of control values, respectively. The impaired mrp2-mediated transport coincided with strongly decreased mrp2 protein levels, without any significant changes in mrp2 RNA levels. Restoration of bile flow after a 48-hour BDL period resulted in a slow recovery of mrp2-mediated transport and protein levels. Immunohistochemical detection of the protein in livers of rats undergoing BDL showed strongly reduced mrp2 staining after 48 hours, which was initiated in the periportal areas of the liver lobule and progressed toward the pericentral areas after 96 hours. Immunofluorescent detection of mrp2 in livers of rats undergoing 48 hours of BDL revealed decreased staining accompanied by intracellular localization of the protein in pericanalicular vesicular structures. Within this intracellular compartment, mrp2 colocalized with the bile salt transporter (bsep) and was still active as shown by vesicular accumulation of the fluorescent organic anion glutathione-bimane (GS-B). We conclude that down-regulation of mrp2 during BDL-induced obstructive cholestasis is mainly posttranscriptionally regulated. We propose that this down-regulation is caused by endocytosis of apical transporters followed up by increased breakdown of mrp2, probably in lysosomes. This breakdown of mrp2 is more severe in the periportal areas of the liver lobule.
Deficient Inhibition as a Marker for Familial ADHD
Authors: Jennifer Crosbie, Russell Schachar
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The authors investigated whether deficient inhibitory control, as measured by the stop-signal paradigm, delineates a familial subgroup of attention deficit hyperactivity disorder (ADHD). METHOD: Subjects were 54 ADHD children defined as having poor or good inhibition (on the basis of stop-signal paradigm performance) and 26 healthy comparison children. Family history of ADHD and measures of neurobiological and psychosocial risk were compared among the three groups. RESULTS: ADHD was significantly more prevalent in the families of the children with ADHD who exhibited poor inhibition (48.1%) than in the families of those exhibiting good inhibition (18.5%) or in the families of healthy comparison children (7.7%). No differences in neurobiological or psychosocial risk were found for the three groups. CONCLUSIONS: Deficient inhibition delineates a familial subtype of ADHD. Psychosocial and neurobiological factors did not account for inclusion in the good inhibition group and did not act conjointly with inhibition to increase the risk for ADHD in the poor inhibition group. This study demonstrates that cognitive measures such as a laboratory measure of inhibition can serve as phenotype markers for genetic analyses.
Regulation of Cardiac Hypertrophic Signaling by Prolyl Isomerase Pin1
Authors: Haruhiro Toko, Mathias H. Konstandin, Shirin Doroudgar, Lucia Ormachea, Eri Joyo, Anya Y. Joyo, Shabana Din, Natalie A. Gude, Brett Collins, Mirko Völkers, Donna J. Thuerauf, Christopher C. Glembotski, Chun-Hau Chen, Kun Ping Lu, Oliver J. Müller, Takafumi Uchida, Mark A. Sussman
Journal: Circulation Research (2013)

Rationale: Cardiac hypertrophy results from the complex interplay of differentially regulated cascades based on the phosphorylation status of involved signaling molecules. Although numerous critical regulatory kinases and phosphatases have been identified in the myocardium, the intracellular mechanism for temporal regulation of signaling duration and intensity remains obscure. In the nonmyocyte context, control of folding, activity, and stability of proteins is mediated by the prolyl isomerase Pin1, but the role of Pin1 in the heart is unknown. Objective: To establish the role of Pin1 in the heart. Methods and Results: Here, we show that either genetic deletion or cardiac overexpression of Pin1 blunts hypertrophic responses induced by transaortic constriction and consequent cardiac failure in vivo. Mechanistically, we find that Pin1 directly binds to Akt, mitogen activated protein kinase (MEK), and Raf-1 in cultured cardiomyocytes after hypertrophic stimulation. Furthermore, loss of Pin1 leads to diminished hypertrophic signaling of Akt and MEK, whereas overexpression of Pin1 increases Raf-1 phosphorylation on the autoinhibitory site Ser259, leading to reduced MEK activation. Conclusions: Collectively, these data support a role for Pin1 as a central modulator of the intensity and duration of 2 major hypertrophic signaling pathways, thereby providing a novel target for regulation and control of cardiac hypertrophy.