tbuckley/cabot-search huggingface dataset:
Lipid-Modifying Therapies and Risk of Pancreatitis
Authors: David Preiss, Matti J. Tikkanen, Paul Welsh, Ian Ford, Laura C. Lovato, Marshall B. Elam, John C. LaRosa, David A. DeMicco, Helen M. Colhoun, Ilan Goldenberg, Michael J. Murphy, Thomas M. MacDonald, Terje R. Pedersen, Anthony C. Keech, Paul M Ridker, John Kjekshus, Naveed Sattar, John J. V. McMurray
Journal: JAMA (2012)

<h3>Context</h3>Statin therapy has been associated with pancreatitis in observational studies. Although lipid guidelines recommend fibrate therapy to reduce pancreatitis risk in persons with hypertriglyceridemia, fibrates may lead to the development of gallstones, a risk factor for pancreatitis.<h3>Objective</h3>To investigate associations between statin or fibrate therapy and incident pancreatitis in large randomized trials.<h3>Data Sources</h3>Relevant trials were identified in literature searches of MEDLINE, EMBASE, and Web of Science (January 1, 1994, for statin trials and January 1, 1972, for fibrate trials, through June 9, 2012). Published pancreatitis data were tabulated where available (6 trials). Unpublished data were obtained from investigators (22 trials).<h3>Study Selection</h3>We included randomized controlled cardiovascular end-point trials investigating effects of statin therapy or fibrate therapy. Studies with more than 1000 participants followed up for more than 1 year were included.<h3>Data Extraction</h3>Trial-specific data described numbers of participants developing pancreatitis and change in triglyceride levels at 1 year. Trial-specific risk ratios (RRs) were calculated and combined using random-effects model meta-analysis. Between-study heterogeneity was assessed using the I<sup>2</sup> statistic.<h3>Results</h3>In 16 placebo- and standard care–controlled statin trials with 113 800 participants conducted over a weighted mean follow-up of 4.1 (SD, 1.5) years, 309 participants developed pancreatitis (134 assigned to statin, 175 assigned to control) (RR, 0.77 [95% CI, 0.62-0.97; P = .03; I<sup>2</sup> = 0%]). In 5 dose-comparison statin trials with 39 614 participants conducted over 4.8 (SD, 1.7) years, 156 participants developed pancreatitis (70 assigned to intensive dose, 86 assigned to moderate dose) (RR, 0.82 [95% CI, 0.59-1.12; P = .21; I<sup>2</sup> = 0%]). Combined results for all 21 statin trials provided RR 0.79 (95% CI, 0.65-0.95; P = .01; I<sup>2</sup> = 0%). In 7 fibrate trials with 40 162 participants conducted over 5.3 (SD, 0.5) years, 144 participants developed pancreatitis (84 assigned to fibrate therapy, 60 assigned to placebo) (RR, 1.39 [95% CI, 1.00-1.95; P = .053; I<sup>2</sup> = 0%]).<h3>Conclusion</h3>In a pooled analysis of randomized trial data, use of statin therapy was associated with a lower risk of pancreatitis in patients with normal or mildly elevated triglyceride levels.
Calnexin Induces Expansion of Antigen-Specific CD4+ T Cells that Confer Immunity to Fungal Ascomycetes via Conserved Epitopes
Authors: Marcel Wüthrich, Tristan T. Brandhorst, Thomas D. Sullivan, Hanna Filutowicz, Alana Sterkel, Douglas Stewart, Mengyi Li, Tassanee Lerksuthirat, Vanessa LeBert, Zu Ting Shen, Gary Ostroff, George S. Deepe, Chiung Yu Hung, Garry Cole, Jennifer A. Walter, Marc K. Jenkins, Bruce Klein
Journal: Cell Host & Microbe (2015)
Pathologic Features of Initial Adenomas as Predictors for Metachronous Adenomas of the Rectum
Authors: G. Yang, H. Yu, S. Zheng, W. Zheng, X.-O. Shu, Q.-R. Sun, W.-D. Li, G.-F. Shen, Y.-Z. Shen, J. D. Potter
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: Colorectal cancer is the third most common cancer in the world, arising mostly from pre-existing adenomatous polyps (adenomas) of the large bowel. Patients with colorectal adenomas are at increased risk of colorectal cancer because of a high recurrence rate for adenomas. We followed a cohort of 1490 patients with rectal adenomas to determine whether recurrence might be related to pathologic characteristics of the initial adenomas. Methods: The patients were identified in Haining County, China, from 1977 through 1978 by means of examination with a 15-cm rigid sigmoidoscope. They were followed by endoscopic examination at years 2, 4, 6, 11, and 16 after their initial polypectomy. New adenomas in the rectum were identified in 280 patients in these follow-up examinations. Results: Statistically significant twofold to threefold elevated risks of metachronous (recurrent) adenomas were observed for patients who had more than two initial adenomas or whose most advanced initial adenoma was more than 1.0 cm in size, was of villous/tubulovillous type, or showed moderate to severe dysplasia. Much stronger associations were observed for advanced metachronous neoplasms, which are defined as cancers or adenomas with severe dysplasia, with multivariate adjusted relative risks (95% confidence interval) of 4.2 (1.8–9.9) for a large initial adenoma (>1.0 cm), 8.1 (4.2–15.6) for villous/tubulovillous architecture, and 14.4 (5.0–41.3) for severe dysplasia. In particular, patients who had a large (>1.0 cm) adenoma with severe dysplasia at baseline had a relative risk of 37 (7.8–174.7) of developing advanced metachronous neoplasms compared with patients who had small adenoma(s) with mild dysplasia. Conclusions: The risk of metachronous adenomas is closely related to the pathology of initial adenomas, thus allowing identification of a high-risk group of adenoma patients for close surveillance after their initial polypectomy.
The good old days
Authors: Liam Farrell
Journal: BMJ (2004)

After I started in general practice I worked a one-in-two night rota for 12 years. By the end, I was thoroughly burnt out and had so little empathy left that I could sit through Spencer Tracy's death scene in Captains Courageous without blubbering. I hated being called out of bed and calling me was as pointless as Tantalus's mother shouting, “Come on, son, eat your dinner.” My only remaining virtues were sarcasm and lust, my only emotions apathy and self …
Treating violence as a public health problem
Authors: Iona Heath
Journal: BMJ (2002)

News p 731 

In every country, to a greater or lesser extent, violence blights lives and undermines health. Acknowledging this, in 1996 the 49th World Health Assembly adopted a resolution (WHA49.25) declaring violence a major and growing public health problem across the world. The resolution ended by calling for a plan of action for progress towards a science based public health approach to preventing violence. The World Health Organization defines violence as the intentional use of physical force or power, threatened or actual, against oneself, another person, or a group or community, that either results in, or has a high likelihood of resulting in, injury, death, psychological harm, maldevelopment, or deprivation.1 In 2000, an estimated 1.6 million people died as a result of violence. Many more suffered injury. Of the deaths, nearly half were suicides, almost a third were homicides—of whom 57 000 were of children—and about a fifth were related to war. This week, the WHO published the World Report on Violence and Health .2 The report includes sections on youth violence, child abuse, violence by intimate partners, abuse of …
Inhibition of neutrophil elastase-induced goblet cell metaplasia by tiotropium in mice
Authors: N. Arai, M. Kondo, T. Izumo, J. Tamaoki, A. Nagai
Journal: European Respiratory Journal (2009)

Airway occlusion by mucus in chronic obstructive disease (COPD) is associated with a poor prognosis. We hypothesised that tiotropium has the ability to inhibit neutrophil elastase (NE)-induced goblet cell metaplasia in mice and mucin production in vitro . On days 1, 4, and 7, tiotropium or vehicle was administered to C57BL/6 mice by inhalation and they were allowed to intranasally aspirate human NE. Bronchoalveolar lavage fluid (BALF) and lung sections were analysed on days 8, 11 and 14. The effect of late administration of tiotropium on the goblet cell metaplasia by NE aspiration was also assessed. NE-induced MUC5AC production by NCI-H292 cells was measured with ELISA. Repeated NE aspiration induced marked goblet cell metaplasia. The grading of goblet cell metaplasia, neutrophil count and eosinophil count in BALF, keratinocyte-derived chemokine level and leukotriene B 4 level in BALF, and M 3 receptor expression by immunohistochemistry, were lower in the tiotropium group than in the vehicle group. Late administration of tiotropium inhibited the established goblet cell metaplasia. Tiotropium inhibited NE-induced MUC5AC production. Tiotropium inhibited NE-induced goblet cell metaplasia and mucin production, probably mediated by suppression of inflammation and a direct action on epithelial cells. This result suggests that tiotropium may be useful for the treatment of mucus overproduction in COPD.
High-dose albumin treatment for acute ischaemic stroke (ALIAS) part 2: a randomised, double-blind, phase 3, placebo-controlled trial
Authors: Myron D Ginsberg, Yuko Y Palesch, Michael D Hill, Renee H Martin, Claudia S Moy, William G Barsan, Bonnie D Waldman, Diego Tamariz, Karla J Ryckborst
Journal: The Lancet Neurology (2013)
THE LATE DR. W. R. HUGGARD.
Authors: Henry Angst, ArnoldF. Bill, J.Mitchell Bruce, W.J. Scudamore Emery, GeraldF. Mcgarel Hogg, RobertW. Perks, R.Douglas Powell, EdwardC. Simmons, D.A.F. Vesey, E.S. Woods, H.C. Wrinch, B. Hudson
Journal: The Lancet (1912)
Characterization of a Cleavage Stimulation Factor, 3′ pre-RNA, Subunit 2, 64 kDa (CSTF2) as a Therapeutic Target for Lung Cancer
Authors: Masato Aragaki, Koji Takahashi, Hirohiko Akiyama, Eiju Tsuchiya, Satoshi Kondo, Yusuke Nakamura, Yataro Daigo
Journal: Clinical Cancer Research (2011)

Abstract Purpose: This study aims to discover novel biomarkers and therapeutic targets for lung cancers. Experimental Design: We screened for genes showing elevated expression in the majority of lung cancers by genome-wide gene expression profile analysis of 120 lung cancers obtained by cDNA microarray representing 27,648 genes or expressed sequence tags. In this process, we detected a gene encoding cleavage stimulation factor, 3′ pre-RNA, subunit 2, 64 kDa (CSTF2) as a candidate. Immunohistochemical staining using tissue microarray consisting of 327 lung cancers was applied to examine the expression of CSTF2 protein and its prognostic value. A role of CSTF2 in cancer cell growth was examined by siRNA experiments. Results: Northern blot and immunohistochemical analyses detected the expression of CSTF2 only in testis among 16 normal tissues. Immunohistochemical analysis using tissue microarray showed an association of strong CSTF2 expression with poor prognosis of patients with non–small cell lung cancer (P = 0.0079), and multivariate analysis showed that CSTF2 positivity is an independent prognostic factor. In addition, suppression of CSTF2 expression by siRNAs suppressed lung cancer cell growth, whereas exogenous expression of CSTF2 promoted growth and invasion of mammalian cells. Conclusions: CSTF2 is likely to play an important role in lung carcinogenesis and be a prognostic biomarker in the clinic. Clin Cancer Res; 17(18); 5889–900. ©2011 AACR.
Fibronectin <sup>EDA</sup> Promotes Chronic Cutaneous Fibrosis Through Toll-Like Receptor Signaling
Authors: Swati Bhattacharyya, Zenshiro Tamaki, Wenxia Wang, Monique Hinchcliff, Paul Hoover, Spiro Getsios, Eric S. White, John Varga
Journal: Science Translational Medicine (2014)

Fibronectin EDA is an endogenous TLR4 ligand in scleroderma.
Shear-Stress and Wall-Stress Regulation of Vascular Remodeling After Balloon Angioplasty
Authors: Jolanda J. Wentzel, Jeroen Kloet, Ivan Andhyiswara, Jan A. F. Oomen, Johan C. H. Schuurbiers, Bart J. G. L. de Smet, Mark J. Post, Dominique de Kleijn, Gerard Pasterkamp, Cornelius Borst, Cornelis J. Slager, Rob Krams
Journal: Circulation (2001)

Background —Constrictive vascular remodeling (VR) is the most significant component of restenosis after balloon angioplasty (PTA). Whereas in physiological conditions VR is associated with normalization of shear stress (SS) and wall stress (WS), after PTA the role of SS and WS in VR is unknown. Furthermore, whereas matrix metalloproteinase inhibition (MMPI) has been shown to modulate VR after PTA, its effect on the SS and WS control mechanisms after PTA is unknown. Methods and Results —PTA was performed in external iliac arteries of 12 atherosclerotic Yucatan pigs, of which 6 pigs (7 vessels) received the MMPI batimastat and 6 pigs (10 vessels) served as controls. Before and after the intervention and at 6-week follow-up, intravascular ultrasound pullback was performed, allowing 3D reconstruction of the treated segment and computational fluid dynamics to calculate the media-bounded area and SS. WS was derived from the Laplace formula. Immediately after PTA, media-bounded area, WS, and SS changed by 20%, 16%, and −49%, respectively, in both groups. VR was predicted by SS and WS. In the control group, SS and WS had been normalized at follow-up with respect to the reference segment. In contrast, for the batimastat group, the SS had been normalized, but not the WS. The latter is attributed to an increase in wall area at follow-up. Conclusions —Vascular remodeling after PTA is controlled by both SS and WS. MMPI inhibited the WS control system.
Oxygen therapy in the breathless patient
Authors: B D Fox
Journal: Thorax (2008)

Beasley and colleagues argue persuasively that oxygen delivery to hypoxaemic patients should be optimised to provide adequate oxygen delivery while reducing the adverse effects of hyperoxaemia and preventing delay in identifying a patient with deteriorating gas exchange.1 However, their consistent use of the term high- flow oxygen instead of high- concentration oxygen perpetuates another widespread misunderstanding regarding oxygen therapy—that oxygen flow …
Frontal and lateral characteristics of the osseous configuration in chronic ankle instability
Authors: O Magerkurth, A Frigg, B Hintermann, W Dick, V Valderrabano
Journal: British Journal of Sports Medicine (2008)

Objective The osseous ankle configuration (tibiotalar sector, talar radius and height) has been discovered as intrinsic risk factor for chronic ankle instability (CAI). These measurements were done on lateral radiographs only. In this study, the osseous characteristics in the frontal plane and further lateral values were measured. Design Level III case-control study. Setting Radiological measurement of frontal and lateral radiographs by one independent, blinded radiologist using a digital DICOM/PACS system. Patients A group of 52 patients with CAI was compared with an age- and sex-matched control group of 52 healthy subjects. Main outcome measurements In the frontal plane, the depth of the talar curvature (frontal curvature (froCu)) and the lateral and medial malleolar lengths were measured. In the lateral plane, the position of the centre of rotation to the tibial axis (talar centre of rotation to the anatomical axis of the tibia (TibCOR)) and the tibial lateral surface angle (TLS) were also measured. Results The froCu was deeper in patients with CAI (1.8 (0.5) mm) than in healthy subjects (1.0 (0.5) mm, p&lt;0.05). The TibCOR was more anterior in patients with CAI (2.5 (1.9) mm) than in healthy subjects (1.6 (2.2) mm, p&lt;0.05). The distance from the fibular tip to the centre of rotation was smaller in patients with CAI (3.5 (3.4) mm) than in healthy subjects (6.5 (3.3) mm, p&lt;0.05). The TLS and the length of the lateral and medial ankle were not significantly different. Conclusions This study supports that the osseous joint configuration is an intrinsic risk factor for CAI. It could be shown that CAI is characterised by a deeper frontal curvature of the talus and a more anterior position of the talus to the tibia.
Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial
Authors: Gunnar Folprecht, Thomas Gruenberger, Wolf O Bechstein, Hans-Rudolf Raab, Florian Lordick, Jörg T Hartmann, Hauke Lang, Andrea Frilling, Jan Stoehlmacher, Jürgen Weitz, Ralf Konopke, Christian Stroszczynski, Torsten Liersch, Detlev Ockert, Thomas Herrmann, Eray Goekkurt, Fabio Parisi, Claus-Henning Köhne
Journal: The Lancet Oncology (2009)
A Phase I Single-Agent Study of Twice-Weekly Consecutive-Day Dosing of the Proteasome Inhibitor Carfilzomib in Patients with Relapsed or Refractory Multiple Myeloma or Lymphoma
Authors: Melissa Alsina, Suzanne Trudel, Richard R. Furman, Peter J. Rosen, Owen A. O'Connor, Raymond L. Comenzo, Alvin Wong, Lori A. Kunkel, Christopher J. Molineaux, Andre Goy
Journal: Clinical Cancer Research (2012)

Carfilzomib is a next-generation, selective, proteasome inhibitor with clinical activity in relapsed and/or refractory multiple myeloma. The objectives of this phase I study were to establish the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of escalating doses of carfilzomib in patients with relapsed or refractory hematologic malignancies.Carfilzomib (doses ranging from 1.2-27 mg/m(2)) was administered i.v. on 2 consecutive days for 3 weeks of a 4-week cycle. Single-agent dose escalation (n = 37) was followed by a dose-expansion phase (n = 11) that comprised 2 cohorts (carfilzomib or carfilzomib + dexamethasone). During dose expansion, carfilzomib was administered starting with 20 mg/m(2) during the first week (days 1, 2) and then escalated to 27 mg/m(2) thereafter.A maximum tolerated dose (MTD) was not reached during dose escalation. Dosing in the expansion cohort was well tolerated. Adverse events were manageable and primarily of grade I or II. The main hematologic adverse events of ≥ grade III were anemia and thrombocytopenia. Notably, there were no observations of grade III or more peripheral neuropathy. Carfilzomib was cleared rapidly with an elimination half-life of less than 30 minutes but still induced dose-dependent inhibition of the 20S chymotrypsin-like proteasome activity. At doses of 15 to 27 mg/m(2), there was evidence of activity among patients with multiple myeloma and with non-Hodgkin lymphoma.Escalated dosing of carfilzomib on a schedule of 2 consecutive days for 3 weeks of a 4-week cycle was tolerable and showed promising activity. This dose regimen has been selected for ongoing and future clinical studies, including PX-171-003A1 and the pivotal trial ASPIRE.
Clinical correlations and prognosis based on hyaluronic acid serum levels in patients with progressive systemic sclerosis
Authors: H. LEVKSQUE, N. BAUDOT, B. DELPECH, M. VAYSSAIRAT, A. GANCEL, PH. LAURET, H. COURTOIS
Journal: British Journal of Dermatology (1991)

The serum levels of hyaluronic acid (sHA) were measured using an affinoimmunoenzymatic assay in patients with distal (n= 16) and proximal (n= 15) progressive systemic sclerosis (PSS) and in 31 controls, The severity of PSS was evaluated using a standardized organ-involvement score. The mean sHA was significantly higher in the patients with PSS than in controls (mean ± SD: 80 ± 43.4μg/l vs. 42.3 ± 19.1 μg/l, P < 0.001). sHA was significantly higher in patients with proximal PSS than in patients with distal PSS (106.4±44.6 μg/l vs. 55.4±23.8 μg/l. P < 0.001). A positive correlation was found between sHA and the disease score (r= 0.67, P < 0.001). sHA was also correlated with lung diffusion capacity for carbon monoxide (r=0. 70. P < 0.001). but only in those patients who had abnormal lung function, and therefore presumably had lung PSS involvement. We suggest that sHA could be an indicator of the degree of systemic involvement in PSS. Its prognostic value and possible use in the follow up of patients with PSS remain to be clarified.
Single-agent CEP-701, a novel FLT3 inhibitor, shows biologic and clinical activity in patients with relapsed or refractory acute myeloid leukemia
Authors: B. Douglas Smith, Mark Levis, Miloslav Beran, Francis Giles, Hagop Kantarjian, Karin Berg, Kathleen M. Murphy, Tianna Dauses, Jeffrey Allebach, Donald Small
Journal: Blood (2004)
Paradoxical responses of plasma glucagon and bile acid levels after duodenal nutrient exclusion
Authors: Po-Chun Chen, Akio Inui, Chih-Yen Chen
Journal: Gut (2014)

Dear Sir,

We read with interest the article by Habegger et al 1 who demonstrated that duodenal nutrient exclusion using duodenal endoluminal sleeve (DES) improves metabolic syndrome and stimulates intestinal villus hyperplasia, especially the bypassed duodenum, in a rodent model of type 2 diabetes mellitus. There were three intriguing results. First, with regard to DES improving glucose homeostasis, the area under curve analysis showed that both sham-operated and the DES group had statistically significant improvements in glucose homeostasis. Nevertheless, since the pair-fed group had received the same sham operation, it is interesting that the sham-operated group rather than the pair-fed group showed …
EFFECT OF REMOVAL OF CHOLESTEROL DIET UPON SERUM SICKNESS-CHOLESTEROL-INDUCED ATHEROSCLEROSIS
Authors: M. Van Winkle, L. Levy
Journal: The Journal of Experimental Medicine (1968)

In this report, the role of vascular allergy (i.e., hypersensitivity) in the potentiation of atherogenesis has been studied. In order to accomplish this, bovine serum albumin (BSA) was administered to rabbits in quantities sufficient to cause the occurrence of serum sickness (a type of hypersensitivity known to cause injury to the endothelial linings of certain blood vessels). This was immediately followed by the feeding of a special cholesterol-supplemented diet, which is known to be capable of initiating a high incidence of atheromatous disease in rabbits after prolonged feeding. Results indicated that those animals which received the combined treatment developed an incidence of pathology after only 2 wk of special diet which was not equaled in the diet-only control groups until they had been treated for 4 wk. This indicated that vascular allergy could potentiate lipemia-induced atherogenesis in the rabbit, and was in confirmation of an earlier study of a similar nature. Indeed, because of the relatively mild vascular injury caused by a single injection of BSA, it would seem as though vascular hypersensitivity was extremely effective in the potentiation of atherogenesis. In addition, these results may have given some indication of the degree of vascular injury necessary for the induction of irreversible atheromatous disease. While the incidence of lesions in serum sickness controls was seen to decrease with passage of time after BSA challenge, it appeared to increase after cessation of treatment in those animals which received the combined treatment of BSA plus 2 wk of cholesterol-supplemented diet. It would therefore appear that the atheromatous lesions seen as early as 2 wk after initiation of the experiment may already have been irreversible in terms of the resolution of established pathology.