tbuckley/cabot-search huggingface dataset:
The emerging epidemic of environmental cancers in developing countries
Authors: P. Vineis, W. Xun
Journal: Annals of Oncology (2008)

In overviews concerning environmental cancers, the definition of 'environmental' can vary considerably in terms of the list of exposures considered, due to differences in inclusion criteria, and the articles tend to focus mainly or exclusively on Western populations. International agencies such as World Health Organisation, that have had considerable success in fighting infectious diseases, seem to be weaker when considering the relevance of environmental carcinogens, particularly in developing countries, and in identifying the exposed populations. The purpose of this paper is to reexamine the issue with a specific focus on developing countries. There are good reasons to believe that the burden of environmental cancers in such countries is high and has been underestimated in previous analyses. We examine the most common pollutants (aflatoxins, arsenic, air pollutants, biomass fuel and coal, polychlorinated biphenyls and wastes). A systematic review was not possible given the sparse nature of the data, but we suggest that the burden of environmental exposures to carcinogens can be substantial in developing countries.
Fracture Risk and Zoledronic Acid Therapy in Men with Osteoporosis
Authors: Steven Boonen, Jean-Yves Reginster, Jean-Marc Kaufman, Kurt Lippuner, Jose Zanchetta, Bente Langdahl, Rene Rizzoli, Stanley Lipschitz, Hans Peter Dimai, Richard Witvrouw, Erik Eriksen, Kim Brixen, Luis Russo, Frank Claessens, Philemon Papanastasiou, Oscar Antunez, Guoqin Su, Christina Bucci-Rechtweg, Josef Hruska, Elodie Incera, Dirk Vanderschueren, Eric Orwoll
Journal: New England Journal of Medicine (2012)

Fractures in men are a major health issue, and data on the antifracture efficacy of therapies for osteoporosis in men are limited. We studied the effect of zoledronic acid on fracture risk among men with osteoporosis.
Molecular and biochemical basis of intermediate maple syrup urine disease. Occurrence of homozygous G245R and F364C mutations at the E1 alpha locus of Hispanic-Mexican patients.
Authors: J L Chuang, J R Davie, J M Chinsky, R M Wynn, R P Cox, D T Chuang
Journal: Journal of Clinical Investigation (1995)

Maple syrup urine disease (MSUD) is caused by a deficiency of the mitochondrial branched-chain alpha-keta acid dehydrogenase (BCKAD) complex. The multienzyme complex comprises five enzyme components, including the E1 decarboxylase with a heterotetrameric (alpha 2 beta 2) structure. Four unrelated Hispanic-Mexican MSUD patients with the intermediate clinical phenotype were diagnosed 7 to 22 mo after birth during evaluation for developmental delay. Three of the four patients were found homozygous for G to A transition at base 895 (exon 7) of the E1 alpha locus, which changes Gly-245 to Arg (G245R) in that subunit. The remaining patient was homozygous for T to G transversion at base 1,253 in the E1 alpha gene, which converts Phe-364 to Cys (F364C) in the gene product. Transfection studies in E1 alpha-deficient lymphoblasts indicate that both G245R and F364C mutant E1 alpha subunits were unable to significantly reconstitute BCKAD activity. Western blotting showed that both mutant E1 alpha subunits in transfected cells failed to efficiently rescue the normal E1 beta through assembly. The putative assembly defect was confirmed by pulse-chase labeling of E1 subunits in a chaperone-augmented bacterial overexpression system. The kinetics of initial assembly of the G245R E1 alpha subunit with the normal E1 beta was shown to be slower than the normal E1 alpha. No detectable assembly of the F364C E1 alpha with normal E1 beta was observed during the 2 h chase. Small amounts of recombinant mutant E1 proteins were produced after 15 h induction with isopropyl thiogalactoside and exhibited very low or no E1 activity. Our study establishes that G245R and F364C mutations in the E1 alpha subunit disrupt both the E1 heterotetrameric assembly and function of the BCKAD complex. Moreover, the results suggest that the G245R mutant E1 alpha allele may be important in the Hispanic-Mexican population.
Estrogen-Dependent Gene Transcription in Human Breast Cancer Cells Relies upon Proteasome-Dependent Monoubiquitination of Histone H2B
Authors: Tanja Prenzel, Yvonne Begus-Nahrmann, Frank Kramer, Magali Hennion, Chieh Hsu, Theresa Gorsler, Corinna Hintermair, Dirk Eick, Elisabeth Kremmer, Mikael Simons, Tim Beissbarth, Steven A. Johnsen
Journal: Cancer Research (2011)

Abstract The estrogen receptor-α (ERα) determines the phenotype of breast cancers where it serves as a positive prognostic indicator. ERα is a well-established target for breast cancer therapy, but strategies to target its function remain of interest to address therapeutic resistance and further improve treatment. Recent findings indicate that proteasome inhibition can regulate estrogen-induced transcription, but how ERα function might be regulated was uncertain. In this study, we investigated the transcriptome-wide effects of the proteasome inhibitor bortezomib on estrogen-regulated transcription in MCF7 human breast cancer cells and showed that bortezomib caused a specific global decrease in estrogen-induced gene expression. This effect was specific because gene expression induced by the glucocorticoid receptor was unaffected by bortezomib. Surprisingly, we observed no changes in ERα recruitment or assembly of its transcriptional activation complex on ERα target genes. Instead, we found that proteasome inhibition caused a global decrease in histone H2B monoubiquitination (H2Bub1), leading to transcriptional elongation defects on estrogen target genes and to decreased chromatin dynamics overall. In confirming the functional significance of this link, we showed that RNA interference–mediated knockdown of the H2B ubiquitin ligase RNF40 decreased ERα-induced gene transcription. Surprisingly, RNF40 knockdown also supported estrogen-independent cell proliferation and activation of cell survival signaling pathways. Most importantly, we found that H2Bub1 levels decrease during tumor progression. H2Bub1 was abundant in normal mammary epithelium and benign breast tumors but absent in most malignant and metastatic breast cancers. Taken together, our findings show how ERα activity is blunted by bortezomib treatment as a result of reducing the downstream ubiquitin-dependent function of H2Bub1. In supporting a tumor suppressor role for H2Bub1 in breast cancer, our findings offer a rational basis to pursue H2Bub1-based therapies for future management of breast cancer. Cancer Res; 71(17); 5739–53. ©2011 AACR.
A randomised trial of lung sealant <i>versus</i> medical therapy for advanced emphysema
Authors: Carolyn E. Come, Mordechai R. Kramer, Mark T. Dransfield, Muhanned Abu-Hijleh, David Berkowitz, Michela Bezzi, Surya P. Bhatt, Michael B. Boyd, Enrique Cases, Alexander C. Chen, Christopher B. Cooper, Javier Flandes, Thomas Gildea, Mark Gotfried, D. Kyle Hogarth, Kumaran Kolandaivelu, William Leeds, Timothy Liesching, Nathaniel Marchetti, Charles Marquette, Richard A. Mularski, Victor M. Pinto-Plata, Michael A. Pritchett, Samaan Rafeq, Edmundo R. Rubio, Dirk-Jan Slebos, Grigoris Stratakos, Alexander Sy, Larry W. Tsai, Momen Wahidi, John Walsh, J. Michael Wells, Patrick E. Whitten, Roger Yusen, Javier J. Zulueta, Gerard J. Criner, George R. Washko
Journal: European Respiratory Journal (2015)

Uncontrolled pilot studies demonstrated promising results of endoscopic lung volume reduction using emphysematous lung sealant (ELS) in patients with advanced, upper lobe predominant emphysema. We aimed to evaluate the safety and efficacy of ELS in a randomised controlled setting.Patients were randomised to ELS plus medical treatment or medical treatment alone. Despite early termination for business reasons and inability to assess the primary 12-month end-point, 95 out of 300 patients were successfully randomised, providing sufficient data for 3- and 6-month analysis.57 patients (34 treatment and 23 control) had efficacy results at 3 months; 34 (21 treatment and 13 control) at 6 months. In the treatment group, 3-month lung function, dyspnoea, and quality of life improved significantly from baseline when compared to control. Improvements persisted at 6 months with >50% of treated patients experiencing clinically important improvements, including some whose lung function improved by >100%. 44% of treated patients experienced adverse events requiring hospitalisation (2.5-fold more than control, p=0.01), with two deaths in the treated cohort. Treatment responders tended to be those experiencing respiratory adverse events.Despite early termination, results show that minimally invasive ELS may be efficacious, yet significant risks (probably inflammatory) limit its current utility.
Anti–HER-2/<b><i>neu</i></b>Immune Responses Are Induced before the Development of Clinical Tumors but Declined following Tumorigenesis in HER-2/<b><i>neu</i></b>Transgenic Mice
Authors: Noritami Takeuchi, Shin-ichiroh Hiraoka, Xu-Yu Zhou, Masakazu Nagafuku, Shiro Ono, Takahiro Tsujimura, Mitsuhiro Nakazawa, Yoshiaki Yura, Toshiyuki Hamaoka, Hiromi Fujiwara
Journal: Cancer Research (2004)

Abstract HER-2/neu oncogene products have been implicated as a potential target of T cell–mediated immune responses to HER-2/neu–induced tumors. Using HER-2/neu transgenic mice (oncomice), we investigated whether, and if so how, anti–HER-2/neu immune responses are induced and modulated in these oncomice from birth to tumor initiation. Female oncomice carrying the activated HER-2/neu oncogene displayed apparent hyperplasia in mammary glands at 10 weeks of age and developed mammary carcinomas around an average age of 26 weeks. Unfractionated spleen cells from 10- to 15-week-old oncomice that were cultured without any exogenous stimuli exhibited cytotoxicity against the F31 tumor cell line established from an HER-2/neu–induced mammary carcinoma mass. The final antitumor effectors were a macrophage lineage of cells. However, this effector population was activated, depending on the stimulation of oncomouse CD4+ T cells with oncomouse-derived antigen-presenting cell (APC) alone or with wild-type mouse APC in the presence of F31 membrane fractions, suggesting the presence of HER-2/neu–primed CD4+ T cells and HER-2/neu–presenting APC in 10- to 15-week-old oncomice. These antitumor cytotoxic responses were detected at ∼5 weeks of age and peaked at age 10 to 15 weeks. However, the responses then declined at tumor-bearing stages in which the expression of target proteins could progressively increase. This resulted from the dysfunction of CD4+ T cells but not of APC or effector macrophages. These results indicate that an anti–HER-2/neu CD4+ T cell–mediated immune response was generated at the pretumorigenic stage but did not prevent tumorigenesis and declined after the development of clinical tumors.
EORTC 10968: a phase I clinical and pharmacokinetic study of polyethylene glycol liposomal doxorubicin (Caelyx®, Doxil®) at a 6-week interval in patients with metastatic breast cancer
Authors: A. Hamilton, L. Biganzoli, R. Coleman, L. Mauriac, P. Hennebert, A. Awada, M. Nooij, L. Beex, M. Piccart, I. Van Hoorebeeck, P. Bruning, D. de Valeriola
Journal: Annals of Oncology (2002)
Origin of Fasciculations in Amyotrophic Lateral Sclerosis and Benign Fasciculation Syndrome
Authors: Mamede de Carvalho, Michael Swash
Journal: JAMA Neurology (2013)

Fasciculation potentials (FPs) may arise proximally or distally within the peripheral nervous system. We recorded FPs in the tibialis anterior using 2 concentric needle electrodes, ensuring by slight voluntary contraction and electrical nerve stimulation that each electrode recorded motor unit potentials innervated by different axons.Time-locked FPs recorded from both electrodes, suggesting a spinal origin, were most frequent in benign fasciculation syndrome (44%) (P < .001) and amyotrophic lateral sclerosis without reinnervation (27%). Fewer time-locked FPs were found (14%) in the reinnervated tibialis anterior in amyotrophic lateral sclerosis (P < .001).We conclude that in chronic partial denervation FPs are more likely to arise distally and that FPs in benign fasciculation syndrome more frequently arise proximally.
Mometasone furoate/formoterol reduces asthma deteriorations and improves lung function
Authors: E.O. Meltzer, P. Kuna, H. Nolte, A.S. Nayak, C. LaForce
Journal: European Respiratory Journal (2011)

This study evaluated the effect of mometasone furoate (MF)/formoterol (F) versus its monocomponents, each administered via metered-dose inhaler, on asthma deteriorations and lung function. This 26-week, multicentre, double-blind, placebo-controlled study included subjects aged ≥12 yrs with not well-controlled asthma on low-dose inhaled corticosteroids. After a 2-3-week open-label run-in (MF 100 μg b.i.d.), 746 subjects were randomised to receive placebo, F 10 μg, MF 100 μg or MF/F 100/10 μg b.i.d. Co-primary end-points were time to first asthma deterioration (MF/F versus F to assess effect of MF) and change in forced expiratory volume in 1 s (FEV(1)) area under the curve of serial spirometry measurements over the 12-h period following the morning dose (AUC(0-12h)) (baseline to week 12; MF/F versus MF to assess effect of F). The therapeutic effect of MF in the combination was demonstrated by a reduction in asthma deterioration incidence with MF/F versus F and a delayed time to first asthma deterioration (p<0.001). Asthma deterioration incidence was also reduced with MF/F versus MF (p=0.006). The therapeutic effect of F in the combination was demonstrated by MF/F versus MF in FEV(1) AUC(0-12h) change (4.00 versus 2.53 L·h, respectively; p=0.001). MF/F treatment also resulted in a marked improvement in health-related quality of life. MF/F 100/10 μg b.i.d. treatment showed greater clinical efficacy than its individual components or placebo; both components contributed to the efficacy of MF/F.
Lymphocytic Na <sup>+</sup> -H <sup>+</sup> Exchange Increases After an Oral Glucose Challenge
Authors: Martin Tepel, Ralf Schlotmann, Michael Barenbrock, Klaus Kisters, Torsten Klaus, Claus Spieker, Michael Walter, Christian Meyer, Reinhard G. Bretzel, Walter Zidek
Journal: Circulation Research (1995)

Abstract The effects of oral glucose challenge on plasma glucose concentration, plasma insulin concentration, arterial blood pressure, cytosolic pH (pH i ), cytosolic free Na + concentration ([Na + ] i ), and cellular Na + -H + exchange activity were investigated in 16 healthy subjects. The pH i , [Na + ] i , and Na + -H + exchange activity were measured in intact lymphocytes by using the fluorescent dye technique. The oral glucose challenge significantly increased plasma glucose, plasma insulin, and the lymphocytic Na + -H + exchange activity, measured as change of pH i per second (control [0 hours], 5.20±0.53×10 −3 dpH i /s; 1 hour after glucose administration, 8.28±1.07×10 −3 dpH i /s; 2 hours after glucose administration, 8.15±1.18×10 −3 dpH i /s; P =.002). The lymphocytic Na + -H + exchange was significantly correlated with plasma glucose concentration ( r =.357, P =.041). During steady state euglycemic hyperinsulinemic clamp, the Na + -H + exchange activity was not significantly changed compared with baseline values. The study shows that changes of blood glucose levels can induce an acute increase in Na + -H + exchange activity. Systolic blood pressure and Na + -H + exchange activity were significantly ( P &lt;.001) but weakly correlated during an oral glucose challenge.
* 'Really doctor! I have coeliac disease? That's ok i'm wealthy and university educated'
Authors: S. M. Barratt, A. Arnaout, K. E. Evans, J. S. Leeds, D. S. Sanders
Journal: Gut (2011)

<h3>Introduction</h3> The gluten-free diet (GFD) is the mainstay of treatment in Coeliac Disease, however, this diet is potentially very difficult to follow presenting an array of obstacles. Due to such difficulties some patients do not consistently adhere to a GFD, or do not follow a GFD at all. We aimed to determine what patient characteristics are associated with sub-optimal GFD adherence. In doing so we hoped to identify poor prognostic indicators of treatment compliance. <h3>Methods</h3> Postal survey of 225 histologically proven Coeliac Disease patients (5% 18–25 years, 4% 26–35 years, 18% 36–45 years, 19% 46–55 years, 26% 56–65 years, 28% &gt;66 years) of which 25% were male. Mean disease duration 8 years, range 0.5–51years. Questionnaire included age, sex, highest educational qualification and marital status. Postcodes were used to assign A.C.O.R.N. categories (A Classification of Residential Neighbourhoods). These categories are based on geo-demographic variables including income, housing and government census and lifestyle survey data. Medical records were used to determine disease duration and method of presentation at diagnosis (Typical: GI symptoms; Atypical: non-GI symptoms; Screen-detected: asymptomatic). Patients stated their level of GFD adherence in the previous 28 days: Full Adherence (FA): everyday with no dietary transgressions, or Partial/None Adherence (PNA): less than FA. <h3>Results</h3> Age was not a confounding factor. ACORN groups other than ‘Wealthy Executives’ had a reduced likelihood of FA (OR 0.33, 95% CI 0.15 to 0.75, p=0.0077). Deprived ACORN groups ‘Hard Pressed’ and ‘Moderate Means’ had a reduced likelihood of FA compared to the affluent ‘Comfortably Off’, ‘Urbanites’ and ‘Wealthy Executives’ (OR 0.32, 95% CI 0.14 to 0.70, p= 0.0057). 28% of FA patients held a university degree versus 16% of PNA patients (p=0.064). 25% of FA and 24% of PNA patients were male (p=ns). 72% of FA and 71% of PNA patients were married (p=ns). 4% of FA and 12% of PNA patients were under 35 years of age (p=0.085). 26% of FA and 31% of PNA patients had a disease duration of three years or less (p=ns). 13% of FA and 21% of PNA patients had a screen-detected method of presentation (p=ns). <h3>Conclusion</h3> Poor socio-economic background and educational achievement that is below university (i.e. degree) level are associated with reduced or absent GFD adherence. This suggests wealthier patients can ‘buy’ greater food choices to accommodate this restrictive diet and higher educational achievement may promote greater awareness of the diet and strategies to overcome problems. A disease duration less than three years and being under 35 years of age are also associated with reduced GFD adherence, but to a statistically insignificant level. Our findings allow professionals to identify ‘at risk’ patients in Coeliac Disease.
Transurethral Resection With Subarachnoid Block
Authors: J. Antonio Aldrete
Journal: JAMA (1969)

It has been suggested that spinal anesthesia is the technique of choice for transurethral resection of the prostate. 1,2 Adequate muscular relaxation, analgesia, lack of explosion hazard, moderate drop of blood pressure (resulting in less bleeding), lack of depressant effects of respiratory function, and having an awake patient have been cited as advantages. Peculiar to this urologic procedure are the intermittent bladder distention required for adequate visualization of the operating field and the passage of nonelectrolyte solution from the bladder through the open venous sinuses of the prostatic bed into the venous circulation. 1   Hypotension commonly occurs within 20 minutes of onset of anesthesia. However, we have observed sudden episodes of bradycardia and hypotension occurring in the late phase of transurethral resection with the patient under spinal anesthesia. Two such instances are discussed here.  Report of Cases  Case 1.—  A 73-year-old man was to have transurethral resection of the prostate for
A randomised controlled trial of endoscopic sphincterotomy in acute cholangitis without common bile duct stones
Authors: C-K Hui, K-C Lai, W-M Wong, M-F Yuen, S-K Lam, C-L Lai
Journal: Gut (2002)

<b>Background:</b> Biliary decompression with endoscopic sphincterotomy (EPT) is beneficial in patients with biliary obstruction due to common bile duct (CBD) stones. However, it is not known whether EPT with decompression of the bile duct is beneficial in patients with acute cholangitis and gall bladder stones but without evidence of CBD stones. <b>Aim:</b> A randomised controlled study to assess the effect of EPT on the outcome of patients suffering from acute cholangitis with gall bladder stones but with no CBD stones on initial endoscopic retrograde cholangiopancreatography. <b>Patients:</b> A total of 111 patients were recruited into the study. <b>Methods and results:</b> Fifty patients were randomised to receive EPT while 61 patients received no endoscopic intervention. There was a significant difference in the duration of fever in the EPT and non-EPT groups (mean (SD): 3.2 (2.2) days <i>v</i> 4.3 (2.1) days; p&lt;0.001). Duration of hospital stay was also shorter in the EPT group than in the non-EPT group (mean (SD): 8.1 (3.0) <i>v</i> 9.1 (3.2) days; p=0.04). Patients were followed up for a mean (SD) of 42.4 (11.1) months. Twenty three patients (20.3%) developed recurrent acute cholangitis (RAC): 14 patients (12.6%) in the EPT group and nine patients (8.1%) in the non-EPT group (p=0.09). <b>Conclusion:</b> EPT in patients with acute cholangitis without CBD stones decreased the duration of acute cholangitis and reduced hospital stay but it did not decrease the incidence of RAC.
Mucosal changes in gastric ulceration and their response to carbenoxolone sodium.
Authors: H W Steer, D G Colin-Jones
Journal: Gut (1975)

The epithelial differences between the normal stomach (six subjects) and 47 patients with gastric ulcers were compared. The concentrations of intraepithelial lymphocytes and polymorphonuclear leucocytes in lesser curve and prepyloric gastirc ulcers were compared, the effect of treatment with carbenoxolone sodium was studied. There is a statistically significant reduction in the total number of intraepithelial polymorphonuclear leucocytes before and after successful treatment with carbenoxolone sodium. There is also a statistically significant decrease in the quantity of intraepithelial lymphocytes in those patients with lesser curve gastric ulcers successfully treated with carbenoxolone sodium, whereas there is a significant increase in those patients with prepyloric gastric ulcers successfully treated and those patients in whom treatment failed. The value of counts of migrating white blood cells as a method of objectively assessing the effect of healing drugs upon the gastric mucosa is discussed. Pseudomonas aeruginosa was found in many specimens obtained, and evidence is presented that this was not a contaminant. Carbenoxolone appeared to increase the amount of mucus but had little effect upon the number of bacteria found. The possible contribution of Pseudomonas aeruginosa to gastric ulceration is discussed.
Surgery rates in IBD: Table 1
Authors: Anders Tøttrup, Bente Mertz Nørgård, Niels Qvist
Journal: Gut (2014)

With great interest we have read the paper by Rungoe et al 1 describing a possible decrease rate in surgery in patients with IBD. The authors have identified all Danish patients with IBD by their first IBD diagnosis registered in the time period from 1979 to 2011. Data were extracted from the Danish National Patient Register, which contains information about all inpatient hospital contacts including diagnoses and surgical interventions, and outpatient diagnoses were not registered before 1995. Accordingly, Cohorts 1 and 2 represent only patients, who have had conditions requiring first time admissions, whereas Cohorts 3 and 4 represent a mixture of patients having first time diagnoses of IBD as inpatients or as outpatients (probably milder cases). Thus, Cohorts 3 and 4 might represent patients with less severe disease at …