tbuckley/cabot-search huggingface dataset:
Ten-Year Follow-Up of 3 Years of Oral Adjuvant Clodronate Therapy Shows Significant Prevention of Osteoporosis in Early-Stage Breast Cancer
Authors: Tiina Saarto, Leena Vehmanen, Carl Blomqvist, Inkeri Elomaa
Journal: Journal of Clinical Oncology (2008)

We have previously reported that 3-year adjuvant clodronate treatment prevents bone loss in breast cancer patients. Here we report the 10-year follow-up data of clodronate in the prevention of treatment-related osteoporosis in women with early-stage breast cancer.Two hundred sixty-eight pre- and postmenopausal, node-positive breast cancer patients were randomly assigned to clodronate, 1.6 g orally administered daily, or to control groups for 3 years. Premenopausal women were treated with adjuvant CMF chemotherapy; and postmenopausal women were treated with antiestrogens, either 20 mg tamoxifen or 60 mg toremifene, for 3 years. The bone mineral density (BMD) of the lumbar spine and hip was measured before treatment and at 1, 2, 3, 5, and 10 years after therapy.Eighty-nine disease-free patients were included in the analyses of osteoporosis-free survival. During the 10-year period, 24 of 89 patients were diagnosed with osteoporosis. Fourteen patients developed spinal osteoporosis (three of 41 in the clodronate group, and 11 of 48 in the control group), and 14 of 89 patients were diagnosed with hip osteoporosis (seven of 41 in the clodronate group, and seven of 48 in the control group). The 10-year spinal, osteoporosis-free survival rate was 92.7% in the clodronate group, and 77.0% in the control group (P = .035). No difference was seen in the frequency of hip osteoporosis (85.4% v 82.9%; P = .92). Baseline BMD measurement had a predictive value of 18 of 24 patients (75%) who developed osteoporosis had osteopenia of the lumbar spine at baseline.Three years of clodronate therapy significantly reduces the incidence of lumbar spine osteoporosis. Patients at risk of developing osteoporosis are among those who have pretreatment osteopenia, that is, baseline BMD measurement has predictive value.
Pretreatment EGFR T790M Mutation and BRCA1 mRNA Expression in Erlotinib-Treated Advanced Non–Small-Cell Lung Cancer Patients with EGFR Mutations
Authors: Rafael Rosell, Miguel Angel Molina, Carlota Costa, Sara Simonetti, Ana Gimenez-Capitan, Jordi Bertran-Alamillo, Clara Mayo, Teresa Moran, Pedro Mendez, Felipe Cardenal, Dolores Isla, Mariano Provencio, Manuel Cobo, Amelia Insa, Rosario Garcia-Campelo, Noemi Reguart, Margarita Majem, Santiago Viteri, Enric Carcereny, Ruth Porta, Bartomeu Massuti, Cristina Queralt, Itziar de Aguirre, Jose Miguel Sanchez, Maria Sanchez-Ronco, Jose Luis Mate, Aurelio Ariza, Susana Benlloch, Jose Javier Sanchez, Trever G Bivona, Charles L Sawyers, Miquel Taron
Journal: Clinical Cancer Research (2011)

Advanced non-small-cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations (deletion in exon 19 or L858R) show an impressive progression-free survival of 14 months when treated with erlotinib. However, the presence of EGFR mutations can only imperfectly predict outcome. We hypothesized that progression-free survival could be influenced both by the pretreatment EGFR T790M mutation and by components of DNA repair pathways.We assessed the T790M mutation in pretreatment diagnostic specimens from 129 erlotinib-treated advanced NSCLC patients with EGFR mutations. The expression of eight genes and two proteins involved in DNA repair and four receptor tyrosine kinases was also examined.The EGFR T790M mutation was observed in 45 of 129 patients (35%). Progression-free survival was 12 months in patients with and 18 months in patients without the T790M mutation (P = 0.05). Progression-free survival was 27 months in patients with low BRCA1 mRNA levels, 18 months in those with intermediate levels, and 10 months in those with high levels (P = 0.02). In the multivariate analysis, the presence of the T790M mutation (HR, 4.35; P = 0.001), intermediate BRCA1 levels (HR, 8.19; P < 0.0001), and high BRCA1 levels (HR, 8.46; P < 0.0001) emerged as markers of shorter progression-free survival.Low BRCA1 levels neutralized the negative effect of the T790M mutation and were associated with longer progression-free survival to erlotinib. We advocate baseline assessment of the T790M mutation and BRCA1 expression to predict outcome and provide alternative individualized treatment to patients based on T790M mutations and BRCA1 expression.
Heterotopic cardiac transplantation decreases the capacity for rat myocardial protein synthesis.
Authors: I Klein, A M Samarel, R Welikson, C Hong
Journal: Circulation Research (1991)

Heterotopic cardiac isografts are vascularly perfused hearts that maintain structural and functional integrity for prolonged periods of time. When placed in an infrarenal location, the heart is hemodynamically unloaded and undergoes negative growth, leading to cardiac atrophy. At 7 and 14 days after transplantation, the transplanted heart was decreased in size compared with the in situ heart (p less than 0.001). To assess the possible mechanism(s) to account for this reduction in size we studied in vivo rates of total left ventricular (LV) protein synthesis, total LV RNA content, and 18S ribosomal RNA content by nucleic acid hybridization. The LV protein synthetic rate was 4.7 and 5.3 mg/day in the in situ heart and was significantly decreased to 2.9 and 2.7 mg/day in the transplanted hearts at 7 and 14 days, respectively. LV RNA content of the transplant declined to 53% and 48% of the in situ value at 7 and 14 days, respectively. Hybridization studies revealed that LV 18S ribosomal subunit content was reduced proportionately to total RNA in the heterotopic hearts. As a result of these changes, there was no significant difference in the efficiency of total LV protein synthesis between the in situ and transplanted hearts. The present studies demonstrate that the hemodynamic unloading and cardiac atrophy that is characteristic of heterotopic cardiac transplantation is accompanied by a decrease in LV total RNA content and 18S RNA, resulting in a decreased capacity for myocardial protein synthesis.
Should people at low risk of cardiovascular disease take a statin?
Authors: J. D. Abramson, H. G. Rosenberg, N. Jewell, J. M. Wright
Journal: BMJ (2013)

A review of statins for primary prevention of cardiovascular disease could alter guidance for those with a 10 year risk of less than 10%.<b> John Abramson and colleagues </b>argue that statins have no overall health benefit in this population and that prescribing guidelines should not be broadened
A broad T-cell repertoire diversity and an efficient thymic function indicate a favorable long-term immune reconstitution after cord blood stem cell transplantation
Authors: Kimmo Talvensaari, Emmanuel Clave, Corinne Douay, Claire Rabian, Laurent Garderet, Marc Busson, Federico Garnier, Daniel Douek, Eliane Gluckman, Dominique Charron, Antoine Toubert
Journal: Blood (2002)
Mutation of Nogo-B Receptor, a Subunit of cis-Prenyltransferase, Causes a Congenital Disorder of Glycosylation
Authors: Eon Joo Park, Kariona A. Grabińska, Ziqiang Guan, Viktor Stránecký, Hana Hartmannová, Kateřina Hodaňová, Veronika Barešová, Jana Sovová, Levente Jozsef, Nina Ondrušková, Hana Hansíková, Tomáš Honzík, Jiří Zeman, Helena Hůlková, Rong Wen, Stanislav Kmoch, William C. Sessa
Journal: Cell Metabolism (2014)
The Contribution of Clinical Breast Examination to the Accuracy of Breast Screening
Authors: A. M. Chiarelli, V. Majpruz, P. Brown, M. Theriault, R. Shumak, V. Mai
Journal: JNCI Journal of the National Cancer Institute (2009)

BackgroundThere is controversy about whether adding clinical breast examination (CBE) to mammography improves the accuracy of breast screening. We compared the accuracy of screening among centers that offered CBE in addition to mammography with that among centers that offered only mammography.
Markers of Eosinophilic Inflammation for Diagnosis of Eosinophilic Esophagitis and Proton Pump Inhibitor–Responsive Esophageal Eosinophilia: A Prospective Study
Authors: Evan S Dellon, Olga Speck, Kimberly Woodward, Shannon Covey, Spencer Rusin, Jessica H Gebhart, Xiaoxin Chen, John T Woosley, Nicholas J Shaheen
Journal: Clinical Gastroenterology and Hepatology (2014)
Retraction: GQ5 Hinders Renal Fibrosis in Obstructive Nephropathy by Selectively Inhibiting TGF-β–Induced Smad3 Phosphorylation
Authors: Jun Ai, Jing Nie, Jiangbo He, Qin Guo, Mei Li, Ying Lei, Youhua Liu, Zhanmei Zhou, Fengxin Zhu, Min Liang, Yongxian Cheng, Fan Fan Hou
Journal: Journal of the American Society of Nephrology (2014)

TGF- β 1, via Smad-dependent or Smad-independent signaling, has a central role in the pathogenesis of renal fibrosis. This pathway has been recognized as a potential target for antifibrotic therapy. Here, we identified GQ5, a small molecular phenolic compound isolated from the dried resin of Toxicodendron vernicifluum , as a potent and selective inhibitor of TGF- β 1–induced Smad3 phosphorylation. In TGF- β 1–stimulated renal tubular epithelial cells and interstitial fibroblast cells, GQ5 inhibited the interaction of Smad3 with TGF- β type I receptor (T β RI) by blocking binding of Smad3 to SARA, suppressed subsequent phosphorylation of Smad3, reduced nuclear translocation of Smad2, Smad3, and Smad4, and downregulated the transcription of major fibrotic genes such as α -smooth muscle actin ( α -SMA), collagen I, and fibronectin. Notably, intraperitoneal administration of GQ5 in rats immediately after unilateral ureteral obstruction (UUO) selectively inhibited Smad3 phosphorylation in UUO kidneys, suppressed renal expression of α -SMA, collagen I, and fibronectin, and resulted in impressive renal protection after obstructive injury. Late administration of GQ5 also effectively attenuated fibrotic lesions in obstructive nephropathy. In conclusion, our results suggest that GQ5 hinders renal fibrosis in rats by selective inhibition of TGF- β 1–induced Smad3 phosphorylation.
Quality of Care for Primary Care Patients With Anxiety Disorders
Authors: Murray B Stein, Cathy D Sherbourne, Michelle G Craske, Adrienne Means-Christensen, Alexander Bystritsky, Wayne Katon, Greer Sullivan, Peter P Roy-Byrne
Journal: American Journal of Psychiatry (2004)

This study evaluated quality of care for primary care patients with anxiety disorders in university-affiliated outpatient clinics in Los Angeles, San Diego, and Seattle.Three hundred sixty-six primary care outpatients who were diagnosed with panic disorder, generalized anxiety disorder, social phobia, and/or posttraumatic stress disorder (with or without major depression) were surveyed about care received in the prior 3 months. Quality indicators were mental health referral, anxiety counseling, and use of appropriate antianxiety medication during the previous 3 months.Approximately one-third of patients with anxiety disorders had received counseling from their primary care provider in the prior 3 months. Fewer than 10% had receiving counseling from a mental health professional that included multiple elements of cognitive behavior therapy. Approximately 40% had received appropriate antianxiety medications in the previous 3 months, although only 25% had received them at a minimally adequate dose and duration. Overall, fewer than one in three patients had received either psychotherapy or pharmacotherapy that met a criterion for quality care. In multivariate analyses, patients with comorbid depression and/or medical illness were more likely-and patients from ethnic minorities were less likely-to receive appropriate antianxiety medications.Rates of quality care for anxiety disorders are moderate to low in university-affiliated primary care practices. Although an appropriate type of pharmacotherapy was frequently used, it was often of inadequate duration. Cognitive behavior therapy was markedly underused. These findings emphasize the need for practice guidelines and implementation of quality improvement programs for anxiety disorders in primary care.
Ileitis alters neuronal and enteroendocrine signalling in guinea pig distal colon
Authors: J. R O'Hara, A. E Lomax, G. M Mawe, K. A Sharkey
Journal: Gut (2006)

Intestinal inflammation alters neuronal and enteroendocrine signalling, leading to functional adaptations in the inflamed bowel. Human studies have reported functional alterations at sites distant from active inflammation. Our aims were to determine whether neuronal and enteroendocrine signalling are altered in the uninflamed colon during ileitis.We used neurophysiological, immunohistochemical, biochemical and Ussing chamber techniques to examine the effect of 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced ileitis on the properties of submucosal neurones, enteroendocrine cells and epithelial physiology of the distal colon of guinea pigs.Three days after TNBS administration, when inflammation was restricted to the ileum, the properties of colonic enteric neurones were altered. Submucosal AH neurones were hyperexcitable and had reduced after hyperpolarisations. S neurones received larger fast and slow excitatory postsynaptic potentials, due to an increase in non-cholinergic synaptic transmission. Despite the absence of inflammation in the colon, we found increased colonic prostaglandin E(2) content in animals with ileitis. Ileitis also increased the number of colonic 5-hydroxytryptamine (5-HT)- and GLP-2-immunoreactive enteroendocrine cells. This was accompanied by an increase in stimulated 5-HT release. Functional alterations in epithelial physiology occurred such that basal short circuit current was increased and veratridine-stimulated ion transport was reduced in the colon of animals with ileitis.Our data suggest that inflammation at one site in the gut alters the cellular components of enteric reflex circuits in non-inflamed regions in ways similar to those at sites of active inflammation. These changes underlie altered function in non-involved regions during episodes of intestinal inflammation.
What the 4-metre gait speed measures and why it cannot replace functional capacity tests
Authors: S. S. C. Kon, J. L. Canavan, C. M. Nolan, A. L. Clark, S. E. Jones, P. Cullinan, M. I. Polkey, W. D.-C. Man
Journal: European Respiratory Journal (2014)

distinguish ''biologically '' versus ''chronologically'' aged individuals [6].Thus, its strong correlations with respiratory parameters [2] and its sensitivity to clinical modifications [1] should only be seen as additional evidence of the strong biological foundations of the test, even in a disease-specific population.Nevertheless, in no way may such characteristics allow it to substitute tests measuring specific capacities and functions.
Efficacy of Superoxide Dismutase Mimetic M40403 in Attenuating Radiation-Induced Oral Mucositis in Hamsters
Authors: Christopher K. Murphy, Edward G. Fey, Brynmor A. Watkins, Vivien Wong, David Rothstein, Stephen T. Sonis
Journal: Clinical Cancer Research (2008)

Abstract Purpose: M40403 is a small-molecule superoxide dismutase mimetic that has shown efficacy in animal model disease states in which superoxide anions are thought to play a key role. Radiation treatment and chemotherapy for cancer generate free oxygen radicals that are hypothesized to trigger unwanted side effects in healthy tissue. For some patients undergoing these antineoplastic treatments, one of the most prevalent side effects is oral mucositis, which is a painful, often dose-limiting condition. Preclinical and clinical studies of this condition have shown the positive effect of treatment with compounds that decrease free oxygen radicals. This study investigated the efficacy M40403 in a clinically relevant hamster model of acute, radiation-induced oral mucositis. Methods: Oral mucositis was induced in hamsters by irradiation of the cheek pouch. The ability of i.p. administered M40403 to decrease the duration and severity of oral mucositis was assessed after treatment at different doses and dosing schedules. Oral mucositis was scored using the WHO grading scale. Results: Compared with placebo-treated animals, those irradiated on day 0 and treated twice daily with 30 mg/kg M40403 had significantly less severe and shorter duration mucositis over a range of treatment schedules, including from days -1 to 3, day 0 to 3, and day 0 alone. Similar efficacy was achieved at doses of 10 and 3 mg/kg twice daily on days -1 to 3. Conclusions: These results implicate free oxygen radicals in the onset of oral mucositis and also provide the basis for further development of M40403 in the prevention of this condition in at-risk cancer patients.
Harnessing Molecular Genetics for the Diagnosis and Management of Hypertrophic Cardiomyopathy
Authors: Libin Wang, Jonathan G. Seidman, Christine E. Seidman
Journal: Annals of Internal Medicine (2010)

Unexplained cardiac hypertrophy, the diagnostic criterion for hypertrophic cardiomyopathy (HCM), occurs in 1 in 500 adults. Insights into the genetic cause and molecular pathophysiology of HCM are reshaping clinical paradigms for diagnosis and treatment of this common myocardial disorder. Human genetic studies have established that dominant mutations in the proteins that comprise the contractile apparatus (the sarcomere) cause HCM. With the current availability of clinical gene-based diagnostics, pathogenic mutations in affected patients can be defined, which can suggest a clinical course and allow definitive preclinical identification of family members at risk for HCM. Genetic discoveries have also fostered mechanistic investigations in model organisms that are engineered to carry human HCM mutations. Novel therapeutic targets have emerged from these fundamental studies and are currently under clinical assessment in humans. The combination of contemporary gene-based diagnosis with new strategies to attenuate disease development and progression is changing the natural history of life-long cardiac symptoms, arrhythmias, and heart failure from HCM.

Hypertrophic cardiomyopathy (HCM) is a heritable disorder characterized by increased heart mass and abnormal diastolic function. The remarkable anatomic features of HCM (Figure 1) were first recognized more than 200 years ago, but the contemporary understanding of this disorder is based on integrated investigations into its histopathology, myocardial hemodynamics, and genetics (1–4).



Figure 1

Remodeling in hypertrophic cardiomyopathy (HCM). The mass of the normal myocardium (A) is increased in HCM because of ventricular hypertrophy, which can be asymmetric (B), concentric (C), or focal (not shown). Diastolic dysfunction in HCM leads to atrial ...



Recognition of familial clustering for HCM allowed the application of genetic strategies that ultimately defined its molecular causes. Investigators have identified 13 genes and more than 900 unique mutations (5–7), which makes clinical genetic testing for HCM possible. Molecular diagnosis discriminates between HCM and other hypertrophic heart disorders with distinct clinical courses and thus provides information about expected disease course. Genetic testing also definitively identifies family members who have inherited a mutation and are at high risk for HCM. Finally, knowledge of genetic causes of HCM has fueled mechanistic insights and therapeutic targets. Translation of these into clinical trials is underway. Here, we consider how molecular genetic discoveries provide new opportunities for predictive and personalized medicine in HCM.
Effect Of Oral Anti-histamines On The Thresholds Of Hen'S Egg- And Cow'S Milk-induced Anaphylactic Patients
Authors: T. Utsunomiya, T. Imai, N. Yanagida, S. Sato, T. Komata, M. Tomikawa, A. Shukuya, M. Ebisawa
Journal: Journal of Allergy and Clinical Immunology (2011)
Reply to G. Keramida et al
Authors: Sally F. Barrington, N. George Mikhaeel, Lale Kostakoglu, Michel Meignan, Martin Hutchings, Stefan Müeller, Lawrence H. Schwartz, Emanuele Zucca, Richard I. Fisher, Judith Trotman, Otto S. Hoekstra, Rodney J. Hicks, Michael J. O'Doherty, Roland Hustinx, Alberto Biggi, Bruce D. Cheson
Journal: Journal of Clinical Oncology (2015)

The letter by Keramida and Peters 1 in response to our practice guidelines 2 cites their recently published data from 304 patients undergoing half body [ 18 F]fluorodeoxyglucose (FDG) positron emission tomography/computed tomography scans at their hospital. 3eramida and Peters 1 propose that an assumption be made that FDG tumor kinetics are similar to those in the brain, because some tumors have been shown to have an inverse relationship with blood glucose (namely, gliomas 4 and head and neck cancers 5 ), although not lung cancer. 6 As stated by Keramida and Peters, there are no published data about the relationship of lymphoma to blood glucose.They suggest that, on the basis of their observations, if lymphomatous tumors behave like the brain with respect to blood glucose, lymphoma maximum standardized uptake value (SUVmax) should be normalized to blood glucose when liver SUVmax is used as a comparator in the Deauville criteria.This is an interesting theoretical concept that would probably be most relevant, according to their data, over the steep part of the curve describing the relationship between the ratio of brain SUVmax/liver SUVmax to blood glucose, which lies between 2.5 and 5.0.Because lymphoma is a chemosensitive tumor, FDG uptake decreases rapidly during treatment, and the ratio of uptake between the hottest area of residual tumor and the liver is typically lower than this level.Only patients with a Deauville score of 5, defined by uptake two to three times greater than the uptake in a large region of interest in normal liver, 2 would lie on the steep part of the curve, where the dependence on blood glucose would be most likely to affect quantitative measurement.Patients with ratios of uptake lower than this, whether assessed by visual or quantitative assessment, are likely to be less affected by blood glucose concentration, provided blood glucose is within an acceptable range with proper patient preparation, as recommended by European guidelines, which were recently updated. 7A score of 5 is concerning for treatment failure and above this level, the error in the absolute measurement of SUVmax has little impact on management.Our recommendations support the use of the 5-point visual Deauville score.It is a reproducible and clinically relevant scoring system that, rather than representing a fallacy, is based on a long line of clinical studies.It is acknowledged in our guidelines that work is ongoing to assess optimal tumor and liver metrics.To reiterate previous correspondence, 8 there is scientific merit in trying to develop and improve quantitative imaging parameters in lymphoma and to generate evidence of their clinical efficacy for future recommendations. 2 However, models that have not yet been validated in tumors have no place in practice guidelines.