tbuckley/cabot-search huggingface dataset:
Selectin-mucin interactions as a probable molecular explanation for the association of Trousseau syndrome with mucinous adenocarcinomas
Authors: Mark Wahrenbrock, Lubor Borsig, Dzung Le, Nissi Varki, Ajit Varki
Journal: Journal of Clinical Investigation (2003)

Trousseau described spontaneous, recurrent superficial migratory thrombophlebitis associated with occult cancers, and this was later correlated with disseminated microangiopathy (platelet-rich clots in small blood vessels). Trousseau syndrome often occurs with mucinous adenocarcinomas, which secrete abnormally glycosylated mucins and mucin fragments into the bloodstream. Since carcinoma mucins can have binding sites for selectins, we hypothesized that selectin-mucin interactions might trigger this syndrome. When highly purified, tissue-factor free carcinoma mucin preparations were intravenously injected into mice, platelet-rich microthrombi were rapidly generated. This pathology was markedly diminished in P- or L-selectin–deficient mice. Heparin (an antithrombin-potentiating agent that can also block P- and L-selectin recognition of ligands) ameliorated this platelet aggregation, but had no additional effect in P- or L-selectin–deficient mice. Inhibition of endogenous thrombin by recombinant hirudin also did not block platelet aggregation. Mucins generated platelet aggregation in vitro in hirudinized whole blood, but not in platelet-rich leukocyte-free plasma nor in whole blood from L-selectin–deficient mice. Thus, Trousseau syndrome is likely triggered by interactions of circulating carcinoma mucins with leukocyte L-selectin and platelet P-selectin without requiring accompanying thrombin generation. These data may also explain why heparin ameliorates Trousseau syndrome, while vitamin K antagonists that merely depress thrombin production do not.
Pulmonary Auscultatory Skills During Training in Internal Medicine and Family Practice
Authors: SALVATORE MANGIONE, LINDA Z. NIEMAN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

We conducted a multicenter, cross-sectional assessment of pulmonary auscultatory skills among medical students and housestaff. Our study included 194 medical students, 18 pulmonary fellows, and 656 generalists-in-training from 17 internal medicine and 23 family practice programs in the Mid- Atlantic area of the United States. All participants listened to 10 pulmonary events recorded directly from patients, and answered by completing a multiple choice questionnaire. Proficiency scores were expressed as the percentage of respondents per year and type of training who correctly identified each event. In addition, we calculated a series of cumulative scores for sound recognition, disease identification, and basic knowledge of lung auscultation. Trainees' cumulative scores ranged from 0 to 85 for both internal medicine and family practice residents (median = 40). On average, internal medicine and family practice trainees recognized less than half of all respiratory events, with little improvement per year of training, and were not significantly better than medical students in their scores. Pulmonary fellows had the highest diagnostic and knowledge scores of all groups. These data indicate that there is very little difference in auscultatory proficiency between internal medicine and family practice trainees, and suggest the need for revisiting these time-honored skills during residency training.
THE ECONOMIC ASPECT IN EYE INJURIES: A PLEA FOR EARLY TREATMENT
Authors: T. L. Llewellyn
Journal: BMJ (1921)

1~~~~~~~~~~~~~~~~~~Cases such as this mav be taken to justify my conten- tion that there are more surgical ways than one of curing toxic stasis, and that every case should be treated in accordance with the spscial indications it presents.Neither, although I have been speaking as a surgeon, am I advocating surgery as the only remedy.Diet, drugs, aperients, paran, massage, exercises, posture, abdominal supports, regulation of -life, change of climate, spa treatment, removal of toxic foci-all have their place in the treatment of intestinal stasis.In treatment, operative and non-operative, the psychic factor must not be over- looked.The rest and careful after-treatment is of benefit after all abdominal operations.The prevention of stasis and toxic foci should begin in babyhood and continue.The earlier the treatment the better, and then the less severe and the more effective it is.Prevention is indeed our final goal.Man steers his life's perilous course through the physical evils which beset him, and our hope for the future is that for the prevention of these evils we shall all work and strive so that stasis and its manifold ill effects may from being a problem of the present become a memory of the past.
CERVICAL DYSPLASIA AND HIV INFECTION
Authors: Brian Spurrett, DavidShelley Jones, Graeme Stewart, P. Crocchiolo, A. Lizioli, F. Goisis, C. Giorgi, E. Buratti, G. Bedarida, M. Nardella, M.P. Panzeri, G. Cambié, F. D'Agostino, Micheline Byrne, David Taylor-Robinson, J.R.W. Harris
Journal: The Lancet (1988)
Diabetic Ketoacidosis and Related Events in the Canagliflozin Type 2 Diabetes Clinical Program
Authors: Ngozi Erondu, Mehul Desai, Kirk Ways, Gary Meininger
Journal: Diabetes Care (2015)

OBJECTIVE This study assessed the incidence of serious adverse events of diabetic ketoacidosis (DKA) among patients with type 2 diabetes treated with canagliflozin. RESEARCH DESIGN AND METHODS All serious adverse events of DKA and related events (ketoacidosis, metabolic acidosis, and acidosis) from 17,596 patients from randomized studies of canagliflozin through 11 May 2015 were analyzed. RESULTS Serious adverse events of DKA and related events were reported in 12 patients (0.07%), including 4 (0.07%), 6 (0.11%), and 2 (0.03%) treated with canagliflozin 100 and 300 mg and comparator, respectively; corresponding incidence rates were 0.522, 0.763, and 0.238 per 1,000 patient-years, respectively. Most patients with DKA and related events had a blood glucose &amp;gt;300 mg/dL (16.7 mmol/L) at presentation of DKA, were on insulin, and had DKA-precipitating factors, including some with type 1 diabetes/latent autoimmune diabetes of adulthood. CONCLUSIONS DKA and related events occurred at a low frequency in the canagliflozin type 2 diabetes program, with an incidence consistent with limited existing observational data in the general population with type 2 diabetes.
652 VIROLOGICAL RESPONSE TO ENTECAVIR IS ASSOCIATED WITH LOW PROBABILITY OF DEVELOPING HEPATOCELLULAR CARCINOMA IN CHRONIC HEPATITIS B PATIENTS WITH CIRRHOSIS
Authors: S.S. Kim, S.J. Ahn, S.Y. Park, G.W. Song, J.Y. Cheong, S.W. Cho
Journal: Journal of Hepatology (2013)
Targeting Hypoxia, HIF-1, and Tumor Glucose Metabolism to Improve Radiotherapy Efficacy
Authors: Tineke W.H. Meijer, Johannes H.A.M. Kaanders, Paul N. Span, Johan Bussink
Journal: Clinical Cancer Research (2012)

Abstract Radiotherapy, an important treatment modality in oncology, kills cells through induction of oxidative stress. However, malignant tumors vary in their response to irradiation as a consequence of resistance mechanisms taking place at the molecular level. It is important to understand these mechanisms of radioresistance, as counteracting them may improve the efficacy of radiotherapy. In this review, we describe how the hypoxia-inducible factor 1 (HIF-1) pathway has a profound effect on the response to radiotherapy. The main focus will be on HIF-1–controlled protection of the vasculature postirradiation and on HIF-1 regulation of glycolysis and the pentose phosphate pathway. This aberrant cellular metabolism increases the antioxidant capacity of tumors, thereby countering the oxidative stress caused by irradiation. From the results of translational studies and the first clinical phase I/II trials, it can be concluded that targeting HIF-1 and tumor glucose metabolism at several levels reduces the antioxidant capacity of tumors, affects the tumor microenvironment, and sensitizes various solid tumors to irradiation. Clin Cancer Res; 18(20); 5585–94. ©2012 AACR.
New-generation taxoid SB-T-1214 inhibits stem cell-related gene expression in 3D cancer spheroids induced by purified colon tumor-initiating cells
Authors: Galina I Botchkina, Edison S Zuniga, Manisha Das, Yuan Wang, Hichao Wang, Shu Zhu, Anne G Savitt, Rebecca A Rowehl, Yan Leyfman, Jingfang Ju, Kenneth Shroyer, Iwao Ojima
Journal: Molecular Cancer (2010)

Growing evidence suggests that the majority of tumors are organized hierarchically, comprising a population of tumor-initiating, or cancer stem cells (CSCs) responsible for tumor development, maintenance and resistance to drugs. Previously we have shown that the CD133high/CD44high fraction of colon cancer cells is different from their bulk counterparts at the functional, morphological and genomic levels. In contrast to the majority of colon cancer cells expressing moderate levels of CD133, CD44 and CD166, cells with a high combined expression of CD133 and CD44 possessed several characteristic stem cell features, including profound self-renewal capacity in vivo and in vitro, and the ability to give rise to different cell phenotypes. The present study was undertaken for two aims: a) to determine stem cell-related genomic characteristics of floating 3D multicellular spheroids induced by CD133high/CD44high colon cancer cells; and b) to evaluate CSC-specific alterations induced by new-generation taxoid SB-T-1214. Selected CSC phenotype was isolated from three independent invasive colon cancer cell lines, HCT116, HT29 and DLD-1. A stem cell-specific PCR array assay (SA Biosciences) revealed that colonospheres induced by purified CD133high/CD44high expressing cells display profound up-regulation of stem cell-related genes in comparison with their bulk counterparts. The FACS analysis has shown that the 3D colonospheres contained some minority cell populations with high levels of expression of Oct4, Sox2, Nanog and c-Myc, which are essential for stem cell pluripotency and self-renewal. Single administration of the SB-T-1214 at concentration 100 nM-1 μM for 48 hr not only induced growth inhibition and apoptotic cell death in these three types of colon cancer spheroids in 3D culture, but also mediated massive inhibition of the stem cell-related genes and significant down-regulation of the pluripotency gene expression. PCR array and FACS data were confirmed with western blotting. Importantly, viable cells that survived this treatment regimen were no longer able to induce secondary floating spheroids and exhibited significant morphological abnormalities. We report here that a new-generation taxoid SB-T-1214 possesses significant activity against colon cancer spheroids induced by and enriched with drug resistant tumorigenic CD133high/CD44high cells and efficiently inhibited expression of the majority of stem cell-related genes. Our data indicates that the previously observed long-term efficacy of SB-T-1214 against drug resistant colon tumors in vivo may be explained by the down-regulation of multiple stem cell-related genes in the tumorigenic cell population, in addition to its known efficacy as a mitotic poison against proliferating cancer cells.
Intramural neurofibroma of the trachea treated by multiple stents
Authors: J H Cranshaw
Journal: Thorax (2001)

The case history is presented of a patient in whom an intramural tracheal neurofibroma developed, causing severe airway stenosis.The patient was treated with multiple stents over a period of 5 years because of progression of the disease and associated airflow limitation.Clinicians should be aware of this rare complication of neurofibromatosis.
Idiopathic bile acid malabsorption--a review of clinical presentation, diagnosis, and response to treatment.
Authors: A J Williams, M V Merrick, M A Eastwood
Journal: Gut (1991)

Between 1982 and 1989, the seven day retention of 75SeHCAT was measured in 181 patients with chronic diarrhoea that remained unexplained after full investigation. Altogether 121 of the 181 had a seven day 75SeHCAT retention greater than or equal to 15% and thus had no evidence of abnormal bile acid turnover. Twenty one had a seven day 75SeHCAT retention greater than or equal to 10% but less than 15%. Their clinical features were typical of the irritable bowel syndrome, and none of eight treated with cholestyramine showed symptomatic improvement. Sixteen patients had a seven day retention greater than or equal to 5% and less than 10%, six of whom had improved symptoms after treatment with bile acid chelating agents. The remaining 23 patients had a 75SeHCAT retention of less than 5% at seven days and responded to bile acid chelators. This group had a characteristic illness with intermittent watery diarrhoea, but no constitutional upset. It was not possible to distinguish the patients with bile acid malabsorption exclusively on the basis of the clinical symptoms and investigations, other than 75SeHCAT retention. We conclude that the measurement of 75SeHCAT retention is useful, appropriate, and necessary in patients with unexplained chronic diarrhoea.
Correlation between insulin-like growth factor binding protein-3 serum level and melanoma progression
Authors: Vincenzo Panasiti, Antimo Naspi, Valeria Devirgiliis, Michela Curzio, Vincenzo Roberti, Gianfranca Curzio, Silvia Gobbi, Stefano Calvieri, Paola Londei
Journal: Journal of the American Academy of Dermatology (2011)
Prognostic Factors in Advanced Cancer Patients: Evidence-Based Clinical Recommendations—A Study by the Steering Committee of the European Association for Palliative Care
Authors: Marco Maltoni, Augusto Caraceni, Cinzia Brunelli, Bert Broeckaert, Nicholas Christakis, Steffen Eychmueller, Paul Glare, Maria Nabal, Antonio Viganò, Philip Larkin, Franco De Conno, Geoffrey Hanks, Stein Kaasa
Journal: Journal of Clinical Oncology (2005)

Purpose To offer evidence-based clinical recommendations concerning prognosis in advanced cancer patients. Methods A Working Group of the Research Network of the European Association for Palliative Care identified clinically significant topics, reviewed the studies, and assigned the level of evidence. A formal meta-analysis was not feasible because of the heterogeneity of published studies and the lack of minimal standards in reporting results. A systematic electronic literature search within the main available medical literature databases was performed for each of the following four areas identified: clinical prediction of survival (CPS), biologic factors, clinical signs and symptoms and psychosocial variables, and prognostic scores. Only studies on patients with advanced cancer and survival ≤ 90 days were included. Results A total of 38 studies were evaluated. Level A evidence-based recommendations of prognostic correlation could be formulated for CPS (albeit with a series of limitations of which clinicians must be aware) and prognostic scores. Recommendations on the use of other prognostic factors, such as performance status, symptoms associated with cancer anorexia-cachexia syndrome (weight loss, anorexia, dysphagia, and xerostomia), dyspnea, delirium, and some biologic factors (leukocytosis, lymphocytopenia, and C-reactive protein), reached level B. Conclusion Prognostication of life expectancy is a significant clinical commitment for clinicians involved in oncology and palliative care. More accurate prognostication is feasible and can be achieved by combining clinical experience and evidence from the literature. Using and communicating prognostic information should be part of a multidisciplinary palliative care approach.
Tabalumab, an anti-BAFF monoclonal antibody, in patients with active rheumatoid arthritis with an inadequate response to TNF inhibitors
Authors: Mark C Genovese, Roy M Fleischmann, Maria Greenwald, Julie Satterwhite, Melissa Veenhuizen, Li Xie, Pierre-Yves Berclaz, Stephen Myers, Olivier Benichou
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To evaluate the efficacy and safety of tabalumab, a monoclonal antibody that neutralises membrane-bound and soluble B-cell activating factor (BAFF), in patients with active rheumatoid arthritis (RA) who showed inadequate response to tumour necrosis factor (TNF) inhibitors. <h3>Methods</h3> Patients on stable methotrexate and with inadequate response to one or more TNF inhibitors were randomised to placebo (n=35), 30 mg tabalumab (n=35) or 80 mg tabalumab (n=30) given intravenously at 0, 3 and 6 weeks. The primary outcome was the proportion of patients achieving an American College of Rheumatology 50% response (ACR50) at week 16 (all tabalumab-treated patients vs placebo). <h3>Results</h3> At week 16, no significant differences were observed in the combined tabalumab group versus placebo in ACR50 (12.7% vs 2.9%, p=0.101) or ACR20 response rates (27.0% vs 17.1%, p=0.198). However, significant differences between the combined tabalumab group and placebo were observed at earlier time points for ACR20, ACR50 and Disease Activity Score in 28 joints (DAS28)-C-reactive protein (CRP) reduction. Treatment-emergent adverse events (AEs) were similar with 30 mg tabalumab (65.7%), 80 mg tabalumab (76.7%) and placebo (71.4%), although certain events occurred more often with tabalumab than placebo (eg, infection, anaemia and gastrointestinal events). Serious AEs occurred in two (6.7%) patients receiving 80 mg tabalumab and three (8.6%) receiving placebo, with one serious infection in the placebo group. Initial increases in total and mature B cells were followed by progressive decreases, despite declines in serum tabalumab. <h3>Conclusions</h3> At week 16, the primary end point was not achieved, but an indication of efficacy was observed at earlier time points. Safety findings for tabalumab were consistent with other biological RA therapies. <h3>Clinical trial registration number</h3> NCT00689728.
SLCO4C1 Transporter Eliminates Uremic Toxins and Attenuates Hypertension and Renal Inflammation
Authors: Takafumi Toyohara, Takehiro Suzuki, Ryo Morimoto, Yasutoshi Akiyama, Tomokazu Souma, Hiromi O. Shiwaku, Yoichi Takeuchi, Eikan Mishima, Michiaki Abe, Masayuki Tanemoto, Satohiro Masuda, Hiroaki Kawano, Koji Maemura, Masaaki Nakayama, Hiroshi Sato, Tsuyoshi Mikkaichi, Hiroaki Yamaguchi, Shigefumi Fukui, Yoshihiro Fukumoto, Hiroaki Shimokawa, Ken-ichi Inui, Tetsuya Terasaki, Junichi Goto, Sadayoshi Ito, Takanori Hishinuma, Isabelle Rubera, Michel Tauc, Yoshiaki Fujii-Kuriyama, Hikaru Yabuuchi, Yoshinori Moriyama, Tomoyoshi Soga, Takaaki Abe
Journal: Journal of the American Society of Nephrology (2009)

Hypertension in patients with chronic kidney disease (CKD) strongly associates with cardiovascular events. Among patients with CKD, reducing the accumulation of uremic toxins may protect against the development of hypertension and progression of renal damage, but there are no established therapies to accomplish this. Here, overexpression of human kidney-specific organic anion transporter SLCO4C1 in rat kidney reduced hypertension, cardiomegaly, and inflammation in the setting of renal failure. In addition, SLCO4C1 overexpression decreased plasma levels of the uremic toxins guanidino succinate, asymmetric dimethylarginine, and the newly identified trans-aconitate. We found that xenobiotic responsive element core motifs regulate SLCO4C1 transcription, and various statins, which act as inducers of nuclear aryl hydrocarbon receptors, upregulate SLCO4C1 transcription. Pravastatin, which is cardioprotective, increased the clearance of asymmetric dimethylarginine and trans-aconitate in renal failure. These data suggest that drugs that upregulate SLCO4C1 may have therapeutic potential for patients with CKD.
Quantitative ultrastructural analysis of the human parietal cell during acid inhibition and increase of gastric potential difference by glucagon.
Authors: K J Ivey, A Tarnawski, D Sherman, W J Krause, K Ackman, M Burks, J Hewett
Journal: Gut (1980)

Glucagon inhibits gastric acid secretion and increases the negativity of gastric mucosal potential difference (PD) in man. To test the hypothesis that the increased negativity of PD after glucagon in man could be due to decreased parietal cell canalicular membrane area, a quantitative ultrastructural analysis was carried out. Four healthy volunteers with normal gastric mucosa were submitted to biopsy before and 20 minutes after intravenous injection of 2 mg glucagon (G). This time corresponded with the maximal change in PD and a decrease in gastric acid secretion. Canalicular and tubulovesicular membrane area of 80 parietal cells (40 cells before glucagon and 40 cells after glucagon) were quantified by the Loud morphometric method. After glucagon, the oxyntic cell canalicular membrane area was reduced by one-fourth (P less than 0.05), while tubulovesicular membrane area showed an increase (P less than 0.05) at the same time. The decrease in the area of parietal cell canalicular membrane caused by glucagon may in part be responsible for increased negativity of the gastric PD caused by this hormone.
Primary Transpupillary Thermotherapy for Choroidal Melanoma in 391 Cases
Authors: Arman Mashayekhi, Carol L Shields, Pukhraj Rishi, Hatice T Atalay, Marco Pellegrini, John P McLaughlin, Kaitlin A Patrick, Spenser J Morton, Meredith H Remmer, Anthony Parendo, Meghan A Schlitt, Jerry A Shields
Journal: Ophthalmology (2014)
BRAF Inhibitor Resistance Mechanisms in Metastatic Melanoma: Spectrum and Clinical Impact
Authors: Helen Rizos, Alexander M. Menzies, Gulietta M. Pupo, Matteo S. Carlino, Carina Fung, Jessica Hyman, Lauren E. Haydu, Branka Mijatov, Therese M. Becker, Suzanah C. Boyd, Julie Howle, Robyn Saw, John F. Thompson, Richard F. Kefford, Richard A. Scolyer, Georgina V. Long
Journal: Clinical Cancer Research (2014)

Multiple BRAF inhibitor resistance mechanisms have been described, however, their relative frequency, clinical correlates, and effect on subsequent therapy have not been assessed in patients with metastatic melanoma.Fifty-nine BRAF(V600)-mutant melanoma metastases from patients treated with dabrafenib or vemurafenib were analyzed. The genetic profile of resistance mechanisms and tumor signaling pathway activity was correlated with clinicopathologic features and therapeutic outcomes.Resistance mechanisms were identified in 58% progressing tumors and BRAF alterations were common. Gene expression analysis revealed that mitogen-activated protein kinase (MAPK) activity remained inhibited in 21% of resistant tumors, and the outcomes of patients with these tumors were poor. Resistance mechanisms also occurred in pretreatment biopsies and heterogeneity of resistance mechanisms occurred within patients and within tumors. There were no responses to subsequent targeted therapy, even when a progressing tumor had a resistance mechanism predicted to be responsive.Selecting sequential drugs based on the molecular characteristics of a single progressing biopsy is unlikely to provide improved responses, and first-line therapies targeting multiple pathways will be required.
Bevacizumab-Erlotinib As Maintenance Therapy in Metastatic Colorectal Cancer. Final Results of the Gercor Dream Study
Authors: B. Chibaudel, C. Tournigand, B. Samson, W. Scheithauer, P. Mesange, G. Lledo, F. Viret, J.F. Ramée, N. Tubiana-Mathieu, J. Dauba, O. Dupuis, Y. Rinaldi, M. Mabro, N. Aucoin, J. Latreille, F. Bonnetain, C. Louvet, A.K. Larsen, T. André, A. De Gramont
Journal: Annals of Oncology (2014)
The illusory triumph of machine over mind: Wegner's eliminativism and the real promise of psychology
Authors: Anthony I. Jack, Philip Robbins
Journal: Behavioral and Brain Sciences (2004)

Wegner's thesis that the experience of will is an illusion is not just wrong, it is an impediment to progress in psychology. We discuss two readings of Wegner's thesis and find that neither can motivate his larger conclusion. Wegner thinks science requires us to dismiss our experiences. Its real promise is to help us to make better sense of them.