tbuckley/cabot-search huggingface dataset:
Geographic Proximity and Racial Disparities in Cancer Clinical Trial Participation
Authors: Norma F. Kanarek, Hua-Ling Tsai, Sharon Metzger-Gaud, Dorothy Damron, Alla Guseynova, Justin F. Klamerus, Charles M. Rudin
Journal: Journal of the National Comprehensive Cancer Network (2010)

This study assessed the effects of race and place of residence on clinical trial participation by patients seen at a designated NCI comprehensive cancer center. Clinical trial accrual to cancer case ratios were evaluated using a database of residents at the continental United States seen at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins from 2005 to 2007. Place of residence was categorized into 3 nonoverlapping geographic areas: Baltimore City, non–Baltimore City catchment area, and non–catchment area. Controlling for age, sex, county poverty level, and cancer site, significant race and place of residence differences were seen in therapeutic or nontherapeutic clinical trials participation. White non–Baltimore City catchment area residents, the designated reference group, achieved the highest participation rate. Although the test of interaction (control group compared with all others) was not significant, some race–geographic area group differences were detected. In therapeutic trials, most race–place of residence group levels were statistically lower and different from reference; in nontherapeutic trials, race-specific Baltimore City groups participated at levels similar to reference. Baltimore City residents had lower participation rates only in therapeutic trials, irrespective of race. County poverty level was not significant but was retained as a confounder. Place of residence and race were found to be significant predictors of participation in therapeutic and nontherapeutic clinical trials, although patterns differed somewhat between therapeutic and nontherapeutic trials. Clinical trial accruals are not uniform across age, sex, race, place of residence, cancer site, or trial type, underscoring that cancer centers must better understand their source patients to enhance clinical trial participation.
Effect of Immunization on the Spread of Transplanted Mouse Lymphoma Cells2
Authors: Eva Klein
Journal: JNCI Journal of the National Cancer Institute (1973)

The outgrowth of 2 Moloney lymphomas carried in transplantation was inhibited by preimmunization in syngeneic animals. These tumors usually grow as generalized lymphomas with lymph node enlargement without visible tumor formation at the site of inoculation. When animals were challenged before immunity fully developed, the growth pattern changed to solid tumors.
The influence of bronchial asthma as a comorbidity of COPD on the COPD assessment test (CAT)
Authors: Taisuke Jo, Yasuhiro Yamauchi, Reiko Okudaira, Akira Saito, Nobuaki Hirota, Yasushi Goto, Osamu Narumoto, Kousuke Watanabe, Mitsuhiro Sunohara, Yosuke Amano, Masafumi Horie, Yu Mikami, Satoshi Noguchi, Hirotaka Matsuzaki, Goh Tanaka, Kazutaka Takami, Nobuya Ohishi, Tadashi Kohyama, Takahide Nagase
Journal: European Respiratory Journal (2014)

Introduction: Bronchial asthma (BA) represents features similar to Chronic Obstructive Pulmonary Disease (COPD). Despite, in intervention study, distinction from one another is required which may lead to a study population dissociated from that we face in clinical practice. The concept that these two disease actually coexist in one airway has become widely accepted. The aim of this study is to see if BA as a comorbidity of COPD has affected the COPD assessment test (CAT). Methods: Records of Total 75 COPD patients who entered the University of Tokyo Hospital from 2012 onwards were analyzed. Results: Out of 20 patients who were diagnosed as having BA alongside with COPD (COPD/BA+) by their respective attending physicians, 16 had inhaled corticosteroid (ICS) when CAT was performed. Ratio of patients who met the criteria of CAT≥10 was 0.60 for both COPD patients without BA (COPD/BA-) and COPD/BA+, 12.7 ± 0.89 (mean ± SEM) and 12.3 ± 1.6, respectively. The ratio was 0.56 (11.9 ± 1.87) for COPD/BA+ with ICS (ICS+) and 0.75 (13.8 ± 3.3) for COPD/BA+ without ICS (ICS-). Whilst, in COPD/BA- patients, it was 0.80 (14.7 ± 1.95) for ICS+ and 0.52 (12.2 ± 1.28) for ICS-. ΔCAT (CAT maximum−CAT minimum) was evaluated for 35 patients whose CAT was followed up for over 6 months. In COPD/BA-, ΔCAT was 7.5 ± 1.91 and 5.93 ± 1.27, for ICS+ and ICS- respectively. In COPD/BA+, it was 5.57 ± 0.48 and 9.33 ± 3.67 for ICS+ and ICS- respectively. Conclusion: Our preliminary data seems to suggest that CAT of COPD/BA+ is more susceptible to ICS compared to COPD/BA-. We will further process this cohort analysis in desire to have a better understanding of COPD patients associated with BA.
The number of exacerbations in children and adolescents with cystic fibrosis (CF) can be predicted by computed tomography (CT) bronchiectasis (BE) score and quality of life scores
Authors: Leonie Tepper, Elisabeth Utens, Alexandra Quittner, Karla Gonzalez-Graniel, Hugo Duivenvoorden, Harm Tiddens
Journal: European Respiratory Journal (2011)

Background:  CF is characterized by progressive BE and small airways disease. BE is related to the number of exacerbations and Health Related Quality of Life (HRQoL), assessed by the Cystic Fibrosis Questionnaire-Revised (CFQ-R).   Objective:  1) Investigate predictive value of BE score and CFQ-R respiratory domain score (CFQ-R resp) for exacerbations. 2) Determine added predictive value of CFQ-R resp on top of BE score to predict number of exacerbations in the year following.   Methods:  Cohort study (July 2007 to Jan 2010) in clinical stable children and adolescents with CF, whom had routine chest CT and CFQ-R as part of their (bi-)annual examination. CT scans were anonymized and randomly scored using CFCT BE score, expressing BE as% of maximum score. CFQ-R was completed by children aged 6-13 years and their parents or by adolescents aged ≥ 14 years. Score-range 0-100, higher scores indicate better HRQoL. To compute predictive value of BE-score and CFQ-R resp the negative binomial regression was used and for added predictive value McFadden9s R 2 .   Results:  CF patients (n=72); CFQ-Rs: child CFQ-Rs (n=40); parental CFQ-Rs (n=37); adolescent CFQ-Rs (n=32). Median CFQ-R resp score 83 (range 11-100) points. BE score positive predictive (p s =0.11), CFQ-R resp negative predictive (p s =-0.04) for number of exacerbations. Added predictive value of CFQ-R resp on top of BE score to predict number of exacerbations equalled 6%.   Conclusion:  BE and HRQoL have potentialities to predict the number of exacerbations in CF. A point increase on the CFQ-R resp results in a 6% reduction of the number of exacerbations.
Longitudinal Distribution of Blood in the Rabbit in Relation to the Heart, with Observations on the Contribution of Different Organs
Authors: C. John DICKINSON, ROGER H. SECKER Walker
Journal: Circulation Research (1970)

The distribution of blood along the length of an animal is relevant to the stability of cardiac filling pressure during tilting. We investigated the longitudinal distribution of blood in conscious, anesthetized, and dead, rabbits by a scanning technique, after labeling red blood cells with 51 Cr. The mean longitudinal distributions of blood were computed after standardization for body size and radioactivity. The longitudinal distribution of blood showed a large main peak near the level of the tricuspid valve. General anesthesia produced very little change in blood distribution, but after death blood left the lower abdomen and accumulated in the upper abdomen, probably in the liver. The liver made much the greatest contribution (25 to 30%) to the total pool of blood, but the blood contained within it was labile and could be largely removed by bleeding the animal, or transferred to the lungs during pulmonary congestion.
Nitric Oxide Increases Albumin Permeability of Isolated Rat Glomeruli via a Phosphorylation-Dependent Mechanism
Authors: Bing Li, Jian Yao, Tetsuo Morioka, Takashi Oite
Journal: Journal of the American Society of Nephrology (2001)

ABSTRACT. Nitric oxide (NO) has been implicated in the induction of proteinuria in acute inflammatory glomerulonephritis and in the increased vascular permeability seen in various other disease conditions. The complicated interactions of NO with other factors in vivo hinder analysis of the mechanisms involved. By use of a recently introduced method for measuring albumin permeability (Pa) in isolated glomeruli, the question of whether NO has a direct effect on the permeability barrier of glomerular tufts was examined and the potential mechanisms were explored. Exposure of isolated glomeruli to three NO donors, s-nitroso-N-acetyl-penicillamine (SNAP), (Z)-1-[-2-(aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NONOate), and sodium nitroprusside, all increased the Pa. This action of NO was time- and concentration-dependent and could be mimicked by 8-bromoguanosine 3′, 5′-cyclic monophosphate. Western blot analysis of the proteins from NO donor-treated glomeruli revealed an increase of phosphotyrosine levels of proteins of molecular mass about 120 and 70 kD. The demonstration that pretreatment of glomeruli with the tyrosine kinase inhibitor, genistein, could largely prevent the effect of SNAP and DETA-NONOate confirmed the crucial role of tyrosine phosphorylation in the NO-induced increase of Pa. Furthermore, the tyrosine phosphatase inhibitor, phenylarsine oxide (PAO), could mimic the action of NO on Pa. NO-enhanced tyrosine phosphorylation was further confirmed by immunofluorescence staining, where positive cells in SNAP- and PAO-treated glomeruli were much more frequent than that in controls. By use of dual-label staining in combination with podocyte specific marker, nephrin, it was observed that most of the phosphorylated positive cells corresponded to podocytes. These results suggest that NO impairs the glomerular permeability barrier through a tyrosine phosphorylation-dependent mechanism.
Abstract 2446: Determination of Key Sites of CFAE-targeted AF Ablation and Correlation with Cardiac Ganglionic Plexi
Authors: Evan E Lockwood, Koonlawee Nademanee
Journal: Circulation (2007)

Substrate-targeted AF ablation relies on accurate locating of sites with Complex Fractionated Atrial Electrograms (CFAE). Our objectives were to determine if key sites of CFAE are predictably located and to determine the overlap of these sites with the locations of ganglionic plexi (GP). Utilizing a cardiac CT via image integration, we mapped all sites of CFAE on 54 pts (age 66 ±10 yrs; 78% male; 26% paroxysmal (pAF), 74% persistent or permanent AF (ppAF)) undergoing AF ablation. All patients were in SR at the end of the procedure. Ibutilide was used in 21% pAF vs. 85% ppAF (p&lt;0.001) &amp; DDCV was used in none of the pAF vs. 20% ppAF (p=ns). Mean number of lesions &amp; mean RF duration were 46 ± 27 &amp; 29.5 ±12 min for pAF; 62 ± 23 &amp; 30 ±12 min for ppAF (p=0.04 &amp; p=ns, respectively). A detailed grid of 44 regions in the LA, RA, &amp; CS was created and applied to each CARTOMERGE (mean alignment 2.39 ± 0.43 mm). The prox CS &amp; septal wall anterior to the RSPV were most common sites of CFAE regardless of AF type. The RSPV, LSPV, &amp; anterior wall medial to the LAA were with next most common in pAF and the anterior wall medial to the LAA, the ridge between the LAA &amp; LSPV, and the septal wall anterior to the RIPV were the next in ppAF. A CTI line was done in 21% pAF and 8% ppAF (p=ns) and targeted ablation within any PV antrum in 86% pAF and 83% ppAF (p=ns). Ablation near a GP occurred in &gt;98% of pts (Figure shows pts with ablation on each GP as %pAF / %ppAF). Conclusion: the distribution of substrate that perpetuates AF (as indicated by CFAE) is not homogeneous, and predominant sites are the CS and areas near the PV’s and LAA. A PVI technique utilizing a wide antrum lesion set would affect similar areas in patients with pAF, but not necessarily ppAF.
High blood pressure is warning sign in pregnant women with new headaches, study finds
Authors: Susan Mayor
Journal: BMJ (2015)

High blood pressure and no history of headaches can be warning signs of complications such as pre-eclampsia in pregnant women presenting with severe headache and should trigger further investigation, a US study shows.

The study, published in Neurology ,1 analysed the health records of every pregnant woman referred for a neurological consultation after presenting with acute headache at a New York hospital over a five year period from 1 July 2009 to 30 June 2014.

“Headaches during pregnancy are …
Late-breaking abstract: Nocturnal intermittent hypoxia strongly predicts systemic hypertension in the European Sleep Apnoea Cohort Study
Authors: Ruzena Tkacova, Walter McNicholas, Martin Javorsky, Ingo Fietze, Gianfranco Parati, Pawel Sliwinski, Ludger Grote, Jan Hedner
Journal: European Respiratory Journal (2011)

Background:  Systemic hypertension is independently associated with obstructive sleep apnoea syndrome (OSAS). The underlying mechanisms of this association are incompletely understood. A collaborative European network of 22 sleep centres facilitated the establishment of a European Sleep Apnoea Database (ESADA), designed to evaluate associations between OSAS and cardiovascular diseases. The present study employed ESADA to study associations between OSAS and systemic hypertension.   Methods:  5103 adult subjects evaluated for suspected OSAS underwent overnight sleep studies. The association of prevalent hypertension with OSAS was examined and adjusted for relevant covariates such as age, smoking, obesity, dyslipidaemia and diabetes. We compared the predictive value of the apnoea-hypopnoea index (AHI) and oxygen desaturation index (ODI) for the presence of hypertension.   Findings:  Patients were 72% male; 29% were >60 years; 79.4% had AHI >5 and 42.9% had systemic hypertension. Both AHI and ODI were related to prevalent hypertension after adjustment for relevant covariates (P   Interpretation:  These findings support ODI as an important predictor of systemic hypertension in OSAS patients and chronic intermittent hypoxia as a central pathophysiological mechanism.  Funding: ResMed and Phillips Respironics.
Ofatumumab added to dexamethasone in patients with relapsed or refractory chronic lymphocytic leukemia: Results from a phase II study
Authors: Michael Doubek, Yvona Brychtova, Anna Panovska, Ludmila Sebejova, Olga Stehlikova, Jana Chovancova, Jitka Malcikova, Jana Smardova, Karla Plevova, Pavlina Volfova, Martin Trbusek, Marek Mraz, Denisa Bakesova, Jakub Trizuljak, Marketa Hadrabova, Petra Obrtlikova, Josef Karban, Lukas Smolej, Alexandra Oltova, Eva Jelinkova, Sarka Pospisilova, Jiri Mayer
Journal: American Journal of Hematology (2015)

The treatment of relapsed/refractory chronic lymphocytic leukemia (CLL) remains a challenging clinical issue. An important treatment option is the use of high‐dose corticosteroids. The purpose of this clinical trial was to determine the efficacy and toxicity of an ofatumumab–dexamethasone (O‐Dex) combination in relapsed or refractory CLL. The trial was an open‐label, multicenter, nonrandomized, Phase II study. The O‐Dex regimen consisted of intravenous ofatumumab (Cycle 1: 300 mg on day 1, 2,000 mg on days 8, 15, and 22; Cycles 2–6: 1,000 mg on days 1, 8, 15, and 22) and oral dexamethasone (40 mg on days 1–4 and 15–18; Cycles 1–6). The O‐Dex regimen was given until best response, or a maximum of six cycles. Thirty‐three patients (pts) were recruited. Twenty‐four (73%) pts completed at least three cycles of therapy. The remaining nine pts were prematurely discontinued owing to Grade 3/4 infections (seven pts), disease progression (one pt), or uncontrollable diabetes mellitus (one pt). Overall response rates/complete remissions (ORR/CR) were achieved in 22/5 pts (67/15%). The median progression‐free survival (PFS) was 10 months. In pts with p53 defects ( n = 8), ORR/CR were achieved in 5/2 pts (63/25%) with a median PFS of 10.5 months. The median overall survival (OS) was 34 months. The Grades 3–5 infectious toxicity in 33% of pts represented the most frequent side effect during the treatment period. In conclusion, the O‐Dex regimen shows a relatively high ORR and CR with promising findings for PFS and OS. The study was registered at www.clinicaltrials.gov (NCT01310101). Am. J. Hematol. 90:417–421, 2015. © 2015 Wiley Periodicals, Inc.
The Changing Profile of Poisoning and its Management
Authors: A F MacNamara, M S Riyat, D N Quinton
Journal: Journal of the Royal Society of Medicine (1996)

To identify changes in treatment methods and types of drugs taken in overdoses over a 10-year period we conducted a retrospective study in the accident and emergency department of a large teaching hospital. The influence of a protocol to direct medical management was also studied. Results were compared with those of a 1984 survey at the same institution. 409 cases of accidental and deliberate poisoning were reviewed. In deliberate poisoning 52% of drugs taken were prescription drugs, 41.6% over-the-counter medications and the remaining 6.4% illicit drugs. Only 13% of patients had a stomach emptying procedure compared with 75.2% of patients in the previous survey. Charcoal was administered or offered in over 95% of cases. Medical management of overdoses in this centre changed drastically over 10 years. A department protocol had been adhered to in the great majority of cases, and we recommend that all accident and emergency departments as well as medical and paediatric teams establish similar protocols. Over-the-counter drugs are increasingly troublesome, especially paracetamol, which accounts for 28.8% of drugs taken in deliberate overdose.
Molecular Basis of Hypokalemia-Induced Ventricular Fibrillation
Authors: Arash Pezhouman, Neha Singh, Zhen Song, Michael Nivala, Anahita Eskandari, Hong Cao, Aneesh Bapat, Christopher Y. Ko, Thao P. Nguyen, Zhilin Qu, Hrayr S. Karagueuzian, James N. Weiss
Journal: Circulation (2015)

Hypokalemia is known to promote ventricular arrhythmias, especially in combination with class III antiarrhythmic drugs like dofetilide. Here, we evaluated the underlying molecular mechanisms.Arrhythmias were recorded in isolated rabbit and rat hearts or patch-clamped ventricular myocytes exposed to hypokalemia (1.0-3.5 mmol/L) in the absence or presence of dofetilide (1 μmol/L). Spontaneous early afterdepolarizations (EADs) and ventricular tachycardia/fibrillation occurred in 50% of hearts at 2.7 mmol/L [K] in the absence of dofetilide and 3.3 mmol/L [K] in its presence. Pretreatment with the Ca-calmodulin kinase II (CaMKII) inhibitor KN-93, but not its inactive analogue KN-92, abolished EADs and hypokalemia-induced ventricular tachycardia/fibrillation, as did the selective late Na current (INa) blocker GS-967. In intact hearts, moderate hypokalemia (2.7 mmol/L) significantly increased tissue CaMKII activity. Computer modeling revealed that EAD generation by hypokalemia (with or without dofetilide) required Na-K pump inhibition to induce intracellular Na and Ca overload with consequent CaMKII activation enhancing late INa and the L-type Ca current. K current suppression by hypokalemia and dofetilide alone in the absence of CaMKII activation were ineffective at causing EADs.We conclude that Na-K pump inhibition by even moderate hypokalemia plays a critical role in promoting EAD-mediated arrhythmias by inducing a positive feedback cycle activating CaMKII and enhancing late INa. Class III antiarrhythmic drugs like dofetilide sensitize the heart to this positive feedback loop.
Pulmonary alveolar proteinosis: revealing a wider defect in host immunity
Authors: Samudra Mukherjee
Journal: Thorax (2007)

▴ Uchida K, Beck DC, Yomamoto T, et al . GM-CSF autoantibodies and neutrophil dysfunction in pulmonary alveolar proteinosis. NEJM2007;356:567–79.

[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4]



Pulmonary alveolar proteinosis (PAP) is a rare disorder of excessive accumulation of surfactant components in alveoli. The inhibition of granulocyte-macrophage colony-stimulating factor (GM-CSF) by blocking autoantibodies seems to lead to impaired surfactant clearance by alveolar macrophages. The authors explored the hypothesis that common and opportunistic pulmonary and disseminated infections reported in PAP are secondary to the effect of GM-CSF autoantibody (GM-CSF-Ab) on …

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Achievement of Optimal Medical Therapy Goals for U.S. Adults With Coronary Artery Disease
Authors: Todd M Brown, Jenifer H Voeks, Vera Bittner, David A Brenner, Mary Cushman, David C Goff, Stephen Glasser, Paul Muntner, Paul B Tabereaux, Monika M Safford
Journal: Journal of the American College of Cardiology (2014)
Cyclin D1 Loss Distinguishes Prostatic Small-Cell Carcinoma from Most Prostatic Adenocarcinomas
Authors: Harrison Tsai, Carlos L. Morais, Mohammed Alshalalfa, Hsueh-Li Tan, Zaid Haddad, Jessica Hicks, Nilesh Gupta, Jonathan I. Epstein, George J. Netto, William B. Isaacs, Jun Luo, Rohit Mehra, Robert L. Vessella, R. Jeffrey Karnes, Edward M. Schaeffer, Elai Davicioni, Angelo M. De Marzo, Tamara L. Lotan
Journal: Clinical Cancer Research (2015)

Small-cell neuroendocrine differentiation in prostatic carcinoma is an increasingly common resistance mechanism to potent androgen deprivation therapy (ADT), but can be difficult to identify morphologically. We investigated whether cyclin D1 and p16 expression can inform on Rb functional status and distinguish small-cell carcinoma from adenocarcinoma.We used gene expression data and immunohistochemistry to examine cyclin D1 and p16 levels in patient-derived xenografts (PDX), and prostatic small-cell carcinoma and adenocarcinoma specimens.Using PDX, we show proof-of-concept that a high ratio of p16 to cyclin D1 gene expression reflects underlying Rb functional loss and distinguishes morphologically identified small-cell carcinoma from prostatic adenocarcinoma in patient specimens (n = 13 and 9, respectively). At the protein level, cyclin D1, but not p16, was useful to distinguish small-cell carcinoma from adenocarcinoma. Overall, 88% (36/41) of small-cell carcinomas showed cyclin D1 loss by immunostaining compared with 2% (2/94) of Gleason score 7-10 primary adenocarcinomas at radical prostatectomy, 9% (4/44) of Gleason score 9-10 primary adenocarcinomas at needle biopsy, and 7% (8/115) of individual metastases from 39 patients at autopsy. Though rare adenocarcinomas showed cyclin D1 loss, many of these were associated with clinical features of small-cell carcinoma, and in a cohort of men treated with adjuvant ADT who developed metastasis, lower cyclin D1 gene expression was associated with more rapid onset of metastasis and death.Cyclin D1 loss identifies prostate tumors with small-cell differentiation and may identify a small subset of adenocarcinomas with poor prognosis. Clin Cancer Res; 21(24); 5619-29. ©2015 AACR.