tbuckley/cabot-search huggingface dataset:
Predictive Value of Bone Resorption and Formation Markers in Cancer Patients With Bone Metastases Receiving the Bisphosphonate Zoledronic Acid
Authors: Robert E. Coleman, Pierre Major, Allan Lipton, Janet E. Brown, Ker-Ai Lee, Matthew Smith, Fred Saad, Ming Zheng, Yong Jiang Hei, John Seaman, Richard Cook
Journal: Journal of Clinical Oncology (2005)

Three large, randomized trials of patients with bone metastases recently demonstrated that zoledronic acid reduces the risk of skeletal-related events. These trials provide an opportunity for investigating the correlation between bone metabolism and clinical outcome during bisphosphonate therapy.Urinary measurements of N-telopeptide (Ntx) and serum bone alkaline phosphatase (BAP) were obtained in 1,824 bisphosphonate-treated patients-1,462 with zoledronic acid (breast, 490; prostate, 411; myeloma, 210; non-small-cell lung, 183; other, 168) and 362 with pamidronate (breast, 254; myeloma, 108). This exploratory cohort analysis grouped patients by baseline and most recent levels of Ntx as low (< 50 nmol/mmol creatinine), moderate (50 to 99 nmol/mmol creatinine), or high (> or = 100 nmol/mmol creatinine), and BAP as low (< 146 U/L) or high (> or = 146 U/L). The relative risks for negative clinical outcomes were estimated for each group using multiple-event and Cox regression models with time-varying covariates.Patients with high and moderate Ntx levels had 2-fold increases in their risk of skeletal complications and disease progression compared with patients with low Ntx levels (P < .001 for all). High Ntx levels in each solid tumor category were associated with a 4- to 6-fold increased risk of death on study, and moderate Ntx levels a 2- to 4-fold increased risk compared with low Ntx levels (P < .001 for all). Bone alkaline phosphatase also showed some correlation with risk of negative clinical outcomes.The bone resorption marker Ntx provides valuable prognostic information in patients with bone metastases receiving bisphosphonates.
Coronary Vascular Effects of Glucagon in the Isolated Dog Heart
Authors: THOMAS W. MOIR, WINIFRED G. NAYLER
Journal: Circulation Research (1970)

Glucagon decreases peripheral vascular resistance by direct action on the arterioles. The present experiments were performed to study the effect of glucagon on the coronary resistance vessels. In isolated hearts from eight dogs the coronary arteries were perfused at a constant rate and the change in coronary pressure was used as an index of change in resistance after the intracoronary injections of glucagon (50 µg/kg). In the beating heart, glucagon caused a 22% decrease in the average coronary pressure (from 102 to 80 mm Hg); however, with this decrease in coronary resistance, myocardial contractility rose an average of 45% (from 11 to 16 units), the average heart rate increased 38% (from 156 to 213 beats/min), and the average coronary venous oxygen saturation decreased from 79.7% to 63.7%. However, when similar intracoronary injections of glucagon were made after cardiac arrest by potassium there was no change in coronary venous oxygen saturation and no significant decrease in coronary pressure. We conclude that the decrease in coronary resistance in the beating heart after glucagon injection is secondary to the metabolic effects of the increased myocardial contractility and heart rate, and that there is no significant direct vasodilating effect on the coronary resistance vessels.
The prevalence, incidence and severity of low back pain among international-level rowers
Authors: Craig Newlands, Duncan Reid, Priya Parmar
Journal: British Journal of Sports Medicine (2015)

Background/aims There is a paucity of prospective cohort studies investigating the incidence of low back pain (LBP) in rowing. We investigated (1) the prevalence and incidence of LBP among international-level rowers in New Zealand, (2) the relationship between training volume and LBP and (3) the effect of LBP on rowers’ ability to train and compete. Methods This was a prospective cohort study of 76 New Zealand representative rowers, including 46 men (mean age 22, SD=4) and 30 women (mean age 21, SD=4). Data were collected using an online questionnaire repeated monthly for 12 months. Results The prevalence of LBP ranged from 6% to 25% throughout the year. The incidence of episodes of LBP was 1.67 per 1000 exposure-hours. A total of 72 episodes of LBP were reported by 40 rowers (53%) during 12 months. Of these, 45% had an incidental effect on training. 29% minor, 18% moderate and 9% had a major effect as determined by the length of time the training was interrupted. There was a high correlation between new LBP and total training hours per month (r=0.83, p&lt;0.01). A previous history of LBP was a risk factor in developing new LBP (OR 2.06, 95% CI 1.22 to 3.48, p=0.01). Age was also a risk factor, with the likelihood of developing LBP increasing for every year (OR 1.08, 95% CI 1.01 to 1.15, p=0.02). Conclusions LBP is common among New Zealand representative rowers. There is a high correlation between training load and the development of LBP.
The effects of the coronary capacitance on the interpretation of diastolic pressure-flow relationships.
Authors: C Eng, J H Jentzer, E S Kirk
Journal: Circulation Research (1982)

The effects of coronary capacitance on instantaneous pressure-flow (P/F) relationships were analyzed using a theoretical model of coronary flow during diastole that included capacitance. The magnitude of the discrepancy between actual intramural and instantaneously derived P/F relationships was predicted to be dependent on the ratio of two natural decay constants (central aortic decay constant/intrinsic coronary decay constant). The effects of coronary capacitance are eliminated using constant pressure conditions. The instantaneous (dynamic) and constant pressure (static) P/F relationships were compared experimentally using a reservoir to provide constant pressure perfusion during prolonged diastoles in heart blocked dogs. In the presence of coronary tone, zero flow pressure intercepts (Pzf) of 27.1 +/- 6.6 and 11.0 +/- 3.0 mm Hg were obtained under dynamic and constant pressure conditions respectively, P less than 0.001. After maximal vasodilation, Pzf of 14.2 +/- 4.5 mmHg and 10.7 +/- 2.4 mmHg were obtained under dynamic and constant pressure conditions, respectively, P = NS. Pzf derived under constant pressure conditions were independent of the state of coronary vasomotor tone with a value about 11 mmHg. The slopes of the dynamic P/F relationships tended to be greater than those derived from constant pressure conditions. This may suggest an additional component of increasing coronary resistance during diastole that could not be readily assessed under dynamic conditions. We conclude that coronary capacitive effects and resistance changes during diastole severely limit the interpretation of instantaneous dynamic P/F relationships. Diastolic coronary perfusion ceases at about 11 mm Hg and is independent of coronary tone when capacitive effects are eliminated.
Airway Basal Cells. The “Smoking Gun” of Chronic Obstructive Pulmonary Disease
Authors: Ronald G. Crystal
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Section:ChooseTop of pageAbstract <<Early Lung Abnormalities ...Normal Human Basal CellsConsequences of Smoking o...Genetic Influence on Smok...Transition from “Healthy”...Basal Cells and Lung Canc...How Does COPD Begin? The ...ReferencesCITING ARTICLES
IMMUNOPATHOLOGY OF LYMPHOCYTIC CHORIOMENINGITIS VIRUS INFECTION OF NEWBORN MICE
Authors: Martin S. Hirsch, Frederick A. Murphy, Martin D. Hicklin
Journal: The Journal of Experimental Medicine (1968)

Antithymocyte serum, when administered neonatally to mice, delayed the maturation of the lymphoid system, permitting development of cellular tolerance to LCM virus at an older age than is ordinarily possible. Humoral antibody formation was not prevented and the animals exhibited the paradox of high titers of both circulating virus and antibody. This, in turn, was followed by a chronic immunopathologic glomerulonephritis in most animals. Some animals developed wasting disease between 1 and 2 months of age, characterized by reticular cell hyperplasia and widespread infiltration into tissues and organs.
Fluorouracil, Doxorubicin, and Streptozocin in the Treatment of Patients With Locally Advanced and Metastatic Pancreatic Endocrine Carcinomas
Authors: Maria A. Kouvaraki, Jaffer A. Ajani, Paulo Hoff, Robert Wolff, Douglas B. Evans, Richard Lozano, James C. Yao
Journal: Journal of Clinical Oncology (2004)

Purpose The role of systemic chemotherapy in the management of pancreatic endocrine carcinoma (islet cell carcinoma; PEC) is an area of considerable controversy. Response rates ranging from 6% to 69% have been reported for streptozocin-based chemotherapy. We retrospectively studied 84 patients with locally advanced or metastatic PEC who had been treated with fluorouracil, doxorubicin, and streptozocin (FAS) to determine the objective response rate, duration of progression-free survival (PFS), and duration of overall survival (OS). Patients and Methods Eligible patients had histologic or cytologic confirmation of their tumor and measurable disease on computed tomography or magnetic resonance imaging scans. Response to treatment was evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors Committee. Results Sixty-one of the patients were male and 23 were female, with a median age of 54 years (range, 24 to 78 years). The response rate (RR) to FAS was 39%, with a median response duration of 9.3 months. The 2-year PFS rate was 41%, and the 2-year OS rate was 74%. The extent of liver metastatic disease correlated with a worse PFS (P = .01 by log-rank test) and a worse OS (P &lt; .0001 by log-rank test). Analyses showed that metastatic replacement of more than 75% of the liver and prior chemotherapy were independently associated with inferior PFS. Conclusion Patients with locally advanced or metastatic PEC who are treated with FAS may have a reasonable RR, and responders may experience longer PFS and OS. The volume of metastases in the liver is the most important predictor of outcome.
Personality Disorders in Later Life: Questions About the Measurement, Course, and Impact of Disorders
Authors: Thomas F. Oltmanns, Steve Balsis
Journal: Annual Review of Clinical Psychology (2011)

Lifespan perspectives have played a crucial role in shaping our understanding of many forms of psychopathology. Unfortunately, little attention has been given to personality disorders in middle adulthood and later life. Several issues are responsible for this deficiency, including difficulty applying the diagnostic criteria for personality disorders to older people and challenges in identifying appropriate samples of older participants. The goal of this review is to explore the benefits of considering older adults in the study of personality disorders. Later life offers a unique opportunity for investigators to consider links between personality pathology and consequential outcomes in people's lives. Many domains are relevant, including health, longevity, social adjustment, marital relationships, and the experience of major life events. We review each domain and consider ways in which the study of middle-aged and older adults challenges researchers to evaluate how personality disorders in general are defined and measured.
VITAMINS AND NEURAL TUBE DEFECTS
Authors: GodfreyP. Oakley, MyronJ. Adams, LevyM. James, R.W. Smithells, M.J. Seller, D.W. Fielding, N.C. Nevin, A.P. Read, R. Harris, C.J. Schorah, S. Sheppard, S. Walker, J. Wild
Journal: The Lancet (1983)
Comparison of Two-Phase Treatment With Imipramine or Fluvoxamine, Both Followed by Lithium Addition, in Inpatients With Major Depressive Disorder
Authors: Tom K Birkenhäger, Walter W van den Broek, Paul G Mulder, Jan A Bruijn, Peter Moleman
Journal: American Journal of Psychiatry (2004)

This study was designed to compare the efficacy of two two-phase pharmacological treatment strategies for inpatients with DSM-IV major depressive disorder.During phase I, patients participated in a double-blind study of the effects of imipramine versus fluvoxamine, with final evaluation of response 4 weeks after patients attained the target plasma level. In phase II, for patients without treatment response or with partial response in phase I, lithium was added to imipramine or fluvoxamine. Final evaluation of response was made 3 weeks after the patients attained the target plasma level of lithium (0.6-1.0 mmol/liter).One hundred thirty-eight patients were enrolled in the study. At the end of phase I, remission, defined as a final Hamilton Depression Rating Scale score < or =7, was achieved by 16 (23%) of 70 imipramine-treated patients and 10 (15%) of 68 fluvoxamine-treated patients. At the end of phase II, 41 (59%) of 70 imipramine-treated patients versus 27 (40%) of 68 fluvoxamine-treated patients qualified for remission, a significant difference in favor of the imipramine strategy. Only a small minority of both groups received concomitant medication. In both phase I and phase II, the discontinuation rate was low (5% and 10%, respectively).Imipramine with subsequent lithium addition is superior to a similar strategy with fluvoxamine for treatment of severely depressed inpatients. Both strategies were well tolerated.
Spectral Clustering of Microarray Data Elucidates the Roles of Microenvironment Remodeling and Immune Responses in Survival of Head and Neck Squamous Cell Carcinoma
Authors: Johanna K. Thurlow, Claudia L. Peña Murillo, Keith D. Hunter, Francesca M. Buffa, Shalini Patiar, Guy Betts, Catharine M.L. West, Adrian L. Harris, Eric K. Parkinson, Paul R. Harrison, Bradford W. Ozanne, Max Partridge, Gabriela Kalna
Journal: Journal of Clinical Oncology (2010)

To identify functionally related prognostic gene sets for head and neck squamous cell carcinoma (HNSCC) by unsupervised statistical analysis of microarray data.Microarray analysis was performed on 14 normal oral epithelium and 71 HNSCCs from patients with outcome data. Spectral clustering (SC) analysis of the data set identified multiple vectors representing distinct aspects of gene expression heterogeneity between samples. Gene ontology (GO) analysis of vector gene lists identified gene sets significantly enriched within defined biologic pathways. The prognostic significance of these was established by Cox survival analysis.The most influential SC vectors were V2 and V3. V2 separated normal from tumor samples. GO analysis of V2 gene lists identified pathways with heterogeneous expression between HNSCCs, notably focal adhesion (FA)/extracellular matrix remodeling and cytokine-cytokine receptor (CR) interactions. Similar analysis of V3 gene lists identified further heterogeneity in CR pathways. V2CR genes represent an innate immune response, whereas high expression of V3CR genes represented an adaptive immune response that was not dependent on human papillomavirus status. Survival analysis demonstrated that the FA gene set was prognostic of poor outcome, whereas classification for adaptive immune response by the CR gene set was prognostic of good outcome. A combined FA&CR model dramatically exceeded the performance of current clinical classifiers (P < .001 in our cohort and, importantly, P = .007 in an independent cohort of 60 HNSCCs).The application of SC and GO algorithms to HNSCC microarray data identified gene sets highly significant for predicting patient outcome. Further large-scale studies will establish the usefulness of these gene sets in the clinical management of HNSCC.
Transmural Dispersion of Repolarization in Failing and Nonfailing Human Ventricle
Authors: Alexey V. Glukhov, Vadim V. Fedorov, Qing Lou, Vinod K. Ravikumar, Paul W. Kalish, Richard B. Schuessler, Nader Moazami, Igor R. Efimov
Journal: Circulation Research (2010)

Rationale: Transmural dispersion of repolarization has been shown to play a role in the genesis of ventricular tachycardia and fibrillation in different animal models of heart failure (HF). Heterogeneous changes of repolarization within the midmyocardial population of ventricular cells have been considered an important contributor to the HF phenotype. However, there is limited electrophysiological data from the human heart. Objective: To study electrophysiological remodeling of transmural repolarization in the failing and nonfailing human hearts. Methods and Results: We optically mapped the action potential duration (APD) in the coronary-perfused scar-free posterior-lateral left ventricular free wall wedge preparations from failing (n=5) and nonfailing (n=5) human hearts. During slow pacing (S1S1=2000 ms), in the nonfailing hearts we observed significant transmural APD gradient: subepicardial, midmyocardial, and subendocardial APD80 were 383±21, 455±20, and 494±22 ms, respectively. In 60% of nonfailing hearts (3 of 5), we found midmyocardial islands of cells that presented a distinctly long APD (537±40 ms) and a steep local APD gradient (27±7 ms/mm) compared with the neighboring myocardium. HF resulted in prolongation of APD80: 477±22 ms, 495±29 ms, and 506±35 ms for the subepi-, mid-, and subendocardium, respectively, while reducing transmural APD80 difference from 111±13 to 29±6 ms ( P &lt;0.005) and presence of any prominent local APD gradient. In HF, immunostaining revealed a significant reduction of connexin43 expression on the subepicardium. Conclusions: We present for the first time direct experimental evidence of a transmural APD gradient in the human heart. HF results in the heterogeneous prolongation of APD, which significantly reduces the transmural and local APD gradients.
PPARδ Induces Estrogen Receptor-Positive Mammary Neoplasia through an Inflammatory and Metabolic Phenotype Linked to mTOR Activation
Authors: Hongyan Yuan, Jin Lu, Junfeng Xiao, Geeta Upadhyay, Rachel Umans, Bhaskar Kallakury, Yuhzi Yin, Michael E. Fant, Levy Kopelovich, Robert I. Glazer
Journal: Cancer Research (2013)

Abstract The peroxisome proliferator-activated receptor-δ (PPARδ) regulates a multitude of physiological processes associated with glucose and lipid metabolism, inflammation, and proliferation. One or more of these processes are potential risk factors for the ability of PPARδ agonists to promote tumorigenesis in the mammary gland. In this study, we describe a new transgenic mouse model in which activation of PPARδ in the mammary epithelium by endogenous or synthetic ligands resulted in progressive histopathologic changes that culminated in the appearance of estrogen receptor- and progesterone receptor-positive and ErbB2-negative infiltrating ductal carcinomas. Multiparous mice presented with mammary carcinomas after a latency of 12 months, and administration of the PPARδ ligand GW501516 reduced tumor latency to 5 months. Histopathologic changes occurred concurrently with an increase in an inflammatory, invasive, metabolic, and proliferative gene signature, including expression of the trophoblast gene, Plac1, beginning 1 week after GW501516 treatment, and remained elevated throughout tumorigenesis. The appearance of malignant changes correlated with a pronounced increase in phosphatidylcholine and lysophosphatidic acid metabolites, which coincided with activation of Akt and mTOR signaling that were attenuated by treatment with the mTOR inhibitor everolimus. Our findings are the first to show a direct role of PPARδ in the pathogenesis of mammary tumorigenesis, and suggest a rationale for therapeutic approaches to prevent and treat this disease. Cancer Res; 73(14); 4349–61. ©2013 AACR.
The Chymase, Mouse Mast Cell Protease 4, Constitutes the Major Chymotrypsin-like Activity in Peritoneum and Ear Tissue. A Role for Mouse Mast Cell Protease 4 in Thrombin Regulation and Fibronectin Turnover
Authors: Elena Tchougounova, Gunnar Pejler, Magnus Åbrink
Journal: The Journal of Experimental Medicine (2003)

To gain insight into the biological role of mast cell chymase we have generated a mouse strain with a targeted deletion in the gene for mast cell protease 4 (mMCP-4), the mouse chymase that has the closest relationship to the human chymase in terms of tissue localization and functional properties. The inactivation of mMCP-4 did not affect the storage of other mast cell proteases and did not affect the number of mast cells or the mast cell morphology. However, mMCP-4 inactivation resulted in complete loss of chymotryptic activity in the peritoneum and in ear tissue, indicating that mMCP-4 is the main source of stored chymotrypsin-like protease activity at these sites. The mMCP-4 null cells showed markedly impaired ability to perform inactivating cleavages of thrombin, indicating a role for mMCP-4 in regulating the extravascular coagulation system. Further, a role for mMCP-4 in connective tissue remodeling was suggested by the inability of mMCP-4 null peritoneal cells to process endogenous fibronectin.
Prognostic Value of Bronchiolitis Obliterans Syndrome Stage 0-p in Single-Lung Transplant Recipients
Authors: Vibha N. Lama, Susan Murray, Jeanette A. Mumford, Kevin R. Flaherty, Andrew Chang, Galen B. Toews, Marc Peters-Golden, Fernando J. Martinez
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: Early diagnosis of bronchiolitis obliterans syndrome (BOS) is critical in understanding pathogenesis and devising therapeutic trials. Although potential-BOS stage (BOS 0-p), encompassing early changes in FEV1 and forced expiratory flow, midexpiratory phase (FEF25–75%), has been proposed, there is a paucity of data validating its utility in single-lung transplantation. Objective: The aim of this study was to define the predictive ability of BOS 0-p in single-lung transplantation. Methods: We retrospectively analyzed spirometric data for 197 single-lung recipients. Sensitivity, specificity, and positive predictive value of BOS 0-p were examined over time using Kaplan-Meier methodology. Results: BOS 0-p FEV1 was associated with higher sensitivity, specificity, and positive predictive value than the FEF25–75% criterion over different time periods investigated. The probability of testing positive for BOS 0-p FEV1 in patients with BOS (sensitivity) was 71% at 2 years before the onset of BOS. The probability of being free from development of BOS 0-p FEV1 in patients free of BOS at follow-up (specificity) was 93% within the last year. Of patients who met the BOS 0-p FEV1 criterion, 81% developed BOS or died within 3 years. The specificity and positive predictive value curves for the BOS 0-p FEV1 were significantly different between patients with underlying restrictive versus obstructive physiology (p = 0.05 and 0.01, respectively). Conclusion: The FEV1 criterion for BOS 0-p provides useful predictive information regarding the risk of development of BOS or death in single-lung recipients. The predictive value of this criterion is higher in patients with underlying restriction and is superior to the FEF25–75% criterion.