tbuckley/cabot-search huggingface dataset:
Impact of Graft Mass on the Clinical Outcome of Kidney Transplants
Authors: Magali Giral, Jean Michel Nguyen, Georges Karam, Michelle Kessler, Bruno Hurault de Ligny, Mattias Buchler, Franc[COMBINING CEDILLA]ois Bayle, Carole Meyer, Yohann Foucher, Marie Laure Martin, Pascal Daguin, Jean Paul Soulillou
Journal: Journal of the American Society of Nephrology (2004)

The effect of nephronic mass reduction of kidney transplants has not been analyzed specifically in a large cohort. Transplant injuries in cadaver kidney graft may have led to an underestimation of the magnitude of this factor. The aim of this study was to analyze the consequences of kidney mass reduction on transplantation outcome. The weights of 1142 kidney grafts were collected prospectively immediately before grafting. Donors and recipients <15 yr of age, simultaneous kidney/pancreas grafts, and technical failures before day 7 were excluded from the analysis. The analysis was performed on Cockroft-calculated creatinine clearance and proteinuria in 964 patients for whom all of the necessary information was available. This study reports that the smallest kidneys transplanted into the largest recipients (donor kidney weight/recipient body weight [DKW/RBW] <2 g/kg, n = 88) increased their clearance by 2.38 ml/min every month for 6 mo (P < 0.0001) and by 0.27 ml/min thereafter (P < 0.0001). Conversely, creatinine clearance did not change for the largest kidneys transplanted into the smallest recipients (DKW/RBW ratios >/=4 g/kg). Next, using a Cox model analysis, it was shown that the risk of having a proteinuria >0.5 g/kg was significantly increased for the low DKW/RBW ratios <2 g/kg with 50% of patients having a proteinuria, compared with DKW/RBW ratios >/=4 g/kg (P < 0.001). In cadaver transplant recipients, graft mass has a rapid impact on graft filtration rate and proteinuria. Avoiding major kidney/recipient inadequacy should have a significant influence on long-term transplant function.
Lyn Kinase Controls Basophil GATA-3 Transcription Factor Expression and Induction of Th2 Cell Differentiation
Authors: Nicolas Charles, Wendy T. Watford, Haydeé L. Ramos, Lars Hellman, Hans C. Oettgen, Gregorio Gomez, John J. Ryan, John J. O'Shea, Juan Rivera
Journal: Immunity (2009)
Membrane-Associated Matrix Proteolysis and Heart Failure
Authors: Francis G. Spinale, Joseph S. Janicki, Michael R. Zile
Journal: Circulation Research (2013)

The extracellular matrix (ECM) is a complex entity containing a large portfolio of structural proteins, signaling molecules, and proteases. Changes in the overall integrity and activational state of these ECM constituents can contribute to tissue structure and function, which is certainly true of the myocardium. Changes in the expression patterns and activational states of a family of ECM proteolytic enzymes, the matrix metalloproteinases (MMPs), have been identified in all forms of left ventricle remodeling and can be a contributory factor in the progression to heart failure. However, new clinical and basic research has identified some surprising and unpredicted changes in MMP profiles in left ventricle remodeling processes, such as with pressure or volume overload, as well as with myocardial infarction. From these studies, it has become recognized that proteolytic processing of signaling molecules by certain MMP types, particularly the transmembrane MMPs, actually may facilitate ECM accumulation and modulate fibroblast transdifferentiation; both are critical events in adverse left ventricle remodeling. Based on the ever-increasing substrates and diversity of biological actions of MMPs, it is likely that continued research about the relationship of left ventricle remodeling in this family of proteases will yield new insights into the ECM remodeling process and new therapeutic targets.
Chromosome Translocation, B Cell Lymphoma, and Activation-Induced Cytidine Deaminase
Authors: Davide F. Robbiani, Michel C. Nussenzweig
Journal: Annual Review of Pathology Mechanisms of Disease (2012)

Studies of B cell lymphomas in the early 1980s led to the cloning of genes (c-MYC and IGH) at a chromosome translocation breakpoint. A rush followed to identify recurrently translocated genes in all types of cancer, which led to remarkable advances in our understanding of cancer genetics. B lymphocyte tumors commonly bear chromosome translocations to immunoglobulin genes, which points to a role for antibody gene diversification processes in tumorigenesis. The discovery of activation-induced cytidine deaminase (AID) and the use of murine models to study translocation have led to a new understanding of how these events contribute to the genesis of lymphomas. Here, we review these advances with a focus on AID and insights gained from the study of translocations in primary cells.
OUTBREAK OF CENTRAL-NERVOUS-SYSTEM TOXOPLASMOSIS IN WESTERN EUROPE AND NORTH AMERICA
Authors: BenjaminJ. Luft, Frances Conley, JackS. Remington, Michel Laverdiere, JeromeF. Levine, DonaldA. Strandberg, KennethF. Wagner, PhillipC. Craven, ThomasM. File, Nancy Rice, Françoise Meunier-Carpentier
Journal: The Lancet (1983)
Evaluation of two techniques for measurement of respiratory resistance by forced oscillation: A study in young subjects with obstructive lung disease
Authors: L. I. Landau, P. D. Phelan
Journal: Thorax (1973)

The measurement of respiratory resistance by forced oscillation requires minimal patient co-operation and should be a useful test in children. Sixty-eight children and adolescents with obstructive lung disease were studied using two different techniques. In patients with severe obstructive lung disease, unexpectedly low values for respiratory resistance were found when the measurement was made at points of peak flow (write-out method). Measurements made at simulated resonant frequency (subtraction method) in these patients were more in keeping with other tests of respiratory function; however, they probably did not reflect true respiratory resistance. The subtraction method of measuring respiratory resistance would seem to be of value in separating the normal from the abnormal, but the absolute values in obstructed subjects are difficult to interpret.
Assessment and follow up of patients prescribed long term oxygen treatment.
Authors: L J Restrick, E A Paul, G M Braid, P Cullinan, J Moore-Gillon, J A Wedzicha
Journal: Thorax (1993)

Prescription and use of long term oxygen treatment were audited in a large group of patients after more than five years of use of the guidelines for its prescription.Patients with a concentrator were interviewed at home with a structured questionnaire in three family health service authorities in East London. Stable oxygen saturation (SaO2) breathing air and oxygen, forced expiratory volume in one second (FEV1) and current and previous dated concentrator meter readings were recorded. A further questionnaire was sent to each patient's general practitioner. Hospital case notes of patients who did not meet the criteria for long term oxygen treatment at reassessment were reviewed.A total of 176 patients were studied; 84% had chronic obstructive lung disease and 19% admitted to continued smoking; 140 patients had seen a respiratory physician but results of respiratory assessment were available to their general practitioner in fewer than 54 cases. FEV1 was < 1.5 1 in 158 patients but in 67 SaO2 was less than 91% breathing air, mainly in patients with chronic obstructive lung disease who had been inadequately assessed. Daily oxygen was prescribed for a median of 15 (range 4-24) hours and measured daily use was 15 (0-24) hours; 74% of patients used more than 12 hours. Only 35 patients had problems with oxygen treatment, but 29 had an undercorrected SaO2 of less than 92% when using their concentrator.Guidelines for prescription of long term oxygen treatment are largely followed and most patients complied with treatment. Increased communication about respiratory state is required between hospital doctors and general practitioners. Patients need regular reassessments to ensure that hypoxaemia is corrected and that oxygen is appropriately prescribed.
Company Stock Prices Before and After Public Announcements Related to Oncology Drugs
Authors: Jeffrey M. Rothenstein, George Tomlinson, Ian F. Tannock, Allan S. Detsky
Journal: JNCI Journal of the National Cancer Institute (2011)

Phase III clinical trials and Food and Drug Administration (FDA) regulatory decisions are critical for success of new drugs and can influence a company's market valuation. Knowledge of trial results before they are made public (ie, "inside information") can affect the price of a drug company's stock. We examined the stock prices of companies before and after public announcements regarding experimental anticancer drugs owned by the companies. We identified drugs that were undergoing evaluation in phase III trials or for regulatory approval by the US FDA from January 2000 to January 2009. Stock prices of companies that owned such drugs were analyzed for 120 trading days before and after the first public announcement of 1) results of clinical trials with positive and negative outcomes and 2) positive and negative regulatory decisions. All statistical tests were two-sided. We identified public announcements from 23 positive trials and 36 negative trials and from 41 positive and nine negative FDA regulatory decisions. The mean stock price for the 120 trading days before a phase III clinical trial announcement increased by 13.7% (95% confidence interval = −2.2% to 29.6%) for companies that reported positive trials and decreased by 0.7% (95% confidence interval = −13.8% to 12.3%) for companies that reported negative trials (P = .09). In a post hoc analysis comparing the stock price averaged over 60 trading days before and after day −60 relative to the clinical trial announcement, the mean stock price increased by 9.4% for companies that reported positive trials and decreased by 4.5% for companies that reported negative trials (P = .03). Changes in company stock prices before FDA regulatory decisions did not differ statistically between companies with positive decision and companies with negative decisions. Trends in company stock prices before the first public announcement differ for companies that report positive vs negative trials. This finding has important legal and ethical implications for investigators, drug companies, and the investment industry.
Long-Term Clinical Consequences of Intense, Uninterrupted Endurance Training in Olympic Athletes
Authors: Antonio Pelliccia, Norimitsu Kinoshita, Cataldo Pisicchio, Filippo Quattrini, Fernando M. DiPaolo, Roberto Ciardo, Barbara Di Giacinto, Emanuele Guerra, Elvira De Blasiis, Maurizio Casasco, Franco Culasso, Barry J. Maron
Journal: Journal of the American College of Cardiology (2010)
Effectiveness and safety of leflunomide for pulmonary and extrapulmonary sarcoidosis
Authors: D.H. Sahoo, D. Bandyopadhyay, M. Xu, K. Pearson, J.G. Parambil, C.A. Lazar, J.T. Chapman, D.A. Culver
Journal: European Respiratory Journal (2011)

Leflunomide has been reported as an alternative therapy in sarcoidosis. However, the published data are limited. We performed a retrospective chart review of the tolerance and effects of leflunomide therapy in patients with sarcoidosis. 76 patients were included. The most common reasons for initiation were progression of disease or failure of other immunomodulator therapy. Side-effects attributable to leflunomide were noted in 34% of subjects, prompting discontinuation in 17%. The lungs were a target of therapy in 33 (44%) and extrapulmonary organs were a target in 45 (59%). The mean ± sd change in forced vital capacity in the 6 months prior to leflunomide was -0.1 ± 0.3 L, and it was +0.09 ± 0.3 L in the following 6 months (p=0.01). For extrapulmonary target organ response, 51% had a good response and 32% a partial response. The median corticosteroid dose at initiation was 10 mg (interquartile range 5-20) mg at baseline, and 0 (0-10) mg at the 6-month follow-up (p<0.001). Leflunomide is a viable alternative agent for pulmonary and extrapulmonary sarcoidosis. Leflunomide appears to facilitate reduction of steroid dose and can be considered as monotherapy or as add-on therapy in cases of progressive disease.
A COMPREHENSIVE HOSPITAL-COMMUNITY SERVICE IN A STATE HOSPITAL
Authors: ROBERT C. HUNT, ERNEST M. GRUENBERG, EMANUEL HACKEN, MATTHEW HUXLEY
Journal: American Journal of Psychiatry (1961)

A newly organized, 550 bed hospital, rendering comprehensive, psychiatric care (day hospital, night hospital, post-hospital, pre-hospital and consultation) to residents of Dutchess County, N. Y., has been created within the 5,400 bed Hudson River State Hospital. This is designed to give continuity through close integration of a wide variety of treatment services. Early experiences with the project are reported. Evaluation studies are testing the hypothesis that this type of service will reduce the frequency and severity of disability associated with mental illness, as measured by rates of admission, institutionalization, and deterioration.
Acute hypoxia and endogenous renal endothelin.
Authors: A Nir, A L Clavell, D Heublein, L L Aarhus, J C Burnett
Journal: Journal of the American Society of Nephrology (1994)

Endothelin (ET) is a potent vasoconstrictor peptide of endothelial cell origin. Recent studies have suggested a nonvascular paracrine and/or autocrine role for endothelin in the kidney. This study was designed to elucidate the renal ET response to acute moderate hypoxia, as reflected by urinary ET excretory rate and renal tissue ET immunoreactivity, and to correlate these responses to the hemodynamic and excretory changes during hypoxia. Experiments were conducted in two groups of anesthetized dogs: hypoxic group (10% O2 ventilation: PO2, 44 mm Hg; N = 7) and time control group (room air ventilation: PO2, 111 mm Hg; N = 6). After 60 min of hypoxia or room air ventilation, kidneys were harvested and stained immunohistochemically for ET. Acute moderate hypoxia was associated with significant increases in urinary ET excretion, urine flow, urinary sodium excretion, and fractional excretion of sodium (P < 0.05). There was no significant change in GFR, RBF, renal vascular resistance, or mean arterial pressure. Renal immunohistochemistry for ET revealed increased staining in the proximal and distal tubules in the hypoxic group as compared with controls. This study demonstrates that acute moderate hypoxia results in increased urinary ET excretion and renal tubular ET immunoreactivity, in association with diuresis and natriuresis, and suggests a nonvascular role of endogenously produced renal ET in the regulation of sodium homeostasis during hypoxia.
Exercise testing confirms the role of impaired central circulatory function and elevated right ventricular stroke work index in patients undergoing lung transplantation
Authors: Matthew Bartels, Hilary Armstrong, Tomoko Kato, Matthew Bacchetta, Christian Schulze
Journal: European Respiratory Journal (2012)

Introduction: Right ventricular (RV) workload assessed by RV Stroke Work Index (RVSWI) is a negative predictor of outcome in acute respiratory failure. Cardiopulmonary exercise testing (CPET) may have a role in detecting central circulatory impairment (CCI) in patients before lung transplantation (LTx) at risk for impaired RV function.  Aims and Objectives: To demonstrate correlation of ventilatory inefficiency (VI) on CPET for detection of CCI in patients before LTx with RVSWI.  Methods: 172 patients undergoing evaluation for LTx who had CPET and right heart catheterization were included. RVSWI (stroke volume index*(mean pulmonary arterial pressure - mean right atrial pressure)*0.0136) was calculated from invasive hemodynamic data. Pearson9s correlation, significance 0.05, was assessed between RVSWI and CPET parameters.  Results: RVSWI correlates highly with VI and inversely with hemodynamics on CPET, but not with peak capacity or workload.  Conclusions: High right ventricular workload correlates with ventilatory inefficiency and impaired hemodynamics on CPET. Thus, exercise parameters may predict right ventricular work and LTx outcomes.
Enhanced glycemic responsiveness to epinephrine in insulin-dependent diabetes mellitus is the result of the inability to secrete insulin. Augmented insulin secretion normally limits the glycemic, but not the lipolytic or ketogenic, response to epinephrine in humans.
Authors: M A Berk, W E Clutter, D Skor, S D Shah, R P Gingerich, C A Parvin, P E Cryer
Journal: Journal of Clinical Investigation (1985)

To determine if the enhanced glycemic response to epinephrine in patients with insulin-dependent diabetes mellitus (IDDM) is the result of increased adrenergic sensitivity per se, increased glucagon secretion, decreased insulin secretion, or a combination of these, plasma epinephrine concentration-response curves were determined in insulin-infused (initially euglycemic) patients with IDDM and nondiabetic subjects on two occasions: once when insulin and glucagon were free to change (control study), and again when insulin and glucagon were held constant (islet clamp study). During the control study, plasma C-peptide doubled, and glucagon did not change in the nondiabetic subjects, whereas plasma C-peptide did not change but glucagon increased in the patients. The patients with IDDM exhibited threefold greater increments in plasma glucose, largely the result of greater increments in glucose production. This enhanced glycemic response was apparent with 30-min increments in epinephrine to plasma concentrations as low as 100-200 pg/ml, levels that occur commonly under physiologic conditions. During the islet clamp study (somatostatin infusion with insulin and glucagon replacement at fixed rates), the heightened glycemic response was unaltered in the patients with IDDM, but the nondiabetic subjects exhibited an enhanced glycemic response to epinephrine indistinguishable from that of patients with IDDM. In contrast, the FFA, glycerol, and beta-hydroxybutyrate responses were unaltered. Thus, we conclude the following: Short, physiologic increments in plasma epinephrine cause greater increments in plasma glucose in patients with IDDM than in nondiabetic subjects, a finding likely to be relevant to glycemic control during the daily lives of such patients as well as during the stress of intercurrent illness. Enhanced glycemic responsiveness of patients with IDDM to epinephrine is not the result of increased sensitivity of adrenergic receptor-effector mechanisms per se nor of their increased glucagon secretory response; rather, it is the result of their inability to augment insulin secretion. Augmented insulin secretion, albeit restrained, normally limits the glycemic response, but not the lipolytic or ketogenic responses, to epinephrine in humans.
Thiazide-induced subtle renal injury not observed in states of equivalent hypokalemia
Authors: S. Reungjui, H. Hu, W. Mu, C.A. Roncal, B.P. Croker, J.M. Patel, T. Nakagawa, T. Srinivas, K. Byer, J. Simoni, D. Wesson, V. Sitprija, R.J. Johnson
Journal: Kidney International (2007)
Distinct Transcription Profiles of Primary and Secondary Glioblastoma Subgroups
Authors: Cho-Lea Tso, William A. Freije, Allen Day, Zugen Chen, Barry Merriman, Ally Perlina, Yohan Lee, Ederlyn Q. Dia, Koji Yoshimoto, Paul S. Mischel, Linda M. Liau, Timothy F. Cloughesy, Stanley F. Nelson
Journal: Cancer Research (2006)

Abstract Glioblastomas are invasive and aggressive tumors of the brain, generally considered to arise from glial cells. A subset of these cancers develops from lower-grade gliomas and can thus be clinically classified as “secondary,” whereas some glioblastomas occur with no prior evidence of a lower-grade tumor and can be clinically classified as “primary.” Substantial genetic differences between these groups of glioblastomas have been identified previously. We used large-scale expression analyses to identify glioblastoma-associated genes (GAG) that are associated with a more malignant phenotype via comparison with lower-grade astrocytomas. We have further defined gene expression differences that distinguish primary and secondary glioblastomas. GAGs distinct to primary or secondary tumors provided information on the heterogeneous properties and apparently distinct oncogenic mechanisms of these tumors. Secondary GAGs primarily include mitotic cell cycle components, suggesting the loss of function in prominent cell cycle regulators, whereas primary GAGs highlight genes typical of a stromal response, suggesting the importance of extracellular signaling. Immunohistochemical staining of glioblastoma tissue arrays confirmed expression differences. These data highlight that the development of gene pathway-targeted therapies may need to be specifically tailored to each subtype of glioblastoma. (Cancer Res 2006; 66(1): 159-67)
Research on in vitro release kinetics of isoniazid (IZN) and omeprazole from oral tablets
Authors: Magda Costin, Bogdan Cioroiu, Elena Butnaru
Journal: European Respiratory Journal (2011)

Introduction:  The study aimed to follow the in vitro release kinetics of IZN and omeprazole, the influence of applied methods and release evaluation when associated with other antituberculous drugs.   Materials and method:  As reasearch method on the in vitro release of IZN and omeprazole it has been used the method of resistance in acid enviroment and dissolution method in neutral media. In order to evaluate the resistance in acidic conditions, 6 samples were taken in the time interval 5–110 minutes, while for dissolution in neutral media evaluation 11 samples were collected in the time interval from 10 to 320 minutes.   Results:  Solubilization in acidic media: For IZN it was found a release degree of 85.9% at 5 minute and of 88.7% at 110 minutes. When associated with omeprazole, the maximum release degree it was identified at 30 minutes of 95.1%; when associated with other antituberculous drugs, the maximum release degree was found at 15 minutes of 99.6%. We found a very loz release degree for omeprazole; the first concentrations being detected after 75 minutes and after 110 minutes we found a releae degree of only 8.1%. Solubilization in neutral conditions: the lack of any IZN traces reveals that complete dissolution took place in acidic media, while for omeprazole it was found a 5.8% release degree at 10 minutes and of 40.2% after 320 minutes.   Conclusions:  IZN shows a sensitive release pattern in the presence of antotuberculous drugs and a slightly sensitive release pattern in the presence of omeprazole. Instead, omeprazole shows a very low release pattern when associated with IZN or other anituberculous drugs, which could cause modifications of the plasma concentrations.
Pitolisant versus placebo or modafinil in patients with narcolepsy: a double-blind, randomised trial
Authors: Yves Dauvilliers, Claudio Bassetti, Gert Jan Lammers, Isabelle Arnulf, Geert Mayer, Andrea Rodenbeck, Philippe Lehert, Claire-Li Ding, Jeanne-Marie Lecomte, Jean-Charles Schwartz
Journal: The Lancet Neurology (2013)