tbuckley/cabot-search huggingface dataset:
Low-Dose Vasopressin in the Treatment of Septic Shock in Sheep
Authors: Qinghua Sun, George Dimopoulos, Duc Nam Nguyen, Zizhi Tu, Nathalie Nagy, Anh Dung Hoang, Peter Rogiers, Daniel De Backer, Jean-Louis Vincent
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

After induction of cecal perforation, 20 anesthetized sheep were randomized to be treated, when arterial blood pressure fell below 75 mm Hg, with vasopressin (fixed dose of 0.02 U/minute), norepinephrine (0.5–5 μg/kg/minute titrated to maintain mean arterial pressure between 75 and 85 mm Hg), vasopressin + norepinephrine (vasopressin at fixed dose 0.01 U/minute plus norepinephrine titrated as for norepinephrine only group), or no vasopressor (Ringer's lactate [control]). Mean arterial pressure was well maintained in all treatment groups. Superior mesenteric arterial blood flow was significantly lower in the vasopressin + norepinephrine group than in the vasopressin group. Vasopressin alone or combined with norepinephrine limited the increase in blood lactate concentration and ileal PCO2-gap compared with control and norepinephrine groups. Urine output was higher in the vasopressin group than in control and norepinephrine groups. Survival time was longer in the vasopressin (30 ± 6 hours) and vasopressin + norepinephrine (30 ± 3 hours) groups than in the norepinephrine group (20 ± 1 hours, p < 0.05) and in all treatment groups than in the control group (17 ± 2 hours, p < 0.05). Tissue injury was less severe in the vasopressin and vasopressin + norepinephrine groups than in the others. In this clinically relevant model of septic shock due to peritonitis, vasopressin administration (alone or with norepinephrine) can prolong survival.
Senescence and Death of Primitive Cells and Myocytes Lead to Premature Cardiac Aging and Heart Failure
Authors: Cristina Chimenti, Jan Kajstura, Daniele Torella, Konrad Urbanek, Hubert Heleniak, Claudia Colussi, Franca Di Meglio, Bernardo Nadal-Ginard, Andrea Frustaci, Annarosa Leri, Attilio Maseri, Piero Anversa
Journal: Circulation Research (2003)

Chronological myocardial aging is viewed as the inevitable effect of time on the functional reserve of the heart. Cardiac failure in elderly patients is commonly interpreted as an idiopathic or secondary myopathy superimposed on the old heart independently from the aging process. Thus, aged diseased hearts were studied to determine whether cell regeneration was disproportionate to the accumulation of old dying cells, leading to cardiac decompensation. Endomyocardial biopsies from 19 old patients with a dilated myopathy were compared with specimens from 7 individuals of similar age and normal ventricular function. Ten patients with idiopathic dilated cardiomyopathy were also analyzed to detect differences with aged diseased hearts. Senescent cells were identified by the expression of the cell cycle inhibitor p16 INK4a and cell death by hairpin 1 and 2. Replication of primitive cells and myocytes was assessed by MCM5 labeling, myocyte mitotic index, and telomerase function. Aged diseased hearts had moderate hypertrophy and dilation, accumulation of p16 INK4a positive primitive cells and myocytes, and no structural damage. Cell death markedly increased and occurred only in cells expressing p16 INK4a that had significant telomeric shortening. Cell multiplication, mitotic index and telomerase increased but did not compensate for cell death or prevented telomeric shortening. Idiopathic dilated cardiomyopathy had severe hypertrophy and dilation, tissue injury, and minimal level of p16 INK4a labeling. In conclusion, telomere erosion, cellular senescence, and death characterize aged diseased hearts and the development of cardiac failure in humans.
Kidney-specific alloantigen system in the rat. Characterization and role in transplantation.
Authors: D N Hart, J W Fabre
Journal: The Journal of Experimental Medicine (1980)

The alloantibody response of LEW rats immunized with DA kidney homogenate or given vascularized DA kidney grafts was studied using an 125I-anti-Ig binding assay with kidney homogenate as the target tissue. A major component of the sera was found to be directed at a kidney-specific alloantigen. Analysis of LEW X (DA X LEW) F1 backcross rats showed that the locus coding for this antigen was not linked to the major histocompatibility complex (MHC). The use of these backcross rats, typed for both MHC and the kidney alloantigen, as kidney donors to LEW rats showed that the kidney alloantigen did not induce detectable graft damage and that only the DA MHC was involved in primary graft rejection of DA kidneys by LEW rats. Immunofluorescence studies localized the antigen to the basement membrane of proximal convoluted tubules, and to some Bowman's capsules. Strain distribution studies showed that only 2 of 11 strains were negative for the allele under study; these were the LEW and AS strains. Species cross-reactivity studies showed that rabbit, dog, and human kidneys could absorb this specificity, although more weakly than DA kidney.
p27 and Skp2 immunoreactivity and its clinical significance with endocrine and chemo-endocrine treatments in node-negative early breast cancer
Authors: A. Ravaioli, F. Monti, M.M. Regan, F. Maffini, M.G. Mastropasqua, V. Spataro, M. Castiglione-Gertsch, I. Panzini, L. Gianni, A. Goldhirsch, A. Coates, K.N. Price, B.A. Gusterson, G. Viale
Journal: Annals of Oncology (2008)
Adverse events in analgesic treatment with tramadol associated with CYP2D6 extensive-metaboliser and OPRM1 high-expression variants
Authors: E. Kim, C.-B. Choi, C. Kang, S.-C. Bae
Journal: Annals of the Rheumatic Diseases (2010)

Tramadol, alone or in combination with paracetamol, is an effective analgesic that relieves the moderate to severe pain that accompanies various disorders (including osteoarthritis) and follows surgical operations. However, this synthetic atypical opioid frequently evokes various adverse events (AEs), and the most frequent are nausea and vomiting.1 Although the mode of tramadol-induced nausea/vomiting is unclear, opioid receptors on the chemoreceptor trigger zone in the human brain can bind opioids to cause nausea/vomiting.2 A major pathway of tramadol metabolism is demethylation to O -desmethyltramadol by cytochrome P450 enzyme 2D6 (CYP2D6),3 and O -desmethyltramadol has an orders of magnitude higher affinity for the μ-opioid receptor (OPRM1) than tramadol and other metabolites.4

Because many genetic variations in CYP2D6 confer large interindividual differences in enzyme activity,5 and several variations in OPRM1 substantially affect expression level,6 this study examined genotype–phenotype associations between functional polymorphisms in CYP2D6 …
Disproportionate elevation of N-terminal pro-brain natriuretic peptide in scleroderma-related pulmonary hypertension
Authors: S. C. Mathai, M. Bueso, L. K. Hummers, D. Boyce, N. Lechtzin, J. Le Pavec, A. Campo, H. C. Champion, T. Housten, P. R. Forfia, A. L. Zaiman, F. M. Wigley, R. E. Girgis, P. M. Hassoun
Journal: European Respiratory Journal (2009)

N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of neurohormonal activation that is useful in the diagnosis and prognosis of various forms of pulmonary arterial hypertension (PAH). We sought to characterise and compare NT-proBNP in a cohort of PAH related to systemic sclerosis (PAH-SSc) and idiopathic PAH (IPAH) patients. NT-proBNP levels, collected from PAH-SSc and IPAH patients followed prospectively, were compared and correlated with haemodynamic variables. Cox proportional hazard models were created to assess the predictive value of NT-proBNP. 98 patients (55 PAH-SSc, 43 IPAH) were included. Haemodynamics were similar, except for lower mean pulmonary arterial pressure in PAH-SSc. NT-proBNP levels were significantly higher in PAH-SSc (3,419±3,784 <i>versus</i> 1,393±1,633 pg·mL<sup>−1</sup>; p&lt;0.01) and were more closely related to haemodynamics in PAH-SSc than IPAH. 28 patients died. NT-proBNP predicted survival (hazard ratio (HR) 3.18; p&lt;0.01) in the overall cohort; however, when stratified by group, predicted survival only in PAH-SSc (HR 3.07, p&lt;0.01 <i>versus</i> 2.02, p = 0.29 in IPAH). This is the first description showing NT-proBNP levels are 1) significantly higher in PAH-SSc than IPAH despite less severe haemodynamic perturbations, and 2) stronger predictors of survival in PAH-SSc, suggesting that neurohormonal regulation may differ between PAH-SSc and IPAH. Future studies to define pertinent mechanisms are warranted.
Peripheral T-cell lymphomas: Initial features, natural history, and prognostic factors in a series of 174 patients diagnosed according to the R.E.A.L. Classification
Authors: A. López-Guillermo, J. Cid, A. Salar, A. López, C. Montalbán, J.M. Castrillo, M. González, J.M. Ribera, S. Brunet, J. García-Conde, A. Fernández de Sevilla, F. Bosch, E. Montserrat
Journal: Annals of Oncology (1998)
Can resistance training change the strength, body composition and self-concept of overweight and obese adolescent males? A randomised controlled trial
Authors: Natasha Schranz, Grant Tomkinson, Natalie Parletta, John Petkov, Tim Olds
Journal: British Journal of Sports Medicine (2013)

Resistance training is an exercise modality at which overweight and obese adolescents can excel and which can therefore positively affect their psychological well-being. The aim of this study was to determine the effect of a 6-month resistance training intervention on the self-concept strength and body composition of overweight and obese adolescent males.56 overweight and obese males aged 13-17 years were randomly allocated to an Intervention (n=30) or Control (n=26) group. Primary (psychological) and secondary (strength and body composition) outcomes were assessed at baseline as well as at 3 (halfway through the intervention), 6 (immediately postintervention) and 12 months follow-up. Random effects mixed modelling was used to determine the effects of the intervention.Statistically significant differences between the Intervention and Control groups were observed at 3-month and 6-month assessments for exercise self-efficacy, resistance training confidence and self-esteem. Large increases in strength for the Intervention group, relative to Controls, were also observed with no substantial changes in body composition shown for either group. Values for all variables returned to baseline following completion of the programme.A 6-month resistance training intervention can positively affect the self-concept and strength of overweight and obese adolescent boys.
Marcel Proust (1871-1922): reassessment of his asthma and other maladies
Authors: O.P. Sharma
Journal: European Respiratory Journal (2000)

Marcel Proust endured severe allergies and bronchial asthma from early childhood. Those who suffer from the frightening and recurrent pangs of asthma often become dependent on their parents particularly mother; Proust was no exception. In his time asthma was poorly understood by physicians who considered the illness to be a type of hysteria. Decades later, we now understand that the severe, poorly controlled, suffocating episodes of asthma were responsible for the complex persona that Marcel Proust had assumed.
The unfolded von Willebrand factor response in bloodstream: the self-association perspective
Authors: Hailong Yuan, Ning Deng, Songmei Zhang, Yange Cao, Qiong Wang, Xin Liu, Qing Zhang
Journal: Journal of Hematology & Oncology (2012)

Abstract von Willebrand factor (vWF) is a multimeric glycoprotein essential for hemostasis after vascular injury, which modulates platelet-surface and platelet–platelet interactions by linking platelet receptors to the extracellular matrix and to each other. The crucial role of vWF in platelet function is particularly apparent when hemodynamic conditions create blood flow with high shear stress. Through multiple functional domains, vWF mediates the attachment of platelets to exposed tissues, where immobilized vWF is able to support a homotypic and/or heterotypic self-association. The self-association of vWF is also supported by a rapidly expanding reservoir of novel evidences that the thiol/disulfide exchange regulates vWF multimer size in the blood circulation. Moreover, in addition to proteolysis and reduction of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), the regulation of vWF multimer size and self-association may depend on a disulfide bond reductase activity ascribed to thrombospondin-1 (TSP-1). Along with the classical signaling pathways in activated platelets, evidence is emerging that lipid rafts also play important roles in various phases of hemostasis and thrombosis and facilitate the interaction between the key signaling molecules. Developments in these areas will refine our understanding of the role played by vWF self-association in physiological hemostasis and pathological thrombosis.
Nosocomial Legionnaires' Disease Uncovered in a Prospective Pneumonia Study
Authors: Robert R. Muder
Journal: JAMA (1983)

Most hospitals have yet to record a case of nosocomial legionnaires' disease; the importance of isolation of<i>Legionella pneumophila</i>in the water system of such an institution is unclear. We undertook a prospective pneumonia study in tandem at a veterans hospital where legionnaires' disease was known to be endemic and a community teaching hospital where legionnaires' disease had never been documented.<i>Legionella</i>serological tests were performed on all patients with pneumonia; selective culture media and direct fluorescent antibody testing for<i>Legionella</i>were made readily available. Simultaneous environmental surveys for Legionella were performed. At the community hospital, we discovered that 64% of sites in the water distribution system yielded<i>L pneumophila</i>and that 14.3% of nosocomial pneumonias were legionnaires' disease. The epidemiologic implications of these findings are discussed. Options concerning case detection and eradication measures in the face of hospital water contamination with<i>L pneumophila</i>are presented. (<i>JAMA</i>1983;249:3184-3188)
Health Insurance Coverage in Survivors of Childhood Cancer: The Childhood Cancer Survivor Study
Authors: Elyse R. Park, Frederick P. Li, Yan Liu, Karen M. Emmons, Arthur Ablin, Leslie L. Robison, Ann C. Mertens
Journal: Journal of Clinical Oncology (2005)

To examine the prevalence and predictors of health insurance coverage and the difficulties obtaining coverage in a large cohort of childhood cancer survivors.This study included 12,358 5-year survivors of childhood cancer and 3,553 sibling controls participating in the Childhood Cancer Survivor Study. Data were collected by surveys distributed in 1994 (baseline) and 2000 (follow-up).At baseline, 83.9% of adult survivors, compared with 88.3% of siblings, had health insurance coverage (P < .01); 6 years later, small but significant survivor-sibling differences remained (88% v 91%; P < .01). Twenty-nine percent of survivors reported having had difficulties obtaining coverage, compared with only 3% of siblings (P < .01). In multivariate analysis of survivors 18 years of age or older, factors associated with being uninsured included younger age at diagnosis (diagnosis age of 0 to 4 years; odds ratio [OR] = 1.7; 95% CI, 1.3 to 2.2), male sex (OR = 1.3; 95% CI, 1.2 to 1.5), age at baseline survey (age 22 to 24 years; OR = 1.6; 95% CI, 1.2 to 2.1), lower level of attained education (less than high school, OR = 2.6, 95% CI, 2.1 to 3.3; high school graduate, OR = 2.1, 95% CI, 1.8 to 2.5), income less than 20,000 dollars (OR = 5.6, 95% CI, 4.5 to 7.1), marital status (widowed/divorced/separated; OR = 1.3; 95% CI, 1.1 to 1.6), smoking status (current smoker, OR = 2.0, 95% CI, 1.7 to 2.3; former smoker, OR = 1.4, 95% CI, 1.2 to 1.8), and treatment that included cranial radiation (OR = 1.3, 95% CI, 1.0 to 1.6).Compared with siblings, adult survivors of childhood cancer had significantly lower rates of health insurance coverage and more difficulties obtaining coverage. Since lack of coverage likely has serious health and financial implications for this at-risk population, any disparity in availability and quality of coverage is of great concern.
Predictive Impact of Circulating Vascular Endothelial Growth Factor in Four Phase III Trials Evaluating Bevacizumab
Authors: Priti S. Hegde, Adrian M. Jubb, Dafeng Chen, Nicole F. Li, Y. Gloria Meng, Coen Bernaards, Rebecca Elliott, Stefan J. Scherer, Daniel S. Chen
Journal: Clinical Cancer Research (2012)

We evaluated the prognostic and predictive use of circulating VEGF-A levels in phase III trials of bevacizumab in colorectal cancer, lung cancer, and renal cell carcinoma.Baseline plasma samples from 1,816 patients were analyzed for VEGF-A using an ELISA, which recognizes the major isoforms with equivalent sensitivity. HR and 95% confidence intervals (CI) for study end points were estimated using Cox regression analysis. A subset of matched archival tumor samples was analyzed for VEGF-A expression using in situ hybridization.Higher VEGF-A levels showed trends toward adverse prognostic significance in the control arms of multiple trials, reaching statistical significance for overall survival (OS) in AVF2107 (highest vs. lowest 50%: HR = 1.76; 95% CI, 1.28-2.41), AVAiL (HR = 1.52; 95% CI, 1.16-2.00), and AVOREN (HR = 1.67; 95% CI, 1.18-2.36). In predictive analyses, the HRs for progression-free survival were similar across low and high VEGF-A subgroups and favored bevacizumab-containing treatment. In the low VEGF-A subgroups, HRs (95% CIs) were 0.61 (0.43-0.87) in AVF2107, 0.71 (0.43-1.16) in E4599, 0.74 (0.59-0.94) in AVAiL (low-dose), 0.89 (0.70-1.13) in AVAiL (high-dose), and 0.56 (0.40-0.78) in AVOREN. Analyses of OS data have shown similar results. No correlation between primary tumor VEGF-A expression and plasma VEGF-A levels was observed.In this comprehensive evaluation, pretreatment total circulating VEGF-A was prognostic for outcome in metastatic colorectal, lung, and renal cell cancers, but it was not predictive for bevacizumab-based treatment benefit.
Abstract P5-10-15: First Safety Data from a Randomised Phase III (CIBOMA 2004- 01/GEICAM 2003-11) Trial Assessing Adjuvant Capecitabine Maintenance Therapy after Standard Chemotherapy for Triple-Negative Early Breast Cancer
Authors: A Lluch, H Gomez, M Ruiz-Borrego, J Bines, A Llombart, M Ramos, R Torres, JG Martins-Segalla, L Torrecillas, C. Barrios
Journal: Cancer Research (2010)

Abstract Background: A large adjuvant trial programme is exploring the role of capecitabine (C) in early breast cancer (EBC). CIBOMA 2004-01/GEICAM 2003-11 is a multicenter, international randomised phase III trial that focuses on adjuvant C maintenance therapy after conventional induction chemotherapy in triple-negative EBC. Here we report interim safety data from the trial. Materials and methods: Patients (pts) with operable, node-positive (or node-negative with tumour diameter ≥1 cm), hormone receptor-negative, HER2-negative EBC (central laboratory confirmation) who have received standard anthracycline-and/or taxane-containing chemotherapy in the (neo)adjuvant setting are eligible. Pts are randomised to receive 8 cycles of C (1000 mg/m2 bid, d1-14 q21d) (Arm A) or observation (Arm B). The primary endpoint is disease-free survival (DFS). Assuming 30% risk reduction in DFS rate at 5 years (from 64.7% to 73.7%, HR of 0.701) with a power of 80% and a two-tailed log-rank test at 0.05, 834 evaluable patients will be needed. With an expected drop-out rate of 5%, 876 pts will be included. We anticipate completing recruitment by the end of 2010. Efficacy analysis will be triggered after 255 events. Results: To date, 724 pts have been recruited; here we report safety data from the first 278 pts (136 in Arm A and 142 in Arm B). Baseline characteristics are well balanced between the treatment arms. Baseline Characteristics In total, 920 cycles of C were administered (median 8.0, range 0-8). All 8 cycles were completed by 74.3% of pts. Median relative dose-intensity of C was 91.1%. The most common grade 3/4 clinical AEs related to C were: hand-foot syndrome (Grade 3 19.1%), diarrhoea (3.0%), vomiting (1.5%), fatigue (1.5%), nail changes (1.5%) and bilirubin elevation (1.5%). Conclusions: The safety profile of adjuvant C as maintenance therapy is consistent with its known toxicity profile. Safety data from the first 400 randomised pts will be reviewed by an Independent Data Monitoring Committee and used to update this analysis at the meeting. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-15.
Nature of the glomerular capillary injury in human membranous glomerulopathy.
Authors: O Shemesh, J C Ross, W M Deen, G W Grant, B D Myers
Journal: Journal of Clinical Investigation (1986)

A differential solute clearance technique was used to evaluate glomerular capillary wall function in 20 patients with membranous glomerulopathy and massive proteinuria. The clearance of inulin, the filtration fraction, and the fractional clearance of uncharged dextrans of a radius of 28-48 A were depressed significantly below control values in 20 healthy volunteers (P less than 0.01). In contrast, the fractional clearance of dextrans of radius greater than 50 A was elevated markedly. A theoretical model of solute transport that depicts the major portion of the glomerular capillary wall as an isoporous membrane and the minor portion as a nondiscriminatory shunt pathway revealed the calculated glomerular ultrafiltration coefficient to be five times lower and mean pore radius of the major membrane component to be 4 A smaller than control values. However, the fraction of filtrate volume permeating the shunt pathway was three- to fourfold above control values and correlated strongly in individual patients with the fractional clearance of albumin (r = 0.76) and of IgG (r = 0.80). Lowering renal plasma flow by 24% during indomethacin therapy in seven patients resulted in a 74% reduction in proteinuria accompanied by a corresponding diminution of filtrate formed through the shunt pathway. Morphometric analysis of glomerular ultrastructure revealed the magnitude of depression of the glomerular filtration rate and of urinary protein leakage to be related strongly to changes in the epithelial layer of the glomerular capillary wall, but not to the density of subepithelial immune deposits. We conclude that glomerular capillaries in membranous glomerulopathy are characterized by a loss of ultrafiltration capacity and of barrier size-selectivity, and that subepithelial immune deposits do not provide a structural basis for these functional alterations.
The Rotavirus Saga Revisited
Authors: Alan R. Shaw
Journal: Annual Review of Medicine (2012)

Two live oral rotavirus vaccines were approved by the US Food and Drug Administration in 2005 and 2008, following large studies of ∼70,000 each in order to address questions about intussusception triggered by a third earlier vaccine. Both new rotavirus vaccines showed almost identical rates of intussusception in vaccine and placebo recipients. These vaccines have been used extensively in the United States with positive results. Efforts are under way to implement these vaccines in developing countries where the need is greatest.