tbuckley/cabot-search huggingface dataset:
Variceal bleeding: does variable delay in trial entry invalidate comparison between trials?
Authors: D Bullimore
Journal: Gut (1987)

Variation in time of patient admission to studies of prognosis after variceal haemorrhage has been proposed as a major factor in the wide range of reported results. A study of 144 unselected subjects with a low initial mortality (3% at two days) suggests that the effect has been overemphasised and studies in which time of entry is later than the date of bleeding may be usefully compared. Reanalysis of previous work suggests that even in populations with a high initial mortality limited comparisons between studies can still be usefully made. It is stressed that survival analysis must be started from the date of study entry and not from the date of the index bleed which involves incorporating a retrospective period of survivorship.
Breathing retraining for dysfunctional breathing in asthma: a randomised controlled trial
Authors: M Thomas
Journal: Thorax (2003)

Functional breathing disorders may complicate asthma and impair quality of life. This study aimed to determine the effectiveness of physiotherapy based breathing retraining for patients treated for asthma in the community who have symptoms suggestive of dysfunctional breathing.33 adult patients aged 17-65 with diagnosed and currently treated asthma and Nijmegen questionnaire scores > or =23 were recruited to a randomised controlled trial comparing short physiotherapy breathing retraining and an asthma nurse education control. The main outcome measures were asthma specific health status (Asthma Quality of Life questionnaire) and Nijmegen questionnaire scoresOf the 33 who entered the study, data were available on 31 after 1 month and 28 at 6 months. The median (interquartile range) changes in overall asthma quality of life score at 1 month were 0.6 (0.05-1.12) and 0.09 (-0.25-0.26) for the breathing retraining and education groups, respectively (p=0.018), 0.42 (0.11-1.17) and 0.09 (-0.58-0.5) for the symptoms domain (p=0.042), 0.52 (0.09-1.25) and 0 (-0.45-0.45) for the activities domain (p=0.007), and 0.50 (0-1.50) and -0.25 (-0.75-0.75) for the environment domain (p=0.018). Only the change in the activities domain remained significant at 6 months (0.83 (-0.10-1.71) and -0.05 (-0.74-0.34), p=0.018), although trends to improvement were seen in the overall score (p=0.065), the symptoms domain (p=0.059), and the environment domain (p=0.065). There was a correlation between changes in quality of life scores and Nijmegen questionnaire scores at 1 month and at 6 months. The number needed to treat to produce a clinically important improvement in health status was 1.96 and 3.57 at 1 and 6 months.Over half the patients treated for asthma in the community who have symptoms suggestive of dysfunctional breathing show a clinically relevant improvement in quality of life following a brief physiotherapy intervention. This improvement is maintained in over 25% 6 months after the intervention.
Gene expression deregulation by KRAS G12D and G12V in a BRAF V600E context
Authors: Massimiliano Monticone, Emanuela Biollo, Massimo Maffei, Alessandra Donadini, Francesco Romeo, Clelia Tiziana Storlazzi, Walter Giaretti, Patrizio Castagnola
Journal: Molecular Cancer (2008)

Abstract Background KRAS and BRAF mutations appear of relevance in the genesis and progression of several solid tumor types but the co-occurrence and interaction of these mutations have not yet been fully elucidated. Using a microsatellite stable (MSS) colorectal cancer (CRC) cell line (Colo741) having mutated BRAF and KRAS WT , we also aimed to investigate the KRAS-BRAF interaction. Gene expression profiles for control KRAS WT , KRAS G 12 V and KRAS G 12 D transfected cells were obtained after cell clone selection and RT-PCR screening. Extensive qPCR was performed to confirm microarray data. Results We found that the KRAS G 12 V state deregulated several genes associated to cell cycle, apoptosis and nitrogen metabolism. These findings indicated a reduced survival and proliferation with respect to the KRAS WT state. The KRAS G 12 D state was, instead, characterized by several other distinct functional changes as for example those related to chromatin organization and cell-cell adhesion without affecting apoptosis related genes. Conclusion These data predict that the G12D mutation may be more likely selected in a BRAF mutated context. At the same time, the presence of the KRAS G 12 V mutation in the cells escaping apoptosis and inducing angiogenesis via IL8 may confer a more aggressive phenotype. The present results get along with the observations that CRCs with G12V are associated with a worse prognosis with respect to the WT and G12D states and may help identifying novel CRC pathways and biomarkers of clinical relevance.
The ingestible telemetric body core temperature sensor: a review of validity and exercise applications
Authors: Christopher Byrne, Chin Leong Lim
Journal: British Journal of Sports Medicine (2006)

An ingestible telemetric temperature sensor for measuring body core temperature (Tc) was first described 45 years ago, although the method has only recently gained widespread use for exercise applications. This review aims to (1) use Bland and Altman's limits of agreement (LoA) method as a basis for quantitatively reviewing the agreement between intestinal sensor temperature (Tintestinal), oesophageal temperature (Toesophageal) and rectal temperature (Trectal) across numerous previously published validation studies; (2) review factors that may affect agreement; and (3) review the application of this technology in field-based exercise studies. The agreement between Tintestinal and Toesophageal is suggested to meet our delimitation for an acceptable level of agreement (ie, systematic bias <0.1 degrees C and 95% LoA within +/-0.4 degrees C). The agreement between Tintestinal and Trectal shows a significant systematic bias >0.1 degrees C, although the 95% LoA is acceptable. Tintestinal responds less rapidly than Toesophageal at the start or cessation of exercise or to a change in exercise intensity, but more rapidly than Trectal. When using this technology, care should be taken to ensure adequate control over sensor calibration and data correction, timing of ingestion and electromagnetic interference. The ingestible sensor has been applied successfully in numerous sport and occupational applications such as the continuous measurement of Tc in deep sea saturation divers, distance runners and soldiers undertaking sustained military training exercises. It is concluded that the ingestible telemetric temperature sensor represents a valid index of Tc and shows excellent utility for ambulatory field-based applications.
Outcome of Kidney Transplantation in Patients with Inherited Thrombophilia
Authors: Stefan Heidenreich, Ralf Junker, Heiner Wolters, Detlef Lang, Sabine Hessing, Gitta Nitsche, Ulrike Nowak-Go[Combining Diaeresis]ttl
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Inherited prothrombotic risk factors predispose patients to thromboembolic events. In kidney transplant recipients, thrombophilia may manifest itself with venous thrombosis, microvascular occlusion, or acute rejection with major consequences for allograft survival. This is a prospective study on 165 renal allograft recipients to evaluate the contribution of genetic thrombophilic risk factors to transplant outcome. Besides antithrombin, protein C, and protein S deficiencies, none of which was found in our patient group, factor V G1691A (FV G1691A), prothrombin G20210A (PT G20210A) mutations, and methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphisms were studied. The primary endpoint of the study was occurrence of an acute rejection within the first 90 d and transplant loss within 1 yr. Heterozygous FV G1691A and PT G20210A mutations and the MTHFR T677T variant were significantly associated with acute rejections with rejection rates of 68%, 67%, and 71%, respectively, as compared with 35% in patients not carrying these genotypes. Many rejections that were histologically proven were acute vascular ones. Transplant loss was significantly associated exclusively with the PT G20210A group (50% 1-yr graft survival; odds ratio, 10.0; 95% confidence interval, 1.8 to 56.1). PT G20210A patients exerted the highest prothrombotic activity pretransplant, as determined by prothrombin 1.2 fragments (PT F1.2), which may be the background for minor outcome. In conclusion, common prothrombotic mutations are significantly associated with acute rejections, especially vascular rejections, and for PT G20210A also with early transplant failure. Screening for hypercoagulable states pretransplant is recommended to intensify anticoagulatory treatment posttransplant. E-mail: [email protected]
Tetrahydrobiopterin-dependent formation of nitrite and nitrate in murine fibroblasts.
Authors: G Werner-Felmayer, E R Werner, D Fuchs, A Hausen, G Reibnegger, H Wachter
Journal: The Journal of Experimental Medicine (1990)

The present study demonstrates that murine dermal fibroblasts produce nitrite (NO2-) and nitrate (NO3-) upon treatment with interferon gamma (IFN-gamma). This formation is dependent on L-arginine and can be inhibited by the L-arginine analogue NG-monomethyl-L-arginine. The effect of IFN-gamma is drastically increased by cotreatment with tumor necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1), or lipopolysaccharide (LPS). The tested cytokines also induce formation of tetrahydrobiopterin in murine fibroblasts. Inhibition of guanosine triphosphate-cyclohydrolase I, the key enzyme of tetrahydrobiopterin de novo synthesis with 2,4-diamino-6-hydroxy-pyrimidine, leads to decreased formation of NO2- and NO3-. This effect can be reversed by addition of sepiapterin, which provides tetrahydrobiopterin via a salvage pathway. Methotrexate, which inhibits the salvage pathway, blocks the restoration of NO2- and NO3- production by sepiapterin. The cytotoxic effect of combinations of IFN-alpha with TNF-gamma, IL-1, or LPS is attenuated by inhibition of tetrahydrobiopterin synthesis. These results show that intracellular concentrations of tetrahydrobiopterin control the amount of NO2- and NO3- produced in situ and suggest that the role of cytokine-induced tetrahydrobiopterin synthesis is to provide cells with the active cofactor for production of nitrogen oxides.
1121-58 A double-blind randomized dose finding study of gamma radiation for in-stent restenosis
Authors: Paul S Teirstein, Jeffrey Moses, Martin Leon, Michael Collins, Roxanna Mehran, Eve Aymong, Manuela Neogota, Huan Giap, Shirish Jani, Stephen Balter, Jack Dalton, Roberto Lipsztein, Neal Sawhney, Prabahakkar Tripuraneni
Journal: Journal of the American College of Cardiology (2004)
Disruption of calcium homeostasis and arrhythmogenesis induced by mutations in the cardiac ryanodine receptor and calsequestrin
Authors: N. Liu, S. G. Priori
Journal: Cardiovascular Research (2007)

Development of cardiac arrhythmias in several degenerative cardiac disorders such as heart failure is precipitated by abnormalities in intracellular calcium regulation. Recently, the identification of mutations in proteins responsible for the control of intracellular calcium has been associated with an inherited arrhythmogenic syndrome called catecholaminergic polymorphic ventricular tachycardia (CPVT). Here, we review the current knowledge about the molecular pathophysiology of CPVT and we discuss some potentially innovative strategies for controlling calcium-handling abnormalities in CPVT that may provide novel therapeutic options for affected patients.
Transforming Growth Factor-β Regulates House Dust Mite–induced Allergic Airway Inflammation but Not Airway Remodeling
Authors: Ramzi Fattouh, N. Gabriela Midence, Katherine Arias, Jill R. Johnson, Tina D. Walker, Susanna Goncharova, Kailene P. Souza, Richard C. Gregory, Scott Lonning, Jack Gauldie, Manel Jordana
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

It is now believed that both chronic airway inflammation and remodeling contribute significantly to airway dysfunction and clinical symptoms in allergic asthma. Transforming growth factor (TGF)-beta is a powerful regulator of both the tissue repair and inflammatory responses, and numerous experimental and clinical studies suggest that it may play an integral role in the pathogenesis of asthma.We investigated the role of TGF-beta in the regulation of allergic airway inflammation and remodeling using a mouse model of house dust mite (HDM)-induced chronic allergic airway disease.We have previously shown that intranasal administration of an HDM extract (5 d/wk for 5 wk) elicits robust Th2-polarized airway inflammation and remodeling that is associated with increased airway hyperreactivity. Here, Balb/c mice were similarly exposed to HDM and concurrently treated with a pan-specific TGF-beta neutralizing antibody.We observed that anti-TGF-beta treatment in the context of either continuous or intermittent HDM exposure had no effect on the development of HDM-induced airway remodeling. To further confirm these findings, we also subjected SMAD3 knockout mice to 5 weeks of HDM and observed that knockout mice developed airway remodeling to the same extent as HDM-exposed littermate controls. Notably, TGF-beta neutralization exacerbated the eosinophilic infiltrate and led to increased airway hyperreactivity.Collectively, these data suggest that TGF-beta regulates HDM-induced chronic airway inflammation but not remodeling, and furthermore, caution against the use of therapeutic strategies aimed at interfering with TGF-beta activity in the treatment of this disease.
Potential Role of Ultrafine Particles in Associations between Airborne Particle Mass and Cardiovascular Health
Authors: Ralph J. Delfino, Constantinos Sioutas, Shaista Malik
Journal: Environmental Health Perspectives (2005)

Numerous epidemiologic time-series studies have shown generally consistent associations of cardiovascular hospital admissions and mortality with outdoor air pollution, particularly mass concentrations of particulate matter (PM) < or = 2.5 or < or = 10 microm in diameter (PM2.5, PM10). Panel studies with repeated measures have supported the time-series results showing associations between PM and risk of cardiac ischemia and arrhythmias, increased blood pressure, decreased heart rate variability, and increased circulating markers of inflammation and thrombosis. The causal components driving the PM associations remain to be identified. Epidemiologic data using pollutant gases and particle characteristics such as particle number concentration and elemental carbon have provided indirect evidence that products of fossil fuel combustion are important. Ultrafine particles < 0.1 microm (UFPs) dominate particle number concentrations and surface area and are therefore capable of carrying large concentrations of adsorbed or condensed toxic air pollutants. It is likely that redox-active components in UFPs from fossil fuel combustion reach cardiovascular target sites. High UFP exposures may lead to systemic inflammation through oxidative stress responses to reactive oxygen species and thereby promote the progression of atherosclerosis and precipitate acute cardiovascular responses ranging from increased blood pressure to myocardial infarction. The next steps in epidemiologic research are to identify more clearly the putative PM casual components and size fractions linked to their sources. To advance this, we discuss in a companion article (Sioutas C, Delfino RJ, Singh M. 2005. Environ Health Perspect 113:947-955) the need for and methods of UFP exposure assessment.
Food Intake Patterns Associated With Incident Type 2 Diabetes
Authors: Angela D. Liese, Kristina E. Weis, Mandy Schulz, Janet A. Tooze
Journal: Diabetes Care (2008)

OBJECTIVE—Markers of hemostasis and inflammation such as plasminogen activator inhibitor-1 (PAI-1) and fibrinogen have been associated with risk of type 2 diabetes. We aimed to identify food intake patterns influencing this pathway and evaluate their association with incident diabetes. RESEARCH DESIGN AND METHODS—The Insulin Resistance Atherosclerosis Study cohort included 880 middle-aged adults initially free of diabetes. At the 5-year follow-up, 144 individuals had developed diabetes. Usual dietary intake was ascertained with a 114-item food frequency questionnaire. Using reduced rank regression, we identified a food pattern maximizing the explained variation in PAI-1 and fibrinogen. Subsequently, the food pattern–diabetes association was evaluated using logistic regression. RESULTS—High intake of the food groups red meat, low-fiber bread and cereal, dried beans, fried potatoes, tomato vegetables, eggs, cheese, and cottage cheese and low intake of wine characterized the pattern, which was positively associated with both biomarkers. With increasing pattern score, the odds of diabetes increased significantly (Ptrend &amp;lt; 0.01). After multivariate adjustment, the odds ratio comparing extreme quartiles was 4.3 (95% CI 1.7–10.8). Adjustment for insulin sensitivity and secretion and other metabolic factors had little impact (4.9, 1.8–13.7). CONCLUSIONS—Our findings provide support for potential behavioral prevention strategies, as we identified a food intake pattern that was strongly related to PAI-1 and fibrinogen and independently predicted type 2 diabetes.
Umbilical-cord-blood banking: lessons learned from gamete donation
Authors: Moshe Zilberstein, Michael Feingold, Machelle M Seibel
Journal: The Lancet (1997)

Storage and donation of stem cells from human umbilicalcord blood is a promising medical technology. 1 Varadi G Elchalal U Shushan A Schenker JG Nagler A Umbilical cord blood for use in transplantation. Obstet Gynecol Survey. 1995; 50: 611-617 Crossref PubMed Scopus (16) Google Scholar , 2 McCullough J Clay ME Fautsch S et al. Proposed policies and procedures for establishment of cord blood bank. Blood Cells. 1994; 20: 609-626 PubMed Google Scholar Cord blood stored at birth may be used to treat disorders in later life. Commercial companies advertise this message to prospective parents; cord blood can be collected and processed for about $1500 and $95 annually for storage. 3 Kong D Safe deposit?. Boston Globe. 1996, Jan 22; : p27 Google Scholar , 4 Bates B For hire: fetal cord blood storage. Ob Gyn News. 1996; 31: 1 Google Scholar
Evaluating the State Children's Health Insurance Program: Critical Considerations
Authors: Barbara Starfield
Journal: Annual Review of Public Health (2000)

▪ Abstract The Balanced Budget Act of August 1997 was intended to improve the insurance coverage of low-income children. Although no specific mandates for evaluation accompanied the legislation, states are expected to assess its impact. Insurance improves access to and use of health services. The extent to which this is associated with better health depends on the kinds of services received. Access to a regular source of care is a critical characteristic. If this source of care provides good primary care, a variety of benefits would be expected to accrue. Thus, evaluation of the benefits of the State Children's Health Insurance Program should address not only improved coverage by health insurance for eligible children, but also the extent to which children receive high-quality primary care, including appropriate referrals when needed. Maternal access to and use of services is also a critical factor. Targets for evaluation include state activities to (a) enroll through outreach, inform through education, and develop information systems for tracking; (b) assess the degree of penetration of insurance among low-income children and their mothers, the availability of health care personnel, and the adequacy of benefits conferred by the insurance, primary-care services, and back-up specialty services; and (c) obtain evidence of improved health status. This article details approaches that can appropriately be used to address each of these aspects of concern.
Distribution of myocardial blood flow and capillary diffusion capacity across the canine heart wall
Authors: O. AMTORP, P. ELIASEN, U. ABILDGAARD, S. HAUNSO
Journal: Cardiovascular Research (1984)

Myocardial capillary permeability was determined in 20 dogs by applying a new method which resembles the tissue-uptake technique. The method consisted of a bolus injection of 5lCr-EDTA into the left atrium, determination of the average arterial tracer concentration and subsequent assay of myocardial tissue activity 10, 20 and 30 s after injection. Under the fundamental assumption of no back-diffusion of tracer to capillary blood, uptake of 51Cr-EDTA into myocardium allowed calculation of the transfer constant, Kin, independent of blood flow. Regional plasma flow, fpl, was simultaneously determined from tissue content and average arterial concentration of radioactive microspheres and haematocrit. From estimates of Kin and fpl the fractional extraction, E, of 5lCr-EDTA was calculated as E=Kin/fpl. The capillary permeability-surface area product, PS, was calculated as PS=-fpl·k·1n (1 - E). Constant fractional extraction of 5lCr-EDTA indicates that the method can be employed 10 to 20 s after injection without risk of back-diffusion. From tissue samples taken from subendocardial and subepicardial layers of the left and right ventricular walls and from left and right side parts of the septal region we measured similar PS values. Letting capillary surface area, S, equal 500 cm2·g−1 the permeability coefficient for 51Cr-EDTA was 1.39·10−5cm·s−1.
A Randomized Trial of Prenatal versus Postnatal Repair of Myelomeningocele
Authors: N. Scott Adzick, Elizabeth A. Thom, Catherine Y. Spong, John W. Brock, Pamela K. Burrows, Mark P. Johnson, Lori J. Howell, Jody A. Farrell, Mary E. Dabrowiak, Leslie N. Sutton, Nalin Gupta, Noel B. Tulipan, Diana L. Farmer
Journal: New England Journal of Medicine (2011)

Prenatal repair of myelomeningocele, the most common form of spina bifida, may result in better neurologic function than repair deferred until after delivery. We compared outcomes of in utero repair with standard postnatal repair.We randomly assigned eligible women to undergo either prenatal surgery before 26 weeks of gestation or standard postnatal repair. One primary outcome was a composite of fetal or neonatal death or the need for placement of a cerebrospinal fluid shunt by the age of 12 months. Another primary outcome at 30 months was a composite of mental development and motor function.The trial was stopped for efficacy of prenatal surgery after the recruitment of 183 of a planned 200 patients. This report is based on results in 158 patients whose children were evaluated at 12 months. The first primary outcome occurred in 68% of the infants in the prenatal-surgery group and in 98% of those in the postnatal-surgery group (relative risk, 0.70; 97.7% confidence interval [CI], 0.58 to 0.84; P<0.001). Actual rates of shunt placement were 40% in the prenatal-surgery group and 82% in the postnatal-surgery group (relative risk, 0.48; 97.7% CI, 0.36 to 0.64; P<0.001). Prenatal surgery also resulted in improvement in the composite score for mental development and motor function at 30 months (P=0.007) and in improvement in several secondary outcomes, including hindbrain herniation by 12 months and ambulation by 30 months. However, prenatal surgery was associated with an increased risk of preterm delivery and uterine dehiscence at delivery.Prenatal surgery for myelomeningocele reduced the need for shunting and improved motor outcomes at 30 months but was associated with maternal and fetal risks. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00060606.).