tbuckley/cabot-search huggingface dataset:
Value of Magnetic Resonance Imaging for the Noninvasive Detection of Stenosis in Coronary Artery Bypass Grafts and Recipient Coronary Arteries
Authors: Susan E. Langerak, Hubert W. Vliegen, J. Wouter Jukema, Patrik Kunz, Aeilko H. Zwinderman, Hildo J. Lamb, Ernst E. van der Wall, Albert de Roos
Journal: Circulation (2003)

Magnetic resonance imaging (MRI) is a potential noninvasive diagnostic tool to detect coronary artery bypass graft stenosis, but its value in clinical practice remains to be established. We investigated the value of MRI in detecting stenotic grafts, including recipient vessels.We screened for inclusion 173 consecutive patients who were scheduled for coronary angiography because of recurrent chest pain after coronary artery bypass grafting (CABG). We studied 69 eligible patients with 166 grafts (81 single vein, 44 sequential vein, and 41 arterial grafts). MRI with baseline and stress flow mapping was performed. Both scans were successful in 80% of grafts. Grafts were divided into groups with stenosis > or =50% (n=72) and > or =70% (n=48) in the graft or recipient vessels. Marginal logistic regression was used to predict the probability for the presence of stenosis per graft type using multiple MRI variables. Receiver operator characteristics (ROC) analysis was performed to assess the diagnostic value of MRI. Sensitivity (95% confidence interval)/specificity (95% confidence interval) in detecting single vein grafts with stenosis > or =50% and > or =70% were 94% (86 to 100)/63% (48 to 79) and 96% (87 to 100)/92% (84 to 100), respectively.MRI with flow mapping is useful for identifying grafts and recipient vessels with flow-limiting stenosis. Flow scans could be obtained in 80% of the grafts. This proof-of-concept study suggests that noninvasive MRI detection of stenotic grafts in patients who present with recurrent chest pain after CABG may be useful in selecting those in need of an invasive procedure.
Trends in cerebral palsy among infants of very low birthweight (&lt;1500 g) or born prematurely (&lt;32 weeks) in 16 European centres: a database study
Authors: Mary Jane Platt, Christine Cans, Ann Johnson, Geraldine Surman, Monica Topp, Maria Giulia Torrioli, Inge Krageloh-Mann
Journal: The Lancet (2007)
Next generation sequencing analysis of nine Corynebacterium ulcerans isolates reveals zoonotic transmission and a novel putative diphtheria toxin-encoding pathogenicity island
Authors: Dominik M Meinel, Gabriele Margos, Regina Konrad, Stefan Krebs, Helmut Blum, Andreas Sing
Journal: Genome Medicine (2014)

Toxigenic Corynebacterium ulcerans can cause a diphtheria-like illness in humans and have been found in domestic animals, which were suspected to serve as reservoirs for a zoonotic transmission. Additionally, toxigenic C. ulcerans were reported to take over the leading role in causing diphtheria in the last years in many industrialized countries.To gain deeper insights into the tox gene locus and to understand the transmission pathway in detail, we analyzed nine isolates derived from human patients and their domestic animals applying next generation sequencing and comparative genomics.We provide molecular evidence for zoonotic transmission of C. ulcerans in four cases and demonstrate the superior resolution of next generation sequencing compared to multi-locus sequence typing for epidemiologic research. Additionally, we provide evidence that the virulence of C. ulcerans can change rapidly by acquisition of novel virulence genes. This mechanism is exemplified by an isolate which acquired a prophage not present in the corresponding isolate from the domestic animal. This prophage contains a putative novel virulence factor, which shares high identity with the RhuM virulence factor from Salmonella enterica but which is unknown in Corynebacteria so far. Furthermore, we identified a putative pathogenicity island for C. ulcerans bearing a diphtheria toxin gene.The novel putative diphtheria toxin pathogenicity island could provide a new and alternative pathway for Corynebacteria to acquire a functional diphtheria toxin-encoding gene by horizontal gene transfer, distinct from the previously well characterized phage infection model. The novel transmission pathway might explain the unexpectedly high number of toxigenic C. ulcerans.
Young Women With Type 1 Diabetes Have Lower Bone Mineral Density That Persists Over Time
Authors: Lucy D. Mastrandrea, Jean Wactawski-Wende, Richard P. Donahue, Kathleen M. Hovey, Angela Clark, Teresa Quattrin
Journal: Diabetes Care (2008)

Individuals with type 1 diabetes have decreased bone mineral density (BMD), yet the natural history and pathogenesis of osteopenia are unclear. We have previously shown that women with type 1 diabetes (aged 13-35 years) have lower BMD than community age-matched nondiabetic control subjects. We here report 2-year follow-up BMD data in this cohort to determine the natural history of BMD in young women with and without diabetes.BMD was measured by dual-energy X-ray absorptiometry at baseline and 2 years later in 63 women with type 1 diabetes and in 85 age-matched community control subjects. A1C, IGF-1, IGF binding protein-3, serum osteocalcin, and urine N-teleopeptide were measured at follow-up.After adjusting for age, BMI, and oral contraceptive use, BMD at year 2 continued to be lower in women >or=20 years of age with type 1 diabetes compared with control subjects at the total hip, femoral neck, and whole body. Lower BMD values were observed in cases <20 years of age compared with control subjects; however, the differences were not statistically significant. Lower BMD did not correlate with diabetes control, growth factors, or metabolic bone markers.This study confirms our previous findings that young women with type 1 diabetes have lower BMD than control subjects and that these differences persist over time, particularly in women >or=20 years of age. Persistence of low BMD as well as failure to accrue bone density after age 20 years may contribute to the increased incidence of osteoporotic hip fractures seen in postmenopausal women with type 1 diabetes.
Outcome of Photodynamic Therapy Using NPe6 for Bronchogenic Carcinomas in Central Airways &amp;gt;1.0 cm in Diameter
Authors: Jitsuo Usuda, Shuji Ichinose, Taichirou Ishizumi, Hiroki Hayashi, Keishi Ohtani, Sachio Maehara, Shoutarou Ono, Hidetoshi Honda, Naohiro Kajiwara, Osamu Uchida, Hidemitsu Tsutsui, Tatsuo Ohira, Harubumi Kato, Norihiko Ikeda
Journal: Clinical Cancer Research (2010)

Most centrally located early lung cancers (CLELC) <1.0 cm in diameter do not invade beyond the bronchial cartilage, and photodynamic therapy (PDT) with Photofrin is currently recommended as a treatment option for such lesions. NPe6 is a second-generation photosensitizer, and because it has a longer absorption band (664 nm) than Photofrin (630 nm), we hypothesized that NPe6-PDT would exert a strong antitumor effect against cancer lesions >1.0 cm in diameter, which are assumed to involve extracartilaginous invasion and to be unsuitable for treatment with Photofrin-PDT.Between June 2004 and December 2008, 75 patients (91 lesions) with CLELC underwent NPe6-PDT after the extent of their tumors had been assessed by fluorescence bronchoscopy for photodynamic diagnosis and tumor depth had been assessed by optical coherence tomography.Seventy cancer lesions < or =1.0 cm in diameter and 21 lesions >1.0 cm in diameter were identified, and the complete response rate was 94.0% (66 of 70) and 90.4% (19 of 21), respectively. After the mass of large tumors and deeply invasive tumors had been reduced by electrocautery, NPe6-PDT was capable of destroying the residual cancer lesions.NPe6-PDT has a strong antitumor effect against CLELCs >1.0 cm in diameter that have invaded beyond the bronchial cartilage, thereby enabling the destruction of residual cancer lesions after mass reduction of large nodular- or polypoid-type lung cancers by electrocautery. The PDT guidelines for lung cancers should therefore be revised because use of NPe6-PDT will enable expansion of the clinical indications for PDT.
PF-00477736 Mediates Checkpoint Kinase 1 Signaling Pathway and Potentiates Docetaxel-Induced Efficacy in Xenografts
Authors: Cathy Zhang, Zhengming Yan, Cory L. Painter, Qin Zhang, Enhong Chen, Maria E. Arango, Kyle Kuszpit, Kenneth Zasadny, Max Hallin, Jill Hallin, Anthony Wong, Dana Buckman, Guizhen Sun, Ming Qiu, Kenna Anderes, James G. Christensen
Journal: Clinical Cancer Research (2009)

Checkpoint kinase 1 (Chk1) plays a critical role in the activation of mitotic spindle checkpoint and DNA damage checkpoint. We examined the preclinical use of the Chk1 inhibitor PF-00477736 as a docetaxel-sensitizing agent. Specifically, we investigated the correlation between PF-00477736-mediated modulation of biomarkers and the sensitization of docetaxel efficacy.In vitro and in vivo studies using COLO205 and other cell lines were done to assess PF-00477736-induced enhancement of docetaxel efficacy and effects on associated biomarkers.PF-00477736 significantly enhanced the docetaxel-induced efficacy in tumor cells and xenografts. Docetaxel induced dose- and time-dependent increase in the levels of phosphorylated Chk1 (Ser(345)), phosphorylated histone H3 (Ser(10)), and gammaH2AX foci and promoted the cytoplasmic localization of phosphorylated Cdc25C (Ser(216)). PF-00477736 cotreatment suppressed docetaxel-induced changes in phosphorylated histone H3 and cytoplasmic phosphorylated Cdc25C (Ser(216)) levels and concurrently sensitized the docetaxel-induced apoptosis. Docetaxel alone or in combination with PF-00477736 induced significant antiproliferative activity in xenografts, shown via [18F]FLT-PET imaging. However, changes in [18F]FLT uptake did not reflect the potentiation of docetaxel efficacy. In contrast, bioluminescence imaging showed that PF-00477736 sensitized docetaxel-induced suppression of tumor survival.Docetaxel triggers mitotic spindle checkpoint activation at low concentrations and activates both the DNA damage checkpoint and the spindle checkpoint at high concentrations. In combination with docetaxel, PF-00477736 abrogates the mitotic checkpoint, as well as the DNA damage checkpoint, and results in sensitization to docetaxel. Chk1 inhibitor PF-00477736 offers a therapeutic potential for the enhancement of taxane therapy.
Polymerase γ Gene POLG Determines the Risk of Sodium Valproate-Induced Liver Toxicity
Authors: Joanna D. Stewart, Rita Horvath, Enrico Baruffini, Iliana Ferrero, Stefanie Bulst, Paul B. Watkins, Robert J. Fontana, Christopher P. Day, Patrick F. Chinnery
Journal: Hepatology (2010)

Sodium valproate (VPA) is widely used throughout the world to treat epilepsy, migraine, chronic headache, bipolar disorder, and as adjuvant chemotherapy. VPA toxicity is an uncommon but potentially fatal cause of idiosyncratic liver injury. Rare mutations in POLG, which codes for the mitochondrial DNA polymerase γ (polγ), cause Alpers-Huttenlocher syndrome (AHS). AHS is a neurometabolic disorder associated with an increased risk of developing fatal VPA hepatotoxicity. We therefore set out to determine whether common genetic variants in POLG explain why some otherwise healthy individuals develop VPA hepatotoxicity. We carried out a prospective study of subjects enrolled in the Drug Induced Liver Injury Network (DILIN) from 2004 to 2008 through five US centers. POLG was sequenced and the functional consequences of VPA and novel POLG variants were evaluated in primary human cell lines and the yeast model system Saccharomyces cerevisiae. Heterozygous genetic variation in POLG was strongly associated with VPA-induced liver toxicity (odds ratio = 23.6, 95% confidence interval [CI] = 8.4-65.8, P = 5.1 × 10⁻⁷). This was principally due to the p.Q1236H substitution which compromised polγ function in yeast. Therapeutic doses of VPA inhibited human cellular proliferation and high doses caused nonapoptotic cell death, which was not mediated through mitochondrial DNA depletion, mutation, or a defect of fatty acid metabolism. These findings implicate impaired liver regeneration in VPA toxicity and show that prospective genetic testing of POLG will identify individuals at high risk of this potentially fatal consequence of treatment.
Targeted Disruption of Migration Inhibitory Factor Gene Reveals Its Critical Role in Sepsis
Authors: Marcelo Bozza, Abhay R. Satoskar, Guosheng Lin, Bao Lu, Alison A. Humbles, Craig Gerard, John R. David
Journal: The Journal of Experimental Medicine (1999)

To study the biologic role of migration inhibitory factor (MIF), a pleiotropic cytokine, we generated a mouse strain lacking MIF by gene targeting in embryonic stem cells. Analysis of the role of MIF during sepsis showed that MIF−/− mice were resistant to the lethal effects of high dose bacterial lipopolysaccharide (LPS), or Staphylococcus aureus enterotoxin B (SEB) with d-galactosamine and had lower plasma levels of tumor necrosis factor α (TNF-α) than did wild-type mice, but normal levels of interleukin (IL)-6 and IL-10. When stimulated with LPS and interferon γ, macrophages from MIF−/− mice showed diminished production of TNF-α, normal IL-6 and IL-12, and increased production of nitric oxide. MIF−/− animals cleared gram-negative bacteria Pseudomonas aeruginosa instilled into the trachea better than did wild-type mice and had diminished neutrophil accumulation in their bronchoalveolar fluid compared to the wild-type mice. Thioglycollate elicited peritoneal exudates in uninfected MIF−/− mice, but showed normal neutrophil accumulation. Finally, the findings of enhanced resistance to P. aeruginosa and resistance to endotoxin-induced lethal shock suggest that the counteraction or neutralization of MIF may serve as an adjunct therapy in sepsis.
Food allergy: an overview.
Authors: Rhoda Sheryl Kagan
Journal: Environmental Health Perspectives (2003)

Food allergy affects between 5% and 7.5% of children and between 1% and 2% of adults. The greater prevalence of food allergy in children reflects both the increased predisposition of children to develop food allergies and the development of immunologic tolerance to certain foods over time. Immunoglobulin (Ig) E-mediated food allergies can be classified as those that persist indefinitely and those that are predominantly transient. Although there is overlap between the two groups, certain foods are more likely than others to be tolerated in late childhood and adulthood. The diagnosis of food allergy rests with the detection of food-specific IgE in the context of a convincing history of type I hypersensitivity-mediated symptoms after ingestion of the suspected food or by eliciting IgE-mediated symptoms after controlled administration of the suspected food. Presently, the only available treatment of food allergies is dietary vigilance and administration of self-injectable epinephrine.
Estrogen alters thresholds for B cell apoptosis and activation
Authors: Christine M. Grimaldi, James Cleary, A. Selma Dagtas, Dariush Moussai, Betty Diamond
Journal: Journal of Clinical Investigation (2002)

Estrogen is thought to contribute to the increased frequency of autoimmune disorders occurring in females, but a molecular basis for its effects on autoimmunity remains to be elucidated. We have shown previously that estrogen leads to the survival and activation of autoreactive cells in the naive repertoire. To identify the molecular pathways involved in B cell tolerance, we sought to identify genes that are differentially regulated by estrogen in mouse B cells. Several genes involved in B cell activation and survival, including cd22, shp-1, bcl-2, and vcam-1, were upregulated by estrogen in B cells. We found that overexpression of CD22 and SHP-1 in B cells decreased B cell receptor signaling. Estrogen receptors α and β are expressed on B cells and are functional, since they can directly upregulate expression of CD22, SHP-1, and Bcl-2. Estrogen treatment protected isolated primary B cells from B cell receptor–mediated apoptosis. These results suggest that estrogen induces a genetic program that alters survival and activation of B cells in a B cell–autonomous fashion and thus skews the naive immune system toward autoreactivity.
Predictive factors of survival in patients with advanced colorectal cancer: an individual data analysis of 602 patients included in irinotecan phase III trials
Authors: E. Mitry, J.-Y. Douillard, E. Van Cutsem, D. Cunningham, E. Magherini, D. Mery-Mignard, L. Awad, P. Rougier
Journal: Annals of Oncology (2004)
β<sub>2</sub>-Adrenergic Receptor Haplotypes in Mild, Moderate and Fatal/Near Fatal Asthma
Authors: TRACEY D. WEIR, NOA MALLEK, ANDREW J. SANDFORD, TONY R. BAI, NASSAR AWADH, J. M. FITZGERALD, DON COCKCROFT, ALAN JAMES, STEPHEN B. LIGGETT, PETER D. PARÉ
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Excess β2-agonist use in asthmatics has been associated with increased mortality and morbidity. The mechanisms responsible for these observations are unknown. We hypothesized that polymorphisms of the β2-adrenergic receptor ( β2AR) at amino acid positions 16, 27, and 164, which are known to alter receptor functions in vitro, may predispose asthmatics to fatal/near-fatal asthma and/or modify asthma severity. In preliminary studies we found significant differences in allele frequencies due to ethnic background: Caucasian, Black, Asian Gly16 = 0.61, 0.50, 0.40 and Gln27 = 0.57, 0.73, 0.80, respectively. β2AR genotyping was performed on DNA from Caucasians classified as nonasthmatic/nonatopic (n = 84), fatal/near-fatal asthmatics (n = 81) and mild/moderate asthmatics (n = 86). No polymorphism or haplotype was found to be associated with fatal/near-fatal asthma. However, the Gly16/Gln27 haplotype, which undergoes enhanced downregulation in vitro, was substantially more prevalent in moderate asthmatics than in mild asthmatics (p = 0.003, odds ratio = 3.1). We conclude that the β2AR genotype is not a major determinant of fatal or near-fatal asthma. Furthermore, allele frequency variation among ethnic groups must be considered in clinical studies of β2AR polymorphisms in asthma.
Ultrasound as the new stethoscope: AMSSM pioneers curriculum (gently!)
Authors: Karim M Khan
Journal: British Journal of Sports Medicine (2010)

Five landmark moments in sport and exercise medicine: (1) Bannister's 3:59.4 at Iffley Road; (2) Ron Clarke collapses at the Mexico Olympic Games; (3) Jerry Morris publishes Exercise: today's best buy in public health ; (4) the Concussion Consensus Meetings in Vienna, Prague & Zurich; (5) the first World Congress on Sports Injury Prevention in Oslo; (6) Keith Richards falls out of a palm tree at the Wakaya Club in Fiji and injures his back during the tour appropriately called ‘A Bigger Bang.’ ‘Hey!!!!, but that’s like eight events' says my 16-year-old personality. Be that as it may, it's a highly contrived segue to highlight that office ultrasound for diagnosis and procedures has arrived—ready …
Longitudinal PET Evaluation of Cerebral Metabolic Decline in Dementia: A Potential Outcome Measure in Alzheimer’s Disease Treatment Studies
Authors: Gene E. Alexander, Kewei Chen, Pietro Pietrini, Stanley I. Rapoport, Eric M. Reiman
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: It is well established that regional cerebral metabolic rates for glucose assessed by [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in patients with Alzheimer's disease in the mental resting state (eyes and ears covered) provide a sensitive, in vivo metabolic index of Alzheimer's disease dementia. Few studies, however, have evaluated longitudinal declines in regional cerebral glucose metabolism in patients with dementia caused by Alzheimer's disease. In addition, the available studies have not used recently developed brain mapping algorithms to characterize the progression of Alzheimer's disease throughout the brain, and none considered the statistical power of regional cerebral glucose metabolism in testing the ability of treatments to attenuate the progression of dementia. METHOD: The authors used FDG PET and a brain mapping algorithm to investigate cross-sectional reductions in regional cerebral glucose metabolism, longitudinal decline in regional cerebral glucose metabolism after a 1-year follow-up, and the power of this method to evaluate treatments for Alzheimer's disease in patients with mild to moderate dementia. PET scans were initially acquired in 14 patients with Alzheimer's disease and 34 healthy comparison subjects of similar age and sex. Repeat scans were obtained in the patients 1 year later. Power analyses for voxels showing maximal decline over the 1-year period in regional cerebral glucose metabolism (mg/100 g per minute) were computed to estimate the sample sizes needed to detect a significant treatment response in a 1-year, double-blind, placebo-controlled treatment study. RESULTS: The patients with Alzheimer's disease had significantly lower glucose metabolism than healthy comparison subjects in parietal, temporal, occipital, frontal, and posterior cingulate cortices. One year later, the patients with Alzheimer's disease had significant declines in glucose metabolism in parietal, temporal, frontal, and posterior cingulate cortices. Using maximal glucose metabolism reductions in the left frontal cortex, we estimated that as few as 36 patients per group would be needed to detect a 33% treatment response with one-tailed significance of p≤0.005 and 80% power in a 1-year, double-blind, placebo-controlled treatment study. CONCLUSIONS: These findings indicate that brain metabolism as assessed by FDG PET during mental rest is a sensitive marker of disease progression in Alzheimer's disease over a 1-year period. These findings also support the feasibility of using FDG PET as an outcome measure to test the ability of treatments to attenuate the progression of Alzheimer's disease.
Evidence-based practice of photopheresis 1987-2001: a report of a workshop of the British Photodermatology Group and the U.K. Skin Lymphoma Group
Authors: K.E. McKenna, S. Whittaker, L.E. Rhodes, P. Taylor, J. Lloyd, S. Ibbotson, R. Russell-Jones
Journal: British Journal of Dermatology (2005)

Photopheresis or extracorporeal photochemotherapy (ECP) is a novel immunomodulatory therapy which involves separation of the patient's leucocyte-rich plasma, followed by ex vivo administration of a photosensitizer and ultraviolet A radiation, before reinfusion. ECP has been used successfully for the treatment of cutaneous T-cell lymphoma (CTCL: Sézary syndrome), graft-versus-host disease (GVHD) and cardiac transplant rejection. ECP has a dose-sparing effect on concurrent immunosuppressive therapy. The procedure induces apoptosis of the irradiated lymphocytes, but the exact mechanism by which ECP exerts its therapeutic effect in these different conditions is uncertain. The treatment has very few adverse effects and in particular is not associated with an increased incidence of opportunistic infections. The evidence for the efficacy of ECP has been appraised by a combined British Photodermatology Group and U.K. Skin Lymphoma Group workshop on the basis of evidence published up to the end of 2001 and on the consensus of best practice. There is fair evidence for the use of ECP in erythrodermic CTCL and steroid-refractory GVHD, but randomized controlled studies are needed. There is good evidence supporting the use of ECP in preventing cardiac rejection following transplantation. Randomized controlled trials have also shown a therapeutic benefit in type 1 diabetes mellitus, but the inconvenience associated with the procedure outweighed the clinical benefit. There is fair evidence not to use ECP for the treatment of systemic sclerosis and multiple sclerosis, and good evidence not to use ECP for other forms of CTCL.