tbuckley/cabot-search huggingface dataset:
P116 Outcomes of DCD Lung Offers: A Single Centre Experience in the UK
Authors: C Newark, J Parmar, J Dunning, S Tsui
Journal: Thorax (2012)

<h3>Introduction</h3> Lung transplantation is the treatment of choice for a variety of end stage lung diseases. It offers prognostic benefit and an improvement in quality of life for carefully selected patients. There sadly remains a critical shortage of lung donors. One way to increase the donor pool, and potentially the number of lung transplants, is to utilise organs which are Donated following Circulatory Death (DCD). Here we review our experience with DCD offers received during a two-and-a-half year period. <h3>Methods</h3> This is a retrospective study using data collected prospectively from all lung offers received between 01/2009 – 09/2011. We look at the proportion of DCD lung offers and track the fate of each of these down to transplantation. We look at the documented reasons for declining all DCD lung offers, the rate of DCD lung transplantation and the survival rate in this cohort. <h3>Results</h3> Overall, 80 lung transplants were performed during the study period. 7 were performed using DCDs, therefore, 9% of lung transplants are from DCD donors. Survival rate at 1 year post-DCD lung transplantation is approximately 80%. 233(86%) of DCD lung offers were initially declined. Numerous reasons were documented; the most common reason given (122 donors) was due to evidence of infection. In 37 cases, the donor was unlikely to meet extubation criteria. Interestingly, 42 donors were declined as a result of having no suitable recipient on the transplant waiting list alone. A large proportion of offers were initially accepted but not used. In 5 cases consent for transplantation was withdrawn from family, 7 cases were declined due to time/logistical factors and 10 donors were declined on inspection from the retrieval team. <h3>Conclusion</h3> Despite offering good short term outcomes, a large number of DCD lungs are declined for a variety reasons. Donors declined due to having no suitable recipient could be reduced by increasing the number of patients on the waiting list. Increased public awareness and better communication leading up to donation may lead to fewer cases of consent being withdrawn from family. A lower threshold for attending donors who might not meet criteria may also yield more organs.
Right-sided aortic arch with Kommerell's diverticulum: 64-DCTA with 3D reconstructions
Authors: I Carbone, P Sedati, N Galea, E Algeri, R Passariello
Journal: Thorax (2008)

Right-sided aortic arch with Kommerell's diverticulum: 64-DCTA with 3D reconstructions A 75-year-old woman was referred with a long history of dysphagia and wheezing.A chest radiograph revealed the presence of bilateral paratracheal stripes of abnormal appearance (fig 1).Computed tomography angiography with 64 detectors (64-DCTA) of the chest revealed the presence of a right-sided aortic arch with an aberrant retro-oesophageal left subclavian artery arising from a Kommerell's diverticulum (fig 2).Kommerell's diverticulum can occur in a number of anomalies of the aortic arch system. 1 It may cause symptoms of tracheal or oesophageal compression, but not in all cases. 3In this patient the left subclavian artery arises from a right-sided aortic arch as the fourth branch passing behind the oesophagus to the left arm.64-DCTA with isotropic submillimetre acquisition allowed high quality 3D volume-rendered images to be generated that readily showed this complex vascular anomaly.
The effect of cholestyramine on intestinal absorption.
Authors: R J West, J K Lloyd
Journal: Gut (1975)

Cholestyramine in a mean dosage of 0-6 g/kg/day has been given to 18 children with familial hypercholesterolaemia for between one and two and a half years. With prolonged treatment folate deficiency occurred, as evidenced by a fall in the mean serum folate concentration from 7-7 ng/ml before treatment to 4-4 ng/ml for patients on treatment for over one year; a corresponding lowering of red cell folate was also seen. Oral folic acid 5 mg daily overcame this depletion, and should be given to all patients on long-term anion exchange resins. Prothrombin time has remained normal in all patients; there has been a significant decrease in the mean serum concentrations of vitamins A and E and of inorganic phosphorus over the first two years of treatment, although values remain within the normal range. The routine administration of fat-soluble vitamins appears unnecessary but it is prudent to measure prothrombin time and serum vitamins A and E at intervals. In children who were having a normal intake of dietary fat five out of seven tested had faecal fat of over 5 g/day while on cholestyramine. No chold has developed diarrhoea, and growth has been normal. The concentrations of serum iron, vitamin B12, plasma calcium, and protein did not change significantly in any patient.
Fine needle aspiration in the diagnosis of metastatic melanoma
Authors: Lori K.E. Rodrigues, Stanley P.L. Leong, Britt-Marie Ljung, Richard W. Sagebiel, Nancy Burnside, Tsu-lung William Hu, Brenda W. Ng, James R. Miller, Mohammed Kashani-Sabet
Journal: Journal of the American Academy of Dermatology (2000)
Squamous-cell carcinoma of the pleura.
Authors: J R Ruttner, S Heinzl
Journal: Thorax (1977)

There are few reports of primary malignant tumours of the pleura other than mesothelioma. Reports of squamous-cell carcinoma of the pleura are especially rare. Epidermoid carcinoma of the pleura may occur in connection with persistent empyema drained by a pleurocutaneous fistula or long-standing extrapleural pneumothorax without fistula.
Association of Human Connexin40 Gene Polymorphisms With Atrial Vulnerability as a Risk Factor for Idiopathic Atrial Fibrillation
Authors: Mehran Firouzi, Hemanth Ramanna, Bart Kok, Habo J. Jongsma, Bobby P.C. Koeleman, Pieter A. Doevendans, W. Antoinette Groenewegen, Richard N.W. Hauer
Journal: Circulation Research (2004)

Alterations in distribution, density, and properties of cardiac gap junctions, which mediate electrical coupling of cardiomyocytes, are considered potentially arrhythmogenic. We recently reported 2 linked polymorphisms within regulatory regions of the gene for the atrial gap junction protein connexin40 (Cx40) at nucleotides -44 (G-->A) and +71 (A-->G), which were associated with familial atrial standstill. The present study examined whether these Cx40 polymorphisms were associated with increased atrial vulnerability in vivo and arrhythmia susceptibility. In 30 subjects without structural heart disease, of whom 14 had documented sporadic paroxysmal atrial fibrillation (AF) and 16 had no AF history, inducibility of AF was assessed using an increasingly aggressive atrial stimulation protocol. Coefficient of spatial dispersion of refractoriness (CD) was calculated. CD was defined as the SD of 12 local mean fibrillatory intervals recorded at right atrial sites, expressed as a percentage of the overall mean fibrillatory interval. Cx40 genotypes were determined by direct DNA sequencing. Subjects were stratified according to normal or increased CD with a cutoff value of 3.0, because CD >3.0 was previously shown to be strongly associated with enhanced atrial vulnerability. The prevalence of the minor Cx40 allele (-44A) and -44AA genotype was significantly higher in subjects with increased dispersion (n=13) compared with those with CD < or =3.0 (n=17; P=0.00046 and P=0.025; odds ratios of 6.7 and 7.4) and a control population (n=253; P=0.00002 and P=3.90x10(-7)). Carriers of -44AA genotype had a significantly higher CD compared with those with -44GG genotype (6.37+/-1.21 versus 2.38+/-0.39, P=0.018), whereas heterozygotes had intermediate values (3.95+/-1.38, NS). All subjects with increased CD had a history of idiopathic AF compared with only 1 subject with normal CD. The -44A allele and -44AA genotype were significantly more frequent in subjects with prior AF than in those without (P=0.0019 and P=0.031; odds ratios 5.3 and 6.2). This study provides strong evidence linking Cx40 polymorphisms to enhanced atrial vulnerability and increased risk of AF. The full text of this article is available online at http://circres.ahajournals.org.
Impact of an Interactive Online Nursing Educational Module on Insulin Errors in Hospitalized Pediatric Patients
Authors: Mary M. Sullivan, Colette R. O'Brien, Stephen E. Gitelman, Susan E. Shapiro, Robert J. Rushakoff
Journal: Diabetes Care (2010)

OBJECTIVE To determine the effectiveness of an online module for reducing insulin administration errors by nurses caring for hospitalized pediatric patients. RESEARCH DESIGN AND METHODS Pediatric nursing staff completed a mandatory online educational module teaching insulin pharmacokinetics and the insulin order form, using diluted insulin and finishing with 15 interactive cases. A chart audit to determine all possible insulin errors of patients receiving insulin was done before and 2–6 months after the educational module. RESULTS All of the medical center's 283 pediatric nurses successfully completed the educational module. A total of 24 charts were audited in the preintervention phase and 22 in the postintervention phase. The preintervention insulin error rate was 14.8%, reduced to 1.7% (P &amp;lt; 0.001) postintervention. Improvement occurred in correct insulin dosing and type, timing of administration, and timely blood glucose monitoring and documentation. CONCLUSIONS An interactive online educational module can be an effective strategy for reducing pediatric nurses' insulin administration errors.
Prodromal face of a study: High dose rate endobronchial brachytherapy (HDERB) as a first step introductory treatment of a multimodality therapy approach in non operable NSCLC with endobronchial obstruction
Authors: Konstantina Papalla, Danai Bisirtzoglou, Vasilis Anastasakos, Athanasios Zetos, Charalampos Marketos, Ioannis Katsilieris, Georgios Politis
Journal: European Respiratory Journal (2012)

Introduction:  Lung cancer patients frequently present with advanced stage. HDREB has always been used as a palliative treatment option in end-stage disease, and has not yet been thought of as a first-step therapeutic approach of a multimodality treatment strategy. We strongly feel that HDERB could be the method of choice in carefully selected patients with endobronchial obstruction, prior to other treatments.  Aim:  HDERB could be used as a first-step, introductory treatment in selected patients with inoperable obstructive endobronchial carcinoma of the lungs.  Methods:  A catheter is placed through bronchoscopy in the obstructed lumen. HDREB is delivered in two sessions separated by one week. Bronchoscopy is performed 3 weeks later. Pulmonary function tests are preformed before and after HDREB monthly. Evaluation of quality of life is assesed with Saint Georges Respiratory Questionaire. Obstruction score is also evaluated before and after treatment.  Results:  Six patients with previously untreated, inoperable NSCLC associated with endobronchial obstruction, were treated with HDREB as an introductory treatment of a multimodality therapeutic approach. We found significant improvement on symptoms (cough, dyspnoea, hemoptysis) and intraluminal reduction of the obstruction.  Conclusions:  HDREB is a low-cost, semi-invasive, and well-tolerated method that has been applied with a limited palliative purpose, whilst it could provide an improved performance status and partial disease regression early enough, giving the patient the opportunity of a better outcome of treatment, overall.
Leptin and Amylin Act in an Additive Manner to Activate Overlapping Signaling Pathways in Peripheral Tissues
Authors: Hyun-Seuk Moon, John P. Chamberland, Kalliope N. Diakopoulos, Christina G. Fiorenza, Florencia Ziemke, Benjamin Schneider, Christos S. Mantzoros
Journal: Diabetes Care (2010)

OBJECTIVE Amylin interacts with leptin to alter metabolism. We evaluated, for the first time, amylin- and/or leptin-activated signaling pathways in human peripheral tissues (hPTs). RESEARCH DESIGN AND METHODS Leptin and amylin signaling studies were performed in vitro in human primary adipocytes (hPAs) and human peripheral blood mononuclear cells (hPBMCs) and ex vivo in human adipose tissue (hAT) from male versus female subjects, obese versus lean subjects, and subjects with subcutaneous versus omental adipose tissue. RESULTS The long form of leptin receptor was expressed in human tissues and cells studied in ex vivo and in vitro, respectively. Leptin and amylin alone and in combination activate signal transducer and activator of transcription 3 (STAT3), AMP-activated protein kinase, Akt, and extracellular signal-regulated kinase signaling pathways in hAT ex vivo and hPAs and hPBMCs in vitro; all phosphorylation events were saturable at leptin and amylin concentrations of ∼50 and ∼20 ng/ml, respectively. The effects of leptin and amylin on STAT3 phosphorylation in hPAs and hPBMCs in vitro were totally abolished under endoplasmic reticulum stress and/or in the presence of a STAT3 inhibitor. Results similar to those in the in vitro studies were observed in hAT studied ex vivo. CONCLUSIONS Leptin and amylin activate overlapping intracellular signaling pathways in humans and have additive, but not synergistic, effects in signaling pathways studied in hPTs in vitro and ex vivo.
<i>Nucleophosmin</i> Mutations in <i>De novo</i> Acute Myeloid Leukemia: The Age-Dependent Incidences and the Stability during Disease Evolution
Authors: Wen-Chien Chou, Jih-Luh Tang, Liang-In Lin, Ming Yao, Woei Tsay, Chien-Yuan Chen, Shang-Ju Wu, Chi-Fei Huang, Rong-Jing Chiou, Mei-Hsuan Tseng, Dong-Tsamn Lin, Kai-Hsin Lin, Yao-Chang Chen, Hwei-Fang Tien
Journal: Cancer Research (2006)

Abstract Nucleophosmin (NPM) mutations have been found in a significant proportion of adults with de novo acute myeloid leukemia (AML), especially in those of a normal karyotype. These results provide a basis for studies of the pathogenesis in this specific subgroup of AML. In this study, NPM mutations were analyzed in 173 Chinese patients of de novo AML, including adults and children. We found that NPM mutations were present in 19.1% of the overall population and 40.3% of those with a normal karyotype. Adults had a significantly higher incidence of NPM mutations than children [32 of 126 (25.4%) versus 1 of 47 (2.1%), P &amp;lt; 0.001]. NPM mutations were closely associated with normal karyotype (P &amp;lt; 0.001) and internal tandem duplication of FLT3 (P = 0.002), but negatively associated with CEBPA mutations (P = 0.032) and expression of CD34 (P &amp;lt; 0.001) and HLA-DR (P = 0.003). Serial analyses of NPM mutations showed the mutation disappeared at complete remission, but the same mutation reappeared at relapse, except for one who lost the mutation at the second relapse, when new cytogenetic abnormalities emerged. None acquired novel mutations during the follow-up period. In conclusion, NPM mutations occur in an age-dependent fashion. Moreover, the findings that NPM mutations are stable during disease evolution and closely associated with disease status make it a potential marker for monitoring minimal residual disease. (Cancer Res 2006; 66(6): 3310-6)
Novel therapies in genitourinary cancer: an update
Authors: David Chu, Shenhong Wu
Journal: Journal of Hematology & Oncology (2008)

In recent years, new treatment for renal cell carcinoma (RCC) has been a spotlight in the field of cancer therapeutics. With several emerging agents branded as 'targeted therapy' now available, both medical oncologists and urologists are progressively more hopeful for better outcomes. The new remedies may provide patients with improved survival and at the same time less toxicity when compared to traditional cytotoxic agents. This article will center on current and emerging treatment strategies for advanced RCC and other GU malignancies with updates from 2008 annual ASCO meeting.
Tumor Characteristics and Clinical Outcome of Elderly Women With Breast Cancer
Authors: S. G. Diab
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: The number of elderly patients with breast cancer is increasing. Limited age-related information available about this disease prompted this study. Patients and Methods: The study population was derived from 50828 and 256287 patients with invasive breast cancer in San Antonio breast cancer databases and the Surveillance, Epidemiology, and End Results (SEER) registry, respectively. Tumor biologic and clinical characteristics, local and systemic therapies, and survival according to the patient's age were analyzed. Survival was also compared with that of age-matched women from the general population. Results: In patients 55 years old or older, there was an association between increasing age at diagnosis and the presence of more favorable biologic characteristics of the tumor, including more tumors that express steroid receptors, lower proliferative rates, diploidy, normal p53, and absence of the expression of epidermal growth factor receptor and c-erbB2. In older patients with lymph node-negative disease and/or small tumors, the observed and expected survivals were almost identical. In the SEER registry, the 8-year survival of lymph node-negative patients relative to the expected survival of age-matched women from the general population was 1.01 (95% confidence interval [CI] = 0.98–1.04) for patients 70–74 years old, 1.06 (95% CI = 1.01–1.11) for patients 75–79 years old, and 1.09 (95% CI = 0.98–1.20) for patients 80–84 years old. Conclusion: In women 55 years old or older, advancing age is associated with more favorable tumor biology, and breast cancer survival in older women is similar to survival in the general population irrespective of disease status. This favorable outcome should be considered when making clinical decisions in older patients.
Hepatitis C Virus Infection Downregulates the Ligands of the Activating Receptor NKG2D
Authors: Chaoyang Wen, Xiang He, Hongfang Ma, Ningbo Hou, Congwen Wei, Ting Song, Yanhong Zhang, Liping Sun, Qingjun Ma, Hui Zhong
Journal: Cellular and Molecular Immunology (2008)
Hepatic mitochondrial oxidative metabolism and lipid peroxidation in experimental hexachlorobenzene-induced porphyria with dietary carbonyl iron overload†
Authors: Edward S. Feldman, Bruce R. Bacon
Journal: Hepatology (1989)

Both human porphyria cutanea tarda and experimental hexachlorobenzene-induced porphyria are associated with hepatic injury and are potentiated by excess hepatic iron. The mechanisms whereby cellular injury occurs and the synergistic role of iron overload are unknown. In the present experiments, we studied hepatic mitochondrial function and lipid peroxidation in rats with hexachlorobenzene-induced porphyria in which iron loading was achieved by dietary carbonyl iron supplementation. Female rats were treated for 8 weeks, receiving a chow diet supplemented with hexachlorobenzene (0.2%, w/w), carbonyl iron (1.0%, w/w) or hexachlorobenzene + iron. Hepatic total porphyrins were increased 100-fold in rats receiving hexachlorobenzene (hexachlorobenzene alone and hexachlorobenzene + Fe), and total hepatic iron was increased approximately 10-fold in rats receiving iron supplementation (Fe alone and hexachlorobenzene + Fe). There was a significant increase in mitochondrial lipid peroxidation in rats treated with hexachlorobenzene alone and hexachlorobenzene + Fe. A significant reduction in mitochondrial respiratory control ratios and in oxidative phosphorylation (ADP/O ratios) using glutamate and succinate as substrates was demonstrated when rats were treated with hexachlorobenzene + iron. The reductions in respiratory control ratios were due to a combination of an inhibitory defect in electron transport as evidenced by an irreversible decrease in State 3 respiration and an uncoupling effect as evidenced by an increase in State 4 respiration. These findings suggest that lipid peroxidation and mitochondrial dysfunction may contribute to the hepatotoxicity seen in hexachlorobenzene-induced porphyria.
The effects of an anti-CD4 monoclonal antibody, keliximab, on peripheral blood CD4+ T-cells in asthma
Authors: O.M. Kon, B.S. Sihra, L.C. Loh, J. Barkans, C.H. Compton, N.C. Barnes, M. Larché, A.B. Kay
Journal: European Respiratory Journal (2001)

CD4+ T-cells are likely to be involved as a source of pro-inflammatory cytokines in asthma. This study assessed the effects of an infusion of keliximab (IDEC CE9.1), an anti-CD4+ monoclonal antibody, on peripheral blood CD4+ T-cells in corticosteroid-dependent asthmatics. Three cohorts of patients (termed C 0.5 : n=6, C 1.5 : n=5, and C 3.0 : n=5) received a single infusion of 0.5, 1.5 or 3.0 mg·kg −1 , respectively, with a fourth receiving placebo (C pl : n=6), and were followed-up for 4 weeks. By flow cytometry in peripheral blood, pre- and postinfusion assessment was made of: a) CD4 and CD8 counts and mean fluorescence; b) CD25, human leukocyte antigen-DR (HLA-DR), CD45RO and CD45RA expression on CD4+ T-cells; and c) interferon (IFN)-γ, interleukin (IL)-4 and IL-5 expression in CD4+ T-cells. Keliximab's in vitro effects on allergen-specific peripheral blood mononuclear cells (PBMC) proliferation in atopic asthmatics were also evaluated. There was a significant increase in lung function (peak expiratory flow rate) in the C 3.0 group. Following infusion in C 0.5 , C 1.5 and C 3.0 but not C pl : 1) the CD4, but not CD8 count was significantly decreased; 2) there was total loss of Leu3a staining; 3) there were significant reductions in the mean fluorescence of OKT4 binding; and 4) there were significant reductions in the numbers of CD25, HLA-DR, CD45RO and CD45RA/CD4+ cells. There were no changes in CD4+ cell expression of IFN-γ, IL-4 or IL-5. Keliximab caused a significant reduction in T-cell proliferation as compared to a control monoclonal antibody. Keliximab, as an anti-CD4 monoclonal antibody, leads to a transient reduction in the number of CD4+ T-cells and modulation of CD4+ receptor expression in severe asthmatics. The effects of keliximab may be mediated through a decrease in CD4+ surface expression and T-lymphocyte numbers, in addition to a reduction in allergen-induced proliferation.
Mechanisms of regulation of G protein-coupled receptor kinases (GRKs) and cardiovascular disease
Authors: P PENELA, C MURGA, C RIBAS, A TUTOR, S PEREGRIN, F MAYORJR
Journal: Cardiovascular Research (2005)

The G protein-coupled receptor kinases (GRKs) participate with arrestins in the regulation and signal propagation of multiple G protein-coupled receptors (GPCR) of key physiological and pharmacological relevance in the cardiovascular system. The complex mechanisms of regulation of GRK expression, degradation and function are being unveiled gradually. The levels of these kinases are known to change in pathological situations such as heart failure, hypertrophy and hypertension, and in animal models of these diseases. A better understanding of the mechanisms underlying these changes and of how these alterations participate in the triggering or progression of cardiovascular disease may contribute to the design of novel diagnostic and therapeutic strategies.