tbuckley/cabot-search huggingface dataset:
P281 Impact of an Electronic Chronic Disease Management System For Chronic Obstructive Pulmonary Disease
Authors: A Sykes, M Nyadzayo, S Elkin
Journal: Thorax (2012)

<h3>Introduction and Objectives</h3> The chronic disease management system (CDMS) is an electronic patient record developed by healthcare professionals (HCP) across inner northwest London for care of patients with COPD. It was introduced across Imperial NHS and Central London Community Healthcare in January 2012. The aim was to improve patient management by promoting real time information sharing across and between organisations. The objectives of this study were to assess: The acceptability and use of the COPD CDMS by HCPs. Whether healthcare professionals using the system felt it benefitted patient care. <h3>Methods</h3> All healthcare professionals (42) in the integrated COPD MDT were asked to complete an anonymous questionnaire at month 3 after the introduction to paperless working and again four months (month 7) later to assess whether opinions had changed. <h3>Results</h3> 35/42 members of the COPD MDT completed questionnaires in March 2012 and 28/42 in July 2012. Initial questionnaire: 33 (94%) of healthcare professionals were using the COPD CDMS with 17 (52%) multiple times a day. The most frequent reasons for using the COPD CDMS was that it gave access to timely information pertinent to patient care (25/89%) and increasing information sharing across teams (25/89%). 19 (58%) felt it improved patient care and 10 (35%) users felt it improved the patient’s experience. 18 (55%) rated the system as very or extremely useful. Repeat Questionnaire: Responses in the follow up questionnaire were similar to the initial results with a similar number using it (89%) and rating it as very or extremely useful (52%). The system was also being used more out of hours (17% - 32%) and there were increases in the number of users who believe it improves patient experience (45%) and care (67%). Table 1 indicates factors influencing the use of COPD CDMS by HCP. <h3>Conclusions</h3> Introduction of an electronic patient record is acceptable to the integrated COPD teams. The majority will use from day 1 with no drop off of use over 7 months. Over time, out of hours usage increases and the belief using the electronic record improves patient care increases. This information will help others who plan similar changes across their care communities. <h3>Acknowledgements</h3> NW London CLAHRC.
Family History and Cardiovascular Risk in Familial Hypercholesterolemia
Authors: Albert Wiegman, Jessica Rodenburg, Saskia de Jongh, Joep C. Defesche, Henk D. Bakker, John J.P. Kastelein, Eric J.G. Sijbrands
Journal: Circulation (2003)

Elevated LDL cholesterol (LDL-C) levels in childhood predict cardiovascular disease (CVD) later in life. Familial hypercholesterolemia (FH) represents the paradigm of this relation.The objectives of this study were to (1) establish the LDL-C level that provides the most accurate diagnosis of FH in children from families with known FH and (2) assess whether lipoprotein variation in these children is associated with premature CVD in relatives. Foremost, however, it was our objective to identify children with FH who are at high risk and in need of early intervention. A total of 1034 consecutive children from FH kindreds were investigated. First, LDL-C levels >3.50 mmol/L had a 0.98 post-test probability (95% CI, 0.96 to 0.99) of predicting the presence of an LDL receptor mutation. Second, children with FH in the highest LDL-C tertile (>6.23 mmol/L) had a 1.7-times higher incidence (95% CI, 1.24 to 2.36) of having a parent with FH suffering from premature CVD (P=0.001). In addition, such a parent was found 1.8 times more often (95% CI, 1.20 to 2.59) among children with FH who had HDL-C <1.00 mmol/L (P=0.004). Last, children with FH whose lipoprotein(a) was >300 mg/L had a 1.45-times higher incidence (95% CI, 0.99 to 2.13) of having a parent with FH suffering from premature CVD (P=0.05).In FH families, LDL-C levels allow accurate diagnosis of FH in childhood. Moreover, increased LDL-C and lipoprotein(a) and decreased HDL-C levels in children identify FH kindreds with the highest CVD risk.
Virus Binding to a Plasma Membrane Receptor Triggers Interleukin-1α-Mediated Proinflammatory Macrophage Response In Vivo
Authors: Nelson C. Di Paolo, Edward A. Miao, Yoichiro Iwakura, Kaja Murali-Krishna, Alan Aderem, Richard A. Flavell, Thalia Papayannopoulou, Dmitry M. Shayakhmetov
Journal: Immunity (2009)
High-throughput oncogene mutation profiling in human cancer
Authors: Roman K Thomas, Alissa C Baker, Ralph M DeBiasi, Wendy Winckler, Thomas LaFramboise, William M Lin, Meng Wang, Whei Feng, Thomas Zander, Laura E MacConaill, Jeffrey C Lee, Rick Nicoletti, Charlie Hatton, Mary Goyette, Luc Girard, Kuntal Majmudar, Liuda Ziaugra, Kwok-Kin Wong, Stacey Gabriel, Rameen Beroukhim, Michael Peyton, Jordi Barretina, Amit Dutt, Caroline Emery, Heidi Greulich, Kinjal Shah, Hidefumi Sasaki, Adi Gazdar, John Minna, Scott A Armstrong, Ingo K Mellinghoff, F Stephen Hodi, Glenn Dranoff, Paul S Mischel, Tim F Cloughesy, Stan F Nelson, Linda M Liau, Kirsten Mertz, Mark A Rubin, Holger Moch, Massimo Loda, William Catalona, Jonathan Fletcher, Sabina Signoretti, Frederic Kaye, Kenneth C Anderson, George D Demetri, Reinhard Dummer, Stephan Wagner, Meenhard Herlyn, William R Sellers, Matthew Meyerson, Levi A Garraway
Journal: Nature Genetics (2007)
Renal Expression of Fibrotic Matrix Proteins and of Transforming Growth Factor-β (TGF-β) Isoforms in TGF-β Transgenic Mice
Authors: MIKLOS M. MOZES, ERWIN P. BÖTTINGER, TERRY A. JACOT, JEFFREY B. KOPP
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Renal pathology in mice that are transgenic for the murine albumin enhancer/promoter linked to a full-length porcine transforming growth factor-β1 (TGF-β1) gene has been described previously. In these mice, transgene expression is limited to the liver and the plasma level of TGF-β is increased. The earliest renal pathologic change is glomerulosclerosis, at 3 wk of age, and this is followed by tubulointerstitial fibrosis. In this study, it was hypothesized that circulating TGF-β1 increases renal extracellular matrix accumulation and activates local TGF-β gene expression. Immunostaining at 5 wk revealed increased amounts of collagen I and III within the mesangium, glomerular capillary loops, and interstitium, while the amount of collagen IV was normal. Similarly, Northern analysis showed increased expression of mRNA encoding collagen I and III, as well as biglycan and decorin, while the expression of collagen IV was unchanged. These changes began as early as 1 wk of age, a time before the appearance of glomerulosclerosis. To evaluate matrix degradation, collagenase IV activity was evaluated by gelatin zymography and an increase in matrix metalloproteinase-2 was found. Finally, the production of tissue inhibitors of metalloproteinase was evaluated. Tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA was increased 18-fold, while TIMP-2 and TIMP-3 were unchanged. In 2-wk-old transgenic kidney, local expression of TGF-β1, β2, and β3 protein was similar to wild-type mice. In 5-wk-old transgenic mice, TGF-β1 and β2 protein was present in increased amounts within glomeruli, and renal TGF-β1 mRNA was increased threefold. It is concluded that elevated levels of circulating TGF-β1 may act on the kidney to increase matrix protein production and decrease matrix remodeling. Only after glomerulosclerosis is established does local glomerular overproduction of TGF-β become manifest.
Pulmonary artery pseudoaneurysm secondary to metastatic angiosarcoma
Authors: P P Agarwal
Journal: Thorax (2006)

Pulmonary artery pseudoaneurysm secondary to metastatic angiosarcoma A 70 year old woman presented to the emergency department with haemoptysis and right sided chest pain.Of significance was a prior history of angiosarcoma arising from soft tissues in the neck.A contrast enhanced helical CT scan of the thorax was performed to exclude pulmonary emboli.Multiple lung nodules were seen, some of which were cavitary.This was associated with a small left hydropneumothorax and a small right pleural effusion (fig 1A).Several lung nodules were surrounded by ground glass opacity, and one of the right lower lobe lung metastases was observed to be contiguous with a subsegmental branch of the right anterior basal pulmonary artery and a pseudoaneurysm (fig 1B) which was better appreciated on the maximum intensity projection (MIP) image (fig 2).There was no history of pulmonary angiography, Swan-Ganz catheterisation, percutaneous needle biopsy of the lung, or pneumonia.The patient had no further haemoptysis and the chest pain abated on its own after a few hours so, because of her age and diffuse metastatic disease, no intervention was performed.It is presumed that the pseudoaneurysm resulted from erosion of an angiosarcoma metastasis into a subsegmental pulmonary artery resulting in haemoptysis.Angiosarcoma lung metastases are commonly solid nodules and thin walled cysts often admixed with haemorrhage. 1 The CT halo sign (lung nodule with surrounding ground glass density) has been described in angiosarcoma metastases because of haemorrhage into the surrounding lung parenchyma.Subpleural cystic lesions can give rise to pneumothorax, as illustrated in this case.However, pulmonary artery pseudoaneurysm is an unusual and previously unreported manifestation of angiosarcoma metastases.Pulmonary artery pseudoaneurysms are commonly iatrogenic or mycotic in origin. 2 They have rarely been reported secondary to tumours.
REDEEM: A Pragmatic Trial to Reduce Diabetes Distress
Authors: Lawrence Fisher, Danielle Hessler, Russell E. Glasgow, Patricia A. Arean, Umesh Masharani, Diana Naranjo, Lisa A. Strycker
Journal: Diabetes Care (2013)

To compare three interventions to reduce diabetes distress (DD) and improve self-management among non-clinically depressed adults with type 2 diabetes mellitus (T2DM).In REDEEM, 392 adults with T2DM and DD were randomized to computer-assisted self-management (CASM), CASM plus DD-specific problem solving (CAPS), or a computer-administered minimal supportive intervention. Primary outcomes were Diabetes Distress Scale (DDS) total, the Emotional Burden (EB) and Regimen Distress (RD) DDS subscales, and diet, exercise, and medication adherence.Significant and clinically meaningful reductions in DD (DDS, EB, and RD) and self-management behaviors occurred in all three conditions (P < 0.001), with no significant between-group differences. There was, however, a significant group × baseline distress interaction (P < 0.02), in which patients with high baseline RD in the CAPS condition displayed significantly larger RD reductions than those in the other two conditions. RD generated the most distress and displayed the greatest distress reduction as a result of intervention. The pace of DD reduction varied by patient age: older patients demonstrated significant reductions in DD early in the intervention, whereas younger adults displayed similar reductions later. Reductions in DD were accompanied by significant improvements in healthy eating, physical activity, and medication adherence, although not by change in HbA1c.DD is malleable and highly responsive to intervention. Interventions that enhance self-management also reduce DD significantly, but DD-specific interventions may be necessary for patients with high initial levels of DD. Future research should identify the minimal, most cost-effective interventions to reduce DD and improve self-management.
Lymphocytic bronchitis/bronchiolitis in a patient with primary biliary cirrhosis
Authors: G Chatte, N Streichenberger, O Boillot, D Gille, R Loire, JF Cordier
Journal: European Respiratory Journal (1995)

A 39 year old woman with severe primary biliary cirrhosis progressively developed exercise dyspnoea due to airflow obstruction. Sjogren's syndrome was not present. Bronchial and pulmonary biopsies demonstrated constrictive lymphocytic bronchitis/bronchiolitis, possibly a component of a generalized autoimmune process in this patient.
Insulin Resistance and Hyperinsulinemia
Authors: Alfredo Quiñones Galvan, Fabio Galetta, Andrea Natali, Elza Muscelli, Anna Maria Sironi, Giuseppe Cini, Stefania Camastra, Ele Ferrannini
Journal: Circulation (2000)

Background —Hyperinsulinemia and insulin resistance may contribute to the development of cardiac hypertrophy. In humans, however, the evidence is inconclusive. Methods and Results —We studied 50 nondiabetic subjects covering a wide range of age (20 to 65 years), body mass index (BMI, 19 to 40 kg · m − 2 ), and mean blood pressure (72 to 132 mm Hg). Plasma insulin concentrations and secretory rates were measured at baseline and during an oral glucose tolerance test; insulin sensitivity was measured by the insulin clamp technique. Left ventricular mass (LVM) (by 2D M-mode echocardiography) was distributed normally and was higher in obese (BMI ≥27 kg · m − 2 , n=16) or hypertensive patients (blood pressure &gt;140/90 mm Hg, n=21) (50±8 and 55±10 g · m − 2.7 , respectively) than in 13 nonobese, normotensive subjects (40±8 g · m − 2.7 , P =0.0004). In a multivariate model adjusting for sex, age, BMI, and blood pressure, neither insulin concentrations (fasting or postglucose) nor insulin sensitivity or secretory rates were significant correlates of LVM. Systolic blood pressure ( P =0.003) and BMI ( P =0.01) were the only independent correlates of LVM. From the regression, the impact of hypertension (as a systolic pressure of 180 versus 140 mm Hg=+20%) was twice as large as that of obesity (as a BMI of 35 versus 25 kg · m − 2 =+11%), the two factors being additive. Conclusions —When adequate account is taken of body mass and blood pressure, insulin, as concentration, secretion, or action, is not an independent determinant of LVM in nondiabetic subjects.
Nasal potential difference: a clinical diagnostic test for cystic fibrosis
Authors: EW Alton, D Currie, R Logan-Sinclair, JO Warner, ME Hodson, DM Geddes
Journal: European Respiratory Journal (1990)

Patients with cystic fibrosis (CF) demonstrate a markedly more negative potential difference (PD) across respiratory epithelia than normal or "diseased" controls. A technique is described for the measurement of nasal PD in both children and adults. 145 non-CF subjects showed a mean PD of -19.0 mV (range -2 to -36) in comparison to 60 patients with cystic fibrosis with mean of -46.0 mV (range -32 to -77). Amongst the latter group those with more severe disease had a more negative PD. Measurement of nasal PD is easily learnt and rapidly performed and may provide an additional means of diagnosis for CF.
MEGA5: Molecular Evolutionary Genetics Analysis Using Maximum Likelihood, Evolutionary Distance, and Maximum Parsimony Methods
Authors: K. Tamura, D. Peterson, N. Peterson, G. Stecher, M. Nei, S. Kumar
Journal: Molecular Biology and Evolution (2011)

Comparative analysis of molecular sequence data is essential for reconstructing the evolutionary histories of species and inferring the nature and extent of selective forces shaping the evolution of genes and species. Here, we announce the release of Molecular Evolutionary Genetics Analysis version 5 (MEGA5), which is a user-friendly software for mining online databases, building sequence alignments and phylogenetic trees, and using methods of evolutionary bioinformatics in basic biology, biomedicine, and evolution. The newest addition in MEGA5 is a collection of maximum likelihood (ML) analyses for inferring evolutionary trees, selecting best-fit substitution models (nucleotide or amino acid), inferring ancestral states and sequences (along with probabilities), and estimating evolutionary rates site-by-site. In computer simulation analyses, ML tree inference algorithms in MEGA5 compared favorably with other software packages in terms of computational efficiency and the accuracy of the estimates of phylogenetic trees, substitution parameters, and rate variation among sites. The MEGA user interface has now been enhanced to be activity driven to make it easier for the use of both beginners and experienced scientists. This version of MEGA is intended for the Windows platform, and it has been configured for effective use on Mac OS X and Linux desktops. It is available free of charge from http://www.megasoftware.net.
Immunohistochemical evidence of disease recurrence after liver transplantation for primary biliary cirrhosis
Authors: J Van de Water
Journal: Hepatology (1996)

Whether primary biliary cirrhosis (PBC) recurs after liver transplantation has remained an interesting and controversial issue; rejection, viral hepatitis, and drug effects all may mimic recurrent PBC histologically and biochemically. Furthermore, reliable clinical criteria for PBC recurrence are lacking. In this study, the issue of disease recurrence using a well-characterized monoclonal antibody (MAb), C355.1, that reacts with the immunodominant mitochondrial autoantigen of PBC (pyruvate dehydrogenase complex [PDC-E2]) was addressed. When used in an immunohistochemical assay, C355.1 produces intense apical staining of bile duct epithelium specifically in liver sections of patients with PBC and may be the earliest known marker of PBC. Immunohistochemical and histological analysis of serial liver biopsy specimens of 67 patients pre- and post-orthotopic liver transplantation (OLT), including 38 patients with PBC and 29 non-PBC liver disease controls, was performed. Sections were stained with MAb C355.1 or the control MAb C315 and analyzed to determine whether there was a recurrence of apical reactivity in the bile ducts of the posttransplantation biopsy specimens. The immunohistochemical staining was correlated with the histological findings and serum biochemistries at the time of the biopsy. Our data indicate that a significant number of patients who underwent transplantation for PBC (28 of 38) but not controls (0 of 29) develop a staining pattern of liver bile duct epithelium with MAb C355.1 that is indistinguishable from the pretransplantation pattern. Of the 28 patients with this apical staining pattern, 8 were characterized histologically as possible recurrent PBC, 2 as chronic rejection, 2 as acute rejection, 9 as nonspecific changes, 4 as normal or near normal, and 3 had other histological changes. Only 50% of the patients with apical C355.1 staining had liver enzyme levels suggestive of cholestasis. Thus, there appears to be immunohistochemical evidence that supports the concept of recurrence of PBC after OLT. The appearance of biliary epithelial abnormalities before the clinical appearance of disease is important not only for liver transplantation but also for understanding the natural history of PBC.
We are both doctors: an Israeli doctor writes to a Palestinian colleague
Authors: A. M. Clarfield
Journal: BMJ (2014)

<b>A Mark Clarfield</b> reflects on life in a war zone, sharing his thoughts on the violence with an imagined Palestinian colleague in Gaza. Read a Palestinian doctor’s response (<i>BMJ</i> 2014;349:g5106, doi:10.1136/bmj.g5106)
IMMUNOCHEMICAL STUDIES ON THE SPECIFICITY OF CELLULAR HYPERSENSITIVITY
Authors: John R. David, Stuart F. Schlossman
Journal: The Journal of Experimental Medicine (1968)

The immunochemical specificity of antigen-induced inhibition of peritoneal exudate cell migration was studied in animals sensitized to chemically defined alpha,DNP(Lys)(18) peptides. It was shown that sensitized peritoneal exudate cells could discriminate between various DNP-oligolysines. Only immunogenic members of the homologous series of alpha,DNP-L-lysines equal to or larger in size than the heptamer inhibited the migration of specifically sensitized peritoneal exudate cells. In contrast, nonimmunogenic alpha,DNP-L-lysines, a D-lysine containing stereoisomer of alpha,DNP L(Lys)(9) (alpha,DNP-L(4)DL(4)) and (Lys)(9)epsilon, DNP were not inhibitory to the migration of peritoneal exudate cells derived from animals immunized to alpha,DNP(Lys)(18). The exquisite specificity of the in vitro reaction of sensitized cells with antigen contrasts with the previously observed in vivo or in vitro specificity of anti-alpha,-DNP(Lys)(n) antibody, but parallels the specificity of the in vivo delayed or anamnestic response. These results suggest the presence of a still undefined but highly specific binding site, which functions as the cellular receptor for antigen on the sensitized lymphoid cell or on some "processing" cell.
Can right ventricular performance be assessed by equilibrium radionuclide ventriculography?
Authors: Q F Xue, W MacNee, D C Flenley, W J Hannan, C J Adie, A L Muir
Journal: Thorax (1983)

Although right ventricular function may be examined by following the passage (first pass) of a bolus of radionuclide through the right heart before it reaches the left heart, the counts detected with conventional gamma cameras in such a short time interval are low; moreover, repeated determinations would result in an unacceptable radiation burden to the patient. We have modified the gated equilibrium blood pool method to allow repeated assessment of the right ventricular ejection fraction (RVEF) and have compared the results with the first-pass method in 43 patients. Good agreement was obtained between the two methods (r = 0.91, p less than 0.001). The mean difference between the two methods was 0.04 with an intra-observer variation for the equilibrium studies of 0.03 and an inter-observer difference of 0.04. The mean difference in RVEF for seven patients studied on two separate occasions 30 minutes apart was only 0.02. In four patients the mean RVEF measured at rest was 0.44 +/- 0.05 (SEM) and after exercise it was 0.48 +/- 0.06. After infusion of isoprenaline at 1 microgram/min the mean rose to 0.64 +/- 0.04 (p less than 0.02) and after infusion of a new beta 1-sympathomimetic agent, prenalterol, at doses of 1 and 2 mg it was 0.56 +/- 0.02 (p less than 0.02) and 0.59 +/- 0.03 (p less than 0.01) respectively, where the significance levels are relative to the resting values. In nine patients with good ventricular function the vasodilator nifedipine caused right and left ventricular ejection fractions to increase by the same amount; while in six patients with severe impairment of left ventricular function due to ischaemic heart disease the RVEF increased from 0.58 +/- 0.03 to 0.73 +/- 0.03 (p less than 0.01) after 2 mg of prenalterol, but the left ventricular ejection fraction increased only from 0.22 +/- 0.04 to 0.26 +/- 0.04. We conclude that repeated estimation of right ventricular performance is possible by equilibrium radionuclide ventriculography.
Identification of Amino Acid Residues Important for Ligand Binding to Fas
Authors: Gary C. Starling, Jürgen Bajorath, John Emswiler, Jeffrey A. Ledbetter, Alejandro Aruffo, Peter A. Kiener
Journal: The Journal of Experimental Medicine (1997)

The interaction of Fas (CD95), a member of the tumor necrosis factor receptor (TNFR) family, and its ligand (FasL) triggers programmed cell death (apoptosis) and is involved in the regulation of immune responses. Although the Fas-FasL interaction is conserved across species barriers, little is currently known about the molecular details of this interaction. Our aim was to identify residues in Fas that are important for ligand binding. With the aid of a Fas molecular model, candidate amino acid residues were selected in the Fas extracellular domain 2 (D2) and D3 and subjected to serine-scanning mutagenesis to produce mutant Fas molecules in the form of Ig fusion proteins. The effects of these mutations on FasL binding was examined by measuring the ability of these proteins to inhibit FasL-mediated apoptosis of Jurkat cells and bind FasL in ELISA and BIAcore assays. Mutation of two amino acids, R86 and R87 (D2), to serine totally abolished the ability of Fas to interact with its ligand, whereas mutants K84S, L90S, E93S (D2), or H126S (D3) showed reduced binding compared with wild-type Fas. Two mutants (K78S and H95S) bound FasL comparably to wild type. Therefore, the binding of FasL involves residues in two domains that correspond to positions critical for ligand binding in other family members (TNFR and CD40) but are conserved between murine and human Fas.