tbuckley/cabot-search huggingface dataset:
The ‘crossover’ tip-stitch in O-T flap repair
Authors: W. Hussain, P.J.M. Salmon, N.J. Mortimer
Journal: British Journal of Dermatology (2009)

Journal Article The ‘crossover’ tip‐stitch in O‐T flap repair Get access W. Hussain, W. Hussain Dermatological Surgical Unit, Skin Centre Specialist Medical Facility, 171 Cameron Road, Mount Maunganui, New Zealand E‐mail: dr_w_hussain@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar P.J.M. Salmon, P.J.M. Salmon Dermatological Surgical Unit, Skin Centre Specialist Medical Facility, 171 Cameron Road, Mount Maunganui, New Zealand E‐mail: dr_w_hussain@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar N.J. Mortimer N.J. Mortimer Dermatological Surgical Unit, Skin Centre Specialist Medical Facility, 171 Cameron Road, Mount Maunganui, New Zealand E‐mail: dr_w_hussain@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 1, 1 January 2010, Pages 219–220, https://doi.org/10.1111/j.1365-2133.2009.09524.x Published: 01 January 2010
Changes in Antitumor Response in C57BL/6J-Min/+ Mice during Long-term Administration of a Selective Cyclooxygenase-2 Inhibitor
Authors: Adelaide M. Carothers, Amy E. Moran, Nancy L. Cho, Mark Redston, Monica M. Bertagnolli
Journal: Cancer Research (2006)

Abstract Selective cyclooxygenase-2 (COX-2) inhibitors are widely prescribed for severe arthritis and are currently under study in human chemoprevention trials. Recently, long-term use of these agents has come under scrutiny due to reports of treatment-associated cardiovascular toxicity. On short-term administration, the selective COX-2 inhibitor celecoxib inhibits adenoma growth in animal tumor models, including the C57BL/6J-Min/+ (Min/+) mouse. With uninterrupted long-term celecoxib administration, intestinal tumors in Min/+ mice initially regressed and then recurred to levels comparable with untreated controls. Celecoxib treatment initially suppressed COX-2 and prostaglandin E2 (PGE2) expression, but long-term use produced significantly higher levels of these molecules and reactivated PGE2-associated growth factor signaling pathways in tumor and normal tissues. These results indicate that COX-2 is an important chemoprevention target and that inhibition of this enzyme alters a paracrine enterocyte regulatory pathway. Chronic uninterrupted celecoxib treatment, however, induces untoward effects that enhance early progression events in intestinal tumorigenesis and may contribute to treatment toxicity. (Cancer Res 2006; 66(12): 6432-8)
Increasing Anticarcinoma Activity of an Anti-erbB2 Recombinant Immunotoxin by the Addition of an Anti-EpCAM sFv
Authors: Brad J. Stish, Hua Chen, Yanqun Shu, Angela Panoskaltsis-Mortari, Daniel A. Vallera
Journal: Clinical Cancer Research (2007)

Abstract Purpose: erbB2, the product of the Her2-neu gene, is a well-established therapeutic target for antibody-based biologicals, but anti-erbB2 antibody-toxin fusion proteins are limited in their activity. The goal of this study was to determine if genetically adding an sFv targeting epithelial cell adhesion molecule (EpCAM) to an anti-Her2 sFv immunotoxin would result in enhanced antitumor activity. Experimental Design: In vitro studies were done in which the new bispecific immunotoxin DTEpCAM23 was compared with monospecific immunotoxins (DTEpCAM and DT23) to quantitate immunotoxin activity. Mixtures of monospecific immunotoxins were tested to determine if they were as effective as the bispecific immunotoxin. Binding and internalization studies were also done. In vivo, bispecific immunotoxins were given i.t. to athymic nude mice bearing HT-29 human colon cancer flank tumors and i.p. to mice with i.p. tumors. Results: DTEpCAM23 bispecific immunotoxins showed far greater activity than monospecific immunotoxin (sometimes over 2,000-fold) against most tumor lines. Bispecific immunotoxin was superior and selective in its activity against different carcinoma cell lines. Bispecific immunotoxin had greater activity than monospecific immunotoxin indicating an advantage of having both sFv on the same single-chain molecule. Binding and internalization studies did not explain the differences between bispecific immunotoxin and monospecific immunotoxin activity. Orientation of the sFvs on the molecule had a significant effect on in vitro and in vivo properties. The bispecific immunotoxins were more effective than the monospecific immunotoxin in the flank tumor mouse model. Conclusions: The synthesis of bispecific immunotoxin created a new biological agent with superior in vitro and in vivo activity (over monospecific immunotoxin), more broad reactivity, more efficacy against tumors in vivo, and diminished toxic effects in mice.
Acute Hypoglycemia Decreases Myocardial Blood Flow Reserve in Patients With Type 1 Diabetes Mellitus and in Healthy Humans
Authors: Omar Rana, Christopher D. Byrne, David Kerr, David V. Coppini, Soha Zouwail, Roxy Senior, Joe Begley, Jeremy J. Walker, Kim Greaves
Journal: Circulation (2011)

Hypoglycemia is associated with increased cardiovascular mortality, but the reason for this association is poorly understood. We tested the hypothesis that the myocardial blood flow reserve (MBFR) is decreased during hypoglycemia using myocardial contrast echocardiography in patients with type 1 diabetes mellitus (DM) and in healthy control subjects.Twenty-eight volunteers with DM and 19 control subjects underwent hyperinsulinemic clamps with maintained sequential hyperinsulinemic euglycemia (plasma glucose, 90 mg/dL [5.0 mmol/L]) followed by hyperinsulinemic hypoglycemia (plasma glucose, 50 mg/dL [2.8 mmol/L]) for 60 minutes each. Low-power real-time myocardial contrast echocardiography was performed with flash impulse imaging using low-dose dipyridamole stress at baseline and during hyperinsulinemic euglycemia and hyperinsulinemic hypoglycemia. In control subjects, MBFR increased during hyperinsulinemic euglycemia by 0.57 U (22%) above baseline (B coefficient, 0.57; 95% confidence interval, 0.38 to 0.75; P<0.0001) and decreased during hyperinsulinemic hypoglycemia by 0.36 U (14%) below baseline values (B coefficient, -0.36; 95% confidence interval, -0.50 to -0.23; P<0.0001). Although MBFR was lower in patients with DM at baseline by 0.37 U (14%; B coefficient, -0.37; 95% confidence interval, -0.55 to -0.19; P=0.0002) compared with control subjects at baseline, the subsequent changes in MBFR during hyperinsulinemic euglycemia and hyperinsulinemic hypoglycemia in DM patients were similar to that observed in control subjects. Finally, the presence of microvascular complications in the patients with DM was associated with a reduction in MBFR of 0.52 U (24%; B coefficient, -0.52; 95% confidence interval, -0.70 to -0.34; P<0.0001).Hypoglycemia decreases MBFR in both healthy humans and patients with DM. This finding may explain the association between hypoglycemia and increased cardiovascular mortality in susceptible individuals.
ATP-Binding Cassette Transporter A1 Gene Transcription Is Downregulated by Activator Protein 2α
Authors: Noriyuki Iwamoto, Sumiko Abe-Dohmae, Makoto Ayaori, Nobukiyo Tanaka, Masatoshi Kusuhara, Fumitaka Ohsuzu, Shinji Yokoyama
Journal: Circulation Research (2007)

ATP-binding cassette transporter A1 (ABCA1) is a rate-limiting factor for high-density lipoprotein (HDL) biogenesis. The ABCA1 gene expression is known to be upregulated by various transcriptional factors. However, negative regulation factors would be better targets for pharmacological modulation of HDL biogenesis. Doxazosin, an alpha(1)-adrenoceptor blocker, increased ABCA1 mRNA, its protein, and apolipoprotein A-I-mediated HDL biogenesis in THP-1 macrophages and CHO-K1 cells, independent of alpha(1)-adrenoceptor blockade. Analysis of the human ABCA1 promoter indicated that the region between the positions -368 and -147 that contains an activator protein (AP)2-binding site responsible for the effects of doxazosin. Overexpression of AP2alpha inhibited ABCA1 transcription in a dose-dependent fashion. Mutation in the AP2-binding site caused increase of the basal promoter activity and cancelling both the transactivation by doxazosin and the trans-repression by AP2alpha. Doxazosin had no effect on ABCA1 mRNA level in HepG2 cells, which lack endogenous AP2alpha, and it reversed the inhibitory effect of AP2alpha expression in this type of cells. Chromatin immunoprecipitation and gel shift assays revealed that doxazosin reduced specific binding of AP2alpha to the ABCA1 promoter, as it suppressed phosphorylation of AP2alpha. Finally, doxazosin increased ABCA1 expression and plasma HDL in mice. We thus concluded that AP2alpha negatively regulates the ABCA1 gene transcription. Doxazosin inhibits AP2alpha activity independent of alpha(1)-adrenoceptor blockade and increases the ABCA1 expression and HDL biogenesis. AP2alpha is a potent pharmacological target for the increase of HDL.
Functional TLR5 Genetic Variants Affect Human Colorectal Cancer Survival
Authors: Sascha N. Klimosch, Asta Försti, Jana Eckert, Jelena Knežević, Melanie Bevier, Witigo von Schönfels, Nils Heits, Jessica Walter, Sebastian Hinz, Jesus Lascorz, Jochen Hampe, Dominik Hartl, Julia-Stefanie Frick, Kari Hemminki, Clemens Schafmayer, Alexander N.R. Weber
Journal: Cancer Research (2013)

Abstract Toll-like receptors (TLR) are overexpressed on many types of cancer cells, including colorectal cancer cells, but little is known about the functional relevance of these immune regulatory molecules in malignant settings. Here, we report frequent single-nucleotide polymorphisms (SNP) in the flagellin receptor TLR5 and the TLR downstream effector molecules MyD88 and TIRAP that are associated with altered survival in a large cohort of Caucasian patients with colorectal cancer (n = 613). MYD88 rs4988453, a SNP that maps to a promoter region shared with the acetyl coenzyme-A acyl-transferase-1 (ACAA1), was associated with decreased survival of patients with colorectal cancer and altered transcriptional activity of the proximal genes. In the TLR5 gene, rs5744174/F616L was associated with increased survival, whereas rs2072493/N592S was associated with decreased survival. Both rs2072493/N592S and rs5744174/F616L modulated TLR5 signaling in response to flagellin or to different commensal and pathogenic intestinal bacteria. Notably, we observed a reduction in flagellin-induced p38 phosphorylation, CD62L shedding, and elevated expression of interleukin (IL)-6 and IL-1β mRNA in human primary immune cells from TLR5 616LL homozygote carriers, as compared with 616FF carriers. This finding suggested that the well-documented effect of cytokines like IL-6 on colorectal cancer progression might be mediated by TLR5 genotype-dependent flagellin sensing. Our results establish an important link between TLR signaling and human colorectal cancer with relevance for biomarker and therapy development. Cancer Res; 73(24); 7232–42. ©2013 AACR.
The impact of hemoglobin levels on fatigue and quality of life in cancer patients
Authors: B. Holzner, G. Kemmler, R. Greil, M. Kopp, A. Zeimet, M. Raderer, M. Hejna, S. Zöchbauer, G. Krajnik, H. Huber, W.W. Fleischhacker, B. Sperner-Unterweger
Journal: Annals of Oncology (2002)
Induction of T lymphocyte apoptosis by sulphasalazine in patients with Crohn's disease
Authors: J Doering
Journal: Gut (2004)

Lamina propria T lymphocytes (LPL) of the intestinal mucosa are chronically activated in Crohn's disease (CD). Defective apoptosis of activated LPL was proposed as a key pathogenic mechanism. In fact, increased expression of antiapoptotic molecules was observed in CD LPL. In the present work, we aimed to analyse the effects and underlying molecular mechanisms of 5-amino salicylic acid (5-ASA) and derivatives on apoptosis of LPL and peripheral blood lymphocytes (PBL) in patients with CD compared with ulcerative colitis (UC) and in non-inflammatory controls.PBL and LPL were isolated by Ficoll-Hypopaque gradient centrifugation and the EGTA-collagenase method, respectively. PBL/LPL were stimulated with FasL, 5-ASA, sulphapyridine, and sulphasalazine for 24/48 hours and apoptosis was quantified by flow cytometry (annexin V- propidium iodide method) and immunofluorescence. The molecular mechanisms of drug induced apoptosis were analysed in wild-type and FADD-/- Jurkat T cells using western blots and caspase assays.While PBL displayed a normal apoptosis pattern after Fas stimulation in patients with active CD, LPL from inflammatory areas were highly resistant. Comparable resistance to apoptosis was observed in LPL of UC patients. In contrast with 5-ASA, which did not induce apoptosis in lymphocytes, sulphasalazine proved to be a potent proapoptotic agent. Sulphasalazine induced T lymphocyte apoptosis was independent of the Fas pathway but associated with marked downregulation of antiapoptotic bcl-xl and bcl2, activation of the mitochondrial apoptosis signalling pathway, and subsequent activation of caspase-9 and caspase-3.The beneficial effect of sulphasalazine in treating inflammatory bowel disease is at least in part attributable to its proapoptotic effects on LPL which allows potent downregulation of lymphocyte activation.
Echocardiographic Evaluation in Asymptomatic Relatives of Patients with Dilated Cardiomyopathy Reveals Preclinical Disease
Authors: Niall G. Mahon, Ross T. Murphy, Calum A. MacRae, Alida L.P. Caforio, Perry M. Elliott, William J. McKenna
Journal: Annals of Internal Medicine (2005)

Background: Idiopathic dilated cardiomyopathy is often familial, and apparently healthy relatives may have latent, early, or undiagnosed established disease. Objective: To determine the prevalence and natural history of asymptomatic cardiac abnormalities among sampled relatives of unselected patients referred for management of dilated cardio-myopathy. Design: Prospective cohort study. Patients: 767 asymptomatic relatives of 189 consecutive unselected patients with dilated cardiomyopathy. Measurements: Clinical evaluation, including history, physical examination, electrocardiography, and echocardiography, was performed. Participants were classified in accordance with published echocardiographic criteria. Sampled relatives who did not have evidence of dilated cardiomyopathy at the initial evaluation were followed for a median of 57 months (range, 1 to 133 months). Results: Of the 767 patients evaluated, 592 (77.2%) were assessed as healthy, 35 (4.6% [95% CI, 3.7% to 7.6%]) had dilated cardiomyopathy, 119 (15.5% [CI, 12.5% to 18.8%]) had left ventricular enlargement without systolic dysfunction, and 21 (2.7% [CI, 1.9% to 4.9%]) had depressed fractional shortening without ventricular dilatation. At follow-up, progression to dilated cardiomyopathy occurred in 13 (10%) relatives with left ventricular enlargement or depressed fractional shortening versus 3 (1.3%) healthy relatives. In a multivariate model, only left ventricular enlargement or depressed fractional shortening independently predicted progression to dilated cardiomyopathy (hazard ratio, 10.0 [CI, 2.8 to 35.5]; P < 0.001). Limitations: Because relatives had to be willing to participate and be available geographically, selection bias may have occurred. Conclusion: Treatable asymptomatic dilated cardiomyopathy was identified in 4.6% of asymptomatic relatives. In addition, left ventricular enlargement and depressed fractional shortening were common in asymptomatic relatives of patients with dilated cardiomyopathy and were associated with a statistically significant medium-term risk for disease progression. Evaluation of relatives of patients with cardiomyopathy is recommended.
A multi-centre, blinded, randomised, placebo-controlled, laboratory-based study of MQX-503, a novel topical gel formulation of nitroglycerine, in patients with Raynaud phenomenon
Authors: Laura K Hummers, Carin E Dugowson, Frederick J Dechow, Robert A Wise, Jeffrey Gregory, Joel Michalek, Gayane Yenokyan, John McGready, Fredrick M Wigley
Journal: Annals of the Rheumatic Diseases (2012)

Objective MQX-503 is a novel nitroglycerine preparation designed to absorb quickly and allow local vasodilatation in the skin. We examined the efficacy and tolerability of this medication in Raynaud phenomenon (RP) in a laboratory-based study. Methods In this multi-centre, double-blind, randomised, placebo-controlled, cross-over study, subjects were treated with 0.5% or 1.25% nitroglycerine or placebo gel. Subjects received each dose twice in a randomised order. Each study session consisted of baseline laser Doppler measurements, study gel application and 5 min of cold chamber exposure (−20°C). Blood flow (BF) was measured at the end of exposure and for the next 120 min at set intervals. Other outcome measures included achievement of baseline BF; the time to achieve 50% and 70% baseline skin temperature (ST); and pain, tingling and numbness scores. Results 37 subjects completed 214 treatment periods. Time to achieve baseline BF was significantly shorter in the two treated groups (HR=1.77 and 2.02 for 0.5% and 1.25% vs placebo, respectively). The proportion of subjects achieving baseline BF was 45.8% for placebo, 66.2% for 0.5% and 69% for 1.25% (p=0.01 and p=0.002 for 0.5% and 1.25% vs placebo, respectively). No meaningful differences were seen in ST or pain/numbness/tingling scores. Treatment was well tolerated with no serious adverse events. Conclusions Treatment with MQX-503 caused a significant improvement in skin BF compared with placebo. Data from this proof of concept study suggest benefit of MQX-503 in subjects with RP.
Value of the time trade off method for measuring utilities in patients with rheumatoid arthritis
Authors: G J Tijhuis
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVE</h3> To assess the feasibility, reliability, and validity of the time trade off (TTO) in patients with rheumatoid arthritis (RA). <h3>METHODS</h3> The TTO was applied in 194 patients with RA with increasing difficulty in performing activities of daily living. The test-retest reliability was determined in 35 of these patients and was calculated by the intraclass correlation coefficient (ICC). Construct validity was evaluated with the following sets of variables: measures of utility (rating scale), quality of life (RAND 36 item Health Status Survey (RAND-36) and RAQoL), functional status (Health Assessment Questionnaire, grip strength, and walk test), and disease activity (doctor9s global assessment, disease activity score, pain, and morning stiffness). <h3>RESULTS</h3> Ten patients (5%) did not complete the TTO. The median value of the TTO was 0.77 (range 0.03–1.0). The test-retest ICC of the TTO was 0.85 (p&lt;0.001). Construct validity testing of the TTO showed poor to moderate correlations (Spearman9s <i>r</i><sub>s</sub>between 0.19 and 0.36, p&lt;0.01) with all outcome measures except for the subscale role limitation (physical problem) of the RAND-36, the walk test, the doctor9s global assessment of disease activity, and morning stiffness. Multiple regression analysis showed that only 17% of the variance of the TTO scores could be explained. <h3>CONCLUSIONS</h3> The TTO method appeared to be feasible and reliable in patients with RA. The poor to moderate correlations of the TTO with measures of quality of life, functional ability, and disease activity suggest that the TTO considers additional attributes of health status. This may have implications for the application of the TTO in clinical trials in patients with RA.
Bullous pemphigoid and pemphigus vulgaris--incidence and mortality in the UK: population based cohort study
Authors: S M Langan, L Smeeth, R Hubbard, K M Fleming, C J P Smith, J West
Journal: BMJ (2008)

<b>Objective</b> To determine the incidence of and mortality from bullous pemphigoid and pemphigus vulgaris in the United Kingdom. <b>Design</b> Retrospective historical cohort study. <b>Setting</b> Computerised medical records from the health improvement network, a large population based UK general practice database. <b>Participants</b> Patients with pemphigus vulgaris and bullous pemphigoid diagnostic codes and age, sex, and practice matched controls. <b>Main outcome measures</b> Incidence and mortality compared with the control population by calendar period, age group, sex, geographical region, and degree of social deprivation. <b>Results</b> 869 people with bullous pemphigoid and 138 people with pemphigus vulgaris were identified. The median age at presentation for bullous pemphigoid was 80 (range 23-102) years, and 534 (61%) patients were female. The median age at presentation for pemphigus vulgaris was 71 (21-102) years, and 91 (66%) patients were female. Incidences of bullous pemphigoid and pemphigus vulgaris were 4.3 (95% confidence interval 4.0 to 4.6) and 0.7 (0.6 to 0.8) per 100 000 person years. The incidence of bullous pemphigoid increased over time; the average yearly increase was 17% (incidence rate ratio=1.2, 95% confidence interval 1.1 to 1.2). An average yearly increase in incidence of pemphigus vulgaris of 11% (incidence rate ratio=1.1, 1.0 to 1.2) occurred. The risk of death for patients with bullous pemphigoid was twice as great as for controls (adjusted hazard ratio=2.3, 95% confidence interval 2.0 to 2.7). For pemphigus vulgaris, the risk of death was three times greater than for controls (adjusted hazard ratio=3.3, 2.2 to 5.2). <b>Conclusions</b> Incidences of bullous pemphigoid and pemphigus vulgaris are increasing. The reasons for the changes in incidence are not clearly understood but have implications for identifying causative factors. Both disorders are associated with a high risk of death. Previous estimates may have underestimated the risk of death associated with these diseases.
The impact of oral food challenge tests on food allergy health‐related quality of life
Authors: L. Soller, J. Hourihane, A. DunnGalvin
Journal: Allergy (2014)

Food allergy health-related quality of life (FAQOL) has been shown to improve after food challenge, but it is unknown whether this improvement is attributed to the procedure itself. Using the Food Allergy Quality of Life Questionnaire-Parent Form, we assessed FAQOL changes over time for children who underwent food challenges in the only paediatric allergy clinic in Ireland. Of 54 children who had a food challenge between September 2012 and February 2013, 25 were positive (allergic) and 29 were negative (nonallergic). FAQOL improved significantly from 2 months prechallenge to 2 months postchallenge for both groups, but began to decrease at 6 months postchallenge in allergic patients. Our findings confirm the positive therapeutic effect of the food challenge on FAQOL; however, the effect appears to wane between 2 and 6 months postchallenge in those confirmed food-allergic, highlighting the importance of regular contact with families of food-allergic children after the food challenge.