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GST Primary GST Primary Best Strategies for Health Care Quality Im... Best Strategies for Health Care Quality Improvement - Diabetes Quality Improvement Strategies for Antibio... Kathryn McDonald, Stanford-UCSF Evidence-b... Systematic review assessing the effect of ... Quality Improvement Strategies for Antibiotics Management Kathryn McDonald, Stanford-UCSF Evidence-based Practice Center, 117 Encina Commons, Stanford, CA 94305-6019, Kathy.mcdonald@stanford.edu Systematic review assessing the effect of quality improvement strategies on appropriate prescribing of antibiotics and appropriate choice of antibiotics. Adherence Adherence Assistive Devices Assistive Devices Childhood Burn Hanson MacMillan Childhood Burn Hanson MacMillan CLSA_9 CLSA_9 Cyberabuse Cyberabuse Cognitive Behavioural Therapy for Violent ... This review included randomized trials abo... Cognitive Behavioural Therapy for Violent Men who Batter Their Partners This review included randomized trials about the effects of cognitive behavioral therapy on domestic violence. The intervention included programs based on the Duluth Model. The violence had to be committed by a male toward his female partner. The violence also had to be physical. The primary outcomes were new arrests and convictions, and new reports of violence. CABG vs PCI CABG vs PCI Quality Improvement Strategies for Prevent... Quality Improvement Strategies for Preventing Nosocomial Infections (Created 17-Feb-06) Quality Improvement Strategies for Asthma ... Quality Improvement Strategies for Asthma Control Erectile Dysfunction (Created 30-Jan-06) Erectile Dysfunction (Created 30-Jan-06) Inequality - Smoking Cessation to Reduce S... This review was the first part of a projec... Inequality - Smoking Cessation to Reduce Socio-Economic Differences This review was the first part of a project about inequality. It included randomized trials about the effect of smoking cessation interventions on reducing socio-economic differences. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Diet and Physical Activity to Reduce Socio... This review was the second part in a proje... Diet and Physical Activity to Reduce Socio-Economic Differences This review was the second part in a project about inequality. It included randomized trials about the effect of interventions on reducing socio-economic differences in diet and physical activity. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Workfare The data in SRS are not identical to the d... Workfare The data in SRS are not identical to the data in the published report. We used SRS only for an updated search. The review included randomized trials about the effect of welfare-to-work programs. Participants were welfare recipients. There were basically two types of programs. The educational type tried to build knowledge and skills in order to help the welfare recipients acquire jobs that could support them economically. The "work first" approach was more aimed at getting the participants quickly into a job. Exercise interventions for the management ... The objective of this systematic review wa... Exercise interventions for the management of frailty The objective of this systematic review was to examine the effectiveness of current exercise interventions on the management of frailty. A comprehensive search of Medline, Embase, Psycinfo, Cinahl, Scopus, Ageline, Eric, and SportDiscus databases was conducted and produced 1808 citations. So far we have completed 2 levels of “title and abstract” screening and we ended up with 262 articles. We have just started the full text screening. Eligibility criteria included original studies whose participants were identified as frail or prefrail with specific criteria and in which structured physical activity was included as at least one component of the intervention. Create a free account, build a dictionary with saved terms to re-use later! Public Domestic Violence - Using Cognitive Behavior Therapy Smoking Cessation to Reduce Socio-Economic Differences Diet and Physical Activity to Reduce Socio-Economic Differences Workfare Exercise Interventions for the Management of Frailty Search     Simple Advanced Refine (4 coded questions)  Any of these:   Exact Phrase: All of these: None of these: Author: Periodical: Projects: No restrictions   Libraries: Public   Select SRS Projects Show Saved Terms Select Library Show articles that do not have abstracts  Type of Article Clinical Trial Editorial Letter Meta-Analysis Practice Guideline Randomized Controlled Trial Review Addresses Bibliography Biography Case Reports Classical Article Clinical Conference Clinical Trial, Phase I Clinical Trial, Phase II Clinical Trial, Phase III Clinical Trial, Phase IV Comment Comparative Study Consensus Development Conference Consensus Development Conference, NIH Controlled Clinical Trial Corrected and Republished Article Dictionary Directory Duplicate Publication English Abstract Evaluation Studies Festschrift Government Publications Guideline Historical Article Interview In Vitro Journal Article Lectures Legal Cases Legislation Multicenter Study News Newspaper Article Overall Patient Education Handout Periodical Index Published Erratum Retracted Publication Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 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Retraction of Publication Scientific Integrity Review Support of Research Technical Report Twin Study Validation Studies Not a Primary Study or Review Unknown Primary Study Case Series Case Control Cohort Study Observational Study Qualitative Research CBA or ITS Registry Double Blind Controlled before after study Quasi-randomized trial Simple before after study Cluster-RCT Non-Randomized Study Report Book Book chapter Dissertation Conference procedings Secondary Research Not RCT Humans or Animals Humans Animals Ages All Infant: birth-23 months All Child: 0-18 years All Adult: 19+ years Newborn: birth-1 month Infant: 1-23 months Preschool Child: 2-5 years Child: 6-12 years Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Middle Aged + Aged: 45+ years Aged: 65+ years 80 and over: 80+ years Undetermined Language English French German Italian Japanese Russian Spanish Afrikaans Albanian Unknown Arabic Armenian Azerbaijani Bosnian Bulgarian Catalan Chinese Croatian Czech Danish Dutch Esperanto Estonian Finnish Georgian Greek, Modern Hebrew Hindi Hungarian Icelandic Indonesian Kinyarwanda Korean Latin Latvian Lithuanian Macedonian Malay Malayalam Maori Multiple Languages Norwegian Persian Polish Portuguese Pushto Romanian Sanskrit Scottish gaelic Serbian Slovak Slovenian Swedish Thai Turkish Ukrainian Vietnamese Not English Not French Results(1-25 of 393) Sort By: Publication Date Relevance Took: 1.102 seconds to search 17,750,454  Action: Copy Results to new Clipboard Build Search Link Page 1 of 16 1 2 3 4 > Last >> (393 articles found) Molecular genetics of tetrahydrobiopterin (BH4) deficiency in the Maltese population. Mar 2007 Rosienne Farrugia,Christian A Scerri,Simon Attard Montalto,Raymond Parascandolo,Brian G R Neville,Alex E Felice Deficient activity of the Dihydropteridine Reductase enzyme (DHPR; EC 1.5.1.34; OMIM 261630) is due to mutations in the Quinoid Dihydropteridine Reductase gene on 4p15.3 (QDPR; RefSeq NM_000320). It results in defective recycling of tetrahydrobiopterin (BH(4)) and homozygotes have a rare form of at... ( view more )ypical Hyperphenylalaninaemia and Phenylketonuria (aPKU). The heterozygote frequency in the Maltese population is high at 3.3%. The more recently described and rarer type of BH(4) deficiency due to Sepiapterin Reductase enzyme deficiency (SR; EC 1.1.1.153; OMIM 182125), which presents as an atypical form of Dopa Responsive Dystonia (DRD) [L. Bonafe, B. Thony, J.M. Penzien, B. Czarnecki, N. Blau, Mutations in the sepiapterin reductase gene cause a novel tetrahydrobiopterin-dependent monoamine-neurotransmitter deficiency without hyperphenylalaninemia, Am. J. Hum. Genet. 69 (2001) 269-277; B.R.G. Neville, R. Parascandalo, S. Attard Montalto, R. Farrugia, A.E. Felice, A congenital dopa responsive motor disorder: a Maltese variant due to sepiapterin reductase deficiency, Brain 128 (Pt10) (2005) 2291-2296.] has also been identified at high frequency (4.6%) in this population. Two mutations, the c.68G>A in QDPR (p.G23D), and the new SPR, IVS2-2A>G mutation at the splice site consensus sequence in intron 2 of the Sepiapterin Reductase gene (SPR; RefSeq NM_003124) on 2p14-p12, were found to be the sole causative mutations in all the patients with DHPR deficiency and SR deficiency studied. All parents were heterozygotes for the corresponding mutation and showed no clinical symptoms. Three polymorphisms, c.96C>T (p.A32A), c. 345G>A (p.S115S) and c. 396G>A (p.L132L), have also been identified in the QDPR gene, defining four wild-type frameworks, useful in molecular epidemiology studies. The c. 68G>A mutation in QDPR was found only on framework I, suggesting a founder effect. In contrast no additional sequence diversity was found in the SPR gene whether in wild-type or mutant alleles which is also consistent with a founder effect. ( view less ) View Full Abstract View Article Details   Related Articles The Relative Distribution of Membranous and Cytoplasmic Met Is a Prognostic Indicator in Stage I and II Colon Cancer. Jun 15, 2008 Fiona Ginty,Sudeshna Adak,Ali Can,Michael Gerdes,Melinda Larsen,Harvey Cline,Robert Filkins,Zhengyu Pang,Qing Li,Michael C Montalto PURPOSE: The association hepatocyte growth factor receptor (Met) tyrosine kinase with prognosis and survival in colon cancer is unclear, due in part to the limitation of detection methods used. In particular, conventional chromagenic immunohistochemistry (IHC) has several limitations including the ... ( view more )inability to separate compartmental measurements. Measurement of membrane, cytoplasm, and nuclear levels of Met could offer a superior approach to traditional IHC. EXPERIMENTAL DESIGN: Fluorescent-based IHC for Met was done in 583 colon cancer patients in a tissue microarray format. Using curvature and intensity-based image analysis, the membrane, nuclear, and cytoplasm were segmented. Probability distributions of Met within each compartment were determined, and an automated scoring algorithm was generated. An optimal score cutpoint was calculated using 500-fold crossvalidation of a training and test data set. For comparison with conventional IHC, a second array from the same tissue microarray block was 3,3'-diaminobenzidine immunostained for Met. RESULTS: In crossvalidated and univariate Cox analysis, the membrane relative to cytoplasm Met score was a significant predictor of survival in stage I (hazard ratio, 0.16; P = 0.006) and in stage II patients (hazard ratio, 0.34; P ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Anabolic androgenic steroids differentially affect social behaviors in adolescent and adult male Syrian hamsters. Feb 2008 Kaliris Y Salas-Ramirez,Pamela R Montalto,Cheryl L Sisk Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone used by over half a million adolescents in the United States for their tissue-building potency and performance-enhancing effects. AAS also affect behavior, including reports of heightened aggression and changes in sexual l... ( view more )ibido. The expression of sexual and aggressive behaviors is a function of complex interactions among hormones, social context, and the brain, which is extensively remodeled during adolescence. Thus, AAS may have different consequences on behavior during adolescence and adulthood. Using a rodent model, these studies directly compared the effects of AAS on the expression of male sexual and aggressive behaviors in adolescents and adults. Male Syrian hamsters were injected daily for 14 days with either vehicle or an AAS cocktail containing testosterone cypionate (2 mg/kg), nandrolone decanoate (2 mg/kg), and boldenone undecylenate (1 mg/kg), either during adolescence (27-41 days of age) or in adulthood (63-77 days of age). The day after the last injection, males were tested for either sexual behavior with a receptive female or agonistic behavior with a male intruder. Adolescent males treated with AAS showed significant increases in sexual and aggressive behaviors relative to vehicle-treated adolescents. In contrast, AAS-treated adults showed significantly lower levels of sexual behavior compared with vehicle-treated adults and did not show heightened aggression. Thus, adolescents, but not adults, displayed significantly higher behavioral responses to AAS, suggesting that the still-developing adolescent brain is more vulnerable than the adult brain to the adverse consequences of AAS on the nervous system and behavior. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Individualized treatment duration for hepatitis C genotype 1 patients: A randomized controlled trial. Jan 2008 Alessandra Mangia,Nicola Minerva,Donato Bacca,Raffaele Cozzolongo,Giovanni L Ricci,Vito Carretta,Francesco Vinelli,Gaetano Scotto,Giuseppe Montalto,Mario Romano,Giuseppe Cristofaro,Leonardo Mottola,Fulvio Spirito,Angelo Andriulli It was hypothesized that in hepatitis C virus (HCV) genotype 1 patients, variable treatment duration individualized by first undetectable HCV RNA is as effective as standard 48-week treatment. Patients (n = 696) received peginterferon alfa-2a, 180 mg/week, or peginterferon alfa-2b, 1.5 mg/kg/week, ... ( view more )plus ribavirin, 1000-1200 mg/day, for 48 weeks (standard, n = 237) or for 24, 48, or 72 weeks if HCV-RNA-negative at weeks 4, 8, or 12, respectively (variable, n = 459). Sustained virologic response (SVR) was achieved in 45.1% [95% confidence interval (CI) 38.8-51.4] of the patients in the standard group and in 48.8% (CI 44.2-53.3) of the patients in the variable group (P = 0.37). The percentages of patients who first achieved undetectable HCV RNA at weeks 4, 8, or 12 were 26.7%, 27.8%, and 11.3%, respectively. In the standard treatment group, 87.1%, 70.3%, and 38.1% of patients who first achieved undetectable HCV RNA at 4, 8, or 12 weeks attained SVRs, respectively. In the variable group, corresponding SVR rates were 77.2%, 71.9%, and 63.5%. Low viremia levels and young age were independent predictors of response at week 4 [rapid virologic response (RVR)]. RVR patients with baseline viremia >or=400,000 IU/mL achieved higher SVR rates when treated for 48 weeks rather than 24 weeks (86.8% versus 73.1%, P = 0.14). The only predictive factor of SVR in RVR patients was advanced fibrosis. Conclusion: Variable treatment duration ensures SVR rates similar to those of standard treatment duration, sparing unnecessary side effects and costs. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Classification of malabsorption syndromes. 2008 Massimo Montalto,Luca Santoro,Ferruccio D'Onofrio,Valentina Curigliano,Dina Visca,Antonella Gallo,Giovanni Cammarota,Antonio Gasbarrini,Giovanni Gasbarrini Malabsorption syndrome is usually defined as the complex of symptoms secondary to maldigestion and/or malabsorption, realizing when the extension of the disease exceeds the ability of intestine compensation. Several conditions have been recognized as being responsible for this syndrome. Up to now, ... ( view more )different criteria have been used to order them, but a definitive classification is still not available because of the complexity of the absorption process, the involvement of different organs and structures, and the coexistence of different mechanisms in some diseases causing malabsorption. We propose a new classification of diseases causing malabsorption syndrome according to the responsible etiopathogenetic mechanisms: (a) alteration of digestive processes; (b) alteration of uptake and transport caused by damage or reduction of absorption surface, and (c) miscellaneous. A comment about the mechanisms responsible for malabsorption is given for all the cited diseases. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Role of natural killer cells in the pathogenesis and progression of multiple sclerosis. Jan 2008 Barbara Morandi,Placido Bramanti,Irene Bonaccorsi,Erika Montalto,Daniela Oliveri,Gaetana Pezzino,Michele Navarra,Guido Ferlazzo Natural killer (NK) cells are a subset of lymphocytes which have long been alleged to play an immunoregulatory role in the prevention of autoimmune diseases. Here, we briefly review NK cell features and the major findings from studies on NK cells in human and animals susceptible to multiple scleros... ( view more )is (MS). Although most studies in human seem to suggest an association between disease and deficiencies in NK cells, it is also clear that NK cells can be both protective and pathogenic in MS models. These contrasting observations could result from differences in experimental procedures as well as from differences in NK cell subset targeted. Whatever the case, the functional features of these cells and their potential role in regulation of autoimmunity suggest that NK cell-based therapies might be an interesting approach for the treatment of multiple sclerosis. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Intestine: organ or apparatus? 2008 Giovanni Gasbarrini,Massimo Montalto,Luca Santoro,Valentina Curigliano,Ferruccio D'Onofrio,Antonella Gallo,Dina Visca,Antonio Gasbarrini It is well known that human intestine is involved in different important functions. First of all, it is responsible for digestion and absorption of nutrients, electrolytes, water, bile salts and drugs, but it also has immunologic, endocrine and motor functions. Moreover, intestinal microflora, comp... ( view more )osed by a large diversity of bacterial cells, provides several beneficial functions for the host and is, nowadays, defined by many authors as an organ itself. In consideration of intestine complexity, we tried to understand if it can be considered only an organ or if it is an apparatus itself. We have analyzed the different components and their relationships, showing that a continuous collaboration is required among enterocytes, endocrine intestinal cells, gut immune system and microflora to assure an efficient mechanism of defense. In consideration of the complexity of intestinal components, together with the emergent role of microflora, we think that we could start to consider gut as a real apparatus, and not only as an organ. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Fecal calprotectin concentrations in patients with small intestinal bacterial overgrowth. 2008 Massimo Montalto,Luca Santoro,Sara Dalvai,Valentina Curigliano,Ferruccio D'Onofrio,Emidio Scarpellini,Giovanni Cammarota,Simona Panunzi,Antonella Gallo,Antonio Gasbarrini,Giovanni Gasbarrini BACKGROUND/AIMS: Small intestinal bacterial overgrowth (SIBO) is defined by any condition in which the proximal part of the small bowel harbors for a long time > 10(5) bacteria/ml of the intestinal juice. No data are currently available about direct or indirect parameters indicating the presence of... ( view more ) leukocytes in the gut wall and mucosal neutrophil turnover in patients with SIBO. In our pilot study we evaluate fecal calprotectin concentrations (FCC) in patients with SIBO in order to identify a possible presence of subclinical intestinal inflammation. METHODS: 40 consecutive patients with SIBO resulting positive to hydrogen glucose breath test, and 40 adult healthy volunteers were included in the study. FCC were determined by ELISA. Mean FCC were compared by means of the t-test for independent samples. RESULTS: FCC in patients with SIBO were not significantly different compared to controls (p = 0.907). CONCLUSION: Our study shows for the first time that FCC in patients with SIBO do not significantly differ from controls, suggesting that in SIBO there are no intestinal subclinical inflammatory changes involving principally the neutrophils. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Adverse reactions to food: allergies and intolerances. 2008 Massimo Montalto,Luca Santoro,Ferruccio D'Onofrio,Valentina Curigliano,Antonella Gallo,Dina Visca,Giovanni Cammarota,Antonio Gasbarrini,Giovanni Gasbarrini All the anomalous reactions secondary to food ingestion are defined as 'adverse reactions to food'. In 1995 the European Academy of Allergology and Clinical Immunology suggested a classification on the basis of the responsible pathogenetic mechanism; according to this classification, non-toxic reac... ( view more )tions can be divided into 'food allergies' when they recognize immunological mechanisms, and 'food intolerances' when there are no immunological implications. The diagnostic approach to adverse reactions to food is based on accurate clinical history and objective examination, and further execution of specific tests when allergy or intolerance is suspected. The therapy for food allergies is the elimination of the food to which hypersensibility has been found; this strategy can lead, especially in pediatric age, to tolerance. If elimination diets cannot be completely performed, or if it is not possible to identify the food to eliminate, some drugs (e.g. antihistaminics, steroids, etc.) can be administered. Specific allergen immunotherapy has been recently introduced. Fundamental is food allergy prevention, especially in high-risk subjects. The therapeutic approach to secondary food intolerances is based principally on primitive disease resolution; on the other hand, some specific treatments (e.g. beta-galactosidases in lactose malabsorption) are available in case of primary intolerance. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Response to antiviral therapy and hepatic expression of cyclooxygenases in chronic hepatitis C. Nov 2007 Lydia Giannitrapani,Maurizio Soresi,Sabrina Ingrao,Emanuele La Spada,Onofrio Vuturo,Ada Maria Florena,Melchiorre Cervello,Giuseppe Montalto OBJECTIVES: The aims of this study were to investigate the expression of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2) in chronic hepatitis C (CHC) by immunohistochemistry, based on the hypothesis that COXs expression could vary according to genotype, viral load, liver steatosis, BMI and ... ( view more )response to therapy and to determine whether the addition of selective COX inhibitors could have a rationale in increasing the efficacy of antiviral therapy. METHODS: We used 35 formalin-fixed, paraffin-embedded liver tissue samples obtained by needle biopsy from patients with CHC (17F/18M) with one of two types of genotype (1b and 3a). The presence of COX-1 and COX-2 in the cytoplasm of hepatocytes was scored on the basis of: (i) maximum intensity; (ii) dominant intensity; and (iii) extent. RESULTS: No significant differences were found in COX-1 and COX-2 expression in CHC patients divided according to genotype or according to the type of response to combination therapy with pegylated-interferon and ribavirin. The only significant correlations were observed between the dominant intensity of COX-2 and the presence of histological steatosis (P<0.01) and an inverse correlation between COX-2 extent and the viral load (P<0.02). CONCLUSIONS: The lack of correlation between COXs tissue expression and response to antiviral treatment suggests that there is no rationale to adding selective COX inhibitors to increase the efficacy of antiviral therapy, although further studies on larger patient populations are needed. On the contrary, there is a potential application for their use in the prevention and treatment of liver steatosis. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Best site on right ventricle for open-chest biventricular pacing. Oct 2007 Giampaolo Luzi,Andrea Montalto,Vincenzo Polizzi,Cesare C D'Alessandro,Mariano Vicchio,Francesco Musumeci Cardiac resynchronization therapy is effective in patients with a low ejection fraction and left bundle branch block, but 20%-30% do not respond despite selection of the optimal site for pacing on the left ventricle. We investigated whether optimizing the site for placement of the pacing lead on th... ( view more )e right ventricle could further improve left ventricular function during cardiac resynchronization in 19 patients (mean age, 63 +/- 5 years) undergoing coronary artery bypass with post-ischemic dilated myocardiopathy (ejection fraction, 25.8% +/- 2%) and left bundle branch block. The hemodynamic response to pacing was tested with the right ventricular lead positioned at the interventricular septum, atrioventricular junction, acute margin, and the pulmonary trunk. Biventricular stimulation improved left ventricular function. When the right ventricular lead was sited at the interventricular septum, a significant improvement in all hemodynamic parameters compared to the other sites was obtained. Biventricular pacing is important to optimize cardiac resynchronization. Although further studies are needed to confirm these findings, accurate lead placement is recommended for cardiac resynchronization therapy in patients with poor cardiac function and left bundle branch block. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Clinical and molecular phenotype of Aicardi-Goutieres syndrome. Oct 2007 Gillian Rice,Teresa Patrick,Rekha Parmar,Claire F Taylor,Alec Aeby,Jean Aicardi,Rafael Artuch,Simon Attard Montalto,Carlos A Bacino,Bruno Barroso,Peter Baxter,Willam S Benko,Carsten Bergmann,Enrico Bertini,Roberta Biancheri,Edward M Blair,Nenad Blau,David T Bonthron,Tracy Briggs,Louise A Brueton,Han G Brunner,Christopher J Burke,Ian M Carr,Daniel R Carvalho,Kate E Chandler,Hans-Jurgen Christen,Peter C Corry,Frances M Cowan,Helen Cox,Stefano D'Arrigo,John Dean,Corinne De Laet,Claudine De Praeter,Catherine Dery,Colin D Ferrie,Kim Flintoff,Suzanna G M Frints,Angels Garcia-Cazorla,Blanca Gener,Cyril Goizet,Francoise Goutieres,Andrew J Green,Agnes Guet,Ben C J Hamel,Bruce E Hayward,Arvid Heiberg,Raoul C Hennekam,Marie Husson,Andrew P Jackson,Rasieka Jayatunga,Yong-Hui Jiang,Sarina G Kant,Amy Kao,Mary D King,Helen M Kingston,Joerg Klepper,Marjo S van der Knaap,Andrew J Kornberg,Dieter Kotzot,Wilfried Kratzer,Didier Lacombe,Lieven Lagae,Pierre Georges Landrieu,Giovanni Lanzi,Andrea Leitch,Ming J Lim,John H Livingston,Charles M Lourenco,E G Hermione Lyall,Sally A Lynch,Michael J Lyons,Daphna Marom,John P McClure,Robert McWilliam,Serge B Melancon,Leena D Mewasingh,Marie-Laure Moutard,Ken K Nischal,John R Ostergaard,Julie Prendiville,Magnhild Rasmussen,R Curtis Rogers,Dominique Roland,Elisabeth M Rosser,Kevin Rostasy,Agathe Roubertie,Amparo Sanchis,Raphael Schiffmann,Sabine Scholl-Burgi,Sunita Seal,Stavit A Shalev,C Sierra Corcoles,Gyan P Sinha,Doriette Soler,Ronen Spiegel,John B P Stephenson,Uta Tacke,Tiong Yang Tan,Marianne Till,John L Tolmie,Pam Tomlin,Federica Vagnarelli,Enza Maria Valente,Rudy N A Van Coster,Nathalie Van der Aa,Adeline Vanderver,Johannes S H Vles,Thomas Voit,Evangeline Wassmer,Bernhard Weschke,Margo L Whiteford,Michel A A Willemsen,Andreas Zankl,Sameer M Zuberi,Simona Orcesi,Elisa Fazzi,Pierre Lebon,Yanick J Crow Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3'-->5' exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease compl... ( view more )ex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B, and RNASEH2C were observed in 31, 3, 47, and 18 families, respectively. In five families, we identified an RNASEH2A or RNASEH2B mutation on one allele only. In one child, the disease occurred because of a de novo heterozygous TREX1 mutation. In 22 families, no mutations were found. Null mutations were common in TREX1, although a specific missense mutation was observed frequently in patients from northern Europe. Almost all mutations in RNASEH2A, RNASEH2B, and RNASEH2C were missense. We identified an RNASEH2C founder mutation in 13 Pakistani families. We also collected clinical data from 123 mutation-positive patients. Two clinical presentations could be delineated: an early-onset neonatal form, highly reminiscent of congenital infection seen particularly with TREX1 mutations, and a later-onset presentation, sometimes occurring after several months of normal development and occasionally associated with remarkably preserved neurological function, most frequently due to RNASEH2B mutations. Mortality was correlated with genotype; 34.3% of patients with TREX1, RNASEH2A, and RNASEH2C mutations versus 8.0% RNASEH2B mutation-positive patients were known to have died (P=.001). Our analysis defines the phenotypic spectrum of AGS and suggests a coherent mutation-screening strategy in this heterogeneous disorder. Additionally, our data indicate that at least one further AGS-causing gene remains to be identified. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Early nifurtimox-induced biochemical and ultrastructural alterations in rat heart. Oct 2007 L C Bartel,M Montalto de Mecca,S L Fanelli,C Rodriguez de Castro,E G Diaz,J A Castro Nifurtimox (Nfx) and Benznidazole (Bz) are being used for the treatment of the acute phase of Chagas' disease. Recently, they were also considered for use in the indeterminate phase. Both the nitroheterocyclic drugs have serious toxic side effects. The mechanism of Nfx toxicity is associated with t... ( view more )he formation of reactive oxygen species (ROS) generated during nitroreduction. Potential effects on cardiac function have not been established yet, despite the well-known cardiopathy often produced by the disease itself. We describe experiments testing some acute effects of Nfx on the male Sprague Dawley rat heart. Nifurtimox was present in the heart at 1, 3 and 6 h after intragastric (i.g) treatment. In vitro studies on Nfx microsomal and cytosolic nitroreductase activities showed that only the microsomal fraction had the ability to nitroreduce it. Cytochrome P450 and cytochrome P450 reductase would be involved in the process as suggested by their response to specific inhibitors. Nifurtimox increased the cardiac protein carbonyl content at 1 and 3 h and decreased the protein sulfhydryl content at 3 h. In addition, 24 h after treatment ultrastructural alterations such as marked cytoplasmic vacuolization, separation and loss of myofibrils and mitochondrial swelling were observed. Results suggest that Nfx administration might aggravate pre-existing adverse cardiac conditions. Human & Experimental Toxicology (2007) 26, 781 -788. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Gastrointestinal involvement in a case of hereditary angioedema: could the early weaning have had a role? Sep 2007 Massimo Montalto,Francesca Ancarani,Luca Santoro,Valentina Curigliano,Fabio Rotondi,Antonella Gallo,Giovanni Gasbarrini Hereditary angioedema (HAE) is a noninflammatory disorder due to reduced C1-inhibitor level and/or function and characterized by recurrent, circumscribed, and self-limiting episodes of cutaneous and mucous membrane swellings involving different organs. A heterogeneous group of mutations in the C1-i... ( view more )nhibitor gene have been found. HAE might present with diverse clinical pictures, even within families with the same mutation, but the cause of this variability is not known yet. We describe the case of type II HAE in a young adult presenting with recurrent abdominal pain for many years, occasionally associated with ascites. We suppose that an early weaning might have influenced his phenotype, making his gastrointestinal tract a "vulnerable organ," in which hereditary angioedema could express itself. ( view less ) View Full Abstract View Article Details   Related Articles Potentiation of the antitumor effects of both selective cyclooxygenase-1 and cyclooxygenase-2 inhibitors in human hepatic cancer cells by inhibition of the MEK/ERK pathway. Sep 2007 Antonella Cusimano,Daniela Foderà,Natale D'Alessandro,Nadia Lampiasi,Antonina Azzolina,Giuseppe Montalto,Melchiorre Cervello The molecular mechanisms behind the anti-neoplastic effects of non-steroidal anti-inflammatory drugs (NSAIDs) are not completely understood and cannot be explained by the inhibition of the cyclooxygenase (COX) enzymes COX-1 and COX-2 alone. We previously reported that both the selective COX-1 inhib... ( view more )itor SC-560 and the selective COX-2 inhibitor CAY10404 exhibit anti-tumor effects in human hepatoma cells. NSAID inhibitors have many COX-independent actions and, among others, the mitogen-activated protein kinase (MAPK) pathways are targets for NSAIDs. Here, we examined the role of MEK/ERK1/2 signaling in the anti-neoplastic effects of both selective COX-1 and COX-2 inhibitors in two human hepatoma cell lines. Treatment of hepatoma cells with the selective COX-1 inhibitor SC-560, as well as with the selective COX-2 inhibitor CAY10404, was associated with activation of ERK1/2 in a time- and dose-dependent manner. Treatment with COX-1 and COX-2 inhibitors in the presence of the selective MEK1/2 inhibitor U0126 effectively suppressed ERK1/2 activation and combinations of either SC-560 or CAY10404 with U0126 resulted in synergistic effects on cell growth inhibition and induction of apoptosis. In HuH-6 hepatoma cells the combination-induced apoptosis was associated with caspase-9 and -3 activation, PARP cleavage, release of cytochrome c from the mitochondria into the cytosol and down-regulation of survivin and beta-catenin levels. In conclusion, our study showed that growth inhibitory concentrations of selective COX-1 and COX-2 inhibitors increased ERK1/2 phosphorylation in hepatoma cells, and that inhibition of the MEK/ERK signaling pathway potentiates the antitumor activity of both types of inhibitors. Therefore, our results provide preclinical support for a combined chemotherapeutic approach with selective NSAIDs and MEK inhibitors for the treatment of hepatocellular carcinoma. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Validation of self-reported smoking status using saliva cotinine: a rapid semiquantitative dipstick method. Sep 2007 Norman J Montalto,Wayne O Wells PURPOSE: This study evaluated the performance characteristics of a novel rapid method for verifying smoking status in individuals by measurement of cotinine, the primary metabolite of nicotine, in saliva samples using an immunochromatographic strip in a "dipstick" format compared with liquid chroma... ( view more )tography/mass spectrometry (LC/MS). MATERIALS AND METHODS: A prospective comparison was made of smoking status as determined by measurement of cotinine in urine by LC/MS (the gold standard) and in saliva using a semiquantitative dipstick assay that uses cotinine-specific monoclonal antibodies attached to gold particles and a series of avidity traps to measure cotinine levels (saliva NicAlert). One hundred seventy-two individuals from a family practice/general medical setting agreed to participate after informed consent and institutional review board approval. Saliva NicAlert tests were done by untrained operators who followed written directions. RESULTS: Comparison of smoking status as determined by urine cotinine measurement by LC/MS (50 ng/mL cutoff) with the saliva strip test results, averaged over the two operators, indicated that the saliva test strip results had a sensitivity of 99% and a specificity of 96%. Saliva NicAlert also identified four smokers who reported being nonsmokers but were confirmed to be smokers by LC/MS. CONCLUSIONS: The saliva NicAlert assay seems to be a valid, highly sensitive, and specific method for validating self-reported smoking status and may have clinical applications in selected medical settings. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Faecal calprotectin concentrations in untreated coeliac patients. Aug 2007 Massimo Montalto,Luca Santoro,Valentina Curigliano,Ferruccio D'Onofrio,Giovanni Cammarota,Simona Panunzi,Riccardo Ricci,Antonella Gallo,Antonio Grieco,Antonio Gasbarrini,Giovanni Gasbarrini OBJECTIVE: Calprotectin is a granulocyte cytosolic protein that is considered to be a promising marker of subclinical inflammation. High faecal calprotectin concentrations (FCCs) have been found in several intestinal diseases, but no data are currently available on patients with coeliac disease. Th... ( view more )e purpose of this pilot study was to evaluate FCCs in untreated coeliac patients and to correlate them with clinical score and histological characteristics. MATERIAL AND METHODS: Twenty-eight consecutive coeliac patients were recruited. Thirty healthy adult volunteers participated as the control group. FCCs were determined by ELISA. Clinical assessment was carried out in all patients. The histological severity of lesions and the infiltration of neutrophil polymorphs in the intestinal mucosa were also evaluated. Mean FCCs in patients and the control group were compared by means of the t-test for independent samples. In coeliac patients, differences in FCCs in subgroups identified by clinical score, lesion severity and neutrophil infiltration were evaluated by the Kruskal-Wallis non-parametric test. RESULTS: FCCs in untreated coeliac patients were not significantly different from those in controls (p=0.163). Among coeliac patients, FCCs were not significantly different in relation to the level of clinical score, lesion severity or neutrophil infiltration (p=0.92, p=0.96 and p=0.74, respectively). CONCLUSIONS: This study shows, for the first time, that FCCs in untreated coeliac patients do not differ significantly from those in controls. ( view less ) View Full Abstract View Article Details   Related Articles Circulating levels of adhesion molecules in chronic kidney disease correlate with the stage of renal disease and with C-reactive protein. Jul 2007 Francesco Vaccaro,Giuseppe Mulè,Santina Cottone,Maurizio Soresi,Lydia Giannitrapani,Anna Vadalà,Vito Sparacino,Sergio Calabrese,Francesco P Picone,Giuseppe Montalto,Giovanni Cerasola BACKGROUND: Patients with chronic renal failure (CRF) suffer from a series of complications linked to the atherosclerotic process in which the endothelial dysfunction mediated by the activation of some adhesion molecules plays an important role. This study aims to evaluate circulating levels of int... ( view more )ercellular adhesion molecules-1 (ICAM-1) and vascular cell adhesion molecules-1 (VCAM-1) in patients with predialysis CRF, on maintenance hemodialysis (HD) and after kidney transplantation (KTx) and to correlate them with some inflammation and nutritional indexes. METHODS: Thirty two patients with predialysis CRF, 30 on maintenance HD, 36 after KTx and 28 subjects as a control group (C) were included in this study. Circulating levels of ICAM-1 and VCAM-1 were assayed using a specific sandwich ELISA kit. As inflammation indexes, TNFalpha and C-reactive protein (CRP) and, as nutritional indexes, body mass index (BMI), serum albumin, cholesterol, triglycerides, and fibrinogen (F) were evaluated. RESULTS: Serum levels of ICAM-1 and VCAM-1 were progressively higher from C to KTx patients, to those with CRF and those on HD (ANOVA for both; p <0.001). TNFalpha values were lower in HD subjects than in CRF patients, even if in both groups TNFalpha levels were greater than in Tx and control subjects. F and CRP were higher in CRF and HD vs. Tx and control subjects (ANOVA for both p <0.001). No significant correlations were observed between soluble adhesion molecules, albumin and cholesterol, whereas significant correlations were found between CRP and ICAM-1 (r = 0.41; p <0.01), CRP and VCAM-1 (r = 0.39; p <0.01) and between CRP and TNFalpha (r = 0.42; p <0.01). These correlations remained statistically significant even after adjustment for age and blood pressure (all p <0.01). BMI did not differ in the three patient groups. CONCLUSIONS: Circulating levels of adhesion molecules in our study correlated positively with the stage of disease and with one of the inflammatory indexes (CRP), but not with nutritional indexes such as BMI, cholesterol and albumin. The clinical significance of our findings warrants further investigation. ( view less ) View Full Abstract View Article Details   Related Articles Histamine and spontaneously released mast cell granules affect the cell growth of human hepatocellular carcinoma cells. Jun 30, 2007 Nadia Lampiasi,Antonina Azzolina,Giuseppe Montalto,Melchiorre Cervello The role of mast cells in tumor growth is still controversial. In this study we analyzed the effects of both histamine and pre-formed mediators spontaneously released by mast cells on the growth of two human hepatocellular carcinoma cell lines, HA22T/VGH and HuH-6, with different characteristics of... ( view more ) differentiation, biological behavior and genetic defects. We showed that total mast cell releasate, exocytosed granules (granule remnants) and histamine reduced cell viability and proliferation in HuH-6 cells. In contrast, in HA22T/VGH cells granule remnants and histamine induced a weak but significant increase in cell growth. We showed that both cell lines expressed histamine receptors H(1) and H(2) and that the selective H(1) antagonist terfenadine reverted the histamine-induced inhibition of HuH-6 cell growth, whereas the selective H(2) antagonist ranitidine inhibited the histamine-induced cell growth of HA22T/VGH cells. We demonstrated that histamine down-regulated the expression of beta-catenin, COX-2 and survivin in HuH-6 cells and that this was associated with caspase-3 activation and PARP cleavage. On the contrary, in HA22T/VGH cells expression of survivin and beta-catenin increased after treatment with granule remnants and histamine. Overall, our results suggest that mediators stored in mast cell granules and histamine may affect the growth of liver cancer cells. However, mast cells and histamine may play different roles depending on the tumor cell features. Finally, these data suggest that histamine and histamine receptor agonists/antagonists might be considered as "new therapeutic" drugs to inhibit liver tumor growth. ( view less ) View Full Abstract View Article Details   Related Articles Nifurtimox nitroreductase activity in different cellular fractions from male rat pancreas. Biochemical and ultrastructural alterations. Jun 20, 2007 María Montalto de Mecca,Silvia L Fanelli,Laura C Bartel,Carmen R de Castro,Edith G Díaz,José A Castro Nifurtimox (Nfx) is a nitroheterocyclic drug used in the treatment of Chagas' disease. It has serious side effects which frequently force to interrupt the treatment. Nfx toxicity has been linked to its nitroreduction to a nitroanion radical with a subsequent redox cycling which generate reactive ox... ( view more )ygen species. We analyzed the ability of Sprague Dawley male rat pancreas to nitroreduce Nfx and whether this drug may cause deleterious effects in this organ. The microsomal fraction exhibited Nfx nitroreductase activity in the presence of NADPH under anaerobic atmosphere, which was fully inhibited under air but not altered when N2 was replaced by pure CO. The cytosol nitroreduced Nfx in the presence of hypoxanthine under N2; it was inhibited by allopurinol and negligible in aerobiosis. Nfx reached pancreatic tissue at 1, 3 or 6 h after intragastric administration (100 mg/kg). Six hours after drug administration, a significant increase in t-buthylhydroperoxide promoted chemiluminiscence was detected. Pancreatic protein sulfhydryl content significantly decreased at either 1, 3 or 6 h after Nfx administration. No changes in either protein carbonyl or in lipid hydroperoxides were observable. Ultrastructural alterations were observed in the endoplasmic reticulum and nuclei from acinar cells and in the insulin-containing granules from the pancreas. However, the seric amylase levels were not changed, but the blood glucose levels were slightly but significantly increased 24 h after Nfx administration. These studies might suggest that Nfx treatment could impose an increased risk to patients exposed to other insults provoking oxidative stress or having preexisting pathologies in the pancreas. ( view less ) View Full Abstract View Article Details   Related Articles Overview and new strategies in metastatic breast cancer (MBC) for treatment of tamoxifen-resistant patients. Jun 2007 V Adamo,M Iorfida,E Montalto,V Festa,C Garipoli,A Scimone,M Zanghì,N Caristi The treatment with aromatase inhibitors (AIs) and fulvestrant has been demonstrated to be active in a proportion of tamoxifen-resistant breast cancer patients, obtaining, in some cases, a long-term control of tumor growth. Results from clinical trials indicate that treatment with fulvestrant might ... ( view more )either precede or follow AIs. However, the AIs are now replacing tamoxifen as first-line advanced and adjuvant therapies, and thus, other options following tamoxifen failure are required. Fulvestrant may be effective in this setting, even if there is also evidence of a lack of cross-resistance between nonsteroidal and steroidal AIs, resulting in the potential use of steroidal AIs following nonsteroidal AI failure and vice versa. Resistance mechanisms to these therapies appear to be related to a cross talk between estrogen receptor (ER) and growth factor-signaling cascades. Novel therapeutic approaches for ER+ patients, which combine hormonal agents and signal transduction inhibitors, have been developed to overcoming resistance. Several trials are now investigating signal transduction inhibitors combined with endocrine agents. This approach might provide efficient treatments and delay the onset of antihormone resistance, thereby significantly improving patient's survival. ( view less ) View Full Abstract View Article Details   Related Articles [Abnormal liver function in Mediterranean spotted fever] Jun 2007 Anna Micalizzi,Emanuele La Spada,Sveva Corsale,Angela Arculeo,Monica La Spada,Pasquale Quartararo,Lydia Giannitrapani,Maurizio Soresi,Mario Affronti,Giuseppe Montalto In this study we retrospectively assessed the prevalence of impaired liver function in all 49 patients suffering from Mediterranean Spotted Fever (MSF) consecutively admitted to our department over the last four years. The main parameters of liver function and ultrasound of upper abdomen were perfo... ( view more )rmed at entry and at the end of treatment. At admission mean values of transaminases were above the normal limits and significantly higher when compared to mean serum levels at recovery. 55% and 51% of patients had serum values of GOT and GPT, respectively, above the normal limits versus 1% and 2% at the end of treatment. Mean serum values of alkaline phosphatase (AP) were within the normal limits at entry in hospital, but 22 of them had serum values above the normal limits. The same proportion was seen for gamma glutamiltranspeptidase values. Eighteen patients (36.7%) had both transaminases and AP above the normal limits. There were no significant differences among serum values of albumin, bilirubin and gamma globulin before and after therapy. Platelet count, on the contrary, was significantly reduced at admission (p < 0.0001). At ultrasound half of the patients showed hepatomegaly with a hepatitis-like pattern and 39% of patients had splenomegaly. In conclusion, this study confirms previous data from the literature showing a high frequency of liver impairment during the course of MSF, which is usually mild-moderate. In a few cases, however, the increase of transaminases could be serious and the recovery delayed, but never, in our experience, has there been progression toward chronic liver disease. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Gossypol inhibits proliferation of endometrioma cells in culture. May 2007 Shawky Z A Badawy,Abdul-Kader Souid,Violeta Cuenca,Nicholas Montalto,Frances Shue AIM: To evaluate the anti-proliferative activity and mitochondrial toxicity of gossypol in endometrioma cells maintained in short-term cultures. METHODS: (A) Three endometrioma cell lines from patients were treated with 25 or 50 nmol/L gossypol for up to 12 days. The effect of gossypol on the cell ... ( view more )growth was recorded. (B) A phosphorescence oxygen analyzer was used to determine the effects of gossypol on mitochondrial oxygen consumption of six endometrioma cell lines from patients. (C) Cellular gossypol accumulations in three endometrioma cell lines from patients were measured by high-pressure liquid chromatography. RESULTS: Proliferation of the endometrioma cells was inhibited by 25 and 50 nmol/L gossypol. Respiration of the endometrioma cells was inhibited by 10 micromol/L gossypol. Cellular gossypol was detected in the endometrioma cell lines that were treated for 24 h with 10 and 0.3 micromol/L gossypol. CONCLUSION: Gossypol invokes a potent toxicity on cultured endometrioma cells. ( view less ) View Full Abstract View Article Details   Related Articles Treatment of patients with pulmonary embolism entirely in Hospital in the Home. May 2007 Benjamin Lui,Anh Tran,Michael Montalto BACKGROUND: Low molecular weight heparin (LMWH) has revolutionised the management of venous thromboembolism (VTE). An important feature of the use of LMWH is the ability to manage acute VTE in the home. This study examined the outcomes of patients with pulmonary embolism (PE) who were transferred t... ( view more )o Hospital in the Home (HIH) within 24 hours of presentation for treatment with LMWH. METHODS: The authors reviewed records of all patients with PE who presented to two major hospitals in Melbourne (Victoria) and who were transferred to HIH for treatment with LMWH within 24 hours of presentation. The main outcome measures were length of stay, unexpected staff callouts, unexpected returns to hospital, recurrent embolism, bleeding, and death. RESULTS: Twenty-one patients were included in the study over 5 years, with a mean age of 56 years. Patients spent a mean of 9 hours in hospital before transfer and spent a mean of 6 nights in HIH. One patient required an unexpected staff callout. There were no unexpected returns to hospital. No patient deaths or instances of major bleeding were recorded. Three patients developed minor bleeding. DISCUSSION: Despite the long study period, this is a small cohort of patients and no control group is offered. However, all eligible patients were included in the study. With appropriate risk assessment and medical model of HIH, it might be safe to treat low risk patients with PE in HIH for their entire hospital stay. ( view less ) View Full Abstract View Article Details   Related Articles Celiac disease in the developing countries: a new and challenging public health problem. Apr 21, 2007 Francesco Cataldo,Giuseppe Montalto In the past, celiac disease was believed to be a chronic enteropathy, almost exclusively affecting people of European origin. The availability of new, simple, very sensitive and specific serological tests (anti-gliadin, anti-endomysium and anti-transglutaminase antibody assays) have shown that celi... ( view more )ac disease is common not only in Europe and in people of European ancestry but also in the developing countries where the major staple diet is wheat (Southern Asia, the Middle East, North West and East Africa, South America), both in the general population and in the groups at risk. Gluten intolerance thus appears to be a widespread public health problem and an increased level of awareness and clinical suspicion are needed in the New World where physicians must learn to recognize the variable clinical presentations (classical, atypical and silent forms) of celiac disease. In the developing countries, both serological screening in the general population and serological testing in groups at risk are necessary for an early identification of celiac patients. The gluten-free diet poses a challenging public health problem in the developing countries, especially since commercial gluten-free products are not available. ( view less ) View Full Abstract View Article Details   Related Articles Page 1 of 16 1 2 3 4 > Last >> (393 articles found)

      
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