Variable viral clearance despite adequate ganciclovir plasma levels during valganciclovir treatment for cytomegalovirus disease in D+/R- transplant recipients.

ABSTRACT: BACKGROUND: Valganciclovir, the oral prodrug of ganciclovir, has been demonstrated equivalent to iv ganciclovir for CMV disease treatment in solid organ transplant recipients. Variability in ganciclovir exposure achieved with valganciclovir could be implicated as a contributing factor for explaining variations in the therapeutic response. This prospective observational study aimed to correlate clinical and cytomegalovirus (CMV) viral load response (DNAemia) with ganciclovir plasma concentrations in patients treated with valganciclovir for CMV infection/disease. METHODS: Seven CMV D+/R- transplant recipients (4 kidney, 2 liver and 1 heart) were treated with valganciclovir (initial dose was 900-1800 mg/day for 3-6.5 weeks, followed by 450-900 mg/day for 2-9 weeks). DNAemia was monitored by real time quantitative PCR and ganciclovir plasma concentration was measured at trough (Ctrough) and 3 h after drug administration (C3h) by HPLC. RESULTS: Four patients presented with CMV syndrome, two had CMV tissue-invasive disease after prophylaxis discontinuation, and one liver recipient was treated pre-emptively for asymptomatic rising CMV viral load 5 weeks post-transplantation in the absence of prophylaxis. CMV DNAemia decreased during the first week of treatment in all recipients except in one patient (median decrease: -1.2 log copies/mL, range: -1.8 to 0) despite satisfactory ganciclovir exposure (AUC0-12 = 48 mg.h/L, range for the 7 patients: 40-118 mg.h/L). Viral clearance was obtained in five patients after a median of time of 34 days (range: 28-82 days). Two patients had recurrent CMV disease despite adequate ganciclovir exposure (65 mg.h/L, range: 44-118 mg.h/L). CONCLUSIONS: Valganciclovir treatment for CMV infection/disease in D+/R- transplant recipients can thus result in variable viral clearance despite adequate ganciclovir plasma concentrations, probably correlating inversely with anti-CMV immune responses after primary infection.

Comparative cost-effectiveness analyses of cardiovascular magnetic resonance and coronary angiography combined with fractional flow reserve for the diagnosis of coronary artery disease.

BACKGROUND: According to recent guidelines, patients with coronary artery disease (CAD) should undergo revascularization if significant myocardial ischemia is present. Both, cardiovascular magnetic resonance (CMR) and fractional flow reserve (FFR) allow for a reliable ischemia assessment and in combination with anatomical information provided by invasive coronary angiography (CXA), such a work-up sets the basis for a decision to revascularize or not. The cost-effectiveness ratio of these two strategies is compared. METHODS: Strategy 1) CMR to assess ischemia followed by CXA in ischemia-positive patients (CMR + CXA), Strategy 2) CXA followed by FFR in angiographically positive stenoses (CXA + FFR). The costs, evaluated from the third party payer perspective in Switzerland, Germany, the United Kingdom (UK), and the United States (US), included public prices of the different outpatient procedures and costs induced by procedural complications and by diagnostic errors. The effectiveness criterion was the correct identification of hemodynamically significant coronary lesion(s) (= significant CAD) complemented by full anatomical information. Test performances were derived from the published literature. Cost-effectiveness ratios for both strategies were compared for hypothetical cohorts with different pretest likelihood of significant CAD. RESULTS: CMR + CXA and CXA + FFR were equally cost-effective at a pretest likelihood of CAD of 62% in Switzerland, 65% in Germany, 83% in the UK, and 82% in the US with costs of CHF 5'794, euro 1'517, £ 2'680, and $ 2'179 per patient correctly diagnosed. Below these thresholds, CMR + CXA showed lower costs per patient correctly diagnosed than CXA + FFR. CONCLUSIONS: The CMR + CXA strategy is more cost-effective than CXA + FFR below a CAD prevalence of 62%, 65%, 83%, and 82% for the Swiss, the German, the UK, and the US health care systems, respectively. These findings may help to optimize resource utilization in the diagnosis of CAD.

Disseny i implementació d'una etapa d'acondicionament per a mesures de conductivitat realitzades amb un microscopi de forces atòmiques

En aquest treball, s’ha dissenyat un mòdul d’acondicionament a fi de millorar les mesures de conductivitat realitzades amb un AFM (Microscopi de Forces Atòmiques). L’equip actual disposa d’un preamplificador de baix soroll amb un guany de 10 10V/A. Donat que els corrents que es pretenen mesurar són extremadament petits (~pA), s’ha dissenyat un filtre per eliminar diferents fonts de soroll, com ara el soroll que introdueix la xarxa elèctrica a 50Hz. Es pretén reduir aquesta component freqüencial un factor mínim de 10 (20dB). També s’ha afegit un filtre passa baixos per eliminar els soroll que es troba fora de l’amplada de banda del preamplificador. S’ha introduït una etapa d’amplificació de guany variable: 1, 10 i 100 per augmentar la flexibilitat de l’equip i finalment també s’ha dissenyat una etapa per eliminar la tensió d’offset d’aquest amplificador. L’abast del treball anirà des del disseny fins la implementació final sobre una placa PCB.

Antibody-mediated status epilepticus: a retrospective multicenter survey.

Background: In recent years, an increasing number of auto-antibodies (AB) have been detected in the CSF and serum of patients with new onset epilepsy. Some of these patients develop convulsive or nonconvulsive status epilepticus (AB-SE), necessitating intensive medical care and administration of multiple antiepileptic and immunomodulatory treatments of uncertain effectiveness. Objectives: In this retrospective multicenter survey we aimed to determine the spectrum of gravity, the duration and the prognosis of the disorder. In addition, we sought to identify the antibodies associated with this condition, as well as determine whether there is a most effective treatment regime. Methods: 12 European Neurology University Clinics, with extensive experience in the treatment of SE patients, were sent a detailed questionnaire regarding symptoms and treatment of AB-SE patients. Seven centers responded positively, providing a total of 13 patients above the age of 16. Results: AB-SE affects mainly women (12/13, 92%) with a variable age at onset (17-69 years, median: 25 years). The duration of the disease is also variable (10 days to 12 years, median: 2 months). Only the 3 oldest patients died (55-69 years). Most patients were diagnosed with anti NMDAR encephalitis (8/13) and had oligoclonal bands in the CSF (9/13). No specific treatment regimen (antiepileptic, immunomodulatory) was found to be clearly superior. Most of the surviving 10 patients (77%) recovered completely or nearly so within 2 years of index poststatus. Conclusion: AB-SE is a severe but potentially reversible condition. Long duration does not seem to imply fatal outcome; however, age older than 50 years at time of onset appears to be a risk factor for death. There was no evidence for an optimal antiepileptic or immunomodulatory treatment. A prospective multicenter study is warranted in order to stratify the optimal treatment algorithm, determine clear risk factors of unfavorable outcome and long-term prognosis.

On the number of higher order Delaunay triangulations

"Vegeu el resum a l'inici del document del fitxer adjunt."

Social personality trait and fitness.

Several recent studies have explored various aspects of animal personality and their ecological consequences. However, the processes responsible for the maintenance of personality variability within a population are still largely unknown. We have recently demonstrated that social personality traits exist in the common lizard (Lacerta vivipara) and that the variation in sociability provides an explanation for variable dispersal responses within a given species. However, we need to know the fitness consequences of variation in sociability across environmental contexts in order to better understand the maintenance of such variation. In order to achieve this, we investigated the relationship between sociability and survival, body growth and fecundity, in one-year-old individuals in semi-natural populations with varying density. 'Asocial' and 'social' lizards displayed different fitness outcomes in populations of different densities. Asocial lizards survived better in low-density populations, while social females reproduced better. Spatiotemporal variation in environmental conditions might thus be the process underlying the maintenance of these personality traits within a population. Finally, we also discuss the position of sociability in a more general individual behavioural pattern including boldness, exploration and aggressiveness.

Validació creuada en població penitenciària de criteris psicomètrics i tècnics per la predicció de conductes adaptatives i factors de risc

La predicció del grau d’adaptació de les persones que ingressen als centres penitenciaris és un element clau per poder minimitzar problemes regimentals i, alhora, facilitar el procés de rehabilitació. Els elements predictors es poden fonamentar en variables psicomètriques (mesurades mitjançant qüestionaris psicològics) i també en judicis tècnics professionals, basats en l’acumulació d’experiència obtinguda pel treball. En aquesta investigació, es validen dos qüestionaris psicomètrics que poden ser útils per predir el grau d’adaptació regimental: un de personalitat, el CPS (Cuestionario de Personalidad Situacional) i l’altre d’impulsivitat, el BARRAT (BIS-11). Els resultats demostren que les variables del CPS prediuen millor el comportament conflictiu, mentre que la impulsivitat mesurada pel BARRAT prediu millor el comportament adaptat. També es validen els criteris tècnics psicològic (judici tècnic emès per part del psicòleg) i criminològic (judici tècnic emès per part del jurista criminòleg). El pas següent ha estat fer una validació creuada que consisteix en la comparació mútua entre el criteris psicomètrics i els tècnics, per veure quines variables són finalment seleccionades de cara a la predicció de la variable més rellevant de l’adaptació regimental: haver tingut o no una regressió de grau de tractament penitenciari. Els resultats demostren que no hi ha una superioritat dels criteris psicomètrics sobre els criteris tècnics i que no estan oposats, sinó que es reforcen mútuament per millorar la predicció del grau d’adaptació regimental. El poder predictiu de les variables seleccionades és encara més alt quan es tracta de predir l’adaptació al règim penitenciari dels interns primaris (els que ingressen per primera vegada a la presó) que quan es refereix als reincidents. D’altra banda, s’ha baremat el qüestionari d’impulsivitat de BARRAT (BIS-11) en població penitenciària per convertir-lo en una eina de pronòstic, tant de comportament regimental com de reincidència penal.

Variable phenotypic expressivity in a Swiss family with autosomal dominant retinitis pigmentosa due to mutation T494m in the Prpf3 gene

Purpose:to describe the clinical features in a five generations family segregating autosomal dominant retinitis pigmentosa and to identify the causative gene Patient and Methods:Twenty five individuals of a large five-generation family originating from Western Switzerland were ascertained for phenotypic and genotypic characterization. Ophthalmologic evaluations included color vision testing, Goldman perimetry and digital fundus photography. Some patients had autofluorescence (AF) imaging, ocular coherence tomography (OCT) and ISCEV-standard full-field electroretinography (ERG). Blood samples were collected from 10 affected (4 to 70 years of age) and 15 unaffected members after informed consent. DNA was isolated and exons and intron-exons junctions of known adRP genes were sequenced using a Big Dye sequencing kit 1.1. Results:Age of onset of nightblindness and severity of progression of the disease was variable between members of the family. Some patients had early onset of nightblindess aged 3, others at mid-twenties. Most patients had visual acuity above 0.6 for the first 4 decades. Two older patients still had good vision (0.4) in their seventies. Myopia (range: -2 to -5) was noticed in most affected subjects. Fundus findings showed areas of atrophy along the arcades. The AF imaging showed a large high density ring bilaterally. A T494M change was found in exon 11 of PRPF3 gene. The change segregates with the disease in the family. Conclusion: A mutation in the PRPF3 gene is rare compared with other genes causing ADRP. Although a T494M change has been reported, our family is the first one with a variable expressivity. Mutations in PRPF3 gene can cause a variable phenotype of ADRP unlike the previously described Danish and English families. Our report gives a better understanding as to the phenotype/genotype description of ADRP due to PRPF3 mutation.

Use of the 2,3-diacyl-trehalose and the purified protein derivative in the serodiagnosis of tuberculosis in AIDS

The effect of the human immunodeficiency virus (HIV) infection on IgG production against purified protein derivative (PPD) and 2,3-diacil-trehalose (SL-IV) was investigated by an enzyme-linked immunosorbent assay (ELISA) test. Comparison between the antigens showed that immunocompetent patients produce preferentially antibodies to SL-IV than to PPD (73.3% versus 63.3%). Combination of these results showed an increase of the sensitivity to 80%, which decreased over the spectrum of immunodepression caused by HIV. In the tuberculous HIV seropositive group the sensitivities of SL-IV and PPD were 36.4% versus 40% and 0% versus 22.2% in the tuberculosis/acquired immunodeficiency syndrome (TB/AIDS) group. Combination of these results gave respectively 54.5% and 20%, showing that serological tests have limited value for diagnosis of tuberculosis in HIV infected patients. High antibody levels were observed in HIV seropositive asymptomatic group, but only two individuals were positive for both antigens. In the follow up, one of them developed tuberculous lymphadenitis, indicating that further work is needed to access the value of serological tests in predicting tuberculosis in HIV infected individuals.

Les TIC a l'ensenyament de la modelització matemàtica en Ciències Econòmiques i en Ciències Experimentals

Aquest projecte proposa materials didàctics per a un nou plantejament de les assignatures de Matemàtiques dels primers cursos de Ciències Empresarials i d'Enginyeria Tècnica, més acord amb el procés de convergència europea, basat en la realització de projectes que anomenem “Tallers de Modelització Matemàtica” (TMM) en els quals: (1) Els alumnes parteixen de situacions i problemes reals per als quals han de construir per sí mateixos els models matemàtics més adients i, a partir de la manipulació adequada d’aquests models, poden obtenir la informació necessària per donar-los resposta. (2) El treball de construcció, experimentació i avaluació dels models es realitza amb el suport de la calculadora simbòlica Wiris i del full de càlcul Excel com a instruments “normalitzats” del treball matemàtic d’estudiants i professors. (3) S’adapten els programes de les assignatures de matemàtiques de primer curs per tal de poder-les associar a un petit nombre de Tallers que parteixen de situacions adaptades a cada titulació. L’assignatura de Matemàtiques per a les Ciències Empresarials s’articula entorn de dos tallers independents: “Matrius de transició” pel que fa a l’àlgebra lineal i “Previsió de vendes” per a la modelització funcional en una variable. L’assignatura de Matemàtiques per a l’Enginyeria s’articula entorn d’un únic taller, “Models de poblacions”, que abasta la majoria de continguts del curs: successions i models funcionals en una variable, àlgebra lineal i equacions diferencials. Un conjunt d’exercicis interactius basats en la calculadora simbòlica WIRIS (Wiris-player) serveix de suport per al treball tècnic imprescindible per al desenvolupament de les dues assignatures. L’experimentació d’aquests tallers durant 2 cursos consecutius (2006/07 i 2007/08) en dues universitats catalanes (URL i UAB) ha posat en evidència tant els innegables avantatges del nou dispositiu docent per a l’aprenentatge dels estudiants, així com les restriccions institucionals que actualment dificulten la seva gestió i difusió.

Site-specific conjugation of a radioiodinated phenethylamine derivative to a monoclonal antibody results in increased radioactivity localization in tumor.

The preparation of a novel radioiodination reagent, the (aminooxy)acetyl derivative of (p-[125]-iodophenyl)ethylamine, is described. Conventional radioiodination of proteins involves the formation of iodotyrosine residues, but for in vivo applications such as thyroid or stomach immunoscintigraphy, the susceptibility of these residues to tissue dehalogenases constitutes a serious disadvantage. Using our new compound, which has a particularly nonreactive aromatic ring, we confirm and extend studies published by other workers indicating the much greater in vivo stability of iodophenyl compounds compared to the more conventional iodophenolic ones. In addition, the aminooxy group of our reagent gives a stable and specific linkage to aldehyde groups formed by periodate oxidation on the sugar moiety of antibody molecules. In vitro, favorable binding activity and high stability was obtained with a (([125I]iodoaryl)amino)oxy labeled monoclonal antibody directed against carcinoembryonic antigen. In vivo, using paired labeling experiments in nude mice bearing colon carcinoma xenografts, the (([125I]iodoaryl)amino)oxy-MAb (MAb = monoclonal antibody) was compared with the same MAb 131I-labeled by conventional chloramine-T method. Tumor 125I concentration of (arylamino)oxy MAb (measured as percent injected dose per gram) was significantly higher as compared to values obtained with a conventionally labeled 131I antibody. Additionally, thyroid uptake, an indicator of iodine release from the antibody, was up to 25 times lower after injection of 125I-MAb obtained by the new method as compared to the conventionally iodinated 131I-MAb.

Comparative Histopathology of Biomphalaria glabrata, B. tenagophila and B. straminea with Variable Degrees of Resistance to Schistosoma mansoni Miracidia

A comparative histopathological study of three snails species - Biomphalaria glabrata, B. tenagophila and B. straminea - which had been infected with Schistosoma mansoni miracidia revealed similar qualitative features, consisting of areas of sporocyst proliferation and differentiation associated with reactive host reaction, at the time they were actively eliminating great number of cercariae. However, in specimens that were exposed to miracidia but failed to eliminate cercariae later on, different histopathological pictures were observed in different snail species. While B. glabrata exhibited frequent focal (granulomatous) proliferation of amebocytes in several organs, B. tenagophila and B. straminea only rarely showed such reactive changes, suggesting that the mechanism of resistance to miracidial infection probably follows different pathways in the snail species studied

Two monoclonal rat antibodies with specificity for the beta-chain variable region V beta 6 of the murine T-cell receptor.

Two rat monoclonal antibodies (mAbs), 44-22-1 and 46-6B5, which recognize an alloreactive cytotoxic clone, 3F9, have been further tested on a panel of T hybridomas and cytotoxic T-cell clones for binding and functional activities. The mAbs recognized only those cells sharing the expression of the T-cell receptor beta-chain variable region gene V beta 6 with 3F9. All V beta 6+ cells were activated by these mAbs under cross-linking conditions and their antigen-specific activation was blocked by soluble mAb. Furthermore, depletion of 46-6B5+ normal lymph node T cells eliminated all cells expressing the epitope recognized by 44-22-1 and V beta 6 mRNA.

Giant cell arteritis with spontaneous remission.

BACKGROUND: Clinical manifestations of giant cell arteritis (GCA) are variable. Whether signs and symptoms present in an explosive fashion or insidiously, once manifest the course is usually progressive unless treatment is initiated. METHODS: A retrospective review of patients with GCA seen in an outpatient neuro-ophthalmology clinic. RESULTS: We report four patients with biopsy-proven GCA who experienced spontaneous remission. Clinical manifestations consisted of headache and diplopia in two patients, constitutional symptoms in one patient and facial pain in another. CONCLUSIONS: Clinicians should be aware of this aspect of the disease in order to avoid a delay in diagnosis and treatment.