Giant warts in a kidney transplant patient: regression with sirolimus.

Purpose: Recent reports have suggested that intraabdominal postoperative infection is associated with higher rates of overall and local recurrence and cancer-specific mortality. However, the mechanisms responsible for this association are unknown. We hypothesized that the greater inflammatory response in patients with postoperative intraabdominal infection is associated to an increase in local and systemic angiogenesis. Methods: We designed a prospective cohorts study with matched controls. Patients with postoperative intra-abdominal infection (abscess and/or anastomotic leakage) (group 1; n=17) after elective colorectal cancer resection operated on for cure were compared to patients with an uncomplicated postoperative course (group 2; n=17). IL-6 and VEGF levels were determined by ELISA in serum and peritoneal fluid at baseline, 48 hours and postoperative day 4 or at the time the peritoneal infection occurred. Results: No differences were observed in age, gender, preoperative CEA, tumor stage and location and type of procedure performed. Although there were no differences in serum IL-6 levels at 48 hours, this pro-inflammatory cytokine was higher in group 1 on postoperative day 4 (group 1: 21533 + 27900 vs. group 2: 1130 + 3563 pg/ml; p < 0.001). Serum VEGF levels were higher in group 1 on postoperative day 4 (group 1: 1212 + 1025 vs. group 2: 408 + 407 pg/ml; p < 0.01). Peritoneal fluid VEGF levels were also higher in group 1 at 48 hours (group 1: 4857 + 4384 vs. group 2: 630 + 461 pg/ml; p < 0.001) and postoperative day 4 (group 1: 32807 + 98486 vs. group 2: 1002 + 1229 pg/ml; p < 0.001). A positive correlation between serum IL-6 and VEGF serum levels was observed on postoperative day 4 (r=0.7; p<0.01). Conclusions: These results suggest that not only the inflammatory response but also the angiogenic pathways are stimulated in patients with intra-abdominal infection after surgery for colorectal cancer. The implications of this finding on long-term follow-up need to be evaluated.

Subcellular fractionation of stored red blood cells reveals a compartment-based protein carbonylation evolution.

During blood banking, erythrocytes undergo storage lesions, altering or degrading their metabolism, rheological properties, and protein content. Carbonylation is a hallmark of protein oxidative lesions, thus of red blood cell oxidative stress. In order to improve global erythrocyte protein carbonylation assessment, subcellular fractionation has been established, allowing us to work on four different protein populations, namely soluble hemoglobin, hemoglobin-depleted soluble fraction, integral membrane and cytoskeleton membrane protein fractions. Carbonylation in erythrocyte-derived microparticles has also been investigated. Carbonylated proteins were derivatized with 2,4-dinitrophenylhydrazine (2,4-DNPH) and quantified by western blot analyses. In particular, carbonylation in the cytoskeletal membrane fraction increased remarkably between day 29 and day 43 (P<0.01). Moreover, protein carbonylation within microparticles released during storage showed a two-fold increase along the storage period (P<0.01). As a result, carbonylation of cytoplasmic and membrane protein fractions differs along storage, and the present study allows explaining two distinct steps in global erythrocyte protein carbonylation evolution during blood banking. This article is part of a Special Issue entitled: Integrated omics.

Structure of a multisubunit complex that promotes DNA branch migration.

The RuvA and RuvB proteins of Escherichia coli, which are induced in response to DNA damage, are important in the formation of heteroduplex DNA during genetic recombination and related recombinational repair processes. In vitro studies show that RuvA binds Holiday junctions and acts as a specificity factor that targets the RuvB ATPase, a hexameric ring protein, to the junction. Together, RuvA and RuvB promote branch migration, an ATP-dependent reaction that increases the length of the heteroduplex DNA. Electron microscopic visualization of RuvAB now provides a new insight into the mechanism of this process. We observe the formation of a tripartite protein complex in which RuvA binds the crossover and is sandwiched between two hexameric rings of RuvB. The Holliday junction within this complex adopts a square-planar structure. We propose a molecular model for branch migration, a unique feature of which is the role played by the two oppositely oriented RuvB ring motors.

Congenital giant aneurysm of the left coronary artery.

We report an unusual case of congenital giant coronary aneurysm. A 23 year-old male with a history of acute myocardial infarction presented an abnormal shadow in the left cardiac border on routine X-ray. Electrocardiogram and physical examination were normal without any clinical signs of inflammation, but computed tomography (CT) scan and cardiac magnetic resonance imaging (MRI) revealed a giant (>50mm) coronary aneurysm. Coronary artery bypass grafting (CABG) with coronary artery aneurysm (CAA) resection resolved the CAA. Coronary artery aneurysms are entities of localised dilation and can be common events in chronic infectious disease as a result of the systemic inflammatory state; however, giant coronary aneurysms (measuring more than 50mm) are rare. This is especially true where the pathological aetiology was not clearly defined or was believed to be of congenital origin. To date only a few published case reports exist for this type of pathological entity.

Proyecto de salud communitaria en un barrio marginal de Quito : evaluación de las necesidades y planteamiento de una red de prevención y attención primaria : documento para la acción local

Résumé du document de thèse Quito, capitale andine de près de deux millions d'habitants, a vu se développer des quartiers ghettos réunissant une population en constante évolution. Mouvements migratoires mal connus, hétérogénéité ethnique et socioculturelle, accès limité aux services publics et conditions de vie difficiles jouent un rôle essentiel mais complexe dans la planification des services de santé. L'étude ciblée de cette problématique est un sérieux défi à relever car les mégalopoles latino-américaines connaissent une importante urbanisation avec pour corollaire une augmentation de la pauvreté urbaine. Les indicateurs de santé tels que mortalité infantile, espérance de vie ou incidence des maladies infectieuses montrent une amélioration globale qui ne reflète toutefois pas les importantes disparités caractéristiques du continent. La démarche exposée dans ce document est une réponse à la demande d'un appui médical par une communauté urbaine défavorisée, pour laquelle peu de données étaient disponibles. Une évaluation des conditions de vie et des besoins en soins a donc été effectuée par trois étudiants en médecine de Lausanne au moyen d'une enquête et d'ateliers qui ont permis de réunir les opinions des différents acteurs sociaux et sanitaires. Cette étude a pu identifier et mesurer les déterminants de santé, comprendre certaines dynamiques locales pour enfin cibler les principales lignes d'actions d'un centre de santé communautaire. Ce document décrit l'ensemble du processus conduit durant cinq ans et expose les données brutes ainsi que leur analyse ; il propose des recommandations concrètes pour une promotion de la santé adaptée aux besoins d'une communauté urbaine défavorisée d'Amérique du Sud. Son objectif est de fournir des données utilisables par les acteurs de santé locaux et de participer ainsi à la réflexion en cours sur la réforme du système de santé équatorien. Il comporte également une bibliographie, point de départ pour d'autres études sur le sujet. Le dossier, construit de manière chronologique, présente l'information de façon accessible et cohérente. Il se veut un témoignage utile, avec ses forces et ses faiblesses, à l'action locale sous forme d'une publication en espagnol qui sera distribuée aux différents acteurs sociaux et sanitaires concernés.

Disease-causing mutations improving the branch site and polypyrimidine tract: pseudoexon activation of LINE-2 and antisense Alu lacking the poly(T)-tail.

Cryptic exons or pseudoexons are typically activated by point mutations that create GT or AG dinucleotides of new 5' or 3' splice sites in introns, often in repetitive elements. Here we describe two cases of tetrahydrobiopterin deficiency caused by mutations improving the branch point sequence and polypyrimidine tracts of repeat-containing pseudoexons in the PTS gene. In the first case, we demonstrate a novel pathway of antisense Alu exonization, resulting from an intronic deletion that removed the poly(T)-tail of antisense AluSq. The deletion brought a favorable branch point sequence within proximity of the pseudoexon 3' splice site and removed an upstream AG dinucleotide required for the 3' splice site repression on normal alleles. New Alu exons can thus arise in the absence of poly(T)-tails that facilitated inclusion of most transposed elements in mRNAs by serving as polypyrimidine tracts, highlighting extraordinary flexibility of Alu repeats in shaping intron-exon structure. In the other case, a PTS pseudoexon was activated by an A>T substitution 9 nt upstream of its 3' splice site in a LINE-2 sequence, providing the first example of a disease-causing exonization of the most ancient interspersed repeat. These observations expand the spectrum of mutational mechanisms that introduce repetitive sequences in mature transcripts and illustrate the importance of intronic mutations in alternative splicing and phenotypic variability of hereditary disorders.

Giant extraskeletal myxoid chondrosarcoma of the thigh treated by wide extraarticular resection and reconstruction with a tumor prosthesis

Introduction: Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue tumour with a high risk for local recurrence and metastases. While this entity is resistant to radio- or chemo-therapy, wide resection remains the treatment of choice. Case report: A 60 year old man presented to our service with a large mass in his right thigh, slowly evolving over the past 7 years. His main complaint was the volume of his thigh. Imaging showed a 23x13x14 cm tumour in the quadriceps, eroding the cortical bone and with potential contamination of the knee joint. The risk of a pathological fracture was estimated considerable. A CT-guided core-needle biopsy revealed a FNCLCC grade 2 EMC. A thoraco-abdominal CT scan showed multiple pulmonary metastases. Due to the palliative situation with a very slow disease progression, a wide extraarticular resection of the distal femur and reconstruction with a megaprosthesis were performed. Extensive skin necrosis necessitated three revision procedures for débridement and confection of a pediculated lateral gastrocnemius muscle flap. No complementary treatment was possible for the pulmonary metastases. At 18 months follow-up, he walked without crutches, was able to do his activities of daily living. He was painfree and highly satisfied with the result. During the follow-up, slow progression of the pulmonary metastases was noted, which remained asymptomatic. Conclusion: Extraskeletal myxoid chondrosarcoma is a rare soft tissue tumour, and wide excision remains the treatment of choice. Whenever possible, limb salvage should be proposed to preserve function and quality of life.

Time and temperature dependant changes in red blood cell analytes used for testing recombinant erythropoietin abuse in sports.

There has been a long debate since the introduction of blood analysis prior to major sports events, to find out whether blood samples should be analysed right away on the site of competition or whether they should be transported and analysed in an anti-doping laboratory. Therefore, it was necessary to measure blood samples and compare the results obtained right after the blood withdrawal with those obtained after a few hours delay. Furthermore, it was interesting to determine the effect of temperature on the possible deterioration of red blood cell analytes used for testing recombinant erythropoietin abuse. Healthy volunteers were asked to give two blood samples and one of these was kept at room temperature whereas the second one was put into a refrigerator. On a regular basis, the samples were rolled for homogenisation and temperature stabilisation and were analysed with the same haematological apparatus. The results confirmed that blood controls prior to competition should be performed as soon as possible with standardised pre-analytical conditions to avoid too many variations notably on the haematocrit and the reticulocyte count. These recommendations should ideally also be applied to the all the blood controls compulsory for the medical follow up, otherwise unexplainable values could be misinterpreted and could for instance lead to a period of incapacity.

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.

Analysis and clinical relevance of microparticles from red blood cells.

PURPOSE OF REVIEW: The mechanisms involved in the formation of red blood cell (RBC) microparticles in vivo as well as during erythrocyte storage are reviewed, and the potential role of microparticles in transfusion medicine is described. RECENT FINDINGS: Microparticles release is an integral part of the erythrocyte ageing process, preventing early removal of RBCs. Proteomics analyses have outlined the key role of band 3-ankyrin anchoring complex and the occurrence of selective RBC membrane remodelling mechanisms in microparticles formation. The presence of several RBC antigens, expressed on microparticles, has been demonstrated. The potential deleterious effects of RBC microparticles in transfused recipients, including hypercoagulability, microcirculation impairment and immunosuppression, are discussed. SUMMARY: Formation and role of RBC microparticles are far from being completely understood. Combining various approaches to elucidate these mechanisms could improve blood product quality and transfusion safety. Implementation of RBC microparticles as biomarkers in the laboratory routine needs to overcome technical barriers involved in their analysis.

Characterization of pupil responses to blue and red light stimuli in autosomal dominant retinitis pigmentosa due to NR2E3 mutation.

PURPOSE: We characterized the pupil responses that reflect rod, cone, and melanopsin function in a genetically homogeneous cohort of patients with autosomal dominant retinitis pigmentosa (adRP). METHODS: Nine patients with Gly56Arg mutation of the NR2E3 gene and 12 control subjects were studied. Pupil and subjective visual responses to red and blue light flashes over a 7 log-unit range of intensities were recorded under dark and light adaptation. The pupil responses were plotted against stimulus intensity to obtain red-light and blue-light response curves. RESULTS: In the dark-adapted blue-light stimulus condition, patients showed significantly higher threshold intensities for visual perception and for a pupil response compared to controls (P = 0.02 and P = 0.006, respectively). The rod-dependent, blue-light pupil responses decreased with disease progression. In contrast, the cone-dependent pupil responses (light-adapted red-light stimulus condition) did not differ between patients and controls. The difference in the retinal sensitivity to blue and red stimuli was the most sensitive parameter to detect photoreceptor dysfunction. Unexpectedly, the melanopsin-mediated pupil response was decreased in patients (P = 0.02). CONCLUSIONS: Pupil responses of patients with NR2E3-associated adRP demonstrated reduced retinal sensitivity to dim blue light under dark adaptation, presumably reflecting decreased rod function. Rod-dependent pupil responses were quantifiable in all patients, including those with non-recordable scotopic electroretinogram, and correlated with the extent of clinical disease. Thus, the chromatic pupil light reflex can be used to monitor photoreceptor degeneration over a larger range of disease progression compared to standard electrophysiology.

Carcinome baso-cellulaire géant de la paupière chez une patiente noire Camerounaise [Giant basal cell carcinoma of the eyelid in a black patient from Cameroon].

Basal cell carcinoma of the skin is the most common human cancer. It is also the most frequent malignant tumor of the eyelid. In Europe, its most common clinical presentation is a hard indurated, and sometimes ulcerated nodule. The authors report a giant palpebral basal cell carcinoma in a black non albinos Cameroonian patient. The ethnic origin, localization and macroscopic aspect are discussed. The problems connected with diagnosis and treatment of malignant tumors in Africa are noted.

Des céphalées, cinq avis spécialisés: les pièges diagnostiques pour la maladie de Horton [Headaches, five expert opinions: the pitfalls involved in the diagnosis of giant cell arteritis].

Giant cell arteritis (GCA) (or Horton's disease) is a systemic disease affecting the vessels of medium and large sizes. The incidence increases with age (the disease develops rarely before age 50) and the etiology remains unknown. Clinical manifestations may vary (including asthenia, temporal headache, visual disturbances, etc.) and GCA can potentially lead to dramatic consequences (permanent loss of vision). Although some anomalies in the investigations may help in the diagnosis of GCA, research and confirmation of the diagnosis of GCA may be difficult, especially when the symptoms presented by patients are spread out in time and appear to be nonspecific at first.

The E.coli RuvAB proteins branch migrate Holliday junctions through heterologous DNA sequences in a reaction facilitated by SSB.

During genetic recombination a heteroduplex joint is formed between two homologous DNA molecules. The heteroduplex joint plays an important role in recombination since it accommodates sequence heterogeneities (mismatches, insertions or deletions) that lead to genetic variation. Two Escherichia coli proteins, RuvA and RuvB, promote the formation of heteroduplex DNA by catalysing the branch migration of crossovers, or Holliday junctions, which link recombining chromosomes. We show that RuvA and RuvB can promote branch migration through 1800 bp of heterologous DNA, in a reaction facilitated by the presence of E.coli single-stranded DNA binding (SSB) protein. Reaction intermediates, containing unpaired heteroduplex regions bound by SSB, were directly visualized by electron microscopy. In the absence of SSB, or when SSB was replaced by a single-strand binding protein from bacteriophage T4 (gene 32 protein), only limited heterologous branch migration was observed. These results show that the RuvAB proteins, which are induced as part of the SOS response to DNA damage, allow genetic recombination and the recombinational repair of DNA to occur in the presence of extensive lengths of heterology.