Malignant gastroduodenal obstruction: palliation with self-expanding metallic stents.

PURPOSE: To evaluate the feasibility, efficacy, and tolerance of self-expanding metallic stent insertion under fluoroscopic guidance for palliation of symptoms related to malignant gastroduodenal obstruction. MATERIALS AND METHODS: Seventy-two patients (38 men, 34 women) aged 25-98 years (mean, 62 years) with duodenal (n = 43), antropyloric (n = 13), surgical gastrojejunostomy (n = 10), or pyloroduodenal (n = 6) malignant obstruction were referred for insertion of self-expanding metallic stents over a 6-year period. Stent insertion was performed with use of a peroral or transgastric approach when necessary (n = 11). RESULTS: Stents were successfully inserted in 70 of the 72 patients (97%) and provided symptom relief in 65 patients (90%). Inserted stents were mainly uncovered vascular (n = 55) or enteral (n = 10) Wallstents. One hundred eight stents were initially inserted: one, two, three, or four stents were indicated in 43, 17, nine, and one patient, respectively. Mean follow-up was 119 days (range, 4-513 days). Mean stent patency was 113 days (range, 4-513 days). Mean survival of patients was 120 days. During follow-up, stent obstruction occurred in seven patients as a result of tumoral overgrowth (n = 5) or ingrowth (n = 2). Complications occurred in 12 of the 72 patients (17%), including stent migration (n = 8), stent fracture (n = 1), duodenal perforation (n = 1), and death related to general anesthesia (n = 1). CONCLUSION: Despite a significant complication rate, self-expanding metallic stent insertion under fluoroscopic guidance appears to be a feasible and useful technique in the palliative management of malignant gastroduodenal obstruction.

[Orvieto. Duomo]

Référence bibliographique : Weigert, 299

[Venise. Basilica di San Marco]

Référence bibliographique : Weigert, 729

[Venise. Basilica di San Marco]

Référence bibliographique : Weigert, 730

The histone-interacting domain of nuclear factor I activates simian virus 40 DNA replication in vivo.

Efficient initiation of SV40 DNA replication requires transcription factors that bind auxiliary sequences flanking the minimally required origin. To evaluate the possibility that transcription factors may activate SV40 replication by acting on the chromatin structure of the origin, we used an in vivo replication system in which we targeted GAL4 fusion proteins to the minimally required origin. We found that the proline-rich transcriptional activation domain of nuclear factor I (NF-I), which has been previously shown to interact with histone H3, specifically activates replication. Evaluation of a series of deletion and point mutants of NF-I indicates that the H3-binding domain and the replication activity coincide perfectly. Assays with other transcription factors, such as Sp1, confirmed the correlation between the interaction with H3 and the activation of replication. These findings imply that transcription factors such as NF-I can activate SV40 replication via direct interaction with chromatin components, thereby contributing to the relief of nucleosomal repression at the SV40 origin.

Cost Analysis of Long-Term Treatment of Patients with Symptomatic Gastroesophageal Reflux Disease (GERD) with Esomeprazole On-Demand Treatment or Esomeprazole Continuous Treatment: An Open, Randomized, Multicenter Study in Switzerland.

Objectives: To assess the difference in direct medical costs between on-demand (OD) treatment with esomeprazole (E) 20 mg and continuous (C) treatment with E 20 mg q.d. from a clinical practice view in patients with gastroesophageal reflux disease (GERD) symptoms. Methods: This open, randomized study (ONE: on-demand Nexium evaluation) compared two long-term management options with E 20 mg in endoscopically uninvestigated patients seeking primary care for GERD symptoms who demonstrated complete relief of symptoms after an initial treatment of 4 weeks with E 40 mg. Data on consumed quantities of all cost items were collected in the study, while data on prices during the time of study were collected separately. The analysis was done from a societal perspective. Results: Forty-nine percent (484 of 991) of patients randomized to the OD regimen and 46% (420 of 913) of the patients in the C group had at least one contact with the investigator that would have occurred nonprotocol-driven. The difference of the adjusted mean direct medical costs between the treatment groups was CHF 88.72 (95% confidence interval: CHF 41.34-153.95) in favor of the OD treatment strategy (Wilcoxon rank-sum test: P < 0.0001). Adjusted direct nonmedical costs and productivity loss were similar in both groups. Conclusions: The adjusted direct medical costs of a 6-month OD treatment with esomeprazole 20 mg in uninvestigated patients with symptoms of GERD were significantly lower compared with a continuous treatment with E 20 mg once a day. The OD therapy represents a cost-saving alternative to the continuous treatment strategy with E.

Jean-Baptiste Perronneau (ca. 1715-1783). Un portraitiste dans l'Europe des Lumières

Les monographies consacrées à Jean-Baptiste Perronneau (ca 1715-1783) à la fin du XIXe siècle et au début du XXe siècle traduisaient l'engouement pour l'art du XVIIIesiècle qui se déployait dans le Tout Paris de la Belle Époque. Elles rendaient justice au peintre de l'Académie royale de peinture et de sculpture de Paris, et à l'un des peintres favoris des contemporains des Impressionnistes qu'elles présentaient comme un artiste éclipsé de son vivant par son prestigieux aîné, Maurice Quentin Delatour (1704-1788). La première partie de la thèse étudie la carrière parisienne du peintre, ses appuis artistiques et sociaux, ses pratiques au pastel et à l'huile, de l'agrément en 1746 à la réception en 1753 et avant le début de la période des voyages en 1756. La rivalité avec Delatour, mise en scène dans un esprit d'émulation au Salon du Louvre pendant plus de vingt ans, y est largement évoquée. Un même nombre de portraits exposés fait comprendre que Perronneau avait de son vivant la faveur des artistes et du public. Il permet de mesurer les effets de la rivalité avec le peintre de Cour sur sa carrière. Delatour faisait exposer en 1750 son autoportrait à côté de son portrait demandé à Perronneau. Les qualités des deux peintres étaient comparées par la nouvelle critique. Notre étude s'attache à ce qui les rapproche comme à ce qui les sépare. Dans la deuxième partie, les peintres des milieux artistiques qu'il fréquente, Louis Tocqué, Jean-Baptiste Oudry, Charles Nicolas Cochin, pour citer les principaux, sont convoqués pour évaluer l'art de Perronneau dans ce que Cochin appelle la « ressemblance savante ». Les peintres les plus ambitieux s'attachent à son interprétation malgré les difficultés dues aux réactions de leur clientèle. La façon dont procède Perronneau est ici envisagée suivant deux aspects : d'une part, la composition du portrait selon une idée du naturel qui détermine l'attitude et une certaine imitation des défauts ; d'autre part, l'imitation de la nature qui réside dans les qualités de l'art, et donc picturales, appréciées des amateurs avertis. La façon qui lui est propre est de composer un naturel selon des poses variées, fondé sur la noblesse de l'attitude conjuguée à la simplicité, conformément à l'idéal courtois en vigueur depuis le XVIe siècle ; elle reste immuable au long de sa carrière. Dans l'imitation de la nature, sont mis en évidence des aspects cachés du faire lors de la mise en place du relief de la figure, les références aux maîtres anciens, Rembrandt, Van Dyck, la conscience de la distance à laquelle le tableau doit être vu, qui atténue la vigueur de la touche, comme le fait le verre qui sert aussi de vernis au pastel. L'idée de sprezzatura qui régit la distinction légère de la pose se décèle à la surface de ses portraits à travers l'apparence de facilité qu'il s'attache à leur donner, et jusque dans l'inimitable retouche finale. Grâce à la qualité de sa retouche, Perronneau accroît sensiblement dans certaines oeuvres à partir de 1768 l'expression savante et inventive de son sentiment. Afin de peindre comme il l'entend tout en gagnant sa vie et celle de sa famille, le peintre prend le parti de voyager comme l'y autorisait la libéralité de son statut. Dans la troisième partie est étudiée la trame de ses voyages que constituent les recommandations dont il bénéficie. Les identités des quatre cent dix modèles peints en France et en Europe de 1740 à 1782 sont systématiquement étudiées dans le catalogue ainsi que les conditions de leur rencontre avec le peintre. Elles décrivent une clientèle variée représentative de la mobilité des statuts dans l'Europe d'ancien Régime dont la composante nouvelle est la clientèle du monde de la banque internationale et du grand commerce. Leurs portraits peints à l'étranger ou dans les villes de Province que Perronneau présente au Salon irritent et inquiètent l'élite parisienne et donne lieu à de nouvelles tensions avec l'éternel rival, Delatour, au Salon de 1767. Perronneau se sent à juste titre évincé de Paris. Alors que l'on avait pu penser qu'il avait peu souffert des critiques du philosophe qui ne furent publiées qu'après sa mort, il apparaît que sa réputation pâtit de ses jugements diffusés par les nouvelles à la main au-delà des frontières et jusqu'auprès de la prestigieuse clientèle qui lui était acquise. Le travail sur son la carrière et l'oeuvre de Perronneau permet surtout une compréhension nouvelle de l'art du portrait au milieu du siècle, au moment où la représentation individuelle n'a jamais encore touché un aussi large public et où l'Académie ambitionne d'élever cet art au plus haut degré.

A pilot study of the efficacy of IL1 blockade by anakinra in acute calcific periarthritis of the rotator cuff

Background/Purpose: Calcific periarthritis of rotator cuff can induce acute and severe shoulder pain and is accompnied by signs of acute inflammation. The calcific deposits are composed of calcium phosphate crystals such as hydroxyapatite or basic calcium phosphate. These crystals stimulate the production and release of IL1b from macrophages, in an analogous manner to MSU and CPPD crystals. As IL1 blockade is effective in reducing signs and symptoms of inflammation in acute gout, we performed a pilot study to study if it is also effective in calcific periarthritis Methods: 5 consecutive patients were included (mean age: 62, 3 females, 2 males) between March 2011 and March 2012. Symptoms of acute shoulder pain at rest had to be present for _7 days before inclusion, associated with limitation of shoulder mobility and the presence on calcification in the rotator cuff by conventional radiography. None of the patients had responded to at least 48 hours of high doses of NSAIDs. Exclusion criteria included no corticosteroid therapy in the last 2 weeks and the exclusion of other rheumatologic or infectious diseases- .Clinical evaluation consisted of patient assessment of pain (total, rest and activity) by VAS (100mm scale) at days 0, 1, 3, 15, 42 and clinical examination of shoulder mobility at days 0, 3, 15. ESR and CRP were measured at days 0, 3. Plain radiographs were performed at days 0 and 15 and an ultrasound examination (including Doppler) was performed at days 0, 3, 15. Anakinra 100mg daily was administered for 3 consecutive days after the first evaluation (day 0). Rescue analgesics were allowed and recorded. Results: At inclusion, all patients had severe shoulder pain: mean (SD) VAS day pain of 72mm (_25mm), mean VAS night pain of 96 (_ 5) and impaired shoulder mobility. CRP was elevated in all of them (mean of 3X). Treatment with anakinra lead to rapid relief of pain in all patients, starting already on the first night following the first injection. The reduction of VAS pain was particularly striking for rest pain: mean (SD) VAS of 4mm (_ 5) at day 1 and this response was maintained for the 5 patients at the end of the three injections without any need of rescue medication. Mean rest VAS was 6 (_8) at day 3. The effect on day pain was less spectacular: mean (SD) VAS at D1 of 30 (_ 18), at D3 of 27 (_ 11). Shoulder mobility also improved and the CRP normalized in 4 of 5 patients at day 3. At day 42, 4 of 5 the patients were still totally asymptomatic. On X rays and US, the calcifications were reduced in size: mean maximal diameter of 21 mm at day 0 to 12 mm at day 15, but did not disappear in any patient. The main change on US was a significant and rapid (at day 3) reduction of Doppler activity around the calcification. Conclusion: This pilot open study suggests that IL-1_ inhibition may be an interesting therapeutic approach in acute calcific periarthritis, especially in patients who have not responded adequately to NSAIDs. The effect on pain seems to be more rapid (within a few hours) than steroid injection although a randomized controlled study needs to be performed to confirm this observation.

Four-corner bone arthrodesis with dorsal rectangular plate: series and personal technique.

Controversy exists about the best method to achieve bone fusion in four-corner arthrodesis. Thirty-five patients who underwent this procedure by our technique were included in the study. Surgical indications were stage II-III SLAC wrist, stage II SNAC wrist and severe traumatic midcarpal joint injury. Mean follow-up was 4.6 years. Mean active flexion and extension were 34 degrees and 30 degrees respectively; grip strength recovery was 79%. Radiological consolidation was achieved in all cases. The mean DASH score was 23 and the postoperative pain improvement by visual analogue scale was statistically significant. Return to work was possible at 4 months for the average patient. Complications were a capitate fracture in one patient and the need for hardware removal in four cases. Four-corner bone wrist arthrodesis by dorsal rectangular plating achieves an acceptable preservation of range of motion with good pain relief, an excellent consolidation rate and minimal complications.

Canakinumab Relieves Symptoms of Acute Flares and Improves Health-Related Quality Of Life (HRQoL) in Difficult-To-Treat Gouty Arthritis Patients by Suppressing Inflammation: Results of a Randomized, Dose-Ranging Study

RATIONALE:We investigated the impact of canakinumab, a fully human anti-interleukin-1b monoclonal antibody on inflammation and HRQoL in gouty arthritis patients.METHODS: In this 8-week, single-blind, dose-ranging study, patients with acute gouty arthritis flares, unresponsive/intolerant or contraindicated to NSAIDs and/or colchicine were randomized to single subcutaneous canakinumab (10, 25, 50, 90, or 150mg, N5143) or single intramuscular triamcinolone acetonide (TA, 40mg, N557). Patients assessed pain (Likert scale), physicians assessed clinical signs of joint inflammation, and HRQoL was recorded using SF-36.RESULTS: At baseline, 98% patients had moderate-to-extreme pain, 85% had moderate/severe joint swelling, 64-79% had elevated inflammatory markers and HRQoL scores indicated impaired physical function. Percentage of patients with no/mild pain was numerically greater in most canakinumab groups vs. TA, 24-72h post-dose; difference significant for 150mg group at these time-points (P<0.05). Canakinumab 150mg was associated with significantly lower Likert scores for tenderness [OR, 3.2; 95% CI, 1.27-7.89; P50.014] and swelling (OR, 2.7; 95% CI, 1.09-6.50, P50.032) at 72h vs. TA; erythema was not different. Median CRP and SAA levels normalized by 7 days post-dose in most canakinumab groups, but remained elevated in TA. Physical function improved at 7 days postdose in all groups, highest improvement for canakinumab 150mg. SF-36 scores for physical functioning and bodily pain with canakinumab 150mg approached US general population scores by 7 days post-dose and exceeded normal values by 8 weeks post-dose.CONCLUSION: Canakinumab 150mg produced significantly greater and rapid pain-relief and improvements in HRQoL vs. TAin acute gouty arthritis patients.

Pob1 participates in the Cdc42 regulation of fission yeast actin cytoskeleton.

Rho GTPases regulate the actin cytoskeleton in all eukaryotes. Fission yeast Cdc42 is involved in actin cable assembly and formin For3 regulation. We isolated cdc42-879 as a thermosensitive strain with actin cable and For3 localization defects. In a multicopy suppressor screening, we identified pob1(+) as suppressor of cdc42-879 thermosensitivity. Pob1 overexpression also partially restores actin cables and localization of For3 in the mutant strain. Pob1 interacts with Cdc42 and this GTPase regulates Pob1 localization and/or stability. The C-terminal pleckstrin homology (PH) domain of Pob1 is required for Cdc42 binding. Pob1 also binds to For3 through its N-terminal sterile alpha motif (SAM) domain and contributes to the formin localization at the cell tips. The previously described pob1-664 mutant strain (Mol. Biol. Cell. 10, 2745-2757, 1999), which carries a mutation in the PH domain, as well as pob1 mutant strains in which Pob1 lacks the N-terminal region (pob1DeltaN) or the SAM domain (pob1DeltaSAM), have cytoskeletal defects similar to that of cdc42-879 cells. Expression of constitutively active For3DAD* partially restores actin organization in cdc42-879, pob1-664, pob1DeltaN, and pob1DeltaSAM. Therefore, we propose that Pob1 is required for For3 localization to the tips and facilitates Cdc42-mediated relief of For3 autoinhibition to stimulate actin cable formation.

Tislauskolonnin varopurkauksen laskeminen dynaamisen simuloinnin avulla

Työn tavoitteena oli tutkia tislauskolonnin dynamiikkaa ja dynaamista mallintamista simulointien avulla. Dynaamisen simulointimallin avulla selvitettiin pentaanin erotuskolonnin toimintaa poikkeus- ja häiriötilanteissa. Lisäksi pyrittiin arvioimaan työssä käytettyjen simulointiohjelmistojen soveltuvuutta tislauksen dynaamiseen simulointiin. Työn kirjallisuusosassa käsiteltiin tislauskolonnindynamiikan mallintamista matemaattisten mallien avulla sekä tislauskolonnimallin rakentamista simulointiohjelmistoon. Kirjallisuusosassa esiteltiin myös tislauskolonnin häiriötilanteita ja niiden aiheuttamia varopurkaustapauksia. Tämän lisäksi kirjallisuusosassa käytiin läpi tislauskolonnin varoventtiilien mitoittamisen perusteita. Työn soveltavassa osassa muodostettiin tislauskolonnille dynaaminen simulointimalli Aspen HYSYS Dynamics ja PROSimulator-simulointiohjelmistolla. Mallien avulla tarkasteltiin erilaisten häiriöiden ja poikkeustilanteiden vaikutusta kolonnin käyttäytymiseen ja varopurkaus-tapauksiin. Työssä arvioitiin myös ohjelmistojen soveltuvuutta tislauksen dynaamiseen simulointiin. Työssä saatujen tulosten perusteella voidaan todeta, että dynaamisen simuloinnin avulla saadaan hyödyllistä tietoa tislauskolonnin toiminnasta häiriö- ja poikkeustilanteissa. Dynaamisen simuloinnin onnistuminen ja luotettavien tulosten saaminen edellyttää kuitenkin tarkasteltavan prosessin tuntemista ja ohjelmiston käytön hallintaa. Työssä käytetyn Aspen HYSYS Dynamics simulointiohjelmiston käytettävyydessä havaittiin puutteita ja ohjelmisto vaatii vielä kehitystyötä. Työssä käytetty PROSimulator-simulointiohjelmisto soveltui pienistä puutteista huolimatta hyvin tislauskolonnin häiriötilanteiden tutkimiseen.

Persistent Candida albicans colonization and molecular mechanisms of azole resistance in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) patients.

Objectives: Patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, APS-I) suffer from chronic candidosis caused mainly by Candida albicans, and repeated courses of azole antifungals have led to the development of resistance in the APECED patient population in Finland. The aim of our study was to address whether the patients are persistently colonized with the same or genetically closely related strains, whether epidemic strains are present and which molecular mechanisms account for azole resistance. Methods: Sets of C. albicans (n?=?19) isolates from nine APECED patients reported with decreased susceptibility to fluconazole isolated up to 9 years apart were included. The strains were typed by multilocus sequence typing. CDR1/2, MDR1 and ERG11 mRNA expression was analysed by northern blotting and Cdr1, Cdr2 and Mdr1 protein expression by western blotting, and TAC1 and ERG11 genes were sequenced. Results: All seven patients with multiple C. albicans isolates analysed were persistently colonized with the same or a genetically closely related strain for a mean of 5 years. All patients were colonized with different strains and no epidemic strains were found. The major molecular mechanisms behind the azole resistance were mutations in TAC1 contributing to overexpression of CDR1 and CDR2. Six new TAC1 mutations were found, one of which (N740S) is likely to be a gain-of-function mutation. Most isolates were found to have gained multiple TAC1 and ERG11 point mutations. Conclusions: Despite clinically successful treatment leading to relief of symptoms, colonization by C. albicans strains is persistent within APECED patients. Microevolution and point mutations occur within strains, leading to the development of azole-resistant isolates.

Representació de grans escenes urbanes emprant jerarquies d'impostors en relleu

Relief Mapping is giving great results for the creation of 3D impostor models. An impostor model is a simplication of an original geometric model that is used to replace it. Then, the original volume can be reproduced in a high quality representation with very few artifacts or cracks and a high compactness. We have studied the state of the art on Relief Impostors and some current techniques related to them. In particular, we have implemented the Omni-directional Relief Impostors (ORI) technique and its hierarchical extension (HORI), througn the usage of spatial partition methods. We expose an alternative to the spatial distribution and selection of the impostors. Furthermore, we show a different computation for the rendering view distance in order to guarantee a minimal quality for the simplified representation. Finally, we discuss the obtained results and propose some new ideas or approaches to enhance the efficiency and quality of the final rendering using ORIs' and HORIs' techniques. In addition, our implementation has involved a software engineering study in the Open Source field.

Fungus ball in the urinary tract: A rare entity.

A fungal mass in the urinary tract (fungus ball), mainly occurring in compromised patients, is a rare and dangerous complication of candiduria. We report 2 cases of fungus ball associated with hydronephrosis and sepsis. As reported in the literature, we treated the first patient by prompt relief of obstruction by nephrostomy and local and systemic antifungal agent. The second patient failed to respond to this treatment due to a distal ureteral stenosis and required open surgery with fungus ball removal and ureteral reimplantation. Despite a large success in urinary tract drainage with antifungal treatments, some cases need a modified approach due to anatomical modification.