Consultations infectiologiques ambutatoires non VIH: analyse d'un centre universitaire sur cinq ans [Non-HIV infectious disease outpatient consultations: a 5-year study in a Swiss University Hospital].

Few studies have examined the workload or clinical spectrum of non-HIV infectious diseases outpatient consultations (IDOC). This retrospective study aims to describe IDOC referrals over the past 5 years. In total, 483 patients were referred (with an increase of 63% between 2009 and 2013). Most referrals were received from primary care clinicians (45%). Median patient age was 47 years, 57% of patients were men and 17% were immunosuppressed. Of the diagnoses retained, 74% were infectious, 20% were non-infectious and 6% were of unknown aetiology. Two community outbreaks were identified (tattoo-related mycobacterial infection and Q fever). In conclusion, the infectious diseases outpatient clinic, which has expanded progressively in the past 5 years, provides a specialised service for primary health clinicians and for public health.

Normal values for pancreatic stone protein in different age groups.

BACKGROUND: Pancreatic stone protein (PSP) has been identified as a promising sepsis marker in adults, children and neonates. However, data on population-based reference values are lacking. This study aimed to establish age-specific reference values for PSP. METHODS: PSP was determined using a specific ELISA. PSP serum concentrations were determined in 372 healthy subjects including 217 neonates, 94 infants and children up to 16 years, and 61 adults. The adjacent categories method was used to determine which age categories had significantly different PSP concentrations. RESULTS: PSP circulating levels were not gender-dependent and ranged from 1.0 to 99.4 ng/ml with a median of 9.2 ng/ml. PSP increased significantly between the age categories, from a median of 2.6 ng/ml in very preterm newborns, to 6.3 ng/ml in term newborns, to 16.1 ng/ml in older children (p < 0.001). PSP levels were higher on postnatal day three compared to levels measured immediately post delivery (p < 0.001). Paired umbilical artery and umbilical vein samples were strongly correlated (p < 0.001). Simultaneously obtained capillary heel-prick versus venous samples showed a good level of agreement for PSP (Rho 0.89, bias 19 %). CONCLUSIONS: This study provides age-specific normal values that may be used to define cut-offs for future trials on PSP. We demonstrate an age-dependent increase of PSP from birth to childhood.

Pancreatic adenocarcinoma: the impact of preneoplastic lesion pattern on survival.

Pancreatic adenocarcinoma is associated with a very poor prognosis, characterized with a 5-year survival rate of only 5%. Surgery is the only curative treatment for selected patients. Nevertheless, recurrence is very frequent. Identifying prognostic factors is thus warranted. Like numerous other tumors, adenocarcinomas are preceded by preneoplastic lesions. The role and the impact of these lesions remain unclear. This study aimed to assess the impact of the preneoplastic lesion pattern and histo-morphological features, on survival after pancreatic resection. Thirty-five patients who underwent pancreatic resection for pancreatic adenocarcinoma were identified from a prospective database of a single center, between 2003 and 2008. We considered demographics, tumor characteristics and type of treatment. The major outcome was survival. Analyzes were separated into two groups, according to the preneoplastic lesions: Pancreatic intraepithelial neoplasia (PanIN)-related carcinomas and intracanalar papillary mucinous neoplasia (IPMN)-related carcinomas. The former were more frequent, accounting for 63% (22/35). Moreover, they displayed more aggressive features, with a higher tumor stage (p = 0.01) and higher rate of positive lymph nodes (p = 0.019). Lymphatic (p = 0.009) and perinervous (p = 0.019) invasions were also more frequent. Survival was negatively influenced by PanIN preneoplastic lesions (p = 0.015), T3-4 tumor stage (p = 0.038), positive lymph nodes (p = 0.044), lymphatic (p = 0.019) and vascular (p = 0.029) invasions. Pancreatic adenocarcinoma displays different behavior according to its preneoplastic lesion. Indeed, PanIN-related adenocarcinoma showed more aggressive features and lower survival rate. Preneoplastic lesions may represent predictive factors for survival. Their role and predictive value should be investigated more thoroughly.

Computed tomography-guided percutaneous biopsy of pancreatic masses using pneumodissection

Objective To describe the technique of computed tomography-guided percutaneous biopsy of pancreatic tumors with pneumodissection. Materials and Methods In the period from June 2011 to May 2012, seven computed tomography-guided percutaneous biopsies of pancreatic tumors utilizing pneumodissection were performed in the authors' institution. All the procedures were performed with an automatic biopsy gun and coaxial system with Tru-core needles. The biopsy specimens were histologically assessed. Results In all the cases the pancreatic mass could not be directly approached by computed tomography without passing through major organs and structures. The injection of air allowed the displacement of adjacent structures and creation of a safe coaxial needle pathway toward the lesion. Biopsy was successfully performed in all the cases, yielding appropriate specimens for pathological analysis. Conclusion Pneumodissection is a safe, inexpensive and technically easy approach to perform percutaneous biopsy in selected cases where direct access to the pancreatic tumor is not feasible.

Sorcin links pancreatic β cell lipotoxicity to ER Ca2+ stores.

NlmCategory="UNASSIGNED">Preserving β cell function during the development of obesity and insulin resistance would limit the worldwide epidemic of type 2 diabetes (T2DM). Endoplasmic reticulum (ER) calcium (Ca(2+)) depletion induced by saturated free fatty acids and cytokines causes β cell ER stress and apoptosis, but the molecular mechanisms behind these phenomena are still poorly understood. Here, we demonstrate that palmitate-induced sorcin (SRI) down-regulation, and subsequent increases in glucose-6-phosphatase catalytic subunit-2 (G6PC2) levels contribute to lipotoxicity. SRI is a calcium sensor protein involved in maintaining ER Ca(2+) by inhibiting ryanodine receptor activity and playing a role in terminating Ca(2+)-induced Ca(2+) release. G6PC2, a GWAS gene associated with fasting blood glucose, is a negative regulator of glucose-stimulated insulin secretion (GSIS). High fat feeding in mice and chronic exposure of human islets to palmitate decreases endogenous SRI expression while levels of G6PC2 mRNA increase. Sorcin null mice are glucose intolerant, with markedly impaired GSIS and increased expression of G6pc2. Under high fat diet, mice overexpressing SRI in the β cell display improved glucose tolerance, fasting blood glucose and GSIS, whereas G6PC2 levels are decreased and cytosolic and ER Ca(2+) are increased in transgenic islets. SRI may thus provide a target for intervention in T2DM.

Two-photon excitation fluorometry in detection of infectious diseases

Because of the heavily overlapping symptoms, pathogen-specific diagnosis and treatment of infectious diseases is difficult based on clinical symptoms alone. Therefore, patients are often treated empirically. More efficient treatment and management of infectious diseases would require rapid point-of-care compatible in vitro diagnostic methods. However, current point-of-care methods are unsatisfactory in performance and in cost structure. The lack of pointof- care methods results in unnecessary use of antibiotics, suboptimal use of virus-specific drugs, and compromised patient care. In this thesis, the applicability of a two-photon excitation fluorometry is evaluated as a tool for rapid detection of infectious diseases. New separation-free immunoassay methodologies were developed and validated for the following application areas: general inflammation markers, pathogen-specific antibodies, pathogen-specific antigens, and antimicrobial susceptibility testing. In addition, dry-reagent methodology and nanoparticulate tracers are introduced in context to the technique. The results show that the new assay technique is a versatile tool for rapid detection of infectious diseases in many different application areas. One particularly attractive area is rapid multianalyte testing of respiratory infections, where the technique was shown to allow simple assay protocols and comparable performance to the state-of-the-art laboratory methods. If implemented in clinical diagnostic use, the new methods could improve diagnostic testing routines, especially in rapid testing of respiratory tract infections.

Positron emission tomography in the diagnosis and staging of pancreatic and neuroendocrine tumors

Tutkimuksen tausta ja tavoitteet: Viimeaikaisesta perinteisten kuvantamismenetelmien kehityksestä huolimatta sekä haima- että neuroendokriinisten (NE) kasvaimien diagnostiikka on haastavaa. Uudentyyppinen kuvantamismenetelmä, fuusio positroniemissiotomografia-tietokonetomografia (PET/TT), on lupaava näiden kasvainten erotusdiagnostiikassa ja levinneisyyden arvioinnissa. Huolimatta alustavista lupaavista tutkimustuloksista, PET/TT:n rooli on toistaiseksi vielä epäselvä sekä haima- että NE-kasvaimissa eikä se näin ollen ole vakiintunut kliiniseen hoitokäytäntöön. Väitöskirjatyön tavoitteena oli selvittää PET/TT -menetelmän käyttökelpoisuutta haima- ja NE-kasvaimien diagnostiikassa. Kahden ensimmäisen osatyön prospektiivisessa tutkimuksessa potilaat, joilla epäiltiin haimakasvainta, kuvannettiin PET/TT:llä käyttäen merkkiaineena fluorideoxyglukoosia (¹⁸F-FDG) kasvaimen aineenvaihdunnan arvioimiseksi ja kasvaimen verenvirtausta arviointiin käyttäen merkkiaineena radiovettä (¹⁵O-H₂O). Kolmen muun osatyön tavoitteena oli selvittää dihydroxyfenylalaniini (18F-DOPA) PET -menetelmää erilaisten NE-kasvaimien diagnostiikassa ja levinneisyyden arvioinnissa. Tulokset: Haimakasvaimien ensivaiheen diagnostiikassa ¹⁸F-FDG-PET/TT:llä oli korkeampi diagnostinen tarkkuus verrattuna titokoneleike- (TT) ja magneettikuvantamiseen (MK) (89% vs. 76% ja 79%). Etenkin pahanlaatuiseksi epäillyn sappitiehytahtauman erotusdiagnostiikassa ¹⁸F-FDG-PET/TT:n positiivinen ennustearvo (92%) oli korkea. Haimasyövän levinneisyyden arvioinnissa ¹⁸F-FDG-PET/TT:n herkkyys oli huono (30%) paikallisen taudin osoittamisessa. Sen sijaan etäpesäkkeiden osoittamisessa ¹⁸F-FDG-PET/TT oli merkittävästi herkempi menetelmä verrattuna TT ja magneettikuvantamiseen (88% vs. 38%). Verrattaessa erilaisten haimakasvaimien ja normaalin haimakudoksen aineenvaihduntaa ja verenvirtausta, aineenvaihdunta/verenvirtaus suhde oli merkittävästi korkeampi pahanlaatuisissa haimakasvaimissa (P<0.05). Lisäksi kasvaimen korkea aineenvaihdunta/verenvirtaus suhde viittasi huonompaan taudin ennusteeseen. ¹⁸F-DOPA-PET löysi seitsemän kahdeksasta insulinoomasta ja oli positiivinen myös kahdella potilaalla, joilla todettiin haiman saarakesoluhyperplasia. Perustuen alustaviin tuloksiin, rutiinikäytössä oleva karbidopa esilääke ennen ¹⁸F-DOPA-PET kuvantamista peitti insulinooma löydöksen kahdella potilaalla kolmesta. NE-kasvaiminen diagnostiikassa 82 potilaan aineisto osoitti ¹⁸F-DOPA PET kuvantamisen tarkkuudeksi 90%. Etenkin feokromosytoomien ensivaiheen diagnostiikassa ja NE-kasvaimen uusiutumaa epäiltäessä menetelmän tarkkuus oli korkea. Kokonaisuudessaan 59%:lla aineiston potilaista ¹⁸F-DOPA-PET kuvantamisella oli vaikutusta kliinisiin hoitoratkaisuihin. Johtopäätökset: PET/TT käyttäen merkkiaineena ¹⁸F-FDG:tä ja radiovettä osoittautui käyttökelpoiseksi menetelmäksi haimakasvaimien erotusdiagnostiikassa. Lisäksi ¹⁸F-FDG-PET/TT oli hyödyllinen haimasyövän etäpesäkkeiden arvioinnissa. Tutkimus osoitti myös ¹⁸F-DOPA-PET kuvantamisen olevan luotettava menetelmä insulinoomien ja muiden vatsan alueen NE-kasvaimien ensivaiheen diagnostiikassa sekä levinneisyyden arvioinnissa, etenkin muiden kuvantamislöydösten ollessa ristiriitaisia. PET kuvantamisella oli merkittävä vaikutus potilaiden kliiniseen hoitokäytäntöön sekä haima- että NE-kasvaimissa.

Pancreatic Cancer Cell Glycosylation Regulates Cell Adhesion and Invasion through the Modulation of a2b1 Integrin and E-Cadherin Function

In our previous studies we have described that ST3Gal III transfected pancreatic adenocarcinoma Capan-1 and MDAPanc-28 cells show increased membrane expression levels of sialyl-Lewis x (SLex) along with a concomitant decrease in α2,6-sialic acid compared to control cells. Here we have addressed the role of this glycosylation pattern in the functional properties of two glycoproteins involved in the processes of cancer cell invasion and migration, α2β1 integrin, the main receptor for type 1 collagen, and E-cadherin, responsible for cell-cell contacts and whose deregulation determines cell invasive capabilities. Our results demonstrate that ST3Gal III transfectants showed reduced cell-cell aggregation and increased invasive capacities. ST3Gal III transfected Capan-1 cells exhibited higher SLex and lower α2,6-sialic acid content on the glycans of their α2β1 integrin molecules. As a consequence, higher phosphorylation of focal adhesion kinase tyrosine 397, which is recognized as one of the first steps of integrin-derived signaling pathways, was observed in these cells upon adhesion to type 1 collagen. This molecular mechanism underlies the increased migration through collagen of these cells. In addition, the pancreatic adenocarcinoma cell lines as well as human pancreatic tumor tissues showed colocalization of SLex and E-cadherin, which was higher in the ST3Gal III transfectants. In conclusion, changes in the sialylation pattern of α2β1 integrin and E-cadherin appear to influence the functional role of these two glycoproteins supporting the role of these glycans as an underlying mechanism regulating pancreatic cancer cell adhesion and invasion

Detection and partial characterization of a carlavirus causing stem necrosis of soybean in Brazil

Stunting and stem necrosis were noticed in soybeans (Glycine max) grown in 2000/2001 in West Central Brazil the same condition was also observed in the following year in plantations as far as 2,000 km from the initial area. Based on transmission (mechanical, graft, insect vector), purification and serology, electron microscopy and molecular studies the causal agent was determined to be a whitefly-borne carlavirus which is possibly related to Cowpea mild mottle virus (CpMMV).