Sniff nasal inspiratory pressure in patients with chronic obstructive pulmonary disease.

In subjects with normal lung mechanics, inspiratory muscle strength can be reliably and easily assessed by the sniff nasal inspiratory pressure (SNIP), which is the pressure measured in an occluded nostril during a maximal sniff performed through the contralateral nostril. The aim of this study was to assess the validity of the SNIP in patients with chronic obstructive pulmonary disease (COPD), where pressure transmission from alveoli to upper airways is likely to be dampened. Twenty eight patients with COPD were studied (mean forced expiratory volume in one second (FEV1) = 36% of predicted). The SNIP and the sniff oesophageal pressure (sniff Poes) were measured simultaneously during maximal sniffs, and were compared to the maximal inspiratory pressure obtained against an occlusion (MIP). All measurements were performed from functional residual capacity in the sitting position. The ratio SNIP/sniff Poes was 0.80, and did not correlate with the degree of airflow limitation. The ratio MIP/sniff Poes was 0.87, and the ratio SNIP/MIP was 0.97. Inspiratory muscle weakness, as defined by a low sniff Poes, was present in 17 of the 28 patients. A false diagnosis of weakness was made in eight patients when MIP was considered alone, in four when SNIP was considered alone, and in only three patients when MIP and SNIP were combined. We conclude that both the sniff nasal inspiratory pressure and the maximal inspiratory pressure moderately underestimate sniff oesophageal pressure in chronic obstructive pulmonary disease. Although suboptimal in this condition, the sniff nasal inspiratory pressure appears useful to complement the maximal inspiratory pressure for assessing inspiratory muscle strength in patients with chronic obstructive pulmonary disease.

Comparative phylogeography and postglacial colonization routes in Europe.

The Quaternary cold periods in Europe are thought to have heavily influenced the amount and distribution of intraspecific genetic variation in both animals and plants. The phylogeographies of 10 taxa, including mammals (Ursus arctos, Sorex spp., Crocidura suaveolens, Arvicola spp.), amphibians (Triturus spp.), arthropods (Chorthippus parallelus), and plants (Abies alba, Picea abies, Fagus sylvatica, Quercus spp.), were analysed to elucidate general trends across Europe. Only a small degree of congruence was found amongst the phylogeographies of the 10 taxa, but the likely postglacial colonization routes exhibit some similarities. A Brooks parsimony analysis produced an unrooted area phylogram, showing that: (i) the northern regions were colonized generally from the Iberic and Balkanic refugia; and (ii) the Italian lineages were often isolated due to the presence of the Alpine barrier. The comparison of colonization routes highlighted four main suture-zones where lineages from the different refugia meet. Some of the intraspecific genetic distances among lineages indicated a prequaternary divergence that cannot be connected to any particular cold period, but are probably related mainly to the date of arrival of each taxon in the European continent. As a consequence, molecular genetics so far appears to be of limited use in dating Quaternary events.

Interactions between cancer stem cells and their niche govern metastatic colonization.

Metastatic growth in distant organs is the major cause of cancer mortality. The development of metastasis is a multistage process with several rate-limiting steps. Although dissemination of tumour cells seems to be an early and frequent event, the successful initiation of metastatic growth, a process termed 'metastatic colonization', is inefficient for many cancer types and is accomplished only by a minority of cancer cells that reach distant sites. Prevalent target sites are characteristic of many tumour entities, suggesting that inadequate support by distant tissues contributes to the inefficiency of the metastatic process. Here we show that a small population of cancer stem cells is critical for metastatic colonization, that is, the initial expansion of cancer cells at the secondary site, and that stromal niche signals are crucial to this expansion process. We find that periostin (POSTN), a component of the extracellular matrix, is expressed by fibroblasts in the normal tissue and in the stroma of the primary tumour. Infiltrating tumour cells need to induce stromal POSTN expression in the secondary target organ (in this case lung) to initiate colonization. POSTN is required to allow cancer stem cell maintenance, and blocking its function prevents metastasis. POSTN recruits Wnt ligands and thereby increases Wnt signalling in cancer stem cells. We suggest that the education of stromal cells by infiltrating tumour cells is an important step in metastatic colonization and that preventing de novo niche formation may be a novel strategy for the treatment of metastatic disease.

Citrobacter rodentium Requires Intestinal Neural Wiskott-Aldrich Syndrome Protein (N-WASp) for Actin Pedestal Formation, Colonization and Epithelial Barrier Disruption In Vivo

Background: Citrobacter rodentium is a natural mouse pathogen that is genetically closelyrelated to the human enteric pathogens enteropathogenic and enterohemorrhagic E. coli.Among the repertoire of conserved virulence factors that these pathogens deliver via typeIII secretion, Tir and EspF are responsible for the formation of characteristic actin-richpedestals and disruption of tight junction integrity, respectively. There is evidence In Vitrothese effectors accomplish this, at least in part, by subverting the normal host cellularfunctions of N-WASP, a critical regulator of branched chain actin assembly. Although NWASPhas been shown to be involved in pedestal formation In Vitro, the requirements ofN-WASP-mediated actin pedestals for intestinal colonization by attaching/effacing (A/E)pathogens In Vivo is not known. Furthermore, it is not known whether N-WASP is requiredfor EspF-mediated tight junction disruption. Methods: To investigate the role of N-WASPin the gut epithelium, we generated mice with intestine-specific deletion of N-WASP(iNWKO), by mating mice homozygous for a floxed N-WASP allele (N-WASPL2L/L2L) tomice expressing Cre recombinase under the villin promoter. Separately housed groups ofWT and iNWKO mice were inoculated with 5x108 GFP-expressing C. rodentium by intragastriclavage. Stool was collected 2, 4, 7, and 12 days after infection, and recoverablecolony forming units (CFUs) of C. rodentium were quantified by plating serial dilutions ofhomogenized stool on MacConkey's agar. GFP+ colonies were counted after 24 hoursincubation at 37°C. The presence of actin pedestals was investigated by electron microscopy(EM), and tight junction morphology was assessed by immunofluorescence staining ofoccludin, ZO-1 and claudin-2. Results: C. rodentium infection did not result in mortalityin WT or iNWKO mice. Compared to controls, iNWKO mice exhibited higher levels ofbacterial shedding during the first 4 days of infection (day 4 average: WT 5.2x104 CFU/gvs. iNWKO 4.7x105 CFU/g, p=0.08), followed by a more rapid clearance of C. rodentium, (day7-12 average: WT 2x106 CFU/g vs. iNWKO 2.7x105, p=0.01). EM and immunofluorescencerevealed the complete lack of actin pedestals in iNWKO mice and no mucosa-associatedGFP+ C. rodentium by day 7. WT controls exhibited tight junction disruption, reflected byaltered distribution of ZO-1, whereas iNWKO mice had no change in the pattern of ZO-1.Conclusion: Intestinal N-WASP is required for actin pedestal formation by C. rodentium InVivo, and ablation of N-WASP is associated with more rapid bacterial clearance and decreasedability of C. rodentium to disrupt intercellular junctions.

Nasal immunization of mice with virus-like particles protects offspring against rotavirus diarrhea.

Rotavirus is the major cause of diarrhea among young infants in both humans and animals. Immune protection of newborns by vaccination is difficult to achieve since there is not enough time to mount an immune response before exposure to the virus. We have designed a vaccination strategy mediating transfer of neutralizing antibodies from the mother to the offspring during pregnancy and/or lactation. Adult female mice were nasally immunized with virus-like particles (VLPs) made of viral proteins VP2 and 6 (VLP2/6) or VP 2, 6, and 7 (VLP2/6/7) derived from the RF rotavirus strain in the presence or absence of cholera toxin. Both vaccines elicited serum and milk antibodies against the respective VPs. Four days after parturition, suckling pups were challenged orally with RF rotavirus. Pups from mothers immunized with VLP2/6/7 but not VLP2/6 were protected against rotavirus diarrhea, indicating that VP7 plays a key role in protection. Protection was mediated by milk rather than serum antibodies, and mucosal adjuvants were not required. In conclusion, VLPs containing VP7 administered nasally to mothers represent a promising vaccine candidate for the protection of suckling newborns against rotavirus-induced diarrhea, even in the absence of a mucosal adjuvant.

Impact of enterococcal colonization and infection in solid organ transplantation recipients from the Swiss Transplant Cohort Study.

BACKGROUND: The burden of enterococcal infections has increased over the last decades with vancomycin-resistant enterococci (VRE) being a major health problem. Solid organ transplantation is considered as a risk factor. However, little is known about the relevance of enterococci in solid organ transplantation recipients in areas with a low VRE prevalence. METHODS: We examined the epidemiology of enterococcal events in patients followed in the Swiss Transplant Cohort Study between May 2008 and September 2011 and analyzed risk factors for infection, aminopenicillin resistance, treatment, and outcome. RESULTS: Of the 1234 patients, 255 (20.7%) suffered from 392 enterococcal events (185 [47.2%] infections, 205 [52.3%] colonizations, and 2 events with missing clinical information). Only 2 isolates were VRE. The highest infection rates were found early after liver transplantation (0.24/person-year) consisting in 58.6% of Enterococcus faecium. The highest colonization rates were documented in lung transplant recipients (0.33/person-year), with 46.5% E. faecium. Age, prophylaxis with a betalactam antibiotic, and liver transplantation were significantly associated with infection. Previous antibiotic treatment, intensive care unit stay, and lung transplantation were associated with aminopenicillin resistance. Only 4/205 (2%) colonization events led to an infection. Adequate treatment did not affect microbiological clearance rates. Overall mortality was 8%; no deaths were attributable to enterococcal events. CONCLUSIONS: Enterococcal colonizations and infections are frequent in transplant recipients. Progression from colonization to infection is rare. Therefore, antibiotic treatment should be used restrictively in colonization. No increased mortality because of enterococcal infection was noted.

Does colonization asymmetry matter in metapopulations?

Despite the considerable evidence showing that dispersal between habitat patches is often asymmetric, most of the metapopulation models assume symmetric dispersal. In this paper, we develop a Monte Carlo simulation model to quantify the effect of asymmetric dispersal on metapopulation persistence. Our results suggest that metapopulation extinctions are more likely when dispersal is asymmetric. Metapopulation viability in systems with symmetric dispersal mirrors results from a mean field approximation, where the system persists if the expected per patch colonization probability exceeds the expected per patch local extinction rate. For asymmetric cases, the mean field approximation underestimates the number of patches necessary for maintaining population persistence. If we use a model assuming symmetric dispersal when dispersal is actually asymmetric, the estimation of metapopulation persistence is wrong in more than 50% of the cases. Metapopulation viability depends on patch connectivity in symmetric systems, whereas in the asymmetric case the number of patches is more important. These results have important implications for managing spatially structured populations, when asymmetric dispersal may occur. Future metapopulation models should account for asymmetric dispersal, while empirical work is needed to quantify the patterns and the consequences of asymmetric dispersal in natural metapopulations.

Workers exposed to wood dust have an increased micronucleus frequency in nasal and buccal cells: results from a pilot study

Wood dust is recognised as a human carcinogen, based on the strong association of wood dust exposure and the elevated risk of malignant tumours of the nasal cavity and paranasal sinuses [sino-nasal cancer (SNC)]. The study aimed to assess genetic damage in workers exposed to wood dust using biomarkers in both buccal and nasal cells that reflect genome instability events, cellular proliferation and cell death frequencies. Nasal and buccal epithelial cells were collected from 31 parquet layers, installers, carpenters and furniture workers (exposed group) and 19 non-exposed workers located in Switzerland. Micronucleus (MN) frequencies were scored in nasal and buccal cells collected among woodworkers. Other nuclear anomalies in buccal cells were measured through the use of the buccal micronucleus cytome assay. MN frequencies in nasal and buccal cells were significantly higher in the exposed group compared to the non-exposed group; odds ratio for nasal cells 3.1 [95% confidence interval (CI) 1.8-5.1] and buccal cells 1.8 (95% CI 1.3-2.4). The exposed group had higher frequencies of cells with nuclear buds, karyorrhectic, pyknotic, karyolytic cells and a decrease in the frequency of basal, binucleated and condensed cells compared to the non-exposed group. Our study confirms that woodworkers have an elevated risk for chromosomal instability in cells of the aerodigestive tract. The MN assay in nasal cells may become a relevant biomonitoring tool in the future for early detection of SNC risk. Future studies should seek to standardise the protocol for MN frequency in nasal cells similar to that for MN in buccal cells.

Role of CD4+CD25+ regulatory T cells in the antigen specific induction of tolerance "via" the nasal route

ABSTRACT Asthma is a complex inflammatory syndrome caused by environmental factors in predisposed individuals (atopics). Its severity correlates with the presence of activated T lymphocytes and eosinophils in the bronchoalveolar lavage fluid (BALF). Induction of tolerance via the nasal route results in reduced recruitment of eosinophils into BALF upon challenge, inhibition of TH2 pro-inflammatory cytokine secretion and T cell hyporesponsiveness. Recently, CD4+CD25+ natural regulatory T cells (Treg) were proposed as key players in controlling the development of asthma and allergic disease. The objective of the present study is to investigate the role of CD4+CD25+ regulatory T cells in the mechanisms leading to tolerance in an established model of asthma. In this goal we depleted CD4+CD25+ T cells at different times during asthma and tolerance induction protocol in mice and looked at efficiency of tolerization (intranasal application of high dose of allergen) in the absence of natural Tregs. First, ovalbumin-sensitized mice were depleted of CD25+ T cells by intraperitoneal injection of anti-CD25 mAb (PC61) either for along-term (repeated injections of anti-CD25 from day 31 until the end of the protocol) or a short-term period (single injection of anti-CD25 before or after tolerance induction). We demonstrated that the long-term depletion of CD4+CD25+ T cells severely hampered tolerance induction (marked enhancement in eosinophil recruitment into BALF and a vigorous antigen specific T cell response to OVA upon allergen challenge) whereas transient depletions were not sufficient to do so. We then characterized T cell subsets by flow cytometry and observed that a large part of CD4+CD25+ T cells express Foxp3, an established marker of regulatory T cells. We also tested in-vitro suppressor activity of CD4+CD25+ T cells from tolerized mice by cell proliferation assay in coculture and observed a strong suppressive activity. Our data suggest that CD4+CD25+ T cells with regulatory properties play a crucial role in the induction of tolerance via the nasal route. The relationship between CD25+ natural Treg and inducible IL-10+ TRl-type Treg will have to be defined. RESUME L'asthme est un syndrome inflammatoire complexe provoqué par des facteurs environnementaux chez des individus génétiquement prédisposés (atopiques). Sa sévérité corrèle avec la présence des lymphocytes T activés et d'éosinophiles dans le lavage bronchoalvéolaire (BAL). L'induction de la tolérance par la voie nasale résulte en une diminution du recrutement des eosinophils dans le BAL, une inhibition de la sécrétion de cytokines pro-inflammatoires de type TH2 et de l'hypo-réponse des cellules T à l'allergène. Récemment, les cellules régulatrices «naturelles » de type CD4+CD25+ T (Tregs) ont été proposées comme acteurs essentiels dans le développement de l'asthme et de l'allergie. L'objectif de cette étude est d'étudier le rôle des cellules régulatrices CD4+CD25+ T dans les mécanismes menant à la tolérance dans un modèle établi d'asthme. Dans ce but nous avons déplété les cellules de CD4+CD25+ T à différents temps au cours du protocole d'induction d'asthme et de tolérance et nous avons regardé l'efficacité de l'induction de tolérance (application intranasale d'une dose importante d'allergène) en l'absence de Tregs. Dans un premier temps des souris sensibilisées à l'ovalbumine (OVA) ont été déplétées en cellules CD25+ T par l'injection intrapéritonéale d'anti-CD25 mAb (PC61) pour une longue période (injections répétées d'anti-CD25 du jour 31 jusqu'à la fin du protocole) ou pour une courte période (injection unique d'anti-CD25 avant ou après l'induction de tolérance). Nous avons démontré que la déplétion à long t erme des cellules de CD4+CD25+ T a empêché l'induction de tolérance (recrutement accru d'éosinophiles dans le BAL et une réponse vigoureuse des cellules T spécifiques de l'antigène après exposition à l'allergène) tandis des déplétions à court-terme n'ont pas cet effet. Nous avons ensuite caractérisé des sous-populations de cellules T par cytométrie de flux. Nous avons observé que la majorité des cellules CD4+CD25+ T expriment Foxp3, un marqueur établi des cellules régulatrices. Nous avons également examiné in vitro l'activité régulatrice des cellules T CD4+CD25+ issues de souris tolérisées. La prolifération de cellules T en coculture a démontré une forte activité suppressive des cellules CD4+CD25+. Nos données suggèrent que des cellules T CD4+CD25+ ayant des propriétés régulatrices jouent un rôle crucial dans l'induction de la tolérance par la voie nasale. Le rapport entre les cellules régulatrices naturelles CD4+CD25+ et les cellules régulatrices inductible de type TR1 I1-10+ devra être défini. RESUME DESTINE A UN LARGE PUBLIC L'asthme est une maladie inflammatoire des bronches, caractérisée par des crises de dyspnée (gêne respiratoire) témoignant d'une activation brutale des muscles bronchoconstricteurs, auxquelles s'associent un oedème et une hypersécrétion des muqueuses des voies aériennes ainsi qu'une importante production d'anticorps de l'allergie (IgE). Chez la plupart des enfants atteints et chez près de la moitié des adultes concernés par l'asthme, c'est une allergie à des substances présentes dans l'air environnant (acariens, pollens ou poils d'animaux) qui est à l'origine de la maladie. . Le traitement actuel de l'asthme repose d'une part sur le soulagement des symptômes grâce à des produits à base de stéroïdes ou des bronchodilatateurs. D'autre part, l'immunothérapie spécifique (aussi appelée désensibilisation) permet d'améliorer l'asthme et de «reprogrammer» le système immunitaire. C'est à ce jour, le seul moyen connu de faire régresser une allergie. Cependant l'immunothérapie prend beaucoup de temps (3 à 5 ans) et ne marche pas à tous les coups ni pour tous les antigènes. Il est donc important de mieux comprendre les mécanismes impliqués lors d'un tel traitement afin d'en améliorer l'efficacité. Af n de pouvoir investiguer en détail ces mécanismes des modèles d'immunothérapie ont été mis au point chez la souris. Notre étude se base sur un modèle d'asthme allergique chez la souris. Des souris sont rendues allergiques à l'ovalbumine (OVA) et présentent alors les caractéristiques majeures de l'asthme humain (recrutement de cellules inflammatoires dans les poumons, augmentation de la production d'IgE et de la résistance des bronches aux flux respiratoires). Ces souris asthmatiques une fois traitées par l'application nasale d'OVA (forme d'immunothérapie muqueuse) ne développent plus de réaction allergique lors d'une ré-exposition à l'allergène. Notre hypothèse est que cette «guérison» (tolérance) est liée à l'action de cellules (lymphocytes T CD4) dites «régulatrices» et caractérisées par le marqueur CD25. Pour le démontrer, nous avons éliminé ces cellules «régulatrices» CD25 de nos souris asthmatiques grâce à un anticorps monoclonal spécifique. Nous n'avons dès lors plus été en mesure d'induire une tolérance à l'allergène. Ceci suggère donc un rôle clé des cellules «régulatrices» T CD4+CD25+ dans la réussite de l'immunothérapie nasale dans notre modèle. Nos résultats n'excluent pas la participation d'autres cellules telles que les lymphocytes producteurs d'IL-10 (lymphocytes régulateurs induits). Le rôle respectif de ces sous-populations régulatrices devra être examiné dans les études à venir. Une meilleure maîtrise des mécanismes de régulation pourrait s'avérer cruciale pour améliorer les thérapies de l'asthme.

Effects of colonization asymmetries on metapopulation persistence.

Ocean currents, prevailing winds, and the hierarchical structures of river networks are known to create asymmetries in re-colonization between habitat patches. The impacts of such asymmetries on metapopulation persistence are seldom considered, especially rarely in theoretical studies. Considering three classical models (the island, the stepping stone and the distance-dependent model), we explore how metapopulation persistence is affected by (i) asymmetry in dispersal strength, in which the colonization rate between two patches differs in direction, and (ii) asymmetry in connectivity, in which the overall colonization pattern displays asymmetry (circulating or dendritic networks). Viability can be drastically reduced when directional bias in dispersal strength is higher than 25%. Re-colonization patterns that allow for strong local connectivity provide the highest persistence compared to systems that allow circulation. Finally, asymmetry has relatively weak effects when metapopulations maintain strong general connectivity.

Transmission of MRSA and MSSA between humans and farm animals

Human nares are the main niche of Staphylococcus aureus, but farm animals can be also infected (cows) or colonized (pigs) constituting significant reservoir of this pathogen. Previous studies indicated that human and animal strains are quite distinct but the extent of cross-species specialization and transmission remains largely unknown. However, recent reports from several European countries as well as USA and Canada have indicated that employment in farming is an emerging risk factor for MRSA carriage. Pigs were found to be frequently colonized with MRSA, usually with a strain belonging to CC398. It is not known whether animal-human transmission was specific to this particular MRSA strain. S. aureus isolates from cow mastitis and pig colonization isolates were collected in parallel to nasal swab isolates from the animals' caretakers. The isolates were genotyped by AFLP, spatyping, and when appropriate by MLST. The isolates from cow mastitis were genetically uniform in comparison with human isolates. They were quite distinct from farmers\' carriage isolates, indicating pronounced hostspecialization. However, several cases where an infected cow and a colonized farmer had the same strain were detected, including one farm where two farmers were colonized and two cows were infected with MRSA belonging to CC398. Pig isolates were genetically more diverse than cow isolates. They were different from both human and cow isolates with one notable exception. Large fraction of pigs (20%) and pig caretakers (50%) were colonized with isolates belonging to CC398, majority of which were MSSA (2 cases of MRSA). These results indicate that host specialization in S. aureus is quite pronounced. Transmission between humans and farm animals was consequently quite rare. Both MSSA and MRSA strains belonging to otherwise pig-specific CC398 had increased capacity to colonize humans. Study of the genetic factors responsible for host specialization is underway.

Nosocomial nontyphoidal salmonellosis after antineoplastic chemotherapy: reactivation of asymptomatic colonization?

An increased frequency of nontyphoidal salmonellosis is well established in cancer patients, but it is unclear whether this represents increased susceptibility to exogenous infection or opportunistic, endogenous reactivation of asymptomatic carriage. In a retrospective study, a simple case definition was used to identify the probable presence of reactivation salmonellosis in five cancer patients between 1996 and 2002. Reactivation salmonellosis was defined as the development of nosocomial diarrhea >72 h after admission and following the administration of antineoplastic chemotherapy in an HIV-seronegative cancer patient who was asymptomatic on admission, in the absence of epidemiological evidence of a nosocomial outbreak. Primary salmonellosis associated with unrecognized nosocomial transmission or community acquisition and an unusually prolonged incubation period could not entirely be ruled out. During the same time period, another opportunistic infection, Pneumocystis pneumonia, was diagnosed in six cancer patients. Presumably, asymptomatic intestinal Salmonella colonization was converted to invasive infection by chemotherapy-associated intestinal mucosal damage and altered innate immune mechanisms. According to published guidelines, stool specimens from patients hospitalized for longer than 72 h should be rejected unless the patient is neutropenic or >or=65 years old with significant comorbidity. However, in this study neutropenia was present in only one patient, and four patients were <65 years old. Guidelines should thus be revised in order not to reject stool culture specimens from such patients. In cancer patients, nosocomial salmonellosis can occur as a chemotherapy-triggered opportunistic reactivation infection that may be similar in frequency to Pneumocystis pneumonia.

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.

Effects of nasal continuous airway pressure on pulmonary and systemic output in preterm infants

Objective: Respiratory assistance with nasal continuous positive airway pressure (n-CPAP) is an effective treatment in premature newborns presenting respiratory distress. The aim of the study was to depict cardiac function, systemic (Qs) and pulmonary output (Qp) by echocardiography in stable premature infants requiring prolonged n-CPAP. Our hypothesis was that n-CPAP could reduce pulmonary blood flow. Patients and methods: All premature infants < 32 weeks gestation, > 7 days-old, requiring n-CPAP without severe respiratory compromise nor need for additional oxygen were prospectively included. Every patient had a first echocardiography while on n-CPAP. N-CPAP was then discontinued for two hours and a second echocardiography was performed. Results: 17 premature infants were included. Mean gestational age was 28 ± 2 weeks and mean weight 1.1 ± 0.3 kg. Following retrieval of n-CPAP we observed an increase in Qp of 53 ml/kg/min (95% CI 19-87 ml/kg/min), but no significant change in Qs. Consecutively a significant increase in Qp/Qs ratio of 16% was found (95% CI 7-29%). Conclusions: Nasal continuous positive airway pressure has hemodynamic effects in preterm infants in stable pulmonary and cardiac conditions. It reduces pulmonary output without interference with systemic output.