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Entre 2002 et 2020, 172 anaphylaxies alimentaires observées chez le sénior ont été rapportées au RAV. On observe un sex-ratio H/F de 0,85 et une moyenne d’âge de 67,3 ans (60–93). Les allergènes les plus fréquents sont d’origine végétale : en premier, les légumineuses (20 cas), puis les céréales (16 cas) et les fruits à coque (15 cas), principalement la noisette. Les protéines PR-10 sont en cause dans au moins 11,7 % des anaphylaxies. À l’instar du soja, les anaphylaxies attribuées à Cor a 1 sont surtout rapportées par des allergologues exerçant en Belgique et dans le nord-est de la France. Les anaphylaxies liées aux viandes rouges et abats sont les plus fréquentes (24 cas soit 13,9 %), toujours associées à un syndrome alphaGal quand il est recherché, 16 sont attribuées aux crustacés, 8 aux mollusques et aux poissons respectivement et 6 cas à Anisakis. Cette série confirme la rareté de l’allergie au lait de vache et à l’œuf chez le sénior. Le RAV a colligé 4 anaphylaxies de grade I, 77 de grade II, 84 de grade III et 5 de grade IV dont un décès. La gravité est significativement liée à des antécédents de cardiopathie ou HTA. Quarante pour cent des sujets avaient déjà présenté une allergie dans le passé avec l’aliment suspecté et seulement 55 % disposaient d’un stylo d’adrénaline et 33 % d’un plan d’action. Cette grande série souligne l’intérêt d’un bilan allergologique détaillé chez le sujet âgé. Leur prise en charge doit non seulement comporter un protocole de soins d’urgence avec auto-injecteur d’adrénaline, mais aussi une éducation thérapeutique et diététique pour le patient et son entourage. Elle devrait être formalisée par un PAI, à l’instar de l’enfant scolarisé, compte tenu du risque de récidive, des comorbidités et perte d’autonomie pour certains.

Background Hypersensitivity reactions (HSR) to antineoplastic agents are an increasing problem, especially when they lead to treatment discontinuation, sometimes without any equivalent therapeutic option. HSR to folinic acid (FA), used particularly for the treatment of digestive carcinoma along with oxaliplatin and 5-fluorouracil, are rare. Only seven publications report HSR to FA, mainly confirmed by the disappearance of symptoms after the withdrawal of FA from chemotherapy. Only two papers describe allergy testing. Due to the difficult diagnosis, patients usually receive several further cycles of chemotherapy with progressively more intense symptoms before the withdrawal of FA. Case presentation Here we document two cases of HSR to FA, initially misattributed to oxaliplatin. The first patient described successive cycles with first back muscle pain, then chills and facial oedema and finally diffuse erythema with labial edema despite premedication. The allergy assessment highlighted high acute tryptase levels and intradermal tests positive for FA, pointing to an immunoglobulin E (IgE)-mediated mechanism. The second patient also had lower back muscle pain and chills in addition to tachycardia and desaturation during the administration of FA. Skin tests were negative and tryptase levels normal. After withdrawing FA, the symptoms did not recur, thus allowing the patient to continue chemotherapy. The mechanism of FA hypersensitivity is still unclear. The chronology of symptoms suggests an IgE-mediated mechanism that was not documented in the allergy assessment. A non-IgE-mediated mast cell/basophil activation could be involved, through complement activation or through Mas-related G protein-coupled receptors X2 (MRGPRX2) particularly. Conclusions These two cases of anaphylaxis to FA document the clinical manifestations associated with two different mechanisms of HSR. This paper provided the opportunity to review the limited literature on HSR to FA. Through these cases, we hope to draw the practitioner’s attention to FA as a potential agent of severe hypersensitivity, especially if symptoms remain after withdrawing the most suspected chemotherapeutic agents. We want also to stress the importance of allergy testing.

BACKGROUND: The diagnosis of cutaneous leishmaniasis (CL) is often difficult because of the diversity of clinical presentations, its often-misleading appearance and the very long incubation period (time between the endemic stay and the onset of skin lesions). CASE: We report the case of an otherwise healthy 67-year-old man who presented with inflammatory skin lesions on the scalp and face for the past 7 years. The lesions were first mistaken as cutaneous sarcoidosis, mycobacterial infection, and cutaneous lymphoma. Finally, the diagnosis was made by RT-PCR analysis on a punch-biopsy specimen, which was positive for Leishmania infantum. DISCUSSION AND CONCLUSION: To date, the choice of treatment for complex cutaneous leishmaniases is based on the Leishmania species. Our patient successfully responded to liposomal amphotericin B.

Background Toxocara canis and Toxocara cati are globally distributed roundworms and causative agents of human toxocariasis, via ingestion of Toxocara eggs. Control of Toxocara infections is constrained by a lack of sensitive methods for screening of animal faeces and environmental samples potentially contaminated by Toxocara eggs. In this work, a pre-analytical method for efficient extraction of DNA from Toxocara eggs in environmental samples was set up using our previously validated T. canis- and T. cati-specific quantitative real-time polymerase chain reaction (qPCR). For this purpose, the influence of different methods for egg lysis, DNA extraction and purification for removal of PCR inhibitors were assessed on environmental samples. Methods To select the best egg disruption method, six protocols were compared on pure T. canis egg suspensions, including enzymatic lysis and thermal or mechanical disruption. Based on the selected best method, an analytical workflow was set up to compare two DNA extraction methods (FastDNA™ SPIN Kit for Soil versus DNeasy® PowerMax® Soil Kit) with an optional dilution and/or clean-up (Agencourt® AMPure®) step. This workflow was evaluated on 10-g soil and 10-g sand samples spiked with egg suspensions of T. canis (tenfold dilutions of 104 eggs in triplicate). The capacity of the different methods, used alone or in combination, to increase the ratio of positive tests was assessed. The resulting optimal workflow for processing spiked soil samples was then tested on environmental soil samples and compared with the conventional flotation-centrifugation and microscopic examination of Toxocara eggs. Results The most effective DNA extraction method for Toxocara eggs in soil samples consisted in the combination of mechanical lysis of eggs using beads, followed by DNA extraction with the DNeasy® PowerMax® Soil Kit, and completed with an additional DNA clean-up step with AMPure® beads and a sample DNA dilution (1:10). This workflow exhibited a limit of detection of 4 and 46 T.canis eggs in 10-g sand and 10-g soil samples, respectively. Conclusions The pre-analytical flow process developed here combined with qPCR represents an improved, potentially automatable, and cost-effective method for the surveillance of Toxocara contamination in the environment. Graphical Abstract

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A 71-year-old woman with history of treated high blood pressure and atrial fibrillation presented with a painful eruption of the right arm and forearm. Symptoms started the day following the second dose of the BNT162b2 COVID-19 vaccine (Pfizer/BioNTech) with a localized injection site reaction that progressively worsened. She had no reaction after the first vaccine injection 3 weeks before.

A 49-year-old woman, with no particular medical history other than quiescent Crohn's disease, was admitted for acute gastroenteritis. Three days after admission, she developed large purpuric, ecchymotic targetoid skin lesions and oedema, predominantly on the buttocks and thighs (Figure 1A and B). The lesions were not pruritic but slightly painful at palpation. She denied any history of vaccination or injections at the sites of the skin lesions. The patient remained afebrile. Platelet counts, coagulation tests and immunoglobulin A serum levels were within normal limits. Renal function was normal and proteinuria was excluded. Bacteriological stool samples were negative.

Objectives Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are an increasingly significant cause of hospital- and community-acquired infections worldwide. Whereas several reports have highlighted their increased prevalence also in North African countries, genomic data on isolates associated with these infections are still scarce. This study aimed to provide data on ESBL-producing E. coli isolates from patients with extraintestinal infections at the Military Teaching Hospital Mohamed V of Rabat, Morocco. Methods Whole-genome sequencing was carried out on 18 ESBL-producing extraintestinal pathogenic E. coli (ExPEC) isolates for analysis of phylogenomic evolution, virulence factors and antimicrobial resistance genes. Data were compared with ExPEC lineages from several surrounding countries using multilocus sequence typing (MLST) and single nucleotide polymorphism-based phylogenetic approaches. Results The majority of E. coli isolates were ST131 (n = 15), followed by ST617 (n = 2) and a novel sequence type (ST10703) that is closely related to the pandemic ST405 clone. All ST131 isolates belonged to the O25b-ST131 pandemic clone. They harboured more virulence genes than their non-ST131 counterparts. IncF plasmid replicons and the blaCTX-M-15 β-lactamase gene were identified in all isolates. No ESBL-producing E. coli isolates carried any known carbapenemase gene. Conclusion Our findings underscore the pre-eminence of ST131 as the major factor driving the expansion of ExPEC in the Rabat region while highlighting the potential links with isolates circulating in other neighbouring countries.

Background: Very few studies have investigated whether unilateral choanal atresia is associated with permanent olfactory deficits. Objective: This study aimed to evaluate the olfactory performance of patients with unilateral choanal atresia postsurgically. Methods: Three patients with unilateral atresia were examined in terms of olfactory performance with the Sniffin’ Sticks test (odor identification, threshold, and discrimination), size of the olfactory bulb, and volumetric brain changes. Results: All patients demonstrated significantly lower olfactory performance in terms of odor threshold on the same side with the choanal atresia. Grey matter reductions were found ipsilaterally in the hippocampus. Conclusions: This pilot study indicates that persistent olfactory deficits and volumetric brain changes are present in patients with unilateral choanal atresia.

BACKGROUND: Pediatric LT are at particular risk of HAT, and its management still constitutes a matter of debate. Our purpose was to study predisposing factors and outcome of HAT post-LT, including the impact of surgical revisions on survival and biliary complications. METHODS: Among 882 primary pediatric LT performed between 1993 and 2015, 36 HAT were encountered (4.1%, 35 fully documented). Each HAT case was retrospectively paired with a LT recipient without HAT, according to diagnosis, age at LT, type of graft, and era. RESULTS: Five-year patient survivals were 77.0% versus 83.9% in HAT and non-HAT paired groups, respectively (P = .321). Corresponding graft survivals were 20.0% versus 80.5% (P < .001), and retransplantation rates 77.7% versus 10.7%, respectively (P < .001). One-year biliary complication-free survivals were 16.6% versus 83.8% in the HAT and non-HAT groups, respectively (P < .001). Regarding chronology of surgical re-exploration, only HAT cases that occurred within 14 days post-LT were re-operated, fourteen of them being explored within 7 days post-LT (revascularization rate: 6/14), versus two beyond 7 days (no revascularization). When revascularization was achieved, graft and biliary complication-free survival rates at 1 year were 33.3% and 22.2%, respectively, both rates being 0.0% in case of failure. CONCLUSIONS: The pejorative prognosis associated with HAT in terms of graft survival is confirmed, whereas patient survival could be preserved through retransplantation. Results suggest that HAT should be re-operated if occurring within 7 days post-LT, but not beyond.

Les compléments alimentaires à base de produits de la ruche sont plébiscités par les consommateurs. Cependant, ils ne sont pas dénués de risque allergique pour les patients atopiques, comme le souligne l’avis rendu par l’ANSES en 2018. Nous présentons l’étude rétrospective descriptive des cas d’anaphylaxie alimentaire aux pollens en pelote et autres produits apicoles déclarés au Réseau d’Allergo-Vigilance® de 2002 à juin 2021. Résultats. – Au total, 32 cas d’anaphylaxie ont été déclarés, soit 1,26 % de la totalité des déclarations d’anaphylaxie alimentaire, dont 16 cas au pollen en pelote (50 %), 14 au miel (40,6 %), 2 à la gelée royale (6,3 %) et 1 à la propolis (3,1 %). Il s’agit principalement d’adultes (81,3 %), avec la moitié de réactions anaphylactiques de grade 2 et un tiers de grade 3. Les 2 cas d’anaphylaxie à la gelée royale étaient de grade 3 avec de l’asthme. Une hospitalisation/surveillance a été réalisée chez 37,5 % des patients, seule- ment 21,9 % ont bénéficié d’un traitement par adrénaline. Une sensibilisation pollinique était retrouvée dans 87,5 % des cas et 53,2 % avaient une rhinite saisonnière. Dans l’anaphylaxie au pollen en pelote, tous les patients (100 %) étaient sensibilisés à des pollens, dont 75 % à ceux des composées. Concernant l’anaphylaxie au miel, seuls 3 patients ne présentaient pas de sensibilisation aux pollens. Conclusions. – Il s’agit de la plus grande série rapportée d’anaphylaxie aux produits de la ruche. L’allergie alimentaire au pollen en pelote est liée le plus souvent à la présence de pollens de composées (pollens entomophiles mais aussi anémophiles), de même que pour l’allergie au miel, avec cependant la possibilité d’un lien avec des protéines de sécrétions apiaires comme MRJP1, qui est l’allergène incriminé dans l’anaphylaxie à la gelée royale.

Background: The literature describes several risk factors for hypersensitivity (HS) reactions to iodinated contrast media (ICM). Objective: To analyze the characteristics of patients experiencing HS reactions to ICM with a focus on oncological status. Methods: All patients (n=80) with suspected HS to ICM who underwent an allergy evaluation in a Belgian University Hospital over a 5-year period were retrospectively included. Results: Overall, forty patients (50%) had a history of neoplasia, and this group was characterized by less atopy (p

Auditory neuropathy spectrum disorder (ANSD) refers to a range of hearing impairments characterized by deteriorated speech perception, despite relatively preserved pure-tone detection thresholds. Affected individuals usually present with abnormal auditory brainstem responses (ABRs), but normal otoacoustic emissions (OAEs). These electrophysiological characteristics have led to the hypothesis that ANSD may be caused by various dysfunctions at the cochlear inner hair cell (IHC) and spiral ganglion neuron (SGN) levels, while the activity of outer hair cells (OHCs) is preserved, resulting in discrepancies between pure-tone and speech comprehension thresholds. The exact prevalence of ANSD remains unknown; clinical findings show a large variability among subjects with hearing impairment ranging from mild to profound hearing loss. A wide range of prenatal and postnatal etiologies have been proposed. The study of genetics and of the implicated sites of lesion correlated with clinical findings have also led to a better understanding of the molecular mechanisms underlying the various forms of ANSD, and may guide clinicians in better screening, assessment and treatment of ANSD patients. Besides OAEs and ABRs, audiological assessment includes stapedial reflex measurements, supraliminal psychoacoustic tests, electrocochleography (ECochG), auditory steady-state responses (ASSRs) and cortical auditory evoked potentials (CAEPs). Hearing aids are indicated in the treatment of ANSD with mild to moderate hearing loss, whereas cochlear implantation is the first choice of treatment in case of profound hearing loss, especially in case of IHC presynaptic disorders, or in case of poor auditory outcomes with conventional hearing aids.

Small cell lung cancer (SCLC) has a poor prognosis. Focal adhesion kinase (FAK) is a non–receptor tyrosine kinase regulating cell proliferation, survival, migration, and invasion, which is overexpressed and/or activated in several cancers, including SCLC. We wanted to determine whether FAK contributes to SCLC aggressive behavior. We first evaluated the effect of FAK small-molecule inhibitor PF-573,228 in NCI-H82, NCI-H146, NCI-H196, and NCI-H446 SCLC cell lines. PF-573,228 (0.1–5 μmol/L) inhibited FAK activity by decreasing phospho-FAK (Tyr397), without modifying total FAK expression. PF-573,228 decreased proliferation, decreased DNA synthesis, induced cell-cycle arrest in G2–M phases, and increased apoptosis in all cell lines. PF-573,228 also decreased motility in adherent cell lines. To make sure that these effects were not off-target, we then used a genetic method to inhibit FAK in NCI-H82 and NCI-H446, namely stable transduction with FAK shRNA and/or FAK-related nonkinase (FRNK), a splice variant lacking the N-terminal and kinase domains. Although FAK shRNA transduction decreased total and phospho-FAK (Tyr397) expression, it did not affect proliferation, DNA synthesis, or progression through cell cycle. However, restoration of FAK-targeting (FAT) domain (attached to focal adhesion complex where it inhibits pro-proliferative proteins such as Rac-1) by FRNK transduction inhibited proliferation, DNA synthesis, and induced apoptosis. Moreover, although FAK shRNA transduction increased active Rac1 level, FRNK reexpression in cells previously transduced with FAK shRNA decreased it. Therefore, FAK appears important in SCLC biology and targeting its kinase domain may have a therapeutic potential, while targeting its FAT domain should be avoided to prevent Rac1-mediated protumoral activity.

L’anaphylaxieinduite par l’exercice physique est une forme particulière d’allergie physique décrite pour la première fois voilà un peu plus de 30 ans.Ils’agit,comme son nom l’indique,d’une forme d’anaphylaxie dontl’unique facteur déclenchant identifié à ce jour est un effort physique d’intensité plus ou moins soutenue.Lasymptomatologie se développe dans des circonstances banales et difficiles à éviter puisque même un effort minime est susceptible d’induire unecrise ce qui peut rendre la vie du malade très difficile.Ce la est d’autant plus un handicap pour lui qu’aucun traitement prophylactique efficace n’estconnu jusqu’à présent.Nous reviendrons dans cet article sur l’état desconnaissances concernant l’anaphylaxie induite par l’exercice physique(manifestations cliniques,points connus et hypothétiques de la physiopathologie,diagnostic, traitement) ainsi que sur ses principaux diagnostics différentiels:l’anaphylaxie induite par l’alimentation et l’exercice physique et l’urticaire cholinergique.

The source of acquisition of Pseudomonas aeruginosa in cystic fibrosis (CF) patients remains unknown. Patient-to-patient transmission has been well documented but the role of the environment as a source of initial infection is as yet unclear. In the present study, the origin of the first P. aeruginosa isolate in CF patients was investigated by comparing the P. aeruginosa genotype(s) from newly infected patients with genotypes of P. aeruginosa isolates from the home environment and from other patients from the same CF centre. A total of 50 newly infected patients were studied. P. aeruginosa could be cultured from 5.9% of the environmental samples, corresponding to 18 patients. For nine of these, the genotype of the environmental P. aeruginosa isolate was identical to the patient's isolate. In total, 72% of the environmental P. aeruginosa isolates were encountered in the bathroom. Patient-to-patient transmission within the CF centre could not be ruled out for three patients. In summary, a low prevalence of Pseudomonas aeruginosa was found in the home environment of the newly infected cystic fibrosis patients. The bathroom should be targeted in any preventive cleaning procedures. An environmental source of the new infection could not be ruled out in nine patients.

Rationale: The Third National Health and Nutrition Examination Survey (NHANES III) reference is currently recommended for interpreting spirometry results, but it is limited by the lack of subjects younger than 8 years and does not continuously model spirometry across all ages. Objectives: By collating pediatric data from other large-population surveys, we have investigated ways of developing reference ranges that more accurately describe the relationship between spirometric lung function and height and age within the pediatric age range, and allow a seamless transition to adulthood. Methods: Data were obtained from four surveys and included 3,598 subjects aged 4–80 years. The original analyses were sex specific and limited to non-Hispanic white subjects. An extension of the LMS (lambda, mu, sigma) method, widely used to construct growth reference charts, was applied. Measurements and Main Results: The extended models have four important advantages over the original NHANES III analysis as follows: (1) they extend the reference data down to 4 years of age, (2) they incorporate the relationship between height and age in a way that is biologically plausible, (3) they provide smoothly changing curves to describe the transition between childhood and adulthood, and (4) they highlight the fact that the range of normal values is highly dependent on age. Conclusions: The modeling technique provides an elegant solution to a complex and longstanding problem. Furthermore, it provides a biologically plausible and statistically robust means of developing continuous reference ranges from early childhood to old age. These dynamic models provide a platform from which future studies can be developed to continue to improve the accuracy of reference data for pulmonary function tests.

BACKGROUND: Data from the Belgian Cystic Fibrosis Registry consistently show that in one of the seven reference centres, the prevalence of Pseudomonas aeruginosa is half that observed at the national level. OBJECTIVES: To report the characteristics of non-transplanted patients in this clinic at the end of 2003, with special focus on paediatric patients. To describe and discuss our policy of inhaled antibiotic therapy. FINDINGS: The prevalence of P. aeruginosa among 116 patients is 20.7%. The chronic colonization rate is 19.8% but only 2.8% in patients aged under 18 (n=72). Serologic data strongly support these results. Most paediatric patients (95%) are prescribed inhaled antibiotics, at least on an intermittent basis but the mean number of days of intravenous antibiotic treatment is four times lower than in other CF children in Belgium. 70% of children have an FEV1> or =90% predicted. DISCUSSION: We have reported a distinctly low rate of chronic colonization by P. aeruginosa in a cohort of CF children and suspect that a strategy of early, often <> use of inhaled antibiotics, progressively implemented for over 15 years has substantially contributed to these results. Given the major impact of chronic P. aeruginosa colonization on prognosis in CF, it is suggested that a large prospective study of this approach is warranted.

In Belgian cystic fibrosis (CF) clinics, sputum samples are evaluated on selective MAST medium routinely every 3 months. In this study, in 1993 and 1999, isolates were further examined by recA restriction fragment length polymorphism analysis and pulsed-field gel electrophoresis of genomic DNA restricted with SpeI. In 1993, 12 patients were colonised with Burkholderia cepacia complex (Bcc): B. cenocepacia (n=6), B. multivorans (n=3), B. stabilis (n=3). Four patients were colonised with the same B. cenocepacia strain; two with the same B. stabilis strain. After 5 yrs, three B. cenocepacia- and one B. multivorans-colonised patients had died. In 1999, Bcc was isolated in 12 patients: B. multivorans (n=9), B. stabilis (n=1) and B. cenocepacia (n=2). Three patients were colonised by the same B. multivorans strain. Compared to matched controls, the 5 yr outcome was poor; four B. cepacia patients died and none of the control patients died. Lung-function evolution was poor. In conclusion, the rate of colonisation in Belgian cystic fibrosis patients is stable and low. Burkholderia cenocepacia was most prevalent in 1993; Burkholderia multivorans in 1999. The cross-infection rate is low. Three patients had transient colonisation. The impact of Burkholderia cepacia complex on morbidity in the Belgian cystic fibrosis population is high and not limited to Burkholderia cenocepacia.

We showed that IgA induces IL-10 in monocytes and dendritic cells. Because reciprocal inhibition exists between IL-10 and IL-12, we explored whether IgA could regulate this other immunoregulatory cytokine. In human monocytes and monocyte-derived dendritic cells preincubated with IFN-γ before stimulation by LPS, suppression of p40 and IL-12p70 production was observed upon IgA treatment during IFN-γ priming. Washout experiments and inhibition of IFN-γ-induced CXCL10 (IP-10) and FcgRI (CD64) indicated that inhibition by IgA occurred at both the LPS and IFN-γ levels. Inhibition was not affected by blockade of IL-10 or MAPK but involved FcaRI/CD89-mediated suppression of STAT1 phosphorylation. These data indicate that FcaRI ligation on human monocytes and dendritic cells inhibits IL-12 expression and type 1 activation by interfering with STAT1 activation. Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved.

Anti-IgE therapy was proposed to two teenagers with cystic fibrosis (CF) with allergic bronchopulmonary aspergillosis (ABPA) exacerbation, reluctant to a further course of oral steroids. Both patients experienced ABPA exacerbations within the past 3 years, requiring oral steroid bursts. Clinical, laboratory and radiographic features were consistent with ABPA exacerbations (representing at the time of evaluation the fourth and third episodes for patient 1 and 2, respectively). Total serum IgE was very high, >1000 kU/litre in both cases. Treatment consisting of subcutaneous injections of 375 mg anti-IgE (omalizumab) twice monthly was successful in rapidly improving respiratory symptoms and lung function. Based on clinical and functional improvement, interval between injections was progressively increased and treatment could be withdrawn after 11 injections, without recurrence at 20 weeks of follow-up after withdrawal.

In chronic obstructive pulmonary disease (COPD), chronic inflammation is accompanied by peribronchial lymphoid aggregates. Lymphotoxin (LT)-alpha, crucial in secondary lymphoid organogenesis, may be involved in lymphoid neogenesis. We examined cigarette smoke (CS)-induced pulmonary lymphoid neogenesis and inflammation in vivo in LT alpha knockout (LT alpha(-/-)) and wild-type (WT) mice and studied the expression of lymphoid chemokines by lung fibroblasts in vitro. T-cell numbers (in bronchoalveolar lavage fluid (BALF) and lungs) and lymphoid aggregate numbers were significantly higher in air-exposed LT alpha(-/-) mice than in WT animals, and increased upon chronic CS exposure in both genotypes. In contrast, local immunoglobulin A responses upon chronic CS exposure were attenuated in LT alpha(-/-) mice. CXC chemokine ligand (CXCL) 13 and CC chemokine ligand (CCL) 19 mRNA in total lung and CXCL13 protein level in BALF increased upon CS exposure in WT, but not in LT alpha(-/-) mice. In vitro lymphotoxin-beta receptor (LT beta R) stimulation induced CXCL13 and CCL19 mRNA in WT lung fibroblasts. Furthermore, in vitro exposure to CS extract upregulated CXCL13 mRNA expression in WT, but not in LT beta R-/-, lung fibroblasts. In this murine model of COPD, CS induces pulmonary expression of lymphoid chemokines CXCL13 and CCL19 in a LT alpha beta-LT beta R-dependent fashion. However, LT alpha is not required for CS-induced pulmonary lymphocyte accumulation and neogenesis of lymphoid aggregates.

A 31-year-old patient presented with a diagnosis of granulomatous dermatophytosis based on the clinical aspect of the lesions and the rare presence of hyphae on direct microscopic examination of clinical material. A chronic evolution and progression of the disease, its resistance to a wide range of antifungal agents, the occasional presence of hyphae on direct examination but consistently negative cultures over a 5-year period prompted the use of amplification-based DNA analyses of several successive swab samples or skin biopsies. DNA was extracted using a combination of two semi-automated DNA isolation methods (FastPrep(R) preparation and NucliSENS(R) lysis magnetic extraction method). Identification relied both on sequence analysis of amplicons after SYBR(R) Green real-time PCR of the panfungal internal transcribed spacer 1 (ITS1) genetic target, as well as the unique amplicon melting curve profile of positive samples. Accordingly, Trichophyton rubrum was unambiguously identified in several clinical samples collected over a 7-month period. This case illustrates the contribution of DNA-based assays applied directly to sample biopsies for identifying causative agents in cases in which fungal pathogens are highly suspected but culture are repeatedly negative. It also pinpoints the benefit of combining semi-automated DNA preparation methods, analysis of ITS1 amplicon melting curve profiles and sequence analysis on repeated skin biopsy samples for unambiguous identification of the causative fungal species.

AIMS: To assess a panel of antibodies on Bouin's fixed bone marrow trephine (BMT) biopsies. These biopsies are widely used in routine diagnosis of various haematological malignancies and may be the sole material available in many centres; however, information regarding the immunostaining of this material is lacking. METHODS: Biopsies were taken from 72 patients presenting with various haematological malignancies (leukaemia, 38; lymphoma, 14; multiple myeloma, 20). A panel of antibodies was assessed on Bouin's fixed BMT biopsies by the alkaline phosphatase-antialkaline phosphatase method. RESULTS: Three B (MB2, LN-2, Ki-B5) and two T cell lineage antibodies (UCHL-1, CD3-r) reliably identified lymphoid cells, while MPO-r, Leu-M1/CD15, and KP-1/CD68 recognised cells from the myeloid or histiocytic/macrophage series. Reed-Sternberg cells were stained by LN-2, Leu-M1, and CD30. Antibodies specific for plasma cells (VS38) and hairy cells (DBA.44) gave a variable pattern of staining. Among the proliferation markers, proliferative cell nuclear antigen but not Ki-67 related antibodies were effective. CONCLUSION: This study presents a panel of antibodies with reactivity not restricted to common fixatives that are also suitable for Bouin's fixed BMT biopsies.

P Eloy, E Leruth, B Bertrand, Ph RombauxENT and HNS department, Cliniques Universitaires de Mont-Godinne, Université Catholique de Louvain, 5530, Yvoir, BelgiumAbstract: Wegener’s granulomatosis (WG) is one form of idiopathic autoimmune vasculitis. The disease has a predilection for the upper and lower respiratory tracts (lungs, nose, sinus), and kidneys. WG may be systemic, severe, and potentially lethal, but it may also be limited to the otolaryngological area or to the eyes and the orbits. Obstruction of the lacrimal pathway is a possible complication of the disease that affects approximately 7% of patients with WG. It usually occurs as a direct extension of sinonasal disease and typically is a late manifestation. Management of such a condition is generally viewed as difficult. We report the case of a patient with a quiescent WG limited to the otolaryngological area. This patient presented a bilateral obstruction of the nasolacrimal ducts caused by bilateral extensive adhesions in the nasal cavity. Because she had several episodes of left-side acute dacryocystitis which necessitated several courses of broad-spectrum antibiotics, she successfully underwent an endonasal endoscopic dacryocystorhinostomy using a diode laser and powered instrumentation. The authors describe the clinical case, the surgical technique, and review the literature.Keywords: Wegener’s granulomatosis, recurrent dacryocystitis, endonasal DCR, diode, laser, powered instrumentation

Philippe Eloy, Vincent Bachy, Véronique Grulois, Bernard BertrandDepartment of Otorhinolaryngology,Head and Neck Surgery, University Hospital of Mont-Godinne, Université Catholique de Louvain, Yvoir, BelgiumAbstract: JNA (Juvenile nasopharyngeal angiofibroma) is a benign but highly vascular and aggressive tumor that takes its origin in the basisphenoid region close to the sphenopalatine foramen. It occurs invariably in male teenagers. Surgery is the treatment of choice. In the past, external transfacial approaches were recommended. Nowadays endonasal endoscopic approach is performed by experienced teams even for extended tumor. The authors report a case of a pyocele of the lachrymal sac occurring 60 years after a transantral surgery for a JNA. The patient was then successfully operated with an endonasal endoscopic dacryocystorhinostomy using a powered instrumentation and a navigation system. This case confirms the necessity of a long follow-up for all the patients who had a transantral surgery with resection of the medial wall of the maxillary sinus and dissection of the nasolacrymal duct.Keywords: pyocele of the lachrymal sac, complication, surgery for JNA, JNA, endonasal DCR, navigation system

Stem cells from extra- or intrahepatic sources have been recently characterized and their usefulness for the generation of hepatocyte-like lineages has been demonstrated. Therefore, they are being increasingly considered for future applications in liver cell therapy. In that field, liver cell transplantation is currently regarded as a possible alternative to whole organ transplantation, while stem cells possess theoretical advantages on hepatocytes as they display higher in vitro culture performances and could be used in autologous transplant procedures. However, the current research on the hepatic fate of stem cells is still facing difficulties to demonstrate the acquisition of a full mature hepatocyte phenotype, both in vitro and in vivo. Furthermore, the lack of obvious demonstration of in vivo hepatocyte-like cell functionality remains associated to low repopulation rates obtained after current transplantation procedures. The present review focuses on the current knowledge of the stem cell potential for liver therapy. We discuss the characteristics of the principal cell candidates and the methods to demonstrate their hepatic potential in vitro and in vivo. We finally address the question of the future clinical applications of stem cells for liver tissue repair and the technical aspects that remain to be investigated.

AIMS: To date, the risk relating to the handling or allografting of human immunodeficiency virus type 1 (HIV-1) infected postmortem skin remains hypothetical. While blood screening for HIV antibodies is still the key safety procedure to detect HIV infected cadavers, false negative results are a concern. Conversely, false positive results may hamper the collection of skin allografts. Accordingly, viral culture was used to clarify skin infectivity and the nested polymerase chain reaction (PCR) was used to assess the reliability of skin PCR testing. METHODS: Viral culture and nested PCR performed with gag and pol specific primers were investigated in cadaveric skin and blood from 12 HIV-1 infected patients. Samples were collected repeatedly between one and five days in seven patients. In most cases, analyses were performed on triplicate skin samples: fresh (n = 26); cryopreserved in 5% dimethylsulphoxide (n = 21), or cryopreserved in 30% glycerol (n = 26). RESULTS: HIV was isolated in two of 26 cultures of fresh skin specimens (8%), seven of 47 cryopreserved skin specimens (15%), and eight of 26 blood specimens (31%). The nested PCR detected HIV-1 in all skin samples (n = 73), regardless of the postmortem interval or cryopreservation. In blood, a positive signal was found in eight of 12 patients but two of them had discordant results on successive samples. CONCLUSIONS: These data suggest that nested PCR on postmortem skin samples can detect HIV more reliably than on blood. They also demonstrate the potential viral infectivity of fresh or stored skin postmortem samples in HIV infected patients. They underscore the need for caution during the handling of skin tissue from HIV infected cadavers and confirm the potential risk related to accidental allografting of HIV contaminated skin.