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Biomedical subjects

Jean-Silvain Lacroix

Publications and source records attributed to Jean-Silvain Lacroix.

14 recordsLinked to original sources
PubMed2006

Rhamnolipids are virulence factors that promote early infiltration of primary human airway epithelia by Pseudomonas aeruginosa.

The opportunistic bacterium Pseudomonas aeruginosa causes chronic respiratory infections in cystic fibrosis and immunocompromised individuals. Bacterial adherence to the basolateral domain of the host cells and internalization are thought to participate in P. aeruginosa pathogenicity. However, the mechanism by which the pathogen initially modulates the paracellular permeability of polarized respiratory epithelia remains to be understood. To investigate this mechanism, we have searched for virulence factors secreted by P. aeruginosa that affect the structure of human airway epithelium in the early stages of infection. We have found that only bacterial strains secreting rhamnolipids were efficient in modulating the barrier function of an in vitro-reconstituted human respiratory epithelium, irrespective of their release of elastase and lipopolysaccharide. In contrast to previous reports, we document that P. aeruginosa was not internalized by epithelial cells. We further report that purified rhamnolipids, applied on the surfaces of the epithelia, were sufficient to functionally disrupt the epithelia and to promote the paracellular invasion of rhamnolipid-deficient P. aeruginosa. The mechanism involves the incorporation of rhamnolipids within the host cell membrane, leading to tight-junction alterations. The study provides direct evidence for a hitherto unknown mechanism whereby the junction-dependent barrier of the respiratory epithelium is selectively altered by rhamnolipids.

Adult↗
PubMed2006

Postoperative/posttraumatic gustatory dysfunction.

Clinical taste testing in humans is far from being routinely performed in ear, nose and throat (ENT) clinics. Consequently, most reports on posttraumatic and postoperative taste disorders are case reports and mainly consist of qualitative (e.g. dysgeusia, metallic taste) taste changes after either head injury or ENT surgery. Since quantitative taste deficiencies (ageusia, hypogeusia) often go unnoticed by the patients, the real incidence of ageusia and hypogeusia after head trauma and various surgical procedures remains largely unknown. This lack of reliable clinical data is partly due to the lack of easy, reproducible and rapid clinical taste testing devices. The present chapter tries to resume the current knowledge on postoperative and posttraumatic taste disorders. Despite the sparse literature, the chapter focuses on those ENT surgical procedures where at least some prospective and systematic studies on gustatory dysfunction exist. Accordingly, taste disorders after middle ear surgery, tonsillectomy and dental interventions are largely discussed.

Brain Injuries↗
PubMed2005

Evidence of an intracellular reservoir in the nasal mucosa of patients with recurrent Staphylococcus aureus rhinosinusitis.

Severe infections due to Staphylococcus aureus require prolonged therapy for cure, and relapse may occur even years after the first episode. Persistence of S. aureus may be explained, in part, by nasal carriage of S. aureus, which occurs in a large percentage of healthy humans and represents a major source of systemic infection. However, the persistence of internalized S. aureus within mucosal cells has not been evaluated in humans. Here, we provide the first in vivo evidence of intracellular reservoirs of S. aureus in humans, which were assessed in endonasal mucosa specimens from patients suffering from recurrent S. aureus rhinosinusitis due to unique, patient-specific bacterial clonotypes. Heavily infected foci of intracellular bacteria located in nasal epithelium, glandular, and myofibroblastic cells were revealed by inverted confocal laser scan fluorescence and electron microscopic examination of posttherapy intranasal biopsy specimens from symptom-free patients undergoing surgery on the sinuses. Intracellular residence may provide a sanctuary for pathogenic bacteria by protecting them from host defense mechanisms and antibiotic treatment during acute, recurrent S. aureus rhinosinusitis.

Biopsy↗
PubMed2005

Effects of amphotericin B on ion transport proteins in airway epithelial cells.

Topical intranasal application of the antifungal Amphotericin B (AmphoB) has been shown as an effective medical treatment of chronic rhinosinusitis. Because this antibiotic forms channels in lipid membranes, we considered the possibility that it affects the properties and/or cell surface expression of ion channels/pumps, and consequently transepithelial ion transport. Human nasal epithelial cells were exposed apically to AmphoB (50 microM) for 4 h, 5 days (4 h daily), and 4 weeks (4 h daily, 5 days weekly) and allowed to recover for 18-48 h. AmphoB significantly reduced transepithelial potential difference, short-circuit current, and the amiloride-sensitive current. This was not due to generalized cellular toxicity as judged from normal transepithelial resistance and mitochondrial activity, but was related to inhibitory effects of AmphoB on ion transport proteins. Thus, cells exposed to AmphoB for 4 h showed decreased apical epithelial sodium channels (ENaC) activity with no change in basolateral Na(+)K(+)-ATPase activity and K(+) conductance, and reduced amount of alphaENaC, alpha1-Na(+)K(+)-ATPase, and NKCC1 proteins at the cell membrane, but no change in mRNA levels. After a 5-day treatment, there was a significant decrease in Na(+)K(+)-ATPase activity. After a 4-week treatment, a decrease in basolateral K(+) conductance and in alphaENaC and alpha1-Na(+)K(+)-ATPase mRNA levels was also observed. These findings may reflect a feedback mechanism aimed to limit cellular Na(+) overload and K(+) depletion subsequently to formation of AmphoB pores in the cell membrane. Thus, the decreased Na(+) absorption induced by AmphoB resulted from reduced cell surface expression of the ENaC, Na(+)K(+)-ATPase pump and NKCC1 and not from direct inhibition of their activities.

Amphotericin B↗
PubMed2005

[Clinical aspects of dysosmia and presentation of European Olfactory Test of "sniffin sticks": a review].

The medical community has neglected olfactory dysfunction for a long time. However, over the last two decades, remarkable progress has been made in terms of understanding the sense of smell and both the assessment and diagnosis of olfactory dysfunction. Currently, there are only a few validated olfactory tests. The most commonly used one is the University of Pennsylvania Smell Identification Test. Owing to its cultural biases, this test is mostly used in the United States. "Sniffin' Sticks" are one of the first European tests to be widely used. Since their development in 1996, they have been applied in numerous studies and have found increasing use in otolaryngology clinics. The goal of this article is to present Sniffin' Sticks and to provide a review of clinical olfactory research during recent years.

Bacterial Infections↗
PubMed2004

Skull base cerebrospinal fluid fistula: a novel detection method based on two-dimensional electrophoresis.

BACKGROUND: The detection of the presence of cerebrospinal fluid (CSF) in nasal secretions contaminated with blood and mucus remains a challenging clinical problem. METHODS: A prospective study was conducted from November 1998 to February 2002, including 42 patients. Samples (250 microL) of nasal secretions were analyzed by two-dimensional electrophoresis (2-DE). Plasma, mucus, and CSF were identified by specific proteins markers corresponding to characteristic trains of spots. Intrathecal injection of fluorescein followed by the detection of fluorescein on endoscopic examination of the nasal cavities was considered a positive reference for CSF rhinorrhea. RESULTS: In all cases of positive fluorescein test, we unambiguously observed the presence of several specific CSF markers onto the 2-DE gels. Conversely, all negative fluorescein tests were associated with the absence of CSF-specific spots. CONCLUSIONS: Two-DE analyses of biologic fluids of nasal origin should be considered as a reliable diagnostic tool in case of suspicion of CSF leak.

Adolescent↗
PubMed2004

N-acetylcysteine inhibits Na+ absorption across human nasal epithelial cells.

N-acetylcysteine (NAC) is a widely used mucolytic drug in patients with a variety of respiratory disorders. The mechanism of action is based on rupture of the disulfide bridges of the high molecular glycoproteins present in the mucus, resulting in smaller subunits of the glycoproteins and reduced viscosity of the mucus. Because Na(+) absorption regulates airway surface liquid volume and thus the efficiency of mucociliary clearance, we asked whether NAC affects the bioelectric properties of human nasal epithelial cells. A 24-h basolateral treatment with 10 mM of NAC decreased the transepithelial potential difference and short-circuit current (I(SC)) by 40%, and reduced the amiloride-sensitive current by 50%, without affecting the transepithelial resistance. After permeabilization of the basolateral membranes of cells with amphotericin B in the presence of a mucosal-to-serosal Na(+) gradient (135:25 mM), NAC inhibited 45% of the amiloride-sensitive current. The Na(+)-K(+)-ATPase pump activity and the basolateral K(+) conductance were not affected by NAC treatment. NAC did not alter total cell mRNA and protein levels of alpha-epithelial Na(+) channel (EnaC) subunit, but reduced abundance of alpha-ENaC subunits in the apical cell membrane as quantified by biotinylation. This effect can be ascribed to the sulphydryl (SH) group of NAC, since N-acetylserine and S-carboxymethyl-l-cysteine were ineffective. Given the importance of epithelial Na(+) channels in controlling the thin layer of fluid that covers the surface of the airways, the increase in the fluidity of the airway mucus following NAC treatment in vivo might be in part related to downregulation of Na(+) absorption and consequently water transport.

Acetylcysteine↗
PubMed2004

Chronic panrhinosinusitis without nasal polyps: long-term outcome after functional endoscopic sinus surgery.

OBJECTIVE: The goal of this study was to evaluate the long-term outcome after functional endoscopic sinus surgery (FESS) for chronic panrhinosinusitis without nasal polyps by using symptom scoring and an endoscopic outcome evaluation. STUDY DESIGN: Seventy-seven patients with chronic panrhinosinusitis without nasal polyps (Kennedy computed tomography [CT] scan stages I to III) were followed up for at least 3 years after FESS. Preoperative evaluation included a CT scan and an immunoallergologic evaluation. Three years after FESS, all patients were interviewed and scored endoscopically. RESULTS: Ninety-two percent of the patients showed a marked global improvement after FESS. The endoscopic control showed normal findings in 54% of all ethmoidal cavities. The postoperative endoscopic score correlated significantly with the subjective satisfaction ratings (P < 0.001). The preoperative CT staging proposed by Kennedy was predictive for necessity of revision surgery in 15% of the patients. CONCLUSIONS: Our data suggest that FESS for chronic panrhinosinusitis without nasal polyps has a good long-term outcome on subjective symptoms and endoscopic findings. SIGNIFICANCE: According to this study, subjective improvement correlates significantly with the postoperative endoscopic findings in the ethmoidal cavities of patients with chronic panrhinosinusitis without polyps at a long-term follow-up.

Adolescent↗
PubMed2003

Retronasal olfactory function in nasal polyposis.

OBJECTIVE: To investigate the question of whether there is a difference in retronasal olfactory function between patients suffering from chronic rhinosinusitis with nasal polyposis (NP) and healthy controls. This question was based on the clinical observation that many of these patients present with smell loss without complaining about loss of the appreciation of foods. STUDY DESIGN: Open prospective study comparing symptomatic patients with healthy controls. METHODS: A total of 56 healthy volunteers and 42 NP patients were tested for orthonasal and retronasal odor identification. All subjects received detailed nasal endoscopy; NP was staged according to the Malm classification. Patients rated their olfactory function on visual analogue scales. Orthonasal testing was performed using the "Sniffin' Sticks" test kit. Retronasal testing was evaluated with odorized powders applied to the oral cavity. In both tests, subjects were asked to identify 10 items using a forced choice paradigm. RESULTS: Overall, odor identification was better in controls compared with NP patients (P <.001). Although controls exhibited no difference between orthonasal and retronasal smelling (P =.26), in NP patients, olfactory function was significantly better when odors were applied through the retronasal route (P <.001). Ratings of general olfactory abilities correlated with retronasal and orthonasal olfactory function in NP patients (P <.001) but not in healthy controls (P =.34). CONCLUSION: Better retronasal than orthonasal olfactory function seems to be associated with the presence of mechanical obstruction in the anterior portion of the olfactory cleft. In turn, these data indicate that olfactory loss in NP seems to be caused by regional mechanical or inflammatory factors.

Adult↗
PubMed2002

Loss of dipeptidylpeptidase IV activity in chronic rhinosinusitis contributes to the neurogenic inflammation induced by substance P in the nasal mucosa.

In this study, we have found that dipeptidylpeptidase IV (DPPIV) plays in vivo an active role in the modulation of the inflammatory response of chronic rhinosinusitis. Human nasal mucosa expresses DPPIV-like immunoreactivity in submucosal seromucus glands, leukocytes, and endothelial cells of blood vessels. DPPIV enzymatic activity in nasal tissue biopsies taken from patients suffering from chronic rhinosinusitis was correlated inversely with the density of inflammatory cells in the nasal mucosa, and the DPPIV activity rose when chronic rhinosinusitis was treated. By using a pig animal model, we have shown that the intranasal administration of recombinant DPPIV decreased the vasodilatation induced by exogenous substance P (SP), a proinflammatory peptide released by sensory nerves. In contrast, an inhibitor of DPPIV enhanced the vasodilatatory effect at low doses of SP. SP5-11 was 100- to 1000-fold less potent than SP as a vasodilator of the nasal mucosa. The vasodilatatory effect of SP was abolished by a NK1 receptor antagonist. In conclusion, these results suggest a new pathophysiological pathway for rhinitis based on clinical observations in humans, indicating the involvement of an enzyme to modulate non-adrenergic and non-cholinergic substrate that occurred during nasal dysfunctions.

Animals↗
PubMed2002

Effect of anti-fungal nasal lavage with amphotericin B on nasal polyposis.

Recent studies have suggested that allergic fungal rhino-sinusitis could be involved in the development of nasal polyposis. The aim of this study was to evaluate the response of anti-fungal nasal lavages. Patients performed nasal lavage with 20 ml of a one per one thousand amphotericin B suspension in each nostril, twice a day, for four weeks. In addition, all patients continued their saline nasal lavage and their conventional topical corticosteroid spray. This study included 74 patients, with a mean age of 46 years (range from 19 to 73). Before anti-fungal treatment, the distribution of nasal polyposis, according to Malm, was: 13 patients in stage I (17.5 per cent), 48 patients in stage II (65 per cent) and 13 patients in stage III (17.5 per cent). After anti-fungal nasal lavages, the total disappearance of nasal polyposis was observed in 29 patients (39 per cent). Eight patients were stage I, 21 stage II, and none stage III. In patients who have had previous endoscopic polypectomy and functional endoscopic sinus surgery, total disappearance of nasal polyposis was seen in 24 patients (47 per cent). Hyper-reactivity to fungal organisms could be one of the mechanisms underlying the development of nasal polyposis. A direct effect of amphotericin B suspension on the integrity of the cell membrane of the polyps' epithelium could not be excluded.

Adult↗
PubMed2002

Endoscopic removal of a nasal septum chondrosarcoma.

We describe an alternative, endoscopical technique for the surgical removal of a rare chondrosarcoma on the nasal septum. The technique requires a resection of the whole tumour within margins in healthy osteocartilaginous nasal septum under endoscopic guidance and includes bilateral middle turbinectomy and ethmoidectomy. We present the case of a 57-year-old woman with a well-differentiated chondrosarcoma (Grade I) of the nasal septum. Endoscopical surgery resulted without any cosmetic deformity problems, and the functional result was favourable. No recurrence was evidenced after a follow-up of 3 years. The main advantages of this technique are the excellent functional and cosmetic results without any surgical reconstructive techniques. This approach may provide a minimally invasive method to remove well-differentiated, low-grade (Grade I) and size limited malignant cartilaginous tumours of the nasal septum.

Chondrosarcoma↗
PubMedDate not supplied

Src signaling links mediators of inflammation to Cx43 gap junction channels in primary and transformed CFTR-expressing airway cells.

Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) is associated with recurrent pulmonary infections and inflammation. We previously reported that tumor necrosis factor (TNF)-alpha decreases gap junction connectivity in cell lines derived from the airway epithelium of non-cystic fibrosis (non-CF) subjects, a mechanism that was defective in cells derived from CF patients, and identified the tyrosine kinase c-Src as a possible bridge between TNF-alpha and Cx43. To examine whether this modulation also takes place in primary epithelial cells, the functional expression of Cx43 was studied in non-CF and CF airway cells, obtained from surgical polypectomies and turbinectomies, which were grown either on culture dishes or permeable filters. Expression of Cx43 was detected by immunofluorescence on cells grown under both culture conditions. Non-CF and CF airway cells also showed intercellular diffusion of Lucifer Yellow. Dye coupling was rapidly abolished in non-CF cells in the presence of TNF-alpha, lipopolysaccharide and lysophosphatidic acid, and could be prevented by tyrphostin47, an inhibitor of Src tyrosine kinases. This down-regulation, however, was not detected in CF airway cells. These data indicate that CFTR dysfunction is associated with altered Src signaling, resulting in the persistence of gap junction connectivity in primary and transformed CF airway cells.

Caveolin 1↗