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Biomedical subjects

J M Klossek

Publications and source records attributed to J M Klossek.

At least 19 recordsLinked to original sources

Paranasal sinus fungus ball: epidemiology, clinical features and diagnosis. A retrospective analysis of 173 cases from a single medical center in France, 1989-2002.

Over the last decade, we have observed a high frequency of Aspergillus rhinosinusitis in french medical centers. The epidemiological data, clinical presentations, radiology, mycology and histology results of 173 consecutive patients with paranasal sinus fungus balls who were admitted from 1989 to 2002 have been reviewed. The most common symptoms included purulent nasal discharges and nasal obstructions, with the maxillary sinus being the most common site of infection (152 cases, 87.8%). Computed tomography scans (CT scan) were performed in 92% (159/173) of the cases and heterogeneous opacities were observed in 132 patients (83%). Histology examinations were performed in all cases and proved positive in 162 patients. Fungi were recovered, mainly Aspergillus fumigatus, from samples of 50 patients, while specimens from the remaining 123 patients were negative. Since no specific clinical sign could be found, a diagnosis of fungus ball is frequently made after a long term symptomatic period. CT scan findings of metallic or calcified densities within an opacified sinus cavity are highly suggestive of a fungus ball, but mycological and histological studies are essential to confirm the diagnosis. Treatment consisted of functional endonasal sinus surgery and was successful in 172 out of 173 cases.

Academic Medical Centers↗

Prevalence of nasal polyposis in France: a cross-sectional, case-control study.

BACKGROUND: The prevalence of nasal polyposis (NP) has never been established in France due to the lack of diagnostic tools for population-based studies. METHODS: Using a recently validated questionnaire/algorithm (90% specificity and sensitivity) in a population-based random sample, the present cross-sectional, case-control study allowed to determine NP prevalence and describe the principal aspects of NP epidemiology. A total of 10 033 subjects (>/=18 years) were screened. After identification of subjects with NP and those without, another questionnaire was submitted to NP patients only for further data collection. Controls were individuals without NP, matched by gender and age to NP patients. RESULTS: Nasal polyposis prevalence was 2.11% (95% CI 1.83-2.39). NP patients (n = 212, 45% males) were aged 49.4 +/- 17.6 years. No gender preponderance was observed, but NP tended to increase with age. Mean duration of nasal symptoms was 22.4 +/- 15.7 years. Among the 145 patients having already seen a doctor for their symptoms, 77.2% have been referred to a specialist, and 18.6% had a diagnosis of NP. Rhinorrhoea was reported by 39.9% of NP patients, blocked nose by 30.8%, and anosmia by 28.9%. Only 6.9% reported facial discomfort while 24.6% complained about general discomfort. Most NP patients (61.3%) had a pharmacological treatment, a nasal spray for the major part (76.9%). CONCLUSION: The present study provides valuable and reliable information on NP epidemiology in France; the collected information are in accordance with most published international data.

Administration, Intranasal↗

Update on treatment guidelines for acute bacterial sinusitis.

Acute bacterial sinusitis (ABS) is a common complication of viral upper respiratory tract infections and represents a considerable social burden both in terms of diminished quality of life for the patient and the economic implications of decreased productivity and treatment costs. Several national health authorities have developed guidelines for the management of ABS, which aim to promote rational selection of anti-bacterial therapy to optimise clinical outcomes while minimising the potential for selection of anti-bacterial resistance as a result of inappropriate anti-bacterial usage. This article provides an overview of current guidelines, with particular focus on the clinical significance of variations in treatment recommendations and new treatment options, such as the ketolide telithromycin, which was recently added to a number of national treatment guidelines.

Anti-Bacterial Agents↗

How should nasal symptoms be investigated in asthma? A comparison of radiologic and endoscopic findings.

BACKGROUND: To improve asthma control, the management of rhinosinusitis often leads the physician to perform sinonasal imaging and/or nasal endoscopy, but their respective contributions are still insufficiently understood. OBJECTIVE: To evaluate the potential contribution of a symptoms questionnaire, sinus radiography (SR) and computed tomography (CT) scan to the diagnosis of nasal diseases in asthmatic patients when compared with ENT examination. METHODS: A total of 124 patients completed a questionnaire on nasal symptoms administered by the chest physician. Then, they underwent ENT examination. On the same day, SR and CT scans were performed independently. RESULTS: Patients (80.3%) had nasal symptoms during the month preceding the consultation. The ENT examination was normal in 8.1% (n = 10) and revealed rhinitis in 57.3% (n = 71), rhinosinusitis in 14.5% (n = 18) and nasal polyposis in 20.2% (n = 25). For rhinitis, the negative predictive value of bilateral nasal obstruction was 87.8%. Both SR and CT had low sensitivity and specificity. For rhinosinusitis, the negative predictive value of nasal symptoms varied from 85.4 to 95.2%. Sinus CT was at least as accurate as SR for the diagnosis of rhinosinusitis. In a multivariate analysis, only the CT scan (score > or =12) appeared to be significantly associated with the diagnosis of nasal polyposis. CONCLUSION: In asthmatic patients, physicians need to enquire systematically about the existence of nasal symptoms by using this simple questionnaire which is sensitive for rhinitis, and has good negative predictive value for excluding rhinosinusitis and nasal polyposis.

Adult↗

[Sinusal penetration of amoxicillin-clavulanic acid. Formulation 1 g./125 mg., twice daily versus formulation 500 mg./125 mg., three times daily].

INTRODUCTION: In order to meet the evolution of pneumococcus resistance to beta-lactam antibiotics, a new formulation of amoxicillin (AMX) and clavulanic acid (CA), with twice as much AMX (1 g/125 mg vs. 500 mg/125 mg) was developed for the treatment of acute pneumonia in patients at risk. This formulation can also be used in the treatment of acute maxillary sinusitis using a 1 g/125 mg regimen twice-daily. OBJECTIVES: Compare the sinusal penetration of AMX and CA (1 g/125 mg twice-daily vs. 500 mg/125 mg three times a day) when administered at both regimens to demonstrate equivalent pharmacokinetic and pharmacodynamic behaviour of the former when compared to the latter. METHODS: Concentrations of AMX and CA were measured in the anterior ethmoid, maxillary, posterior ethmoid sinus and in the middle nasa concha in 62 patients undergoing surgery for nasosinusal polyps. Patients randomised in two groups corresponding to 2 oral regimens, received either 1 g/125 mg twice a day or 500 mg/125 mg three times a day for 4 days. The last dose in both groups was administered 1 h 30, 3, 5 or 8 hrs prior to surgery. Serum samples were taken simultaneously to tissue samples. AMX and CA were measured by high performance liquid chromatography. Exogenous and above all endogenous blood contamination were taken into account with the hematocrit as well as blood and tissue haemoglobin concentrations. Comparisons of tissue concentrations were made for each sampling time, according to values obtained for a specific tissue with both doses on one hand, and on the other to values obtained with a specific dose in different tissues. The calculated pharmacodynamic parameters, which are considered to be predictive for bacteriological and clinical efficacy, result directly from tissue concentrations of AMX. tissue inhibitory quotients (IQtissue = Tissue concentration/MIC). time above MICs for serum and tissue concentrations (T > MIC). RESULTS: As regards AMX, whatever the dose, at 1 h 30 and at 3 hrs, tissue concentrations did not differ significantly whatever the tissue studied (from 1.1 to 2.5 micrograms/g). Conversely, at 5 and 8 hrs, they were greater than after the 1 g/125 mg regimen given twice-daily (0.06-0.7 vs. 0.7-1.8 micrograms/g). If we consider a given dose, the comparison between the various tissues showed identical concentrations in the four tissues studied at each sampling time, except in two cases with the dose of 500 mg/125 mg 3 times a day. T > MIC for serum and tissue showed higher values than those required for AMX/pneumococcus association (40-50%) with, nevertheless, greater tissue values for the 1 g/125 mg dose given twice-daily when MIC was of 1 microgram/ml (40-52% vs. 50-66%). The maximum tissue inhibitory quotients were also greater with the twice-daily 1 g/125 mg dose, when calculated with MIC 50 or 90 of S. Pneumoniae, H. influenzae, M. catarrhalis or S. pyogenes. As for CA, concentrations were equivalent for both doses at each sampling time and greater than those required in vitro during respectively 4 and 5 hours for beta-lactamases H. influenzae and M. catarrhalis. DISCUSSION-CONCLUSION: A least an equivalence between both dose regimens was observed, with occasionally a superiority of the twice-daily 1 g/125 mg dose, in terms of pharmacokinetics, tissue penetration and pharmacodynamics for both AMX and CA. This new regimen therefore appears more appropriate for the treatment of acute maxillary sinusitis in adults.

Acute Disease↗

Epidemiological and clinical aspects of nasal polyposis in France; the ORLI group experience.

Nasal polyposis (NP) is a common condition in patients consulting ENT practitioners in France. A multicenter prospective study was performed to evaluate symptoms, demography, environmental factors, personal and family history and associated conditions like asthma, and food or drugs sensitivity (FDS) in patients suffering from NP. In each investigation center assessments were performed at the moment of the initial consultation by the same investigator, then updated with complementary exploration results required by the protocol. The chi 2 test and the Fisher test were used for statistical analysis. In this study 224 patients were included. Males were predominant at 63%. Asthma was found in 45% of cases without relevant sex difference. However, FDS, positive in 31% of the patients, was statistically higher in females than in males (42.9% vs. 24.4%). Severe and major symptoms were more frequently found in the female population. Environment and habitat factors did not appear to be relevant. High rates of NP (52.66%) and asthma (43.58%) were found in the family history. Hereditary factors were suggested and lead us to further study the genetic factors potentially involved in this pathology.

Asthma↗

[Epistaxis and hospitalization: a retrospective observational study over 4 years of 260 patients].

OBJECTIVE: Epistaxis is a frequent emergency for which guidelines and treatment are well known. Nevertheless few studies have evaluated the factors that may influence the decision for hospitalisation. Through a retrospective study we have searched to define potential factors which lead to taking such a decision. METHODS: Retrospective analysis of charts of 260 patients hospitalized for epistaxis. For each patient we have reviewed several data including, age, associated pathologies, current treatment, duration of the stay, complications, recurrences etc... RESULTS: If the severity of the bleeding is one of the major factor, socio-economic factors are also taken into account and may influence the decision to hospitalize. Age, associated pathologies (hypertension, hemopathy) and their treatment (anti-coagulant) also play a role in this decision. Furthermore an obvious strategy in the choice of the different treatment may help to reduce the length of stay and the morbidity of each treatment. CONCLUSION: We propose some modifications to our strategy to improve the management of epistaxis. This includes the use of endoscopic techniques for diagnosis and treatment.

Adolescent↗

Frontal sinus irrigation: indications, results, and complications.

Management, diagnosis, and surgical treatment of the frontal sinus pathology remain a challenge for the rhinologist. Since the introduction of endoscopic instrumentation, the frontal recess may be reached easily and a variety of endonasal approaches have been rediscovered. Although the endoscopic technique allows direct visualization and manipulation, some problems remain, from localization of the frontal sinus ostium during the procedure to the management of the postoperative care to prevent stenosis. The frontal irrigation is suggested as a useful adjunct during the endonasal approach to locate the frontal drainage.

Endoscopy↗

Local safety of intranasal triamcinolone acetonide: clinical and histological aspects of nasal mucosa in the long-term treatment of perennial allergic rhinitis.

Intranasal corticosteroids are increasingly used to treat allergic rhinitis and their long-term use is generally safe. However, the long-term safety of each molecule should be assessed. The main aim of this multicenter, prospective, randomized, open-label study was to evaluate the effect of triamcinolone acetonide aqueous intranasal spray on nasal mucosal thickness, macroscopic appearance, and mucociliary function. Patients with perennial allergic rhinitis were treated with triamcinolone acetonide 220 micrograms/day for six months. Nasal biopsies taken before and after treatment were compared with biopsies from patients who had been randomized to oral cetirizine 10 mg day or intranasal beclomethasone dipropionate 400 micrograms/day. In the evaluable population (n = 70), there were no significant differences between groups in terms of histologically evaluated thickness and endoscopically evaluated macroscopic appearance of the nasal mucosa, or indigocarmine saccharine test mucociliary function. In the intent-to-treat population (n = 92), there was no difference between treatment groups in the incidence of overall adverse events. This study indicates that sustained treatment with intranasal triamcinolone acetonide does not lead to atrophy of the nasal mucosa or impairment of mucociliary function.

Administration, Intranasal↗

[French multicenter prospective epidemiologic study (ORLI Group) of allergic and lung diseases associated with nasal polyposis].

224 patients presenting with nasal polyposis (NP) were included in a french prospective multicenter study. NP was evaluated by nasal endoscopy and computed tomography. Allergic status was documented using skin prick-tests and/or specific IgE. Pneumologic assessment included spirometry with carbamyl-choline hyper-reactivity test or beta 2 mimetic broncho-dilation test. Minimal follow up period was 1 year. 45% of the whole population were considered as asthmatic. Asthma onset occurred before and after the NP onset in respectively 45.7%, 22.3% and 32% of cases; these two conditions started simultaneously in 32% of patients. Skin prick-tests and/or specific IgE were positive in 32.5% of cases. In most of the cases (80%), patients were polysensitized to house dust mite and/or pollens and/or animal danders and/or fungi. 31% of the population had idiosyncrasy, caused by drugs in general and especially aspirin in 44% of cases. The global population could be divided in two groups according to the occurrence of previous polypectomy or not. The group "polypectomy" and the group "no polypectomy" were similar regarding the frequency, the age of onset, the course and the severity of associated asthma. Familial history (parents, children, brothers and sisters) was of great interest: 58.7% of the patients had one (or more) relative suffering from NP, 43.6% of the patients had one (or more) relative suffering from asthma and 12.2% of the patients had one (or more) relative suffering from idiosyncrasy. These results support a genetic etiology for NP.

Adult↗

[Rhino-sinus polyposis].

Nasal polyposis is a chronic inflammatory disease, involving mainly adults. Nasal obstruction and olfactory disorders are the main symptoms due to the presence of bilateral polyps in the nasal cavities. Association with asthma is frequently noted. Medical management is dominated by intranasal steroid. Recent studies lead to a better understanding of the pathophysiology of this pathology and to propose a better long term management including an information for the patient due to the chronicity of the disease.

Adrenal Cortex Hormones↗

Motogenic effect of recombinant HGF on airway epithelial cells during the in vitro wound repair of the respiratory epithelium.

Cell migration is the earliest mechanism involved in the wound repair process of the respiratory epithelium and could be potentially enhanced by growth factors. In the present work, we investigated the localisation of the hepatocyte growth factor (HGF) receptor (c-Met) during wound repair and evaluated the effect of recombinant HGF (rHGF) on cell migration by using an in vitro model of airway epithelial wound repair. By using immunohistochemical methods, we observed that the immunoreactivity of the c-Met proto-oncogene was increased in epithelial cells engaged in the process of tissue repair. The incubation of wounded cultures with increasing concentrations of rHGF (0.2, 2, 20, and 200 ng/ml) induced a significant (P < 0.02) dose-dependent effect on the wound repair index, with a maximum effect produced at 20 ng/ml (+31.3%). The cell migration speed reached 50.2 micrometer/h at this concentration, compared to 20.4 micrometer/h in the absence of rHGF. No significant effect on cell proliferation was observed in the repairing area in the presence of rHGF. These results suggest that rHGF is able to improve the wound repair process of the airway epithelium by increasing cell migration.

Cell Movement↗

Pseudomonas aeruginosa virulence factors delay airway epithelial wound repair by altering the actin cytoskeleton and inducing overactivation of epithelial matrix metalloproteinase-2.

To investigate the role of P. aeruginosa virulence factors in the repair of human airway epithelial cells (HAEC) in culture, we evaluated the effect of stationary-phase supernatants from the wild-type strain PAO1 on cell migration, actin cytoskeleton distribution, epithelial integrity during and after repair of induced wounds, and the balance between matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP). PAO1 supernatant altered wound repair by slowing the migration velocity in association with altered actin cytoskeleton polymerization in the lamellipodia of migrating airway epithelial cells and delaying or inhibiting the restoration of epithelial integrity after wound closure. PAO1 virulence factors overactivated two of the gelatinolytic enzymes, MMP-2 and MMP-9, produced by HAEC during repair. During HAEC repair in the presence of PAO1 virulence factors, enhanced MMP-2 activation was associated with decreased rates of its specific inhibitor TIMP-2, whereas enhanced MMP-9 activation was independent of changes of its specific inhibitor TIMP-1. These inhibitory effects were specific to P. aeruginosa elastase-producing strains (PAO1 and lipopolysaccharide-deficient AK43 strain); supernatants from P. aeruginosa strain elastase-deficient PDO240 and Escherichia coli strain DH5alpha had no inhibitory effect. To mimic the effects of P. aeruginosa, we further analyzed HAEC wound closure in the presence of increasing concentrations of activated MMP-9 or MMP-2. Whereas increasing concentrations of active MMP-9 accelerated repair, excess activated MMP-2 generated a lower migration velocity. All these data demonstrate that P. aeruginosa virulence factors, especially elastase, may impede airway epithelial wound closure by altering cell motility and causing an imbalance between pro- and activated forms of MMP-2.

Actins↗