Is there any effect of neurotrophin-3 on the pathogenesis of non-allergic nasal polyps?

BACKGROUND: Although the role of neurotrophins such as nerve growth factor and brain-derived neurotrophic factor in nasal polyps development has been studied, the contribution of neurotrophin-3 has not been evaluated yet. This study aimed to investigate the possible role of neurotrophin-3 in nasal polyps pathogenesis. METHODS: The study group comprised 70 non-allergic nasal polyps patients and the control group consisted of 53 patients with middle turbinate concha bullosa. Specimens were taken, during surgery, from the ethmoid sinus nasal polyps in the nasal polyps group and from the lateral part of the middle turbinate concha bullosa in the control group. Tissue and serum levels of neurotrophin-3 were assessed by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. RESULTS: Nasal polyps patients had higher tissue neurotrophin-3 scores (p < 0.001). There was no statistically significant difference between groups regarding serum neurotrophin-3 levels (p = 0.417). Tissue neurotrophin-3 staining scores in the nasal polyps group had no statistically significant correlation with Lund-Mackay scores (p = 0.792). CONCLUSION: Neurotrophin-3 may have a local effect in nasal polyps pathogenesis, without joining systemic circulation.

IL-5 and IL-6 are increased in the frontal recess of eosinophilic chronic rhinosinusitis patients.

BACKGROUND: Eosinophilic chronic frontal sinusitis is difficult to treat compared with non-eosinophilic sinusitis because of recurring inflammation and polyp formation in the frontal recess after the post-operative follow-up period. Studying inflammatory mediators in the frontal recess of eosinophilic chronic rhinosinusitis (ECRS) patients and non-eosinophilic chronic rhinosinusitis (non-ECRS) patients may lead to a better understanding of the pathogenesis of chronic frontal sinusitis. METHODS: Homogenates of sinonasal mucosa from 20 non-ECRS patients and 36 ECRS patients were measured for levels of transforming growth factor (TGF)-ß, interleukin (IL)-5, IL-6, and inducible nitric oxide synthase (iNOS) using real-time RT-PCR and TaqMan gene expression assays. Sinonasal mucosal specimens were obtained from the frontal recess, ethmoid sinus, and nasal polyp separately. RESULTS: The expression of IL-5 was significantly elevated in all sinonasal regions tested in the ECRS group, but absent in non-ECRS patients. Furthermore, the ECRS patients showed significantly increased levels of IL-5 in the frontal recess mucosa compared with ethmoid sinus mucosa. IL-6 was also significantly increased in the frontal recess mucosa compared with ethmoid sinus mucosa and nasal polyps in these patients. There were no significant differences in the levels of TGF-ß or iNOS between the ECRS and non-ECRS groups in any sinonasal region tested. CONCLUSIONS: This study is the first to characterize the cytokine milieu in the frontal recess of ECRS patients. We should keep these cytokine profiles in mind when we treat ECRS patients with frontal sinusitis.

[Staphylococcus aureus biofilm influences the expression of lysozyme, SLPI and gp340 in a human sinonasal explant model].

OBJECTIVE: To investigate the influences of staphylococcus aureus in planktonic and biofilm forms on the expression of lysozyme, SLPI and gp340 in the human sinonasal explant model. METHOD: Mucosa samples from ethmoid sinus were collected from ten patients of cerebrospinal fluid leak and were cultured with and without S. aureus biofilms and planktonic cells. After the infection, the explant model was confirmed by CLSM, and the secretion of lysozyme, SLPI and gp340 was detected by enzyme-linked immunosorbent assay (ELISA) at 8, 16, and 24 h after S. aureus challenge. Expressions of lysozyme, SLPI and gp340 in mRNA and protein levels after 24 h S. aureus challenge were detected using RT-PCR, immunohistochemistry and Western bolt assay respectively. RESULT: The secretion of lysozyme, SLPI and gp340 in the explant model was observed with a trend to increase in a time-dependent manner. At 8 and 16 h after S. aureus challenge, the secretion of lysozyme, SLPI and gp340 in biofilms group was significantly higher than these in planktonic cells group and control group (P<0. 05). S. aureus biofilms enhanced the mRNA expressions of lysozyme, SLPI and gp340 significantly compared with planktonic cells and controls, and the mRNA expressions in the explant model challenged by planktonic cells were significantly higher than controls (P < 0.05). Although the Western bolt assay showed no differences between the lysozyme expression in the planktonic cells group and control group (P > 0.05), the biofilms enhanced the expressions of lysozyme, SLPI and gp340 significantly compared with planktonic cells and controls (P < 0.05). CONCLUSION: S. aureus biofilm induced the expressions of lysozyme, SLPI and gp340 to a higher level than planktonic cells, indicating that S. aureus biofilm was an influencing factor on the innate immune system.

Enhanced expressions of lysozyme, SLPI and glycoprotein 340 in biofilm-associated chronic rhinosinusitis.

Lysozyme, secretory leukocyte proteinase inhibitor (SLPI) and glycoprotein 340 (gp340) are important effectors of the innate immune system in sinonasal mucosa. Bacterial biofilms (BBF) are highly organized bacterial communities resistant to host defense systems. The aim of this study was to investigate the expression of lysozyme, SLPI and gp340 in sinus mucosa from chronic rhinosinusitis (CRS) patients with different BBF status. In this prospective cohort study, 63 CRS patients undergoing endoscopic sinus surgery and 20 controls were enrolled and their mucosal samples from ethmoid sinus were obtained. Biofilms were examined by confocal scanning laser microscopy (CSLM), and the expressions of lysozyme, SLPI and gp340 in mRNA and protein levels were detected using reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and Western blot assay, respectively. As a result, 35/63 (55.6%) of the patients were BBF positive in the CRS group and none in controls. Both mRNA and protein levels of lysozyme, SLPI and gp340 in patients with CRS were significantly higher than those in controls. When sub-classified according to BBF status, the CRS patients with BBF revealed the significantly enhanced mRNA and protein levels of lysozyme, SLPI and gp340. In conclusion, our study demonstrates that lysozyme, SLPI and gp340 are constitutively expressed in sinus mucosa and their up-regulated expressions on both the mRNA and protein levels are associated with BBF in CRS patients. These findings may offer an insight into the interaction between BBF and the innate immune system.

Trail overexpression inversely correlates with histological differentiation in intestinal-type sinonasal adenocarcinoma.

INTRODUCTION: Despite their histological resemblance to colorectal adenocarcinoma, there is some information about the molecular events involved in the pathogenesis of intestinal-type sinonasal adenocarcinomas (ITACs). To evaluate the possible role of TNF-related apoptosis-inducing ligand (TRAIL) gene defects in ITAC, by investigating the immunohistochemical expression of TRAIL gene product in a group of ethmoidal ITACs associated with occupational exposure. MATERIAL AND METHODS: Retrospective study on 23 patients with pathological diagnosis of primary ethmoidal ITAC. Representative formalin-fixed, paraffin-embedded block from each case was selected for immunohistochemical studies using the antibody against TRAIL. Clinicopathological data were also correlated with the staining results. RESULTS: The immunohistochemical examination demonstrated that poorly differentiated cases showed a higher percentage of TRAIL expressing cells compared to well-differentiated cases. No correlation was found with other clinicopathological parameters, including T, stage and relapses. CONCLUSION: The relationship between upregulation of TRAIL and poorly differentiated ethmoidal adenocarcinomas suggests that the mutation of this gene, in combination with additional genetic events, could play a role in the pathogenesis of ITAC.

Increased exhaled nitric oxide and its oxidation metabolism in eosinophilic chronic rhinosinusitis.

OBJECTIVE: Monitoring of fractional concentrations of exhaled nitric oxide (FeNO) has become a reliable marker of inflammation in human nose and paranasal sinuses. However, it is still unknown to what extent nasal NO levels contribute to the pathology of chronic rhinosinusitis (CRS). In the present study, we aimed to examine FeNO levels and the underlying mechanism of NO production and metabolism in patients with eosinophilic chronic rhinosinusitis (ECRS) and non-ECRS. METHODS: Thirty-three untreated ECRS patients, 16 non-ECRS patients, and 38 normal subjects were enrolled in this cross-sectional study of FeNO levels. Oral and nasal FeNO levels were measured before treatment using an electrochemical NO analyzer (NObreath(®)) with a nose adaptor. The mRNA expression of three nitric oxide synthase (NOS) isoforms, interleukin-5 (IL-5), and transforming growth factor-beta (TGF-ß) in the ethmoid sinus mucosa and nasal polyps were analyzed by real-time PCR. Immunohistological localization of inducible NOS (iNOS) and nitrotyrosine (NT), a marker for oxidized NO metabolites, was also examined. RESULTS: ECRS patients showed significantly higher oral FeNO levels compared to non-ECRS patients and normal subjects (mean values, 47.6, 13.5, and 15.3ppb, respectively). Nasal FeNO levels of the non-ECRS patients (30.5ppb) were significantly lower than those of the ECRS patients (53.9ppb) and normal subjects (45.5ppb). Positive correlations existed between the blood eosinophil percentage and FeNO levels in ECRS patients. Histologically, ECRS patients showed higher eosinophil accumulation in the ethmoid mucosa than non-ECRS patients (103.1 vs. 16.3cells/HPF). Real-time PCR analysis showed significant upregulation of iNOS and IL-5 mRNA expression in the ethmoid mucosa of the ECRS patients compared to those of non-ECRS patients. Positive iNOS immunoreactivity was observed in ciliated epithelial cells, submucosal glands and associated inflammatory cells in both groups. NT immunoreactivity was detected in the epithelium and around inflammatory cells. Intense NT staining was co-localized with eosinophil accumulation and ECRS patients showed significantly higher rates of NT-positive cells than non-ECRS patients. CONCLUSION: A combination of oral and nasal FeNO measurement is a valid marker for the classification and definition of different CRS subtypes in Japan. Higher levels of oral and nasal FeNO in ECRS patients may reflect the persistence of eosinophilic inflammation in sinus mucosa with concomitant iNOS upregulation and accompanying deposition of oxidized NO metabolites.

Endoscopic neural blockade for rhinogenic headache and facial pain: 2011 update.

BACKGROUND: Over 45 million Americans suffer from recurrent headaches, and an estimated $11.9 million was spent on doctor's visits for rhinogenic pain last year. Sphenopalatine blocks have been described for various facial pain syndromes, but their use and the type of blockade agents remain controversial. The objective of this study was to demonstrate that endoscopic nerve blocks, using a mixture of bupivicaine and triamcinolone-40, injected into the anterior ethmoid or sphenopalatine regions, can be a relative safe and effective option for refractory pain. METHODS: The charts of all patients undergoing endoscopic neural blockade, in a private practice setting from 1998 to 2008 were retrospectively reviewed. A 1:1 mixture of 0.5% bupivicaine and triamcinolone acetonide injectable suspension was injected into the patients' anterior ethmoid or sphenopalatine neural distribution, or both, depending on the pain distribution. Charts were reviewed to assess outcomes and any adverse events from nerve blocks. RESULTS: A total of 882 nerve blocks were administered to 147 patients, over the course of 431 office visits. Four mild complications, 2 moderate complications, and no severe or permanent complications were noted. No permanent visual complications were observed. Of all the charts, 85% had documented effects of the nerve block at follow-up. Of those, 81.3% claimed improvement, 17.9% reported feeling the same, and 0.79% stated they had worse pain. CONCLUSION: Endoscopic neural blockade appears to be a relatively safe and viable option in the treatment of refractory headache and facial pain with a rhinogenic component.

Primary diffuse large B-cell lymphoma of the ethmoid sinus.

Malignant lymphoma of the ethmoid sinus is very rare. A case of diffuse large B-cell lymphoma (DLBCL) of the left ethmoid sinus is presented here. A 79-year-old Japanese man was consulted to our hospital because of head ache and disturbance of left eye movement. Nasal endoscopy revealed a tumor, and imaging modalities including CT and MRI detected a tumor in the left ethmoid sinus. The tumor was invasive into left eye and left nose. A biopsy was performed via the nasal cavity. The biopsy revealed a diffuse proliferation of atypical lymphocytes. The atypical lymphocytes were large and had enlarged hyperchromatic nuclei. Mitotic figures were scattered. Hodgkin's cells were absent. Follicular structures were not seen. Immunohistochemically, the tumor cells were negative for cytokeratins (AE1/2, polyclonal, KL-1, and CAM5.2, Dako) and epithelial membrane antigen, CD3, CD15, CD30, CD45RO, and TdT. In contrast, the tumor cells were positive for CD20, CD45, CD79α, and p53. KI-67 labeling was 100%. Light chain restriction was present; there were numerous λ-chain-positive cells, while κ-chain-positive cells were scant. The pathological diagnosis was DLBCL of the left ethmoid sinus. Imaging of the whole body revealed no tumors and lymphadenopathy other than the ethmoid DLBCL. The patient was treated with chemoradiation, and is now alive 3 months after the presentation. In conclusion, a very rare case of DLBCL of the ethmoid sinus was reported.

Evaluation of bacterial biofilms in chronic rhinosinusitis.

OBJECTIVE: We investigated the presence of biofilms in patients with chronic rhinosinusitis. DESIGN: Prospective study. METHODS: Thirty patients with chronic rhinosinusitis scheduled for endoscopic sinus surgery were enrolled in this study. Nasal swab cultures were taken at the time of surgery. Samples were cultured using conventional methods for Haemophilus influenzae, Pseudomonas aeruginosa, Streptococcus pneumoniae, and Staphylococcus aureus. MAIN OUTCOME MEASURES: Culture-positive samples were evaluated for slime-forming ability. Qualitative detection of biofilm formation by all slime-producing strains was studied by culturing the strains on Congo red agar plates. RESULTS: Twenty-three of 30 patients' samples were culture positive (76.6%). Thirteen S. aureus and 10 P. aeruginosa cultures were identified on 23 specimens. Bacterial biofilms were present on 15 of 23 (65.2%) culture-positive specimens. Nine of 13 (69.2%) S. aureus cultures and 6 of 10 (60%) P. aeruginosa cultures produced bacterial biofilms. CONCLUSION: This conventional method is capable of demonstrating biofilm-forming ability in bacteria recovered from patients with chronic rhinosinusitis. The biofilm-forming ability was higher in S. aureus compared with P. aeruginosa.

Upregulation of elafin and cystatin C in the ethmoid sinus mucosa of patients with chronic sinusitis.

OBJECTIVES: To investigate the expression levels and distribution patterns of elafin and cystatin C in normal and inflammatory human sinus mucosa and to evaluate their roles in chronic sinusitis. DESIGN: A controlled, prospective study. SETTING: A tertiary academic institution. PATIENTS: Normal sinus mucosa was obtained from the ethmoid sinus during surgery in 30 patients with blowout fractures. Inflammatory sinus mucosa was obtained from 30 patients undergoing endoscopic sinus surgery for chronic polypoid sinusitis. INTERVENTIONS: Reverse transcription-polymerase chain reaction, immunohistochemical analysis, and Western blotting. MAIN OUTCOME MEASURES: Expression levels and distribution patterns of elafin and cystatin C in normal and inflammatory mucosa. RESULTS: Expression of elafin and cystatin C messenger RNAs and proteins analyzed by means of reverse transcription-polymerase chain reaction and Western blot was detected in all normal and inflammatory sinus mucosa tested. Their expression levels were increased in inflammatory vs normal mucosa. Elafin in normal and inflammatory sinus mucosa was distinctly expressed in goblet cells, which are increased in inflammatory sinus mucosa. Elafin in submucosal glands was usually weak in staining intensity, except for a few scattered submucosal glands showing moderate intensity in inflammatory sinus mucosa. Cystatin C was also localized in goblet cells and submucosal glands in normal and inflammatory mucosa. Staining intensity was increased more in inflammatory vs normal sinus mucosa. CONCLUSION: Elafin and cystatin C may play an important role in the protection of normal sinus mucosa and further in regulation of the inflammatory condition in chronic sinusitis.

Increased expression of glycoprotein 340 in the ethmoid sinus mucosa of patients with chronic sinusitis.

OBJECTIVES: To investigate the expression and distribution of glycoprotein 340 (gp340), a secretory glycoprotein, in normal human sinus mucosa and inflammatory sinus mucosa and evaluate the possible effects of gp340 on the development of chronic sinusitis. Glycoprotein 340 was identified as a key element in the innate host defense mechanism on many mucosal surfaces and is directly involved in defense functions aimed at clearing gram-positive and gram-negative bacteria. DESIGN: Prospective study. SETTING: Tertiary academic institution. PATIENTS: Normal sinus mucosa was obtained from the ethmoid sinus mucosa of 8 patients with blowout fractures undergoing endoscopic reduction. Inflammatory sinus mucosa was taken from 25 patients with chronic polypoid sinusitis during endoscopic sinus surgery. INTERVENTION: Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemical analysis, and Western blotting were performed. MAIN OUTCOME MEASURES: The expression level and distributional pattern of gp340 in normal and inflammatory sinus mucosa were analyzed. RESULTS: Transcripts of the gp340 gene were detected in all human sinus tissues analyzed by RT-PCR. Immunohistochemical analysis revealed that gp340 is mainly localized in submucosal gland of both normal and inflammatory sinus mucosa. Semiquantitative RT-PCR and Western blot analysis showed the increased expression levels of gp340 in the inflammatory sinus mucosa compared with the normal sinus mucosa. CONCLUSION: These results suggest that gp340 may play a constitutive role in nasal defense and may be up-regulated in response to inflammation, participating in antimicrobial defense in chronic sinusitis.

D2-40 immunohistochemical assessment of lymphangiogenesis in normal and edematous sinus mucosa and nasal polyp.

OBJECTIVE: The lymphatic system plays an important role in the maintenance of tissue fluid homeostasis, which facilitates interstitial protein transport. Until recently, the lymphatic system of the sinonasal mucosa has been relatively poorly studied. The authors aimed to investigate the distributional and quantitative changes of the lymphatic vessels in inflammatory sinus mucosa and nasal polyps in comparison with healthy sinus mucosa using D2-40 antibody. METHODS: Immunohistochemistry and Western blotting with D2-40 antibody were applied to normal and edematous ethmoid sinus mucosa and nasal polyps. The number, size, and length densities of lymphatic vessels were evaluated using tissue sections and whole mount preparations. RESULTS: Most lymphatic vessels in normal and edematous ethmoid sinus mucosa were distributed in the subepithelial layer. Some of these vessels were dilated, whereas others were compressed and had a slit-like lumen. No D2-40 positive vessels were found in samples of nasal polyps. Lymphatic vessels showed no statistically significant difference in their number, size, or length density between normal and edematous ethmoid sinus mucosa. Western blot also showed no differences in their expression levels. CONCLUSION: These findings indicate that lymphangiogenesis does not occur in edematous ethmoid sinus mucosa, which may not reuptake interstitial fluid efficiently in inflammatory conditions, resulting in the formation of mucosal edema in chronic inflammation.

Distributional characteristics of lymphatic vessels in normal human nasal mucosa and sinus mucosa.

An immunohistochemical staining technique with the D2-40 antibody was undertaken to examine the functional and morphological features of lymphatic networks in tissue sections and whole-mount preparations of normal nasal mucosa and ethmoid sinus mucosa. In normal nasal mucosa, most lymphatic vessels were found in the superficial mucosa beneath the epithelial layer. Some of these vessels were dilated, whereas others were compressed and had a slit-like lumen. Whole-mount preparations revealed the extent of lymphatic vessels in normal ethmoid sinus mucosa. A network of lymphatic vessels was mainly found in the subepithelial layer, where lymphatic vessels represented rich networks, possessing antler-like branches and typical blind ends. However, these lymphatic networks were not arranged in the form of lymphangion chains, with each lymphangion consisting of a contractile compartment and valve. Thus, recognition of the distinctive features of the lymphatic network in normal nasal and sinus mucosa might aid investigations of lymphatic involvement in sinonasal diseases, such as rhinitis, sinusitis, and malignancy.

Characterization of oxidative pathways in chronic rhinosinusitis and sinonasal polyposis.

BACKGROUND: Eosinophils are a characteristic inflammatory cell infiltrate in both chronic rhinosinusitis (CRS) and sinonasal polyposis (SNP). The posttranslational modifications, 3-bromo-tyrosine (Br-Tyr) and 3-chloro-tyrosine (Cl-Tyr), serve as specific molecular markers for production of brominating and chlorinating oxidants, respectively, by the eosinophil peroxidase and myeloperoxidase systems of leukocytes. The aim of this study was to identify mechanisms of oxidative protein modifications in sinonasal mucosa of CRS and SNP patients by measuring Br-Tyr, Cl-Tyr, and alternative molecular markers of distinct oxidative pathways. METHODS: Levels of Br-Tyr; Cl-Tyr; di-Tyrosine (di-Tyr), a specific oxidative cross-link; ortho-tyrosine (o-Tyr) and meta-tyrosine (m-Tyr), markers for protein modification by hydroxyl radical-like oxidants; and nitro-tyrosine (NO2-Tyr), a stable product of nitric oxide (NO)-derived oxidants, were measured in anterior ethmoid mucosa tissue from CRS and SNP patients, as well as in middle turbinate mucosa from normal volunteers, using tandem mass spectrometry. RESULTS: Tissue levels of Br-Tyr were significantly higher in the CRS group compared with the control group (797 micromol/mol versus 515 micromol/mol tyrosine, p < 0.015), but no differences were detected for Cl-Tyr, di-Tyr, m-Tyr, o-Tyr, and NO2-Tyr. Tissue levels of both Br-Tyr and di-Tyr were significantly higher in the SNP group compared with the control group (879 micromol/mol versus 515 micromol/mol, p < 0.005; 5090 micromol/mol versus 1700 micromol/mol, p < 0.024, respectively), but no differences were detected for Cl-Tyr, m-Tyr, o-Tyr, and NO2-Tyr. CONCLUSION: Br-Tyr, a molecular footprint predominantly formed by eosinophil peroxidase-catalyzed tissue damage, may serve as an objective index of CRS and SNP disease activity.

Altered expression of genes associated with innate immunity and inflammation in recalcitrant rhinosinusitis with polyps.

BACKGROUND: The role of the innate immune system in the pathophysiology of chronic rhinosinusitis (CRS) is poorly understood. In this study, we compared sinonasal expression of toll-like receptors (TLRs), complement components, serum amyloid A, and inflammatory genes (chemokines and cytokines) in control subjects and patients undergoing sinus surgery for CRS. METHODS: Eleven control subjects and 30 subjects with CRS unresponsive to medical management were enrolled prospectively before undergoing endoscopic sinus surgery. Ethmoid mucosal specimens were obtained surgically and processed for RNA extraction. Real-time polymerase chain reaction was used to quantitate the level of expression of messenger RNA (mRNA) for TLR, acute phase proteins, and cytokine genes. Subjects were followed for a minimum of 6 months postoperatively with nasal endoscopy to assess for recurrence of polyps. RESULTS: mRNA for all target genes was detected in the ethmoid mucosa of both control and CRS subjects. The level of gene expression was normalized to the housekeeping genes 18s RNA and glyceraldehyde-3-phosphate dehydrogenase. As compared with controls, CRS was associated with significantly higher expression of TLR2 and the inflammatory genes macrophage-inflammatory protein alpha, RANTES, and granulocyte-macrophage colony-stimulating factor. Patients with early recurrence of polyps after surgery had significantly decreased expression of TLR2, 9, and serum amyloid A and increased expression of macrophage-inflammatory protein alpha compared with surgery-responsive patients. CONCLUSION: This study shows the increased levels of expression of TLR2 and a variety of inflammatory genes in sinonasal mucosa of CRS patients compared with controls. Whether these differences play a role in pathogenesis or are merely manifestations of disease activity is worthy of investigation.

Bacteriology of chronic sinusitis in relation to middle meatal secretion.

BACKGROUND: The bacteriology of chronic sinusitis has been studied widely, but some factors may affect the results, such as sample sources and sampling techniques. However, whether the presence of secretion in the middle meatus affects the culture result has been studied rarely. METHODS: When patients with chronic sinusitis underwent functional endoscopic sinus surgery, swab specimens were taken from the ipsilateral middle meatuses and ethmoid sinuses under endoscopic guidance. While taking specimens from the middle meatuses, we observed the presence of secretions in the middle meatuses. The severity of chronic sinusitis was evaluated by preoperative computed tomography, which was scored by the Lund-Mackay system. The scores of the frontal, anterior ethmoid, maxillary sinus, and ostiomeatal complex were cumulated. RESULTS: Between March 2001 and February 2004, 210 pairs of specimens were collected. The secretion was present in 82 middle meatuses and was absent in the other 128 middle meatuses. The culture rates of middle meatus and ethmoid sinus specimens were 70.7 and 51.2%, respectively, for patients with secretions in the middle meatuses and 53.1 and 44.5%, respectively, for patients without secretions in the middle meatuses. The culture rate was significantly different for middle meatus specimens (p = 0.011) and the mean cumulated computed tomography score also was significantly higher in patients with secretions in the middle meatuses than in patients without secretions in the middle meatuses (p < 0.001). CONCLUSION: The results of this study suggest that the presence of secretion in the middle meatus indicates more severe disease in the anterior group of paranasal sinuses.

Expression of interleukin-5, interleukin-8, and interleukin-10 mRNA in the osteomeatal complex in nasal polyposis.

BACKGROUND: Several cytokines are expressed in chronic sinusitis with and without underlying allergy. Their local production and regulation in the osteomeatal complex, the key area of paranasal sinuses, still is not fully understood. This study was performed to investigate differences of cytokine messenger RNA (mRNA) expression between the medial and the lateral part of the middle turbinate and anterior ethmoid mucosa of allergic and nonallergic patients. METHODS: Using the LightCycler system for real-time reverse-transcription polymerase chain reaction, we investigated the content of interleukin (IL)-5, IL-8, and IL-10 mRNA in tissue samples from middle turbinates and anterior ethmoids of 18 patients with chronic sinusitis and nasal polyps. Inferior turbinate mucosa of six control subjects without sinusitis and allergy served as control. RESULTS: IL-5 mRNA was detectable in 32 (60%) of 54 samples (two of six controls) in significant different amounts between the various locations (p < or = 0.001). Anterior ethmoid mucosa (0.96+/-0.99) expressed the highest amount of IL-5 mRNA followed by the lateral (0.37+/-0.54) and the medial portion of the middle turbinate (0.12+/-0.29) with no difference between allergic and nonallergic subgroups. IL-8 was detected in significant higher amounts in all three origins with no significant difference in concentrations between the examined locations as compared with controls. Patients expressed either IL-5 or IL-8 or both cytokine mRNA. IL-10 was expressed in all three specimens from five of eight allergic patients. All five individuals with clinical symptoms of allergy at the time of operation expressed IL-10 in at least one specimen. CONCLUSION: IL-5 cytokine expression in the osteomeatal complex is linked to the presence of nasal polyps, whereas IL-8 is up-regulated without distinct correlation to nasal polyps. IL-10 expression was detectable in five of eight allergic patients.

[Sinusal penetration of amoxicillin-clavulanic acid. Formulation 1 g./125 mg., twice daily versus formulation 500 mg./125 mg., three times daily]. / Pénétration sinusienne de l'amoxicilline-acide clavulanique. Formulation 1 g/125 mg, 2 fois/jour, versus formulation 500 mg/125 mg, 3 fois/jour.

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.

A prospective, multicentre study of moxifloxacin concentrations in the sinus mucosa tissue of patients undergoing elective surgery of the sinus.

A pharmacokinetic study was carried out to determine moxifloxacin concentrations in sinus tissue, after oral moxifloxacin 400 mg once daily for 5 days to patients with chronic sinusitis, undergoing elective sinus surgery. Patients were randomly allocated to one of seven treatment groups, in which tissues were sampled 2, 3, 4, 6, 12, 24 or 36 h post-dose. A control group with non-infected nasal polyps was also included. Forty-eight patients (13 female, 35 male, mean age 47.1 years) were allocated to one of each active treatment group (n = 42) or to the control group (n = 6). Tissue and plasma samples were taken simultaneously and stored frozen until assayed by HPLC. Thirty-nine patients were fully valid for pharmacokinetic analysis. The geometric mean moxifloxacin plasma concentration increased from 2.32 mg/L at 2 h to a maximum of 3.37 mg/L at 4 h post-dose, decreasing to 0.37 mg/L at 36 h post-dose. The moxifloxacin concentration in sinus mucosa was consistently greater than that in plasma being 4.56-5.73 mg/kg from 2 to 6 h and 2.81-1.25 mg/kg from 12 to 36 h post-dose. The elimination rates in plasma and sinus tissues were similar. The tissue/plasma ratio was c. 200% between 2 and 6 h, and up to 328.9% at 36 h. Results were similar whatever the site of tissue sampling (maxillary sinus, anterior ethmoid sinus or nasal polyps). Tissue levels exceeded the MIC(90) of all pathogens commonly causing acute sinusitis (e.g. 5-30 x MIC for Streptococcus pneumoniae: 0.25 mg/L). These results sup-port the use of moxifloxacin 400 mg once daily as a regimen for the treatment of sinus infections.