Chia-Ming Liu

Bacteriology and antimicrobial susceptibility of pediatric chronic rhinosinusitis: a 6-year result of maxillary sinus punctures.

PURPOSE Few studies in the past decade have focused on antimicrobial resistance of bacteria in pediatric rhinosinusitis. This study aimed to characterize organisms cultured from pediatric chronic rhinosinusitis, as well as current resistance patterns of pathogens. MATERIALS AND METHODS The study was conducted from January 2001 to December 2006. Children with radiograph-proven chronic rhinosinusitis underwent maxillary sinus punctures to obtain pathogens and for analysis of antibiotic resistance. RESULTS The total 295 cultures obtained from 165 children yielded 399 isolates. The most common isolates were alpha-hemolytic Streptococcus (20.8%), Haemophilus influenzae (19.5%), Streptococcus pneumoniae (14.0%), coagulase-negative Staphylococcus (13.0%), and Staphylococcus aureus (9.3%). Anaerobes accounted for 8.0% of all isolates. Susceptibility rates of H influenzae for ampicillin and co-trimoxazole were 44.7% and 42.1%, respectively, in the first 3 years of the study and 25% and 40%, respectively, in the next 3 years. Susceptibility rates of S pneumoniae were 83.3% for penicillin, 0% for erythromycin, and 33.3% for clindamycin in the first 3 years and 73.7%, 5.3%, and 28.9%, respectively, in the latter 3 years. CONCLUSION This study showed a different pattern of antibiotic resistance in pediatric chronic rhinosinusitis as compared with previous studies in both children and adults. The resistance rate of H influenzae for ampicillin appears to be a growing problem in pediatric rhinosinusitis.

Matrix Metalloproteinase-1 and Tissue Inhibitor of Metalloproteinase-1 Gene Expressions and Their Differential Regulation by Proinflammatory Cytokines and Prostaglandin in Nasal Polyp Fibroblasts

Chronic inflammation of the paranasal sinus leads to nasal polyp (NP) formation. In this study, we investigated the effect of stimulation of the proinflammatory cytokines interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α) and prostaglandin (PG) E2 on the production of messenger RNA (mRNA) of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in nasal polyp fibroblasts (NPFs) and nasal mucosa fibroblasts (NFs). The mRNAs of IL-1α, TNF-α, MMP-1, and TIMP-1 in 40 surgical specimens of NPs were studied by in situ hybridization to corroborate the in vitro findings. The results indicated a significant amount of constitutive MMP-1 mRNA in NPFs and cytokine-induced MMP-1 steady-state mRNAs in NFs. The effect of stimulation of cytokines on TIMP-1 mRNA synthesis was unremarkable in NPFs and NFs. Exogenous PGE2 enhanced cytokine-stimulated MMP-1 mRNA synthesis in NPFs. In situ hybridization revealed that cells expressing MMP-1 and TIMP-1 mRNAs (primarily plasma cells, fibroblasts, and endothelial cells) gathered around areas with loose stroma, suggestive of rapid extracellular matrix degradation. These data suggest that the pathogenesis of nasal polyposis could be related to production of MMP-1 and consequent promotion of matrix collagenolysis.

Hypoxia-Stimulated Vascular Endothelial Growth Factor Production in Human Nasal Polyp Fibroblasts: Effect of Epigallocatechin-3-Gallate on Hypoxia-Inducible Factor-1α Synthesis

OBJECTIVE To verify the inhibitory effects of epigallocatechin-3-gallate (EGCG) on the synthesis of hypoxia-induced vascular endothelial growth factor (VEGF) in nasal polyp fibroblasts (NPFs). DESIGN Eight primary cultures of NPFs were established from nasal polyps. Effects of EGCG on the production of hypoxia-inducible factor (HIF)-1 alpha (the most potent VEGF stimulant) and VEGF by NPFs under hypoxic conditions were measured by Western blot analysis. Immunohistochemical staining was used to examine the in vivo expressions of HIF-1 alpha and VEGF in 20 sections of nasal polyps. RESULTS Western blot analysis showed that cobalt chloride induced HIF-1 alpha and VEGF synthesis in NPFs in a time-dependent manner, reaching a plateau at 4 and 8 hours, respectively, following treatment. Epigallocatechin-3-gallate attenuated the level of HIF-1 alpha induced by cobalt chloride and also reduced cobalt chloride-stimulated VEGF production by suppressing HIF-1 alpha synthesis. Furthermore, oligomycin (a specific HIF-1 alpha inhibitor) combined with EGCG resulted in a more profound inhibition of VEGF synthesis compared with oligomycin or EGCG treatment alone. Nevertheless, the synergistic effect seemed smaller than the sum of their individual actions. Immunohistochemical analysis revealed the presence of HIF-1 alpha and VEGF in NPFs and mononuclear round cells. Intimate alignment of VEGF-positive fibroblasts and proliferating small capillaries was frequently found. CONCLUSIONS Nasal polyp fibroblasts contribute to the pathogenesis of nasal polyps by producing VEGF to promote angiogenesis under hypoxic conditions. Epigallocatechin-3-gallate substantially diminishes HIF-1 alpha and VEGF synthesis in NPFs.

Videostrobolaryngoscopy of Mucus Layer during Vocal Fold Vibration in Patients with Laryngeal Tension-Fatigue Syndrome:

The mucus layer on the vocal folds was examined by videostrobolaryngoscopy in patients with laryngeal tension-fatigue syndrome, a chronic functional dysphonia due to vocal abuse and misuse. Besides the findings in previous reports (such as abnormal glottal closure, phase or amplitude asymmetry, and the irregular mucosal wave), the vocal folds during vibration had an uneven mucus surface. The occurrence of an uneven mucus layer on vocal folds was significantly greater in subjects with this voice disorder (83% or 250 of 301 patients in this series) than in those without voice disorders (18.5% or 5 of 27). The increase of mucus viscosity, mucus aggregation, and the formation of rough surfaces on the vocal folds alter the mechanical properties that contribute to vibration of the cover of the vocal folds, and thereby worsen the symptoms of dysphonia in patients with laryngeal tension-fatigue syndrome.

Tumor necrosis factor-alpha stimulates the expression of C-C chemokine ligand 2 gene in fibroblasts from the human nasal polyp through the pathways of mitogen-activated protein kinase.

Background Recruitment of macrophages is crucial to the pathogenesis of the nasal polyp (NP) because this disease is believed to be inflammation related. Information regarding the expression of C-C chemokine ligand 2 (CCL2), an essential modulator of monocyte chemotaxis in nasal polyp fibroblasts (NPFs), remains unavailable. In this study, the effects of tumor necrosis factor (TNF)-α on CCL2 expression in NPFs and the signaling pathway involved were investigated. Methods Primary cultures of NPFs were established from NPs. The expressions of CCL2, c-Fos, and c-Jun mRNAs in NPF after TNF-α stimulation were detected by Northern blot. Western blot was used to examine the activation of mitogen-activated protein kinase (MAPK) signaling pathways. Activator protein (AP) 1/DNA interactions were evaluated by electrophoretic mobility shift assay (EMSA). Results Northern blot showed that TNF-α stimulated CCL2 gene expression in NPFs. Significant increase of B-Raf, phosphorated MAPK including mitogen-activated ERK-activate kinase (MEK)1/2, extracellular signal-related kinase 1/2, and p38 were detected by Western blot. c-Fos and c-Jun mRNAs were induced by TNF-α, and PD98059 (MEK inhibitor) and SB203580 (p38 inhibitor) abolished the up-regulation of c-Fos. EMSA revealed that TNF-α increased AP-1/DNA binding, and PD98059 and SB203580 attenuated this reaction, possibly via reducing c-Fos synthesis. PD98059 and curcumin (AP-1 inhibitor) markedly suppressed the TNF-α–induced CCL2 expression, whereas the effect of SB203580 was less noted. Conclusion TNF-α induces CCL2 transcription in NPFs. B-Raf/MEK/ERK signaling cascade and to a less extent the p38 pathway are responsible for c-Fos activation and the subsequent AP-1/DNA interaction leading to CCL2 expression.

Comparison of Maxillary Sinus Puncture with Endoscopic Middle Meatal Culture in Pediatric Rhinosinusitis

Background Although maxillary sinus puncture is considered the gold standard for obtaining bacterial cultures, there is an increasing field of evidence indicating that results of endoscopic middle meatal culture correlate well with those of maxillary sinus punctures. However, the subjects of these studies were adults and there was no prior study comparing endoscopic middle meatal culture with maxillary sinus punctures in children with rhinosinusitis. The aims of this study were to compare the results obtained by endoscopic middle meatal culture and maxillary sinus punctures in children with rhinosinusitis. Methods A prospective study of children with community-acquired rhinosinusitis was conducted. Results obtained by endoscopic culture were compared with those of maxillary sinus puncture, and the correlation of these 2 techniques was investigated. Results There were 41 specimen sets sent for aerobic cultivation. Correlation obtained from the middle meatus with those from the maxillary sinus puncture was demonstrated in 32 of 41 specimens (78.0%). When looking at the diagnostic usefulness of endoscopic middle meatus sampling versus maxillary sinus puncture, endoscopic sampling provided a sensitivity of 75.0%, a specificity of 88.9%, a predictive value of a positive result of 96.0%, a predictive value of a negative result of 50.0%, and an accuracy of 78.0%. Conclusion We demonstrated that, when performed in pediatric patients, the correlation between endoscopic middle meatal culture and maxillary sinus puncture was not as favorable as in the case of adult patients.

Soluble Adhesion Molecules and Cytokines in Perennial Allergic Rhinitis

BACKGROUND Increasing evidence suggests adhesion molecules and cytokines in patients with inflammatory airway diseases are involved in steps of entrapment and migration of inflammatory cells. Recently, soluble forms of adhesion molecules and cytokines have been detected in the sera and other body fluids of patients with various diseases. OBJECTIVE Eosinophilia in nasal mucosa is characteristic of allergic rhinitis. Vascular adhesion molecules expressed on the endothelium are essential for eosinophils to move from the peripheral blood into the sites of inflammation. Herein, soluble forms of vascular adhesion molecules and eosinophil-activating cytokines are measured to investigate the significance of their appearance in the sera with eosinophil infiltration in the nasal mucosa of perennial allergic rhinitis. METHODS With the quantitative sandwich enzyme immunoassay technique, the sera of 36 patients of perennial allergic rhinitis and 20 nonatopic subjects were used to measure the levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (endothelial leukocyte adhesion molecule-1, sELAM-1), interleukin-3 (IL-3), and interleukin-5 (IL-5). RESULTS No significant differences in the levels of soluble vascular adhesion molecules were noted between the two groups. Eosinophil-activating cytokines, IL-3 and IL-5, were significantly increased in the group with perennial allergic rhinitis, and were correlated with eosinophil infiltration in nasal scrapings. CONCLUSION Although the vascular adhesion molecules expressed on the endothelium are necessary for eosinophils to appear in allergic tissues, eosinophil-activating cytokines as IL-3 and IL-5 are likely to be essential for eosinophils to function in tissues. The elevated concentrations of IL-3 and IL-5 in allergic rhinitis may reflect the inflammatory response occurring in the T cell activation and in relation to manifestation of eosinophils.

Hypoxia induces cysteine-rich 61, vascular endothelial growth factor, and interleukin-8 expressions in human nasal polyp fibroblasts: An implication of neutrophils in the pathogenesis of nasal polyposis.

Background The purpose of this article was to elucidate the roles of neutrophils and angiogenesis factors in the pathogenesis of nasal polyposis. The effect of hypoxia on the expressions of angiogenesis factors as cysteine-rich 61 (Cyr61) and vascular endothelial growth factor (VEGF) and neutrophil chemoattractant as interleukin (IL)-8 in nasal polyp fibroblasts (NPFs), and the role of nuclear factor kappa B (NF-kappaB) in this reaction were investigated. The action of Cyr61 on the synthesis of VEGF and IL-8 in NPFs was also examined. Methods Primary cultures of NPFs were established from nasal polyps (NPs). Productions of Cyr61, VEGF, and IL-8 by NPFs under hypoxia were detected by Western blot (Cyr61 and VEGF) or enzyme-linked immunosorbent assay (ELISA; IL-8). Immunohistochemical staining was used to examine the relation between fibroblastic expression of Cyr61 and neovascularization/neutrophil infiltration in NPs. Results Western blot showed that the hypoxia inducer CoCl2 stimulated Cyr61 synthesis in NPFs in a time-dependent manner, reaching a peak at 24 hours. Bay-117082 (a specific NF-kappaB inhibitor) attenuated the levels of Cyr61 stimulated by hypoxia. Cyr61 induced IL-8 secretion and VEGF synthesis by NPFs, as evidenced by Western blot and ELISA analysis. Bay-117082 abolished hypoxia-stimulated IL-8 and VEGF synthesis, whereas Cyr61 restored the stimulative effect of hypoxia readily. Immunohistochemical staining revealed the presence of Cyr61 and IL-8 in NPFs. Neutrophils and capillaries aggregating around these NPFs were frequently found. Conclusion Under hypoxia, NPFs contribute to NP propagation by expressing Cyr61, which subsequently stimulates VEGF and IL-8 production, leading to angiogenesis and activating neutrophil infiltration in NPs.

Soluble adhesion molecules and cytokines in tumor-associated tissue eosinophilia of nasopharyngeal carcinoma

The phenomenon of tumor-associated tissue eosinophilia (TATE) is seen in some cases of nasopharyngeal carcinoma (NPC) and is characterized by the eosinophils breaking through the vascular wall and pervading the tumor stroma. The margination and trans-endothelial migration of eosinophils in a typical inflammatory reaction depend on the activating effects of certain cytokines and the expression of adhesion molecules on the eosinophils and endothelial cells. In order to investigate whether the adhesion molecules and activating cytokines play a role in eosinophil tumor infiltration, we measured the serum levels of 3 adhesion molecules, intercellular adhesion molecule-1, E-selectin and vascular cell adhesion molecule-1, and 2 cytokines, IL-3 and IL-5, in 60 NPC patients and 40 normal healthy subjects. We found that the NPC patients had higher serum levels of all three soluble adhesion molecules than the normal subjects but the levels of adhesion molecules failed to correlate with the TATE phenomenon. The levels of IL-3 and IL-5 appeared not to differ between the NPC and control groups. We postulate that the three soluble adhesion molecules do not play a major role in TATE and that their elevation in serum may be due to local and/or systemic immune responses.

A rare complication of functional endoscopic sinus surgery: Maxillary atelectasis-induced spontaneous enophthalmos

Background The first case report of spontaneous enophthalmos due to maxillary atelectasis as a late complication of FESS is presented. Methods Chart review of a 24-year-old male who developed a left progressive enophthalmos within three months post bilateral functional endoscopic sinus surgery. Results The preoperative computed tomography showed a normal left maxillary sinus. The postoperative computed tomography revealed a left maxillary atelectasis with a descending orbital floor. The subject received revised endoscopic sinus surgery and his enophthalmos was stable without further progression after the operation. Conclusions This may have been caused by an ostium occlusion with retention of secretions inducing sinus inflammation, osteolytic activity, and osseous remodeling of the sinus walls. A negative pressure may develop. When the pressure gradient exceeds the sinus wall tension, maxillary atelectasis and enophthalmos occur. Prevention of this complication of FESS should include making a patent naso-antral window, minimizing mucosal trauma, and careful postoperative sinoscopic treatment. A “functional” sinus is the goal.