Combining sinus plain film and sinus ultrasound as a screening tool for maxillary fungal sinusitis.

BACKGROUND: Early identification of fungal sinusitis remains a challenge. Previously, we observed a high false negative rate of using A-mode ultrasound to diagnose maxillary fungal sinusitis. This study aims to assess the accuracy of the diagnosis of fungal maxillary sinusitis using sinus plain film and ultrasound. METHODS: The screening criteria is defined as the combination of a positive sinus plain film and a false negative sinus ultrasound. We retrospectively reviewed preoperative imaging of patients with fungal sinusitis and unilateral bacterial sinusitis of the maxillary sinus undergoing functional endoscopic sinus surgery from May 2013 to December 2019 in our hospital and evaluated the diagnostic performance of this screening method. RESULTS: Forty-eight patients were included. Twenty-two and 26 patients were diagnosed with fungal sinusitis and bacterial sinusitis, respectively. Sixteen patients (72.7%) with fungal sinusitis presented with a false negative sinus ultrasound and met our screening criteria for fungal sinusitis. The screening criteria reached significance in the receiver operating characteristic curve analysis (p < 0.001). The area under the curve was 0.829. The sensitivity, specificity, and accuracy are 72.7%, 93.2%, and 88.4%, respectively. CONCLUSION: A high false negative rate of sinus ultrasound in patients with fungal sinusitis was found. A positive sinus plain film combined with a false negative sinus ultrasound can potentially become an easy and cost-effective screening tool for diagnosing fungal maxillary sinusitis before consideration of computed tomography scanning.

Chitosan-microencapsulated rhEGF in promoting wound healing.

AIMS: Chitosan and epidermal growth factor (EGF) have been shown to improve wound healing. This study investigates the healing effects of a spray solution (NewEpi, JoyCom Bio-Chem Co. Ltd., Taiwan) containing recombinant human EGF (rhEGF) delivered via a newly patented technology-chitosan microencapsulated nanoparticles. METHODS: On Wistar rats, two full-thickness wounds on the dorsum bilateral of the spine were created. The rats were randomised to the following treatment groups: hydrogel, wet dressing, foam, rhEGF spray and rhEGF spray+foam. Sterile dressings were applied and changed daily. A total of 2µg of rhEGF was administered in two sprays during each dressing change. All animals were euthanised on day 14. Tissue samples were taken from the wound bed, including an area of 2cm surrounding the wound margin for histological evaluations. RESULTS: Wounds treated with the rhEGF spray achieved the greatest size reduction by day 14 compared with other types of conventional dressings. An overall significant difference in levels of collagen synthesis existed between groups (p<0.01). Pair-wise comparisons showed that the rhEGF spray treatment significantly promoted higher levels of mature Type I collagen than any other conventional dressings (p<0.01), whereas non-rhEGF treatments resulted in higher levels of Type III collagen. The regenerated tissue in rhEGF spray treatment groups was also in alignment with that of normal skin. Epidermis, dermis and hair follicles were easily observed in wounds treated with the rhEGF spray. CONCLUSION: The major challenge of topical application of rhEGF was overcome by using a new drug delivery technology: chitosan-rhEGF nanoparticles. The positive healing effects observed in this study suggest the therapeutic potentials of this novel rhEGF topical spray solution.

Invasive Fungal Rhinosinusitis with and without Orbital Complications: Clinical and Laboratory Differences.

BACKGROUND: Invasive fungal rhinosinusitis (IFS) is a rare but often fatal disease. There are limited studies regarding IFS with orbital complications (IFSwOC). The present study aimed to identify the clinical signs associated with IFSwOC and prognosticators of the disease. METHODS: A retrospective case series was conducted of patients histopathologically confirmed IFS or fungal rhinosinusitis with clinically apparent neuro-orbital complications who underwent surgery between 2008 and 2018. Demographic data, presenting symptoms and signs, culture data, laboratory results, and patient outcomes were obtained from medical records. RESULTS: A total of 38 patients were identified, including 9 patients with IFSwOC, and 29 patients with IFS without orbital complications (IFSsOC). The clinical signs associated with developing orbital complications include headache, fever, sphenoid sinus, or posterior ethmoid sinus involvement, CRP level ≥ 1.025 mg/dL, or ESR level ≥ 46.5 mm/h. In IFSwOC group, male, posterior ethmoid sinus involvement, WBC count ≥ 9000 µL, CRP level ≥ 6.91 mg/dL, or ESR level ≥ 69 mm/h were correlated with a significantly poorer prognosis. CONCLUSION: IFS patients with sphenoid or posterior ethmoid sinus involvement, headache or fever as presenting symptoms, elevated CRP, and ESR level were at risk of developing orbital complications. Timely surgical debridement followed by systemic antifungal treatment may improve treatment outcomes.

Pretreatment age and serum lactate dehydrogenase as predictors of synchronous second primary cancer in patients with nasopharyngeal carcinoma.

OBJECTIVES: Nasopharyngeal carcinoma (NPC) is a common cancer and is treated primarily by chemotherapy and radiotherapy. However, NPC with synchronous second primary cancer (SSPC) is very rare and its risk factors, treatment and prognosis remain unclear. In this study, we aimed to analyze patients with NPC and SSPC, and attempt to find potential predictors for these patients. MATERIALS AND METHODS: We retrospectively collected 681 patients with NPC from 2006 to 2018. Patients in this study were divided into two groups: those patients with SSPC and those without SSPC. We then analyzed the demographic data and survival of these two groups. Independent predictors of SSPC were determined by multivariate regression analysis. A comprehensive review of the literature was also performed. RESULTS: We identified 17 NPC patients with SSPC in our case series and 13 cases in the literatures, and the most common SSPC is lung (16.1%). In univariate analysis, NPC patients with SSPC had older age (P < 0.001) and higher serum lactate dehydrogenase (LDH) (P = 0.008), compared with those without SSPC. In multivariate analysis, old age (P = 0.001) and high serum LDH (P = 0.023) remained independent predictors of SSPC, and a predictive equation model was established. NPC patients with SSPC had a significantly lower 5-year disease-specific survival rate compared with patients without SSPC (34.0% vs. 77.6%, P < 0.001) CONCLUSION: This study demonstrated that pretreatment age and serum LDH were independent predictors for SSPC in NPC patients. These independent factors can be used for early detection, and better facilitate the design of more appropriate treatment by medical professionals.

Survival impacts of different nodal characteristics and T-classification in N3 nasopharyngeal carcinoma patients.

OBJECTIVES: We investigated the survival impacts of various nodal characteristics and T-classification on nasopharyngeal carcinoma (NPC) patients with the 8th AJCC/UICC staging criteria N3. MATERIALS AND METHODS: Pretreatment MRIs from 110 staged N3 NPC patients were reviewed. There were 23 T1, 25 T2, 32 T3, and 30 T4, respectively. All except one patient belonged to WHO type II pathology. All patients received curative radiotherapy 68.0-76.8 Gy plus different chemotherapy, including induction, concurrent, adjuvant or any combination. Various endpoints, including OS (overall survival), DFS (disease-free survival), LRFFS (locoregional failure-free survival), DMFFS (distant metastasis failure-free survival) were compared between different nodal characteristics and T-classification. RESULTS: There were no statistically significant differences in all analyzed survival curves between various nodal characteristics, including unilateral N3 vs. bilateral N3, "large" nodes (>6 cm) alone vs. "low" nodes (below the caudal border of cricoid cartilage) alone vs. combined "large" and "low" nodes, risk score 1 vs. 2 vs. 3 vs. 4 (by counting the sum of "large" and "low" nodes in the same case), and radiologic extra-nodal extension. Patients with T4, compared with those of T1-3 have worse OS (5-year rates, 42.2% vs. 82.8%, P < 0.0001), DFS (5-year rates, 43.9% vs. 68.9%, P = 0.0037), LRFFS (5-year rates, 69.3% vs. 82.7%, P = 0.0432), and DMFFS (5-year rates, 57.2% vs. 77.7%, P = 0.0163). CONCLUSIONS: Our results support merging previous N3a and N3b as a N3 category in the 8th edition new staging system. Patients with T4N3 diseases have extremely poor outcome and deserve to strengthen the treatment intensity in future trials.

Nasopharyngeal Lymphoma: A 22-Year Review of 35 Cases.

Nasopharyngeal (NP) lymphoma is a rare primary malignancy of the head and neck and represents a minority of malignancies originating from the nasopharynx. For this reason, there are limited data regarding epidemiologic and treatment outcomes. This is a retrospective review of patients diagnosed with NP lymphoma from 1995 to 2017 at a tertiary medical center. The patients' demographic data, clinical presentations, treatment modalities, Epstein-Barr virus (EBV)-encoded small RNA (EBER) staining, and outcomes were investigated. We considered a total of 35 patients, including 20 males and 15 females, diagnosed with NP lymphoma. The age ranged from 17 to 88 years (mean = 59.6). The common presentations were nasal obstruction, epistaxis, and neck mass. In our study, the most common pathological diagnosis of NP lymphoma was diffuse large B cell lymphoma (DLBCL) (n = 17), followed by NK/T cell lymphoma (NKTCL) (n = 9). Other pathologic diagnoses included extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALToma), small lymphocytic lymphoma, mantle cell lymphoma. There were 13 cases showing EBER positivity, including 7 cases of NKTCL, 5 cases of DLBCL, and 1 case of post-transplant lymphoproliferative disorder (PTLD). Most patients received chemotherapy alone, while some patients received both chemotherapy and radiotherapy. Seven patients had local recurrence, and fewer than half of the patients (n = 16) were alive at the time of the study (mean follow-up duration: 54.4 months). The five-year overall survival was 50.4%. NP lymphoma is very rare, and the most common pathologic type is DLBCL. EBER positivity is found in both NKTCL and DLBCL. Identifying more effective therapeutic agents is extremely important to improve patients' survival.

Metastatic Tumors of the Sinonasal Cavity: A 15-Year Review of 17 Cases.

Extranasal cancers that metastasize to the sinonasal cavity are very rare. To date, there are only limited reports regarding this rare condition within the literature. Therefore, we retrospectively reviewed all patients diagnosed with metastatic cancer of the sinonasal tract from 2003 to 2018 at a tertiary academic medical center. Patient demographic data, clinical presentation, treatment modalities, and outcomes were investigated. There were a total of 17 patients (9 males and 8 females) included in the analysis. The mean age was 56.8 years (range 27-80). The most common primary malignancies were hepatocellular carcinoma (n = 3) and gastrointestinal tract adenocarcinoma (n = 3). The most common site of metastasis was the nasal cavity (n = 8). Five patients received radical tumor resection and the others underwent radiotherapy, chemotherapy, or combined chemoradiotherapy. The 2-year survival was 28%. In summary, metastasis to the sinonasal cavity remains extremely rare. A high degree of suspicion regarding the possibility of metastatic spread to the sinonasal region is necessary for patients with a previous history of malignancy who present with new sinonasal symptoms. The treatment strategy of sinonasal metastatic cancer is usually palliative therapy and the prognosis remains poor. However, early detection and diagnosis, coupled with aggressive treatment, may improve patient quality of life.

Efficacy of sinus ultrasound in diagnosis of acute and subacute maxillary sinusitis.

BACKGROUND: The aim of this study was to evaluate the diagnostic efficacy of sinus ultrasound for acute and subacute maxillary sinusitis (ASMS) by investigating the agreement between different tools. We also proposed a confirmatory tool directed protocol for adult acute sinusitis, to enhance diagnostic accuracy. METHODS: This prospective cohort study enrolled patients who were older than 18 years, with a diagnosis of maxillary sinusitis. The duration of symptoms was confined to less than 12 weeks. Rigid nasal endoscopy, sinus ultrasound, and plain sinus film were performed for all patients on the same day to confirm the diagnosis. Kappa statistics were used to test interrater reliability. RESULTS: A total of 148 maxillary sinuses in 74 patients (38 men, 36 women) were evaluated. Sinus ultrasound and rigid nasal endoscopy disclosed the best agreement (agreement = 0.78, κ = 0.556). The agreement of rigid nasal endoscopy and plain sinus film was relatively poor (agreement = 0.72, κ = 0.446). Sinus ultrasound and plain sinus film had the poorest diagnostic consistency (agreement = 0.67, κ = 0.338). CONCLUSION: Sinus ultrasound is a quick, safe, cost effective, and relatively easy-to-use technique for clinicians to evaluate the maxillary sinus. Sinus ultrasound and rigid nasal endoscopy are complementary tests to confirm the diagnosis of ASMS.

Sinonasal seromucinous hamartoma.

INTRODUCTION: Seromucinous hamartoma (SH) is a rare benign glandular proliferation of the sinonasal tract and nasopharynx. Only few cases have been reported in recent years. MATERIALS AND METHODS: We performed a retrospective medical record review of seven patients diagnosed with sinonasal SH who underwent endoscopic endonasal surgery. RESULTS: There were 5 males and 2 females, ranged in age from 40 to 98 years (mean 60 years, SD ± 18.9). Two lesions arise from middle turbinate, two from uncinate process, and 3 (but 4 specimens) from nasal septum. Pathological features revealed a polypoid lesion with submucosal proliferation of seromucinous glands arranged in lobular and haphazard patterns. In immunohistochemical study, the seromucinous glands of SH were reactive for cytokeratin, including CK7, CK19, HMWK, but negative for CK20. CONCLUSION: Sinonasal SH is a rare diagnosis characterized by a polypoid lesion with a haphazard proliferation of seromucinous glands. The rhinologists should consider it in the differential diagnosis of a polypoid lesion in the nasal cavity.

CD44 and CD24 coordinate the reprogramming of nasopharyngeal carcinoma cells towards a cancer stem cell phenotype through STAT3 activation.

Cell surface proteins such as CD44 and CD24 are used to distinguish cancer stem cells (CSCs) from the bulk-tumor population. However, the molecular functionalities of CD24 and CD44, and how these two molecules coordinate in CSCs remain poorly understood. We found that nasopharyngeal carcinoma (NPC) cells with high expression of CD44 and CD24 proteins presented with pronounced CSC properties. Accordingly, a subpopulation of NPC cells with co-expression of CD44 and CD24 were specially enriched in high-stage clinical samples. Furthermore, ectopically expressing the epithelial-mesenchymal transition (EMT) regulator Twist was able to upregulate the stemness factors, and vice versa. This indicates a reciprocal regulation of stemness and EMT. Intriguingly, we found that this reciprocal regulation was differentially orchestrated by CD44 and CD24, and only simultaneous silencing the expression of CD44 and CD24 led to a broad-spectrum suppression of CSC properties. Oppositely, overexpression of CD44 and CD24 induced the reprogramming of parental NPC cells into CSCs through STAT3 activation, which could be blunted by STAT3 inhibition, indicating that CD44 and CD24 collaboratively drive the reprogramming of NPC cells through STAT3-mediated stemness and EMT activation. Consequently, targeting of the CD44/CD24/STAT3 axis may provide a potential therapeutic paradigm for the treatment of NPC through repressing CSC activities.

Fractionated Boron Neutron Capture Therapy in Locally Recurrent Head and Neck Cancer: A Prospective Phase I/II Trial.

PURPOSE: To investigate the efficacy and safety of fractionated boron neutron capture therapy (BNCT) for recurrent head and neck (H&N) cancer after photon radiation therapy. METHODS AND MATERIALS: In this prospective phase 1/2 trial, 2-fraction BNCT with intravenous L-boronophenylalanine (L-BPA, 400 mg/kg) was administered at a 28-day interval. Before each fraction, fluorine-18-labeled-BPA-positron emission tomography was conducted to determine the tumor/normal tissue ratio of an individual tumor. The prescription dose (D80) of 20 Gy-Eq per fraction was selected to cover 80% of the gross tumor volume by using a dose volume histogram, while minimizing the volume of oral mucosa receiving >10 Gy-Eq. Tumor responses and adverse effects were assessed using the Response Evaluation Criteria in Solid Tumors v1.1 and the Common Terminology Criteria for Adverse Events v3.0, respectively. RESULTS: Seventeen patients with a previous cumulative radiation dose of 63-165 Gy were enrolled. All but 2 participants received 2 fractions of BNCT. The median tumor/normal tissue ratio was 3.4 for the first fraction and 2.5 for the second, whereas the median D80 for the first and second fraction was 19.8 and 14.6 Gy-Eq, respectively. After a median follow-up period of 19.7 months (range, 5.2-52 mo), 6 participants exhibited a complete response and 6 exhibited a partial response. Regarding acute toxicity, 5 participants showed grade 3 mucositis and 1 participant showed grade 4 laryngeal edema and carotid hemorrhage. Regarding late toxicity, 2 participants exhibited grade 3 cranial neuropathy. Four of six participants (67%) receiving total D80 > 40 Gy-Eq had a complete response. Two-year overall survival was 47%. Two-year locoregional control was 28%. CONCLUSIONS: Our results suggested that 2-fraction BNCT with adaptive dose prescription was effective and safe in locally recurrent H&N cancer. Modifications to our protocol may yield more satisfactory results in the future.

Menthol suppresses laryngeal C-fiber hypersensitivity to cigarette smoke in a rat model of gastroesophageal reflux disease: the role of TRPM8.

Patients with gastroesophageal reflux disease (GERD) display enhanced laryngeal reflex reactivity to stimuli that may be due to sensitization of the laryngeal C-fibers by acid and pepsin. Menthol, a ligand of transient receptor potential melastatin-8 (TRPM8), relieves throat irritation. However, the possibility that GERD induces laryngeal C-fiber hypersensitivity to cigarette smoke (CS) and that menthol suppresses this event has not been investigated. We delivered CS into functionally isolated larynxes of 160 anesthetized rats. Laryngeal pH 5-pepsin treatment, but not pH 5-denatured pepsin, augmented the apneic response to CS, which was blocked by denervation or perineural capsaicin treatment (a procedure that blocks the conduction of C fibers) of the superior laryngeal nerves. This augmented apnea was partially attenuated by capsazepine [an transient receptor potential vanilloid 1 (TRPV1) antagonist], SB-366791 (a TRPV1 antagonist), and HC030031 [a transient receptor potential ankyrin 1 (TRPA1) antagonist] and was completely prevented by a combination of TRPV1 and TRPA1 antagonists. Local application of menthol significantly suppressed the augmented apnea and this effect was reversed by pretreatment with AMTB (a TRPM8 antagonist). Our electrophysiological studies consistently revealed that laryngeal pH 5-pepsin treatment increased the sensitivity of laryngeal C-fibers to CS. Likewise, menthol suppressed this laryngeal C-fiber hypersensitivity and its effect could be reversed by pretreatment with AMTB. Our results suggest that laryngeal pH 5-pepsin treatment increases sensitivity to CS of both TRPV1 and TRPA1, which are presumably located at the terminals of laryngeal C-fibers. This sensory sensitization leads to enhanced laryngeal reflex reactivity and augmentation of the laryngeal C-fiber responses to CS, which can be suppressed by menthol acting via TRPM8.

Fractionated BNCT for locally recurrent head and neck cancer: experience from a phase I/II clinical trial at Tsing Hua Open-Pool Reactor.

To introduce our experience of treating locally and regionally recurrent head and neck cancer patients with BNCT at Tsing Hua Open-Pool Reactor in Taiwan, 12 patients (M/F=10/2, median age 55.5 Y/O) were enrolled and 11 received two fractions of treatment. Fractionated BNCT at 30-day interval with adaptive planning according to changed T/N ratios was feasible, effective and safe for selected recurrent head and neck cancer in this trial.

Dural metastasis of nasopharyngeal carcinoma: rare, but worth considering.

Metastasis of nasopharyngeal carcinoma (NPC) to the dura, an extremely rare condition, can be symptomatically silent and mistaken for a benign entity radiographically. Missed diagnosis can lead to serious consequences or prove immediately fatal. We report a woman with dural metastasis of NPC that mimicked a meningioma on radiography. Craniectomy with tumour resection was performed due to rapid progression from the onset of symptoms to disability. The patient was still alive two years after surgery. This case emphasises the need to keep in mind the possibility of dural metastasis of NPC in patients with abnormal imaging features. This would not only avoid wrong and optimistic diagnosis, but also allow for appropriate treatment in a timely manner. To our knowledge, this is the first report of metastasis of NPC to the dura. We provide detailed information on the neoplastic lesion, which masqueraded as a benign entity and caused potentially fatal consequences.

Ruptured internal carotid artery aneurysm presenting as a sinonasal organized hematoma: conventional approach may endanger life.

Sinonasal organized hematoma (SOH) is an uncommon benign entity with locally aggressive behavior. The conventional approach is complete resection. This approach, however, can cause massive hemorrhage and mortality in our patient due to a ruptured internal carotid artery (ICA) aneurysm hidden inside the SOH. To the best of our knowledge, this is the first case of a huge SOH with skull base invasion caused by a hidden ICA aneurysm, which usually would not be large enough to result in a sinonasal mass lesion. This case suggests that the possibility of an aneurysm should always be considered if a SOH is suspected, especially when it is huge and close to the ICA. Surgical resection may not be the first therapeutic choice unless the differential cause of a hidden aneurysm can be excluded.

Using computational strategies to predict potential drugs for nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a unique cancer. Refinement of current therapy by discovering potential drugs may be approached by several computational strategies. METHODS: We collected NPC genes from published microarray data and the literature. The NPC disease network was constructed via a protein-protein interaction (PPI) network. The Connectivity Map (CMap) was used to predict potential chemicals, and support vector machines (SVMs) were further utilized to classify the effectiveness of tested drugs against NPC using their gene expression from CMap. RESULTS: A highly interconnected network was obtained. Several chemically sensitive genes were identified and 87 drugs were predicted with the potential for treating NPC by SVM, in which nearly half of them have anticancer effects according to the literature. The 2 top-ranked drugs, thioridazine and vorinostat, were demonstrated to be effective in inhibiting NPC cells. CONCLUSION: This in silico approach provides a promising strategy for screening potential therapeutic drugs for NPC treatment.

Reconstructed bone chip detachment is a risk factor for sinusitis after transsphenoidal surgery.

OBJECTIVES/HYPOTHESIS: Sphenoid sinusitis is a complication associated with endoscopic transsphenoidal pituitary surgery. Studies that address the relationship between methods of sellar defect reconstruction and postoperative sinusitis are rare. The purpose of this study was to investigate the incidence, the possible risk factors, and the causative pathogens of sphenoid sinusitis after endoscopic transsphenoidal pituitary surgery. STUDY DESIGN: Prospective cohort study. METHODS: We performed a prospective analysis of 182 patients with benign pituitary tumor who underwent endoscopic transsphenoidal pituitary surgery and sellar defect reconstruction with bone chip, from July 2008 through July 2011. All patients were followed up with nasal endoscopy for at least 6 weeks. RESULTS: Fifty-seven (31.3%) patients developed postoperative sphenoid sinusitis. Comparing the sinusitis and nonsinusitis groups, we found that bone chip detachment was a significant risk factor for postoperative sinusitis, with a relative risk of 2.86 (64.1% vs. 22.4%). The most common pathogens present in cases of postoperative sinusitis were methicillin-sensitive Staphylococcus aureus, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. CONCLUSIONS: Regular follow-up with nasal endoscopy can prevent delayed diagnosis of postoperative sphenoid sinusitis. Culture-directed antibiotics with aggressive endoscopic debridement are an effective treatment for these patients. An optimal reconstruction strategy should be further developed to reduce bone chip detachment and secondary sinusitis.

Induction of apoptosis by high-dose gold nanoparticles in nasopharyngeal carcinoma cells.

OBJECTIVE: Nasopharyngeal carcinoma (NPC) is a rare malignancy in most parts of the world, but is a common cancer in southern Asia. Local recurrent disease and distant metastasis of NPC are still the unsolved problems. Recently, gold nanoparticles (AuNPs) have been developed as potential in vivo diagnostic and therapeutic agents. However, their role on nasopharyngeal cancer remains unknown. The object of this study is to investigate if AuNPs can be used as a new therapeutic agent for NPC by evaluating their anti-tumor effect in vitro. METHODS: The AuNPs were prepared by the reduction of chloroauric acid to neutral gold. Their size distribution and microstructures were characterized by transmission electron microscopy (TEM). To evaluate their cytotoxic effect, NPC cell line TW01 and Human Nasal Epithelial Cells (HNEpC) were cultured in various concentrations of AuNPs for 3 days. Cell viability was evaluated by Trypan Blue viability assay while morphologic findings were observed via light microscopy. Terminal deoxynucleotidyltransferase-mediated dUPT nick end labeling (TUNEL) assay was used to detect apoptosis. RESULTS: AuNPs prepared in this study had an average diameter of 20.5nm and they were observed under light microscopy as dark material aggregated in the cells after treatment. Contrary to the HNEpC, the AuNPs reduced cell viability of NPC cell in a concentration-dependant manner by Trypan Blue assay, especially at high concentration. Besides, cell apoptosis was demonstrated by positive TUNEL assay. CONCLUSIONS: The AuNP possesses specific imaging properties and is cytotoxic to NPC cells at high concentrations.

Evaluating the autonomic nervous system in patients with laryngopharyngeal reflux.

OBJECTIVES: The pathogenesis of laryngopharyngeal reflux (LPR) remains unclear. It is linked to but distinct from gastroesophageal reflux disease (GERD), which has been shown to be related to disturbed autonomic regulation. The aim of this study is to investigate whether autonomic dysfunction also plays a role in the pathogenesis of LPR. STUDY DESIGN: Case-control study. SETTING: Tertiary care center. SUBJECTS AND METHODS: Seventeen patients with LPR and 19 healthy controls, aged between 19 and 50 years, were enrolled in the study. The patients were diagnosed with LPR if they had a reflux symptom index (RSI) ≥ 13 and a reflux finding score (RFS) ≥ 7. Spectral analysis of heart rate variability (HRV) analysis was used to assess autonomic function. Anxiety and depression levels measured by the Beck Anxiety Inventory (BAI) and Beck Depression Inventory II (BDI-II) were also conducted. RESULTS: In HRV analysis, high frequency (HF) represents the parasympathetic activity of the autonomic nervous system, whereas low frequency (LF) represents the total autonomic activity. There were no significant differences in the LF power and HF power between the 2 groups. However, significantly lower HF% (P = .003) and a higher LF/HF ratio (P = .012) were found in patients with LPR, who demonstrated poor autonomic modulation and higher sympathetic activity. Anxiety was also frequently observed in the patient group. CONCLUSION: The study suggests that autonomic dysfunction seems to be involved in the pathogenesis of LPR. The potential beneficial effect of autonomic nervous system modulation as a therapeutic modality for LPR merits further investigation.

Role of TRPA1 and TRPV1 in the ROS-dependent sensory irritation of superior laryngeal capsaicin-sensitive afferents by cigarette smoke in anesthetized rats.

BACKGROUND: Laryngeal exposure to cigarette smoke (CS) evokes sensory irritation, but the mechanisms are largely unclear. The TRPA1 and TRPV1 receptors are two types of Ca(2+)-permeant channels located at the terminals of airway capsaicin-sensitive afferents. We investigated the mechanisms underlying the airway reflex evoked by laryngeal CS exposure in anesthetized rats. METHODS: CS (7 ml) was delivered into a functionally isolated larynx, while the animals (n = 201) breathed spontaneously. Respiratory parameters were measured. All use of pharmacological agents involved pretreatment by laryngeal application. RESULTS: Laryngeal CS exposure immediately evoked a concentration-dependant apneic response that was unrelated to the nicotine content of the CS. This inhibition of breathing was abolished by bilateral sectioning of the superior laryngeal nerves (SLNs) or by perineural capsaicin treatment of the SLNs (selective blocking of capsaicin-sensitive afferent neural conduction), suggesting the involvement of superior laryngeal capsaicin-sensitive afferents in the reflex. The reflex apnea was significantly attenuated by N-acetyl-l-cysteine (antioxidant), EGTA (extracellular Ca(2+) chelator) and BAPTA-AM (intracellular Ca(2+) chelator), indicating the importance of reactive oxygen species (ROS) and Ca(2+). This reflex apnea was also partially reduced by HC030031 (TRPA1 receptor antagonist) and capsazepine (TRPV1 receptor antagonist), and was nearly abolished by a combination of these two antagonists, suggesting a central role for the TRPA1 and TRPV1 receptors. Furthermore, the reflex apnea was attenuated by indomethacin (cyclooxygenase inhibitor); however, the attenuation by indomethacin was not increased by pretreatment with HC030031 or capsazepine, indicating that TRPA1 and TRPV1 receptor functionality is, at least in part, linked to cyclooxygenase metabolites. CONCLUSIONS: The reflex apnea evoked by laryngeal CS requires activation of both TRPA1 and TRPV1 receptors, which are likely to be located at the terminals of superior laryngeal capsaicin-sensitive afferents. Laryngeal sensory irritation by CS seems to depend on the actions of ROS and cyclooxygenase metabolites on these two types of receptors.