Prevention of Incident Hypertension in Patients With Obstructive Sleep Apnea Treated With Uvulopalatopharyngoplasty or Continuous Positive Airway Pressure: A Cohort Study.

Purpose: To determine whether treatment with uvulopalatopharyngoplasty (UPPP) or continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) prevents hypertension, compared to those not receiving any treatment. Methods: A retrospective cohort study was conducted among 413 patients with OSA (age ≥ 35 years) at the Shuang Ho Hospital between 2009 and 2016. The patients were divided into three groups: UPPP, CPAP, and non-treatment groups. Data about the personal characteristics, history of comorbidities, and polysomnography (PSG) reports were collected at baseline. A Cox model with inverse probability of treatment weighting was used to adjust for confounders and baseline diversity. Results: After multivariate adjustment and weighting for incident hypertension, patients in both the CPAP and UPPP groups showed a significant preventive effect on hypertension than in the non-treatment group. Moreover, patients in the CPAP group had lower event rates than those in the UPPP group. Conclusion: UPPP can prevent the development of new-onset hypertension in patients with OSA. CPAP had a better preventive effect than UPPP. UPPP might be a good alternative for reducing the risk of the onset of hypertension when compliance to CPAP is poor.

Iatrogenic Vocal Fold Paralysis: A Population-Based Cohort Study in Taiwan.

OBJECTIVE: Iatrogenic vocal fold paralysis is an important issue in laryngology, yet there are few population-based studies regarding the epidemiology. This study used a nationwide population-based claims database (the National Health Insurance Research Database) to investigate the epidemiology of iatrogenic unilateral and bilateral vocal fold paralysis (UVFP/BVFP) among the general adult population in Taiwan. METHOD: This study analyzed patients (20-90 years old) who underwent thyroid, parathyroid, thoracic, cardiac, or anterior cervical spine operations with vocal fold paralysis among adults in Taiwan from January 1, 2007 to December 31, 2013. The codes for vocal fold paralysis were defined by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Claims data in the Taiwan National Health Insurance Research Database were used. RESULTS: The most commonly performed operations which were related to vocal fold paralysis in Taiwan were, in descending order of frequency, thyroid, cervical spine, cardiac, thoracic (esophagectomy), and parathyroid operations. The operations that put laryngeal nerves at risk (ONRs) most commonly associated with a diagnosis of UVFP were, in descending order of frequency, thoracic, thyroid, parathyroid, cardiac, and cervical spine. For both UVFP and BVFP, the most commonly associated age group was 51 to 60. For both UVFP and BVFP, the more commonly associated sex was women. Increased length of stay was associated with a higher incidence of UVFP and BVFP. Charlson medical co-morbidity index (CCI) was not associated with UVFP but BVFP was associated with higher Charlson medical co-morbidity scores. CONCLUSIONS: Thyroid operations, age 51 to 60, longer hospital stays are associated with vocal fold paralysis. Overall women are more surgically affected than men. This is the first population-based study of iatrogenic vocal fold paralysis.

Causes of Vocal Fold Paralysis.

BACKGROUND: Vocal fold paralysis (VFP) can result from a variety of diseases or surgeries and has various causes. This study determined concurrent etiologies in patients who were treated in a teaching hospital (tertiary medical center). METHODS: A retrospective review of medical records of patients with VFP from September 2010 to December 2019 was performed to determine the etiology. Patients with laryngeal/hypopharyngeal malignancies, those with incomplete examination and follow-up data were excluded from the study. During the follow-ups, cases involving recovery were also excluded. RESULTS: One hundred and ninety-four patients with a determined etiology were included: 113 males and 81 females. Unilateral VFP was present in 178 patients, and 16 presented with bilateral VFP. The causes of unilateral VFP were surgical for 61.3%, neoplastic for 17.5%, idiopathic for 10.3%, traumatic for 1.5%, central for 4.7%, cardiovascular for 2%, radiation-induced for 1.5%, and inflammatory for 1%. Thyroidectomy was the most common surgery for unilateral VFP and was the cause for 54 patients. Lung cancer was responsible for 15 cases and was the most common neoplastic etiology of unilateral VFP. For those who presented with bilateral VFP, surgery was the most common cause and accounted for 56.3% of the incidences. In terms of gender, surgery was the most common cause for both sexes, accounting for 62 of 113 male patients and 57 of 81 female patients. Four cases recovered during the follow-ups and these were excluded. CONCLUSION: Surgery and in particular, thyroidectomy, was the most common cause of VFP for these series. Central nervous system disorders were the cause of VFP (4.5%). Central nervous system disorders, especially cerebrovascular accidents that induced VFP, could not be neglected. Radiation-induced cranial nerve paralysis in the head and neck cancer was possible causes. The percentage for the causes of unilateral VFP, surgery increased and the percentage for neoplasm decreased for Taiwan.

REM-related obstructive sleep apnea and vertigo: A retrospective case-control study.

BACKGROUND: In recent population-based case-control studies, sleep apnea was significantly associated with a higher incidence (hazard ratio, 1.71) of vertigo and the risk of tinnitus was found to increase 1.36 times in patients with sleep apnea. The possibility that obstructive sleep apnea (OSA) might affect neurotological consequences was not noticed, until studies using polysomnography (PSG) for these patients. OBJECTIVES: The purpose of this study was to investigate the relationship between vertigo and OSA. METHODS: The collected data among patients from May 1st, 2018 to October 31th, 2018 at Shuang Ho Hospital. Eligibility criteria included an age older than 20 years, a diagnosis of obstructive sleep apnea. The diagnosis of OSA was defined as an oxygen desaturation index of at least 5, was established with the use of polysomnographic examination at hospital. Patients were excluded from the study if they had head injury, brain tumour, headache history and hearing loss. Patients who had vertigo were labeled as Vertigo group. In the other hand, patients who had no dizziness were labeled as control group. 58 patients were in the Vertigo group, and 113 were in the control group. RESULTS: After PSG examination, 58 patients who had vertigo, were diagnosed OSA (29 males, average age = 57.07 years old, BMI = 26.64, RDI = 24.69, ESS = 8.65), and 24 patients of them (41.3%) were REM-related OSA. Meanwhile, in the control group, 113 patients had OSA (92male, average age = 49.66 years old, BMI = 26.06, RDI = 35.19, ESS = 11.43), and 18 patients of them (15.9%) were REM-related OSA (Table 1). Therefore, patient who had vertigo, would have higher proportion of REM OSA (P<0.001). CONCLUSIONS: The vertigo patients have a higher rate of REM-related OSA, and the acceptance rate to CPAP use is low. Further research is needed to explore novel therapeutic approaches, or combination of currently available non-CPAP therapies, in patients with REM OSA.

Menthol inhibiting parasympathetic function of tracheal smooth muscle.

Menthol is used as a constituent of food and drink, tobacco and cosmetics nowadays. This cold receptor agonist has been used as a nasal inhalation solution in the daily life. The effect of menthol on nasal mucosa in vivo is well known; however, the effect of the drug on tracheal smooth muscle has been rarely explored. Therefore, during administration of the drug for nasal symptoms, it might also affect the trachea via oral intake or inhalation. We used our preparation to test the effectiveness of menthol on isolated rat tracheal smooth muscle. A 5 mm long portion of rat trachea was submersed in 30 ml Krebs solution in a muscle bath at 37ºC. Changes in tracheal contractility in response to the application of a parasympathetic mimetic agent were measured using a transducer connected to a Pentium III computer equipped with polygraph software. The following assessments of menthol were performed: (1) effect on tracheal smooth muscle resting tension; (2) effect on contraction caused by 10-6 M methacholine as a parasympathetic mimetic; (3) effect of the drug on electrically induced tracheal smooth muscle contractions. Results indicated that addition of a parasympathetic mimetic to the incubation medium caused the trachea to contract in a dose-dependent manner. Addition of menthol at doses of 10-5 M or above elicited a relaxation response to 10-6 M methacholine-induced contraction. Menthol could also inhibit electrical field stimulation (EFS) induced spike contraction. However, it alone had a minimal effect on the basal tension of trachea as the concentration increased. We concluded that the degree of drug-induced tracheal contraction or relaxation was dose-dependent. In addition, this study indicated that high concentrations of menthol might actually inhibit parasympathetic function of the trachea.

Targeting annexin A2 reduces tumorigenesis and therapeutic resistance of nasopharyngeal carcinoma.

The expression of annexin A2 (ANXA2) in nasopharyngeal carcinoma (NPC) cells induces the immunosuppressive response in dendritic cells; however, the oncogenic effect and clinical significance of ANXA2 have not been fully investigated in NPC cells. Immunohistochemical staining for ANXA2 was performed in 61 patients and the association with clinicopathological status was determined. Short hairpin (sh)RNA knockdown of ANXA2 was used to examine cellular effects of ANXA2, by investigating alterations in cell proliferation, migration, invasion, adhesion, tube-formation assay, and chemo- and radiosensitivity assays were performed. RT-qPCR, Western blotting, and immunofluorescence were applied to determine molecular expression levels. Clinical association studies showed that the expression of ANXA2 was significantly correlated with metastasis (p = 0.0326) and poor survival (p = 0.0256). Silencing of ANXA2 suppressed the abilities of cell proliferation, adhesion, migration, invasion, and vascular formation in NPC cell. ANXA2 up-regulated epithelial-mesenchymal transition associated signal proteins. Moreover, ANXA2 reduced sensitivities to irradiation and chemotherapeutic drugs. These results define ANXA2 as a novel prognostic factor for malignant processes, and it can serve as a molecular target of therapeutic interventions for NPC.

Benzydamine oral spray inhibiting parasympathetic function of tracheal smooth muscle.

OBJECTIVES: Benzydamine is a nonsteroidal anti-inflammatory agents agent with anti-inflammatory and local anesthesia properties that is available in the entire world as an oral spray for oral mucositis patients who are suffering from radiation effects. The effect of benzydamine on oral mucositis in vivo is well known; however, the effect of the drug on tracheal smooth muscle has rarely been explored. During administration of the benzydamine for oral symptoms, it might affect the trachea via oral intake or inhalation. METHODS: We examined the effectiveness of benzydamine on isolated rat tracheal smooth muscle. The following assessments of benzydamine were performed: effect on tracheal smooth muscle resting tension; effect on contraction caused by 10(-6)M methacholine as a parasympathetic mimetic; and effect of the drug on electrically induced tracheal smooth muscle contractions. RESULTS: Addition of methacholine to the incubation medium caused the trachea to contract in a dose-dependent manner. Addition of benzydamine at doses of 10(-5)M or above elicited a significant relaxation response to 10(-6)M methacholine-induced contraction. Benzydamine could inhibit electrical field stimulation-induced spike contraction. It alone had a minimal effect on the basal tension of trachea as the concentration increased. CONCLUSION: This study indicated that high concentrations of benzydamine might actually inhibit parasympathetic function of the trachea. Benzydamine might reduce asthma attacks in oral mucositis patients because it could inhibit parasympathetic function and reduce methacholine-induced contraction of tracheal smooth muscle.

Dendritic cells respond to nasopharygeal carcinoma cells through annexin A2-recognizing DC-SIGN.

Dendritic cells (DCs) play an essential role in immunity and are used in cancer immunotherapy. However, these cells can be tuned by tumors with immunosuppressive responses. DC-specific intercellular adhesion molecule 3-Grabbing Nonintegrin (DC-SIGN), a C-type lectin expressed on DCs, recognizes certain carbohydrate structures which can be found on cancer cells. Nasopharyngeal carcinoma (NPC) is an epithelial cell-derived malignant tumor, in which immune response remains unclear. This research is to reveal the molecular link on NPC cells that induces the immunosuppressive responses in DCs. In this article, we report identification of annexin A2 (ANXA2) on NPC cells as a ligand for DC-SIGN on DCs. N-linked mannose-rich glycan on ANXA2 may mediate the interaction. ANXA2 was abundantly expressed in NPC, and knockdown of ANXA2 suppressed NPC xenograft in mice, suggesting a crucial role of ANXA2 in NPC growth. Interaction with NPC cells caused DC-SIGN activation in DCs. Consequently DC maturation and the proinflammatory interleukin (IL)-12 production were inhibited, and the immunosuppressive IL-10 production was promoted. Blockage of either DC-SIGN or ANXA2 eliminated the production of IL-10 from DCs. This report suggests that suppression of ANXA2 at its expression or glycosylation on NPC may improve DC-mediated immunotherapy for the tumor.

The effect of temperature on basal tension and thyroarytenoid muscle contraction in an isolated rat glottis model.

The pitch of voice is closely related to the vocal fold tension, which is the end result of coordinated movement of the intralaryngeal muscles, and especially the thyroarytenoid muscle. It is known that vocal quality may be affected by surrounding temperature; however, the effect of temperature on vocal fold tension is mostly unknown. Thus, the aim of this study was to evaluate the effect of temperature on isolated rat glottis and thyroarytenoid muscle contraction induced by electrical field stimulation. In vitro isometric tension of the glottis ring from 30 Sprague-Dawley rats was continuously recorded by the tissue bath method. Electrical field stimulation was applied to the glottis ring with two wire electrodes placed parallel to the glottis and connected to a direct-current stimulator. The tension changes of the rat glottis rings that were either untreated or treated with electrical field stimulation were recorded continuously at temperatures from 37 to 7 °C or from 7 to 37 °C. Warming from 7 to 37 °C increased the basal tension of the glottis rings and decreased the electrical field stimulation-induced glottis ring contraction, which was chiefly due to thyroarytenoid muscle contraction. In comparison, cooling from 37 to 7 °C decreased the basal tension and enhanced glottis ring contraction by electrical field stimulation. We concluded that warming increased the basal tension of the glottis in vitro and decreased the amplitude of electrical field stimulation-induced thyroarytenoid muscle contraction. Thus, vocal pitch and the fine tuning of vocal fold tension might be affected by temperature in vivo.

Apoptotic toxicity of destruxin B in human non-Hodgkin lymphoma cells.

Destruxins are fungal toxins used as insecticides. Recent reports demonstrated the potential anti-cancer activities of destruxin B (DB). This study is to discover the effects of DB in lymphoma. Flow cytometry and Western blotting were used to analyze apoptosis and protein expression, respectively, in Toledo human non-Hodgkin lymphoma cells in response to DB. Administration of DB, induced apoptosis via death receptor pathway activating Fas associated death domain (FADD), caspase 8 and caspase 3, and suppressed the cell growth. In addition, DB alterated mitochondrial membrane potential by increasing the expressions of tBid and Bax, but decreasing the levels of Bcl-2, resulting in the release of apoptosis-inducing factor (AIF). In conclusion, apoptosis of human non-Hodgkin lymphoma cells in response to DB is induced through the death receptor pathway and involves an alteration of the mitochondrial membrane potential. These findings may aid the development of novel treatment of non-Hodgkin lymphoma.

Plasma RANTES and eotaxin levels are correlated with the severity of chronic rhinosinusitis.

Eosinophilia occurs in up to 75-90% of nasal polyps in Caucasians. The chemokines eotaxin and RANTES increase eosinophil recruitment, activation, and survival, and these chemokines are significantly expressed in nasal polyps. We hypothesized that eotaxin and RANTES plasma levels might be correlated with disease severity. We compared the eotaxin and RANTES plasma levels in 20 Taiwanese patients with chronic rhinosinusitis and nasal polyps and 20 Taiwanese healthy controls. Eotaxin and RANTES plasma levels were measured by ELISA and disease severity was scored by CT scans. Compared to controls, patients with nasal polyps had significantly elevated plasma levels of eotaxin and RANTES and increased peripheral blood eosinophils (p < 0.001). Eotaxin plasma levels were significantly correlated with disease severity in patients with chronic rhinosinusitis to a greater extent than were RANTES levels. RANTES and eotaxin levels were also positively correlated with the percentages of peripheral blood eosinophils. Eotaxin plasma levels are significantly correlated with disease severity in Taiwanese patients with nasal polyposis to a greater degree than are RANTES levels. Additional studies are needed to assess whether eotaxin plasma levels can be used to monitor disease progression and attenuation.

Regulation of MMP-3 expression and secretion by the chemokine eotaxin-1 in human chondrocytes.

BACKGROUND: Osteoarthritis (OA) is characterized by the degradation of articular cartilage, marked by the breakdown of matrix proteins. Studies demonstrated the involvement of chemokines in this process, and some may potentially serve as diagnostic markers and therapeutic targets; however, the underlying signal transductions are not well understood. METHODS: We investigated the effects of the CC chemokine eotaxin-1 (CCL11) on the matrix metalloproteinase (MMP) expression and secretion in the human chondrocyte cell line SW1353 and primary chondrocytes. RESULTS: Eotaxin-1 significantly induced MMP-3 mRNA expression in a dose-dependent manner. Inhibitors of extracellular signal-regulated kinase (ERK) and p38 kinase were able to repress eotaxin-1-induced MMP-3 expression. On the contrary, Rp-adenosine-3',5'-cyclic monophosphorothioate (Rp-cAMPs), a competitive cAMP antagonist for cAMP receptors, and H-89, a protein kinase A (PKA) inhibitor, markedly enhanced eotaxin-1-induced MMP-3 expression. These results suggest that MMP-3 expression is specifically mediated by the G protein-coupled eotaxin-1 receptor activities. Interestingly, little amount of MMP-3 protein was detected in the cell lysates of eotaxin-1-treated SW1353 cells, and most of MMP-3 protein was in the culture media. Furthermore we found that the eotaxin-1-dependent MMP-3 protein secretion was regulated by phospholipase C (PLC)-protein kinase C (PKC) cascade and c-Jun N-terminal kinase (JNK)/mitogen-activated protein (MAP) kinase pathways. These data indicate a specific regulation of MMP-3 secretion also by eotaxin-1 receptor activities. CONCLUSIONS: Eotaxin-1 not only induces MMP-3 gene expression but also promotes MMP-3 protein secretion through G protein-coupled eotaxin-1 receptor activities. Chemokines, such as eotaxin-1, could be a potential candidate in the diagnosis and treatment of arthritis.

Intraparotid Kikuchi-Fujimoto disease masquerading as a parotid gland tumor.

The Kikuchi-Fujimoto disease, also known as histiocytic necrotizing lymphadenitis, is a self-limiting lesion of unknown cause first described in 1972 independently by Kikuchi and Fujimoto et al. This self-limiting disorder usually occurs in Asian women in their late 20s or early 30s. Typically, it runs a benign course and appears to resolve spontaneously 1 to 6 months after definite diagnosis. The Kikuchi-Fujimoto disease usually manifests as a localized cervical lymphadenopathy; therefore, most patients with this disease are seen in ears, nose, and throat practice. Nodal involvement other than in the neck area or extranodal involvement is rare. In this situation, however, the Kikuchi-Fujimoto disease is easily confused with other less-benign conditions. We describe a case of Kikuchi-Fujimoto disease in a 30-year-old man that presented as a parotid gland tumor. This is the third study to document intraparotid Kikuchi-Fujimoto disease in the English literature. Our report illustrates the clinical features of this unusual condition and emphasizes potential confusion with other diagnoses.

Pediatric Kikuchi-Fujimoto disease masquerading as a submandibular gland tumor.

Kikuchi-Fujimoto disease, also known as histiocytic necrotizing lymphadenitis, is a rare disorder that typically affects the cervical lymph nodes. The disease usually occurs in women in their late 20s or early 30s. Reports in the pediatric literature are sparse. Most authors consider Kikuchi-Fujimoto disease as a self-limiting disorder that requires no specific management but long-term follow-up. The clinical features of Kikuchi-Fujimoto disease are easily confused with other less-benign conditions. Thus, an early biopsy is instrumental in making definite diagnosis and preventing unnecessary investigations. We describe a case of Kikuchi-Fujimoto disease in an 8-year-old boy which presenting as a submandibular gland tumor. The case illustrates the clinical features of this unusual condition and emphasizes the potential confusion with other diagnoses.