Serotonin receptor 5-HT2B mediates serotonin-induced mechanical hyperalgesia.

Serotonin [5-hydroxytryptamine (5-HT)] released from mast cells or platelets in peripheral tissues is one of the important inflammatory mediators in pain and hyperalgesia. The involvement of 5-HT in pain is complex because it could inhibit or facilitate nociceptive transmission, reflecting the presence of multiple 5-HT subtype receptors on peripheral and central nociceptors. The present study aimed to investigate the involvement of 5-HT(2B) in 5-HT-induced pain and whether the subtype exists in dorsal root ganglion (DRG) neurons. Injecting the 5-HT or 5-HT(2) agonist in hindpaws of mice induced significant hyperalgesia to mechanical stimuli, which was inhibited by the 5-HT(2B/2C) antagonist but not by 5-HT(1A), 5-HT(2A), or 5-HT(3A) antagonists. Therefore, 5-HT(2B) or 5-HT(2C) may be involved in 5-HT-induced mechanical hyperalgesia. The 5-HT(2B/2C) antagonist also blocked 5-HT-induced transient [Ca(2+)] signaling in DRG neurons. All subtypes of 5-HT receptors except 5-HT(2C) and 5-HT(6) are present in DRGs. In situ hybridization also demonstrated 5-HT(2B) mainly expressed in small- to medium-diameter DRG neurons that respond to pain. Likely, 5-HT(2B) mediates 5-HT-induced mechanical hyperalgesia in mice.

Regression of advanced maxillary sinus cancer with orbital invasion by combined chemotherapy and immunotherapy: A one-year follow-up case report.

A case of advanced maxillary cancer undergoing a combination of chemotherapy and immunotherapy is reported. The subject a 59-year-old man had a history of nasopharyngeal carcinoma treated with concurrent chemoradiotherapy in 2004. The patient was diagnosed with a right maxillary sinus carcinoma invading the right orbital fossa (cT4aN0M0, stage IVA) in 2019. Computed tomography revealed soft tissue swelling involving the right maxillary sinus, right nasal cavity, inferior extraconal space of the right eye, right cheek and right hard palate with extension into the right pterygopalatine fossa. The patient refused surgery and radiotherapy but accepted chemotherapy in combination with immunotherapy. A marked regression of advanced maxillary sinus cancer with orbital invasion using this regimen was noted in the one-year follow-up period. A literature review on treatment for advanced maxillary sinus cancer was also conducted and the results revealed that this combination regimen may play a role in the treatment of advanced maxillary sinus cancer but further investigation is required to determine the effect of combination of chemotherapy and immunotherapy on advanced maxillary sinus cancer.

The effect of lexical tone experience on English intonation perception in Mandarin-speaking cochlear-implanted children.

To examine the effect of lexical tone experience on English intonation perception in Mandarin-speaking cochlear-implanted children during second language acquisition in Taiwan. A retrospective cohort study. A tertiary referred center. Fourteen children with cochlear implant (CI) in the experimental group, and 9 normal hearing children in the control group were enrolled in this study. Cochlear implantation and hearing rehabilitation. Two speech recognition accuracies were examined: (1) Lexical tone recognition (4-alternative forced choice, AFC), (2) English Sentence Intonation (2AFC). The overall accuracies for tone perception are 61.13% (standard deviation, SD = 10.84%) for CI group and 93.82% (SD = 1.80%) for normal hearing group. Tone 4 and Tone 1 were more easily to be recognized than tone 2 and tone 3 in the pediatric CI recipients (cCI) group. In English intonation perception, the overall accuracies are 61.82% (SD = 16.85%) for CI group, and 97.59% (SD = 4.73%) for normal hearing group. Significant high correlation (R = .919, P ≦ .000) between lexical tone perception and English intonation perception is noted. There is no significant difference for English intonation perception accuracies between Mandarin-speaking cCI (61.82%) and English-speaking cCI (70.13%, P = .11). Mandarin-speaking cochlear-implanted children showed significant deficits in perception of lexical tone and English intonation relative to normal hearing children. There was no tonal language benefit in Mandarin-speaking cochlear-implanted children's English intonation perception, compared to the English-speaking cochlear-implanted peers. For cochlear-implanted children, better lexical tone perception comes with better English intonation perception. Enhancing Mandarin prosodic perception for cochlear-implanted children may benefit their command of intonation in English.

Expression and function of proton-sensing G-protein-coupled receptors in inflammatory pain.

BACKGROUND: Chronic inflammatory pain, when not effectively treated, is a costly health problem and has a harmful effect on all aspects of health-related quality of life. Despite the availability of pharmacologic treatments, chronic inflammatory pain remains inadequately treated. Understanding the nociceptive signaling pathways of such pain is therefore important in developing long-acting treatments with limited side effects. High local proton concentrations (tissue acidosis) causing direct excitation or modulation of nociceptive sensory neurons by proton-sensing receptors are responsible for pain in some inflammatory pain conditions. We previously found that all four proton-sensing G-protein-coupled receptors (GPCRs) are expressed in pain-relevant loci (dorsal root ganglia, DRG), which suggests their possible involvement in nociception, but their functions in pain remain unclear. RESULTS: In this study, we first demonstrated differential change in expression of proton-sensing GPCRs in peripheral inflammation induced by the inflammatory agents capsaicin, carrageenan, and complete Freund's adjuvant (CFA). In particular, the expression of TDAG8, one proton-sensing GPCR, was increased 24 hours after CFA injection because of increased number of DRG neurons expressing TDAG8. The number of DRG neurons expressing both TDAG8 and transient receptor potential vanilloid 1 (TRPV1) was increased as well. Further studies revealed that TDAG8 activation sensitized the TRPV1 response to capsaicin, suggesting that TDAG8 could be involved in CFA-induced chronic inflammatory pain through regulation of TRPV1 function. CONCLUSION: Each subtype of the OGR1 family was expressed differently, which may reflect differences between models in duration and magnitude of hyperalgesia. Given that TDAG8 and TRPV1 expression increased after CFA-induced inflammation and that TDAG8 activation can lead to TRPV1 sensitization, it suggests that high concentrations of protons after inflammation may not only directly activate proton-sensing ion channels (such as TRPV1) to cause pain but also act on proton-sensing GPCRs to regulate the development of hyperalgesia.

Radial forearm and forehead flap reconstruction following resection of a nasal arteriovenous malformation: A case report.

Arteriovenous malformation (AVM) is a structural vascular abnormality in which the arterial vasculature connects with the venous vasculature without capillary connections. AVM confined to the nasal cavity is considerably rare. Blurred vision can be one of the associated symptoms. A combined approach of complete surgical resection with prior superselective embolization is the treatment of choice. Following resection, the reconstruction of facial defects, particularly in the nasal area, is challenging. The present study reports the rare case of a patient with an AVM in the nasal cavity, in which embolization, resection and flap reconstruction were performed. Embolization and complete surgical resection were used to avoid recurrence. Subsequently, a combination of free radial forearm and forehead flaps was used for the reconstruction of the nasal defect, without prosthesis. To the best of our knowledge, this is the first report of AVM confined to the nasal cavity, managed by a combination of free radial forearm and forehead flap reconstruction following complete resection. The cosmetic results of the procedure were acceptable.

A long-term study on hearing status in patients with nasopharyngeal carcinoma after radiotherapy.

OBJECTIVE: To study the long-term sensorineural hearing status after radiotherapy in patients suffering from nasopharyngeal carcinoma. STUDY DESIGN: A prospective study of 220 patients (395 ears) with a median follow-up of 36 months. SETTING: A university hospital. PATIENTS: Four criteria were needed. The patient had to have had at least 12 months of audiologic follow-up, no concurrent chronic ear disease, no direct tumor invasion of ear, and no significant sensorineural hearing loss before radiotherapy. INTERVENTION: Pure-tone audiography and impedance audiometry-which were performed before and at the third month after completion of radiotherapy and at a yearly interval thereafter-formed the basis of the study. MAIN OUTCOME MEASURES: The significance level in this study was defined as a bone conduction threshold increase of more than 10 dB between the initial audiogram and those obtained after the completion of radiotherapy. An increase of more than 30 dB was defined as severe loss. RESULTS: Paired t test indicated that the mean bone conduction threshold before and after radiotherapy were significantly different (paired t test, p < 0.05). Logistic regression showed that patient age was related to the significant loss at speech frequency but not to the loss at 4 kHz. The presence of postradiation otitis media with effusion, preirradiation hearing status, and addition of chemotherapy were found to be not influential on hearing change. CONCLUSION: Hearing deterioration may begin as early as 3 months after the completion of radiotherapy. Early change may be transient, but the effect of radiation on hearing tended to be chronic and progressive.

Hearing loss in patients with nasopharyngeal carcinoma after chemotherapy and radiation.

In light of the possible adverse effects of radiation on hearing, we conducted a study to evaluate the long-term sensorineural hearing status following radiotherapy (RT) in patients suffering from nasopharyngeal carcinoma. Audiologic examinations were performed at regular intervals before and after RT. We also analyzed the effects of age, chemotherapy, pre-RT hearing status, and post-RT otitis media with effusion (OME) on post-RT hearing change. A total of 150 patients (261 ears) were enrolled in this study and followed up for a mean of 43.8 months. After RT, 8.9-28.8% of ears had at least a 10 dB loss in bone conduction threshold at speech frequency, which was defined as an average of hearing threshold at 0.5 kHz, 1 kHz, and 2 kHz, while the percentage was 18-34.2% at 4 kHz. Patient age was related to these changes at speech frequency, and the presence of post-RT OME was related to significant loss at both speech frequency and 4 kHz. Pre-RT hearing status and chemotherapy did not influence hearing change. To sum up, sensorineural hearing loss began as early as after completion of RT. Early changes may be transient, but the effect of radiation on hearing tended to be chronic and progressive.

Space infection of the head and neck.

Deep neck infection may be lethal, especially when life-threatening complications occur. We conducted a retrospective analysis of 184 patients with deep neck infection who were treated at Kaohsiung Medical University Hospital during the past 6 years. Factors such as age, sex, hospitalization days, clinical presentations, involved spaces, imaging studies, microbiology, and treatment method were analyzed. There were 122 men and 62 women with a mean age of 41.7 years. The average hospitalization was 8.4 days. The involved spaces, determined by physical examination and radiologic findings, were the peritonsillar space (59 patients), parapharyngeal space (77 patients), submandibular space (55 patients), and retropharyngeal space (20 patients). Of the 49 patients for whom the origin of infection was identified, 29 were infected via the upper respiratory tract and 13 had infection of odontogenic origin. The most common isolated organism was Klebsiella pneumoniae. One hundred and thirty-seven patients (74.5%) underwent surgery, including repeated needle aspiration (87 patients) and surgical drainage (50 patients). The remaining 47 patients recovered uneventfully with antibiotic therapy alone. Eighteen patients developed life-threatening complications, such as descending mediastinitis, sepsis, airway obstruction, and jugular vein thrombosis. Two patients died of septic shock. The combination of accurate diagnosis, effective antibiotic therapy, airway maintenance, and intensive surgical debridement for those who fail to respond to conservative treatment will lead to a good prognosis.

Cancer survival in patients with HIV/AIDS in the era of highly active antiretroviral therapy in Taiwan: a population-based cohort study.

OBJECTIVES: HIV-related immunosuppression has been associated with the development of AIDS-defining malignancies. We examined the overall survival of HIV-infected patients who developed cancer. DESIGN: A retrospective cohort study. METHODS: Using the Taiwan Longitudinal Health Insurance Database, we compared patients diagnosed with HIV (n=9918) between January 1, 2002, and December 31, 2007 with age-matched controls (n=99,180). Each patient was followed until the end of 2009 (least 2 years after the initial HIV diagnosis) to evaluate the incidence of malignancies. RESULTS: The risk of overall malignancies in the HIV-infected cohort was 1.88 times higher than the risk of a first malignancy in the age-matched non-HIV infected cohort (incidence rate ratio [IRR])=2.05, p<0.0001). The diagnosis of a malignancy was negatively correlated with survival in the HIV-infected cohort (p<0.0011), and HIV infection had a synergistic effect on the survival of patients with malignancies compared with the non-HIV infected cohort, all of who had been newly diagnosed with cancer (p<0.0001). However, the difference in the risk of developing nasopharyngeal carcinoma (NPC), a highly prevalent malignancy in Taiwan, between the two cohorts was not significant (IRR=0.22, 95% CI=0.03-1.65). CONCLUSIONS: The risk of cancer in HIV-infected patients in Taiwan has increased significantly in the era of highly active antiretroviral therapy. A history of HIV significantly affected the survival of the patients in our study cohort after they developed cancer. Evidence level: 2B.