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Background: In this study, the μ-Opioid receptor activity was assessed pre-operatively for its association with postoperative pain level and second analgesic requirement in patients undergoing septoplasty., Methods: In our prospective study, 120 adult patients underwent septoplasty from June 2015 to January 2019 were randomly divided into 2 pre-operative groups. The first group (n = 60) was patients given tramadol (1-2 mg/kg) for post-operative analgesia, and the second group (control group) (n = 60) was initially prescribed only fentanyl (1 μg/ kg-i.v.) in the induction. Acetaminophen with codeine analgesic 325/30 mg (p.o.) was used as an rescue painkiller in the post-operative period. The μ-Opioid receptor activity was investigated in pre-operative blood samples and compared to post-operative pain level and time required for second round of analgesic administration. The visual analogue score (VAS) was used to evaluate the post-operative pain degree (0 no pain; 10 worst pain). The patients' post-operative VAS scores were evaluated upon arrival to recovery room, and at the 1st, 3rd, 7th, 10th, and 24th hour post-operative period., Results: Demographic data and peri-operative variables were similar in both study group (p < 0.05).There was no significant difference between the receptor levels in both groups and the mean receptor level was 200.94 ± 15.34 pg/mL (max:489.92 ± 22.36 pg/mL, min: 94.56 ± 11.23 pg/mL).In patients who used tramadol as the levels of μ-Opioid receptors increased, VAS scores of patients and second analgesic use decreased in post-operative period.The VAS scores in patients with higher receptor levels were lower in the recovery room (p < 0.05), 1st (p < 0.05) and 3rd hours (p < 0.05).The VAS scores were lower in the tramadol group compared to the control group (p < 0.05).Number of secondary analgesic requirement was significantly lower in patients of the tramadol group with higher receptor levels compared to the ones with lower receptor (p < 0.05) for arrival at the recovery room and 1st hour. Patients in the tramadol group needed a second pain killer much later than patients in the control group., Conclusions: Our study demonstrates that patients with higher μOR levels have a higher efficacy of opioid analgesic agents and an lesser need for additional analgesic agents., Trial Registration: This trial was registered retrospectively (The ACTRN: ACTRN12619001652167 , registration date: 26/11/2019).

Objectives/hypothesis: We investigated the effect of intranasal topical curcumin on nasal septum mucosa wound healing in a nasal septal perforation model produced in rabbits., Study Design: Experimental study., Methods: Fourteen male New Zealand rabbits were included in the study. For each rabbit, 5-mm-diameter circular perforations were created at 5 mm away from the columella to the nasal septum. Curcumin (study group) and saline (control group) were administered intranasally once daily for 10 days. At the end of the 10th day, the animals were sacrificed and the nasal septum specimens were sent for histological examination. Epithelial regeneration and degeneration, cartilage degeneration and regeneration, presences of fibroblast, eosinophil, acute/chronic inflammatory and giant cells, capillary density, amounts of granulation tissue and collagen, and macroscopic closure rate of perforation parameters were compared in each group., Results: Epithelial and cartilage regeneration, and the amounts of collagen and granulation tissue were significantly higher in the curcumin group compared to the control group (P < .05). No statistically significant difference was found in comparison of other parameters (P > .05)., Conclusions: Topical application of curcumin improves the wound-healing process of nasal septum perforation in the animal model. Therefore, curcumin can be used as a safe and effective medical agent to prevent the development of septal perforation., Level of Evidence: NA Laryngoscope, 129:E349-E354, 2019., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Vasculitic midline destructive lesions can be a complication of cocaine use. We report a 44-year-old man who presented with a two months history of left facial pain associated with ipsilateral facial paralysis and a cheek phlegmon. Magnetic resonance imaging showed broad soft tissue destruction linked to important cranial nerve involvement. Antibiotic and antifungal therapy was started and multiple surgical debridement procedures were performed, with no clinical improvement. Microbiological analysis was negative. Finally, thanks to the histologic findings corresponding to vasculitis and granuloma formation and the history of cocaine abuse, a cocaine induced midline destructive lesion was diagnosed.

Orbital inflammatory disease and secondary optic neuropathy is a rare but devastating complication of long-term intranasal cocaine abuse. We describe 2 patients with a history of intranasal cocaine consumption who presented with subacute onset of unilateral vision loss from optic neuropathy and limitation of abduction in the affected eye. Magnetic resonance imaging findings included an orbital mass in combination with absent nasal septum and partial destruction of the paranasal sinuses. Biopsies and histopathologic examination of the nasal cavity and the orbital mass revealed chronic inflammation. Both patients were treated with oral corticosteroids, ocular movements completely normalized but no improvement of visual acuity was noted. Intranasal cocaine abuse can cause orbital complications from chronic sinonasal inflammatory disease and these patients are at risk to develop optic neuropathy. Optic neuropathy may be caused by compression, infiltration, or ischaemia.

Objectives: The clinical application of allogenic and/or xenogenic cartilage for vocal fold augmentation requires to remove the antigenic cellular component. The objective of this study was to assess the effect of cartilage decellularization and determine the change in immunogenicity after detergent treatment in human nasal septal cartilage flakes made by the freezing and grinding method., Methods: Human nasal septal cartilages were obtained from surgical cases. The harvested cartilages were treated by the freezing and grinding technique. The obtained cartilage flakes were treated with 1% Triton X-100 or 2% sodium dodecyl sulfate (SDS) for decellularization of the cartilage flakes. Hematoxylin and eosin stain (H&E stain), surface electric microscopy, immunohistochemical stain for major histocompatibility complex I and II, and ELISA for DNA contents were performed to assess the effect of cartilage decellularization after detergent treatment., Results: A total of 10 nasal septal cartilages were obtained from surgical cases. After detergent treatment, the average size of the cartilage flakes was significantly decreased. With H&E staining, the cell nuclei of decellularized cartilage flakes were not observed. The expression of major histocompatibility complex (MHC)-I and II antigens was not identified in the decellularized cartilage flakes after treatment with detergent. DNA content was removed almost entirely from the decellularized cartilage flakes., Conclusion: Treatment with 2% SDS or 1% Triton X-100 for 1 hour appears to be a promising method for decellularization of human nasal septal cartilage for vocal fold augmentation., (Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

The nasal route receives a great deal of attention as a non-invasive method for the systemic administration of drugs. For nasal delivery, specific formulations containing excipients are used. Because of the sensitive respiratory mucosa, not only the active ingredients, but also additives need to be tested in appropriate models for toxicity. The aim of the study was to measure the cytotoxicity of six pharmaceutical excipients, which could help to reach larger residence time, better permeability, and increased solubility dissolution rate. The following excipients were investigated on RPMI 2650 human nasal septum tumor epithelial cells: β-d-mannitol, sodium hyaluronate, α and β-cyclodextrin, polyvinyl alcohol and methylcellulose. 3-(4,5-dimethyltiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye conversion assay and real-time impedance analysis were used to investigate cytotoxicity. No excipient showed toxicity at 0.3% (w/v) concentration or below while 1% concentration a significantly reduced metabolic activity was measured by MTT assay for methylcellulose and cyclodextrins. Using impedance measurements, only β-cyclodextrin (1%) was toxic to cells. Mannitol at 1% concentration had a barrier opening effect on epithelial cells, but caused no cellular damage. Based on the results, all additives at 0.3%, sodium hyaluronate and polyvinyl alcohol at 1% concentrations can be safely used for nasal formulations.

The aim of this experimental study was to investigate the cytotoxic effects of intranasal midazolam on nasal mucosal tissue in rats. Forty healthy rats were randomly divided into 5 groups. Group 1 (n = 8) was the control group, group 2 (n = 8) received intranasal saline, group 3 (n = 8) received intranasal midazolam, group 4 (n = 8) received intraperitoneal saline, and group 5 received intraperitoneal midazolam (n = 8). Midazolam and saline were administered via intraperitoneal and intranasal routes at doses of 200 μg/kg. Nasal septal mucosal stripe tissues were removed at the 6th hour. All materials were evaluated according to Ki67 and p53 staining to evaluate proliferation and apoptosis, respectively, and hemotoxylin and eosin staining was performed for histopathology evaluation. Ki67 values and inflammation in group 3 were statistically higher compared to group 1, group 2, and group 4. P53 values in group 3 were statistically higher compared to group 1. Assessment of subepithelial edema between group 3 and the other groups revealed no statistically significant differences. Assessment of cilia loss between group 3 and group 1, group 2, and group 4 revealed no statistically significant difference. The evaluation of goblet cell loss between group 3 and group 1 revealed a statistically significant difference. Intranasal midazolam had adverse effects on nasal mucosa. However, intranasal midazolam is as safe as systemic midazolam administration with respect to nasal mucosa.

With the increasingly widespread illicit use of cocaine, a broad spectrum of clinical pathologies related to this form of drug abuse is emerging. The most frequently used method of administration of powdered cocaine is intranasal inhalation, or "snorting." Consequently, adverse effects of cocaine on the nasal tract are common. Habitual nasal insufflations of cocaine can cause mucosal lesions. If cocaine use becomes chronic and compulsive, progressive damage of the mucosa and perichondrium leads to ischemic necrosis of the septal cartilage and perforation of the nasal septum. Occasionally, cocaine-induced lesions cause extensive destruction of the osteocartilaginous structures of the nose, sinuses, and palate and can mimic other diseases such as tumors, infections, and immunological diseases. In the literature currently available, involvement of the craniovertebral junction in the cocaine-induced midline destructive lesions (CIMDLs) has never been reported. The present case concerns a 44-year-old man who presented with long-standing symptoms including nasal obstruction, epistaxis, dysphagia, nasal reflux, and severe neck pain. A diagnosis of CIMDL was made in light of the patient's history and the findings on physical and endoscopic examinations, imaging studies, and laboratory testing. Involvement of the craniovertebral junction in the destructive process was evident. For neurosurgical treatment, the authors considered the high grade of atlantoaxial instability, the poorly understood cocaine-induced lesions of the spine and their potential evolution overtime, as well as cocaine abusers' poor compliance. The patient underwent posterior craniovertebral fixation. Understanding, classifying, and treating cocaine-induced lesions involving the craniovertebral junction are a challenge.

Objectives: Salubrious effects of the green coffee bean are purportedly secondary to high concentrations of chlorogenic acid. Chlorogenic acid has a molecular structure similar to bioflavonoids that activate transepithelial Cl(-) transport in sinonasal epithelia. In contrast to flavonoids, the drug is freely soluble in water. The objective of this study is to evaluate the Cl(-) secretory capability of chlorogenic acid and its potential as a therapeutic activator of mucus clearance in sinus disease., Study Design: Basic research., Setting: Laboratory., Subjects and Methods: Chlorogenic acid was tested on primary murine nasal septal epithelial (MNSE) (CFTR(+/+) and transgenic CFTR(-/-)) and human sinonasal epithelial (HSNE) (CFTR(+/+) and F508del/F508del) cultures under pharmacologic conditions in Ussing chambers to evaluate effects on transepithelial Cl(-) transport. Cellular cyclic adenosine monophosphate (cAMP), phosphorylation of the CFTR regulatory domain (R-D), and CFTR mRNA transcription were also measured., Results: Chlorogenic acid stimulated transepithelial Cl(-) secretion (change in short-circuit current [ΔISC = µA/cm(2)]) in MNSE (13.1 ± 0.9 vs 0.1 ± 0.1; P < .05) and HSNE (34.3 ± 0.9 vs 0.0 ± 0.1; P < .05). The drug had a long duration until peak effect at 15 to 30 minutes after application. Significant inhibition with INH-172 as well as absent stimulation in cultures lacking functional CFTR suggest effects are dependent on CFTR-mediated pathways. However, the absence of elevated cellular cAMP and phosphorylation the CFTR R-D indicates chlorogenic acid does not work through a PKA-dependent mechanism., Conclusion: Chlorogenic acid is a water-soluble agent that promotes CFTR-mediated Cl(-) transport in mouse and human sinonasal epithelium. Translating activators of mucociliary transport to clinical use provides a new therapeutic approach to sinus disease. Further in vivo evaluation is planned., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.)

Purpose: To present a case of topical prostaglandin analogue-induced skin pigmentation in a location previously never reported, with a differential diagnostic significance., Case Report: An 83-year-old man successfully treated for primary open-angle glaucoma of both eyes with the bimatoprost/timolol fixed combination for 6 years reported increased pigmentation of the skin of the nasal septum and alae. According to his report, the darkened skin area was not present when he was a young or middle-aged man. The patient had noted periocular pigmentation and deepening of the upper lid sulcus on both sides, which developed during the years of his bimatoprost/timolol treatment. Dermatology consultation excluded any nevus, malignancy, or other pathology as a cause of the pigmentation. The otorhinolaryngology consultation failed to identify any pathologic condition in the nasal cavity, but described mild chronic senile rhinitis., Conclusions: The acquired pigmentation of the skin of the nasal septum and alae in our patient represents a new form of cutaneous pigmentation induced by topical prostaglandin analogue therapy, which may have differential diagnostic significance in clinical practice. We speculate that the senile rhinitis of the patient increased the exposure of the nasal skin to the prostaglandin analogue solution drained via the nasolacrimal duct, and could therefore play a role in the development of skin pigmentation in this location.

Background: The objective of this work was to determine the role of nasal sound analysis using a software called Odiosoft-Rhino (OR) in evaluation of nasal erectile elements as a cause of nasal obstruction. Comparisons of nasal resistance, amplitude of the nasal sound frequency spectra, and visual analogue score (VAS) were made., Methods: Nasal endoscopy, VAS, rhinomanometry (RMM), and OR were performed on 64 patients with inferior turbinate hypertrophy but without any other nasal problems, both untreated and 15 minutes after the application of topical decongestants (TDs). Results were compared and any correlation was investigated., Results: For inspiration, the OR intervals for both sides at all 5 frequency intervals changes significantly with decongestion, except for the left side at 0.5 to 1 kHz. For expiration, the OR intervals for both sides changed significantly for 0.2 to 0.5 KHz and 2 to 4 kHz, but not for the other 3 frequency intervals. VAS correlated well with physical examination, both inspiratory and expiratory RMM, and 2 to 4 kHz inspiratory and expiratory nasal sound on both sides both before and after TD application. The 2 to 4 kHz inspiratory and expiratory nasal sound on both sides correlated well with inspiratory and expiratory RMM on both sides both before and after TD application., Conclusion: OR is an efficient and reliable method to evaluate the role of the erectile components in nasal patency in the absence of allergy or septal deviation. It is practical and may be used in routine clinical practice., (© 2014 ARS-AAOA, LLC.)

Background: Applying 2-octylcyanoacrylate (2-OCA) tissue adhesive onto scoring incisions may increase efficacy and prevent concavity recurrence after septal deviation treatment. The present study evaluates the utility of 2-OCA adhesive application during endonasal septoplasty., Methods: The postoperative outcomes were compared between two consecutive periods in a single surgical department. Between March 2011 and March 2012, 23 consecutive patients underwent septoplasty using scoring incisions without 2-OCA application (scoring alone group), and between April 2012 and April 2013, the scoring incision gaps were filled with 2-OCA in 27 patients (scoring + CA group). The patients were followed up for more than six months., Results: A straight septum was achieved in 37.0% of patients in the scoring alone group versus 58.3% in the scoring + CA group. The postoperative symptom score for nasal obstruction was significantly improved in both groups. Persistent septal swelling developed in three (12.5%) patients in the scoring + CA group. Neither group experienced major complications such as septal hematoma, abscess, or septal perforation., Conclusions: Application of 2-OCA adhesive onto scoring incisions appears to be a reliable and effective technique to correct deviated cartilage during endonasal septoplasty. However, the volume of 2-OCA applied onto the septum should be minimized to avoid potential foreign body reaction. A long-term follow-up study is warranted.

The objective of the present work was to enhance the effectiveness of the conservative treatment of perforations in the nasal septum (PNS) with the use of the newly developed method that includes septal splinting with the possibility of the long-term targeted medicamental treatment of the affected nasal septum tissue taking into consideration its morphological characteristics. The study included a total of 67 patients presenting with perforations in the nasal septum. The authors distinguished the following four types of septal perforations: non-inflamed (n=4; 6%), subatrophic (n=9; 13.4%), erosive-ulcerative (n=12; 17.9%), and mixed (n=42; 62.7%) ones. Twenty six patients were given conservative treatment by means of the original method including preventive splintage of the nasal septum with the use of silicone splints one of which had a slot-type conduit designed for manipulations. The inclusion of physiotherapeutic procedures in the protocol of the treatment of the perforated nasal septum was substantiated. It is concluded that the proposed original method for the conservative treatment of perforations in the nasal septum has advantages over the traditional approaches for the same purpose; it ensures complete (100%) regeneration of the affected mucous membrane of the nasal septum and a four-fold increase in the duration of remission of the disease.

The objective of the present work was to investigate the influence of the tubercle of the nasal septum thickening on the localization of the regions of precipitation of aerosol particles in the nasal cavity under the experimental conditions. The experiment was conducted using the newly developed 3D stereolithographic model of the nasal cavity. The study has demonstrated that the tubercle of the nasal septum thickening is an aerodynamically-conditioned normal anatomical structure, and its absence deteriorates the aerodynamic characteristics of the airflow through the nasal cavity.

Objectives: The objective of this study was to evaluate the effect of sevoflurane and isoflurane in nasal septal surgery in terms of intraoperative blood loss, operation time, recovery time, and especially postoperative pain., Methods: A total of 90 elective nasal septal surgery patients between the ages of 19 and 58 years (mean age, 32.95 years) who were classified as American Society of Anesthesiologists physical status I and II between January 2011 and June 2012 were included the study. Patients were assigned by randomization to receive 1 of 2 anesthetic agents (n = 45 patients each group): balanced general anesthesia with sevoflurane or isoflurane group. In all patients, the amount of intraoperative blood loss, the duration of operation, recovery time, and postoperative pain scores were recorded., Results: The amount of perioperative bleeding in sevoflurane cases was less than that in the isoflurane group, and the difference was statistically significant (P < 0.05). Similarly, mean operative time was shorter in the sevoflurane group, and again the difference between 2 groups was statistically significant (P < 0.05). No statistically significant differences were observed between the 2 groups with respect to the anesthesia duration, extubation time, recovery time, and postoperative pain scores (P > 0.05)., Conclusions: Sevoflurane, which is one of the volatile anesthetics, leads to a lower amount of intraoperative bleeding, postoperative pain, and operation time than isoflurane during nasal septal surgery.

Background: The small number of epithelial cells that can be isolated from mouse respiratory tract has limited its application to study of the airway. Our purpose in this work was to compare the potential of mouse nasal septal and turbinal epithelium for serving as a cell source for in vitro cell cultures., Methods: The distribution of ciliated epithelial cells in the mouse nasal cavity, and the surface area of the respiratory epithelium in the mouse nasal septum and turbinate were determined by β-tubulin IV immunohistochemistry. Ciliated epithelial cell density of native mouse nasal septum and turbinate, and the morphology of cultured mouse nasal septal and turbinal epithelial cells were examined by scanning electron microscopy (SEM) and β-tubulin IV and zona occludens (ZO)-1 dual-label fluorescent cytochemistry, respectively. Cilia reactivity to exogenous stimuli (adenosine triphosphate or benzalkonium chloride) in cultured nasal septal and turbinal epithelial cells was studied using high-speed digital microscopy., Results: The ciliated epithelial cell density of native nasal epithelium, the morphology and cell yield of in vitro cultured epithelial cells, and cilia reactivity to exogenous stimuli of mouse turbinate are comparable to that of the nasal septum. However, the respiratory epithelium surface area of mouse turbinate is significantly larger than that of the nasal septum., Conclusion: Mouse turbinate may also serve as an ideal source of in vitro epithelial cell cultures. Both nasal septum and turbinate should be harvested to optimize animal use in the establishment of primary murine respiratory epithelial cultures., (Copyright © 2012 American Rhinologic Society-American Academy of Otolaryngic Allergy, LLC.)

Objectives: Our purpose was to compare the ciliary function between the upper and lower airway., Methods: Basal ciliary beat frequency (CBF) and changes in CBF in response to exogenous stimuli [adenosine triphosphate (ATP) or benzalkonium chloride (BAC)] of primary cultured mouse nasal and tracheal epithelial cells were quantified using digital microscopy combined with a beat-by-beat CBF analysis., Results: The basal CBF of the mouse tracheal culture was statistically higher than the nasal culture. Adding 10 or 100 µM ATP caused an increase of CBF in both mouse nasal and tracheal cultures; however, nasal culture induced a more robust increase of CBF than tracheal culture. Treatment with 0.001% BAC increased CBF within 2 min after treatment and then CBF gradually decreased; nasal and tracheal culture manifested a similar change in CBF. With a concentration of 0.01%, BAC induced a rapid and time-dependent decrease of CBF in both mouse nasal and tracheal cultures; however, tracheal culture showed a blunter response to this ciliotoxic agent, with the ciliary beating duration time distinguishably longer than in the nasal culture., Conclusion: The inherent ciliary and physiological function is different in the upper and lower airway in mice., (Copyright © 2012 S. Karger AG, Basel.)

Background: Comparison of the two methods of decongestant and three doses of dexamethasone on reducing edema and ecchymosis after septorhinoplasty., Methods: Seventy-four patients who were candidates for rhinoplasty were randomly divided into three groups. Group A received 8 mg of i.v. dexamethasone preoperatively and again after 24 and 48 hours after surgery, group B received three pseudoephedrine tablets (60 mg) per day for 1 week, and group C received three pseudoephedrine tablets (60 mg) per day for 2 weeks. Finally, their effects on the eye, tip and dorsal edema, and ecchymosis were evaluated., Results: Our findings showed that both decongestant and corticosteroid had significant short-term effects on edema and ecchymosis, but only continuation of pseudoephedrine could reduce the evaluated variables after 1 week., Conclusion: Pseudoephedrine can be effective for reducing eyelid edema and ecchymosis after rhinoplasty. Also, administration of three doses of dexamethasone in the postoperative care of nasal plastic surgery harmlessly diminished postsurgical edema.

Nasal septum perforation is a rare but described complication of the anti-angiogenetic agent bevacizumab. This is the case of a 48-year-old female breast cancer patient, who developed a nasal septum perforation during treatment with paclitaxel and bevacizumab for advanced disease. After 2 cycles the patient developed nasal irritation and occasional epistaxis; after the 4th cycle with bevacizumab the symptoms worsened to include nasal congestion, major epistaxis and rhinorrhoea. Anterior rhinoscopy revealed a large perforation involving the antero-inferior portion of the cartilaginous nasal septum surrounded by necrotic mucosa. The upper septum and the columellar strut were intact. The patient denied use of cocaine or other intranasal irritants. Bevacizumab was discontinued and with only a topical intranasal vitamin application the symptoms improved. One month later anterior rhinoscopy showed that the lesion healed and normal mucosa surrounded the previous site of perforation. The patient continued successfully with other chemotherapy regimens (gemcitabine and then vinorelbine) until irreversible progressive disease led to her death in February 2010. Thus far 8 other cases of bevacizumab-related nasal septum perforation have been published: 5 patients with colorectal cancer, 2 patients with breast cancer and 1 with ovarian cancer. Nasal septum perforation is an emerging challenge with targeted therapies and in particular with antiangiogenetic or antivascular agents. A rapid diagnosis is important and hence we recommend that patients undergoing treatment with bevacizumab and presenting with nasal symptoms (epistaxis, crusting, rhinorrhoea, nasal congestion and local pain or irritation) should undergo anterior rhinoscopy immediately.

Background: Silastic splints have been used as effective tools for septal support, avoiding adhesion, and mucosal healing after septal surgery. Furthermore, although many surgeons insert septal splints, no well-designed trials exist to support their use. A randomized double-blinded controlled trial was performed., Methods: We recruited 40 subjects who had undergone septoplasty only without sinus surgery or turbinoplasty. A silastic septal splint was inserted in one side of the nasal cavity at the end of each septoplasty, with the other side serving as a control. The splint side and control side were randomly selected. Nasal discomfort score (10-point scale) and mucosal status (grades 1-4) were surveyed in a blinded setting on postoperative days 7 and 14., Results: Forty of 83 subjects fulfilled the enrollment criteria. On the 7th postoperative day there was no significant difference in nasal discomfort between the splint and control sides (6.2 ± 1.28 and 5.7 ± 1.27, respectively; p = 0.116), but the mucosal status was better on the splint side than on the control side (1.5 ± 0.51 and 2.5 ± 0.85; p < 0.001). At 14 days postoperatively, the symptom score (2.7 ± 1.06 versus 3.8 ± 1.25; p < 0.001) and mucosal status (1.5 ± 0.55 versus 1.9 ± 0.68; p = 0.013) were significantly better on the splint side compared with the control side., Conclusion: Insertion of a silastic septal splint after septal surgery should be accepted as a routine procedure.

Purpose: In breast cancer patients, Mailliez and others described that 5 of 70 patients (7%) developed a bevacizumab-induced nasal septal perforation. However, to date, no studies have reported such rates in colorectal cancer patients, who derive a survival advantage with this drug., Methods: This study examined the incidence of bevacizumab-induced, clinically symptomatic, otolaryngology specialist-confirmed nasal septal perforation among 100 patients who had been consecutively-treated for metastatic colorectal cancer., Results: The incidence of nasal septal perforation was 1% (95% confidence intervals: -0.95% to 2.95%). This single adverse event was successfully managed conservatively. Within the whole group, 94 had been treated with bevacizumab at 5 mg/kg every two weeks, except for four patients treated at higher doses. The median number of bevacizumab doses (range) was seven (1-96). Concomitant chemotherapy had been prescribed to all patients, consisting of oxaliplatin, 5-fluorouracil, leucovorin, as per one of the FOLFOX regimens (44 patients); irinotecan, 5-fluorouracil, leucovorin, as per the FOLFIRI regimen (13 patients); both these regimens and no other (five patients); or a different regimen (38 patients)., Conclusion: Nasal septal perforation from bevacizumab occurs infrequently among colorectal cancer patients.

A 52-year-old woman, with a metastatic breast cancer, presented with a nasal septum perforation while receiving a treatment combining paclitaxel and bevacizumab. This is the fifth reported case of nasal septum perforation probably related to an anti-angiogenic therapy. A literature review and a discussion concerning the different causes of nasal septum perforation were performed., (Copyright © 2010 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Objectives/hypothesis: Assess for complications of intranasal Bevacizumab application in patients with hereditary hemorrhagic telangiectasia (HHT)-associated epistaxis., Study Design: Retrospective chart review., Methods: In 58 patients presenting with recurrent HHT epistaxis, Bevacizumab was applied intranasally either as a submucosal injection or as a topical spray between October 2006 and June 2010. In many of the injected patients, the potassium titanyl phosphate (KTP) laser was used adjunctively for vessel photocoagulation. A phone interview was performed in July 2010 to assess for treatment complications., Results: Of the 58 treated patients 52 were contacted. Patient surveys were performed 1.5 to 46 months following their initial Bevacizumab treatment. Within the treatment population, five patients had sustained a septal perforation. Notably, these patients were treated early in the study period at which time the cartilaginous septum was often both injected and lasered. Subsequently, the treatment protocol was changed and the cartilaginous septum was neither lasered nor injected. After these changes were made no additional septal perforations were identified. No other adverse events were associated with intranasal Bevacizumab treatment., Conclusions: Bevacizumab applied as either a submucosal injection or as a topical nasal spray, with or without application of the KTP laser, is a safe treatment regimen. Still, when Bevacizumab injections are performed, the cartilaginous nasal septum should be avoided as patients may develop septal perforations., (Copyright © 2010 The American Laryngological, Rhinological, and Otological Society, Inc.)

The use of targeted/biologic therapies is now commonplace in the treatment of malignant and non-malignant diseases. The novel mode of action of these drugs has resulted in unpredictable and in some cases unexpected side effects. Given the widespread use of bevacizumab and its distinct mode of action, it is important that oncologists report any unexpected adverse events that may be associated with the drug. Herein, we report three cases of spontaneous nasal septum perforation secondary to bevacizumab. We hypothesize an etiology for this rare event and reasons why it is reasonable to rechallenge the patient.

Background: Empty nose syndrome (ENS) along with atrophic rhinitis are disease entities that are bothersome for patients and difficult for their doctors to treat. The purpose of this study was to evaluate the usefulness of intranasal injection of hyaluronic acid (HA) gel in patients with symptoms of ENS., Methods: Three patients suffering from ENS and atrophic rhinitis underwent trial treatment consisting of submucosal injections of HA preparations into the inferior nasal concha and under the mucous membrane of the septum., Result: As a result of treatment, the patients' symptoms improved for several months and no complications were recorded., Conclusion: Because of its simplicity, safety, and fairly good, but impermanent clinical effects, HA injections appear to be worth considering in less severe forms of ENS.

Bacteria form complex and highly elaborate surface adherent communities known as biofilms which are held together by a self-produced extracellular matrix. We have previously shown that by adopting a biofilm mode of existence in vivo, the gram negative bacterial pathogens Bordetella bronchiseptica and Bordetella pertussis are able to efficiently colonize and persist in the mammalian respiratory tract. In general, the bacterial biofilm matrix includes polysaccharides, proteins and extracellular DNA (eDNA). In this report, we investigated the function of DNA in Bordetella biofilm development. We show that DNA is a significant component of Bordetella biofilm matrix. Addition of DNase I at the initiation of biofilm growth inhibited biofilm formation. Treatment of pre-established mature biofilms formed under both static and flow conditions with DNase I led to a disruption of the biofilm biomass. We next investigated whether eDNA played a role in biofilms formed in the mouse respiratory tract. DNase I treatment of nasal biofilms caused considerable dissolution of the biofilm biomass. In conclusion, these results suggest that eDNA is a crucial structural matrix component of both in vitro and in vivo formed Bordetella biofilms. This is the first evidence for the ability of DNase I to disrupt bacterial biofilms formed on host organs.

Background: Bevacizumab is an anti-vascular endothelial growth factor approved in association with paclitaxel or docetaxel as first line in patients (pts) with metastatic breast cancer. Rare cases of nasal septum perforations have been reported. We report our experience of nasal perforation in breast cancer pts receiving bevacizumab and chemotherapy either in the adjuvant or in the metastatic settings., Methods: Between 1 January and 31 December 2009, 70 pts received bevacizumab together with chemotherapy. All the pts who had received bevacizumab were referred to the ENT specialist. Symptoms potentially related were looked for. Side effects were graded according to CTCAE., Results: Five nasal septum perforations were diagnosed (5 out of 70; 7.14%). Bevacizumab dose was 15 mg kg(-1) 3 weekly. Three pts were metastatic. Bevacizumab was associated with docetaxel (100 mg m(-2) every 3 weeks) in two pts and with weekly paclitaxel in one. The last two pts received bevacizumab in combination with anthracyclin and then taxanes in the adjuvant setting. In these two cases, nasal septum perforation occurred at the time of docetaxel treatment., Conclusion: A high incidence of nasal septum perforation has been shown in pts with breast cancer receiving bevacizumab together with chemotherapy. Several mechanisms could be involved (mucositis, delayed tissue repair, antiangiogenic action of taxanes).

Objectives: This study was designed to investigate the effects of the tissue adhesive N-butyl cyanoacrylate on nasal septal tissues after septal surgery in a rabbit model., Methods: Forty-two adult New Zealand rabbits were randomly divided into three groups (14 in each group): septoplasty alone, septoplasty plus N-butyl cyanoacrylate, and controls. The open approach was used to explore the nasal septum. After raising mucoperichondrial and mucoperiosteal flaps on both sides of the septum, the septum was detached from the nasal floor in the septoplasty alone and septoplasty plus N-butyl cyanoacrylate groups. In the septoplasty plus N-butyl cyanoacrylate group, the mucoperichondrial and mucoperiosteal flaps were fixed to the septum and the septum was fixed lateral to the nasal spine using N-butyl cyanoacrylate; in the septoplasty alone group, the septum was packed with Merocel. In the control group, no further septal surgery was performed after flap elevation. Animals were observed for bleeding and haematoma formation over the first 24 hours. Seven animals in each group were used to evaluate early histopathological effects on the septal tissues, at four weeks post-operatively; the other seven in each group were used to evaluate late effects, at 12 weeks., Results: Haematoma formation was observed in 10 animals in the septoplasty alone group, in four animals in the control group, and in only one animal in the septoplasty plus N-butyl cyanoacrylate group. The difference in haematoma incidence between the septoplasty alone and the septoplasty plus N-butyl cyanoacrylate groups was significant (p = 0.000). Histopathological evaluation revealed no significant difference between the groups as regards granulation tissue formation at week four versus week 12; however, there was a significant difference between the septoplasty plus N-butyl cyanoacrylate group and the control groups as regards inflammation at week 12 (p = 0.038). There was a significant difference between the septoplasty plus N-butyl cyanoacrylate group and the septoplasty alone group as regards the composition of the bone-cartilage junction zone at week four (p = 0.001). There was also a significant difference between the septoplasty plus N-butyl cyanoacrylate group and the control group as regards the cellular structure of new cartilage formation at week 12 (p = 0.004)., Conclusions: In this rabbit septoplasty model, N-butyl cyanoacrylate appeared to be an effective nasal tissue adhesive, with a low complication rate.

Methotrexate is a dihydrofolate reductase inhibitor with application both as a chemotherapeutic agent and as a disease-modifying antirheumatic drug. Although its ability to inhibit cellular proliferation is a desired effect in its role as an antineoplastic agent, this property may also hinder normal physiologic regeneration of the nasal epithelium. This effect may predispose patients to septal cartilage ischemia, necrosis and, eventually, perforation. We report 2 cases of septal perforations in the setting of prolonged methotrexate use and present a literature review. Patient 1 is an 8-year-old boy with juvenile rheumatoid arthritis managed with weekly methotrexate who developed a 4-mm septal perforation with an unremarkable biopsy. This was closed with a mucosal advancement flap without incident. Patient 2 is an 11-year-old boy with non-Hodgkin lymphoma treated with methotrexate. His examination was significant for a large perforation of the dorsocaudal septum. A biopsy was negative for malignancy in this patient. Repair has been deferred-initially for chemotherapy and currently for treatment relapse. We hypothesize that prolonged use of methotrexate alters the balance between physiologic desquamation and epithelial regeneration. This imbalance may promote septal ischemia and predispose patients to the development of septal perforations.

A prospective randomized study was designed to compare the effect of different irrigation solutions on mucociliary clearance and nasal patency and to compare the limitations of the used solutions, such as nasal burning by a visual analog scale. Forty-five patients who underwent septoplasty were divided into three groups postoperatively. Each group was administered with 2.3% buffered hypertonic seawater, buffered isotonic saline solution and non-buffered isotonic saline, respectively, as irrigation fluid. Saccharine test and acoustic rhinometer were used to determine mucociliary activity and nasal patency. Patients were asked about the burning sensation using a 10-cm visual analog scale. There was no significant difference in saccharine clearance time (SCT) on the 5th postoperative day between the three groups (P = 0.07). On the 20th day, there was a significant difference in SCT between the hypertonic buffered seawater group and non-buffered isotonic saline (P = 0.003). Buffered hypertonic seawater improved nasal airway patency more than the buffered isotonic saline (P = 0.004). Buffered hypertonic solutions used after endonasal surgery have been advantageous for both mucociliary clearance and postoperative decongestion.

Otolaryngologists should be made aware of a newer cause of nasal septal perforations resulting from the more recent antiangiogenic therapy used to treat malignancies. This case describes a 52-year-old white woman who developed a spontaneous nasal septal perforation after given the antiangiogenic drug, bevacizumab, for metastatic ovarian cancer treatment. Bevacizumab is a recently developed monoclonal antibody against vascular endothelial growth factor receptor used to inhibit angiogenesis. The patient was ultimately treated with a nasal septal button with good symptom relief. This case documents the first report in the otolaryngology literature describing this new etiology for nasal septal perforations.

Objective: To describe the nasal side effects of postmenopausal women suffering from osteoporosis and being treated with intranasal calcitonine (InC)., Method: Two women who presented with nasal complaints, were diagnosed as having nasal septum perforation and septum-concha inferior synechiae respectively. Both were receiving treatment with InC for postmenopausal osteoporosis. A medline search for similar side effects of InC revealed a range of nasal symptoms and several factors that could induce these symptoms., Results: Exclusion of other causative conditions leads us to attribute the nasal findings to the use of InC. The literature mentions mild and usually reversible side effects from use of InC. Substances included in the calcitonine spray (preservatives, accelerators of absorption), the development of antibodies against the hormone and possible implication of coexisting diseases or medications to the provocation of nasal side effects, are discussed., Conclusions: Intranasal administration of calcitonine is an established therapy for postmenopausal osteoporosis and other skeletal diseases. The side effects from its use are commonly local, mild and transient, but there is not sufficient information on how this process begins. An ENT examination before and during therapy with InC would be beneficial to patients for the recognition and prevention of serious side effects.

Objective: The use of tampons after nasal septum surgery is important for both prevention of postoperative bleeding and stabilization of the nasal flaps and the septum. One of the most important factors in achieving rapid postoperative recovery is the choice of the nasal tampon material, among many, to produce minimal damage on the nasal mucosa. In this study, the histopathological effects of the glove finger and merocel tampons, which are commonly used in clinical applications, have been investigated on the nasal mucosa of rabbits., Materials and Methods: In this study, merocel and glove finger tampons were used for nasal packing in one-sided nasal cavities of 16 adult New Zealand rabbits. The animals were randomized into two groups, each consisting of eight animals. The tampons were removed after 48 hours., Results: Histological examination showed that if the merocel was in a glove finger, it did not create any damage to mucosal integrity and lamina propria. However, in the group where merocel was used directly, the epithelium of the nasal mucosa was shortened and demonstrated loss of cilia and in four of the eight specimens, it was partly from lamina propria., Conclusion: It is concluded that the use of merocel in glove finger tampon leads to a lesser degree of damage in the lamina propria, and may facilitate rapid mucosal wound healing postoperatively.

In the UK almost one million individuals use cocaine on a regular basis, implying that dentists are likely to encounter individuals that use cocaine. Regular use of this drug may have several orofacial effects, such as perforation of the nasal septum and palate, gingival lesions and erosion of tooth surfaces. In addition, recent use of cocaine increases the risk of a medical emergency during dental treatment, especially when epinephrine-containing local anaesthetics or retraction cords are used. Therefore, dental treatment should be postponed for 6 to 24 hours after the use of cocaine.

Background: Previous work suggests differences in the distribution of human intranasal trigeminal receptors. The aim of this study was to investigate these topographic differences for different concentrations of different trigeminal irritants using an electrophysiologic measure of trigeminal activation, the negative mucosa potential (NMP)., Materials and Methods: A total of 15 healthy volunteers participated. Presented by a computer-controlled olfactometer CO2 (30% and 40% v/v), ethyl acetate (5.5% and 9.3% v/v) and acetic acid (205 and 40% v/v) were used for stimulation. NMP was recorded at the middle septum, the middle turbinate, and the floor of the nasal cavity., Results: Maximum amplitudes of the NMP were found at the middle septum and were lowest at the nasal floor. Response amplitudes were related to stimulus concentrations. There was no significant difference between responses to the three different stimuli in relation to three recording sites., Conclusions: In agreement with previous work, the present data suggest that there are topographic differences in the responsiveness of the mucosa to chemical irritants.

Infiltration of lignocaine with epinephrine is used with cocaine in septoplasty, in attempt to improve haemostasis and thereby improve the surgical field. This practice is widespread despite the lack of evidence to support its efficacy in the literature. Thirty patients undergoing septoplasty were randomised into two groups -- one in whom infiltration was performed with lignocaine (2%) with adrenaline (1:80,000) and a control group who received lignocaine (2%). Both groups of patients received intranasal application of cocaine paste prior to surgery. The surgeon and anaesthetist were blinded to the contents of the infiltration. The operative field was rated by the surgeon, and the blood loss calculated. No significant difference was demonstrated in blood loss or surgical field between the groups. However there was significant rise in systolic blood pressure in patients who received epinephrine. The use of epinephrine with cocaine paste does not improve haemostasis or surgical field. As the use of epinephrine is associated with cardiac arrhythmias, the authors suggest that combined use of cocaine paste and epinephrine infiltration should be avoided in septal surgery.

The list of bevacizumab's adverse effects continues to grow: the latest additions are reversible posterior leukoencephalopathy and perforation of the nasal septum.

Objectives: To investigate the changes in adult rabbit nasal septal tissues after application of fibrin glue during septoplasty., Study Design: Preclinical animal study., Methods: Nineteen adult albino Vienna rabbits were included in the study. Rabbits were randomly divided into study (n = 14) and control groups (n = 5). The study group was subsequently divided into two subgroups with seven rabbits in each group to investigate short- and long-term effects of fibrin glue. After raising the mucoperichondrial flap on one side of the septum, fibrin glue was used to fix the mucoperichondrial flap over the septal cartilage. Rabbits were killed 3 weeks and 6 weeks after septoplasty. Samples from the excised nasal septa underwent routine tissue procedure for histopathologic investigation., Results: Both short-term and long-term results were compared with the control group and with each other. There was a significant difference regarding mucosal inflammation and cartilaginous damage between groups. A significant difference was found between groups in terms of loss of cilia, loss of goblet cells, the presence and degree of fibrosis. Loss of cartilage was significantly different between groups. In comparing the thickness of the mucosa, thickness of the perichondrium, and thickness of cartilage, there were significant differences between groups., Conclusion: Our results demonstrate that fibrin glue causes distinctive inflammation, creates mucosal damage, increases mucosal thickness, decreases perichondrial thickness and cartilaginous thickness, and causes segmental cartilage loss in rabbits. Further comparative clinical investigations are required to assess the clinical efficacy of fibrin glue in nasal septal surgery in humans.

Objective: To determine the effects of bone morphogenetic proteins (BMP)-2 and -7, and serum, on extracellular matrix production by human septal chondrocytes in alginate., Study Design: Human nasal septal chondrocytes were expanded, suspended in alginate, and cultured in BMP-2 or 7, with and without serum. The optimal concentration of each growth factor was determined based on matrix production. Next, the synergistic effects of BMP-2 and -7 at optimal concentrations were determined on separate beads, based on matrix quantity and histology., Results: Matrix content was highest with concentrations of BMP-2 and -7 of 100 ng/ml and 20 ng/ml, respectively, with serum. Adding both BMP-2 and -7, with serum, increased matrix content by factors of 5.1 versus serum-only cultures, 2.7 versus only BMP-2 with serum, and 2.4 versus only BMP-7 with serum. All comparisons were statistically significant., Conclusion: BMP-2 and -7 significantly increase production of extracellular matrix by septal chondrocytes suspended in alginate. The presence of serum improves matrix production., Significance: BMP-2 and -7 have great potential for use in cartilage tissue engineering.

Background: In clinical practice a perforation of the nasal septum secondary to an occupational exposure to corrosive chemicals is not considered a sequel of rhinitis., Methods: Relevant articles published in the last 26 years were searched and retrieved from PubMed., Results: Patients with nasal septal perforations of occupational origin show a history of rhinitis with a gradual installation of symptoms and damage of the nasal mucosa progressing to ulceration and ultimately to perforation of the nasal septum., Conclusion: Patients with nasal septal perforations of occupational origin exhibit the clinical and histopathological features of rhinitis whereby they should be categorized as rhinitics. This rhinitis should be considered as a type of irritant-induced occupational rhinitis and classified as corrosive rhinitis.

Cocaine use in the United States continues to be a significant problem. Cocaine use is responsible for approximately 143,000 Emergency Department visits annually. The cardiac effects of cocaine are well known and much is written on this topic; this is beyond the scope of this article. Cocaine use is also responsible for a variety of non-cardiac, systemic complications, which it is our purpose to review. Multiple systemic effects of cocaine are seen with both acute and chronic use. These systems include: psychological and psychiatric, neurological, renal, pulmonary, gastrointestinal, obstetrical, and otolaryngological.

We present our experience and results after using polydioxanone (PDS) foil in septal reconstruction. In a period of 2 years, 12 patients who were admitted in our department with severe septal deviation and breathing problems underwent septoplasty under general anaesthesia. The nasal septum was approached via an external approach. In all patients, after resecting and exposing the septum, the removable piece after being divided into straight pieces, was sutured onto an appropriate sized PDS foil and reimplanted together between the mucoperichondrium flaps. Sutures were placed to fixate the "new septum" to the nasal dorsum and to the anterior nasal spine. The immediate postoperative course was unremarkable and in a follow-up appointment 6 months and 1 year postoperatively, one complication occurred, with septum subluxation noted in one patient. Use of PDS foil in septal reconstruction is an important surgical option for the correction of the markedly deviated nasal septum. Fixation of the straightened and replanted septum at the nasal dorsal septum border with the upper lateral cartilages and at the nasal spine is essential.