Bile acids in laryngopharyngeal refluxate: will they enhance or attenuate the action of pepsin?

OBJECTIVES/HYPOTHESIS: To assess if, as previously reported in the literature, bile acids inhibit pepsin activity, resulting in pepsin having a less important role in laryngopharyngeal damage in reflux disease. STUDY DESIGN: Prospective translational research study. METHODS: A total of 78 patient's fasting gastric juice samples were obtained from routine endoscopy. The total bile acid (TBA) content and pepsin activity were measured using a 3α-hydroxysteroid dehydrogenase-based kit for bile acids; and pepsin activity was measured using succinyl albumin/dimethylhaemoglobin as a substrate and the development of new N-terminals. The ability of bile acids to effect pepsin activity was assessed with three primary bile acids, two unconjugated and one taurine conjugated, using the above N-terminal assay. RESULTS: Gastric juice contained median TBA of 40 (range 10-10010) µM and pepsin activity of 408 (range 27-3892)ug/ml. We used this data to inform the relative levels of pepsin and bile acids that might occur in a reflux event, and we used concentrations of bile acids between 10-100µM. Pepsin activity was pH dependent, but 28% of the activity was retained at pH 5.5. None of the bile acids showed any significant effect on pepsin activity across the pH range 2.0-6.0. CONCLUSIONS: At the levels and pH that pepsin and bile acids might occur in an LPR event, bile acids do not attenuate pepsin activity. Pepsin could be considered a damaging factor even at high pH, and it will aggravate further any damaging effects of bile acids in the refluxate. Laryngoscope, 2012.

Laryngeal mucosa: its susceptibility to damage by acid and pepsin.

OBJECTIVES/HYPOTHESIS: Exposure of pig laryngeal mucosa to pepsin and acid will have a differential damaging effect depending on the anatomical site, mirroring the effects seen in the human larynx in laryngopharyngeal reflux (LPR). This study aims to quantitate damage caused to laryngeal tissue by acid alone, and acid and pepsin, and also to determine if the extent of this damage depends on the tissue site. STUDY DESIGN: Prospective translational research study. METHODS: An excised porcine laryngeal damage model in a small Ussing chamber was used to measure the effect of pepsin and acid on five sites (ventricles, vocal folds, posterior commissure, supraglottic, and subglottic mucosa). The tissue samples were incubated on the lumenal side for 1 hour with pH 2 and 4 HCl, pH 2 plus 1 mg/mL pepsin, and pH 4 plus 1 mg/mL pepsin. Damage was assessed by changes in absorbance of the bathing solution at optical density (OD) 260 nm and OD 280 nm and by measurement of released DNA compared to tissues bathed in pH 7.4 buffer. Damage was also assessed histologically. RESULTS: Based on histology, all the tissues were resistant to pH 4.0 except the subglottic mucosa. Only the posterior commissure was not damaged by pH 2.0 plus pepsin. Similar patterns were observed with absorbance changes and DNA release. CONCLUSIONS: The subglottic mucosa was the most susceptible to damage and the posterior commissure the least. Laryngeal tissues are essentially resistant to damage at pH 4.0, but are damaged when pepsin is present. This suggests that in LPR, pH 4.0 or above refluxate would only be damaging if it contains pepsin.

Unilateral secondary (acquired) postmastoidectomy low-set ear: postoperative complication with potential functional and cosmetic implications.

OBJECTIVE: This article reports the development of low-set ear following tympanomastoidectomy via endaural and/or postaural approaches. DESIGN: Description of 10 cases who had developed low-set ear following mastoid surgery undertaken to clear chronic suppurative otitis media. The surgical approach was via endaural or postaural incisions. SETTING: Tertiary care referral hospital. METHOD: The operative history and development of low-set ear complication are described. Potential factors responsible for the development of postoperative low-set ear and a possible way to avoid such a complication are discussed. MAIN OUTCOME MEASURES: The development of postoperative low-set ear following endaural or postaural incisions. RESULTS: The described 10 cases had tympanomastoidectomy. A postaural approach was employed in six cases and an endaural approach in four. Canal wall down mastoidectomy was done in seven cases, whereas canal wall up mastoidectomy was done in three. Seven patients were aware of postoperative auricular changes, and two of them were unhappy with this. Potential predisposing factors include dissection of the auricle and ear canal and lowering of the posterior bony canal wall. This could result in weakening of the supportive elements that keep the auricle in the normal position. CONCLUSION: Low-set ear should be recognized as a potential complication following mastoid surgery. It can have cosmetic and functional implications for the patient. Possible ways to avoid its development are suggested. This is the first report of such a postmastoidectomy complication in the English literature.

Mucin gene expression in hypertrophic adenoids.

CONCLUSION: Membrane-bound mucin MUC4 represents the predominant mucin expressed in the adenoid epithelium followed by MUC5AC (gel-forming mucin). This may suggest that membrane-bound mucins could be involved in pathogen binding and immunological stimulation. OBJECTIVES: The aim of this study was to investigate mucin expression in hypertrophic adenoids. MATERIALS AND METHODS: Adenoidal samples were obtained from 12 children. The expression of eight mucin genes, MUC1-4, MUC5AC, 5B, 6 and 7 was studied by in situ hybridization utilizing digoxigenin-labelled oligonucleotide probes. RESULTS: The dominant mucin genes were MUC4, 3 and 5AC, while MUC1, 2, 5B and 7 were sparsely expressed and MUC6 was not expressed. Expression patterns were very different from those in the upper airways. Most samples expressed two membrane-bound mucins (MUC4 and 3) and one secretory mucin (MUC5AC).

Upper airway mucin gene expression: a review.

INTRODUCTION: The gel-like properties of mucus depend primarily on its content of mucins. The protein backbones of mucins are encoded by mucin genes. Of the currently known 20 mucin genes that encode protein backbone of mucins, 16 have been identified in the airways. METHOD: We explored the current knowledge about upper airway mucin expression in health and disease conditions using a Medline search. We have also studied upper airway mucin gene expression and compared our results with the results from other studies. RESULTS: MUC5AC, MUC5B, and MUC2 are the principal gel-forming mucins secreted in the airway. However, the spectrum of mucin expression in chronic upper airway diseases such as nasal polyps, chronic sinusitis, middle ear effusion, and cystic fibrosis is generally wide and variable. DISCUSSION: The wide spectrum of upper airway mucin expression is possibly caused by various anatomic and histologic features as well as physiologic and pathologic variables. These variables have not been fully explored yet, and the majority of airway mucin expression studies used small numbers of samples. CONCLUSION: Studies including adequate numbers of samples (patients) are more likely to reveal a clearer profile and more precise expression patterns. Generating a clear profile of mucin expression patterns in health and disease requires the analysis of different variables, which can alter that expression. It is also essential to understand the various molecular mechanisms controlling mucin gene and protein expression. This could lead to the invention of novel therapeutic modalities to treat upper airway diseases.

Major secretory mucin expression in chronic sinusitis.

OBJECTIVE: The aim of this study was to investigate mucin expression in chronic sinusitis compared to that in normal nasal mucus. STUDY DESIGN AND SETTING: Sinus mucus samples were collected during functional endoscopic sinus surgery (FESS). The expression of 3 airway mucins, MUC2, MUC5AC, and MUC5B, was determined by ELISA. RESULTS: The 3 mucins are expressed in chronic sinusitis and in normal nasal mucus. MUC5AC and MUC5B represent a major component in sinus mucins while MUC5B and MUC2 predominated in normal nasal mucin. In sinus mucins, upregulation of MUC5AC was associated with downregulation of MUC2 and vice versa. This inverse relationship was strengthened in the presence of nasal polyps. CONCLUSION: At least 3 mucins are expressed at various levels in chronic sinusitis. An inverse relationship was identified between expression of MUC5AC and MUC2. Large prospective studies are required to unravel the complexities of sinus mucus in chronic sinusitis. SIGNIFICANCE: Mucins may be used as markers for assessment of disease severity and may also help as prognostic indicators following medical or surgical treatment.

Mucin gene expression in nasal polyps.

CONCLUSIONS: A large set of mucin genes is expressed in nasal polyps. The expression pattern is complex and may reflect the wide spectrum of variables involved in polyp formation and progression. Prospective studies including subgroups of nasal polyps and involving substantial numbers of cases in each subgroup will be required to elucidate these variables and to understand how they affect mucus secretion. OBJECTIVE: At present, 15 of the 19 known mucin genes are expressed in the human airways. Nasal polyps might be expected to have a mucin expression pattern comparable to that of the airways. The aim of this study was to investigate mucin expression in nasal polyps. MATERIAL AND METHODS: Nasal polyp samples were obtained from 20 patients during functional endoscopic sinus surgery. Normal (control) sphenoid sinus mucosa was obtained from patients undergoing trans-sphenoid hypophysectomy. The expression of eight mucin genes (MUC1-4, -5AC, -5B, -6 and -7) was studied by in situ hybridization utilizing digoxigenin-labelled oligonucleotide probes. RESULTS: MUC6 and -7 were not expressed in sphenoid sinus mucosa, while all the studied mucin genes were expressed in nasal polyps. Expression patterns varied widely between individual polyps. The predominant epithelial mucin genes were MUC4, -5AC and -3, while MUC5B and -7 were mainly of glandular origin. MUC1, -2 and -6 were weakly expressed. The major alteration in gene expression in nasal polyps was found in the submucosal glands. MUC4 and -5AC represent a major component of both submucosal glands and epithelial cells in nasal polyps.

Spontaneous retro- and parapharyngeal haematoma caused by intrathyroid bleed.

A case of spontaneous haemorrhage into the retropharyngeal and parapharyngeal space secondary to bleeding from a thyroid cyst is described. While many conditions are known to cause this entity, no previous papers have reported a thyroid cyst to cause such extensive haemorrhage. Haemorrhage in these spaces is of particular importance as it causes rapid airway compromise and can be life-threatening. Forty cases of non-traumatic retropharyngeal and parapharyngeal haematomas have been reported in the literature to date. Although the diagnosis can be easily established in most patients, no published review of this condition exists. This paper reviews all reports of non-traumatic retropharyngeal and parapharyngeal haematoma published in the literature to date and discusses management guidelines. We also present here for the first time the demographics and treatment results of this rare entity.

Mixed nasal mucus as a model for sinus mucin gene expression studies.

OBJECTIVE/HYPOTHESIS: It is necessary to obtain sinus mucus from the paranasal sinus cavities to study mucin gene expression occurring in the sinuses during chronic sinusitis. This requires an invasive procedure to access the sinus cavity. There are embryological as well as histological similarities between nasal and sinus epithelia; therefore, we postulated that the mucin expression in the secreted nasal and sinus mucins might be similar. Nasal mucus, which can be obtained easily, could then replace sinus mucus in these studies. STUDY DESIGN: Sinus and nasal mucus from six patients with chronic sinusitis were analyzed in this study. METHODS: High-molecular-weight glycoproteins (mucins) were isolated and purified by sequential density gradient centrifugation in caesium chloride (CsCl). Enzyme-linked immunosorbent assay was performed to identify the antigenic identity of these mucins. RESULTS: The MUC2, MUC5AC, and MUC5B mucin genes were all expressed in the nasal and sinus mucus secretions. Antigenic studies showed an inverse relationship between MUC2 and MUC5AC expression in nasal and sinus mucus secretions. The MUC5B gene was the major mucin gene expressed in sinus mucus but not in nasal mucus. Expression of MUC2 was significantly higher in sinus mucus. Expression of MUC5AC was different between nasal and sinus mucus. CONCLUSIONS: Individual mucin expression in sinus and nasal mucus was markedly different. From this preliminary study, we conclude that nasal mucus is not a suitable substitute for sinus mucus in sinus mucin gene studies and that different pathological processes are taking place in nasal and sinus tissue in chronic sinusitis.