John P. Birchall

Is Gastric Reflux a Cause of Otitis Media With Effusion in Children

Objectives/Hypothesis Otitis media with effusion is the most common cause of childhood deafness. Gastroesophageal reflux has been implicated in the disease pathogenesis; therefore, it is necessary to identify the presence or absence of gastric juice in the middle ear.

Reflux of gastric juice and glue ear in children.

Otitis media with effusion (glue ear) is the most frequent cause of deafness in children. We investigated the role of gastric juice reflux in this disease. We measured pepsin concentrations in middle ear effusions from children using ELISA and enzyme activity assays. 45 (83%) of 54 effusions contained pepsin/pepsinogen at concentrations of up to 1000-fold greater than those in serum. Our data suggest that reflux of gastric juice could be a major cause of glue ear in children.

LPS up-regulates mucin and cytokine mRNA expression and stimulates mucin and cytokine secretion in goblet cells.

Bacterial inflammation in mucosa is accompanied by morphological and proliferative changes in goblet cells and mucin hypersecretion. Main stimulators of bacterial inflammation are bacterial lipopolysaccharides (LPS). In vitro investigation of the LPS effect on the molecular processes in goblet cells, using the human mucin-secreting goblet cell line HT29-MTX, showed the following results. LPS up-regulated mucin and cytokine mRNA expression and secretion in goblet cells in a concentration and time-dependent manner, with a maximum output at an LPS concentration of 100 ng/ml. LPS (100 ng/ml) increased mRNA expression of MUC5AC (2.4x), MUC5B (2.1x), and IL-8 (2.3x) and stimulated secretion of mucins (MUC5AC up to 39%, MUC5B up to 31%) and the inflammatory cytokine IL-8 (up to 10x). A significant correlation was found between the LPS-induced IL-8 secretion and secretion of mucins. These results suggest: (1) goblet cells, responding to the direct stimulation of bacterial LPS by two inflammatory-related processes such as production and secretion of the gel-forming mucins and the inflammatory cytokine IL-8, can be considered as an important part of mucosal immunity and (2) LPS- induced goblet cell mucin secretion can occur partly via IL-8-dependent pathway.

Diagnosis of Geriatric Patients with Severe Dizziness

OBJECTIVE: To identify the causes of dizziness in older patients presenting to the general practitioner and the clinical characteristics at presentation that might guide the general practitioner to the likely cause of dizziness and the most appropriate specialty for subsequent referral if referral is required.

Otitis Media with Effusion: Components Which Contribute to the Viscous Properties

Middle ear effusions from children undergoing myringotomy were classified into thick (mucoid) and thin (serous) on the basis of their flow properties. Their composition was analysed and their rheological properties measured. The viscosity of the effusions was measured using a Contraves low shear viscometer and expressed as specific viscosity per mg/ml of non-dialysable solids present. In order to measure the effusion viscosity it was necessary to solubilize the effusion by mild homogenisation in a phosphate buffer pH 6.7 containing a cocktail of proteolytic inhibitors. The viscosity of mucoid effusions was significantly greater than that of the serous effusions. There was a small but measurable amount of proteolytic activity in the effusions, range 0.05-1.79 micrograms/mg of non-dialysable solids. This proteolytic activity was not significantly different between the thick and thin effusions and was therefore unlikely to explain the difference in viscosity. Analysis of the constituents of the effusions showed that glycoprotein and DNA but not protein nor lipid were significantly higher in the mucoid effusions compared to the serous effusions. The viscosity of the effusions correlated with the glycoprotein concentration but not with the protein or lipid concentration. Under certain circumstances the DNA concentration did correlate with the viscosity of the effusion. However, digestion with a proteinase free DNase did not reduce the viscosity of the effusion. These results demonstrate that classifying effusions as thick and thin based on visual inspection and flow properties is valid and that the only constituent present in the effusions that determines viscosity is mucin.

Update on otitis media – prevention and treatment

Acute otitis media and otitis media with effusion are common childhood disorders, a source of significant morbidity, and a leading cause of antibiotic prescription in primary health care. Although effective treatments are available, some shortcomings remain, and thus better treatments would be welcome. Recent discoveries within the field of otitis media research relating to its etiology and pathogenesis have led to further investigation aimed at developing novel treatments. This article provides a review of the latest evidence relating to the understanding of acute otitis media and otitis media with effusion, current treatment strategies, their limitations, new areas of research, and novel strategies for treatment.

A study of haemostasis following tonsillectomy comparing ligatures with diathermy.

The use of diathermy to achieve haemostasis after tonsillectomy remains controversial. We have reviewed the English language literature, and found no convicting evidence that diathermy is any more likely to cause post-operative haemorrhage than the use of ligatures. The results of a prospective, randomized study of 1036 consecutive tonsillectomies are presented. No significant difference was found in post-operative haemorrhage rates when either diathermy or ligatures were used. Diathermy was found to reduce operating time compared to ligatures. The possibilities for day-case tonsillectomy are discussed.

In Vitro Study of IL-8 and Goblet Cells: Possible Role of IL-8 in the Aetiology of Otitis Media with Effusion

One of the main characteristics of otitis media with effusion (OME) is the differentiation of basal cells into goblet cells with subsequent proliferation in a modified respiratory epithelium leading to the formation of mucin-rich effusion in the middle ear cleft. In order to determine the effect of pro-inflammatory cytokines identified in OME, e.g. IL-1 g , tumour necrosis factor (TNF)- f , IL-6 and IL-8, on goblet cells, and to clarify the role of IL-8 in particular, we used the human goblet cell line HT29-MTX, which secretes two OME-related mucins: MUC5AC and MUC5B. IL-1 g and TNF- f stimulated the secretion of IL-8 in HT29-MTX goblet cells. Dose- (2-200 ng ml) and time- (0-5 days) response studies of IL-8-induced mucin secretion were carried out. IL-8 upregulated the secretion of MUC5AC and MUC5B mucins in a concentration-dependent manner, with a maximum response at an IL-8 concentration of 20 ng ml. IL-8 (20 ng ml)-mediated mucin secretion persisted for up to 5 days, with a peak response 72 h after the addition of cytokine. These results suggest that: (i) goblet cells are target cells for the pro-inflammatory cytokines IL-1 g , TNF- f and IL-8 and can contribute to the pathogenesis of OME by increasing both the concentration of IL-8 and the secretion of mucin; and (ii) IL-8 stimulates prolonged mucin secretion from goblet cells and may be involved in the maintenance of the disease in the chronic stage.

Bacterial involvement in otitis media with effusion.

OBJECTIVE Otitis media with effusion (OME), a common chronic childhood condition affecting hearing, is thought to be a result of bacterial infection, with biofilms recently implicated. Although bacterial DNA can be detected by polymerase chain reaction in 80% of patients, typically fewer than half of effusions are positive using standard culture techniques. We adopted an alternative approach to demonstrating bacteria in OME, using a bacterial viability stain and confocal laser scanning microscopy (CLSM): staining allows detection of live bacteria without requiring growth on culture, while CLSM allows demonstration of the three-dimensional structure typical of biofilms. METHODS Effusion samples were collected at the time of ventilation tube insertion, analysed with CLSM and bacterial viability stain, and extended culture techniques performed with the intention of capturing all possible organisms. RESULTS Sixty-two effusions (42 patients) were analysed: 28 (45.2%) were culture-positive, but 51 (82.3%) were CLSM-positive. Combining the two techniques demonstrated live bacteria in 57 (91.8%) samples. Using CLSM, bacteria exhibited biofilm morphology in 25 effusions and were planktonic in 26; the proportion of samples exhibiting biofilm morphology was similar in the culture-positive and culture-negative groups (50.0% and 48.3%, respectively). Biofilm samples contained an average of 1.7 different bacterial isolates and planktonic samples 2.0, with the commonest bacteria identified being coagulase-negative staphylococci. CONCLUSION Live bacteria are present in most effusions, strongly suggesting that bacteria and biofilms are important in the aetiopathogenesis of OME.

Heterogeneity in the protein cores of mucins isolated from human middle ear effusions: evidence for expression of different mucin gene products.

High molecular weight mucins were isolated and purified from human middle ear effusions of children with Otitis Media with Effusion (OME) classified into three groups, (1) thick and (2) thin from anatomically normal children and (3) effusions from cleft palate patients. Amino acid analyses of the purified mucins from the three pools were similar but not identical with characteristic contents of serine threonine and proline (32%, 28%, and 38% for pools (1) (2) and (3) respectively). Proteinase resistant glycopeptide fragments corresponding to the tandem repeat domains of cloned mucin genes showed marked differences both between the three mucin pools and with the composition of the tandem repeat sequences of the cloned mucin genes expressed in the airways. Studies on the antigenic identity of middle ear mucins found an epitope likely to be present on MUC5AC, but only accounting for a maximum of 15% by weight and no reactivity was found with antibodies to MUC2 or MUC1. A polyclonal antibody raised to thick effusion mucins reacted strongly with human salivary mucin suggesting the presence of MUC5B epitopes. These studies suggest that more than one mucin gene product is secreted by the human middle ear mucosa and that there may be further mucin genes expressed by the middle ear that have yet to be cloned.