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Biomedical subjects

J P Birchall

Publications and source records attributed to J P Birchall.

At least 19 recordsLinked to original sources
PubMed2004

Is otitis media with effusion a biofilm infection?

Recent attention has focused on the possibility that otitis media with effusion (OME) may represent a chronic infective state such as those evidenced in conditions secondary to biofilms or small colony variants. This review discusses the evidence suggesting that this may indeed be the case and explains why this may prove to be important in the future management of this condition by discussing recent advances in understanding these bacterial phenotypic variants.

Bacterial Adhesion↗
PubMed2003

Influence of prednisolone on the secretion of mucin from the HT29-MTX cell line.

Glucocorticoids have been used in the treatment of otitis media with effusion with promising but inconsistent results. The HT29-MTX cell line is a completely differentiated and almost exclusively mucus-secreting goblet cell line. To assess the potential of steroids in suppressing mucin secretion, we have studied the response of this cell culture to prednisolone. Confluent cell cultures were trypsinized, subcultured in six-well plates and incubated with five doses of prednisolone from 10-3 M to 10-11 M and over a varying time course from 6 to 36 h. Analysis was performed using a monoclonal mouse antibody to human gastric mucin by dot-blot ELISA. Prednisolone caused a consistent reduction in mucin production from this cell line. Increasing concentrations of prednisolone resulted in increasing suppression of MUC5AC secretion. There is a dose-dependent suppression of mucin secretion by prednisolone, with a maximum effect of 21% over control seen at the highest steroid concentration used.

Anti-Inflammatory Agents↗
PubMed2003

Effect of nitric oxide donation on mucin production in vitro.

Otitis media with effusion (OME) is characterized by the accumulation of a viscous fluid rich in mucins in the middle ear cleft. There is increasing evidence that this fluid is the result of an inflammatory reaction and that nitric oxide (NO) is an important mediator in this reaction. The goblet cell line HT29-MTX produces principally MUC5AC, an important mucin in middle ear effusions, and thus is a good model for the study of mucus-secreting epithelia. Confluent cell cultures were trypsinized, subcultured and incubated with isosorbide dinitrate (ISDN), a NO donor, for 0.5, 1 and 2 h at a concentration of 1 mm and in concentrations of 0.01, 0.1, 0.5, 1 and 2 mm for 1 h. Experiments were performed four times. Mucin production was detected by a slot blot ELISA assay, using a monoclonal mouse antibody to human MUC5AC mucin. Statistical significance was tested using a one-way analysis of variance. NO donation by ISDN caused a consistent rise in mucin production above control. Maximal mucin production of 35% above control occurred at 1 h with 1 mm ISDN. Mucin production increased from 12% above control with 0.1 mm ISDN dinitrate to 45% above baseline with 2 mm ISDN. NO donation by ISDN results in an increase in mucus production, which is both dose and time related. This adds further evidence to an inflammatory model for mucus secretion in OME.

Antibodies, Monoclonal↗
PubMed2003

Short-term learning effects of practice during the performance of the tandem Romberg test.

The tandem Romberg test is possibly the most common static test of postural stability. This study aims to see if practice effects the performance of the tandem Romberg test. Twenty-four subjects were instructed to practice the tandem Romberg test daily for a period of 10 consecutive days, and were tested on five occasions using the sway magnetometry posturographic system. The test was performed with eyes open and eyes closed either on the floor or on foam. Their ability to perform the test for 60 s was used as a pass/fail criterion. With eyes closed, 65% of tandem Romberg tests were successful on hard surface, and 28% on foam. With eyes open, all subjects scored a 'pass'. On hard surface, the mean path length for the first and last day was 371.7 mm (SD 68.56) and 481 mm (SD 145.47) respectively. On foam, it was 506 mm (SD 139) and 530 mm (SD 212). For the 'fail' tandem Romberg tests, the 75th percentile for the time taken for subjects to perform the test on the first and last days were 18.5 and 9 s on floor, and 18 and 37 s on foam respectively. Across all testing sessions and groups, no significant improvement in performance with practice was observed. The absence of improvement in subjects practising the tandem Romberg test indicates a lack of short-term learning effects. The failure rate, however, associated with eye closure, whether on foam or on hard surface, invalidates the use of the tandem Romberg test in assessing postural stability because of its performance variability.

Adult↗
PubMed2002

p53 Expression and keratinocyte hyperproliferation in middle ear cholesteatoma.

Keratinocytes in middle ear cholesteatoma have hyperproliferative properties. There is controversy regarding the role of p53 and its effect on cellular proliferation in cholesteatoma. This study was instituted to examine this. Cholesteatoma and deep meatal skin control specimens were analysed for MIB-1 (n = 7, controls = 7), a marker of cellular proliferation, and p53 (n = 17, controls = 17) expression by immunocytochemistry. Expression of p53 was minimal or absent in both cholesteatoma and controls (P = 0.2). MIB-1 expression was higher, but not significantly so, in cholesteatoma than in controls (P = 0.09). Our study has shown no significant p53 expression in cholesteatoma epithelium. This suggests that there is no dysfunction in the p53-mediated cell cycle control mechanisms in cholesteatoma.

Cell Division↗
PubMed2001

Matrix metalloproteinases 2 and 9 in otitis media with effusion.

A qualitative and quantitative study of the presence of matrix metalloproteinase 2 (MMP 2) and matrix metalloproteinase 9 (MMP 9), in the effusions of otitis media with effusion (OME), was performed. The activity of the above enzymes was compared in thick and thin effusions, and concentrations compared in samples from children with one, two, three and four sets of ventilation tubes. The activity of both MMP 2 and MMP 9 was higher in thick than thin effusions, P = 0.07 and P = 0.04, respectively. The concentrations of MMP 9 did not vary with the number of tube insertions but those of MMP 2 did (ANOVA P < 0.05). MMPs may be involved in tympanic membrane damage and prognosis of OME.

Child↗
PubMed2001

Localization of matrix metalloproteinase 1 in cholesteatoma and deep meatal skin.

HYPOTHESIS: Matrix metalloproteinase 1 (MMP-1) is overexpressed in cholesteatoma. BACKGROUND: Cholesteatoma destroys bone, whereas deep meatal skin does not. MMP-1 is a type I collagenase that may be responsible for this destruction. This prospective study was designed to identify overexpression of MMP-1 by cholesteatoma in comparison with deep meatal skin. METHODS: Ten cholesteatoma specimens and nine deep meatal skin specimens were removed during otologic surgery and then fixed in formalin and embedded in paraffin. Immunocytochemistry studies were performed using a monoclonal antibody to MMP-1. A pathologist assessed the slides in a blinded fashion. Expression of MMP-1 protein in epidermis and in stroma was scored from 0 to 10. Five further cholesteatoma specimens and three deep meatal skin specimens underwent reverse transcriptase polymerase chain reactions to assess messenger ribonucleic acid production. Paired and unpaired Student's t tests were used to assess the difference in expression levels. RESULTS: Cholesteatoma stroma expressed significantly more MMP-1 protein than did deep meatal skin stroma (p = 0.04). MMP-1 was localized to stromal fibroblasts. There was no difference in the epidermal expression levels of the two tissue types (p = 0.42). The reverse transcriptase polymerase chain reaction showed expression at the messenger ribonucleic acid size of MMP-1 (262 base pair) in all cholesteatoma specimens examined. One deep meatal skin specimen showed a weak signal; no signal was seen in the other specimens. CONCLUSIONS: MMP-1 is overexpressed by the stromal fibroblasts present in cholesteatoma as compared with deep meatal skin. It is possible that these cells rather than the keratinocytes are responsible for bone destruction in this disease.

Cell Culture Techniques↗
PubMed2001

Up-regulation of mucin secretion in HT29-MTX cells by the pro-inflammatory cytokines tumor necrosis factor-alpha and interleukin-6.

The pro-inflammatory cytokines IL-6 and TNF-alpha have been implicated in the pathogenesis of otitis media with effusion (OME). A disease where goblet cells proliferate in a modified respiratory epithelium, leading to the accumulation of a mucin-rich effusion in the middle ear cleft. The MUC5AC and MUC5B mucin gene products have been identified as components of these effusions. To determine the effect of IL-6 and TNF-alpha on MUC5AC and MUC5B secretion we have used HT29-MTX goblet cells, which secrete both types of mucins. MUC5AC and MUC5B mucin secretion was measured by an enzyme-linked immunosorbent assay (ELISA) using a specific monoclonal antibody NCL-HGM-45M1 and polyclonal antiserum TEPA, respectively. Time response (0-72 hours) and dose response (1.5-150 ng/ml) studies were carried out. IL-6 and TNF-alpha stimulated MUC5AC and MUC5B mucin secretion in a time dependent manner, both in pre-confluent and post-confluent cells. IL-6 (15 ng/ml and 20 ng/ml) produced a low and prolonged stimulation of mucin secretion that persisted for 72 hours, with peak response at 24 hours after induction. The IL-6-mediated mucin secretion at 24 hours was concentration-dependent, with a maximal effect at 15 ng/ml. TNF-alpha (20 ng/ml) induced rapid stimulation of mucin secretion within the first 24 hours, with peak response at 7 hours after induction. IL-6 and TNF-alpha exposure significantly increased MUC5AC secretion, but not MUC5B secretion. Maximal levels of cytokine-induced mucin secretion were detected in pre-confluent cells that showed one and a half- and two-fold increases in MUC5AC secretion after IL-6 and TNF-alpha stimulation, respectively, in comparison with post-confluent cells. The results presented here suggest that IL-6 and TNF-alpha generate a differential up-regulation of mucin secretion and thus contribute to the expression of mucin genes in inflammatory responses.

Cell Division↗
PubMed2000

TNF-alpha in the regulation of MUC5AC secretion: some aspects of cytokine-induced mucin hypersecretion on the in vitro model.

TNF-alpha has been implicated in the aetiology of otitis media with effusion (OME), where goblet cells proliferate in a modified respiratory epithelium, leading to the accumulation of a mucin-rich effusion in the middle-ear cleft. The MUC5AC mucin gene product has been identified as a component of these effusions. Here we have used the HT29-MTX goblet cell line, which secretes MUC5AC mucin, as a model to study the effect of TNF-alpha on goblet cells. MUC5AC mucin was identified and quantitated with a monoclonal antibody NCL-HGM-45M1. TNF-alpha stimulates MUC5AC mucin secretion in a dose-dependent manner, with 20 ng/ml producing maximal stimulation. Both pre-confluent and confluent cells showed peak stimulation after 7 h, however the pre-confluent cells showed twice the level of mucin hypersecretion. These results suggest that TNF-alpha stimulation of mucin secretion could play an important role in the early acute phase of the development of OME. This hypersecretion of mucin could then lead to the failure of the mucociliary clearance system, resulting in the accumulation of a mucin-rich effusion in the middle ear and the movement to a more chronic phase of the disease.

Antibodies, Monoclonal↗
PubMed2000

The aetiology of otitis media with effusion: a review.

Otitis media with effusion (OME) is the most common cause of deafness in children in the developed world. In this article we aim to present an overview of current research developments on the aetiology of OME and the resulting implications for treatment. In the model we describe, the primary event is inflammation of the middle ear mucosa, usually due to the presence of bacteria. This leads to the release of inflammatory mediators, which cause secretion of a mucin-rich effusion by up-regulating mucin genes. Prolonged stimulation of the inflammatory response and poor mucociliary clearance lead to persistence of the middle ear fluid, giving rise to the clinical presentation of OME. We describe OME in the following sequence: the initial production of the effusion, the composition of the effusion produced, and factors impairing clearance of the effusion.

Humans↗
PubMed1998

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.

Amino Acids↗
PubMed1997

Compositional differences between bilateral middle ear effusions in otitis media with effusion: evidence for a different etiology?

The aim of this study was to clarify the site of primary pathology in otitis media with effusion. Effusions were collected from 64 children with bilateral effusions at the time of myringotomy. The rheological properties and biochemical compositions of effusions were measured for 23 pairs of effusions, and the levels of the inflammatory mediators TNF alpha, IL-1beta, and IL-8 were measured in 41 pairs using specific enzyme-linked immunosorbent assays (ELISAs). Measurements from paired ears were compared using analysis of variance (ANOVA) tests and significant differences were found for reduced specific viscosity, mucin content, protein content, and levels of IL-8. The results demonstrate that the two ears have different immunological processes or rates of processes which might explain the significantly different rheological properties of effusions. This suggests that each ear undergoes pathological changes independently and has implications for using the opposite ear as a control in clinical trials.

Analysis of Variance↗
PubMed1997

Identification of non-organic instability by sway magnetometry.

This paper describes the application of sway magnetometry, which objectively measures stability, to assist in the identification of non-organic instability. Three subject groups were studied; 14 normal subjects, 14 subjects with organic dizziness, and 19 subjects assessed as having possible non-organic dizziness before further clinical investigation. Eight of these 19 were subsequently classed as having non-organic dizziness on grounds of their history, clinical examination and standard audio-vestibular investigations. Movement in the horizontal plane at the hips was measured by sway magnetometry in each subject. The absolute and percentage change in path length and area were determined for 15 s before and 15 s after the subject was informed that the test was starting. For absolute path length and area, five out of the eight subjects with non-organic dizziness showed an increase in sway above the upper limit of normal, while only one out of the other 11 subjects in the group showed such an increase (P < 0.02). None of the subjects in the normal or organic group exceeded the upper limit of normal when results were expressed as absolute change in path length or area. Sway magnetometry can provide valuable data to assist the clinician in identification of non-organic dizziness.

Adolescent↗
PubMed1996

Fourth branchial arch fistula.

A case is presented of a rare congenital anomaly of the fourth branchial arch, which presented as an abscess in the anterior triangle, related to a fistula communicating with the pyriform fossa. Histopathological examination showed the fistula to be associated with thyroid tissue supporting the hypothesis that the ventral wing of the fourth pouch contributes to the thyroid gland.

Abscess↗
PubMed1996

The effect of electrode position in electrocochleography.

This study assessed the effect of needle electrode position on the human cochlear summating potential (SP) obtained by transtympanic electrocochleography (ECochG). Electrocochleography was performed on 10 subjects with large central tympanic membrane perforations with good cochlear function, and in whom a needle electrode could be accurately placed in a series of five pre-determined positions in the middle ear. A comparison of the electrocochleograms revealed a wide scatter of results between different positions in the same patient and between similar positions in different patients. Only when the needle was repositioned at an almost identical recording site in the same subject, was good reproducibility achieved. Such a wide and unpredictable variation in results would suggest great caution is needed when comparing traces obtained using a transtympanic technique which precludes a view of the electrode tip.

Adult↗
PubMed1996

Measurement of the vestibulo-ocular reflex by magnetometry during active head movement.

A new method of measuring the vestibulo-ocular reflex (VOR) during active head movements is presented. Subjects sat and attempted to maintain their gaze upon a fixed point whilst turning their heads from side to side in response to an auditory cue, to attain frequencies of head rotation that increased from 1 Hz to 4 Hz during a 24 s period. Head movements were monitored by a small magnetic field detector worn on the subject's forehead and positioned a set distance from a magnetic field transmitter coil. Eye movements were monitored using the corneo-retinal potential. Gain (eye angle/head angle) and phase difference (eye phase-head phase) were calculated to define the VOR. Three repeat measurements were made on 20 normal subjects. Gain decreased significantly (P < 0.0001) with increasing frequency whilst the phase difference remained unchanged. The 95% prediction intervals were narrow for both gain (+/- 0.28) and phase (+/- 11 degrees). These data, together with the speed and ease of performance of the test, suggest that the test can provide valuable information on the performance of the vestibular system.

Adult↗