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Biomedical subjects

M A Birchall

Publications and source records attributed to M A Birchall.

At least 19 recordsLinked to original sources
PubMed1999

A preclinical model for laryngeal transplantation: anatomy and mucosal immunology of the porcine larynx.

BACKGROUND: A major step in translating work on laryngeal transplantation into clinical practice is the establishment of a preclinical model. We have investigated the anatomy and mucosal immunology of the porcine larynx in eight Minnesota Minipigs (12-37 weeks). METHODS: Neck dissections were carried out and the vascular tree was mapped. Snap-frozen biopsies from epiglottis, supraglottis, glottis, and subglottis were prepared for conventional histology, immunohistochemistry (CD45), and single and two-color immunofluorescence (CD3, MHC-II, CD45). RESULTS: The anatomy of the laryngeal skeleton was broadly similar to that of the human larynx. The blood supply is predominantly via the caudal thyroid vessels, with assistance from the cranial laryngeal artery. The porcine larynx is clearly highly immunologically active. Structured collections of leukocytes were found in the mucosal epithelium, around tubuloacinar glands, and occasionally in the submucosa. MHC-II and CD 3 cells were predominantly found within the epithelium. The highest densities of all cell types were observed in the epiglottis, tailing off caudally. The lowest densities were seen in the vocal cords. CONCLUSIONS: The porcine larynx is both anatomically and immunologically similar to the human larynx and contains a high level of immunological organization. It presents an ideal preclinical model for laryngeal transplantation.

Animals↗
PubMed1999

Do corticosteroids induce apoptosis in nasal polyp inflammatory cells? In vivo and in vitro studies.

OBJECTIVE/HYPOTHESIS: Corticosteroids are an effective treatment for nasal polyposis. The exact mechanism of action is not certain. Recent research demonstrates that apoptosis (programmed cell death) in inflammatory cells is an important factor in the resolution of inflammation, and apoptosis is induced in eosinophils in cell culture with steroids. We hypothesized that inflammatory cell apoptosis is a key feature of regression of nasal polyps on exposure to steroids and examined this hypothesis in vivo and in vitro. METHODS: A double-blind, placebo-controlled pilot study of fluticasone propionate aqueous nasal spray (FPANS) in nasal polyposis in humans in vivo was undertaken, and the effect of treatment on indices of cell death and proliferation measured. In addition, explants of nasal polyp tissue were maintained in vitro in short-term tissue culture with dexamethasone at increasing doses (0.1-50 micromol) over varying time intervals and then analyzed for similar indices of proliferation and cell death. RESULTS: Apart from a marginal increase in apoptotic:mitotic ratio in epithelium, little difference between the effect of FPANS and placebo was demonstrated in vivo. However, in vitro, apoptotic index was significantly increased in the stromal layers in relation to time of incubation (P = .0169), and a significant dose-response relationship was demonstrated at 24 hours between stromal cell apoptosis and dexamethasone concentration (P = .001). Eosinophil apoptosis was confirmed by in situ end labeling and transmission electron microscopy. No steroid or time effect on epithelial cells was demonstrated in vitro. CONCLUSION: Corticosteroids induce apoptosis in inflammatory cells in human nasal polyps in vitro. This is not reflected by a similar response to FPANS at 14 days in vivo, but may still play a part in regression of polyps with other forms of administration or at other time points.

Administration, Topical↗
PubMed1998

Morphometry of paranasal sinus anatomy in chronic rhinosinusitis: a pilot study.

OBJECTIVES: To test the null hypothesis that there is no relationship between anatomical variations around the ostiomeatal complex and a predisposition to chronic rhinosinusitis and to define such variations with increased precision. DESIGN: Case-control study of anatomical variations in diseased and normal sinuses. Eight homologous landmarks defining the ostiomeatal complex were located on coronal computed tomographic scans, and their x and y coordinates were digitized using image analysis. SUBJECTS: Ten patients with unilateral sinus disease and 10 subjects without sinus disease (scanned for facial pain) who were selected retrospectively by case-note analysis. RESULTS: Logistic regression showed that the only significant spatial change predictive of a person with rhinosinusitis was the vertical position of the middle turbinate (P=.04), although this was not confirmed by Wilcoxon testing (P>.10). When examined by sinus, however, the horizontal position of the uncinate process was more laterally placed in persons with rhinosinusitis (P=.01), confirmed on Wilcoxon testing (P=.04), but there was no significant difference when compared with sinuses in persons without rhinosinusitis. CONCLUSIONS: Our findings suggest that there are no anatomical differences within the ostiomeatal complex between patients with and without rhinosinusitis. Patients with rhinosinusitis, however, are more likely to develop it in the side with a more laterally positioned uncinate process. Further studies, with more patients and more advanced techniques, including thin-plate spline analysis, are indicated.

Case-Control Studies↗
PubMed1998

A comparison of the anti-histone and Apop-Tag technique for demonstrating apoptosis with option for silver enhancement.

A novel immunocytochemical method is presented for the qualitative detection of DNA fragmentation in apoptosis. Anti-histone antibody is employed to localize exposed nucleosomal histones (H1, H2a, H2b, H3 and H4) rather than tagging the cut ends of fragmenting DNA as in conventional technique. The method was tested on squamous cell carcinoma of the larynx routinely fixed in formaldehyde and embedded in paraffin wax and compared with results obtained employing Apop-Tag kit (Oncor).

Apoptosis↗
PubMed1998

Laryngectomees' views on laryngeal transplantation.

Loss of a functional larynx has marked implications for quality of life that remain after both laryngectomy and its alternatives. One solution is laryngeal transplantation. We hypothesised that laryngeal transplantation would be unacceptable to a population of laryngectomees, and that such a lack of acceptability would not be affected by age, sex or time elapsed since operation. In addition, we sought the views of laryngectomees on priorities for research. A questionnaire was developed and mailed to 1000 members of laryngectomee clubs. A total of 372 of 404 responses were suitable for analysis. Seventy-five percent of the respondents said they would accept a transplant under ideal conditions; the number dropped to 58.9% when a stoma was to be retained. Fifty percent would accept a graft even if it did not result in a normal voice. A positive response was more likely in younger respondents (P < 0.001 all questions; linear regression). Some 47.3% of respondents thought research money could be better spent on other projects, and this response was commoner in older respondents (P = 0.0001). Highest priorities for research into laryngeal cancer were development of new treatments (63.2%), prevention (60.2%) and optimisation of quality of life (57%). In short, there appears to be a surprisingly high level of support for laryngeal transplantation amongst those who have had a laryngectomy.

Age Factors↗
PubMed1998

Consensus standards for the process of cancer care: a modified expert panel method applied to head and neck cancer. South and West Expert Tumour Panel for Head and Neck Cancer.

There are many pressures to improve the standard of care delivered to cancer patients, including the reforms subsequent to the Calman-Hine report. The establishment of standards is a prerequisite for audit, benchmarking and certification of cancer centres and units. Randomized trials of head and neck cancer are uncommon, and other forms of evidence often conflicting. In the south and west of England, a multidisciplinary expert panel consensus method has been applied to the development of standards. A panel representative of specialties involved in the process of care at all three levels, plus social medicine and lay members, was constructed. A model for the process of care was developed consisting of activity areas. For each activity, a near exhaustive list of tasks and standards was established. A three-iteration method with statistical group response was then used to refine the standards. The same method was also applied to the production of a minimum data set for registration, recording and audit. The resulting standards will be regularly reviewed. We have developed a model of the care process, and an expert panel methodology that is applicable to a wide range of problems in clinical oncology.

Head and Neck Neoplasms↗
PubMed1997

Fluticasone.

Explore the source record for details and available documents.

Androstadienes↗
PubMed1997

Head and neck cancer in the South West of England: influence of socio-economic status on incidence and second primary tumours.

This study examined possible links between the incidence of head and neck squamous cell carcinoma (HNSCC) and social deprivation. Data on all HNSCC registered between 1985 and 1991 in the South West of England were collected. Excluding tumours of the lip and skin there were 1570 cases, 72% in males. Of these, 1467 were identified as first primary tumours. Corrected chi-squared tests, accepting significance at the 5% level, were used to examine the association of socio-economic status (Carstairs index) with incidence at different sites. Overall, the incidence of HNSCC was higher in the socially deprived group. In males, the most deprived group had a significantly higher incidence of oral carcinoma than all other groups (P<0.05), whereas the incidence of laryngeal carcinoma showed a gradual rise with increasing deprivation. In females, where numbers were relatively low, the trend remained, but was less clear. In total, seventy-two (4.9%) cases went on to develop a second primary, of which 35% were in the lung and 13% in the bladder. Socio-economic status did not affect the development of a second primary tumour. The association of HNSCC with carcinoma of the bladder is a new finding.

Adult↗
PubMed1997

Apoptosis, mitosis, PCNA and bcl-2 in normal, leukoplakic and malignant epithelia of the human oral cavity: prospective, in vivo study.

Disordered balance between proliferation and apoptosis may contribute to carcinogenesis. Thirty-two oral biopsies were collected prospectively: 10 normal (N), 10 leukoplakia (dysplasia, D = 5; hyperplasia, H = 5) and 12 squamous cell carcinoma (C: 11). Distant normal tissue was also collected (HN, DN, CN). Based on counts of 1000 cells/slide, mitotic (MI), apoptotic (AI) and proliferating cell nuclear antigen (PCNA: PI) indices were calculated and bcl-2 expression recorded. AI correlated with MI (P < 0.001), but not PI or bcl-2 expression. PCNA was higher in H and HN than other groups (P < 0.0001). bcl-2 was reduced in C and CN (P < 0.001). Peak mitosis shifted basally in dysplasia, whilst peak apoptosis remained unaltered. These data confirm topographical alterations in proliferation relative to apoptosis in dysplasia of the oral cavity. Reduced bcl-2 in carcinoma and related 'normal' epithelium was unexpected, and may contribute to the high incidence of metachronous carcinomas in these patients.

Apoptosis↗
PubMed1996

The ENT manifestations of HIV infection in children.

This study identified the ENT symptoms of 66 HIV infected children over an 8 year period (1986-1993) at Great Ormond Street Hospital for Children. The incidence, nature and age of onset of ENT symptoms were investigated; 91% of the children had ENT symptoms, the most common being cervical lymphadenopathy, oro-oesophageal candidiasis and otitis media. The HIV infected children suffered from the common ENT diseases of childhood. They also presented with specific conditions such as diffuse parotid swelling. Therefore, their clinical features differed from HIV infected adults as well as non-infected children. An increasing incidence of paediatric HIV infection was demonstrated by the study. Most were due to vertical transmission. ENT surgeons are likely to see more HIV infected children in future, either with the usual ENT diseases of childhood (to which they seem more susceptible) or with HIV-specific conditions. Although the diagnosis of HIV may be known, the ENT condition could be the initial presentation suggestive of immunodeficiency.

Adult↗
PubMed1996

A comparison of the effects of an alpha-agonist, an anti-muscarinic agent and placebo on intranasal histamine challenge in allergic rhinitis.

Autonomic receptors play a part in the physiology and pathology of the nasal mucosa. The effect of an alpha-agonist and an anti-muscarinic agent on histamine-challenge was examined on patients with perennial allergic rhinitis. Nine patients received saline, oxitropium bromide 0.075%, or xylometazoline hydrochloride 0.1% in a double-blind fashion. Sequential challenge with increasing doses of histamine were given and resistance changes, sneezes and volume and content of secretion measured. Histamine challenge produced dose-related increases in nasal resistance (P < 0.0001), lavage fluid volume (P < 0.01) and total protein (P < 0.01). Following xylometazoline, histamine produced little increase in resistance compared with saline and oxitropium bromide (P < 0.0001). The latter reduced the dose-related increase in resistance (P < 0.01) and nasal lavage fluid volume (P = 0.0007) and total protein (P = 0.023) seen with saline. These results confirm the importance of alpha-adrenergic and muscarinic receptors in the human nasal mucosa and suggest mechanisms of action for these drugs in perennial allergic rhinitis.

Adrenergic alpha-Agonists↗
PubMed1995

Apoptosis in normal epithelium, premalignant and malignant lesions of the oropharynx and oral cavity: a preliminary study.

To explore the involvement of apoptosis in the development of oral and oropharyngeal squamous cell carcinoma (SCC) in vivo, biopsies were taken from patients with macroscopically normal (n = 6), leukoplakic (n = 12) or malignant (n = 8) mucosa. Leukoplakic lesions were divided histologically into dysplasia (n = 5) or carcinoma in situ (CIS: n = 7). Material was prepared for light and electron microscopy. The apoptotic index (AI), vertical cell position of apoptoses (cp), mitotic index (MI) and AI:MI ratio were calculated for each patient. AI increased from 0.12% +/- 0.07 S.E.M. (normal) to 0.58 +/- 0.13 (CIS) but fell to 0.14 +/- 0.14 in SCC. Apoptoses were suprabasal in normals, but generalised in CIS. MI increased from normal (0.20 +/- 0.06) to SCC (0.32 +/- 0.09), and AI:MI was at its maximum in CIS (1.57; SCC: 0.44). The results suggest that a change in apoptosis accompanies the onset of invasion in a premalignant lesion of the human oral cavity and oropharynx.

Adolescent↗
PubMed1995

The effect of topical fluticasone propionate on intranasal histamine challenge in subjects with perennial allergic rhinitis.

The mechanism of action of topical intranasal steroids is obscure. To investigate this, we have studied the effects of a topical intranasal corticosteroid, fluticasone propionate on nasal airflow resistance (Rnaw), secretions, cytological smears and symptoms. Fluticasone propionate aqueous nasal spray was given to 11 patients with perennial allergic rhinitis in a double-blind, placebo-controlled study. On each day, patients were challenged with ascending doses of histamine. Rnaw, secretion volume, total protein, mucin, lysozyme and albumin were measured. Nasal smears were taken and sneezes counted. Diary card data were collected for both treatment periods. There was a significant, dose-related increase in Rnaw and sneezing on histamine challenge. A single dose of fluticasone had no effect on any parameter. After 4 weeks of treatment, resistance measurements were reduced (post-challenge g.m.2.8 cmH2O/l/s, Q1-Q3 1.6-4.8; placebo 4.2, 2.9-5.3: P < 0.0001) as were baseline secretion volumes (mean 2.4 ml/5 min, c.i.1.9-3.0; placebo 3.3, 2.8-3.8: P < 0.05). Eosinophil counts were suppressed (fluticasone 5.8%, c.i. 4.0-15.7; placebo 23.3%, 12.4-34.1: P < 0.05) and the composite symptom score reduced (P < 0.05). Fluticasone has long-term effects on the nasal response to histamine in perennial allergic rhinitis and part of this effect is likely to be vascular.

Administration, Topical↗