M. W. Green

Quantitative exfoliative cytology of abnormal oral mucosal smears.

In this study quantitative techniques have been applied to smears collected from the buccal mucosa and floor of the mouth. The results display an encouraging success rate for identifying premalignant and malignant lesions. ‘Intrapatient’ normal smears provide a satisfactory control for comparison with pathological smears. Early results indicate that quantitative cytology could be of great value for monitoring and follow-up of suspicious lesions and provide an excellent additional diagnostic test for detecting early oral malignancy.

Apoptosis, proliferation, and angiogenesis in oral tissues. Possible relevance to tumour progression

Experimental animal models have demonstrated that angiogenesis is essential for tumour progression, whilst sustained tumour growth requires a positive balance between tumour cell proliferation and cell death (apoptosis). The aim of this study was to determine the relative contribution of apoptosis, proliferation, and angiogenesis to disease progression in the oral mucosa. Histological sections of 47 archival specimens were examined; these included four groups of oral tissues: normal mucosa (n=12), moderate dysplasia (n=11) severe dysplasia (n=6), and squamous cell carcinoma (n=18). Apoptotic cells were visualized by in‐situ end‐labelling of DNA, proliferative cells by staining with Ki‐67 antibody, and blood vessels with von Willebrand factor (vWF) antibody. One‐way analysis of variance showed that indices of apoptosis (AI), proliferation (PI), and angiogenesis (vascularity) increased significantly with disease progression from normal oral mucosa, through dysplasia, to carcinoma (p<0.0001 for every index). The increase from normal mucosa to moderate dysplasia was significant for PI and vascularity, but not for AI. In contrast, the increase from dysplasia to carcinoma was significant for AI and vascularity, but not for PI. These data suggest that disease progression in the oral mucosa is accompanied by angiogenesis and increases in both epithelial proliferation and apoptosis. Net epithelial growth results from proliferation starting earlier and proceeding at a higher rate than apoptosis. Copyright

Demographics of the UK cystic fibrosis population: implications for neonatal screening

The objective was to determine the composition of the Cystic Fibrosis (CF) Population attending specialist UK CF centres in terms of age, gender, age at diagnosis, genotype and ethnicity. With the planned introduction of the national CF screening programme in the UK, cystic fibrosis transmembrane regulator (CFTR) mutations were compared between different ethnic groups enabling a UK-specific frequency of mutations to be defined. Data were analysed from the patient biographies held in the UK CF Database (see www.cystic-fibrosis.org.uk). The currently registered population of 5274 CF patients is 96.3% Caucasian with a male preponderance that significantly increases with age. The majority of the 196 non-Caucasian CF patients are from the Indian Subcontinent (ISC), of which one in 84 UK CF patients are of Pakistani origin. The commonest CFTR mutation, ΔF508, is found in 74.1% of all CF chromosomes. In the Caucasian CF population, 57.5% are ΔF508 homozygotes but the UK ISC CF population with only 24.7%, has significantly fewer ΔF508 homozygotes patients (95% confidence interval (CI) 0.2–0.4). The distribution of Caucasian patients with ΔF508/ΔF508, ΔF508/Other and Other/Other does not fit the expected distribution with a Hardy–Weinberg model unless those patients without a detected mutation are excluded (P<0.001). The UK CF Database has shown the UK CF population to have distinct characteristics separate from the North American and European CF Registries. The ISC group contains many mutations not recognised by current genetic analysis, and one in four ISC patients have no CFTR mutations identified. The CFTR analysis proposed for the screening programme would detect 96% of patients registered in the database, but is unlikely to achieve the desired >80% detection rates in the ethnic minority groups. Screen-positive, non-Caucasian infants without an identifiable CFTR mutation should be referred for a sweat test and genetic counselling when serum trypsinogen concentrations remain elevated after birth.

Quantitative exfoliative cytology of normal oral squames: an age, site and sex-related survey.

This study describes the development of quantitative cytological techniques and their application to oral smears. Nuclear and cell size has been measured and matched with age, sex and site in an attempt to produce a baseline for comparison with identical measurements carried out on pathological smears. The results displayed a significant variation in nuclear and cytoplasmic area between different sites. Nuclear size varied significantly with advancing age; however, this was not the case for cytoplasmic area. There was no significant variation in either criterion between males and females.

Detection of field change in oral cancer using oral exfoliative cytologic study

Four smears were taken from the normal buccal mucosa of 55 oral cancer patients and 76 cancer‐free patients. In each case, two were stained by the Papanicolaou method and two underwent Feulgen hydrolysis. Quantitative assessment of nuclear area (NA) and cytoplasmic area (CA) of the Papanicolaou smears was undertaken using a semiautomatic image analysis system. DNA profiles were assessed from the Feulgen smears using a Vickers M85 microdensitometer (Vickers Instruments, York, England) and were found to be diploid for all patients. Results were then analyzed with respect to those patients who took alcohol, tobacco, combination of alcohol and tobacco, and those who took neither. A significant reduction in CA for the oral cancer group (P equals 0.001) but no change in NA (P equals 0.74) was observed. A detailed analysis of alcohol and tobacco habits could identify no significant role for these two factors, in the reduction in cytoplasmic area. Such field change may prove to be of value in predicting the development of second malignant tumors.

The association between epithelial proliferation and disease progression in the oral mucosa

The purpose of this study was to examine the possible association between epithelial proliferation and disease progression in the oral mucosa. Archival specimens of normal oral mucosa (n = 12), dysplasia (n = 17) and squamous cell carcinoma (n = 18) were sectioned and proliferating cells visualised by staining with Ki-67 antibody. The proliferative index of the epithelium (PI) was determined by total cell counts and point counting. Similar results were obtained using either method. Comparison of the three groups of tissues by one-way analysis of variance showed a significant increase in PI with increasing lesion severity (p < 0.001). The PI of both dysplasia and carcinoma groups was significantly higher than that of normal oral mucosa (p < 0.001). However, the difference between dysplasia and carcinoma groups was not significant. PI was not associated with tobacco or alcohol consumption. We therefore conclude that Ki-67 expression is an early marker of disease progression in the oral mucosa but, on its own, is not a good indicator of neoplastic transformation.

Evidence of field change in oral cancer

Evidence of field change in oral cancer was assessed using quantitative cytomorphometric analysis of smears taken from normal buccal mucosa in oral cancer and cancer-free patients. The nuclear areas (NA) and cytoplasmic areas (CA) were calculated using a semi-automatic image analysis system. A statistically significant reduction in CA (p = 0.002) but no change in NA was observed for the oral cancer group. This change occurred irrespective of tobacco and alcohol usage. We believe this to be the first evidence for true field change since Slaughters original hypothesis in 1946.

Comparison of Planimetry and Image Analysis For the Discrimination Between Normal and Abnormal Cells In Cytological Smears of Suspicious Lesions of the Oral Cavity

Light microscope analysis of cytological smears of suspicious lesions of the oral cavity is used as a method for detecting early cancer in the oral cavity. the sensitivity of this approach can be improved by quantitative analysis of the cells in the cytological smears.

Effect of radiotherapy on oral mucosa assessed by quantitative exfoliative cytology.

The effect of radiotherapy on normal buccal mucosa was investigated using the quantitative techniques of cytomorphology (measurement of nuclear and cytoplasmic area) and DNA cytophotometry. These techniques were applied to smears obtained before, during, and after irradiation. Nuclear area and cytoplasmic area increased and DNA values were abnormal in most cases as a result of radiotherapy, returning to within normal limits one month after treatment. This contrasts strongly with the changes seen in smears from previously irradiated uterine cervices, where changes in cytomorphology may persist for several years.

On FitzHugh's nerve axon equations

SummaryAfter discussing some general properties which we think desirable in a nerve axon model, we consider a system first proposed by FitzHugh. We show that, assuming the existence of travelling wave solutions, the speed of propagation is bounded above and below.