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Biomedical subjects

S Warnakulasuriya

Publications and source records attributed to S Warnakulasuriya.

At least 37 records · Page 2Linked to original sources

Oral cancer screening as an integral part of general health screening in Tokoname City, Japan.

OBJECTIVES: To measure the attendance and compliance rates in oral mucosal screening (OMS) offered as part of a general health screen (GHS) undertaken as an organised programme in Japan. METHODS: In 1996, all adults over the age of 40 years resident in Tokoname City were invited by letter to attend a free GHS annually, conducted by the municipal cooperation and the medical and dental societies of Tokoname City. In the later years only those who attended in 1996 were reinvited. Females aged less than 39 years were also allowed to attend if they wished to participate in the GHS. The GHS consisted of completion of a self administered questionnaire to identify past and current illnesses and any medications used by the screened population coupled with a routine physical check, chest x ray, ECG, and blood and urine examination. The GHS was programmed annually during the years 1996 to 1998. All those attending the GHS were invited to participate in an OMS conducted under the same roof by a visiting dentist (n=37). A referral pathway was established for screen positives requiring follow up. RESULTS: A total of 19 305 subjects (5955 males, 13350 females; mean age 59.2 years; 7033 in 1996, 6289 in 1997, and 5983 in 1998) attended the GHS. Of those who attended the GHS, 19 056 (98.7%) attended the OMS (1.3% refused). This rate was fairly constant over the three years. Excluding repeat examinations, new cases recruited for OMS over the three years were 8723. Of those participating in OMS, 4269 (60.7%) attended all three years. In the cohorts examined, screening dentists recorded oral mucosal lesions in 5.4% in 1996, in 4.0% in 1997, and in 2.6% in 1998. Overall, this amounted to a positive detection rate of 4.1%, or 4.9% excluding repeat examinations. A higher prevalence of oral pre-cancer was recorded among male smokers. CONCLUSIONS: The overall results suggest that although compliance with attending a free GHS was low (26.2%) among Japanese subjects over 40 years of age, of those who complied 74-76% reattended annually. Hence a satisfactory participation rate can be obtained in Japan for OMS when this is coupled to a GHS conducted at the same visit.

Adult↗

Role of p16/MTS1, cyclin D1 and RB in primary oral cancer and oral cancer cell lines.

One of the most important components of G1 checkpoint is the retinoblastoma protein (pRB110). The activity of pRB is regulated by its phosphorylation, which is mediated by genes such as cyclin D1 and p16/MTS1. All three genes have been shown to be commonly altered in human malignancies. We have screened a panel of 26 oral squamous cell carcinomas (OSCC), nine premalignant and three normal oral tissue samples as well as eight established OSCC cell lines for mutations in the p16/MTS1 gene. The expression of p16/MTS1, cyclin D1 and pRB110 was also studied in the same panel. We have found p16/MTS1 gene alterations in 5/26 (19%) primary tumours and 6/8 (75%) cell lines. Two primary tumours and five OSCC cell lines had p16/MTS1 point mutations and another three primary and one OSCC cell line contained partial gene deletions. Six of seven p16/MTS1 point mutations resulted in termination codons and the remaining mutation caused a frameshift. Western blot analysis showed absence of p16/MTS1 expression in 18/26 (69%) OSCC, 7/9 (78%) premalignant lesions and 8/8 cell lines. One cell line, H314, contained a frameshift mutation possibly resulting in a truncated p16/MTS1 protein. pRB was detected in 14/25 (56%) of OSCC but only 11/14 (78%) of these contained all or some hypophosphorylated (active) pRB. In premalignant samples, 6/8 (75%) displayed pRB, and all three normal samples and eight cell lines analysed contained RB protein. p16/MTS1 protein was undetectable in 10/11 (91%) OSCCs with positive pRB. Overexpression of cyclin D1 was observed in 9/22 (41%) OSCC, 3/9 (33%) premalignant and 8/8 (100%) of OSCC cell lines. Our data suggest p16/MTS1 mutations and loss of expression to be very common in oral cancer cell lines and less frequent in primary OSCC tumours. A different pattern of p16/MTS1 mutations was observed in OSCC compared to other cancers with all the detected p16/MTS1 mutations resulting in premature termination codons or a frameshift. The RB protein was expressed in about half (44%) of OSCCs and its expression inversely correlated with p16/MTS1 expression. In conclusion, we show that abnormalities of the RB pathway are a common mechanism of oral carcinogenesis.

Carcinoma, Squamous Cell↗

Oral mucosal lesions associated with betel quid, areca nut and tobacco chewing habits: consensus from a workshop held in Kuala Lumpur, Malaysia, November 25-27, 1996.

A variety of betel/areca nut/tobacco habits have been reviewed and categorized because of their possible causal association with oral cancer and various oral precancerous lesions and conditions, and on account of their widespread occurrence in different parts of the world. At a recent workshop in Kuala Lumpur it was recommended that "quid" be defined as "a substance, or mixture of substances, placed in the mouth or chewed and remaining in contact with the mucosa, usually containing one or both of the two basic ingredients, tobacco and/or areca nut, in raw or any manufactured or processed form." Clear delineations on contents of the quid (areca nut quid, tobacco quid, and tobacco and areca nut quid) are recommended as absolute criteria with finer subdivisions to be added if necessary. The betel quid refers to any quid wrapped in betel leaf and is therefore a specific variety of quid. The workshop proposed that quid-related lesions should be categorized conceptually into two categories: first, those that are diffusely outlined and second, those localized at the site where a quid is regularly placed. Additional or expanded criteria and guidelines were proposed to define, describe or identify lesions such as chewer's mucosa, areca nut chewer's lesion, oral submucous fibrosis and other quid-related lesions. A new clinical entity, betel-quid lichenoid lesion, was also proposed to describe an oral lichen planus-like lesion associated with the betel quid habit.

Areca↗

p53 alterations and HPV infections are common in oral SCC: p53 gene mutations correlate with the absence of HPV 16-E6 DNA.

To examine the association between HPV infections and p53 gene aberrations, a panel of 28 oral squamous cell carcinomas (SCC) and 12 potentially malignant oral mucosal lesions were analysed for p53 mutations in exons 2-9. p53 protein was analysed by immunocytochemistry using DO7 antibody. The same panel was also examined for the possible presence of HPV infection. p53 overexpression was detected in 13/26 (50%) malignant and 2/9 (22%) premalignant lesions. Mutations in the coding region of the p53 gene were found in 10 malignant samples. None of the premalignant lesions were shown to have p53 mutations. The total number of p53 mutations in 10 samples were 14 of which 12 (85%) were in exon 5 suggesting the presence of hot spots in exon 5 for carcinogens involved in the transformation of oral epithelial cells. The presence of HPV DNA was first screened with consensus primers to the L1 region and nested PCR approach. HPV 6 and HPV 16 were detected in 14/28 (50%) oral SCC and 4 of 12 (33%) precancerous lesions, 7 tumours harboured both types. The samples were then examined for the presence of E6 oncogenic sequence of HPV16 using E6 specific primers. 7/27 (26%) SCC and 5/9 (55%) premalignant lesions harboured E6 DNA of which 6 (3 SCC and 3 premalignant) were negative with L1 primers suggesting possible integration of the specific viral genes or loss of other viral DNA sequences after integration of larger viral fragments. 9/10 (90%) SCC with p53 mutations were negative for E6 DNA. Our results show that both p53 alterations and HPV infection may be important etiological factors in the development of oral cancer. However, there is: i) No concordance between p53 mutations and its overexpression. ii) the presence of HPV capsid DNA (L1) does not necessarily indicate the presence of HPV oncogenic genes. iii) p53 gene mutations, but not overexpression, correlate with the absence of HPV 16-E6 and not L1 gene.

Aged↗

Evaluation of multiple micronutrient supplementation in the management of oral submucous fibrosis in Karachi, Pakistan.

Oral submucous fibrosis (OSF) is an oral precancerous condition characterized by symptoms such as intolerance to spicy food, altered salivation, progressive difficulty in opening the mouth, and signs like vesiculation, ulceration, blanching, rigidity, and stiffening of the oral mucosa and depapillation and altered mobility of the tongue. It is seen mostly among people of Indian subcontinent origin. The major structural change is extensive fibroelastic scarring of the lamina propria and deeper connective tissues. A combination of micronutrients (vitamins A, B complex, C, D, and E) and minerals (iron, calcium, copper, zinc, magnesium, and others) was evaluated for its efficacy in controlling the symptoms and signs of OSF in 117 compliant subjects in Karachi, Pakistan, in a single-arm preliminary study. The subjects received supplementation for one to three years. Significant improvement in symptoms, notably intolerance to spicy food, burning sensation, and mouth opening, was observed at exit. The interincisor distance deteriorated in 11 subjects (10%) at exit; it was stable in 56 subjects (49%) and improved in 48 (41%). The mean interincisor distance was 19.1 +/- 10.8 (SD) mm at exit compared with 16.2 +/- 7.5 mm at baseline. A significant proportion of concomitant lesions like leukoplakia also regressed at exit. The major outcome from this study was a beneficial clinical response in subjects with OSF to multiple micronutrient intervention, which justifies its further evaluation in well-designed randomized controlled trials in other settings in South Asia.

Adolescent↗

Our third year.

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Europe↗

Caries susceptibility of first permanent molars and treatment needs in Sri Lankan children, aged 13-16 years, in 1986.

The caries status of the permanent first molar was studied in 683 school children (aged 13-16 years) selected from six schools in Kandy. Radike (1972) criteria were used for the examination. Of 2732 first molars examined, 37 per cent were found to be carious, filled or missing. Susceptibility to caries was higher in mandibular molars (47 per cent) than in maxillary molars (25 per cent). In 36 per cent of the children all four molars were sound, while in 11 per cent they were all affected by caries. Of 998 DMF units, 676 (68 per cent) were decayed, 189 (19 per cent) filled and 133 (13 per cent) extracted. Seventy-nine per cent of the DF sites were occlusal. Results suggest that a high proportion of carious permanent molars have been neglected without the seeking of professional care. Approaches for preventive and restorative care for the permanent first molar tooth, appropriate in Third World countries, are suggested.

Adolescent↗

Reliability of oral precancer screening by primary health care workers in Sri Lanka.

The accuracy of the field diagnosis is of crucial importance in the successful implementation of a screening programme. In Sri Lanka, the feasibility of using primary health care workers for oral cancer and precancer screening was pilot tested between 1980 and 1982. This paper analyses in detail the categories of false positives referred and the false negatives detected following screening. Among 660 subjects who arrived at the referral centre following screening, 64 (10 per cent) had no apparent oral lesion. The predictive value determined in this study was 58 per cent for a referrable lesion and 98 per cent for non referrable cases.

Adult↗

Compliance following referral in the early detection of oral cancer and precancer in Sri Lanka.

An innovative approach for the early detection of oral cancer and precancer within the context of the primary health care system has been field tested in Sri Lanka. The overall compliance in accepting this particular PHC approach for cancer screening, as estimated by arrival at a referral centre manned by consultant staff, was 54.1%. Nearly 80% of those who turned up without needing an additional reminder, did so within the first 2 weeks of case finding. There was a variation in the degree of compliance depending on the primary health care worker who did the screening and referral. Compliance was greater when the screening area was nearer to the referral centre and in subjects who were diagnosed as having a more advanced stage of the disease. Certain practical considerations that contributed to noncompliance were identified. Postal reminders were seen to increase overall compliance by 10.9%.

Adult↗