A model of oral mucosal carcinogenesis using the water-soluble carcinogen 4-nitroquinoline-1-oxide (4NQO) was combined with a model of oral mucosal candidosis to examine the ability of Candida albicans to promote the development of neoplasia in suitably initiated epithelium. Sprague-Dawley rats were initiated by the application of 4NQO to their palatal and tongue mucosa 3 times weekly for 4 weeks. The animals then received either application of a phorbol ester to act as a promoter, induction of experimental oral mucosal infection with C. albicans, or no further procedures. Animals were killed at 34 or 52 weeks and the tongues and palates sectioned for light-microscopic examination. Control groups with no treatment, mucosal infection only, phorbol ester application only, 4NQO with the tetracycline or vehicle application only were also used. The development of carcinoma in the experimental groups was similar to that in the positive control groups, indicating that the particular strain of Candida used had a similar ability to promote neoplastic changes as the known promoter phorbol-12,13-didecanoate and caused neoplastic changes to occur by week 34 with no additional lesions occurring by week 52. This indicated that the speculation that strains of C. albicans may participate in causing neoplastic transformation in humans was well founded.
Osteonecrosis of the Jaw (ONJ) is a recently recognised and potentially highly morbid complication of bisphosphonate therapy in the setting of metastatic malignancy, including myeloma. Members of the Medical and Scientific Advisory Group of the Myeloma Foundation of Australia formulated guidelines for the management of bisphosphonates around the issue of ONJ, based on the best available evidence in June 2008. Prior to commencement of therapy, patients should have an oral health assessment and be educated about the risks of ONJ. Dental assessment should occur 6 monthly during therapy. If tooth extraction is required, sufficient time should be allowed for complete healing to occur prior to commencement of bisphosphonate. As the risk of ONJ increases with duration of bisphosphonate therapy, we recommend annual assessment of dose with modification to 3 monthly i.v. therapy or to oral therapy with clodronate for those with all but the highest risk of skeletal-related event. Established ONJ should be managed conservatively; a bisphosphonate "drug holiday" is usually indicated and invasive surgery should generally be avoided. These recommendations will assist with clinical decision making for myeloma patients who are at risk of bisphosphonate-associated ONJ.
A model of candidosis in experimental rats was used to study the role of trauma in the aetiology of oral mucosal infections caused by Candida albicans. Standardised thermal trauma was delivered to the dorsum of the tongue of Sprague-Dawley rats and experimental candidosis was induced. Histologically, the site of trauma was invaded by hyphae earlier and more extensively than in control animals, leading to the conclusion that trauma facilitated the establishment of the C. albicans infections.
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