Biomedical subjects
M N Pemberton
Publications and source records attributed to M N Pemberton.
Assessing proliferation, cell-cycle arrest and apoptotic end points in human buccal punch biopsies for use as pharmacodynamic biomarkers in drug development.
Easily accessible normal tissues expressing the same molecular site(s) of drug action as malignant tissue offer an enhanced potential for early proof of anticancer drug mechanism and estimation of the biologically effective dose. Studies were undertaken in healthy male volunteers to assess the tolerability of single and multiple (four in 24 h) 3 mm punch biopsies of the buccal mucosa, and to determine the feasibility of detecting and quantifying a range of proliferation, cell-cycle arrest and apoptosis markers by immunohistochemistry (IHC) for use as potential pharmacodynamic (PD) end points. The biopsy procedure was well tolerated with 100% of volunteers stating that they would undergo single (n = 10) and multiple (n = 12) biopsies again. Total retinoblastoma protein (pRb), phosphorylated pRb (phospho-pRb), total p27, phosphorylated p27 (phospho-p27), phosphorylated-histone H3 (phospho-HH3), p21, p53, Cyclin A, Cyclin E, Ki67 all produced good signal detection, but M30, cleaved caspase 3 and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling did not. Total pRb, phospho-pRb, total p27 and phospho-p27 were quantified further in a multiple biopsy study to allow components of variability to be addressed to inform future sizing decisions on intervention studies. Neither site of biopsy within the oral cavity, nor the nominal time of biopsy had any significant impact on any of the four markers expression levels. Inter- and intrasubject coefficients of variation (CVs) that could be used to size future intervention studies for pRb, phospho-pRb, total p27 and phospho-p27 were 14, 19, 18 and 16%; and 18, 29, 25 and 19%, respectively. In conclusion, quantitation of such markers in 3 mm buccal punch biopsies would be suitable to explore as PD end points within intervention studies of drugs acting on these pathways.
Methotrexate and oral ulceration.
Methotrexate is well established in the drug treatment of various neoplastic diseases. More recently it has become increasingly used as a once-weekly, low-dose treatment of disorders such as psoriasis and rheumatoid arthritis. Clinical trials have shown its effectiveness in these conditions and it is likely that dentists will encounter patients taking this drug in general dental practice. Oral ulceration can occur as a side effect of methotrexate therapy. This may be due to lack of folic acid supplementation or overdosage due to confusion regarding its once-weekly regime. Illustrations of these problems, which have initially presented in a dental setting, are given. Important drug interactions of methotrexate relevant to dentistry are discussed.
Salivary otorrhoea: a case report and a review of the literature.
This report presents an unusual case of spontaneous salivary otorrhoea in which advanced imaging was used to identify a developmental defect in the anterior wall of the bony external auditory meatus. This defect, the so-called foramen of Huschke, was subsequently found to be the source of the fistula. A review of the literature highlights the diagnostic dilemmas that such cases pose for the clinician.
Rofecoxib and dental prescribing.
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Cutaneous facial sinus tract of denture-related aetiology? A case report.
A case is reported of a chronic facial sinus on the mandible. It is postulated that this was due to chronic mucosal trauma associated with a poorly adapted denture in a patient rendered immunosuppressed by poorly controlled type II diabetes. Previous treatment with antibiotics alone was unsuccessful. Healing was only achieved when antibiotics were combined with removal of the denture and improved diabetic control.
Patterns of antifungal prescribing in general dental practice.
OBJECTIVE: To examine the current practice of antifungal prescribing by GDPs in the United Kingdom. Design A postal questionnaire circulated to a random selection of 400 dentists. OUTCOME MEASURES: The questionnaires were analysed and the responses expressed as absolute and relative frequencies. RESULTS: Responses to the questionnaire were received from 297 (74.3%) GDPs. Nystatin was the most popular choice of antifungal agent that GDPs would use, followed by miconazole, amphotericin B and fluconazole. The likelihood of use of miconazole was positively linked to recent date of graduation. Lack of knowledge regarding contraindications and problems with azole antibiotics was found in a significant minority of practitioners (36%). CONCLUSIONS: The present study indicates that azole antifungal agents (especially miconazole) are becoming more widely used by GDPs, but that knowledge regarding potential problems with their use is sub-optimal. Nystatin remains the most popular choice of antifungal agent.
Miconazole oral gel and drug interactions.
Miconazole oral gel is frequently prescribed for the treatment of oral Candidal infections. Its ability to be systemically absorbed and interact with other drugs has previously been recorded but is not universally known. As a reminder, a further case of derangement of anticoagulation following concomitant use of warfarin and miconazole is reported. Other potential drug interactions of miconazole and fluconazole are highlighted.
Oral biopsies: methods and applications.
Biopsies are an important diagnostic tool for the diagnosis of lesions ranging from simple periapical lesions to malignancies. Planning prior to performing a biopsy is essential. It will be beneficial to the receiving pathologist in reaching a helpful and meaningful diagnosis, and therefore ultimately and more importantly, to the patient. This paper presents an updated view of biopsies and discusses some of the potential problems with biopsy technique and specimens and how to overcome them.
Oral tonsils (ectopic oral tonsillar tissue).
Oral tonsils (ectopic oral tonsillar tissue) are rarely remarked upon. They may cause diagnostic confusion, especially when found in the floor of the mouth. We report here two cases of patients presenting because of oral tonsillar tissue, to remind colleagues of its occurrence and the need to consider the lesion in the differential diagnosis of soft tissue nodules of the oral cavity.
Oral mucosal keratinocytes express RANTES and ICAM-1, but not interleukin-8, in oral lichen planus and oral lichenoid reactions induced by amalgam fillings.
Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa characterized by a band-like accumulation of lymphocytes in the connective tissue adjacent to the basement membrane as well as intraepithelially. Amalgam fillings can induce oral lichenoid reactions (OLR) that are similar to OLP. The adhesion molecule ICAM-1 and the chemokines interleukin-8 and RANTES all play central roles in leucocyte trafficking. The aim of this study was to investigate the possible role of these molecules in the migration of leucocytes into the oral mucosa in OLP and OLR. Standard immunoperoxidase techniques were used to visualize the expression of ICAM-1, RANTES and interleukin-8 in frozen biopsy sections. ICAM-1 was expressed by endothelial cells, but not by keratinocytes, in normal oral mucosa. ICAM-1 was expressed by keratinocytes in 11 of 12 biopsies of OLP and in six of seven biopsies of OLR. In all of these cases ICAM-1 was also expressed by endothelial cells and leucocytes. Although not present in normal oral mucosa, RANTES was expressed by keratinocytes in 21 of 24 biopsies of OLP and in seven of seven cases of OLR. Interleukin-8 was not detected in any of the samples. The expression of ICAM-1 and RANTES by epithelial keratinocytes in the oral mucosa in OLP and OLR could be a key inflammatory mechanism in these diseases.
Mycosis fungoides involving the oral mucosa in a child.
Involvement of the oral mucosa in cutaneous T-cell lymphoma is uncommon and is usually associated with a poor prognosis (the majority of patients dying from the disease within 3 years of the diagnosis of oral involvement). We report the first case of intraoral mycosis fungoides occurring in a child. In addition, our patient has had intraoral disease for 3 years and is currently systemically well with no evidence of cutaneous or systemic disease progression.
Adverse reactions associated with the use of eugenol in dentistry.
Eugenol is a material commonly used in dentistry with few reported side effects. It is not however, a bio-friendly material when in contact with oral soft tissues. It can produce both local irritative and cytotoxic effects, as well as hypersensitivity reactions. Here we report on two cases of adverse local reaction to eugenol, contained within a temporary restorative material and a temporary cementation material respectively, which illustrate these problems.
Activation of oral keratinocytes by mercuric chloride: relevance to dental amalgam-induced oral lichenoid reactions.
BACKGROUND: Despite the benefits of mercury-containing amalgam dental fillings there are growing concerns regarding the potential adverse health effects arising from exposure to mercury released from fillings. In some individuals this process may result in a local lichenoid reaction of the oral mucosa. OBJECTIVES: The aim of this study was to investigate the possibility that mercury salts released from amalgam fillings might act directly on oral keratinocytes to induce changes that could promote the development of such lesions. METHODS: In vitro experiments were performed in which normal oral and cutaneous keratinocytes were cultured in the presence of mercuric chloride (HgCl2). ICAM-1 expression and the release of cytokines was determined by enzyme-linked immunosorbent assay techniques. T-cell binding to HgCl2-pretreated keratinocytes was assessed using a colorimetric method. RESULTS: Subcytotoxic concentrations of HgCl2 induced a concentration-related increase in ICAM-1 expression and consequent T-cell binding on oral, but not cutaneous, keratinocytes. HgCl2 also stimulated the release of low levels of tumour necrosis factor-alpha and interleukin-8 (but not RANTES), and inhibited the release of interleukin-1alpha by oral keratinocytes. CONCLUSIONS: This study provides evidence that oral keratinocytes may play an integral part in initiating the pathogenesis of amalgam-induced lichenoid reactions.
Investigation and medical management of trigeminal neuralgia by consultant oral and maxillofacial surgeons in the British Isles.
Trigeminal neuralgia is an extremely painful affliction of the face that is treated by various specialists including oral and maxillofacial surgeons. Some aspects of its management remain controversial, including screening for secondary trigeminal neuralgia, and the monitoring of treatment with carbamazepine. There is, however, little information available about current practice. A postal questionnaire was sent to 254 fellows of the British Association of Oral and Maxillofacial Surgeons (BAOMS) about v arious aspects of the management of trigeminal neuralgia. One hundred and seventy nine replies (70%) were received. Orofacial and cranial nerve examinations were undertaken by the majority of surgeons, but most did not routinely arrange computed tomograp hy or magnetic resonance imaging for all patients, nor did they refer the patient to a neurologist. In contrast with current recommendations, warnings about the adverse effects of carbamazepine were given by only a few surgeons, while most routinely monitored full blood counts.
Oral cancer screening.
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