Oral Medicine for undergraduate dental students in the United Kingdom and Ireland-A curriculum.

INTRODUCTION: Oral Medicine focuses on care for patients with chronic, recurrent and medically related disorders of the orofacial region that are distinct from diseases of the periodontal and tooth tissues, with an emphasis on non-surgical management. At present, there are no shared outcomes for Oral Medicine to define the standards to be achieved before new graduates become registered dentists engaged with ongoing professional development. CURRICULUM: We present a consensus undergraduate curriculum in Oral Medicine agreed by representatives from 18 Dental Schools in the United Kingdom and Republic of Ireland. The scope of Oral Medicine practice includes conditions involving the oral mucosa, salivary glands, neurological system or musculoskeletal tissues that are not directly attributable to dental (tooth and periodontium) pathology. Account is taken of the priorities for practice and learning opportunities needed to support development of relevance to independent clinical practice. The outcomes triangulate with the requirements set out by the respective regulatory bodies in the UK and Republic of Ireland prior to first registration and are consistent with the framework for European undergraduate dental education and greater harmonisation of dental education. CONCLUSIONS: This curriculum will act as a foundation for an increasingly shared approach between centres with respect to the outcomes to be achieved in Oral Medicine. The curriculum may also be of interest to others, such as those responsible for the training of dental hygienists and dental therapists. It provides a platform for future collective developments with the overarching goal of raising the quality of patient care.

Human Disease/Clinical Medical Sciences in Dentistry: Current state and future directions of undergraduate teaching in the UK and Ireland.

In March 2017, a group of teachers of human disease/clinical medical science (HD/CMSD) representing the majority of schools from around the UK and Republic of Ireland met to discuss the current state of teaching of human disease and also to discuss how the delivery of this theme might evolve to inform improved healthcare. This study outlines how the original teaching in medicine and surgery to dental undergraduate students has developed into the theme of HD/CMSD reflecting changing needs as well as guidance from the regulators, and how different dental schools have developed their approaches to reach their current state. Each school was also asked to share a strengths, weakness, opportunities and threats (SWOT) analysis of their programme and to outline how they thought their HD/CMSD programme may develop. The school representatives who coordinate the delivery and assessment of HD/CMSD in the undergraduate curriculum have extensive insight in this area and are well-placed to shape the HD/CMSD development for the future.

The expression of Toll-like receptor 4, 7 and co-receptors in neurochemical sub-populations of rat trigeminal ganglion sensory neurons.

The recent discovery that mammalian nociceptors express Toll-like receptors (TLRs) has raised the possibility that these cells directly detect and respond to pathogens with implications for either direct nociceptor activation or sensitization. A range of neuronal TLRs have been identified, however a detailed description regarding the distribution of expression of these receptors within sub-populations of sensory neurons is lacking. There is also some debate as to the composition of the TLR4 receptor complex on sensory neurons. Here we use a range of techniques to quantify the expression of TLR4, TLR7 and some associated molecules within neurochemically-identified sub-populations of trigeminal (TG) and dorsal root (DRG) ganglion sensory neurons. We also detail the pattern of expression and co-expression of two isoforms of lysophosphatidylcholine acyltransferase (LPCAT), a phospholipid remodeling enzyme previously shown to be involved in the lipopolysaccharide-dependent TLR4 response in monocytes, within sensory ganglia. Immunohistochemistry shows that both TLR4 and TLR7 preferentially co-localize with transient receptor potential vallinoid 1 (TRPV1) and purinergic receptor P2X ligand-gated ion channel 3 (P2X3), markers of nociceptor populations, within both TG and DRG. A gene expression profile shows that TG sensory neurons express a range of TLR-associated molecules. LPCAT1 is expressed by a proportion of both nociceptors and non-nociceptive neurons. LPCAT2 immunostaining is absent from neuronal profiles within both TG and DRG and is confined to non-neuronal cell types under naïve conditions. Together, our results show that nociceptors express the molecular machinery required to directly respond to pathogenic challenge independently from the innate immune system.

Defining the educational needs of recent dental graduates preparing for the Membership of the Faculty of Dental Surgery examination.

OBJECTIVES: On graduation, UK dentists wishing to advance their career enter two years of general professional training aimed at consolidating their undergraduate experience. The Membership of the Faculty of Dental Surgery examination (MFDS) attests to its successful completion and is a pre-requisite for entry into training programmes which lead to specialist status. Most MFDS candidates prepare for the examination on their own while in full-time employment and many reinforce this self-directed learning with participation in short revision courses or through distance learning. Here we seek to obtain data on the specific educational needs of these individuals. METHODS: Questionnaires were used to interrogate 92 UK graduates attending short MFDS revision courses of up to 1 week's duration to identify which topic areas were perceived as particular areas of weakness. To gain greater insight into the responses obtained, 18/92 respondents were selected at random and followed up with semi-structured interviews informed by the questionnaires. RESULTS: Basic medical science, human diseases, law and ethics and health and safety regulations were the areas of weakness most frequently highlighted by the respondents. Most had undergone comprehensive courses in the first two topics; however, the interviews suggested that this was generally in the early stages of undergraduate training when they had difficulty in contextualising large quantities of new information. In the case of the latter two, teaching had been very varied and several interviewees felt that it had been inadequate. CONCLUSION: Recent graduates preparing for MFDS have clear educational needs. These data have begun to characterise the requirements of this group and may inform the planning of short revision courses designed to assist them.

Cell adhesion molecules in human osteoblasts: structure and function.

Osteoblasts and bone lining cells form a near continuous layer covering the bone surface and interactions between these cells and the organic matrix of bone are important determinants of osteoblast proliferation and differentiation. In addition, cells of the osteoblast-lineage form functional communications with each other, with the extra-cellular matrix and with osteocytes through cytoplasmic processes extending through canaliculi in the bone. Together, these cells form a network of putative importance in the regulation of skeletal homeostasis. Cell-cell and cell-matrix interactions are mediated by members of several families of cell adhesion molecules, and knowledge of their interactions will be of fundamental importance in understanding the role of osteoblast in skeletal turnover. Here, the expression pattern of members of the major families of cell adhesion molecules by cells of the osteoblast lineage is reviewed. Special emphasis has been placed on human tissues. In addition, the possibility that cells at progressive stages of the osteoblast lineage have different profiles of cell adhesion molecule expression is explored, and the putative significance of cell-matrix interactions in human skeletal disease briefly discussed.

Patterns of integrin expression in a human mandibular explant model of osteoblast differentiation.

Cell-matrix interaction is crucial in regulating osteoblast differentiation and function. These interactions are themselves regulated, at least in part, by integrins. Although there are some data from mammalian models, few studies have compared integrin expression at different stages of the osteoblast lineage. Here, primary human mandibular osteoblast cultures were grown in the presence of epidermal growth factor (EGF), giving a proliferative, less differentiated phenotype, or of vitamin D(3) and hydrocortisone (D+Hc), giving a more differentiated phenotype. These cultures were compared with those of cells prepared in the absence of EGF or D+Hc by fluorescence-activated cell sorter using a panel of monoclonal antibodies to specific integrin heterodimers. To provide in vivo correlation, the same panel of antibodies was used to stain fresh-frozen, undemineralised sections of human mandibular bone. Under baseline conditions the alpha(3), alpha(5), alpha(v), alpha(v)beta(3), beta(3) and beta(1) integrin subunits were expressed strongly by the cells, with low-level expression of the alpha(1), alpha(2) and alpha(4) subunits. In the presence of EGF there was increased alpha(2) expression. With D+Hc, alpha(3) and alpha(5) expression was elevated. Immunohistochemical analysis demonstrated alpha(2), alpha(3), alpha(5), alpha(v)beta(3), beta(1) and beta(3) subunits in cells of the osteoblast lineage; alpha(2) staining was restricted to cells close to the bone surface whilst alpha(v)beta(3) and beta(3) were most frequently localised in the osteocytes. The results provide evidence that cells at successive stages of the osteoblast lineage show different patterns of integrin expression. These integrins may be important in cell-matrix interactions leading to osteoblast differentiation.

Osteosarcoma of the jaws: a 30-year retrospective review.

OBJECTIVE: This article reviews osteosarcomas of the jaws referred to the Department of Oral Pathology, Eastman Dental Institute, for histologic diagnosis during the 30 years from 1968 to 1998, to compare the clinical behavior of the tumors, to assess how they differ from the reported characteristics of tumors from other sites, and to report on observations of clinical and diagnostic significance. STUDY DESIGN: The clinical, radiographic, and histopathologic records of 25 patients were obtained for retrospective review. Supportive and follow-up clinical and histopathologic material was obtained from the referring clinicians. RESULTS: The mean age of presentation of the primary lesions was 36. 9 years (range, 10-87 years) with a slight female predilection. The most common presenting features were swelling, pain, ulceration, or a neurologic deficit. The radiographic appearance of the lesions was mixed with areas of radiopacity and radiolucency. Histologically, the lesions ranged from those dominated by immature bony trabeculae separated by a cytologically bland stroma to high-grade, cellular lesions with regions of marked atypia and mitotic activity. Most had areas of chondroid formation, in addition to neoplastic osteoid. The main complication was local recurrence. Metastasis was rare and occurred as a solitary process or at a late stage in the disease progression. This was in contrast to lesions metastatic to the jaws, which were higher grade in appearance and had metastasized widely, early in the disease process. Primary osteosarcoma occurring in patients with a history of radiotherapy was typically more aggressive. CONCLUSION: Primary osteosarcomas of the jaws are a group of lesions distinct from those occurring in the long bones. Osteosarcomas of the jaw arising in a former radiation field may be a discrete group of lesions with a more aggressive behavior pattern.

Metalloproteinase expression in normal and malignant oral keratinocytes: stimulation of MMP-2 and -9 by scatter factor.

Matrix metalloproteinases (MMPs) are Zn2+ dependent proteases produced by a variety of cell types. They have a fundamental role in tissue remodelling, tumour invasion and metastasis. Scatter factor (SF), secreted by fibroblasts, has a paracrine action on epithelial cells and binds the trans-membrane c-met receptor inducing loss of adhesion, cell motility and invasiveness in vitro. The purpose of this study was to test if SF can regulate the production of MMPs by epithelial cells. Supernatants from oral squamous cell carcinoma-derived cells (H375 and H376), a human keratinocyte line (UP), and primary cultures of oral mucosal keratinocytes, grown in the presence or absence of SF, were analysed using 0.1% gelatin zymography. MMPs were characterised by comparison with human recombinant enzymes and by the use of specific inhibitors. Oral mucosal keratinocytes, UP, and H357 cells expressed MMP-2 and MMP-9, whilst H376 cells only expressed MMP-2. SF increased the expression of MMP-9 in UP and MMP-2 in H376 supernatants. Both MMP-2 and MMP-9 activity were increased in H357 and normal keratinocyte supernatants. This could be blocked using a human recombinant anti-SF antibody. In all epithelial lines tested, c-Met, the cell surface receptor for SF, could be detected. The results indicate that SF stimulates MMP expression in UP, H376, H357, and normal oral mucosal cells and points to a role for SF in the regulation of oral keratinocyte behaviour in wound healing and neoplasia.

Inhibition of mitosis and induction of apoptosis in MG63 human osteosarcoma-derived cells in vitro by surface proteins from Actinobacillus actinomycetemcomintans.

Gentle saline extraction releases a heterogeneous mixture of proteins associated with the cell surface of Actinobacillus actinomycetemcomintans, termed the surface protein fraction (SF). Some SF components are biologically active and may modulate cell behaviour in a manner of putative importance in the aetiology of periodontitis. To further characterize this activity, the ability of the SF to induce mitosis and apoptosis in MG63 cells was investigated. Cells were plated at 10(3)-10(4) cells/cm(2) and allowed to attach before culture in the serum-free medium in the presence of 25 microg/ml SF for 2-24 h. The apoptotic and mitotic figures present were counted and the results expressed as an apoptotic or mitotic index. The apoptotic and mitotic compartments were very small, but there was an inverse correlation between mitosis and apoptosis. In control experiments the mitotic was higher than the apoptotic index, whilst in the presence of SF this was reversed. These results were confirmed using in situ end-labelling. SF, therefore, may stimulate apoptotic, but inhibit mitotic, activity in MG63 cells. This raises the possibility that components of SF might induce subtle changes in the balance between apoptosis and mitosis, which, in turn, could contribute to the progression of periodontitis.

Induction of apoptotic cell death by photodynamic therapy in human keratinocytes.

The use of photodynamic therapy (PDT) for the treatment of skin and oral cancer has been the subject of several clinical studies but there has been little scientific evaluation of its mechanism of action. Evidence to date suggests that whilst epithelial cell death may be secondary to vascular damage, direct cell killing may occur and may involve an apoptosis-like mechanism. To investigate the mechanism of epithelial cell death following PDT, two cell lines, human epidermal keratinocytes (UP) and oral squamous cell carcinoma-derived cells (H376) were subjected to PDT with aluminium disulphonated phthalocyanine (AlS2Pc) as the photosensitizer and red laser light at 675 nm. Control groups received red laser light, photosensitizer or neither. The effects of PDT were assessed using an MTS cell-proliferation assay, which showed a significant reduction in viability (p < 0.01) for PDT-treated cells compared to controls. For morphological analysis, cells were stained with haemotoxylin and eosin and the numbers showing typical apoptotic features counted. The treated cultures showed significantly increased numbers of apoptotic cells. Moreover, the H376 control cultures showed a baseline level of apoptosis of approx. 15%. Apoptosis was confirmed by ultrastructural analysis and by in situ end-labeling of DNA fragments. The results show that PDT using AlS2Pc as a photosensitizer promotes apoptotic cell death in UP and H376 cells in vitro and suggest that direct killing of epithelial cells may contribute to tumour necrosis in vivo.

Dental problems associated with hypophosphataemic vitamin D resistant rickets.

OBJECTIVE: To review a series of cases of hypophosphataemic vitamin D resistant rickets. SUBJECTS INCLUDED: Seventeen cases, aged between 2 years 1 month and 15 years 9 months at first referral, and with an established diagnosis of vitamin D resistant rickets from twelve families were included in the review. Information was drawn from patient records for follow-up periods between 9 months and 20 years 4 months. SETTING: All subjects had been referred to the Eastman Dental Hospital between 1973 and 1997. FINDINGS: Abscessed non-carious primary and/or permanent teeth were a presenting feature in eleven of the seventeen cases. Although attrition and exposure of the abnormally formed dentine accounted for the route of infection in primary teeth, the route for microbial invasion of pulpal tissues in permanent teeth remained unexplained in a number of patients. The possible part played by infractures of the enamel as a portal of entry for infection is discussed. Enamel defects were observed in only six patients, in three of whom these changes were limited to the primary dentition. Taurodontism of permanent molar teeth was confirmed as a feature of the condition in the more severely affected male subjects.

Oral Mycobacterium avium complex infection in a patient with HIV-related disease. A case report.

Mycobacterium avium complex infection is a common complication of the later stages of AIDS. Although a recognized cause of oral lesions, atypical mycobacteria are rarely detected in AIDS-related oral ulceration. Here we report a case of oral ulceration in a patient in the later stages of AIDS in which atypical mycobacteria were detected both histologically and microbiologically. The features of this case are similar to the one other case previously reported permitting some characterization and comparison of the clinical features of mycobacterium avium complex infection in AIDS.

Immunohistochemical identification of tumours of adipocytic differentiation using an antibody to aP2 protein.

AIM: To determine whether aP2 expression is a useful diagnostic marker in soft tissue tumour pathology. METHODS: A polyclonal antibody to aP2 was used to investigate the immunohistochemical expression of this protein in benign and malignant tumours of adipocytic differentiation and a wide variety of other neoplasms. RESULTS: aP2 was only expressed by lipoblasts (in all types of liposarcoma and in lipoblastomatosis) and by brown fat cells (in both hibernomas and normal periadrenal fetal fat). Other benign adipose tissue tumours and malignant connective tissue or epithelial tumours were distinguished from liposarcoma by the absence of staining for aP2. CONCLUSION: Identification of lipoblasts using markers of aP2 expression is of value in the differential diagnosis of benign and malignant adipose tissue tumours and in distinguishing liposarcomas from other malignant mesenchymal and epithelial neoplasms, some of which contain cells that morphologically resemble lipoblasts.

Teaching information mastery: evaluating information provided by pharmaceutical representatives.

BACKGROUND: The pharmaceutical industry plays a large role in the lifelong learning of family physicians. Controversy exists over how to integrate this potential information source into residency curricula. METHODS: Based on a a faculty and resident needs assessment, a curriculum was designed to teach the evaluation of pharmaceutical representatives' (PRs) presentations. The Pharmaceutical Representative Evaluation Form is the keystone of the curriculum. This evaluation form guides discussion of pharmaceutical presentation to facilitate understanding of the sales process and help residents confirm or dispute the presentation's content, based on the sales methods used. A second goal of the evaluation program is to improve the content of the PRs' presentations. RESULTS: Residents rapidly acquire the ability to identify potential fallacies of logic and other misleading sales techniques in representatives' presentations. Compared with pretest results, residents' posttest scores demonstrate an understanding that PRs and the acceptance of promotional items can affect their prescribing behavior. Most PRs are pleased that their role is seen as educational. CONCLUSIONS: Physicians must function more as information managers than as information repositories, and it is important that residents be able to obtain useful information from PRs. Our curriculum has been effective in increasing residents' abilities to evaluate the pharmaceutical sales process and allowing them to separate the ¿wheat from the chaff¿ contained in this ubiquitous source of information.

Bone morphogenetic protein-2 and -4 expression during murine orofacial development.

In the developing orofacial region, epithelial-mesenchymal interactions induce a differentiation cascade leading to bone and cartilage formation. Although the nature of this interaction is unknown, bone morphogenetic proteins (BMP)-2 and -4 have been suggested as putative signalling molecules. Using 35S-labelled cDNA probes, the expression patterns of BMP-2 and -4 mRNA were examined in murine perioral tissues preceding, during and following the time of the epithelial-mesenchymal interaction leading to mandibular formation. At embryonic age (e) 9.5 days, a restricted pattern of BMP-4 mRNA was expressed in the epithelium of the developing facial processes. This decreased rapidly, with little or no signal on E10.5 or E11.5. By E13.5, BMP-4 signal was restricted to the dental lamina, follicle and papilla. BMP-2 expression was not prominent in the developing face until E13.5. At this stage, signal was widespread throughout mesenchyme of neural-crest, but not somatic origin. Different domains of expression were present in the developing epithelium: for example, there was strong signal in the floor of the mouth and the ventral tongue, in contrast to that of the dorsum of the tongue and primary palate, which were negative. These results support the role of BMP-2 and -4 as regulators of orofacial development and demonstrates different fields of BMP-2 expression in developing oral mucosal epithelium.

A clinicopathological and immunohistochemical analysis of primary oral mucosal melanoma.

Nine cases of primary oral mucosal melanoma in Caucasian patients were reviewed and the tumours analysed for expression of S100, HMB45, NKI/C3, HLA-DR, PCNA, cytokeratin and von Willebrand factor. The clinical, histopathological and immunohistochemical features were quite distinctive and our findings support previous suggestions that oral melanoma should be classified as a separate entity rather than as a sub-type of cutaneous melanoma.

Becoming an information master: a guidebook to the medical information jungle.

The medical information system is a "jungle" in which the unguided visitor can become lost or disoriented. This paper, the second in a series on becoming a medical information master, is a guidebook for traveling through this jungle. It focuses on techniques for efficiently obtaining patient-oriented evidence that matters (POEM). From original research to clinical experience, each source of medical information is valuable; the trick is to learn which source is best for the specific information being sought. Armed with this guide, clinicians can find the most appropriate source of information, evaluate it quickly, and apply it confidently in their efforts to provide the best care for their patients.