Biomedical subjects
M H Thornhill
Publications and source records attributed to M H Thornhill.
A systematic review of placebo-controlled randomized clinical trials of treatments used in oral lichen planus.
BACKGROUND: Oral lichen planus (OLP) is one of the commoner conditions seen in oral medicine clinics. Current treatments are palliative rather than curative. Numerous treatments have been tried but many have not been evaluated in randomized controlled trials (RCTs). OBJECTIVES: To review the effectiveness and safety of any therapy compared with placebo for the treatment of symptomatic OLP. METHODS: A systematic review of 11 RCTs, totalling 223 patients was done. The main outcome measures used were improvement of signs (erythema, reticulation, ulceration) and symptoms (pain, discomfort) usually after 8 weeks of therapy. RESULTS: Eleven interventions were grouped into four therapeutic classes (topical ciclosporins, topical or systemic retinoids, topical steroids and phototherapy) for comparison. No therapy was replicated exactly. Trials recording the same outcomes in each therapeutic class were pooled. The largest number of pooled trials was four. Small odds ratios with very wide confidence intervals indicating statistically significant but imprecisely known treatment benefits were seen in all but one trial. Only systemic agents were associated with treatment toxicities; all other side-effects were mild and mainly local. CONCLUSIONS: The results are tempered by the small study sizes, lack of replication, lack of standardized outcome measures and the very high likelihood of publication bias. Therefore this review provides only circumstantial evidence for the superiority of the assessed interventions over placebo for the palliation of symptomatic OLP. There is a need for larger placebo-controlled RCTs with carefully selected and standardized outcome measures.
Polymorphisms in the IL-10 and IL-12 gene cluster and risk of developing recurrent aphthous stomatitis.
BACKGROUND: Recurrent aphthous stomatitis (RAS) is a common, painful, ulcerative condition of the mouth. Although there is no clear genetic mode of inheritance, there is evidence that inheritance of specific gene polymorphisms may predispose individuals to RAS. AlsoTh1 cell mediated immune responses under the control of IL-10/IL-12 are thought to play an important role in its pathogenesis. OBJECTIVE: The objective of this study was to investigate the possibility that susceptibility to RAS is associated with the inheritance of specific gene polymorphisms for the T cell regulatory cytokines interleukin-10 (IL-10) and interleukin-12 (IL-12). PATIENTS AND METHODS: One hundred RAS patients and 91 ethnically matched controls were genotyped for the IL-10-592, and -1082 polymorphisms, and the IL-12 1188 polymorphism. Chi-square analysis was used to compare the allele frequencies and genotypes of cases and controls. RESULTS: No significant association was identified between inheritance of specific alleles or genotypes of the IL-10-592 and -1082 polymorphisms or IL-12 1188 polymorphism and susceptibility to RAS. CONCLUSIONS: We were unable to demonstrate an association between the inheritance of specific IL-10 or IL-12 gene polymorphisms and RAS susceptibility.
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.
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.
Minor recurrent aphthous stomatitis and smoking: an epidemiological study measuring plasma cotinine.
OBJECTIVE: To compare blood cotinine levels between a group of patients with minor recurrent aphthous stomatitis (RAS) and a group representative of the general population, matched for age and gender. SETTING: Although smoking has been implicated as a protective factor in RAS, few studies have compared the prevalence of smoking in RAS patients with population controls. Cotinine is a smoking derivative with a long half-life in the circulation. Measurement of plasma cotinine levels provides an accurate and objective measurement of an individual's cigarette consumption. METHODS: Blood samples were taken from 84 RAS patients and 81 controls. A microplate enzyme immunoassay (EIA) was used to detect plasma cotinine levels. RESULTS: The number of RAS patients [2 (2.4%)] who were smokers (plasma cotinine > 25 microg ml(-1) was significantly lower than in the control group [12 (14.8%); P = 0.00102]. Furthermore, the mean cotinine level amongst smokers in the RAS group was significantly lower than in smokers in the control group (P = 0.0068). CONCLUSION: This study shows that a group of RAS patients is significantly less likely to contain smokers than a matched control population, and among smokers the level of cigarette use was significantly lower in RAS patients than the control population. The perceived negative association between RAS and smoking was supported by this epidemiological study.
Recurrent aphthous stomatitis and gene polymorphisms for the inflammatory markers TNF-alpha, TNF-beta and the vitamin D receptor: no association detected.
OBJECTIVE: To investigate the possibility that minor recurrent aphthous stomatitis (MiRAS) is associated with the inheritance of specific gene polymorphisms for markers associated with macrophage driven inflammation, i.e. tumor necrosis factor-alpha (TNF-alpha), TNF-beta or the vitamin D receptor (VDR). SETTING: MiRAS is a common, painful, ulcerative condition of the mouth. Its etiology is unknown although mononuclear inflammatory cells are thought to play an important role. There is no clear genetic mode of inheritance, however, many patients report a positive family history and disease concordance is significantly higher in monozygotic than dizygotic twins, suggesting a polygenic mode of inheritance. METHODS: Ninety-five MiRAS patients and an ethnically matched control population were genotyped for TNFA-308, TNFB Ncol and VDR (intron 8 and exon 9) polymorphisms. Chi-square analysis was used to compare the allele frequencies and genotypes of cases and controls. RESULTS: No significant association was identified between inheritance of specific alleles or genotypes of the TNFA-308, TNFB Ncol and VDR (intron 8 and exon 9) polymorphisms and susceptibility to MiRAS. CONCLUSIONS: Inheritance of specific gene polymorphisms for TNF-alpha, TNF-beta or VDR does not appear to be a significant factor in determining susceptibility to MiRAS.
IL-1B and IL-6 gene polymorphisms encode significant risk for the development of recurrent aphthous stomatitis (RAS).
Recurrent aphthous stomatitis (RAS) is an, ulcerative condition of the mouth, with a polygenic mode of inheritance in which cytokines are thought to play an important role. Ninety-one RAS patients and 91 controls were genotyped for known IL-1A, IL-1B, IL-1RN and IL-6 gene polymorphisms. Inheritance of the G allele of the IL-1B -511 polymorphism was strongly associated with RAS (OR = 2.5, P < 0.00002), with increased numbers of G/G homozygotes (OR = 4.5, P < 0.0005). The G allele of IL-6 -174 also occurred more frequently in RAS (OR = 2.6, P < 0.0001) with greatest risk associated with G/G homozygosity (OR = 3.4, P < 0.0001). IL-1RN VNTR 1/1 homozygotes also occurred more frequently in RAS (OR = 2.0, P < 0.02). Inheritance of the G/G genotype of both IL-1B and IL-6 was a particularly strong predictor for RAS (OR = 8.5).
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.
Immune mechanisms in oral lichen planus.
Although we still don't know the cause, there has been much research into the immune and pathological mechanisms that underlie oral lichen planus (OLP) and it is now possible to piece together a much clearer picture of the disease process. There is consensus that in OLP there is chronic, cell-mediated, immune damage to basal keratinocytes in the oral mucosa that are recognized as being antigenically foreign or altered. In most cases, however, the identity of the target antigen remains unknown. It is likely that cytokines released by the affected keratinocytes, and the associated inflammatory infiltrate, play a key role in the selective recruitment of the T-cell-dominated infiltrate that characterizes OLP, through their ability to induce adhesion molecule expression as well as further cytokine and chemokine release. In susceptible individuals, chronic presentation of antigen by basal keratinocytes may perpetuate the condition and direct cell-mediated immune damage on the keratinocytes.
Violence and aggression at work.
The issue of violence and aggression towards healthcare personnel has received increasing attention over recent years. Surveys indicate that such behaviour does occur in both hospital and community dental settings, although in comparison, many other healthcare workers appear to be at greater risk. Information and advice to prevent and manage such situations, should they occur, are available.
Medical emergencies: the experience of staff of a UK dental teaching hospital.
OBJECTIVE: To assess the frequency of faints and other medical emergencies experienced by staff of a UK dental hospital. To investigate the training they had received in the management of medical emergencies, their perception of readiness to deal with emergencies and future training needs. SUBJECTS: All 193 clinical staff (dentists, hygienists, nurses and radiographers) of the University Dental Hospital of Manchester. DESIGN: Structured questionnaire with covering letter, reminders sent to non-responders. RESULTS: There was an 82% response. Fainting was the commonest event: other medical emergency events were experienced with an average frequency of 1.8 events per year, with the highest frequency reported by staff in oral surgery. Most expressed a need for further training: only 3% felt no need. CONCLUSIONS: Medical emergencies occur in dental hospital practice more frequently but in similar proportions to that found in general dental practice. There is a perceived need for further training among dental hospital staff in the management of medical emergencies.
Delayed and immediate hypersensitivity reactions associated with the use of amalgam.
Hypersensitivity to the constituents of dental amalgam is uncommon. When it occurs it typically manifests itself as a lichenoid reaction involving a delayed, type IV, cell-mediated hypersensitivity response. Rarely, a more acute and generalised response can occur involving both the oral mucosa and skin. We describe two cases that illustrate the presentation and management of these two types of reaction.
Growth-regulated peptide-alpha (GRO-alpha) production by oral keratinocytes: a comparison with skin keratinocytes.
Growth regulated peptide (GRO-alpha) is chemotactic for neutrophils. It also stimulates keratinocyte proliferation and migration, and angiogenesis in cutaneous wound healing. We compared GRO-alpha production by normal human skin and oral keratinocytes, and the effects of cytokine stimulation. Resting keratinocytes produced little, if any, GRO-alpha. TNF-alpha induced a large increase in GRO-alpha mRNA and protein production in both cell types (P<0.001). However, the response of oral keratinocytes was significantly higher (P<0.01). Oral, but not skin, keratinocytes also produced significant amounts of GRO-alpha in response to IL-1 alpha (P<0.005) and IL-4 (P<0.01) stimulation. Indeed, there was an additive effect on GRO-alpha production when oral keratinocytes were stimulated with combinations of TNF-alpha and IL-1 alpha or TNF-alpha and IL-4. Neither cell type responded to interferon gamma. Keratinocyte GRO-alpha production may help selectively recruit neutrophils in mucocutaneous inflammatory diseases, and differences in production by skin and oral keratinocyte could explain the different presentation of these diseases at the two sites. The increased GRO-alpha responsiveness of oral keratinocytes may also help explain the excellent wound healing properties of oral mucosa.
Oral and skin keratinocytes are stimulated to secrete monocyte chemoattractant protein-1 by tumour necrosis factor-alpha and interferon-gamma.
Monocyte chemoattractant protein-1 (MCP-1) is a member of the CC subfamily of chemokines. It is chemoattractant for monocytes, activated memory T cells and dendritic cells. We studied MCP-1 mRNA and protein production in cultured human oral keratinocytes (OK) and skin keratinocytes (SK). MCP-1 production was undetectable in resting keratinocytes. However, stimulation with tumour necrosis factors (TNF-alpha) or interferon-gamma (IFN-gamma) induced MCP-1 mRNA and protein synthesis in both cell types. Together, TNF-alpha and IFN-gamma acted synergistically to increase MCP-1 production. In each case MCP-1 production was greater for SK than OK. The kinetics of IFN-gamma-induced MCP-1 production were similar for both cell types, peaking around 72 h. In contrast, TNF-alpha induced a more rapid increase in MCP-1 production by SK than OK, peak production occurring after 24 and 72 h, respectively. IL-1alpha and IL-4 did not induce MCP-1 production. However, in combination with IFN-gamma, they induced a small extra increase in MCP-1 production in SK but not OK.
The effect of sodium lauryl sulphate, triclosan and zinc on the permeability of normal oral mucosa.
OBJECTIVE: Sodium lauryl sulphate (SLS), an important component in many oral health products, is well established as a contact irritant in skin. Recent studies have suggested that it may also affect the structural integrity of oral mucosa. SLS is rarely used alone in dentifrices or mouthwashes and the aim of this study was to establish the effect of SLS both alone and in combination with Triclosan (TCN) and zinc (Zn) on the permeability barrier properties of normal human oral mucosa. METHOD: Ventral tongue mucosa was obtained from nine males and seven females within 60 h of death and stored frozen at -70 degrees C until use. The permeability of the tissue to tritiated water was measured after pretreatment for 15 min with SLS alone, SLS/TCN, SLS/Zn and a SLS/TCN/Zn mixture. Treatment with distilled water (DW) served as control. The histological appearance of the tissue before and after treatment was also examined by light microscopy. RESULTS: SLS treatment caused a significant increase in water permeability compared to control tissue (Kp = 11.7 +/- 1.00; 4.96 +/- 0.50 respectively; P < 0.005). Treatment with a SLS/TCN/Zn mixture, however, had no effect on the permeability to water (Kp = 5.5 +/- 0.56). Histological examination revealed that tissue exposed to SLS had a marked disruption of the epithelial surface whilst tissue treated with a SLS/TCN/Zn mixture was indistinguishable from controls. CONCLUSION: Although mucosa exposed to SLS alone showed an increase in permeability to water, the addition of TCN and Zn to SLS appeared to prevent this effect. As SLS is included in some dental products to solubilise compounds such as TCN, its presence may have no effect on the permeability barrier property of oral mucosa.
Recurrent Kawasaki disease.
Kawasaki disease (mucocutaneous lymph node syndrome) is a disease of unknown aetiology characterised by vasculitis which may affect the coronary arteries. Young children are most commonly affected although the disease has been described in adults. We report a case of recurrent Kawasaki disease which presented to an oral medicine clinic, where early recognition prompted appropriate management.