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New evidence suggests that the extent and severity of periodontal disease may be a significant risk factor for erectile dysfunction, sperm motility and time to conception. This paper reviews the evidence and informs members of the dental team when dealing with this sensitive issue. As more research is forthcoming the topic of oral and sexual health is likely to be part of regular routine medical screening. Any issue concerning oral health as a risk factor for sexual health is likely to be a sensitive subject, rarely discussed in the dental setting. However, as new evidence emerges, this topic is likely to get into the public domain. All members of the dental team should be aware of such an association. Clinical Relevance: Furthermore, the information in this paper may provide further incentive for certain patients to improve their oral health.

Local drug delivery systems (LDDs) are mainly used as adjuncts to root surface instrumentation (RSI) in the management of periodontal disease. A range of antibacterial agents have been used for this purpose and include the tetracyclines, chlorhexidine, metronidazole, azithromycin, clarithromycin and moxifloxacin. More recently, other non-antibacterial agents have been incorporated into local delivery devices and include simvastatin, metformin and alendronate. This paper will review the effectiveness of such agents when used as an adjunct to conventional non-surgical periodontal therapy. Clinical Relevance: The benefits of adjunctive use of local drug delivery in the management of periodontal disease will be discussed.

Periodontal pockets provide an ideal environment for the application of local drug delivery for the management of periodontitis. In this first article, consideration is given to the principles that underlie local drug delivery and the pharmacological challenges. It is essential that such systems are compatible with the periodontal tissues. Potential unwanted effects that can arise from both drug and delivery vehicle are also appraised. Clinical Relevance: Local drug delivery systems still have a place in the management of periodontal diseases. This first article considers the pharmacological principles and unwanted effects that can arise from the use of such systems.

Periodontal disease is caused by inflammatory processes initiated by the presence of a biofilm. The management of this disease process is largely achieved by disrupting the biofilm to allow regression of inflammation and healing. As our patients are living for longer they are likely to have been exposed to systemic medications that aim to reduce inflammation. These drugs have been shown to decrease inflammation within the periodontal tissues despite not being a primary function of their use. This paper aims to review the relative effects of common systemic medications on the periodontal tissues by analyzing their modes of action and discussing current research and the implications for periodontal treatment.

Aggressive periodontitis is a relatively rare periodontal condition that can result in significant attachment loss over a short period of time. As the disease is difficult to manage, owing to its rapid progression and severity, a variety of adjuncts have been advocated in its management. The authors outline concepts of the aetiology and pathogenesis of aggressive periodontitis and how the different treatment regimens relate to the current understanding of the disease process. Clinical Relevance: There is a wide variety of treatment regimens advocated for the treatment of aggressive periodontitis. General dental practitioners and specialists should be aware of the relative advantages and disadvantages of these and how they relate to the disease process.

J Oral Pathol Med (2012) 41: 113–118 Background: Solid organ transplant patients are at an increased risk of developing lip malignancies. The role of HLA mismatch as a risk factor for such changes has only been described in skin. Methods: Lip lesions were evaluated in 403 solid organ transplant patients (immunosuppressed for at least 3 months) and findings compared to age and sex matched, otherwise healthy patients who acted as controls. HLA typing was provided for the transplant patients. All patients provided details of smoking history, alcohol consumption, skin type, as assessed by ease of burning to sunlight, and exposure to sunlight or other forms of ultraviolet radiation. Results: Lip lesions were identified in 36 transplant patients and 29 were biopsied. Fourteen of the biopsies confirmed dysplastic or malignant changes. For the control patients, one lesion was identified as dysplastic. The prevalence of dysplastic and malignant lip lesions was significantly higher (P = 0.006) in the transplant patients when compared to controls. Risk factors for dysplastic/malignant changes in the transplant group included age (P = 0.01), smoking (P = 0.033) and HLA-B mismatch (P = 0.001). Lip covering provided a significant reduction (P = 0.045) in the development of lip changes. Conclusion: All transplant patients should be regularly screened for lip malignancies and consulted on smoking and sunlight exposure. HLA-B mismatch does appear to make these patients more susceptible to dysplastic/malignant changes.

Full-mouth disinfection is a relatively new technique for the management of patients, especially those with moderate to severe chronic periodontitis. In this paper, the technique is reviewed and efficacy evaluated. The methodology and possible outcomes are illustrated with a case report.

Patients diagnosed or being treated for malignant disease can neglect their dental care and be reluctant to undertake dental treatment. This article considers the dental problems that may arise in such patients and how they can be managed. Chemotherapy and its sequelae are the main challenges to the delivery of routine dental care. For such patients, it is important to liaise with their oncologists to obtain an up-to-date haematological profile and time frame for any future treatments. For all such patients, dental care may be neglected, but it is important that dental and oral health is maintained.This article reviews the possible impact that malignant disease and its treatment can have on the delivery of dental care. Chemotherapy-induced bone marrow depression is likely to have the most profound effect on routine dental treatment.

Background There has been a trend over recent years for combining a nonsteroidal antiinflammatory drug (NSAID) with paracetamol (acetaminophen) for pain management. However, therapeutic superiority of the combination of paracetamol and an NSAID over either drug alone remains controversial. We evaluated the efficacy of the combination of paracetamol and an NSAID versus either drug alone in various acute pain models. Methods A systematic literature search of Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, and PubMed covering the period from January 1988 to June 2009 was performed to identify randomized controlled trials in humans that specifically compared combinations of paracetamol with various NSAIDs versus at least 1 of these constituent drugs. Identified studies were stratified into 2 groups: paracetamol/NSAID combinations versus paracetamol or NSAIDs. We analyzed pain intensity scores and supplemental analgesic requirements as primary outcome measures. In addition, each study was graded for quality using a validated scale. Results Twenty-one human studies enrolling 1909 patients were analyzed. The NSAIDs used were ibuprofen (n = 6), diclofenac (n = 8), ketoprofen (n = 3), ketorolac (n = 1), aspirin (n = 1), tenoxicam (n = 1), and rofecoxib (n = 1). The combination of paracetamol and NSAID was more effective than paracetamol or NSAID alone in 85% and 64% of relevant studies, respectively. The pain intensity and analgesic supplementation was 35.0% +/- 10.9% and 38.8% +/- 13.1% lesser, respectively, in the positive studies for the combination versus paracetamol group, and 37.7% +/- 26.6% and 31.3% +/- 13.4% lesser, respectively, in the positive studies for the combination versus the NSAID group. No statistical difference in median quality scores was found between experimental groups. Conclusion Current evidence suggests that a combination of paracetamol and an NSAID may offer superior analgesia compared with either drug alone.

There has been an increase in the diagnosis and treatment options for malignant diseases. In this article we provide an overview of the impact of the treatments of malignant diseases on the oral structures. Whilst some of the complications, such as oral mucositis and oral infection, are of short duration and respond once chemotherapy has been completed, other treatments have a prolonged effect. Of particular concern is the effect of bisphosphonates on bone turnover and the risk of osteonecrosis on the jaw and hormones affecting the periodontal tissues. These unwanted effects all impact upon the quality of life of many patients diagnosed with malignant disease.Treatments of malignant diseases can have a profound effect on oral structures and functions. All members of the dental team need to be aware of adverse effects arising from such treatments and how they can affect oral function and quality of life.

Reports of an ageing population, increasing incidence of malignancy and improved treatments mean that dentists may have an increasing number of patients with, or who have recovered from, a malignancy. Dental professionals are expected to have an understanding of this important disease group so that appropriate dental care can be provided safely. In this first of three articles, we shall describe the important epidemiological and clinical features of the commonest malignancies in the United Kingdom.Dentists should understand the clinical implications of a patient with, or recovering from, a malignancy. This article gives a summary of the relevant features of the commonest malignancies.

Background: The aim of this study was to evaluate the efficacy of a topical hyaluronic acid (HA) gel preparation (0.2%) in the management of oral lichen planus (OLP). Methods: A total of 124 patients with erosive OLP participated in a randomized, placebo-controlled, double-blind trial to evaluate the efficacy of a topical HA preparation. Outcome measures included soreness relief following immediate application, oral function and size of erosive/ulcerative area. Patients were medicated for 28 days and completed a log diary recording oral function and soreness scores. Results: Application of topical HA produced a significant reduction (P 0.05) with respect to oral function. Patients treated with 0.2% HA showed a significant reduction (P

The NICE Guidelines on Prophylaxis against Infective Endocarditis were published early this year. In this review, consideration is given to the evidence that the Working Party evaluated in arriving at their recommendations.The NICE Guidelines will have a very significant impact upon clinical practice. Antibiotic cover to prevent infective endocarditis prior to dental treatment has been a confusing and contentious issue. All members of the dental team should welcome these Guidelines which will impact upon the delivery of dental care to many categories of patient.

BACKGROUND: The aim of this study was to evaluate the efficacy of a topical hyaluronic acid (HA) preparation (0.2%) in the management of recurrent aphthous ulceration (RAU). METHODS: One hundred and twenty patients with RAU participated in a randomized, placebo controlled, doubleblind trial to evaluate the efficacy of the topical HA and preparation. Outcome measures include soreness relief on immediate application (recorded over 60 min). Thereafter, patients completed a log diary recording soreness from the ulcers, occurrence of new ulcers and ulcer duration. RESULTS: Both topical HA and placebo resulted in a significant reduction in ulcer soreness following immediate application (P = 0.0004). Throughout the rest of the investigation period, there was no significant differences (P > 0.05) between the treatments for reducing soreness. Patients treated with topical HA recorded few ulcers on day 5 of the investigation than those treated with placebo (P < 0.001). Likewise, the occurrence of new ulcers was lower in the HA treated group on day 4 when compared with placebo (P = 0.047). CONCLUSION: Topical HA (0.2%) may be of benefit in the management of RAU. Immediate reduction of symptoms appears to be a barrier effect. J Oral Pathol Med (2006) 35: 461–5

Objectives: This review critically evaluates the different therapies that are available to manage drug-induced overgrowth (DIGO). Material and Methods: This review is based on literature identified using the online databases MEDLINE and PUB MED. It is not a systematic review, but a conventional review of the relevant literature. Results: Patients benefit from a non-surgical approach if this can be delivered before commencement of medication although in many instances this may not be practicable. Systemic antibiotic usage has been evaluated in the management of ciclosporin-induced gingival overgrowth. Efficacy appears to be equivocal and long-term use is undesirable. Surgical excision remains the main treatment option especially for patients with severe overgrowth. Few studies have compared different techniques with respect to recurrence rate or post-operative sequelae. Conclusion: DIGO is a common clinical problem that often requires intervention. Non-surgical techniques can limit the occurrence of this unwanted affect, reduce the extent of plaque-induced gingival inflammation and reduce the rate of recurrence. Wherever possible this management strategy should be adopted first. Surgical treatment is often the most reliable option and scalpel gingivectomy remains the treatment of choice. Further investigations are required to develop appropriate management strategies to prevent recurrence of DIGO.

Objectives: This aim of this study was to develop and assess a technique that could be used to assess accurately the gingival volume changes seen in drug-induced gingival overgrowth by the analysis of data obtained from an entire gingival surface by means of three-dimensional imaging. Material and Methods: Stone dental models of patients before and after gingivectomy procedures were digitized with a laser scanner and then regenerated as computer models constructed from the acquired three-dimensional co-ordinate data. A comparison of superposed “before” and “after” surfaces was undertaken to assess and accurately quantify changes in gingival contour. Results: The mean vertical tissue reduction varied from 1.58 to 2.56 mm in the four study subjects and individual differences are shown. The maximum thickness of removed buccal gingival overgrowth was found to range between 1.20 and 3.40 mm. The volume of tissue removed from each inter-dental papilla ranged from 4.2 to 46.1 mm3 and the mean volume of the papilla removed from each subject±SD values was 24.8±13.1 mm3. Conclusion: This method will measure changes in gingival tissues to within 60 μm in one plane, making it ideal for the assessment of longitudinal changes in gingival contour as seen in the development of gingival overgrowth, its recurrence after surgery or the changes in volume brought about by surgery.

An unexpected dose related increase in oral squamous cell carcinomas was observed in a standard 2-year carcinogenicity study with a novel calcium channel blocker, in which Wistar rats received daily doses of 0, 1.5, 7, 20, or 40 mg/kg of the compound mixed with a standard diet containing fibers from barley. This finding was associated with an increased incidence of severe (destructive) periodontitis and the formation of oro-nasal fistulae at the 2 highest doses. Five assays of the compound for genotoxicity were negative indicating that a genotoxic effect was highly improbable. To investigate the underlying pathogenic mechanisms a second 2-year study in the same strain of rats was initiated and the influence of the diet and/or a possible local irritancy by the drug was assessed. In this second study the compound was administered by oral gavage at daily doses of 0, 7, or 40 mg/kg (later reduced to 20 mg/kg due to systemic intolerance) to rats maintained either on the standard diet or on a low fiber diet assumed to be less aggressive in terms of inducing periodontal lesions. Dose dependent gingival overgrowth (a class-related effect) was observed in the incisor and molar teeth area of all treated groups but was independent of the diet used. No oral tumors were found in the standard diet or low fiber diet controls and all treatment groups fed the low fiber diet, whereas in the high-dose group fed the standard diet a total of 8 oral squamous cell carcinomas were detected in association with an increased incidence of severe periodontitis. These results indicate that the increased incidence of squamous cell carcinomas observed upon chronic administration of the compound is not due to a direct tumorigenic effect of the drug. Tumor formation is attributable to severe periodontal disease favored by the diet and class related gingival overgrowth.

Objectives: This study investigates the effect of a range of potential risk factors on the severity of gingival overgrowth in transplant patients medicated with ciclosporin in the absence of any calcium channel blockers. Materials and Methods: One hundred dentate solid organ transplants medicated with ciclosporin (but not calcium channel blockers or phenytoin) were recruited for the study. Demographic, pharmacological and periodontal data were recorded and gingival overgrowth assessed from stone models. Results: Univariate analysis identified the duration of transplant, papilla bleeding index, creatinine serum concentration, azathioprine and prednisolone dosage as risk factors for overgrowth severity. Multivariate modelling, excluding the periodontal parameters, gave a predictive model that included dosages of ciclosporin, azathioprine, prednisolone and weight (p

Periodontal research over the last 40 years has been remarkably prolific. We now understand that severe periodontitis affects approximately 10–15% of the population (representing a large number of individuals in the UK) and gingivitis and mild periodontitis affect a majority of people. Microbiological research has identified some of the key pathogens that are implicated in periodontal disease. Plaque bacteria exist in biofilms, which have evolved to protect individual organisms within the subgingival bacterial community. For this reason, root surface instrumentation (RSI) remains the cornerstone of periodontal treatment, and is necessary to disrupt the subgingival biofilm mechanically and reduce the bacterial bioburden. Although bacteria are necessary for periodontal disease to occur, a susceptible host is also required. The immune-inflammatory response that develops in the gingival and periodontal tissues in response to the chronic presence of plaque bacteria results in destruction of structural components of the periodontium leading, ultimately, to the clinical signs of periodontitis. The nature of the host response is determined primarily by genetic factors and environmental and acquired factors such as smoking. The host response is essentially protective in nature, but both under-activity (hypo-responsiveness) and over-activity (hyper-responsiveness) of aspects of the host response can result in enhanced tissue destruction. The purpose of this paper is to review current thinking in periodontics with special reference to periodontal epidemiology, microbiology, and pathogenesis.

Objective Preliminary animal data has shown that nitrous oxide has a preemptive analgesic effect on postoperative pain. Whether a similar effect occurs in humans is not established. In this prospective randomized crossover study, we investigated the effect of preincisional versus postincisional nitrous oxide on postoperative oral surgical pain. Study design The trial was a crossover study where 36 patients had each of their symmetrical impacted mandibular third molars randomly scheduled for removal in 2 sessions. Each of the 36 patients acted as his or her own control; one side of the jaw was allocated randomly to receive nitrous oxide preoperatively (pretreated side) and the other side postoperatively (posttreated side). The pretreated side received 50% nitrous oxide preoperatively for 20 minutes and 100% oxygen postoperatively for 20 minutes as placebo. The posttreated side received 100% oxygen preoperatively for 20 minutes and 50% nitrous oxide postoperatively for 20 minutes. The difference in postoperative pain between the pretreated and posttreated sides was assessed by 4 primary end-points: pain intensity as measured by a 100-mm visual analog scale (VAS) hourly for 8 hours, time to first analgesic, total analgesic consumption during the first 48 hours, and a 5-point categorical patient global assessment scale (0 = poor, 1 = fair, 2 = good, 3 = very good, and 4 = excellent). Results The VAS scores did not differ between the 2 sides at any time ( P = .50): neither did the time to first analgesic ( P = .8), amount of total analgesic consumption ( P = .77), and patient's global assessment differ ( P = .63). Conclusion Our results do not support the preliminary animal data that nitrous oxide has a preemptive analgesic effect for postoperative pain. 50% nitrous oxide administered preoperatively for 20 minutes has no preemptive analgesic effect on postextraction pain.

Aims: The study aims to determine the prevalence and severity of gingival overgrowth in a group of adult organ transplant recipients immunosuppressed with tacrolimus in comparison with ciclosporin, and to examine various risk factors for the development of gingival overgrowth. Methods: Forty patients taking tacrolimus were compared with 197 ciclosporin patients. Demographic, pharmacological and periodontal data were recorded for all patients. Comparison between the groups was made using independent sample t-tests, χ2 statistic or Mann–Whitney test. The effects of risk variables on overgrowth severity were examined using forward and backward stepwise regression analysis. Results: Those taking tacrolimus had a significantly lower mean gingival overgrowth score (14.1%) compared with ciclosporin (22.4%). Fifteen percent of the tacrolimus group had clinically significant gingival overgrowth compared with 30% in the ciclosporin group (p=0.053). Conclusions: The prevalence and severity of gingival overgrowth is less in adult transplant patients taking tacrolimus compared with ciclosporin. Concomitant use of calcium channel blockers and previous medication with ciclosporin are significant risk factors for the presence and severity of gingival overgrowth. Patients who have alteration of their immunosuppressant from ciclosporin to tacrolimus may persist in demonstrating gingival overgrowth attributable to their ongoing therapy with calcium channel blockers.

Objectives: To provide a critical review of the current evidence that implicates dental-induced bacteraemia as a risk for joint infections in patients fitted with joint prostheses and appraise the need for antibiotic prophylaxis. Design: Retrospective analysis. Setting: Mainly hospital-based patients or subjects. Outcome measures: The relationship between joint infections and dental treatment is equivocal at the best and there is no evidence that antibiotic prophylaxis provides such patients with any protection. Results: Microbiological evidence linking dental treatment-induced bacteraemia to joint infections is weak and if an oral commensal is implicated, it is more likely to have arisen either from a spontaneous bacteraemia or from a dental infection. As a consequence of the latter, we recommended the institution of good dental health prior to joint replacement. There may be a case for providing prophylaxis to the immuno-compromised patient, but only if the immuno-suppression is associated with a neutropenia. In such circumstances, only emergency treatment should be considered until the neutropenia is resolved. Antibiotic regimens that are recommended by orthopaedic surgeons have not been evaluated in a randomised placebo-controlled study and many of the drugs are not licensed for this purpose. The evidence on cost-risk benefit seems to demonstrate that antibiotic prophylaxis with either amoxicillin or penicillin is not cost effective when compared with no prophylaxis. Conclusion: The case for providing antibiotic prophylaxis prior to dental treatment in patients fitted with a joint prosthesis is weak or virtually non-existent. Furthermore, the risk from providing prophylaxis is greater than the risk of a joint infection.

References: Les maladies cardio-vasculaires representent un groupe tres heterogene de conditions qui ont une mortalite et une morbidite importantes. Ces maladies variees et leurs traitements peuvent avoir un impact sur le parodonte et sur le traitement parodontal But: Dans cet article, nous considerons trois aspects principaux et explorons leurs relations avec le parodontiste et l'etablissement du traitement parodontal. Methode: Les aspects qui ont ete passe en revue comprennent: les effets des medicaments cardio-vasculaires sur le parodonte, et la gestion des patients presentant des maladies parodontales; le risque de survenue d'endocardite infectieuse d'origine iatrogene parodontale ; les interrelations entre une maladie parodontale et une maladie des arteres coronaires. Resultats et conclusions: Les bloqueurs des canaux de calcium et du beta adrenocepteur entrainent respectivement une hyperplasie gingivale et une demineralisation dentaire. Des preuves montrent que l'arret des anti-coagulants avant un traitement parodontal entraine plus un risque accru de desordres thrombo-emboliques qu'un risque hemorragique. La relation entre la dentisterie et l'endocardite infectieuse demeure un probleme sujet a controverse. Il apparaitrait que la bacteriemie survenant lors des manoeuvres d'hygiene orale du patient sont plus a meme de provoquer une endocardite qu'une unique intervention parodontale. L'efficacite de la prophylaxie aux antibiotiques est incertaine (et peu susceptible d'etre demontree) et le risque mortel du a la penicilline apparait etre plus important que le risque mortel inherent a l'endocardite infectieuse. Finalement, l'association entre maladie parodontale et maladie des arteres coronaires a ete recherchee et il semble qu'il y ait beaucoup de probleme concemant l'interpretation de la manipulation des donnees. Plusieurs mecanismes putatifs ont ete avances, mais cela souligne cependant la necessite d'etudes d'intervention.

Dental pathology and/or treatment have been linked to a small number of brain abscesses as possible sources of infection. A further case is presented, in which a dental site is implicated. A review of the evidence was undertaken. A wide range of dental procedures had been implicated. In some cases the brain isolate was not of dental origin. In many, the diagnosis was one of exclusion. In order to confirm the role of odontogenic infection in the pathogenesis of brain abscess, modern sampling techniques should be used to precisely identify the isolates. The causal organism should be identified in both oral and cranial sites.

Objective: To determine the efficacy of a new kappa-opioid receptor agonist (R-84760) in patients with pain after third molar removal. Design: Randomised, double-blind, placebo-controlled study evaluating a single subcutaneous dose of R-84760 7μg. Setting: Day-stay oral surgery unit. Patients: 72 adult patients who had undergone removal of their impacted third molars under general anaesthesia. Main Outcome Measures: Pain intensity was assessed on a serial visual analogue scale (VAS) over a 4-hour investigation period. Patients had access to escape analgesics, and when these were taken, the time and dosage were recorded. Results: For all efficacy variables, R-84760 did not differ significantly from placebo (p > 0.05). Nearly all the patients required escape analgesics during the investigation period. Conclusions: R-84760, a kappa agonist, did not show efficacy in the management of postoperative pain after third molar surgery. The finding further highlights the equivocal efficacy of opioids in this pain model.

Background/Aims: Drug-induced gingival overgrowth remains a significant problem for the periodontologist. Many patients medicated with the drugs implicated in this unwanted effect experience significant, recurrent gingival problems that require repeated surgical excisions. In this review, we attempt to identify and quantify the various “risk factors” associated with both the development and expression of the drug-induced gingival changes. Method: The risk factors appraised include age, sex, drug variables, concomitant medication, periodontal variables and genetic factors. Elucidation of such factors may help to identify “at risk patients” and then develop appropriate treatment strategies. Results: Of the factors identified, the only one that can be affected by the periodontologist is the patents' periodontal condition. However, drug variables and concomitant medication do impact upon the expression of gingival overgrowth. Conclusion: The identificatioin of risk factors associated with both the prevalence and severity of drug-induced gingival overgrowth is important for all parties involved with this unwanted effect. Both periodontologist and patient have an important role to play in improving oral hygiene and gingival health. Likewise, there is always an opportinity to establish a close liaison between the patient's physician and the periodontologist to try and identify alternative drug regimens that can help reduce the impact of this unwanted effect.

Aims To determine the comparative efficacy of a new novel adenosine agonist (WAG 994) in postoperative pain after third molar surgery. Methods One hundred and twenty-two patients with postoperative pain after third molar surgery were randomised in a placebo double-blind trial with an active control group. In the early postoperative period patients received either a single dose of WAG 994 1 mg, ibuprofen 400 mg or matched placebos. Pain intensity score was recorded on serial visual analogue scales over a 6 h investigation period. Similarly, pain relief was completed on a 4 point categorical scale at each evaluation point. Patients had access to escape analgesic and if these were taken, the time and dosage were recorded. A sparse sampling technique was used to investigate the relationship between analgesic effects and plasma concentrations of WAG 994. Results All three treatment groups were matched for various demographic variables. For all efficacy measures, WAG 994 was not significantly different from placebo (P >0.05), whereas ibuprofen 400 mg was significantly superior to placebo (P

Interspecies differences in phenytoin (PHT) metabolism to 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH) were examined in human, cat and rat hepatic microsomes in vitro. Rat liver microsomes were 25 and 650 times more efficient at the conversion of PHT to HPPH than human and cat liver microsomes, respectively. Sulphaphenazole (83%) and tolbutamide (TOL) (64%) were the most potent inhibitors of HPPH formation in human liver microsomes, while ciprofloxacin (27%), enoxacin (27%) and TOL (26%) produced the greatest inhibition in cat liver microsomes. TOL was tested for its effect on HPPH formation and gingival overgrowth in cats in vivo. Eight cats received PHT sodium (4 mg/kg/d) and another 8 cats received PHT sodium together with TOL (20 mg/kg/d) for 10 wk. Six cats (75%) in the PHT group and 4 cats (50%) in the PHT & TOL group developed significant gingival overgrowth by the end of the study. However, the extent and incidence of the overgrowth were similar in the 2 groups. There were no significant differences in mean AUC 0-10 weeks for plasma PHT (552.90 +/- 29.6 micrograms.d/mL [PHT alone] vs. 582.41 +/- 24.49 micrograms.d/mL [PHT & TOL]) and unconjugated HPPH (1016.4 +/- 295.5 ng.d/mL [PHT alone] vs. 1174.5 +/- 397.2 ng.d/mL [PHT & TOL]) concentrations between the 2 groups of cats. Neither PHT nor HPPH were detectable in the plasma of 8 rats which received PHT (4 mg/kg/d) over a 10-wk period. The rats showed no sign of gingival inflammation (mean gingival index = 0) or gingival overgrowth (mean gingival overgrowth index = 0). Thirty-six adult epileptic patients on chronic PHT therapy were examined; 17 (47%) of the patients demonstrated clinically significant overgrowth. The mean steady-state plasma PHT concentration was comparable to, and the mean plasma unconjugated HPPH concentration 5-fold greater than, that observed in the cats. The results suggest that the rapid metabolism and elimination of PHT and HPPH in the rat may enable it to become more resistant towards developing gingival overgrowth, compared to the cat and man.

A double-blind, randomised trial was carried out to investigate the relationship between efficacy and various pharmacokinetic variables after single doses of racemic ketoprofen 12.5 and 25mg in patients with postoperative pain after third molar surgery over a 4-hour investigation period. Serial venous blood samples were obtained at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3 and 4 hours after administration for subsequent determination of R(-) and S(+) ketoprofen. The relationship between the R(-) and S(+) ketoprofen concentrations and pain experience was summarised for each patient by the slope of the regression line for that individual. There was no significant difference (p > 0.05) between the two doses of ketoprofen for any of the efficacy measures. Peak plasma concentrations of both R(-) and S(+) ketoprofen were observed between 60 and 90 minutes after dosage. A significant negative correlation (p < 0.002) was observed between the decrease in pain scores and plasma concentrations of both R(-) and S(+) ketoprofen after each dose. However, the amount of variability in each patient's response makes it difficult to identify a causal relationship between these parameters. Low doses of ketoprofen provide satisfactory pain relief in the early postoperative period after third molar surgery. Efficacy of this analgesic does not appear to be dose related or directly related to plasma concentrations of either R(-) or S(+) enantiomers.

This review article considers the changes in antibiotic usage over the past 40 years. Perhaps the most significant advance is in the prophylactic use of these drugs to reduce the effect of dentally induced bacteraemia. A greater understanding of various dental infections and, in particular, the role of bacteria in the pathogenesis of periodontal disease, has led to further interest in the indications for these drugs as adjunctive measures. Whilst new indications for the use of antibiotics become more widespread, all members of the healthcare professions need to be aware that these drugs have significant adverse effects and their misuse can lead to life-threatening infection. Clinical Relevance: Antibiotics have revolutionized the control of infectious diseases and have a significant role in dental practice. Dentists should be fully appraised of the benefits of these drugs and when they should be prescribed. Antibiotics usage should not be a substitute for interventional procedures, such as drainage of pus or removal of sources of infection. Indications for the use of these drugs as prophylactic measures are now reducing.

The role of HLA phenotype as a risk factor for drug-induced gingival overgrowth was investigated in a cohort of 172 transplant recipients. Clinically significant overgrowth warranting surgical correction was observed in 72 patients (42%). Using stepwise regression modelling. 6 clinical parameters were identified as significant risk factors for the severity of gingival overgrowth. These were; age. sex. creatinine plasma level, duration of therapy, papilla bleeding index and concomitant medication with a calcium channel blocking drug. 3 HLA alleles were also identified as risk factors when adjusted for other clinically significant risk factors (HLA -DR2, A24, B37). However, when the p-values for the HLA variables were corrected to compensate for the use of multiple significance testing, only HLA-B37 remained statistically significant at the 5% level. Organ transplant patients are at risk of developing gingival overgrowth, with approximately 25% medicated with cyclosporin alone requiring corrective gingival surgery. This figure more than doubles in patients concomitantly medicated with a calcium blocking drug. The data at present available would suggest that the severity of gingival overgrowth is also significantly associated with the HLA-B37 phenotype.

The distribution of gingival overgrowth was investigated in a cohort of organ transplant patients, who were medicated with cyclosporin or the combination of cyclosporin and a calcium channel blocking drug. Gingival overgrowth scores were significantly higher at buccal sites than lingual-palatally (p0.0001). There was no significant difference between upper and lower overgrowth scores (p = 0.88). The most severe overgrowth was seen in the canine region. Overgrowth between the central incisors was significantly less than in the canine region (por = 0.044) and was similar to that in the molar and premolar region. Although raised overgrowth scores were associated with increased levels of plaque and gingival inflammation, the distribution could not be explained by this observation.

Gingival overgrowth is a well-documented unwanted effect, associated with phenytoin, cyclosporin, and the calcium channel blockers. The pathogenesis of drug-induced gingival overgrowth is uncertain, and there appears to be no unifying hypothesis that links together the 3 commonly implicated drugs. In this review, we consider a multifactorial model which expands on the interaction between drug and/or metabolite, with the gingival fibroblasts. Factors which impact upon this model include age, genetic predisposition, pharmacokinetic variables, plaque-induced inflammatory and immunological changes and activation of growth factors. Of these, genetic factors which give rise to fibroblast heterogeneity, gingival inflammation, and pharmacokinetic variables appear to be significant in the expression of gingival overgrowth. A more thorough understanding of the pathogenesis of this unwanted effect will hopefully elucidate appropriate mechanisms for its control.

1. The effects of aspirin 1000 mg, paracetamol 1000 mg, codeine 60 mg on somatosensory evoked potentials (SEPs) were measured in a four-way cross-over study. 2. SEPs were elicited by electrical stimulation of the skin overlying the digital nerve at intensities close to pain threshold. 3. Amplitudes and latencies of both early and late SEPs were recorded, as well as first sensory threshold and subjective pain threshold. 4. None of the study medications affected the amplitude or latency of the late SEP components (100-250 ms post-stimulus). The amplitude of early components (15-30 ms post-stimulus) was also unaffected, but aspirin shortened the latency 30 min after ingestion. 5. Sensory detection and pain threshold to electrical skin stimulation were also unaffected by any of the study medications despite subjective central effects with codeine.

Much evidence has been published supporting the use of mouthwashes in a number of crucial areas of oral health. These areas include antibacterial activity, home irrigation, maintenance of implant health, postsurgery uses, reduction of bacteria in dental aerosols and bacteraemia reduction. Although other commonly used mouthwashes (e.g. chlorhexidine) have been reviewed in other articles in this Supplement, this article concentrates solely on data supporting essential-oil mouthwash use in these oral health areas.

Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely researched in an attempt to control periodontal diseases. This double-blind parallel group study investigated the effect of a systemic flurbiprofen preparation (100 mg daily), when combined with toothbrushing on the resolution of experimental gingivitis in human volunteers. 47 volunteers abstained from tooth cleaning for 21 days. On day 21, 23 subjects were prescribed 100 mg of flurbiprofen daily whereas 24 subjects were prescribed placebo. In both groups, toothbrushing was re-introduced and all subjects used the Bass technique for 2 min each day. Both treatment regimens were continued for 7 days. Plaque indices, gingival indices and gingival crevicular fluid flow were assessed at baseline (day 0) and on days 21 and 27. There were no significant differences at p = 0.05 between the groups for plaque indices or gingival crevicular fluid flow. The flurbiprofen group, however, demonstrated greater resolution of gingival inflammation by day 27 when compared to the placebo controls (p = 0.04). The plasma levels of flurbiprofen in the test group showed mean concentrations of flurbiprofen of 4.7 (+/- 2.1) micrograms/ml at 1 h after dosing. After 6 h, this had fallen to 4.4 (+/- 1.6) micrograms/ml. It is concluded that these serum concentrations of flurbiprofen are sufficient to produce significant anti-inflammatory effects in the gingival tissues.

1. Recent evidence has hinted at a peripheral site of action of morphine analgesic efficacy. 2. Previous studies by the same authors have developed a model for testing local analgesic efficacy by placing drugs into tooth sockets after third molar surgery. 3. The present studies test the hypothesis of local morphine activity at two dosage concentrations, 100 ng ml-1 and 100 micrograms ml-1 after third molar surgery. 4. No significant analgesic efficacy was found at either dose when compared with placebo.

Background: This case report describes a rare benign tumour, which presented as discrete areas of gingival hyperplasia affecting both the mandible and the maxilla. Method: Surgical excision of the lesions was carried out under local anaesthetic. Histopathological examination confirmed the diagnosis of oral myofibromatosis. Results: The condition responded to surgical excision and appears to have limited growth potential. It affects a wide spectrum of ages and can be alarming due to rapid enlargement and ulceration, so careful diagnosis is important to avoid unnecessary aggressive treatment.

Human herpes simplex 1 virus (HSV-1) is a DNA virus that has the ability to lie latent and be subsequently re-activated at any point during a patient's life. In the immunocompetent patient, resolution of clinical signs and symptoms usually occurs spontaneously after 14 days. In the immunocompromised patient, healing is often delayed and the effects are much more debilitating. Indications for therapeutic regimes of systemic antiviral treatment are discussed. Clinical Relevance: Recurrent oral ulceration caused by HSV-1 may be seen by the general dental practitioner and can cause significant morbidity.

Solid organ transplant patients are at an increased risk of developing lip malignancies. The role of HLA mismatch as a risk factor for such changes has only been described in skin.Lip lesions were evaluated in 403 solid organ transplant patients (immunosuppressed for at least 3 months) and findings compared to age and sex matched, otherwise healthy patients who acted as controls. HLA typing was provided for the transplant patients. All patients provided details of smoking history, alcohol consumption, skin type, as assessed by ease of burning to sunlight, and exposure to sunlight or other forms of ultraviolet radiation.Lip lesions were identified in 36 transplant patients and 29 were biopsied. Fourteen of the biopsies confirmed dysplastic or malignant changes. For the control patients, one lesion was identified as dysplastic. The prevalence of dysplastic and malignant lip lesions was significantly higher (P = 0.006) in the transplant patients when compared to controls. Risk factors for dysplastic/malignant changes in the transplant group included age (P = 0.01), smoking (P = 0.033) and HLA-B mismatch (P = 0.001). Lip covering provided a significant reduction (P = 0.045) in the development of lip changes.All transplant patients should be regularly screened for lip malignancies and consulted on smoking and sunlight exposure. HLA-B mismatch does appear to make these patients more susceptible to dysplastic/malignant changes.

Non-steroidal anti-inflammatory drugs (NSAIDs) have been used as systemic and topical preparations to control chronic periodontal disease in both animal and clinical human trials. Equivocal findings have failed to confirm whether any one NSAID is particularly efficacious, although flurbiprofen appears to be one of the most promising. 49 patients were allocated at baseline to test (25) and control (24) groups in a 12-month, controlled clinical trial. The groups were of similar age and sex distributions. During the first 3 months, both groups were given oral hygiene instruction and received scaling and root planning. The test patients were prescribed a 1% w/w flurbiprofen toothpaste to use 2 x daily for the entire 12 months. Control subjects were prescribed a placebo dentifrice. Plaque scores, bleeding scores, crevicular fluid flow, probing pocket depths and attachment levels were assessed at baseline and at 3, 6, 9 and 12 months. Radiographs were taken at baseline and 12 months using a modified intraoral, repositionable film holder. Both the flurbiprofen and placebo showed significant improvements in the clinical parameters over 12 months and there were no significant differences between the groups. Flurbiprofen-treated patients however, demonstrated a significantly greater proportion of sites (8.0%) with bone gain when compared to the placebo group (3.3%). There were no significant differences between the groups in the number of sites showing bone loss or no change. It is concluded that the 1% w/w flurbiprofen toothpaste exerts a small, yet significant effect on bone metabolism in the absence of any apparent effects on clinical parameters.

Poor oral health has been associated with a variety of systemic diseases. More recent evidence suggests that the extent and severity of periodontal disease and tooth loss may be associated with an increased risk of malignant disease. An association between poor oral health, smoking, increased alcohol consumption as a risk for oral cancer is well established. Associations between oral health and tooth loss with gastric, lung and pancreatic cancers are explored. Some of the associations need further evaluation before patients are warned about their periodontal health increasing the risk of malignant changes elsewhere in the body. The smoking factor may have a commonality linking oral health with an increased risk for malignant disease.This paper reviews the association between oral health (especially the extent and severity of periodontal disease and tooth loss) as a risk for certain malignancies.

The association between periodontal disease and various systemic conditions raises the question of the impact of periodontal therapy on general health. There is increasing evidence that periodontal intervention can reduce the prevalence of an adverse pregnancy outcome, improve glycaemic control in diabetics, reduce systemic markers of inflammation, lower cholesterol levels and improve vascular endothelial function. The magnitude of the impact of periodontal therapy on these modalities needs further quantification/study. Despite such reservations, there are indications that any form of periodontal treatment may have outcomes that extend beyond improving life expectancy of the dentition.This article reviews the possible impact of periodontal therapy on a variety of systemic conditions and evaluates potential benefits.

This investigation examines the incidence of phenytoin-induced gingival overgrowth in a population of epileptic patients who attend General Medical Practices for treatment of their epilepsy and compares the gingival changes with an otherwise healthy group of patients. The plaque score, gingival index, and gingival overgrowth did not differ significantly between the two groups (P>0.05). A significant correlation was observed between plaque score and gingival overgrowth in the phenytoin-treated patient, but in this group there was no correlation between gingival overgrowth and salivary concentration of the drug. The overall incidence of clinically significant overgrowth (13%) is considerably less than in other studies.

This study evaluated the efficacy of and investigated the site of action of aspirin and acetaminophen placed directly into tooth sockets after bilateral third molar surgery under local anaesthesia. On completion of surgery, 12 patients received in random, blind order either a suspension of aspirin in a methyl cellulose gel (100 mg/ml) in their tooth sockets and an oral placebo or the methyl cellulose alone in their sockets and an oral dose of aspirin (50 mg). The remaining 12 patients were treated in the same fashion with use acetaminophen. Patients were asked to record their pain, at intervals, over an 8-hour period on a 10 cm visual analog scale. Significantly less pain (p less than 0.05) was recorded throughout the 8-hour investigation period after both locally placed drugs than after placebo. There was no adverse effect on healing. The peripheral activity of aspirin is confirmed, and our findings suggest that acetaminophen has a significant peripheral effect in mediating its analgesic properties in postoperative pain after third molar surgery.

The gingival health of 19 patients with cardiovascular problems who were medicated with nifedipine was compared with a similar cohort treated with atenolol and a control group of healthy patients. In the nifedipine and atenolol groups, patients had been taking their respective medication for a minimum period of 6 months. Plaque scores were similar for all three groups. However, patients medicated with nifedipine had a significantly higher gingival index (P less than 0.005), gingival overgrowth scores (P less than 0.02) and probing sites greater than 3 mm (P less than 0.005) when compared with the atenolol and control groups. 4 patients in the nifedipine group experienced clinically significant gingival overgrowth which required surgical excision. Gingival changes in the nifedipine patients were not related to drug dosage or plaque scores. It is concluded that nifedipine therapy results in significant gingival changes, an effect which may be mediated by the drug's action on calcium transport.