Oscillatory networks of high-level mental alignment: A perspective-taking MEG study.

Mentally imagining another's perspective is a high-level social process, reliant on manipulating internal representations of the self in an embodied manner. Recently Wang et al. (2016) showed that theta-band (3-7 Hz) brain oscillations within the right temporo-parietal junction (rTPJ) and brain regions coding for motor/body schema contribute to the process of perspective-taking. Using a similar paradigm, we set out to unravel the extended functional brain network in detail. Increasing the angle between self and other perspective was accompanied by longer reaction times and increases in theta power within rTPJ, right lateral prefrontal cortex (PFC) and right anterior cingulate cortex (ACC). Using Granger-causality, we showed that lateral PFC and ACC exert top-down influence over rTPJ, indicative of executive control processes required for managing conflicts between self and other perspectives. Finally, we quantified patterns of whole-brain phase coupling in relation to the rTPJ. Results suggest that rTPJ increases its theta-band phase synchrony with brain regions involved in mentalizing and regions coding for motor/body schema; whilst decreasing synchrony to visual regions. Implications for neurocognitive models are discussed, and it is proposed that rTPJ acts as a 'hub' to route bottom-up visual information to internal representations of the self during perspective-taking, co-ordinated by theta-band oscillations.

Reduced auditory steady state responses in autism spectrum disorder.

BACKGROUND: Auditory steady state responses (ASSRs) are elicited by clicktrains or amplitude-modulated tones, which entrain auditory cortex at their specific modulation rate. Previous research has reported reductions in ASSRs at 40 Hz for autism spectrum disorder (ASD) participants and first-degree relatives of people diagnosed with ASD (Mol Autism. 2011;2:11, Biol Psychiatry. 2007;62:192-197). METHODS: Using a 1.5 s-long auditory clicktrain stimulus, designed to elicit an ASSR at 40 Hz, this study attempted to replicate and extend these findings. Magnetencephalography (MEG) data were collected from 18 adolescent ASD participants and 18 typically developing controls. RESULTS: The ASSR localised to bilateral primary auditory regions. Regions of interest were thus defined in left and right primary auditory cortex (A1). While the transient gamma-band response (tGBR) from 0-0.1 s following presentation of the clicktrain stimulus was not different between groups, for either left or right A1, the ASD group had reduced oscillatory power at 40 Hz from 0.5 to 1.5 s post-stimulus onset, for both left and right A1. Additionally, the ASD group had reduced inter-trial coherence (phase consistency over trials) at 40 Hz from 0.64-0.82 s for right A1 and 1.04-1.22 s for left A1. LIMITATIONS: In this study, we did not conduct a clinical autism assessment (e.g. the ADOS), and therefore, it remains unclear whether ASSR power and/or ITC are associated with the clinical symptoms of ASD. CONCLUSION: Overall, our results support a specific reduction in ASSR oscillatory power and inter-trial coherence in ASD, rather than a generalised deficit in gamma-band responses. We argue that this could reflect a developmentally relevant reduction in non-linear neural processing.

The efficacy of topical hyaluronic acid in the management of oral lichen planus.

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) in soreness scores when compared with placebo for up to 4 h post-application. There was no difference between treatment groups (P > 0.05) with respect to oral function. Patients treated with 0.2% HA showed a significant reduction (P < 0.05) in the size of the erosive/ulcerated area after 28 days of treatment when compared with baseline. There was no significant difference in changes in ulcerative areas between treatment groups. CONCLUSIONS: Topical HA (0.2%) does appear to be of some benefit in the management of erosive lichen planus providing efficacy for up to 4 h after administration. Very frequent applications should be considered to obtain a more significant clinical benefit. Topical HA gel may be a useful addition to the treatment option for OLP.

Brain oscillations and connectivity in autism spectrum disorders (ASD): new approaches to methodology, measurement and modelling.

Although atypical social behaviour remains a key characterisation of ASD, the presence of sensory and perceptual abnormalities has been given a more central role in recent classification changes. An understanding of the origins of such aberrations could thus prove a fruitful focus for ASD research. Early neurocognitive models of ASD suggested that the study of high frequency activity in the brain as a measure of cortical connectivity might provide the key to understanding the neural correlates of sensory and perceptual deviations in ASD. As our review shows, the findings from subsequent research have been inconsistent, with a lack of agreement about the nature of any high frequency disturbances in ASD brains. Based on the application of new techniques using more sophisticated measures of brain synchronisation, direction of information flow, and invoking the coupling between high and low frequency bands, we propose a framework which could reconcile apparently conflicting findings in this area and would be consistent both with emerging neurocognitive models of autism and with the heterogeneity of the condition.

The efficacy of preoperative versus postoperative rofecoxib for preventing acute postoperative dental pain: a prospective randomized crossover study using bilateral symmetrical oral surgery.

BACKGROUND: Previous data have demonstrated that rofecoxib has good analgesic efficacy for acute postoperative dental pain. However, up to half of these patients require rescue analgesics within the first 24 hours. As the timing of analgesic interventions may be an important factor in pain control, the present study tested the hypothesis that rofecoxib administered preoperatively would improve the analgesic efficacy and reduce rescue analgesic requirements within the first 24 hours compared with postoperative administration. METHODS: This was a double-blind, randomized, crossover study where 45 patients had each of their identical impacted mandibular third molars removed under local anesthesia on 2 separate occasions. Patients acted as their own control; one side was pretreated with rofecoxib 50 mg, 2 hours before surgery, followed by placebo 15 minutes after surgery, and the contralateral side was pretreated with placebo 2 hours before surgery and posttreated with rofecoxib 50 mg 15 minutes after surgery. The difference in postoperative pain between 2 sides was assessed by 4 primary end-points: pain intensity as measured by a 100-mm visual analogue scale hourly for 12 hours, time to rescue analgesic, postoperative analgesic consumption, and patient's global assessment. RESULTS: Patients reported significantly lower pain scores (P = 0.04), longer time to rescue analgesic (P = 0.02), lesser postoperative analgesic consumption (P = 0.008), and better global assessment (P = 0.01) in the pretreated compared with the posttreated sides. There were significantly more patients in the pretreated group who did not required rescue analgesic within the first 24 hours (80% vs. 58%, P = 0.01), and the pain scores were extremely low in both groups during the 12 hours postoperative period (9.8 +/- 5.0 mm vs. 14.3 +/- 7.4 mm). CONCLUSION: Rofecoxib is an excellent analgesic for preventing postoperative dental pain and when given 2 hours preoperatively rendered most patients relatively pain free, requiring no rescue analgesics on the first postoperative day.

The efficacy of locally applied aspirin and acetaminophen in postoperative pain after third molar surgery.

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.

Salivary proteins and cytokines in drug-induced gingival overgrowth.

Little is known about the involvement of saliva in gingival overgrowth (GO). It was hypothesized that, in this situation, the composition of saliva is altered. Thus, proteins, albumin, cytokines, and growth factors in whole and glandular saliva were investigated. Differences between glandular and gingival contributions to the composition of saliva were explored in patients medicated with cyclosporin who exhibited GO (responders), those without GO (non-responders), and non-medicated subjects (controls). In whole saliva, interleukin-1alpha (IL-1alpha), IL-6, IL-8, epidermal growth factor (EGF), nerve growth factor (NGF), and albumin were detected, but in glandular saliva only EGF and NGF were identified. Albumin and IL-6 differed significantly between responders and controls, although the overall profile of salivary proteins remained unchanged. Thus, inflammatory cytokines and albumin are confined to whole saliva and are associated with GO, whereas its content of EGF and NGF appears unaffected by cyclosporin.

Plasma and saliva concentrations of phenytoin and 5-(4-hydroxyphenyl)-5-phenylhydantoin in relation to the incidence and severity of phenytoin-induced gingival overgrowth in epileptic patients.

This study examined the relationships between plasma and saliva concentrations of phenytoin and 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH), the major metabolite of phenytoin in man, and the prevalence and severity of gingival overgrowth. Thirty-six adult epileptic patients who had been receiving phenytoin for greater than 6 months without a recent change in dosage were assessed for signs of periodontal disease and gingival overgrowth. Plasma and saliva samples were analyzed by high performance liquid chromatography for the determination of phenytoin and HPPH concentrations. Seventeen patients demonstrated clinically significant gingival over-growth (responders; overgrowth index > or = 30%). There were significant correlations between the gingival overgrowth index and both the papillary bleeding index (r = 0.495; P < 0.005) and probing depth (r = 0.632; P < 0.005). The plaque index correlated with the papillary bleeding index (r = 0.420; P < 0.05) and the probing depth (r = 0.301; P < 0.005), but not with the gingival overgrowth index. The extent of gingival overgrowth did not correlate significantly with either plasma or saliva concentrations of phenytoin or HPPH. Mean plasma and saliva concentrations of phenytoin and HPPH did not differ significantly between non-responders and responders, nor did the mean plaque index. The mean papillary bleeding index (32.5 +/- 21.2 vs. 63.8 +/- 37.7; P < 0.01) and mean probing depth (12.4 +/- 14.4% vs. 35.9 +/- 25.3%; P < 0.02) were significantly greater in the responders. This study found no evidence of a relationship between phenytoin or HPPH concentrations in plasma or saliva and the extent, or prevalence of phenytoin-induced gingival overgrowth. Further studies with larger populations may be necessary to establish the relationship, if any, between phenytoin or HPPH levels and gingival overgrowth.

Iatrogenic gingival overgrowth in cardiac transplantation.

It is well established that both cyclosporin and nifedipine are associated with gingival overgrowth. Although both drugs are widely used in the management of organ transplant patients, there is little information on the prevalence and severity of this unwanted effect in cardiac transplant patients. This study evaluated the gingival health of 94 dentate cardiac transplant patients, all of whom were medicated with cyclosporin as a component of their immunosuppressive therapy. Sixty-three (63) of the patients were also medicated with nifedipine. Significantly higher gingival overgrowth scores (P < 0.0001) and periodontal probing depths (P = 0.001) were observed in patients medicated with the combination of cyclosporin and nifedipine than those medicated with cyclosporin alone. Likewise, there was a significantly greater need to carry out gingival surgery on patients taking the combination (62%), than those medicated with cyclosporin alone (25.8%) (P = 0.001). Patient's age, sex, duration of therapy, gingival bleeding index, and nifedipine therapy were important determinants for both the expression of gingival overgrowth and the need for surgery. Significant sequestration of nifedipine in the gingival crevicular fluid (GCF) was observed. The concentration of nifedipine in GCF did not relate to either the gingival changes or plasma concentration of the drug. Cardiac transplant patients are at risk of developing gingival overgrowth and approximately 50% require surgical intervention. This risk increases significantly when patients are medicated concomitantly with nifedipine.

Prevalence of gingival overgrowth induced by calcium channel blockers: a community-based study.

BACKGROUND: The prevalence of gingival overgrowth induced by chronic medication with calcium channel blockers is uncertain. Although there have been several studies examining this question, the results are conflicting, with previous estimates ranging from 20% to 83%. There have been only 2 studies examining the prevalence of overgrowth induced by diltiazem and amlodipine, with estimates of 74% and 3.3%, respectively. METHODS: The current study aimed to address the problems associated with these studies by examining a sample of patients taking one of 3 calcium channel blockers, who were drawn from a community-based population in northeastern England. Nine hundred eleven (911) subjects were recruited from general medical practices in the area. Of these, 442 were taking nifedipine, 181 amlodipine, and 186 diltiazem. In addition, 102 control subjects were examined. Drug and demographic data for each subject were recorded. The periodontal condition of all subjects was assessed including plaque index, papillary bleeding index, and a photograph of the anterior gingivae for subsequent analysis of overgrowth severity. RESULTS: More than six percent (6.3%) of subjects taking nifedipine were seen to have significant overgrowth. This overgrowth was statistically greater than the amount of overgrowth seen in either of the other 2 drug groups or the control population. The prevalence of gingival overgrowth induced by amlodipine or diltiazem was not statistically significant when compared to the control group. The severity of overgrowth within the nifedipine group was found to be related to the amount of gingival inflammation and also to the gender of the subject, with males being 3 times as likely to develop overgrowth than females. CONCLUSIONS: The prevalence of clinically significant overgrowth related to chronic medication with calcium channel blockers is low, i.e., 6.3% for nifedipine. Males are 3 times as likely as females to develop clinically significant overgrowth. The presence of gingival inflammation is an important cofactor for the expression of this effect.

Incidence and severity of phenytoin-induced gingival overgrowth in epileptic patients in general medical practice.

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.

Pharmacological control of periodontal disease. II. Antimicrobial agents.

Antimicrobial agents are of value in the management of certain types of periodontal disease, notably early onset, juvenile and refractory periodontitis. The diagnosis of these conditions is often made on clinical grounds but microbial sampling of the pocket flora is of value in determining the type of antimicrobial therapy. Routine systemic use of these drugs in the management of chronic adult periodontitis is contraindicated, and is no substitute for root surface debridement and thorough supragingival plaque control. Tetracyclines and metronidazole are the agents most frequently used in the management of periodontal disease. Both drugs can be given systemically or applied topically into the periodontal pocket. The latter route is preferred since the dose is reduced considerably, but the local tissue concentration is increased. The efficacy of local drug delivery is dependent upon the release kinetics of the drug from the delivery vehicle. Although local application can be time consuming, it reduces the risk of adverse reactions and drug interactions. The tetracyclines have the additional advantage of inhibiting collagenases. This property may facilitate repair and new attachment formation. Systemic metronidazole appears to be useful as an adjunct to conventional periodontal therapy. The combination of metronidazole 250 mg and amoxycillin 375 mg has been shown to be effective in the treatment of refractory periodontitis, including cases which are resistant to tetracycline. Clindamycin has also been used in the management of refractory periodontitis, but the unwanted effects of this drug must limit its systemic use for this purpose.

Pharmacological control of periodontal disease. I. Antiplaque agents.

Inhibition of the development of dental plaque remains one of the primary aims of periodontal care. Many patients, however, are unable to master completely the mechanical methods of plaque control and for this reason, considerable research efforts have been directed towards the development and use of chemical agents to inhibit the growth of plaque. This first of two articles, therefore, examines the pharmacological properties and efficacy of commercially available antiplaque agents. We have also summarized the findings of some of the major clinical trials that have provided the scientific basis for the introduction of these agents for the management of gingival inflammation.

Preoperative ketorolac has a preemptive effect for postoperative third molar surgical pain.

There is uncertainty regarding the role of preemptive analgesia in preventing postoperative pain. Most previous studies were of parallel design completed under general anesthesia with many confounding inter-patient's variables. The present study evaluated the efficacy of preemptive ketorolac in a crossover design in patients undergoing bilateral mandibular third molar surgery. This was a double blind, randomized, placebo-controlled study where 34 patients had each of their identical impacted mandibular third molars removed under local anesthesia on two occasions. Each patients acted as their own control; one side was pretreated with intravenous ketorolac 30 mg before surgery followed by placebo injection after surgery, and for the other side, the patient was given placebo injection before surgery and post-treated with intravenous ketorolac 30 mg after surgery. The difference in postoperative pain between pretreated and post-treated side in each patient was assessed by four primary end-points: pain intensity as measured by a 100-mm visual analogue scale hourly for 12 h, time to rescue analgesic, postoperative analgesic consumption, and patient's global assessment. Throughout the 12-h investigation period, patients reported significantly lower pain intensity scores in the ketorolac pretreated sides when compared with the post-treated sides (P = 0.003). Patients also reported a significantly longer time to rescue analgesic (8.9 h versus 6.9 h, P = 0.005), lesser postoperative analgesic consumption (P = 0.007) and better global assessment for the ketorolac pretreated sides (P = 0.01). Pretreatment with intravenous ketorolac has a preemptive effect for postoperative third molar surgery and extended the analgesia by approximately 2 h.

A prospective randomized crossover study of the preemptive analgesic effect of nitrous oxide in oral surgery.

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.

Dentistry and the medically compromised patient.

Certain medical conditions and their accompanying drug treatment do have an impact upon oral structures and the delivery of dental care. Recent evidence suggests that oral health could be a significant risk factor for coronary artery disease. Many medical conditions can affect dental care are often over-stated and lack an evidence base. Examples include the need for antibiotic cover in patients at risk from infective endocarditis and the necessity to provide supplementary corticosteroids for those patients on longterm steroid therapy. By contrast, certain systematic drug treatments can have a profound affect on the oral tissue. The most obvious is drug-induced gingival overgrowth. Drugs frequently implicated in this unwanted effect include phenytoin, ciclosporin and the calcium channel blockers. Several risk factors for drug-induced overgrowth have been identified and include age, sex, peridontal variables and a range of drug pharmacokinetic variables. The relationship between oral health and coronary artery disease opens up a potentially new vista for the delivery of oral care. Although the association is convincing, casualty has not been established. If casualty for this relationship can be confirmed then the delivery of dental care and the promotion of oral health will receive a significant impetus.

Pain measurement in humans.

Sound measurement, an essential component of any scientific discipline, remains a particular problem in pain research. The measurement of pain intensity, for example, is a difficult and often a subjective undertaking. This is of little surprise to clinicians and researchers, because it is well recognised that pain intensity, like other sensations and perceptions, is a private experience that displays considerable variability both across patients and within a patient across time. Nonetheless, pain measurement and discerning factors that may affect its measurement are important for diagnosis and to determine the effectiveness of treatment interventions. This article reviews the basic concepts, roles, instruments used, and factors affecting pain measurement. A variety of the most commonly used pain measurement instruments are evaluated for their advantages and disadvantages. The article aims to assist clinicians and researchers to select the pain measurement instruments that best serve their purposes.

Calcium channel blockers and gingival overgrowth.

Calcium channel blockers are widely used in medical practice for the management of cardiovascular disorders. Of concern to the dental practitioner is the effect of these drugs on the gingival tissues. All classes of calcium channel blockers have been implicated in causing gingival overgrowth. This review considers the prevalence, clinical features, histopathology, pathogenesis and management of this unwanted side-effect.

Is there a link between periodontal disease and coronary heart disease?

OBJECTIVE: To provide a critical review of the studies completed to date that have investigated a link between coronary heart disease and dental health. DESIGN: Retrospective analysis. SETTING: Mainly hospital-based patients or subjects involved in longitudinal health care studies. MAIN OUTCOME MEASURES: The incidence of coronary heart disease and its relationship to dental health and other recognised risk factors. RESULTS: Evidence suggests that dental health, in particular periodontal disease, may be a significant risk factor for coronary heart disease and further coronary events. Possible biological mechanisms that link the two diseases are appraised. CONCLUSIONS: There does appear to be increasing evidence that a relationship exists between dental health and coronary heart disease, especially in males aged 40-50 years. The presence of a hyperinflammatory monocyte phenotype may provide a common biological mechanism that links the two diseases.

Angiotensin converting enzyme (ACE) inhibitors and their implications for the dental surgeon.

Angiotensin enzyme converting (ACE) inhibitors are a widely prescribed group of drugs used in the management of hypertension and heart failure. Several unwanted effects are associated with ACE inhibitors and this paper highlights those significant to the dental surgeon. Of particular concern is the problem of angioedema, which can be life threatening. Three case reports are presented that illustrate this problem and the management is discussed.