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.

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.

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.

Are alcohol containing mouthwashes safe?

Alcohol (ethanol) is a constituent of many proprietary mouthwashes. Some studies have shown that regular use of such mouthwashes can increase the risk of developing oral cancer. Recently, the evidence has been reviewed by two separate authors. The conclusions from these reviews are conflicting. In this paper, we reconsider the epidemiological evidence linking alcohol containing mouthwashes with an increased risk of oral cancer. The evidence is considered in term of sample size, strength of association, confounding variables and data collection. In addition, clinical studies comparing alcohol versus non-alcohol mouthwashes are evaluated. The evidence suggests that the alcohol component of mouthwashes affords little additional benefit to the other active ingredients in terms of plaque and gingivitis control. In view of this outcome and the hypothetical risk of oral cancer, it would seem prudent that members of the dental team advise their patients accordingly.

Is gum disease killing your patient?

There is considerable epidemiological evidence to support the concept that poor oral health, especially the extent and severity of periodontal disease, may put patients at a significant risk for a variety of systemic conditions. This association raises the question that if patients or members of the dental profession ignore oral health, is there an increased risk of morbidity and mortality? In this presentation, the relationship between periodontal disease and many systemic conditions will be explored further. In addition, if periodontal disease does increase the risk of various systemic diseases, it raises the issue as to what the impact of treating periodontal disease is in reducing the magnitude of the risk. There is increasing evidence that reducing the inflammatory component in the periodontal tissues does have potential systemic effects. This has been shown to improve hyperglycaemic control in diabetics, reduce the prevalence of adverse pregnancy outcomes and improve surrogate markers that may be of benefit in patients suffering from coronary heart disease.

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.

Human diseases - the Newcastle experience.

The second edition of The first five years, published by the General Dental Council in 2002, identifies human diseases as a specific subject to be taught as part of the BDS curriculum. It states clearly the particular learning outcomes of such a course and then identifies a range of subjects (pathology, microbiology, medicine, surgery, pharmacology, therapeutics, accident and emergency services and medical emergencies) which should constitute the programme. Previously, many of these topics were taught and examined separately. In this article, we would like to share the Newcastle experience of developing a course in human diseases alongside the GDC guidelines.

Gingival fibroblasts grown from cyclosporin-treated patients show a reduced production of matrix metalloproteinase-1 (MMP-1) compared with normal gingival fibroblasts, and cyclosporin down-regulates the production of MMP-1 stimulated by pro-inflammatory cytokines.

BACKGROUND AND OBJECTIVE: Cyclosporin-induced gingival overgrowth arises from an alteration in collagen homeostasis and is enhanced by inflammatory changes in the gingival tissues. The aim of this study was to investigate the interaction among interleukin-1, oncostatin M, cyclosporin and nifedipine in promoting the up-regulation of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase by gingival fibroblasts. MATERIAL AND METHODS: Fibroblast cultures (n = 5) were obtained from healthy controls and from patients with cyclosporin-induced gingival overgrowth, and cells were harvested between the fourth and ninth passages. Cells were stimulated with interleukin-1 and oncostatin M, alone or in combination, and with different concentrations of cyclosporin (0-2000 ng/mL) and nifedipine (0-200 ng/mL). MMP-1 and tissue inhibitor of metalloproteinase-1 production was determined using an enzyme-linked immunosorbent assay technique. A CyQuant cell proliferation assay was used to determine the DNA concentration in the sample. RESULTS: Fibroblasts obtained from patients with cyclosporin-induced gingival overgrowth produced significantly lower levels of MMP-1 than control fibroblasts (p < 0.001); tissue inhibitor of metalloproteinase-1 levels were significantly lower (p < 0.05), and the ratio of MMP-1 to tissue inhibitor of metalloproteinase-1 was reduced, in the conditioned medium of patients with cyclosporin-induced gingival overgrowth compared with controls. Interleukin-1 and oncostatin M produced a significant increase in the up-regulation of MMP-1, which was reversed when cyclosporin and nifedipine were added to the cell cultures (p < 0.05). CONCLUSION: Pro-inflammatory cytokines significantly up-regulate MMP-1 in cultured gingival fibroblasts. Up-regulation is attenuated by both cyclosporin and nifedipine. The interaction may account for the synergism between inflammation and cyclosporin-induced gingival overgrowth.

Change in cardiovascular risk status after dental clearance.

There is considerable debate over the relationship between periodontal and cardiovascular disease. It has been postulated that inflammatory mediators prevalent in periodontal disease may impact on atheroma formation and the thrombotic process. In cross-sectional, observational studies, periodontitis is associated with elevated C-reactive protein (CRP), hyperfibrinogenaemia and moderate leukocytosis. CRP levels have also been shown to decrease following periodontal therapy. CRP is a reliable marker of the acute phase reaction to infections and/or inflammation and is a powerful predictor of future coronary events.

An evidence-based update on nonsteroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including both traditional nonselective NSAIDs and the selective cyclooxygenase (COX)-2 inhibitors, are widely used for their anti-inflammatory and analgesic effects. NSAIDs are a necessary choice in pain management because of the integrated role of the COX pathway in the generation of inflammation and in the biochemical recognition of pain. This group of drugs has recently come under scrutiny because of recent focus in the literature on the various adverse effects that can occur when applying NSAIDs. This review will provide an educational update on the current evidence of the efficacy and adverse effects of NSAIDs. It aims to answer the following questions: (1) are there clinically important differences in the efficacy and safety between the different NSAIDs, (2) if there are differences, which are the ones that are more effective and associated with fewer adverse effects, and (3) which are the effective therapeutic approaches that could reduce the adverse effects of NSAIDs. Finally, an algorithm is proposed which delineates a general decision-making tree to select the most appropriate analgesic for an individual patient based on the evidence reviewed.

The efficacy of topical hyaluronic acid in the management of recurrent aphthous ulceration.

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, double-blind 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.

The efficacy of three different surgical techniques in the management of drug-induced gingival overgrowth.

OBJECTIVES: The aim of the present study was to evaluate the efficacy of three different surgical techniques in both the management and effect upon rate of overgrowth recurrence of drug-induced gingival overgrowth (DIGO). MATERIALS AND METHODS: Two cohorts of patients who required surgical correction of their DIGO participated in the study. After baseline periodontal measures (plaque index, gingival inflammation and probing pocket depths), the patients underwent surgery. A split-mouth, crossover design was used to compare conventional gingivectomy with flap surgery (n=27), and conventional gingivectomy with laser excision (n=23). The main outcome variable was the rate of recurrence of DIGO following surgery. RESULTS: At 6 months, there was significantly less recurrence (p=0.05) in patients treated with laser excision, compared with those treated by conventional gingivectomy. The differences in rate of recurrence of DIGO were also reflected in changes in several periodontal parameters. Flap surgery offered no advantage over conventional gingivectomy with respect to the rate of recurrence. CONCLUSIONS: DIGO can be managed by a variety of techniques. Laser excision results in a reduced rate of recurrence.

The management of drug-induced gingival overgrowth.

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.

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.

Analysis of changes in gingival contour from three-dimensional co-ordinate data in subjects with drug-induced gingival overgrowth.

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 microm 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.

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.

Lasers in periodontology.

Since the development of the ruby laser by Maiman in 1960, lasers have been widely employed in medicine for a number of years. The purpose of this paper is to summarize potential applications for lasers in dentistry, with special regard to periodontology. This article briefly describes clinical applications of lasers and laser safety. Particularly, the use of a diode laser seems to be promising, especially in already compromised transplant patients, who need to be treated with a technique where the operative and post-operative blood loss, post-operative discomfort and the recurrence of drug-induced gingival overgrowth need to be kept to a minimum or eliminated. Therefore, the use of lasers in periodontology may lead to an alteration in present clinical practice and help to establish the best management strategy because, by maintaining periodontal health, the life quality of patients can be improved.

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.

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.