Role of oral flora in chemotherapy-induced oral mucositis in vivo.

OBJECTIVE: To determine if commensal oral microflora impacts the severity of chemotherapy-induced oral mucositis (OM). DESIGN: Specific-pathogen-free (SPF) and germ-free Swiss Webster mice in the experimental groups were dosed with 5-fluorouracil (5-FU) to induce OM. Mice in the control group received phosphate buffered saline. Comparative analyses of the epithelial thickness and cell proliferation/turnover rates, as well as the expression levels of metalloproteinases and pro-inflammatory mediators in the oral mucosa between the control and experimental groups were determined by histopathological and immunohistochemical analyses. RESULTS: 5-FU-treated SPF and germ-free mice showed characteristic features of OM with reduced oral epithelial thickness, presence of inflammatory cells in the connective tissues, and increased levels of expression of metalloproteinases and pro-inflammatory cytokines compared to the respective control groups. When 5-FU-treated SPF and germ-free mice were compared, 5-FU-treated germ-free mice exhibited less severe epithelial destruction with higher expression of the cell proliferation marker Ki67, coupled with lower expression levels of metalloproteinases and pro-inflammatory cytokine in the oral mucosa. CONCLUSION: This study provides the first histopathological evidence that oral flora has a detrimental effect on chemotherapy-induced OM in vivo.

Systems wide analyses of lipids in the brainstem during inflammatory orofacial pain - evidence of increased phospholipase A(2) activity.

Recent studies suggest that CNS phospholipase A(2) (PLA(2) ) isoforms play a role in nociception, but until now, direct evidence of increased brain PLA(2) activity during allodynia or hyperalgesia is lacking. The present study was carried out, using lipidomics or systems wide analyses of lipids using tandem mass spectrometry, to elucidate possible changes in rat brain lipids after inflammatory pain induced by facial carrageenan injection. The caudal medulla oblongata showed decreases in phospholipids including phosphatidylethanolamine and phosphatidylinositol species, but increases in lysophospholipids, including lysophosphatidylethanolamine, lysophosphatidylinositol and lysophosphatidylserine, indicating increased PLA(2) activity and release of arachidonic acid after facial carrageenan injection. These changes likely occur in the spinal trigeminal nucleus which relays nociceptive input from the orofacial region. High levels of sPLA(2) -III, sPLA(2) -XIIA, cPLA(2) and iPLA(2) mRNA expression were detected in the medulla oblongata. Increase in sPLA(2) -III mRNA expression was found in the caudal medulla of carrageenan-injected rats, although no difference in sPLA(2) -III protein expression was detected. The changes in lipids as determined by lipidomics were therefore consistent with an increase in PLA(2) enzyme activity, but no change in enzyme protein expression. Together, these findings indicate enhanced PLA(2) activity in the caudal medulla oblongata after inflammatory orofacial pain.

Comparison of osteogenesis of human embryonic stem cells within 2D and 3D culture systems.

The objective of this study was to compare the osteogenic potential of human embryonic stem cells (hESCs) within two- and three-dimensional (2D and 3D) culture systems. hESCs of the H1 line (Wicell Inc., Madison, Wisc., USA) were induced to form embryoid bodies (EBs) through 5 days of suspension culture within non-adherent culture dishes. Following enzymatic dissociation, the EB-derived single cells were seeded on either novel 3D porous PLGA scaffolds or 2D culture dishes with the same total cell number. Osteogenic differentiation was induced through culture media supplemented with dexamethasone, L-ascorbic acid and beta-glycerophosphate. After 3 weeks of in vitro culture, quantitative and qualitative assays of osteogenic differentiation were conducted. Osteocalcin secretion and alkaline phosphatase (AP) activities were detected at significantly higher levels within 3D culture compared with the 2D system. Subsequently, the cell-scaffold constructs were implanted in iliac crest defects of immunosuppressed rabbits. After 4 weeks, the constructs were subsequently explanted and characterized by histology and X-ray analysis. Formation of new bone was detected within and around the implanted scaffolds. The results demonstrate that the osteogenic differentiation of human embryonic stem cells is enhanced in a 3D culture system compared to a 2D culture environment. Upon implantation in situ, the differentiating human embryonic stem cells can contribute positively to the repair and regeneration of bone defects.

Temporomandibular articular disorders can be alleviated with surgery.

DATA SOURCES: Medline, Embase and a variety of other sources were searched for English-language articles. Non-journal publications, conferences proceedings from professional organisations and from private and government agencies were screened. Bibliographies and reference lists from peer-reviewed and 'grey' literature were also reviewed. STUDY SELECTION: To meet the inclusion criteria articles must have reported studies of at least 10 patients, involve diagnoses of disc displacement with reduction (DDwR) or without reduction (DDw/oR) or degenerative joint disease (DJD) and include at least one of the following surgical techniques: arthrocentesis; arthroscopy; discectomy without replacement or disc repair/repositioning. DATA EXTRACTION AND SYNTHESIS: The outcome measured was the proportion of patients who reported improvement after treatment. Study success rates were recalculated on an intent-to-treat basis. Meta-analyses were performed along with meta-regressions where heterogeneity was an issue. Three classes of meta-analyses were performed using different artificial, untreated, control groups assuming three levels of spontaneous improvement, namely 0, 37.5 and 75%. RESULTS: Twenty-two studies, comprising 30 patient groups and sample sizes of 11-237 patients, met the inclusion criteria. For studies of patients with DDwR, at the 0 and 37.5% rates of control group improvement, arthroscopy and disc repair/repositioning resulted in treatment effects significantly greater than zero, with no significant differences in the efficacy of these two surgical techniques. For studies of patients with DDw/OR, the proportion of patients who improved after arthroscopy or arthrocentesis was significantly greater than zero at all three levels of estimated control improvement. Disc repair effect size was not significant at the 75% rate. CONCLUSIONS: Surgical treatments appear to have some efficacy for people who have temporomandibular articular disorders that do not respond to nonsurgical therapies.

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.

Bisphosphonates--a word of caution.

There have been recent reports from various centres of a possible association between avascular necrosis of the jaws and the use of bisphosphonates. This commentary reviews the available data and alerts clinicians to a possible adverse reaction in the oral cavity to a group of drugs that are commonly prescribed.

The role of Internet and personal digital assistant in oral and maxillofacial pathology.

Internet usage for dentistry and medicine is growing. Using search engines available on the Internet, websites for oral pathology and oral medicine information resources are explored and evaluated. A framework, whereby the personal digital assistant is used in conjunction with the Internet to enhance the practice and education of oral pathology, is proposed.

Oral pemphigus vulgaris: a case report and literature update.

INTRODUCTION: Pemphigus vulgaris is a rare cause of oral mucosal ulceration. CLINICAL PICTURE: A 47-year-old Chinese man presented with a 3-month history of oral ulceration. There were no lesions on the skin or other mucosal sites. Histology and immunostaining were consistent with pemphigus vulgaris. TREATMENT: Systemic and topical corticosteroids were instituted, together with topical antifungals. Conventional periodontal therapy was carried out to improve gingival/oral health. OUTCOME: Control of oral ulceration was achieved with re-establishment of normal oral function. No other sites to date have been involved. CONCLUSIONS: Chronic oral ulceration can be the sole manifestation of pemphigus vulgaris, at least initially. Early recognition of this lesion may prevent delayed diagnosis and inappropriate treatment of a potentially chronic dermatological condition.

MELAS: a case report.

INTRODUCTION: Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a rare, neurodegenerative and fatal disease caused by mutations in the mitochondrial DNA. Multiple systems of the body, including the oral cavity, can be affected by this disease. An electronic search of Medline spanning the years 1985 to 2003 was carried out using the key words "MELAS, Dentistry." It yielded no literature on the dental aspects of MELAS. CLINICAL PICTURE: This report documents the case of a 6-year-old Chinese boy diagnosed with MELAS and highlights problems encountered in the multidisciplinary management of MELAS patients, including its dental management. TREATMENT AND OUTCOME: Dental management was successfully performed under general anaesthesia with close medical supervision by paediatrician and anaesthetist. CONCLUSIONS: There is no known treatment of the underlying disease and the clinical course is usually unpredictable. Preventive dental care is important in this group of patients as concurrent medical conditions can complicate dental care.

Identification of RANKL in osteolytic lesions of the facial skeleton.

RANKL (receptor activator of nuclear factor kappaB ligand) promotes osteoclast differentiation, stimulates osteoclast activity, and prolongs osteoclast survival and adherence to bone. Abnormalities of the RANKL/RANK/osteoprotegerin system have been implicated in a range of diseases, including osteoporosis. To date, no work has been done in osteolytic lesions of the facial skeleton. In this study, specimens of ameloblastomas, dentigerous cysts, odontogenic keratocysts, and radicular cysts were subjected to immunohistochemical analysis for RANKL and tartrate-resistant acid phosphatase (TRAP). Immunofluorescence staining for TRAP was visualized under confocal microscopy. All specimens demonstrated distinct positive immunoreactivity to RANKL and TRAP. The TRAP-positive cells also stained with in situ hybridization for human calcitonin receptor, a definitive marker for osteoclasts. Mononuclear pre-osteoclasts were observed to migrate from blood to the connective tissue stroma and multinucleate toward the bone surface. It can be concluded that RANKL plays a role in bone resorption in osteolytic lesions of the facial skeleton.

Qualitative light and electron microscope study of glutamate receptors in the caudal spinal trigeminal nucleus of the rat.

Though ionotropic and metabotropic glutamate receptors have recently been recognized to play important roles in the transmission of orofacial nociceptive impulses, their detailed distribution in the spinal trigeminal nucleus has not been systematically investigated. There is also controversy regarding the electron microscope localization of metabotropic receptors. We therefore undertook this investigation to address the above-mentioned issues in the caudal part of the spinal trigeminal nucleus, using light and electron microscope immunocytochemistry, to provide baseline information for the development of agonists and antagonists of these receptors in the clinical treatment of orofacial pain. The results showed some moderately to strongly stained glutamate receptor 1 neurons, and many strongly stained glutamate receptor 2/3 neurons in lamina II of the nucleus, suggesting that the latter may play an important role in orofacial pain processing, with the former playing a minor role. The metabotropic glutamate receptor 1 immunoreactive product was localized mostly in dendrites, while most of the metabotropic glutamate receptors 2/3 immunoreactive product was deposited in axon terminals containing synaptic vesicles of different shapes, suggesting that glutamate receptors 2/3 may control the release of both excitatory and inhibitory neurotransmitters.

Sustained microglial immunoreactivity in the caudal spinal trigeminal nucleus after formalin injection.

Recent studies indicate that glia may be involved in altered nociceptive processing after a peripheral inflammatory lesion produced by injection of inflammatory reagents such as formalin and zymosan. Most of these studies, however, confined their observations to a period shortly after the injections. This study investigated the immunohistochemical responses of microglia in the caudal part of the spinal trigeminal nucleus for up to 60 days after subcutaneous injection of formalin into the lateral faces of Wistar rats. The results showed obvious up-regulation of microglial markers such as OX-18, OX-42 and OX-6 up to 21 days after formalin injection. These were somewhat reduced at 30 days after injection. Electron microscope investigation revealed no evidence of significant phagocytosis of degenerative neuronal elements by microglia in the nucleus at the time--that is, 7 days after formalin injection, when microglial activation was at its peak. Significantly, however, the period of microglial activation corresponded closely to that showing enhanced nociceptive behavior after perioral formalin injection (Cadet et al., 1995). This study indicates a microglial role in the genesis of enhanced nociceptive behavior.

Clinicopathologic study of odontogenic keratocysts in Singapore and Malaysia.

This was a retrospective study of odontogenic keratocysts in people from the Singapore-Malaysian region. The purpose of this study was to present the clinicopathologic features of odontogenic keratocysts in the Oriental population and to compare these data with those from other reported studies. Biopsy records from 1981 to 1992 of 61 cases of odontogenic keratocysts from patients in Malaysia and Singapore showed that 42.6% of patients were female and 57.4% of patients were male. Among patients with cysts, 75.4% were Chinese, 6.6% were Malays, 9.8% were Indians and 8.2% were other ethnic groups. The mean age of these patients was 26.98 +/- 15.38 years with a peak incidence occurring in the second to fourth decades. The location of the lesions was more often in the mandible (65.5%) than the maxilla (31.0%). There was a marked predilection for lesions to occur in the posterior mandible. Histologically, 90.2% of the cysts were lined with a para-keratinized stratified squamous epithelium while only 3.3% of the cysts were lined with orthokeratinized stratified squamous epithelium. Mixed para-keratinized and orthokeratinized epithelial linings were observed in 4 cases (6.5%). The cyst linings were mainly uninflamed (95.1%). Inflammation of the cyst wall was found in 42 cases (68.8%). Twelve (19.7%) cases contained keratin in the lumen. A satellite cyst was observed in only 6 cases (9.8%). In conclusion, most clinical and histological features seen in this study were similar to those found for Caucasians. The only clinical feature that was different was the peak age incidence, that ranged from the second to fourth decades, with an absence of a second peak. Odontogenic keratocysts presenting at the site of the dentigerous cyst were observed in 7 cases (11.5%).

Use of sedation in dentistry.

Fear and avoidance of dental treatment are major deterrents to oral health. Sedation can be used to control both the patient's fear and anxiety so that proper dental care can be provided for these patients. The purpose of this article is to discuss the use of sedation in dentistry and to provide a recommendation on the requirements and medico-legal aspects of sedation for the practitioner interested in incorporating sedation into their practice.

Oral medicine and surgery interests on the Internet.

The Internet is a global network which link millions of people via the information highway. The internet use for dentistry is growing rapidly. This has been accelerated by the use of many browsers. There has been a very rapid increase in the number of media resources and the quality of information over the internet has improved. Many universities, institutions and dental suppliers are establishing web pages. The resources is getting vast and in this paper, we explore the usefulness of the internet. This paper serve as a guide to the oral surgery, oral pathology and oral medicine resources and forums available on the information highway.

Trigeminal neuralgia. A retrospective survey of a sample of patients in Singapore and Malaysia.

This survey was undertaken to study the clinical features of trigeminal neuralgia in an Asian population. Demographic data of 44 patients treated at the Dental Faculty of the National University of Singapore and at the University of Malaya were reviewed. The results of the survey were analysed and comparisons made with those of Caucasian patients as reported in other studies where there was a general similarity in the clinical findings. Trigeminal neuralgia presented predominantly in females. Right-sided involvement occurred at a greater frequency, and the peak age at onset was between the sixth and seventh decades of life. The only significant variant in the present sample was the greater involvement of the mandibular branch of the trigeminal nerve rather than the maxillary division. In addition, there was a much greater representation from Chinese patients over Malays as compared with their ratios in the general population.

Ultrastructural study of NADPH-d positive neurons in laminae I and II of the rat caudal spinal trigeminal nucleus.

The present study investigated the ultrastructure of neurons in the caudal spinal trigeminal nucleus. These neurons which are believed to function as interneurons in the transmission of orofacial nonreflexive nociceptive information, measured 20 microns x 11 microns, and were nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) positive. The reaction product, formazan, was localized in the nuclear envelope, mitochondria, rough endoplasmic reticulum, and multivesicular bodies of these neurons. It was also localized in the membrane of the smooth endoplasmic reticulum at the axon terminal. The neurons were contacted by both axosomatic and axodendritic synapses formed by both NADPH-d positive and NADPH-d negative axon terminals. Two types of NADPH-d positive axon terminals could be recognized. The first was a large terminal containing many stained mitochondria and unstained small round agranular vesicles mixed with some slightly flattened ones. It formed asymmetrical axodendritic synapse. The second type of axon terminals contained pleomorphic synaptic vesicles and formed asymmetrical synapses upon both dendrites and soma. The sources of NADPH-d positive axon terminals were discussed. Most of the unstained axon terminals forming axosomatic and axodendritic synapses with stained cell bodies and dendrites contained flattened vesicles. In addition to the above, complicated synaptic configurations showing NADPH-d positive axoaxonic synapses in relation to NADPH-d negative dendritic spines were also seen in which a NADPH-d negative dendritic spine was completely contacted by a NADPH-d positive bouton which was in turn contacted by another NADPH-d positive bouton.