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.

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.

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.

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.

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.

Reconstruction of soft tissues of the chin and lower lip region following excision of a basal cell carcinoma.

A rather unusual case of basal cell carcinoma of the labio-mental fold area is presented where it was possible to preserve the vermilion of the lower lip after wide excision. This made reconstruction with bilateral nasolabial flaps and a platysma myocutaneous flap possible. Thus the sensitivity of the lower lip could be partly preserved, a competent lip seal obtained, microstoma avoided and a good vestibulum reconstructed.

Serious circulatory disturbance after Le Fort I osteotomy. A case report.

Severe impairment of the blood supply occurred in a patient who underwent a Le Fort I type osteotomy in which the fragment was displaced in a cranio-dorsal direction. Necrosis with sequestration of the torus palatinus present and some permanent parodontal damage ensued. Alternative procedures and management of developing circulatory impairment during surgery are discussed.

A survey of reasons for extraction of permanent teeth in Singapore.

A survey was carried out to determine the reasons for tooth extractions of permanent teeth in Singapore. Data were obtained from 52 dentists practising general dentistry over a period of 12 months. At the end of the 12-month period, data were collected from 1276 patients, from whom a total 272 teeth were extracted. In this population group, the results showed that the percentage of teeth extracted due to periodontal reasons and caries were about the same, that is 35.8% and 35.4%, respectively. There was an increase in teeth extracted due to periodontal reasons with age. In patients above 40 yr, an average of 76% of teeth were lost due to periodontal reasons. An average of 26.7% of teeth were lost due to periodontal reasons in patients under 40 yr old. However, the trend for loss of teeth due to caries is reversed. Posterior teeth were more frequently extract compared to anterior teeth. Third molars accounted for 24.7% of all extractions carried out, whilst central incisors were 8.0% of all extractions. Molars were often lost due to caries and lower anterior teeth were most frequently lost due to periodontal reasons. The results of this study did not demonstrate one predominant reason for extraction. Both caries and periodontal reasons were equally common causes of tooth extraction.

Subsequent treatment of chronic recurrent dislocation of the mandible after eminectomies.

A patient with recurrent bilateral dislocation of the mandible of 10 years duration had been treated by bilateral eminectomies. Recurrent dislocation, however, persisted and a LeClerc procedure, using rigid bone plating, was performed as a salvage operation.

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%).

Binucleated form of plasma cells in oral lesions--their "vital statistics".

Plasma cells are currently held to represent the end-stage differentiation of B-lymphocytes and hence do not undergo division. However, binucleated and occasionally multi-nucleated forms of plasma cells have often been recorded in histological materials containing plasma cell infiltrates. It was decided that a study be conducted to provide more information on the microscopic features of these binucleated cells. Of the fifty surgical specimens from different oral lesions examined by light microscopy, binucleated plasma cells were found in thirty-three specimens. The mean maximum diameter, surface area and volume were 26.87 microns, 534.61 microns 2 and 9466.28 microns 3 respectively. Morphologically, they resembled the mononucleated or single nucleated plasma cells. Their cytoplasm contain abundant basophilic cytoplasm and a prominent perinuclear golgi image. The two nuclei exhibit a clock-face or cartwheel appearance.

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.

A case of Ludwig's angina following tooth extraction.

Ludwig's angina developed in an adult Chinese male following a mandibular third molar extraction. Brawny and tender swellings of the floor of the mouth and neck, with the elevation of the tongue, were classically present. The management of this case was based on the current emphasis of early broad-spectrum and antibiotic therapy with the maintenance of an adequate airway. The role of dental infection in this condition was highlighted.

Retrograde removal of fractured endodontic instruments.

During root canal therapy, accidental fracture of endodontic instruments may occur. While in the majority of such cases the fragment concerned can be retrieved non-surgically, there are some occasions that surgical intervention is needed in order to remove the broken tip lodged within the root canal. In this paper the authors would like to suggest a management approach to this uncommon and extremely unpleasant complication in dental practice.

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.

Intraoral vertical ramus osteotomy.

In corrective surgery for mandibular prognathism, the vertical ramus osteotomy, also known as the vertical subsigmoid osteotomy (VSS) is one of the simplest osteotomy to perform and therefore widely popular with oral & maxillofacial surgeons. Traditionally, the surgical approach for VSS is by the extra-oral approach although the approach may be either extraoral or intraoral. In this paper, the main advantages and disadvantages of the following three techniques, i.e. VSS via extraoral approach, VSS via intraoral approach and the sagittal split ramus osteotomy will be discussed. The vertical ramus osteotomy via the intraoral approach is not usually performed in Singapore until recently. The authors would like to present the observations and a surgical technique employed by them to perform VSS osteotomy via an intraoral approach.

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.

Multiple odontogenic keratocysts of the jaws. Case report.

Single odontogenic cysts are very well documented in the literature. Of those less common reports concerning multiple jaw cysts, many have been associated with systemic conditions or syndromes such as Gorlin-Goltz or basal cell naevus syndrome, Hunter's syndrome and mucopolysaccharidosis, for example, Maroteaux-Lamy syndrome. A case of multiple odontogenic keratocysts unassociated with any syndrome is reported so as to add to the growing number of such cases in the literature. The possibility of this case being a partial expression of the Gorlin-Goltz syndrome is discussed.

Amyloidosis with oral involvement. Case report.

A patient with chronic renal failure was investigated after complaining of oral discomfort which was found to be due to macroglossia and generalized involvement of the oral soft tissues by amyloidosis. A search for multiple myeloma proved to be positive. She also had a previous history of Carpal-tunnel syndrome. Despite an initial good response to treatment with phenylalanine nitrogen mustard (melphalan hydrochloride), she finally succumbed to end-stage renal failure.