Peter J. Giannini

Diagnosis and Management of Oral Candidiasis

Oral candidiasis is the most common fungal infection in both the immunocompetent and the immunocompromised populations. This article reviews the clinical presentations of the different forms of oral candidiasis, as well as the diagnosis and management.

Simvastatin Application to Augment Facial Jaw Bone in a Dog Model: Pilot Study

BACKGROUND Locally injected simvastatin (SIM) has been shown to induce bone growth in rat models. The purpose of this study is to evaluate the effects of locally injected simvastatin in several human-like clinical situations in a beagle dog model. METHODS Four beagle dogs completed the study and were used in a split-mouth design. Dehiscence defects of 5 × 3 mm were created bilaterally on the lateral aspect of the mandibular second premolar (PM2) mesial roots including removal of root cementum. At the same surgery, porous hydroxyapatite-collagen grafts with resorbable membranes with or without 10-mg SIM were placed buccal to the mandibular first molars (M1). One week later, three weekly local injections of 10-mg SIM in ethanol and contralateral ethanol alone were initiated at three sites through the buccal mucosa: 1) 6 mm apical to the cemento-enamel junction (CEJ) of the maxillary fourth premolar (PM4; thin bone over root); 2) 6 mm apical to the CEJ of PM2 (dehiscence defect); and 3) 10 mm distoapical to the CEJ of the maxillary canine (edentulous ridge). Dogs were euthanized 2 months after the final injections. Block sections were harvested and specimens were decalcified and stained with hematoxylin and eosin. Histomorphometry was performed using digitized photographs and analyzed with distribution-free rank tests. RESULTS Regarding M1, the distance between CEJ and the alveolar crest was significantly more coronal in the SIM group (P = 0.038). Regarding the edentulous ridge, the width of new bone was significantly greater in SIM injection specimens (P = 0.0164). Regarding PM2, buccal bone in the dehiscence defects lacking periosteum was not augmented in the SIM group. Regarding PM4, the total width of bone 5 mm apical to the coronal height of contour (thin buccal bone covering the root) was significantly wider on the SIM side (SIM, 0.63 ± 0.53 mm; contralateral ethanol alone, 0.25 ± 0.19 mm; P = 0.0098). CONCLUSION Locally injected SIM has the ability to induce modest amounts of new bone formation in closed injection sites over a periosteal surface.

Oral histoplasmosis: An unusual presentation

Histoplasmosis is a localized or systemic fungal infection which may present as an acute primary or “reactivation” infection in the setting of immunosuppression. Tumor necrosis factor alpha (TNF‐α) antagonists, used in the management of rheumatoid arthritis and Crohn disease, have been linked to reactivation of quiescent histoplasmosis. Microscopically, granulomas are either not evident or are infrequent in histoplasmosis when associated with TNF antagonist therapy presumably due to the suppression of macrophage activity.

Effect of Simvastatin Injections on Temporomandibular Joint Inflammation in Growing Rats

PURPOSE Juvenile idiopathic arthritis often affects the temporomandibular joint (TMJ), resulting in facial deformities, and intra-articular injections of anti-inflammatory steroids used in treatment may inhibit bone growth in the developing condyle. The purpose of this pilot study was to evaluate the anti-inflammatory properties of simvastatin (SIM), a bone anabolic drug, compared with the common steroid triamcinolone hexacetonide (TH) in experimental TMJ arthritis of growing rats. METHODS Joint inflammation was induced by injecting complete Freunds adjuvant (CFA) into the TMJs of 32 growing (4-week-old) Sprague-Dawley rats while simultaneously receiving 1) ethanol drug carrier, 2) 0.1 mg of SIM, 3) 0.5 mg of SIM, or 4) 0.15 mg of TH. Six rats had no treatment to the TMJ. Animals were euthanized 28 days later, and TMJs were decalcified and stained with hematoxylin-eosin. RESULTS Histopathologic TMJ results showed that CFA injection along with drug carrier induced increased thickness of the articular layer on the head of the condyle and inflammation of the retrodiscal area (CFA and ethanol). Although both TH and SIM reduced the articular layer thickness, 0.5 mg of SIM was more effective at reducing subsynovial inflammation. CONCLUSIONS Intra-articular simvastatin showed anti-inflammatory properties in this TMJ model, prompting its further study in the growing TMJ, where bone anabolic properties would be important.

A dentigerous cyst associated with bilaterally impacted mandibular canines in a girl: a case report

IntroductionA dentigerous cyst is the most common developmental odontogenic cyst and is frequently noted as an incidental finding on radiographs. The most common teeth affected are impacted mandibular third molars and permanent maxillary canines. This case involves a dentigerous cyst encompassing the right and left impacted mandibular canines and crossing the midline. This is, to the best of our knowledge, the first reported case of a dentigerous cyst encompassing non-adjacent teeth and crossing the midline.Case presentationThe patient presented to our orthodontic clinic for treatment of malocclusion. The patient was a 10-year, one-month-old Caucasian girl with a dentigerous cyst encompassing the right and left impacted mandibular canines and crossing the midline.ConclusionThis case involves an unusual clinical and radiographic presentation of a dentigerous cyst. It shows a new variant of presentation that medical professionals, specifically dentists and radiologists, should be aware of, since a dentigerous cyst crossing the midline has not been previously reported as far as we are aware. This additional knowledge is important for inclusion on differential diagnosis lists and aids in the development of a proper treatment plan.

S4S8-RPA phosphorylation as an indicator of cancer progression in oral squamous cell carcinomas

Oral cancers are easily accessible compared to many other cancers. Nevertheless, oral cancer is often diagnosed late, resulting in a poor prognosis. Most oral cancers are squamous cell carcinomas that predominantly develop from cell hyperplasias and dysplasias. DNA damage is induced in these tissues directly or indirectly in response to oncogene-induced deregulation of cellular proliferation. Consequently, a DNA Damage response (DDR) and a cell cycle checkpoint is activated. As dysplasia transitions to cancer, proteins involved in DNA damage and checkpoint signaling are mutated or silenced decreasing cell death while increasing genomic instability and allowing continued tumor progression. Hyperphosphorylation of Replication Protein A (RPA), including phosphorylation of Ser4 and Ser8 of RPA2, is a well-known indicator of DNA damage and checkpoint activation. In this study, we utilize S4S8-RPA phosphorylation as a marker for cancer development and progression in oral squamous cell carcinomas (OSCC). S4S8-RPA phosphorylation was observed to be low in normal cells, high in dysplasias, moderate in early grade tumors, and low in late stage tumors, essentially supporting the model of the DDR as an early barrier to tumorigenesis in certain types of cancers. In contrast, overall RPA expression was not correlative to DDR activation or tumor progression. Utilizing S4S8-RPA phosphorylation to indicate competent DDR activation in the future may have clinical significance in OSCC treatment decisions, by predicting the susceptibility of cancer cells to first-line platinum-based therapies for locally advanced, metastatic and recurrent OSCC.

Functional activities and immunohistochemical cellular distribution of glutathione s-transferases in normal, dysplastic, and squamous cell carcinoma human oral tissues.

Clinical data show a strong correlation between tobacco and alcohol use and the development of oral squamous cell carcinoma (SCC). While this association implies that the oral mucosa actively metabolizes carcinogens, there is little information which depicts the carcinogen metabolizing enzymes within the oral cavity. Glutathione S-transferases (GSTs) primary function is to detoxify carcinogens by increasing their water solubility, GSTs represent key carcinogen metabolizing enzymes. Notably, individuals with a null phenotype for certain GST isoforms are at an increased risk to develop cancer. This study investigated the function and distribution of GSTs in human oral tissues. Our results from this pilot study showed a trend towards higher GST activities in SCC tissues relative to normal mucosa. Also, relative to normal tissues, the SCC and epithelial dysplasia samples showed a more intense and uniform GST intracellular distribution. GST activities are increased in many high grade cancers. Similarly, our data suggest that GST upregulation occurs in at least a subset of precancerous and malignant oral lesions.

Standardized rat model testing effects of inflammation and grafting on extraction healing

BACKGROUND Loss of alveolar ridge width and height after tooth extraction is well documented, but models to evaluate ridge preservation are neither standardized nor cost-effective. This rat model characterizes the pattern of bone turnover and inflammation after extraction and bone grafting with or without local simvastatin (SIM). METHODS Fifty retired-breeder rats underwent extraction of the maxillary right first molar and standard surgical defect creation under inhalation/local anesthesia. The left side of each animal served as unmanipulated control. Untreated groups (n = 8 to 9 per group) were compared (analysis of variance, t test) at days 0, 7, 14, and 28 for alveolar ridge height and width and for markers of inflammation and bone turnover by microcomputed tomography, histology, and enzyme-linked immunosorbent assay. Seventeen additional specimens had defects grafted with either bone mineralized matrix (BMM) or a BMM+SIM conjugate. RESULTS Extraction-induced bone loss (BL) was noted on buccal, palatal, and interproximal height (P <0.05) and ridge width (P <0.01). Week 1 inflammation positively correlated with ridge height; thereafter, a more intense inflammatory reaction corresponded to reduction in alveolar bone height and density (r = 0.74; P <0.05; Spearman). BMM+SIM preserved the most interproximal bone height (P <0.01), increased ridge width and bone density (P <0.01), enhanced 7-day prostaglandin E2 (P <0.01), and reduced 28-day inflammation density (P <0.05). CONCLUSIONS The standard defect used in the current study paralleled human postextraction alveolar BL. Defect grafting, especially BMM+SIM, reduced inflammation and preserved bone.

Malignant PEComa involving the mandible: report of a unique case.

We report a unique case of a malignant perivascular epithelioid cell neoplasm (PEComa) presenting as a slow-growing mandibular lesion in a 77-year-old Caucasian female. Primary osseous involvement by PEComas is rare. This is the first reported case of a malignant PEComa arising within the jaw. The patient is currently free of disease 2 years after treatment.

Early Detection of Cherubism with Eventual Bilateral Progression: A Literature Review and Case Report

Cherubism is a rare familial disease of childhood that commonly affects the bilateral mandible and maxilla and typically resolves in adulthood. It has been shown to have a male predilection and has been mapped to the SH3 BP2 gene. Only 2 cases of unilateral cherubism have been documented in the literature; in the first case, the contralateral side was eventually affected. Although rare, unilateral cherubism presents a diagnostic dilemma. This case report describes a unique presentation of unilateral cherubism that progressed to affect the contralateral side and describes some of the considerations in the diagnosis and treatment of unilateral benign giant cell lesions of the jaws.