Oral lesions and immune reconstitution syndrome in HIV+/AIDS patients receiving highly active antiretroviral therapy. Epidemiological evidence

Objective: To determine whether opportunistic oral infections associated to HIV infection (OOI-HIV) are found in HIV+/AIDS patients with immune reconstitution related to highly active antiretroviral therapy (HAART). Methods. From among 1100 HIV+/AIDS patients (Service of Internal Medicine, Carlos Haya Hospital, Malaga, Spain) subjected to review of the oral cavity between January 1996 and May 2007, we identified those examined in 1996 and which were again examined between 1997 and 2007, and were moreover receiving HAART. The following data were collected: age, gender, form of contagion, antiretroviral therapy at the time of review, number of CD4+ lymphocytes/ml, and viral load (from 1997 onwards). We identified those subjects with an increase in CD4+ lymphocytes/ ml associated to HAART, and classified them as subjects with quantitative evidence of immune reconstitution (QEIR). Among these individuals with QEIR we moreover identified those with undetectable viral loads (QEIR+VL), and differentiated those patients with an increase in CD4+ lymphocytes > 500/ml (QEIRm+VL). In each group we determined the prevalence of OOI-HIV, following the diagnostic recommendations of the EC-Clearinghouse (CDC-Atlanta, USA - WHO). In addition, we analyzed the prevalence of OOI-HIV in the different groups in relation to the duration of HAART. Results. A total of 86 subjects were included (44 females and 42 males; 19 heterosexuals, 34 male homosexuals, and 33 intravenous drug abusers). Forty-two patients showed QEIR: 21 belonged to the QEIR+VL group, and 17 conformed the QEIRm+VL group. The prevalence of OOI-HIV per group was as follows: QEIR = 54.8%; QEIR+VL = 33%; QEIRm+VL = 35%. The most prevalent lesion in all groups was erythematous candidiasis. OOI-HIV increased with the duration of HAART (p=0.008), and were seen to be dependent upon late appearance of the mycotic lesions ( after 24 months under HAART). Conclusions: It is suggested that opportunistic oral infections associated to HIV infection form part of the clinical picture of immune reconstitution inflammatory syndrome, though such infections are of late onset.

Periodontal disease in gestational and type 1 diabetes mellitus pregnant women

Objective: The present study evaluated the relationship between periodontal disease and its clinical variables in Brazilian non-diabetic pregnant women (C), gestational diabetes mellitus (GDM), or type 1 diabetes mellitus (T1DM). Subjects and methods: A periodontal exam was performed in one hundred and sixty-one pregnant women (GDM:80; T1DM:31; C:50) by a single-blinded calibrated examiner who recorded plaque index (PI), gingival index (GI), bleeding index (BI), gingival margin location (GM), probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and tooth mobility index (MI). The medical variables were age, pregestational body mass index (pre-BMI), fasting plasma glucose (FPG), and glycated hemoglobin (HbA(1c)). Results: The GI, GM, PD, CAL, BOP, and MI were significantly higher (P < 0.01) among GDM and T1DM than for C. The PI was higher in GDM and similar between C and T1DM. The Adjusted Final Model for medical variables to evaluate the effects of groups on periodontal parameters confirmed these results. Conclusions: The presence of periodontal disease was significantly higher in Brazilian diabetic pregnancies (GDM and T1DM) when compared to non-diabetic pregnant women (C). The degree of periodontal disease was similar between the GDM and T1DM groups. Age, pregestational BMI, and HbA(1c) were factors related to CAL development in these two types of diabetes mellitus.

Periodontal disease in adults with untreated congenital growth hormone deficiency: a case-control study

P>Aim The aim of this study was to investigate the possible associations between isolated growth hormone deficiency (IGHD) and periodontal attachment loss (PAL) in adults affected by congenital IGHD. Materials and methods Forty-five previously identified IGHD subjects were eligible for this study. The final study sample comprised 32 cases (gender:20M/12F; age:44.8 +/- 17.5) matched for age, gender, diabetes, smoking status and income to 32 controls (non-IGHD subjects). Participants were submitted to a full-mouth clinical examination of six sites per tooth and were interviewed using a structured, written questionnaire. Periodontitis was defined as proximal PAL >= 5 mm affecting >= 30% of teeth. Results No significant differences were observed in the percentage of sites with visible plaque between IGHD and non-IGHD subjects (59.4% versus 46.9%, p=0.32). IGHD subjects had significant less supragingival calculus (31.3% versus 59.4%, p=0.02) and more bleeding on probing (71.9% versus 18.8%, p < 0.01) than controls. PAL >= 5 mm was significantly more prevalent (100% versus 71.9%, p < 0.01) and affected more teeth (30.5% versus 6.7%, p < 0.01) in cases than in controls. After adjusting for supragingival calculus, IGHD cases had a higher likelihood of having periodontitis than controls (OR=17.4-17.8, 95% CI=2.3-134.9, p=0.004-0.005). Conclusion Congenital IGHD subjects have a greater chance of having PAL.

The immunohistochemical profile of oral inflammatory myofibroblastic tumors

Objective. The aim of this study was to demonstrate the immunohistochemical profile of oral inflammatory myofibroblastic tumors (IMTs) along with morphologic analysis. Study design. Three cases diagnosed as oral IMTs were selected to compile an immunohistochemical panel constituted by calponin, caldesmon, Bcl-2, desmin, fibronectin, CD68, Ki-67, S100, anaplastic lymphoma kinase (ALK), alpha-smooth muscle actin, cytokeratins AE1/AE3, muscle-specific actin, CD34, and vimentin. An oral squamous cell carcinoma with a focal area of desmoplastic stroma was used as control for the stained myofibroblastic cells. Results. All oral IMTs were positive for calponin, revealing a strong and diffuse expression in the spindle-shaped cells. The lesions were also positive for vimentin (3/3), fibronectin (3/3), alpha-smooth muscle actin (3/3), and muscle-specific actin (1/3) and negative for h-caldesmon, Bcl-2, desmin, CD68, Ki-67, S100, ALK, cytokeratins AE1/AE3, and CD34. Conclusions. Within the results encountered, the present panel should be of great assistance in the diagnosis of oral IMTs. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011; 111: 749-756)

MMP1 and MMP20 contribute to tooth agenesis in humans

Objective: Variations in genes that are critical for tooth formation may contribute to the tooth agenesis. MMPs are potential candidate genes for dental alterations based on the roles they play during embryogenesis. The aim of this study was to investigate the possible association between MMP1, MMP3, and MMP20 and tooth agenesis. Methods: One hundred sixty-seven nuclear families from two different populations were analysed, 116 from Brazil and 51 from Turkey. Probands had at least one congenitally missing tooth. DNA samples were obtained from blood or saliva samples and genotyping was performed using TagMan chemistry. In addition, Mmp20 was selected for quantitative real-time polymerase chain reaction analysis with SYBR Green I Dye in mouse tooth development. Results: Associations between tooth agenesis and MMP1 (p = 0.007), and MMP20 (p = 0.03) were found in Brazilian families. In the total dataset, MMP20 continued to be associated with tooth agenesis (p = 0.01). Mmp20 was not expressed during the initial stages of tooth development. Conclusion: Our findings provide evidence that MMP1 and MMP20 play a role in human tooth agenesis. (C) 2010 Elsevier Ltd. All rights reserved.

The success of endosseous implants in human immunodeficiency virus-positive patients receiving antiretroviral therapy A pilot study

Background. In a pilot study, the authors aimed to determine the success rate of dental implants placed in patients who were positive for human immunodeficiency virus (HIV) and were receiving different regimens of highly active anti-retroviral therapy (HAART). They considered patients` levels of cluster of differentiation (CD) 4(+) cells and viral load, and they attempted to verify whether patients with baseline biochemical signs of bone mineral density loss could experience osseointegration impairment. Materials and Methods. One of the authors, a dentist, placed dental implants in the posterior mandibles of 40 volunteers, divided into three groups: one composed of HIV-positive patients receiving protease inhibitor (PI)-based HAART; a second composed of HIV-positive patients receiving nonnucleoside reverse transcriptase inhibitor based HAART (without PI); and a control group composed of HIV-negative participants. The authors assessed pen-implant health six and 12 months after implant loading. They analyzed the success of the implants in relation to CD4(+) cell counts, viral load and baseline pyridinoline and deoxypyridinoline values. Results. The authors followed 59 implants for 12 months after loading. Higher baseline levels of pyridinoline and deoxypyridinoline found in HIV-positive participants did not interfere with osseointegration after 12 months of follow-up. Average pen-implant bone loss after 12 months was 0.49 millimeters in group 1, 0.47 mm in group 2, and 0.55 mm in the control group. Conclusions. The placement of dental implants in HIV-positive patients is a reasonable treatment option, regardless of CD4(+) cell count, viral load levels and type of antiretroviral therapy. Longer, follow-up periods are necessary to ascertain the predictability of the long-term success of dental implants in these patients. Clinical Implications. Limited published scientific evidence is available to guide clinicians in regard to possible increased risks associated with dental implant placement in HIV-positive patients.

Angiomyolipomatous hamartoma of the upper lip: A rare case in an 8-month-old child and differential diagnosis

Hamartoma is a proliferation of normal tissues that are considered endogenous to the site of occurrence. In the head and neck region, hamartomas composed of other tissues different from blood and lymphatic vessels (hemangiomas and lymphangiomas) are very uncommon. We report an unusual case of upper lip angiomyolipomatous hamartoma in an 8-month-old patient. The patient underwent surgical treatment and the 1-year follow-up revealed no signs of recurrence. Angiomyolipomatous hamartoma is a very rare condition in the paediatric population group, especially in the head and neck region. It should be considered in the differential diagnosis of congenital lesions in childhood. (C) 2010 European Association for Cranio-Maxillo-Facial Surgery.

Gingival Overgrowth Among Patients Medicated With Cyclosporin A and Tacrolimus Undergoing Renal Transplantation: A Prospective Study

Background: The aim of this study is to make a longitudinal evaluation of the incidence and severity of gingival overgrowth (GO) induced by immunosuppressive agents, such as tacrolimus (Tcr) and cyclosporin A (CsA), in the absence of calcium channel blockers in patients undergoing renal transplantation (RT). Methods: This longitudinal study is conducted in 49 patients with RT who were divided into a CsA group (n = 25) and Tcr group (n = 24). The individuals were assessed at four time intervals: before transplant and 30, 90, and 180 days after RTs. Demographic data and periodontal clinical parameters (plaque index, cemento-enamel junction to the gingival margin, probing depth, clinical attachment level, bleeding on probing [BOP], and GO) were collected at all time intervals. Results: The mean GO index was significantly lower in the Tcr group compared to the CsA group after 30 (P = 0.03), 90 (P = 0.004), and 180 (P = 0.01) days of immunosuppressive therapy. One hundred eighty days after RTs, a clinically significant GO was observed in 20.0% of individuals in the CsA group and 8.3% of individuals in the Tcr group. However, this difference was not statistically significant (P = 0.41). There was a reduction in periodontal clinical parameters regarding the time of immunosuppressive therapy for PI and BOP (P<0.001) in both groups. Conclusion: Although there was no statistical difference in the incidences of clinically significant GO after 180 days of immunosuppressive therapy, it was observed that GO occurred later in the Tcr group, and the severity of GO in this group was lower than in patients who used CsA. J Periodontol 2011;82:251-258.

Detection of TGIF1 homeobox gene in oral squamous cell carcinoma according to histologic grading

Objective. TGIF1 homeobox gene involvement in oral cancer has not yet been investigated. This study analyzed the expression of TGIF1 transcripts and protein in oral squamous cell carcinoma (OSCC). Study design. Snap-frozen samples from 16 patients were taken from both OSCC and nontumoral adjacent epithelium (NT) for in situ hybridization (ISH). Forty-six paraffin-embedded samples of OSCC were submitted to immunohistochemistry (IHC). A descriptive analysis of the transcript signal detection was accomplished, and TGIF1 immunoexpression was carried out considering protein levels, localization, and cellular differentiation. Results. ISH reactions showed TGIF1 transcripts with a signal that was frequently intense in NT, and generally weak in OSCC, and that had stronger transcript signal in well-differentiated areas of OSCC when compared with poorly differentiated ones. IHC reactions had poorly differentiated cases associated with TGIF1 protein expression in both the nucleus and cytoplasm (P = .05, Fisher test). Conclusions. TGIF1 gain or loss of function might possibly play a role in oral cancer cell differentiation. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011; 111: 218-224)

The neural histogenetic origin of the oral granular cell tumor: An immunohistochemical evidence

Aims: Granular cell tumor (GCT) is a rare neoplasm that can appear in any site of the body, but most are located intraorally. Its histogenetic origin remains unclear. This report analyzes the immunoprofile of 15 cases of granular cell tumors, occurring in 13 women and 2 men and the lesions were located on the tongue or upper lip. Patient age ranged from 7 to 52. Methods: The patients demographic data and the cytological and architectural features of the lesions were analyzed in oral GCTs (n = 15). The lesions were also submitted to a panel of immunohistochemical stains with antibodies against S-100, p75, NSE, CD-68, Ki-67, Synaptofisin, HHF-35, SMA, EMA, Chromogranin, Progesterone, Androgen and Estrogen. Results: Among the fifteen cases analyzed, the most common location was the tongue (84.6%). Histologically, the tumors exhibited cellular proliferation composed mainly by polygonal cells presenting an abundant granular eosinophilic cytoplasm. The nuclei were central, and the cell membranes were moderately clear. No mitotic figures were observed. The immunohistochemical analysis showed positivity in all cases for S-100, p75, NSE and CD-68, and no immunoreactivity for Ki-67, Synaptofisin, HHF-35, SMA, EMA, Chromogranin, Progesterone, Androgen and Estrogen. Conclusion: The immunoprofile of granular cell tumors showed nerve sheath differentiation - lending support to their neural origin - and helping to establish a differential diagnosis between this lesion and other oral granular cell tumors, whether benign or malignant.

Diagnostic implications of oral intravascular papillary endothelial hyperplasia

This study examined the clinical, histological, and immunohistochemical features as well as the differential diagnoses of oral intravascular papillary endothelial hyperplasia (IPEH) to aid clinicians and pathologists in its diagnosis. Clinical features of five oral IPEH cases were obtained from medical records, and all histopathological diagnoses were reviewed. Immunohistochemical reactions, including anti-CD-34, laminin, vimentin, estrogen receptor alpha, and Ki-67, were assessed. Microscopically, a reactive proliferation of vascular cells composed of small papillary structures with hypocellular and hyalinized cores arising in an organized thrombus was seen. CD-34, vimentin, and laminin staining were strongly positive, while estrogen receptor alpha was negative in all cases. A low percentage of cells were positive for Ki-67 in four of five lesions, but one case was strongly positive. A diagnosis of angiosarcoma was investigated and rejected. IPEH presents specific microscopic characteristics that along with clinical data lead to an accurate diagnosis. The general dentist, the first to participate in the diagnostic process, must share the responsibility for diagnosis with the pathologist, and they must work together to determine the correct diagnosis and management. Oral lesions of IPEH are uncommon. Their main significance is that they show a microscopic resemblance to angiosarcoma. Thus, clinicians should have more information regarding this benign entity. Finally, we suggest that in recurrent cases exhibiting strong immunolabeling of proliferative markers the possibility of angiosarcoma should be investigated.

Cardiovascular responses to different stages of restorative dental treatment unaffected by local anaesthetic type

Background: The aim of this study was to evaluate the cardiovascular effects of maxillary infiltration using 2% lidocaine with 1: 100 000 adrenaline, 4% articaine with 1: 200 000 adrenaline, and 4% articaine with 1: 100 000 adrenaline in different stages during restorative dental procedures. Methods: Twenty healthy patients randomly received 1.8 mL of the three local anaesthetics. Systolic blood pressure, average blood pressure, diastolic blood pressure, and heart rate were evaluated by the oscillometric and photoplethysmograph methods in seven stages during the appointment. Results: Statistical analysis by ANOVA and Tukey tests of cardiovascular parameters did not show significant differences between the anaesthetic associations. There were significant differences for the parameters among different clinical stages. Conclusions: The variation of cardiovascular parameters was similar for lidocaine and articaine with both adrenaline concentrations and showed no advantage of one drug over the other. Cardiovascular parameters were influenced by the stages of the dental procedures, which showed the effect of anxiety during restorative dental treatment.

Release of cytokines by stimulated peripheral blood mononuclear cells in chronic periodontitis

Objective: The emergence of periodontal medicine increased interest in defining the behaviour of peripheral blood cells in periodontitis subjects in comparison with healthy group. The aim of this study was to evaluate the levels of interleukin (IL)-8, tumour necrosis factor-alpha (TNF-alpha), IL-6 and IL-10 released by Escherichia coli lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC) obtained from the peripheral blood of chronic periodontitis subjects. Design: PBMC samples were isolated from 19 systemically healthy donors, divided into generalized chronic periodontitis (n = 10) and healthy (n = 9) subjects. Cells were incubated for 24-48 h in 500 mu L wells containing RPM! 1640 and stimulated with 1.0 ng/mL of E. coli LPS. Supernatants were used to quantify the amounts of IL-8, TNF-alpha, IL-6 and IL-10 released using enzyme-linked immunosorbent assay (ELISA). Results: PBMC cells from periodontitis subjects released higher levels of TNF-alpha and IL-6 than those from healthy subjects (P < 0.05). Conversely, the supernatants of the stimulated PBMC cells obtained from healthy subjects presented higher amounts of IL-8 than those from periodontitis (P < 0.05). No differences were observed in the levels of IL-10 (P > 0.05) between groups. Conclusion: In conclusion, the results of the present study showed that E. coli LPS-stimulated PBMC from subjects with periodontitis present a different pattern of cytokine release when compared to PBMC from healthy subjects. This phenomenon could have implications locally, in periodontitis, as well as in systemic diseases. (C) 2010 Elsevier Ltd. All rights reserved.

Evaluation of the lateral pterygoid muscle using magnetic resonance imaging

Objectives: The aims of this study were to evaluate the visibility of the lateral pterygoid muscle (LPM) in temporomandibular joint (TMJ) images obtained by MRI, using different projections and to compare image findings with clinical symptoms of patients with and without temporomandibular disorders (TMD). Methods: In this study, LPM images of 50 participants with and without TMDs were investigated by MRI. The images of the LPM in different projections of 100 TMJs from 35 participants (70 TMJs) with and 15 participants (30 TMJs) without clinical signs and symptoms of TMD were visible and analysed. Results: The oblique sagittal and axial images of the TMJ clearly showed the LPM. Hypertrophy (1.45%), atrophy (2.85%) and contracture (2.85%) were the abnormalities found in the LPM. TMD signs, such as hypermobility (11.4%), hypomobility (12.9%) and disc displacement (20.0%), could be seen in TMJ images. Related clinical symptoms, such as pain (71.4%), articular sounds (30.4%), bruxism (25.7%) and headache (22.9%), were observed. Conclusions: Patients with TMD can present with alterations in the LPM thickness. Patients without TMD also showed alterations, such as atrophy and contracture, in TMJ images. Recognition of alterations in the LPM will improve our understanding of clinical symptoms and pathophysiology of TMD, and may lead to a more specific diagnosis of these disorders. Dentomaxillofacial Radiology (2010) 39, 494-500. doi: 10.1259/dmfr/80928433

A role for COX2-derived PGE2 and PGE2-receptor subtypes in head and neck squamous carcinoma cell proliferation

The overexpression of cyclooxygenase (COX)-2 is a frequent event in squamous cell carcinomas of the head and neck (HNSCC), and non-steroidal anti-inflammatory drugs, which are potent inhibitors of COX-1 and COX-2, exert chemopreventive effects on HNSCC cancer development. COX-2 promotes the release of the pro-inflammatory mediator prostaglandin E2 (PGE2), which acts on its cell surface G protein-coupled receptors EP1, EP2, EP3, and EP4. Here, we investigated the role of PGE2 and its receptors in cellular proliferation in HNSCC. The expression of COX-2 and EP1-4 was examined in immortalized oral epithelial cells and in a representative panel of HNSCC cell lines, and based on these data EP1-EP3 and COX-2 expression were evaluated by immunohistochemistry in a large clinical sample collection using HNSCC tissue microarrays. The ability of selective COX-2 inhibition to block PGE2 secretion was measured by ELISA specific assays. The effects of PGE2 on cell proliferation were evaluated using PGE2, its stable analog, and EP2 and EP3-specific synthetic agonists. The results presented here show that HNSCC tumoral lesions and their derived cell lines constitutively express COX-2 and the EP1, EP2 and EP3 receptors for PGE2. HNSCC cells secrete PGE2, which can be suppressed by low concentrations of COX-2 selective inhibitors, without inhibiting cell proliferation. Exogenously added stable PGE2 and EP3-specific agonists induce DNA synthesis in all HNSCC cell lines tested. Overall, our study supports the emerging notion that PGE2 produced in the tumor microenvironment by the overexpression of COX-2 in tumoral and inflammatory cells may promote the growth of HNSCC cells in an autocrine and paracrine fashion by acting on PGE2 receptors that are widely expressed in most HNSCC cancer cells. In particular, our findings suggest that EP3 receptor may play a more prominent role in HNSCC cell growth promotion, thus providing a rationale for the future evaluation of this PGE2 receptor as a target for HNSCC prevention strategies. Published by Elsevier Ltd.