Systemic immune response against the oral pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans is associated with the formation and rupture of intracranial aneurysms.

BACKGROUND AND PURPOSE: Periodontal infections are associated with the formation and rupture of intracranial aneurysms (IAs). This study investigated the role of two key periodontal pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. METHODS: Immunoglobulin A (IgA) and IgG antibodies against P. gingivalis and A. actinomycetemcomitans were measured with enzyme immune assay from the serum of 227 IA patients, of whom 64 also underwent clinical oral examination. As a control group, 1096 participants in a cross-sectional health survey, Health 2000, underwent serological studies and oral examination. Logistic regression was used for multivariate analysis. Immunohistochemistry was performed to demonstrate bacteria-derived epitopes in the IA wall. RESULTS: Widespread gingivitis and severe periodontitis were more common in IA patients than in controls (2× and 1.5×, respectively). IgA antibodies against P. gingivalis and A. actinomycetemcomitans were 1.5× and 3-3.4× higher, respectively, in both unruptured and ruptured IA patients compared to controls (p ≤ 0.003). IgG antibodies against P. gingivalis were 1.8× lower in unruptured IA patients (p < 0.001). In multivariate analysis, high IgA, but low IgG, antibody levels against P. gingivalis (odds ratio [OR] = 1.4, 95% confidence interval [Cl] = 1.1-1.8 and OR = 1.5, 95% Cl = 1.1-1.9; OR = 0.6, 95% Cl = 0.4-0.7 and OR = 0.5, 95% Cl = 0.4-0.7) and against A. actinomycetemcomitans (OR = 2.3, 95% Cl = 1.7-3.1 and OR = 2.1, 95% Cl = 1.5-2.9; OR = 0.6, 95% Cl = 0.4-0.8 and OR = 0.6, 95% Cl = 0.5-0.9) were associated with the risk of IA formation and rupture. Immunohistochemistry showed P. gingivalis epitopes in the IA wall. CONCLUSIONS: Exposure to the periodontal pathogens P. gingivalis and A. actinomycetemcomitans and dysfunctional acquired immune response against them may increase the risk of IA formation and IA rupture.

Novel maxillary enlargement technique in congenital nasal pyriform aperture stenosis: a case report and literature review.

Congenital nasal pyriform aperture stenosis (CNPAS) is a rare cause of neonate nasal obstruction. Because newborns are natural nasal breathers, urgent treatment may be needed. CNPAS is diagnosed by clinical symptoms and signs, and CT. In severe cases, surgical approach is needed. The most often used approach is widening of pyriform aperture via sublabial incision with nasal tubing. We report a novel surgical approach as a curative treatment for CNPAS by immediate transverse enlargement of the maxilla. We also review current literature of the condition focusing on surgical management of the disease.

Long-term patient satisfaction and the sense of coherence - a longitudinal study 10-15 years after orthognathic surgery.

OBJECTIVE: This study focuses on evaluating the long-term treatment outcome (10-15 years) and patient satisfaction after orthognathic treatment with bisagittal split osteotomy (BSSO). Furthermore, the aim was to evaluate whether the psychosocial factor, sense of coherence (SOC) associates with long-term patient satisfaction. MATERIALS AND METHODS: Study sample consisted of 57 patients who had orthognathic treatment with BSSO. Self-completion questionnaires were distributed approximately 1.8 years and 10-15 years after surgery to evaluate treatment outcome. SOC was evaluated with a 12-scale questionnaire 10-15 years after the surgery. RESULTS: After 10-15 years following BSSO, 96% of patients were highly or moderately satisfied with the treatment outcome and none expressed dissatisfaction. Less educated patients were more satisfied with the treatment outcome than those with a higher educational level. Patients who felt clear improvement in their facial appearance expressed higher satisfaction than those experiencing only minor facial improvement. Furthermore, patients with improvement in orofacial pains and headaches more often expressed high satisfaction than those without improvement of these symptoms. Patients with strong SOC seemed to have somewhat higher scores for functional aspects of long-term treatment outcome. CONCLUSIONS: Post-treatment satisfaction with orthognathic treatment appears to be long-lasting. Psychosocial factors may play a role in long-term post-treatment satisfaction. Our study strongly suggests that psychosocial factors should be taken into account in the treatment planning of orthognathic patients.

Role of oral pathogens in the pathogenesis of intracranial aneurysm: review of existing evidence and potential mechanisms.

Degeneration of intracranial aneurysm wall is under active research and recent studies indicate an increased risk of rupture of intracranial aneurysm among patients with periodontal diseases. In addition, oral bacterial DNA has been identified from wall samples of ruptured and unruptured aneurysms. These novel findings led us to evaluate if oral diseases could predispose to pathological changes seen on intracranial aneurysm walls eventually leading to subarachnoid hemorrhage. The aim of this review is to consider mechanisms on the relationship between periodontitis and aneurysm rupture, focusing on recent evidence.

Periodontitis and gingival bleeding associate with intracranial aneurysms and risk of aneurysmal subarachnoid hemorrhage.

Oral bacteria DNA has been found in intracranial aneurysms (IA) and a high prevalence of periodontitis was reported in IA patients. We investigated whether periodontitis associates with IA formation and aneurysmal subarachnoid hemorrhage (aSAH). First, we compared in a case-control setting the prevalence of periodontal disease in IA patients (42 unruptured IA, 34 ruptured IA) and in age- and gender-matched controls (n = 70) from the same geographical area (Health 2000 Survey, BRIF8901). Next, we investigated whether periodontitis at baseline associated with aSAH in a 13-year follow-up study of 5170 Health 2000 Survey participants. Follow-up data was obtained from national hospital discharge and cause of death registries. Univariate analysis, logistic regression, and Cox-regression were used. Periodontitis (≥ 4mm gingival pocket) and severe periodontitis (≥ 6mm gingival pocket) were found in 92% and 49% of IA patients respectively and associated with IAs (OR 5.3, 95%CI 1.1-25.9, p < 0.000 and OR 6.3, 95%CI 1.3-31.4, p < 0.001, respectively). Gingival bleeding had an even stronger association, especially if detected in 4-6 teeth sextants (OR 34.4, 95%CI 4.2-281.3). Severe periodontitis in ≥ 3 teeth or gingival bleeding in 4-6 teeth sextants at baseline increased the risk of aSAH during follow-up (HR 22.5, 95%CI 3.6-139.5, p = 0.001 and HR 8.3, 95%CI 1.5-46.1, p = 0.015, respectively). Association of periodontitis and gingival bleeding with risk of IA development and aSAH was independent of gender, smoking status, hypertension, or alcohol abuse. Periodontitis and gingival bleeding associate with increased risk for IA formation and eventual aSAH. Further epidemiological and mechanistic studies are indicated.

Changes in posterior airway space and hyoid bone position after surgical mandibular advancement.

OBJECTIVE: To evaluate cephalometric changes in posterior airway space (PAS) and in hyoid bone distance to mandibular plane (MP) 1-3 years after bilateral sagittal split osteotomy (BSSO). MATERIAL AND METHODS: The sample consisted of 36 females and 16 males who underwent mandibular advancement by BSSO. To observe sagittal changes in PAS and in hyoid bone distance to MP both pre- and postoperative cephalograms were analyzed using WinCeph® 8.0 software. For the statistical analyses paired T-test and multivariate logistic regression models were used. RESULTS: By the surgical-orthognathic treatment the sagittal dimension of PAS showed variable changes but it mainly diminished when the mandibular advancement exceeded 6 mm. In most cases the hyoid bone moved superiorly by BSSO. Logistic regression models showed that males, patients with narrow PAS at the baseline, and those with counterclockwise rotation of the mandible by the treatment gained more increase in PAS. However, an increase in sagittal PAS dimension tended to relapse over time. Concerning the movement of the hyoid it was found that the more PAS increased the less hyoid moved superiorly. In males the change in hyoid position was more obvious than in females. CONCLUSION: Males, patients with narrow PAS at the baseline, and those whose mandible moved in the counterclockwise direction with moderate advancement gained more retrolingual airway patency by BSSO.

Associations of Sedentary Behavior, Physical Activity, Cardiorespiratory Fitness, and Body Fat Content With Pain Conditions in Children: The Physical Activity and Nutrition in Children Study.

UNLABELLED: We investigated the cross-sectional associations of sedentary behavior, physical activity, cardiorespiratory fitness, and body fat content with pain conditions in prepubertal children. The participants were a population sample of 439 children aged 6 to 8 years. Sedentary behavior, physical activity, and pain conditions were assessed using questionnaires, cardiorespiratory fitness using maximal cycle ergometer test, and body fat percentage using dual-energy X-ray absorptiometry. The associations of sedentary behavior, physical activity, cardiorespiratory fitness, and body fat percentage with the risk of pain conditions were analyzed using multivariate logistic regression. Children in the highest sex-specific third of sedentary behavior had 1.95 (95% confidence interval [CI], 1.20-3.17; P = .007 for trend across thirds) times higher odds of any pain than children in the lowest third. Children in the highest sex-specific third of cardiorespiratory fitness had 46% (odds ratio [OR] = .54; 95% CI, .32-.91; P = .019) lower odds of any pain and 50% (OR = .50; 95% CI, .28-.87; P = .015) lower odds of headache than children in the lowest third. Children in the highest sex-specific third of body fat percentage had 44% (OR = .56; 95% CI, .34-.93; P = .023) lower odds of any pain, 49% (OR = .51; 95% CI, .30-.86; P = .011) lower risk of multiple pain, and 48% (OR = .52; 95% CI, .31-.86; P = .010) lower odds of lower limb pain than children in the lowest third. Physical activity was not associated with pain conditions. These findings suggest that prepubertal children with high levels of sedentary behavior, low levels of cardiorespiratory fitness, and low body fat content have increased likelihood of various pain conditions. This information could be used to develop strategies to prevent chronic pain in childhood. PERSPECTIVE: Our findings suggest that low cardiorespiratory fitness, high levels of sedentary behavior, and low body fat content are associated with increased likelihood of various pain conditions among prepubertal children. This information could be used to develop strategies to prevent chronic pain in childhood.

High frequency of BRAF V600E mutations in ameloblastoma.

Ameloblastoma is a benign but locally infiltrative odontogenic neoplasm. Although ameloblastomas rarely metastasise, recurrences together with radical surgery often result in facial deformity and significant morbidity. Development of non-invasive therapies has been precluded by a lack of understanding of the molecular background of ameloblastoma pathogenesis. When addressing the role of ERBB receptors as potential new targets for ameloblastoma, we discovered significant EGFR over-expression in clinical samples using real-time RT-PCR, but observed variable sensitivity of novel primary ameloblastoma cells to EGFR-targeted drugs in vitro. In the quest for mutations downstream of EGFR that could explain this apparent discrepancy, Sanger sequencing revealed an oncogenic BRAF V600E mutation in the cell line resistant to EGFR inhibition. Further analysis of the clinical samples by Sanger sequencing and BRAF V600E-specific immunohistochemistry demonstrated a high frequency of BRAF V600E mutations (15 of 24 samples, 63%). These data provide novel insight into the poorly understood molecular pathogenesis of ameloblastoma and offer a rationale to test drugs targeting EGFR or mutant BRAF as novel therapies for ameloblastoma.

Clinical signs of temporomandibular disorders and various pain conditions among children 6 to 8 years of age: the PANIC study.

AIMS: To examine the prevalence and significance of clinically determined signs of temporomandibular disorders (TMD) and pain in different parts of the body as well as the frequency, intensity, and other features of pain in children. METHODS: The subjects were a population-based sample of children 6 to 8 years of age. Complete data on clinical signs of TMD were available for 483 children. Data on pain during the past 3 months, assessed by a questionnaire administered by parents, were available for 424 children. Differences between the prevalence of at least one sign of TMD and the location or frequency of pain were evaluated using the chi-square test, as well as the associations between the prevalence, frequency, and location of pain and gender, the use of medication, and visits to a physician. The relationship of various pain conditions with the risk of having clinical signs of TMD was analyzed using logistic regression. RESULTS: Of the 483 children, 171 (35%) had at least one clinical sign of TMD. Of the 424 children, 226 (53%) had experienced pain during the past 3 months. Pain was most prevalent in the lower limbs (35%) and head (32%). Of the 226 children with pain, 119 (53%) had experienced frequent pain (≥ once a week). No gender differences were found. The risk of having at least one clinical sign of TMD was 3.0 (95% confidence intervals [CI]: 1.1-8.5, P < .05) times higher in children with back pain, 2.7 (95% CI: 1.2-6.0, P < .05) times higher in children with neck-shoulder pain, and 1.6 (95% CI: 1.1-2.5, P < .05) times higher in children with headache compared to children without these pain symptoms. The risk of having at least one clinical sign of TMD was 12.2 (95% CI: 1.4-101.8, P < .01) times higher among children with palpation tenderness in trapezius muscles than among those without it. CONCLUSION: Clinical signs of TMD and pain symptoms are common in children. The relationship of back pain, neck-shoulder muscle palpation tenderness, and headache with clinical signs of TMD suggests that more attention should be paid to stomatognathic function in children with such pain problems.

Surgical-orthodontic treatment and patients' functional and psychosocial well-being.

INTRODUCTION: Surgical-orthodontic treatment is a common treatment approach for adult patients with skeletal maxillomandibular discrepancy. Some patients report improvement in signs and symptoms of temporomandibular disorder (TMD) after surgery. Whether the correction of malocclusion is responsible for the improvement of TMD symptoms after orthognathic surgery is still controversial. The objectives of this prospective study were to evaluate subjective treatment outcomes in patients with bilateral sagittal split osteotomy (BSSO) and to find out whether signs and symptoms of TMD and changes in occlusion are related to patient satisfaction. METHODS: Eighty-two patients (53 female, 29 male) with a mean age of 32 years (range, 16-53 years) treated with BSSO in the Oral and Maxillofacial Department at Kuopio University Hospital in Finland were examined; 64 had mandibular advancement, and 18 had mandibular setback. Occlusion and signs and symptoms of TMD were registered pre- and postoperatively. At the postoperative examination (mean, 1.8 years after BSSO), the patients were asked to fill out a questionnaire about the influence of treatment on their masticatory function and symptoms of TMD, as well as their satisfaction with the treatment outcome. RESULTS: TMD symptoms were significantly reduced after treatment. Improvements were also reported in facial appearance (82%) and chewing ability (61%); also, facial (56%) and temporomandibular joint (40%) pain disappeared. However, in 12% of the patients, temporomandibular joint problems were worse after treatment. Most patients (73%) were very satisfied with the outcomes; no one expressed dissatisfaction. Multiple logistic regression analysis showed that subjects with improved mastication and self-confidence, and those without long-term neurosensory deficits, expressed high satisfaction with the treatment outcome. Patients with mandibular setback were more pleased with the outcome than those with mandibular advancement. CONCLUSIONS: Orthognathic patients generally experience functional and psychosocial benefits after surgical-orthodontic treatment. In addition to functional and morphological reasons, the psychosocial factors should be more emphasized when making the treatment decision and comparing the alternative treatment approaches.

High stromal versican expression predicts unfavourable outcome in oral squamous cell carcinoma.

BACKGROUND: Versican, an extracellular matrix proteoglycan, has been noted to be expressed in several malignant tumours and has been suggested to play an important role in cancer development and tumour growth. AIMS: To investigate whether the versican expression level in the peritumoural stromal tissue of primary oral squamous cell carcinoma (OSCC) predicts relapse-free or disease-specific survival. Also, to study the associations between versican expression and several other clinicopathological variables, as well as tumour cell proliferation. METHODS: Immunohistochemistry was used to study the expression of versican and tumour cell proliferative activity in 139 OSCCs. All pertinent clinical data were collected retrospectively from the hospital records. RESULTS: In this cohort, versican expression did not correlate with the clinicopathological factors or tumour cell proliferation. In univariate analyses, higher risk for disease recurrence was associated with higher stromal versican expression score (p = 0.02), positive neck node status (p = 0.02), lower Karnofsky performance status (p = 0.03) and higher tumour cell proliferation index (p = 0.04). Increased disease-specific risk of death was associated with high stromal versican expression score (p = 0.005) higher T class (p = 0.002), positive neck node status (p<0.001), higher stage (p<0.001), poorer histological differentiation (p = 0.005), worse general condition of the patient (p = 0.049) and increased tumour cell proliferative index (p = 0.02). In multivariate disease-specific survival analysis, high stromal versican expression score (p = 0.048), poorer histological differentiation (p = 0.047) and higher stage (p = 0.002) independently predicted poorer disease outcome. CONCLUSIONS: In this cohort, increased stromal versican expression correlated with both increased risk for disease recurrence and shortened survival. High stromal versican expression may thus be considered an independent and adverse prognostic marker in OSCC.

Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer with a special reference to activator protein-2, HER2, and prognosis.

PURPOSE: In the present study, we investigated the expression and prognostic value of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer as well as their relation to transcription factor activator protein (AP)-2 and HER2 oncogene. The role of invasion and metastasis-promoting MMPs and their potential regulators, AP-2 and HER2, is currently still unclear in breast cancer. EXPERIMENTAL DESIGN: MMP-2 and MMP-9 expressions were analyzed immunohistochemically in a large prospective series of 421 breast cancer patients diagnosed and treated between 1990 and 1995 at Kuopio University Hospital (Kuopio, Finland). The relation of MMP-2 and MMP-9 expressions to AP-2, HER2, clinicopathological data, and survival was investigated. RESULTS: Both MMP-2 and MMP-9 were expressed in the cytoplasm of malignant and stromal cells. High expression of MMPs in carcinoma cells was related to small tumors (T1, stage I), whereas positive stromal expression of MMPs was associated with aggressive factors. High expression of MMP-2 and MMP-9 in carcinoma cells, but not in stromal cells, was related to high AP-2 expression. Positive stromal MMP-2 expression was associated with HER2 overexpression in the whole patient group and in the node-negative patient subgroup. Positive stromal MMP-9 expression was related to HER2 overexpression in estrogen receptor (ER)-positive disease. In the univariate survival analysis, positive stromal MMP-9 predicted shorter recurrence-free survival (RFS; P=0.0389) and breast cancer-related survival (BCRS; P=0.0081) in ER+ disease, especially in the subgroup of ER+ tumors of < or =2 cm in diameter (T1; P=0.0031 for RFS, and P=0.0089 for BCRS). High MMP-9 expression in cancer cells predicted longer RFS (P=0.0351) in the whole patient group. In the multivariate analysis of the whole patient group, the independent predictors of shorter RFS were reduced MMP-9 expression in carcinoma cells (P=0.0248), HER2 overexpression (P=0.0001), and advanced-stage disease (P=0.0002). Shorter BCRS was predicted by advanced-stage disease (P <0.0001). CONCLUSIONS: Expression of MMP-2 and MMP-9 in breast cancer seems to be partly related to expression of AP-2 and HER2. Positive stromal MMP-9 expression predicts poor survival in the hormone-responsive small tumors, whereas MMP-9 expression in carcinoma cells favors survival. Evaluation of MMP-9 expression seems to add valuable information on breast cancer prognosis.

Reduced nuclear expression of transcription factor AP-2 associates with aggressive breast cancer.

PURPOSE: We proposed to investigate the expression and prognostic significance of activator protein 2 (AP-2) in breast cancer. EXPERIMENTAL DESIGN: AP-2 was immunohistochemically analyzed in a prospective, consecutive series of 420 breast cancer patients diagnosed and treated between 1990 and 1995 at Kuopio University Hospital, Kuopio, Finland. AP-2 expression was further compared with clinicopathological parameters and patients' survival. RESULTS: Nuclear AP-2 expression was lower in carcinomas compared with normal ductal breast epithelium (P < 0.001). Nuclear expression was more often seen in lobular than in ductal or other carcinomas (P = 0.048). Cytoplasmic staining was present in 47% of the carcinomas. Low nuclear AP-2 expression level in carcinomas was associated with advanced stage (P = 0.002), axillary lymph node positivity (P = 0.012), poor differentiation (P = 0.001), and recurrences (P = 0.003). In univariate survival analyses, low nuclear AP-2 expression (P = 0.0028), advanced stage (P < 0.0001), lymph node metastases (P < 0.0001), and poor differentiation (P = 0.0498) predicted shorter recurrence-free survival (RFS). Low nuclear AP-2 staining and/or shift to cytoplasmic expression predicted shorter RFS (P = 0.0050) and breast cancer-related survival (BCRS; P = 0.0314) in univariate analyses. Cytoplasmic expression alone did not have prognostic value. In multivariate analysis, low nuclear AP-2 expression (P = 0.0292) and advanced stage (P = 0.0001) were independent predictors of shorter RFS; and stage (P < 0.0001) and ER-status (P = 0.0321) independently predicted BCRS. In the lymph-node positive patients, RFS was independently predicted by stage (P = 0.0110) and nuclear AP-2 status (P = 0.0151). CONCLUSIONS: AP-2 seems to have a protective role in breast cancer. Low nuclear AP-2 expression was associated with disease progression and increased metastatic capability of the tumor. In addition, reduced nuclear AP-2 expression independently predicted elevated risk of recurrent disease in breast cancer.

Nuclear and cytoplasmic p53 expression in pharyngeal squamous cell carcinoma: prognostic implications.

BACKGROUND: The role of p53 expression in human neoplasms is still controversial, and it has been associated with both favorable and unfavorable outcome of the patients. Also cytoplasmic expression of p53 protein has been reported to affect survival in some cancers. Furthermore, an association between p53 and beta-catenin expression has been demonstrated. We studied the expression of p53 in a large group of oropharyngeal and hypopharyngeal squamous cell carcinomas and its relation to catenin expression, histologic differentiation, clinical data, and prognosis. METHODS: Primary tumors for analyses were obtained from 123 patients diagnosed with squamous cell carcinoma of the oropharynx or hypopharynx between 1975 and 1998 in Eastern Finland. Immunohistochemistry was used to evaluate the expression of p53 as well as alpha-, beta-, and gamma-catenins. RESULTS: In the primary tumors (n = 123), the nuclear p53 expression index was low in 42 (34%), intermediate in 38 (31%), and high in 43 (35%) cases. Cytoplasmic p53 expression was present in 56 (46%) and absent in 67 (54%) tumors. In univariate analyses (Kaplan-Meier), hypopharyngeal primary site (p =.02), high T class (p <.0005), presence of distant metastases (p =.02), low Karnofsky performance index (p <.0005), high nuclear p53 expression index (p =.01), and positive cytoplasmic p53 expression (p =.04) predicted poorer overall survival (OS). In Cox proportional hazards model, only T class (p =.0005), Karnofsky performance index (p =.005), and nuclear beta-catenin expression (p =.038) predicted poorer OS. CONCLUSION: Positive cytoplasmic p53 expression and nuclear p53 overexpression seem to relate to more aggressive features and unfavorable outcome in pharyngeal squamous cell carcinoma (PSCC). However, unlike more traditional variables, p53 expression is not an independent predictor of disease outcome in PSCC.

Inducible nitric oxide synthase expression in pharyngeal squamous cell carcinoma: relation to p53 expression, clinicopathological data, and survival.

OBJECTIVE: To investigate the expression of inducible nitric oxide synthase (iNOS) in oropharyngeal and hypopharyngeal squamous cell carcinoma (SCC) and its relation to p53 expression, histologic differentiation, clinical data, and prognosis. STUDY DESIGN: A retrospective survey. METHODS: Primary tumors for analyses were obtained from 118 patients diagnosed with SCC of the oropharynx or hypopharynx between 1975 and 1998 in eastern Finland. Immunohistochemical analysis was used to evaluate the expression of iNOS and p53. The expression pattern of iNOS was related to p53 expression, clinical data, and survival. RESULTS: High iNOS score was associated significantly with high nuclear p53 expression index (P = .006) and positive cytoplasmic p53 expression (P = .025). The score for iNOS expression was significantly lower in the largest (T4) tumors (P = .043). No association was seen between iNOS score and N or M class, tumor stage, or histologic differentiation. The score for iNOS expression was not related to overall survival. CONCLUSIONS: The expressions of iNOS and p53 seem to be inter-related in pharyngeal SCC, although the causality remains to be clarified. The expression of iNOS shows no prognostic value in pharyngeal SCC.