The Mutational Profile of Unicystic Ameloblastoma.

BRAF V600E is the most common mutation in conventional ameloblastoma (AM) of the mandible. In contrast, maxillary AMs appear to harbor more frequently RAS, FGFR2, or SMO mutations. Unicystic ameloblastoma (UAM) is considered a less aggressive variant of ameloblastoma, amenable to more conservative treatment, and classified as a distinct entity. The aim of this study was to characterize the mutation profile of UAM ( n = 39) and to compare it to conventional AM ( n = 39). The associations between mutation status and recurrence probability were also analyzed. In the mandible, 94% of UAMs (29/31, including 8/8 luminal, 6/8 intraluminal, and 15/15 mural subtypes) and 74% of AMs (28/38) revealed BRAF V600E mutations. Among the BRAF wild-type cases, 1 UAM showed a missense SMO mutation (p.L412F), whereas 2 NRAS (p.Q61R), 2 HRAS (p.Q61R), and 2 FGFR2 (p.C383R) activating mutations were identified in AM. Of the 3 maxillary UAMs, only 1 revealed a BRAF V600E mutation. Taken together, our findings demonstrate high frequency of activating BRAF V600E mutations in both UAM and AM of the mandible. In maxillary UAMs, the BRAF V600E mutation prevalence appears to be lower as was shown for AM previously. It could therefore be argued that UAM and AM are part of the spectrum of the same disease. AMs without BRAF V600E mutations were associated with an increased rate of local recurrence ( P = 0.0003), which might indicate that routine mutation testing also has an impact on prognosis.

Randomized pilot study on probiotic effects on recurrent candidiasis in oral lichen planus patients.

Some patients with oral lichen planus (OLP) experience recurrent oral candidiasis(OC). Probiotic bacteria have shown to reduce the oral Candida count in vivo. OBJECTIVE: To study whether probiotic intervention reduces recurrent OC in patients with OLP. MATERIAL AND METHODS: Twenty-two patients with symptomatic OLP were enrolled in the double-blinded, randomized, placebo-controlled intervention study. Lozenges containing Lactobacilli reuteri (DSM 17938 and ATCC PTA 5289) or placebo were dissolved intra-orally three times daily for 16 weeks, after which patients were followed up for 36 weeks. Mucosal symptoms, VAS pain, OLP severity score, plaque index (PI) and gingival index (GI), Candida count/carriage, and OC and/or need for symptomatic treatment were registered. Statistical significance was set at p < .05. RESULTS: No difference was observed between the groups during the intervention or follow-up in terms of recurrent OC (p = .966) or need for symptomatic treatment (p = 1.000). There was no difference in terms of Candida count (p = .96) or carriage over time (p = .511). GI decreased in the probiotic group and increased in the placebo group (p = .046). OLP severity score decreased in both groups during the study period (p = .039). Across the entire study period, the placebo group had higher VAS pain score (p = .037). CONCLUSIONS: Probiotic intervention did not reduce recurrent OC or Candida count/carriage, but the study experienced recruitment problems, which may have influenced results.

Effect of Probiotic Bacteria on Oral Candida in Frail Elderly.

The aim of this study was to investigate the effect of a daily intake of probiotic lactobacilli on the prevalence and counts of oral Candida in frail elderly patients living in nursing homes. The study had a double-blind randomized placebo-controlled design with 2 parallel arms. The study group consisted of 215 older adults (range, 60 to 102 y) who were enrolled after informed consent. After baseline examination and randomization, the subjects were given 1 lozenge containing 2 strains of the probiotic bacterium Lactobacillus reuteri (DSM 17938 and ATCC PTA 5289) or placebo twice daily (morning and evening). The intervention period was 12 wk, and saliva and plaque samples were collected at baseline and follow-up. The primary end point was prevalence of high Candida counts assessed from chairside tests. Secondary end points were levels of dental plaque and gingival inflammation. The groups were balanced at baseline. The attrition rate to follow-up was 19%. There was a statistically significant reduction in the prevalence of high Candida counts in the probiotic group but not in the placebo group, and the difference was statistically significant in both saliva and plaque (P < 0.05). No significant differences between the groups were noted concerning the levels of supragingival plaque or bleeding on probing. Thus, daily use of probiotic lozenges may reduce the prevalence of high oral Candida counts in frail elderly nursing homes residents (ClinicalTrials.gov NCT02391532).

Subgrouping of patients with oral lichen planus according to cytochrome P450 enzyme phenotype and genotype.

OBJECTIVE: This study aimed to determine if the activity of the environmentally influenced cytochrome P450 enzyme CYP1A2, alone or in combination with CYP2D6*4 genotype, discriminates subgroups of oral lichen planus (OLP) according to lifestyle factors and clinical manifestations. STUDY DESIGN: A total of 111 patients with OLP were categorized according to normal, low, or high CYP1A2 activity and CYP2D6 4 genotype. Lifestyle parameters influencing the CYP1A2 activity and symptoms and manifestations of OLP were recorded. RESULTS: Of the 111 patients, 21% had low, 65% normal, and 14% high CYP1A2 activity. The high-CYP1A2-activity group was more exposed to CYP1A2 inducers than the low-CYP1A2-activity group. In the normal-CYP1A2-activity group, more patients had a CYP2D6 4 genotype (58%) (P = .02), and they presented more symptoms (P = .003) and gingival lesions (P = .03). More patients in the low-CYP1A2-activity group and without CYP2D6 4 genotype presented red lesions (P = .04). CONCLUSIONS: We suggest CYP2D6 4 genotype as a disease-susceptible genotype and low or high CYP1A2 activity levels as indicators of environmental influence in OLP subgroups.

Oral candidosis in lichen planus: the diagnostic approach is of major therapeutic importance.

OBJECTIVES: Candida albicans is the most common fungal pathogen in humans, but other Candida species cause candidosis. Candida species display significant differences in their susceptibility to antimycotic drugs. Patients with symptomatic or erythematous oral lichen planus (OLP) commonly have Candida infection requiring correct identification of Candida species in order to initiate adequate antimycotic therapy. Therefore, conventional cytosmear and culture tests were compared with genetic diagnostics on oral rinse followed by agar culture and material collected by cytobrush from OLP patient mucosal lesion. METHODS: The genetic approach was validated on a reference panel of 60 well-defined unrelated fungal species. The study included 37 OLP patients. Oral candidosis (OC) was established based on clinical signs of OC and/or oral mucosal symptoms and at least one hypha in lesional cytosmear. Antimycotic treatment was initiated after OC diagnosis, and symptomatic treatment was initiated in no-candidosis situations. RESULTS: The composition of Candida species in oral rinse/culture test was different from that of lesional cytobrush sampling as more non-albicans species were detected by the latter. Unexpectedly, Candida dubliniensis was found to be overrepresented among patients with a history of antimycotic treatment indicating unintentional iatrogen selection. Of the 22 OLP patients receiving treatment, 27% of these should have been offered alternative therapy based on the improved diagnostic approach. CONCLUSION: This study highlights the importance of lesional sampling in OLP patients with suspected OC. CLINICAL RELEVANCE: Correct fungal identification is critical in order to initiate adequate antimycotic therapy, thus minimizing iatrogen selection of non-albicans species.

Scandinavian Fellowship for Oral Pathology and Oral Medicine: guidelines for oral pathology and oral medicine in the dental curriculum.

In Scandinavia, as in many European countries, most patients consult their general dentist once a year or more. This gives the dentist a unique opportunity and an obligation to make an early diagnosis of oral diseases, which is beneficial for both the patient and the society. Thus, the dentist must have knowledge of clinical symptoms, local and systemic signs and clinical differential diagnoses to make an accurate diagnosis. The dentist must be competent in selecting appropriate diagnostic tests, for example, tissue biopsy and microbiological samples, and conducting them correctly, as well as in interpreting test results and taking appropriate action accordingly. Furthermore, the dentist must be aware of diseases demanding multidisciplinary cooperation and be able to recognise his/her professional limitation, and to refer to other specialists when required. The dental curriculum changes over time as new approaches, treatments and diagnostic possibilities develop. Likewise, the role of the dentist in the community changes and may vary in different countries. As members of the Scandinavian Fellowship for Oral Pathology and Oral Medicine and subject representatives of oral pathology and oral medicine, we feel obliged to contribute to the discussion of how the guidelines of the dental curriculum support the highest possible standards of dental education. This article is meant to delineate a reasonable standard of oral pathology and oral medicine in the European dental curriculum and to guide subject representatives in curriculum development and planning. We have created an advisory topic list in oral pathology and oral medicine.

Prognosis by C-reactive protein and matrix metalloproteinase-9 levels in stable coronary heart disease during 15 years of follow-up.

BACKGROUND AND AIM: Elevated CRP and matrix metalloproteinase-9 associate with increased risk of cardiovascular events, possibly because these plasma proteins mark vulnerable atherosclerotic plaques. We tested the hypothesis that levels of C-reactive protein (CRP) and matrix metalloproteinase-9 associate with prognosis in patients with stable coronary heart disease. METHODS AND RESULTS: We measured baseline plasma CRP and matrix metalloproteinase-9 in 1090 patients with stable coronary heart disease and as the primary composite endpoint detected incident unstable angina, myocardial infarction and any death during 15 years of follow-up. CRP above versus below the median of 3.0 mg/L was associated with an increased cumulative incidence of unstable angina, myocardial infarction and any death combined (log-rank p < 0.0001). CRP above versus below the median had a corresponding hazard ratio of 1.5(95% CI, 1.3-1.8) after age adjustment, of 1.4(1.2-1.6) after multifactorial adjustment, and of 1.4(1.2-1.6) after multifactorial adjustment including degree of coronary disease. In contrast, matrix metalloproteinase-9 above versus below the median was not associated with risk of unstable angina, myocardial infarction and death. CONCLUSIONS: Elevated CRP, but not elevated matrix metalloproteinase-9, associates with increased risk of unstable angina, myocardial infarction and death in patients with stable coronary heart disease.

Scandinavian Fellowship for Oral Pathology and Oral Medicine: statement on oral pathology and oral medicine in the European Dental Curriculum.

BACKGROUND: For many years, dentists have migrated between the Scandinavian countries without an intentionally harmonized dental education. The free movement of the workforce in the European Union has clarified that a certain degree of standardization or harmonization of the European higher education acts, including the dental education, is required. As a result of the Bologna process, the Association for Dental Education in Europe and the thematic network DentEd have generated guidelines in the document 'Profile and Competences for the European Dentist' (PCD). This document is meant to act as the leading source in revisions of dental curricula throughout Europe converging towards a European Dental Curriculum. In order to render the best conditions for future curriculum revisions providing the best quality dentist we feel obliged to analyse and comment the outlines of oral pathology and oral medicine in the PCD. METHODS: The representatives agreed upon definitions of oral pathology and oral medicine, and competences in oral pathology and oral medicine that a contemporary European dentist should master. The competences directly related to oral pathology and oral medicine were identified, within the PCD. RESULTS: The subject representatives suggested eighteen additions and two rewordings of the PCD, which all were substantiated by thorough argumentation. PERSPECTIVES: Hopefully, this contribution will find support in future revisions of the PCD in order to secure the best quality dental education.

Full-scale control of Mycolata foam by FEX-120 addition.

Foaming incidents in activated sludge treatment plants are a worldwide problem and occur on a regular basis in both municipal and industrial activated sludge treatment plants. Foaming is most often caused by excessive growth of filamentous bacteria, especially the gram-positive ones affiliated within the Actinobacteria, e.g. the branched Mycolata or Candidatus Microthrix parvicella. Previous studies have shown that populations of Microthrix can be controlled by addition of certain polyaluminium compounds, but until now no effective chemicals have been identified to control other important foam formers such as the Mycolata. A new chemical (FilamentEx, FEX-120) was tested in full-scale in a Swedish wastewater treatment plant (WWTP) with immense foaming problems. In total, three different dosing events were carried out for more than 1 year. After only 8-17 weeks in each period, all foam had disappeared, and dosing of FEX-120 was stopped. Another 11 full-scale WWTPs in different countries were treated with FEX-120 because of severe Mycolata foaming on process tanks. In nine out of 11 plants, where the causative organisms were Gordonia or Skermania, a significant reduction of foam up to 100% was observed after treatment for approx. 10 weeks. In two WWTPs with unknown Mycolata organisms, no reduction was observed.

Can the genotype or phenotype of two polymorphic drug metabolising cytochrome P450-enzymes identify oral lichenoid drug eruptions?

BACKGROUND: Lichenoid drug eruptions (LDE) in the oral cavity are adverse drug reactions (ADR) that are impossible to differentiate from oral lichen planus (OLP) as no phenotypic criteria exist. Impaired function of polymorphic cytochrome 450-enzymes (CYPs) may cause increased plasma concentration of some drugs resulting in ADR/LDE. In an earlier study we did not find more patients with OLP (OLPs) with impaired CYP-genotype. OBJECTIVES: To test if more OLPs have an impaired CYP-phenotype than to be expected from the CYP-genotype and to find clinical criteria characterising oral LDE. METHODS: One hundred and twenty OLPs were genotyped for the most common polymorphisms of CYP2D6 and CYP2C19 that result in impaired function. One hundred and ten did a phenotype test of both enzymes. The exposure to drugs and polypharmacy and the CYP metabolism of the drugs were evaluated. The OLP manifestations were registered. RESULTS: The only difference in OLP manifestations was that patients with a CYP2D6 genotype with less than two fully functional alleles presented more asymmetrical OLP distribution in particular in non-medicated patients (P < 0.05). No more OLPs than expected from the genotype had a phenotype with reduced function. However, the established phenotypic categories could not differentiate between the genotypes with two or one fully functional allele. Nevertheless, among the patients with a phenotype with normal function the patients with only one functional allele had a statistically significant higher metabolic ratio compared to patients with two fully functional alleles (P < 0.05). CONCLUSION: It was not possible to identify LDE by impaired function of polymorphic CYPs.

Polymorphic drug metabolizing CYP-enzymes--a pathogenic factor in oral lichen planus?

BACKGROUND: Oral lichen planus (OLP) is a chronic mucosal disease with a characteristic clinical phenotype. Environmental exposures, e.g. drugs have been associated with the pathogenesis. OBJECTIVES: To test the hypothesis that some OLP lesions have a pharmacological pathogenesis related to polymorphisms of the cytochrome P450 enzymes (CYPs) resulting in poor or intermediate CYP metabolism. METHODS: One hundred and twenty patients with OLP and 180 gender-matched controls without OLP were genotyped for CYP2C9, CYP2C19, and CYP2D6 alleles with absent or reduced function. RESULTS: The prevalence of poor or intermediate metabolizers was not higher among the OLPs as compared with the controls; however, there were higher numbers of variant CYP2D6 genotypes among the OLP females (P < 0.05). There were no differences between the groups with regard to intake of drugs metabolized by polymorphic CYPs or drug or herbal products inhibiting CYPs. The prevalence of CYP2D6*4 alleles among the OLPs was higher [28%; 95% confidence interval (CI) 20-36%] than previously reported among Danes (19%; 95% CI 17-22%). Fifty per cent of the OLPs had a CYP2D6*4 genotype as compared with 30% in the background population (P = 0.0001). The CYP2D6*4 protein has sequence homology with human herpes simplex virus type 1 (HSV1) and Candida albicans, which may result in molecular mimicry. CONCLUSION: It was not possible to substantiate a pharmacological pathogenesis of OLP based on poor or intermediate CYP metabolism. However, molecular mimicry between CYP2D6, in particular CYP2D6*4, and common oral pathogens may be involved in the pathogenesis of OLP.

Expression of two drug-metabolizing cytochrome P450-enzymes in human salivary glands.

OBJECTIVE: The oral cavity is constantly lubricated by saliva and even small amounts of xenobiotics and / or their metabolites in the saliva may affect the oral mucosa. Our aim was therefore to clarify if xenobiotic metabolizing enzymes CYP1A2 and CYP3A4 are expressed in salivary glands. METHODS: Formalin-fixed paraffin-embedded specimens from parotid (10), submandibular (7) and labial (10) salivary glands were examined immunohistochemically and by in situ hybridization for expression of CYP1A2 and CYP3A4 protein and mRNA. RESULTS: CYP1A2 and CYP3A4 protein and mRNA were detected in ductal and seromucous / serous acinar cells in all gland types although to a varying degree and intensity. Mucous acinar cells were positive to a lesser extent. CONCLUSION: The results indicate a xenobiotic metabolizing capability of salivary glands. This may have implications for development of oral mucosal disease as a result of mucosal exposure to metabolites originating from internal sources (blood) as well as from saliva.

Identity, abundance and physiology of Aquaspirillum-related filamentous bacteria in activated sludge.

Microcolony-forming bacteria closely related to the genus Aquaspirillum in the Betaproteobacteria were recently observed to be abundant in many nutrient removal wastewater treatment plants. The developed oligonucleotide probe, Aqs997, however, occasionally also targeted some filamentous bacteria in activated sludge samples when fluorescence in situ hybridization was performed. In this study, the identity, abundance, and ecophysiology of these Aqs997-positive filamentous bacteria were studied in detail. Most of the Aqs997-positive filamentous bacteria could morphologically be identified as either Eikelboom Type 1701, Type 0041/0675 or possibly Type 1851, all characterized by epiphytic growth. They were found in almost all 21 wastewater treatment plants investigated. Two morphotypes were found. Type A filaments, which seemed to be the same genotype as the microcolony-forming bacteria targeted by probe Aqs997.Type B filaments also hybridized with probe GNS941, specific for the Chloroflexi phylum, so the true identity remains unclear. Aqs997-positive filaments usually stained Gram-negative, but Gram-positive filaments were also found, stressing the difficulties in identifying bacteria from morphology and simple staining results. Studies on the ecophysiology by microautoradiography showed that Aqs997-positive filamentous bacteria did not consume acetate and glucose, while some took up butyrate, mannose, and certain amino acids. Most likely, some Aqs997-positive filamentous bacteria were able to perform full denitrification such as the Aqs997-positive microcolony-forming bacteria, and some were able to store polyhydroxyalkanoates under anaerobic conditions, potentially being glycogen accumulating organisms.

Oral lichen planus and intake of drugs metabolized by polymorphic cytochrome P450 enzymes.

OBJECTIVE: To study if patients with oral lichen planus (OLP) had a medication profile different from that of a control group without oral mucosal lesions. It was hypothesized that OLP lesions might result from poor drug metabolism (PM) because of genetic variation of the major cytochrome P450-enzymes (CYPs with a PM-risk). SUBJECTS AND METHODS: Dental records of 172 OLP patients were reviewed in this cross-sectional study and 152 sex- and age-matched subjects served as controls. The measures for the drug profiles were medicine type (ATC-code), mono- and polypharmacy, CYP-enzyme metabolism pattern, and medicine with a potential to induce lichenoid drug eruptions. RESULTS: Fifty per cent of the OLP patients consumed daily medications as compared with 59% of the controls. The OLP patients more frequently consumed medicines metabolized by CYPs with a PM-risk (P = 0.03). Furthermore, they consumed more medicine with an inhibitory effect on one or more CYPs than the controls (P = 0.01). CONCLUSION: Confounders like sex, age, systemic diseases, drug distribution into the therapeutic classes, and polypharmacy were similar in the two groups; but the OLP patients consumed more drugs metabolized by CYPs with a PM-risk. The results argue for further investigation of associations between OLP, medication intake and the CYP-enzyme metabolic pathways.

[Primary cardiac lymphoma]. / Primaert, kardialt lymfom.

Primary cardiac non-Hodgkin lymphoma is very rare. Results recently published suggest that the prognosis is good, if the lymphoma is diagnosed early. The symptoms are nevertheless unspecific and a clinical investigation is often inconclusive. We report a case of a woman with symptoms of severe dyspnoea at rest, chest pain, and fatigue. The ECG showed a complete atrioventricular block. Magnetic resonance imaging (MRI) revealed a tumour in the right atrium and ventricle. A myocardial biopsy showed malignant non-Hodgkin lymphoma of the diffuse, large cell B-type. The patient was treated with chemotherapy and control MRI after four treatments showed complete regression of the tumour.