BACKGROUND: We previously described a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre-EPF). METHODS: Here we aimed to investigate disease autoreactivity to vessels in all body organs/systems. We compared 57 patients and 57 controls from the endemic area, matched by demographics, age, sex, and work activity. We performed immunofluorescence, immunohistochemistry, confocal microscopy, immunoblotting, indirect immune electron microscopy studies, and autometallographic studies. We performed ultrasonography on large patient arteries, investigating for vascular anomalies. In addition, we reviewed autopsies on seven patients who died affected by El Bagre-EPF. We immunoadsorbed any positive vessel immunofluorescence with desmoglein (Dsg1), investigating for new autoantigens. RESULTS: Overall, 57/57 patients affected by El Bagre-EPF displayed autoantibodies to vessels in all the organs/systems of the body via all methods (P < 0.01). The autoreactivity was polyclonal, and the patient's antibodies colocalized with commercial antibodies to desmoplakins I and II, p0071, ARVCF, and MYZAP (all from Progen Biotechnik, Germany; P < 0.01; all present at cell junctions). Immunoadsorption with Dsg1 on positive vessel immunofluorescence showed that the immune response against the vessels was directed against non-Dsg1 antigen(s). Autometallographic studies showed deposits of metals and metalloids in vessel cell junctions and in erythrocytes of 85% of patients (P < 0.01). CONCLUSIONS: Immune response to these vascular antigens is likely altering endothelial cells and vessel shapes, thus disturbing hemodynamic flow. The flow alterations likely lead to inflammation and may play a role in the atherogenesis often seen in these patients.

A novel variant of endemic pemphigus foliaceus (EPF) was described among individuals in an area surrounding El Bagre, Colombia, South America. The population in this rural mining community is exposed to high environmental levels of mercury, used for gold extraction, as well as other minerals, metalloids, and trace elements (e.g., quartz, rutile, granite, magnetite, and almenite) and ultraviolet radiation. Fifty con-trol subjects and fifty EPF patients in the endemic area were examined for the presence of mercury in skin biopsies and hair, using autometal-lographic and mass spectroscopic analyses, respectively. Simultane-ously, serum levels of IgE were measured, and cutaneous tests for hy-persensitivity reactions were performed. Using autometallography, mercuric sulfides/selenides were detected in 14 of 51 skin biopsies dis-tributed similarly in the control and patient groups. However, signifi-cantly higher serum IgE levels and mercury concentrations in hair, urine, and nails were found in patients compared with controls. Mi-croscopic analysis revealed mercuric sulfides/selenides concentrated within and around the sweat gland epithelium, as well as in dendritic cells. Five skin biopsies from EPF patients and five from controls that tested positive for the presence of mercuric sulfides/selenides by autometallography were randomly selected for electron microscopic analysis. This analysis revealed a mixed electron-dense and electron-light material closely associated with desmosomes in patients. How-ever, there were intracellular vesicles containing an amalgam of elec-tron-dense and electron-light materials only in the EPF patients. Thus, EPF-affected individuals are exposed to high levels of environmental mercuric sulfides/selenides and other elements. This is the first study reporting mercuric sulfides/selenides in skin biopsies from people liv-ing in a focus of EPF, and these compounds may play a role in the pathogenesis of autoimmunity.

Background. Giant papillae tongue disorder (GRID) is a newly discovered, long-lasting clinical disorder that may develop in organ-transplanted pediatric recipients. The key feature of this disorder is the unique tongue lesion, which comprises swollen fungiform papillae. The aim of this study was to characterize the immunohistopathology of this novel inflammatory condition. Methods. Six organ transplanted children with GRID were included in the study. Routine histopathology and immunohistochemical stainings for CD3, CD4, CD8, CD25, FOXP3, CD20, CD138, CD68, CD1a, CD15, CD23, and mast cell tryptase were performed. Results. Immunohistochemical analyses of the oral lesions revealed a subepithelial infiltrate that was primarily composed of CD3- and CD4-positive T cells, CD20-expressing B cells, macrophages, and CD138-positive plasma cells. The CD20-positive cells did not display the typical B cell morphology, having in general a more dendritic cell-like appearance. The CD138-expressing plasma cells were distinctly localized as a dense infiltrate beneath the accumulation of T cells and B cells. Increased numbers of CD1a-expressing Langerhans cells were detected both in the epithelium and connective tissue. Because no granulomas were observed and only single lesional eosinophils were detected, GPTD does not resemble a granulomatous or eosinophilic condition. Conclusions. We describe for the first time the immunopathological characteristics of a novel inflammatory disorder of the oral cavity, which may develop after solid organ transplantation in children.

The use of Swedish oral moist snuff is a widespread habit in Sweden. In 1999, 25% of the adult male population and 3.1% of the female population were users of snuff. The aim of the present study was to evaluate how variations in pH and nicotine concentrations of snuff affect the oral mucosa, clinically and histologically, salivary pH and daily nicotine intake in 20 habitual users of loose snuff. The subjects were studied during use of their usual brand, after 12 weeks use of a snuff with lower pH and after another 12 weeks use of a snuff with both lower pH and lower nicotine concentration. Consumption data, oral soft tissue changes, salivary pH and nicotine intake were meas-ured. Further, biopsies were taken from the central part of the clinically observed lesions and histological changes were analysed. The subjects maintained their snuff consumption during the observation periods. The average salivary pH was higher during snuff use than in the morning. Further, it was higher shortly after the snuff was removed than during snuff use. After having switched to the snuff with both lower pH and lower nicotine concentrations, they showed a significant reduction in daily nicotine intake and developed significantly less pronounced clinical and histological changes. These results indicate that nicotine is one of the substances in snuff that has a biological effect on the oral mucosa. However, there also seems to be a synergistic effect between the pH and nicotine concentration in the snuff.

Tobaksfritt snus kan leda till förändringar i munslemhinnan som är nästan identiska med de skador som orsakas av tobaksinnehållande snus, visar observationer vid specialisttandvårdskliniken i Halmstad.

En 62-årig man remitterades för undersökning och behandling av en förändring i munslemhinnan innanför överläppen och som orsakats av påsförpackad tobaksfri snusprodukt (ONICO®, Swedish Match). Såväl den kliniska som den histopatologiska bilden var identisk med den man finner vid förändringar orsakade av tobaksbaserade påsförpackade snusprodukter. Patienten ombads att under en treveckorsperiod ändra applikation av snuset från vänster till höger sida. Efter dessa tre veckor hade förändringen helt försvunnit på vänster sida och en ny liknande den ursprungliga uppstått på höger sida.

Recent experimental research demonstrated that non-reducing temporomandibular joint (TMJ) disc displacement in growing rabbits impaired mandibular growth. TMJ disc displacement is also shown to induce histological changes of the condylar cartilage. The authors hypothesized that the severity of these changes would correlate to the magnitude of mandibular growth. Bilateral non-reducing TMJ disc displacement was surgically created in 10 growing New Zealand White rabbits. Ten additional rabbits constituted a sham operated control group. Aided by tantalum implants, growth was cephalometrically determined for each mandibular side during a period equivalent to childhood and adolescence in man. At the end of the growth period, histologically classified cartilage features were correlated with the assessed ipsilateral mandibular growth. Non-reducing displacement of the TMJ disc during the growth period induced histological reactions of the condylar cartilage in the rabbit model. The severity of cartilage changes was inversely correlated to the magnitude and the direction of mandibular growth, which resulted in a retrognathic growth pattern.

This paper describes how dental hygienist students have used and developed a web site during a two year undergraduate programme. The programme is based on a Problem Based Learning concept at the Faculty of Odontology at Malmö University in Sweden. The web site was first used for administration of the courses, but with time different modes of supporting the PBL process were developed. These modes originated from both students and from the course director. In a questionnaire and in interviews, students were asked about how the web site had been used for communication between students and between students and teachers. They were also asked to comment on how their written tutorial reports, posted on the web site after each case, affected the collaboration in the tutorials and also their learning. Finally, we asked if the students thought that their use of the web site and computers in general had changed during the education. The questionnaire and the interviews were completed at the time of graduation. The written notes and reports of the cases enhanced and supported the students’ learning and some students recognized a change in how they used the web site. Most students also declared that their ability to use different computer programmes had improved. The students strongly recommended a continued use of the web site in the dental hygienist education. The communication and feed back between students and teachers were considerably improved, though new ways should be tried in order to stimulate experts to take more active part in the students’ learning process.

genomes from nine individuals covering four Eurasian sites and placed them into an historical context within the established phylogeny. CHE1 (Chechnya, Russia, 18th century) is now the latest Second Plague Pandemic genome and the first non-European sample in the post-Black Death lineage. Its placement in the phylogeny and our synthesis point toward the existence of an extra-European reservoir feeding plague into Western Europe in multiple waves. By considering socioeconomic, ecological, and climatic factors we highlight the importance of a noneurocentric approach for the discussion on Second Plague Pandemic dynamics in Europe.

OBJECTIVES: Medication-related osteonecrosis of the jaw (MRONJ) has a wide range of prevalence, and a standard therapy has not yet been established. The aim of this study was to analyze the prevalence and initiating factors of MRONJ and the outcomes of surgical therapy. STUDY DESIGN: In a prospective cohort study, all patients diagnosed with MRONJ in the Region of Skane, in Sweden, were included. Predictor variables (comorbidity, site, stage, gender) and initiating factors (tooth extraction, periodontitis) were recorded. Surgical treatment was sequestrectomy or block resection, and the outcome variable was healing after 2 months. To estimate the prevalence, data on the use of bisphosphonate and denosumab were used. RESULTS: Fifty-five patients with MRONJ were identified. The prevalence of MRONJ was 0.043% among patients treated with oral bisphosphonates, 1.03% among those on intravenous bisphosphonates and 3.64% in those on high-dose denosumab. Periodontal disease preceded development of MRONJ in 41 patients. Fifty patients were treated surgically and followed up for at least 2 months. Remission or healing occurred in 80% of patients treated with sequestrectomy and in 92.5% of patients treated with block resection. CONCLUSIONS: The prevalence of MRONJ in Sweden is low. Periodontitis is the most common initiating factor. The outcome of treatment of MRONJ is healing in most patients treated surgically.

Our aim was to evaluate the treatment given to patients with intraosseus ameloblastomas with special emphasis on recurrence and the outcomes of primary and secondary resection. Forty-eight patients who were treated for intraosseous ameloblastoma at 8 centres across Sweden met the inclusion criteria. They showed typical distribution of age, sex, site of lesion, and characteristic presenting features. Eleven of the 48 were initially treated with radical resection and none recurred. Twenty-two of the remaining 37 who were initially treated by conservative resection presented with recurrences. Sixteen of the 22 then had conservative secondary resections, which resulted in further recurrence in 6 patients. Initial radical resection is therefore superior to conservative management as far as recurrences are concerned. We argue, however, that a conservative surgical approach is adequate for many intraosseous ameloblastomas with limited extension, because relapse can be followed by radical resection if clinically indicated in selected cases.

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.

Objectives: The aim of this study was to investigate how brightness and contrast settings of the display monitor and ambient light level (illuminance) in the viewing room affect the clinician's ability to diagnose carious lesions in digital radiographs. Methods: Standardized radiographs were taken of 100 extracted teeth. Seven observers evaluated the images for approximal carious lesions twice, once under 50 lux and once under 1000 lux room illumination. Monitor brightness and contrast were varied ±50% and ±6%, respectively, to mimic the normal limits of monitor adjustment by an inexperienced user and one optimal setting. This was done by adjusting radiograph brightness and contrast by ±25%. Thus, five radiographs of each tooth were evaluated. Receiver operating characteristic (ROC) analyses were performed. Histological examinations of the teeth served as the criterion standard. A paired t-test was used to evaluate whether differences in the areas under the ROC curves were significant and kappa was used to evaluate intraobserver agreement. Results: When a monitor with optimal brightness and contrast settings was used to detect approximal carious lesions, ambient light levels less than 50 lux were significantly better than levels above 1000 lux (dentin and enamel lesions, P < 0.01; dentin lesions, P < 0.02). Increasing the contrast setting of the monitor by 6% did not change these results; 50 lux was still significantly better than 1000 lux (enamel lesions, P < 0.01; dentin and enamel lesions, P < 0.02) for evaluating radiographs. Intraobserver agreement differed from fair to good. Conclusions: Reducing ambient light to less than 50 lux significantly increased the accuracy of diagnosing approximal carious lesions on a monitor with an optimal brightness setting and an optimal or slightly higher than optimal contrast setting.

A case of osteomyelitis in a 71-year-old woman with paroxysmal nocturnal hemoglobinuria (PNH) is reported. Osteomyelitis of the jaw is a well known condition of the oral and maxillofacial region that may cause severe morbidity. It is well documented that vaso-occlusive crises in sickle cell anaemia, a hemolytic blood disorder, can make the jaw bone susceptible to osteomyelitis. The authors report a case proposing an association between PNH and osteomyelitis of the mandible.

Only rare cases of osteonecrosis of the auditory canal associated with bisphosphonates, have been published. Our results confirm that similar reports can also be encountered in databases of adverse drug reactions.

PURPOSE: It is well known that oral bisphosphonates can induce necrosis of the osseous structures of the jaws. However, there seems to be a limited awareness that oral bisphosphonates can also induce adverse effects in the soft tissues of the oral cavity, as indicated by the paucity of reported cases in the literature. Because oral bisphosphonates are widely used drugs for several skeletal conditions, it is reasonable to assume that mucosal adverse effects are more common than the small number of published cases indicates. The purpose of this study was to investigate whether this adverse effect of bisphosphonates is represented as reports from health practitioners in an adverse drug reaction database, as well as to gain knowledge about which substances are being associated with adverse drug reactions affecting the oral mucosa. MATERIALS AND METHODS: The database of the Medical Products Agency-Sweden was searched for adverse effects from oral bisphosphonates manifesting in the oral and maxillofacial region. Reports of reactions limited to the soft tissues of the oral cavity were selected and further analyzed. Only those reports showing recovery or improvement after the cessation of bisphosphonate use were included in the study. RESULTS: A total of 83 cases of adverse reactions to oral bisphosphonates were retrieved from the search. Of these, 12 were included in the study. They were associated with the use of alendronate, etidronate and risedronate, in descending order. Sixteen percent of the reports comprising the oral and maxillofacial region were limited to the oral mucosa and reported recovery or improvement after discontinuation of the drug. CONCLUSIONS: Adverse effects of oral bisphosphonates with manifestations in the soft tissue of the oral cavity seem to be more common than the small number of published cases indicates. However, considering that oral bisphosphonates are widely used drugs, the incidence is still low. These adverse drug reactions are not limited to alendronate and may also be induced by etidronate and risedronate. Still, a significant proportion of the cases are associated with alendronate. Regardless of the substance used, discontinuing the drug is an effective treatment for the mucosal lesions.

Irritation of the mucosa of the aerodigestive tract is a well-known adverse effect of alendronate, whereas oral ulceration has been reported in only 14 articles in both the English and non-English literature. All of these have been associated with misuse of the drug. We here present the first case of severe oral ulceration attributable to use of alendronate without inappropriate therapeutic administration of the medication.

PURPOSE:To review the published data on a hitherto not widely known adverse effect of alendronate manifesting as mucosal ulcers in the oral cavity. MATERIALS AND METHODS:The electronic database PubMed was searched for reports of this adverse effect. Publications published up to August 2010 were included. This electronic search was combined with a manual search of the reference lists of the selected publications. RESULTS: A total of 47 publications were retrieved from the electronic and manual searches. Of these, 12 were selected for the review. Mostly, the ulcers were preceded by misuse of alendronate, but they also appeared after correct administration. The appearance of the ulcers varied from a few days to several months after the start of alendronate use. Effective treatment was withdrawal of the drug or revision of the dosing and administration instructions. CONCLUSIONS:Alendronate can cause mucosal ulcerations in the oral cavity, affecting patients with intense pain and causing severe morbidity. Successful treatment of this oral pathosis is achieved by aborting the use of alendronate. This adverse effect of alendronate is a rare entity in published reports but careful monitoring of patients at risk is recommended.

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.

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.

A predominant part of the Swedish population uses toothpaste daily. Besides fluoride preventing caries, toothpastes usually have flavours added to make the user feel fresh and clean. Among potential allergens in toothpastes, flavours are the most common cause of oral or perioral lesions. Flavour concentrations vary between 0.3% and 2.0%, and usually several types of mint are used; however, the true composition of the added aroma is seldom known. l‐Carvone is a mint‐tasting flavour that can act as a potential allergen. Previous findings have shown that approximately 4% of a patch‐tested selected population in southern Sweden had a positive reaction to l‐carvone and half of them had oral inflammatory lesions, notably oral lichenoid lesions. Among patients with lichenoid lesions approximately 12% have a contact allergy to l‐carvone and several other contact allergies are more common in this patient group. The concentration of l‐carvone in toothpastes available for sale on the Swedish market was investigated. Sixty‐six different toothpastes were selected from local stores and pharmacies. l‐Carvone content was extracted from toothpastes using n‐heptane. The sample extracts were separated on a silica column using straight‐phase high‐performance liquid chromatography and a diode‐array detector. Three samples of each toothpaste were analysed, and the mean concentration and relative SD were calculated. Detectable levels of l‐carvone (0.00005–0.35%) were found in 63 of the toothpastes. l‐Carvone was found in half of the toothpastes (n = 32) at a concentration of ≥ 0.01%. A higher concentration (≥ 0.1%) was found in 18% (n = 12). Of the top six toothpastes with highest l‐carvone content (0.15–0.35%), one was intended for use by children. Two of the toothpastes were stated as having fruit flavour, but there were still detectable levels of l‐carvone (0.0003% and 0.00007%, respectively). l‐Carvone was below detectable levels in three of the toothpastes, where one was stated as being without flavour. l‐Carvone is present in virtually all toothpastes on the Swedish market. It is therefore likely that l‐carvone in toothpastes is important for the induction of sensitization to l‐carvone, as contact allergy to l‐carvone is over‐represented in patch‐tested individuals with oral lichenoid reactions. However, are the concentrations demonstrated relevant for causing reactions or aggravating already existing lesions?

Carvone (l-carvone), a mint flavour in spearmint oil, is considered a mild skin sensitizer. Carvone-sensitization may be linked to oral/perioral signs and oral lichen planus, but studies are sparse. The prevalence of patch test reactions to carvone and relevant findings from the positive group were investigated. Records for patch-tested patients at the Malmö clinic, for the period 1996 to 2016, were studied. Carvone-positive and carvone-negative patients were compared regarding patch test data from baseline series and dental series. Dental series-tested carvone-positive patients were also compared with a matched group. A total of 147 out of 4,221 referred patients had a positive patch test to carvone. Sensitized patients had higher mean age and were primarily women; 73% had oral signs and 57% had oral lichen. Concomitant patch test reactions to gold, nickel and mercury were common. In the matched group-comparison carvone-positive patients had a higher frequency of oral lichen, but no difference was found in sensitization to gold and mercury.

Background: Carvone (L-carvone) is naturally found in spearmint oil and is considered a mild skin sensitizer. It commonly serves as a flavoring agent in toothpaste and other mint tasting products. There is recent evidence that carvone may have a relationship with oral lichenoid lesions (OLL). Objectives: The aim was to study the frequency of carvone contact allergy in a Swedish patch test population at the Malmö clinic and to investigate the characteristics of the group with special reference to OLL. Methods: A 15-year retrospective study including all consecutive patients tested positive for carvone with different series containing carvone. The patients’ records were reviewed in regard to symptoms, previous diagnoses, type of referrer and contact allergy. Results: Three thousand eight hundred and twelve patients were patch tested to different series containing l-carvone, the most common being the Swedish dental series. One hundred and forty-three patients (3.7%) were positive to carvone whereof 138 patients had records available for review. Of the carvone-sensitized patients, 46.9% had suspected or previously diagnosed OLL and 8.0% had dermal or genital lichen planus. The majority of the carvone-sensitized patients had also positive reactions to several other allergens. The most common allergens were spearmint oil (39.9%), gold (35.5%) fragrance-mix (17.4%) and nickel (15.5%). The majority of the carvone-sensitized patients with allergy to gold (30/49) or allergy to mercury (16/18) also had OLL. The male-to-female ratio was 1:4.75 among the carvone-sensitized patients compared to 1:2.55 in the overall test groups. Conclusions: The frequency of patients sensitized to carvone seems to correspond with previous findings. Concomitant contact allergy to gold or mercury was often associated with OLL and these patients were often referred for suspected allergy from d ental restorations. The data together with conclusions in recent reports suggests a relationship between OLL and l-carvone contact allergy. The relationship is yet unknown and needs further investigation.

BACKGROUND: Toothpastes have widespread use in the population, and contain flavours used to give a pleasant and often minty aroma. Flavours are prevalent allergens in toothpastes, and adverse reactions often present as perioral dermatitis or stomatitis. l-Carvone, a mint flavour found in spearmint oil, is one of these allergens. There are few studies on contact allergy to l-carvone, and some of them have indicated a positive relationship with oral lichenoid lesions. OBJECTIVES: To qualitatively and quantitatively investigate the presence of l-carvone in commercially available toothpastes on the Swedish market. METHODS: l-Carvone in 66 toothpastes was analysed with straight-phase high-performance liquid chromatography. The product labels were studied with regard to limonene. RESULTS: l-Carvone was found in 64 of 66 toothpastes (concentration: 0.00005-0.35%). In 10 of these, the concentration exceeded 0.1%. Higher concentrations of l-carvone were found if limonene was listed on the label. CONCLUSION: The majority of toothpastes on the Swedish market contain l-carvone, but the concentration hardly relates to the advertised flavour or labelled ingredients. It is hitherto unknown whether the found concentrations are sufficient for induction of contact allergy in individuals with healthy oral mucosa or in those with oral lichenoid lesions or other mucosal disease.

The purpose was to identify cases of squamous cell carcinoma (SCC) of the tongue, in which a biopsy taken at the site preceding the cancer could be verified to show a lichenoid contact type of reaction (LCR). We retrieved all 724 SCC of the tongue from the Swedish Cancer Registry in the period 1995-2000. These cases were cross-searched with our own oral biopsy data files from 1988 to 1994, in order to identify biopsies with LCR-type lesions preceding the cancer. We found four verified and some additional tentative cases. The study demonstrated that there is a low incidence of malignant transformation in LCR-type oral lesions, not much different from what has been previously reported in oral lichen planus.

Whether psoriasis can manifest itself in the oral mucosa has been a matter of debate for many years. If an oral version of psoriasis exists, most researchers regard this manifestation as rare. The present report describes two patients who presented with lesions possibly related to cutaneous psoriasis. One patient had patchy erythematous lesions on the gingiva, and one had serpiginous lesions in the hard palate. We discuss these cases in relation to the existing literature, with special emphasis on the clinical and histopathologic criteria for the diagnosis of oral psoriasis.

Imatinib mesylate is a tyrosine kinase inhibitor which targets Bcr-Abl-protein, c-Kit, and platelet-derived growth factor receptor. The drug was originally developed for treatment of chronic myeloid leukemia but is also regarded as first-line treatment of patients with metastatic gastrointestinal stromal tumours (GIST). Dermatologic side effects are common, with superficial edema and rash as the most frequent. In addition, imatinib mesylate treatment is often associated with hypopigmentation. Intraoral side effects are very rare. The present paper demonstrates 1 patient with GIST and 2 patients with chronic myeloid leukemia treated with imatinib mesylate for 5-6 years. All 3 patients presented with diffuse solitary bluish-brown pigmentations in the hard palate. The lesions persisted at follow-ups. There were no other pigmentations in the oral mucosa. The histopathologic examination showed depositions of melanin pigment in the lamina propria. The possible relationship between the observed melanotic maculae and imatinib mesylate treatment is discussed.

Objective. Non-human primates, dogs, rats, hamsters and ferrets, have frequently been used as laboratory animals in periodontal biology and pathology. In the past, mice have been used less for this purpose, but nowadays attract a lot of interest because gene knockout and transgenic technologies utilize mice primarily. In this study, we investigate the effects of ovariectomy and aging on tooth attachment in female mice. Material and methods. Eight-week-old mice (n=15) were divided into three experimental groups (control, n=5; sham-operated, n=5; ovariectomy, n=5) and ovaries removed bilaterally. Attachment level, assessed by measuring alveolar bone height and apical termination of the junctional epithelium, was determined 6 weeks post-ovariectomy by digital morphometric analysis in sagittal sections of the mandible. The plasma level of the inflammation marker serum amyloid A (SAA) was determined by ELISA. In another series of experiments, tooth attachment was determined in female mice (n=7) at 8–26 weeks of age. Results. Withdrawal of female sex hormone production by ovariectomy had no effect on alveolar bone height and apical termination of the junctional epithelium. The SAA level in plasma was unaffected by removal of the ovaries, suggesting that systemic inflammation is not induced by ovariectomy. Bone height was similar in mice sacrificed at 8–26 weeks of age and apical termination of the junctional epithelium was at the cemento-enamel junction at all ages. Conclusions. Removal of ovarian production of female sex hormones by ovariectomy has no influence on tooth attachment, and further tooth attachment is preserved with age in female mice.

Objective To examine how hospital-affiliated dentists assess risk and evaluate oral foci of infection in patients facing certain medical treatments, and whether the nature of upcoming medical treatment affects the choice of dental intervention. Materials and methods A survey comprising six clinical cases (50 teeth) was sent to hospital-affiliated dentists in Sweden. A treatment option for the affected tooth/teeth in each case was selected whether the patient was facing heart valve surgery, chemotherapy, radiation therapy, intravenous bisphosphonate treatment, solid organ transplantation or was diagnosed with endocarditis. Results Consensus in choice of dental treatment was high in 62%, moderate in 32% and low in 6% of the assessments. High variability of choice of treatment was seen for eight teeth whereas the remaining 42 teeth often received the same therapy regardless of medical issue. Chemotherapy and radiotherapy were thought to entail the highest risk for oral infectious sequelae with a risk ranging from 1% to 100%. Conclusion Pre-medical dental evaluations and recommended treatments are often uniform with the exception of the management of asymptomatic root canal treated teeth with persisting apical radiolucency and heavily decayed molars. In many instances, dental diagnosis has a greater impact on choice of treatment than the underlying medical issue and associated implications thereof.

Objectives The aims of the study were to investigate the prevalence of impaired sensation after minor salivary gland biopsy (MSGB) in two Swedish centres [Karolinska University Hospital (KUH) and Skane University Hospital (SUH)] and to assess its impact on quality of life (QoL) and associated risk factors. Method A questionnaire including questions regarding the presence of impaired sensation, impact on QoL, and impact on everyday life was sent to patients who had undergone MSGB between 2007 and 2016, and their medical notes were scrutinized. Results The study included 630 patients (505 from KUH and 125 from SUH). In KUH the biopsies were performed by rheumatologists and in SUH by dentists or oral and maxillofacial surgeons (OMSs). Long-standing, probably permanent, impaired sensation after MSGB was reported by 21% of patients, and was associated with lower age and absence of anti-SSA antibodies. Patients with long-standing impaired sensation reported the inconvenience (1-10) of impaired sensation as 4.0 (2.0-7.0) [median (interquartile range)], and 32% reported an influence on their QoL, the reported influence (1-10) on everyday life being 3.0 (1.0-5.0). When comparing the outcomes from KUH and SUH, patients from SUH reported a significantly lower frequency of long-standing impaired sensation (14% vs 23%; p = 0.02). Conclusion A high frequency of long-standing impaired sensation after MSGB was found among patients who had undergone MSGB, although it had a low impact on everyday life. The complication frequency was less pronounced when a dentist or an OMS had performed the biopsy.

ObjectiveTo determine the levels of antithyroid antibodies and thyroid hormones in the sera of patients with oral lichen planus (OLP), and to quantify the expression of thyroid proteins in OLP lesions. Subjects and MethodsVenous blood samples were drawn from 110 patients with OLP who had no history of thyroid disease or levothyroxine supplementation (OLP+/LT4-). A random population sample of 657 healthy subjects was used as the control group. Two additional groups were used as comparators. Immunohistochemical and qPCR analyses were performed on tissue specimens collected from the patients with OLP and thyroid disease and healthy subjects. ResultsNo association was found between the presence of antithyroid antibodies and OLP. More patients in the OLP+/LT4- group showed high levels of thyroid-stimulating hormone and low levels of free thyroxine than were seen in the control group. Thyroid-stimulating hormone receptor was more highly expressed in the OLP lesions of patients with thyroid disease than in the healthy oral mucosa. ConclusionsA significant number of patients with OLP who are not previously diagnosed with thyroid disease have thyroid parameters that are compatible with hypothyroidism. The expression of thyroid-stimulating hormone receptor in OLP lesions suggests that mechanisms related to autoimmune thyroid disease are involved in the aetiology of OLP.

In rat parotid, submandibular and sublingual glands and in ovine parotid and in human labial glands, the expression of muscarinic receptor subtypes was examined by immunoblotting and immunohistochemistry. Functional correlates were searched for in rat salivary glands. In the rat submandibular and sublingual glandular tissues clear signals of muscarinic M1 and M5 receptors could be detected in the immunoblotting and vague bands for muscarinic M3 and, in particular for, M4 receptors. The rat parotid gland differed. In this gland, the signal was less obvious for the muscarinic M1 receptor, and further, muscarinic M4 receptors appeared more strongly marked than in the submandibular glands. The results from the immunohistochemistry could be interpreted as the muscarinic M4 receptors are located on nerve fibres, since the outer layer of lobuli were densely stained. Intraglandular vessels in the rat submandibular and parotid glands showed expression of M3 receptors. In contrast to the parotid gland, the submandibular vessels also expressed M1 and M2 receptors. Occasionally M5 receptors appeared in the arteries and veins also. The functional studies in the rat confirmed muscarinic M1 receptor mediated secretion in the submandibular gland. Since the M1 receptor blockade did not affect submandibular blood flow, indirect vascular effects could not in total explain the secretory inhibition. Also in the human labial glands, muscarinic M1, M3 and M5 receptors occurred. No or low amounts of muscarinic M2 and M4 receptors could be detected. In patients with Sjögren-like symptoms an up-regulation of M3, M4 and M5 receptors was apparent in the labial glands. In ovine parotid glands all receptors could be detected, but constantly with vague bands for muscarinic M2 receptors. In conclusion, muscarinic M1 receptors seem to be expressed in seromucous/mucous glands. A secretory effect by muscarinic M5 receptors is not to be excluded, since they were expressed in all the glands examined. However, other functions, such as promotion of inflammation, cell growth and proliferation are possible as well.

CEOT is a rare benign, but locally aggressive odontogenic tumor, and some authors have claimed that the biologic behavior of the clear cell variant is even more aggressive, with greater propensity to recur. We report a rare case of clear cell calcifying epithelial odontogenic tumor (CEOT) and discuss its possibly aggressive behavior. A 40-year-old woman experienced an asymptomatic expansion of the left posterior mandible. After radiographic examination and biopsy, a block resection was performed. Histologic examination included analysis of Ki-67 reactivity as a marker of tumor growth activity. Ki-67 labeling was pronounced in the non-clear cell population in the tumor periphery but low in the central and clear cell portions. Clinical and radiographic follow-up 6 years after resection has not revealed any signs of recurrence. On the basis of a review of the literature and our own findings, there is no clear data to suggest that clear cell CEOT exhibits more aggressive behavior compared with conventional CEOT.

The aim of this retrospective study was to investigate the frequency of different types of oral lesions in biopsies sent to a department of human oral pathology for histologic examination. The impact of gender, age, and breed was assessed. The biopsy specimens were reviewed and diagnosed according to human pathology nomenclature and the classification of different diagnoses used in human and veterinary pathology is discussed. Reactive lesions were diagnosed in 39 % of the biopsies, while benign and malignant neoplasms were diagnosed in 27 %, and 15 % of the biopsies, respectively. The most common diagnosis was reactive gingival hyperplasia (24 %), followed by peripheral odontogenic fibroma (21 %) and melanoma (8 %). Epulides comprised 69 % of all lesions. Dogs with malignant oral tumors were older than those with benign tumors, however there was no significant gender differences for any group of lesions Pure-bred dogs were more prone to develop pathology than mixed-breeds. Of the larger breeds in Sweden, Boxer dogs had the highest prevalence (3.77/1000) of biopsies submitted.

OBJECTIVE: The development of non-Hodgkin's lymphoma (NHL) confers a high risk of mortality in primary Sjögren's syndrome (pSS) patients, but the sensitivity and specificity of proposed lymphoma predictors are insufficient for practical use. The performance of lymphoid organisation in the form of germinal centre (GC)-like lesions was evaluated in labial salivary gland biopsies taken at pSS diagnosis as a potential lymphoma-predicting biomarker. METHODS: Labial salivary gland tissue biopsies available from two Swedish pSS research cohorts (n=175) were re-evaluated by light microscopy in a blind study in order to identify GC-like structures as a sign of ectopic lymphoid tissue formation and organisation. A linkage study was performed with the Swedish Cancer Registry for lymphoma identification. The risk of developing NHL in GC-positive patients in comparison with GC-negative patients was evaluated using Kaplan-Meier statistics and log-rank test. Associations between GC-like structures and clinical and/or laboratory disease markers were also determined using χ(2) or Fisher's exact tests. RESULTS: At diagnosis, 25% of pSS patients had GC-like structures in their salivary glands. Seven of the 175 patients studied (14% GC+ and 0.8% GC-) developed NHL during 1855 patient-years at risk, with a median onset of 7 years following the initial diagnostic salivary gland biopsy. Six of the seven patients had GC-like structures at diagnosis; the remaining patient was GC negative at the time of diagnosis (p=0.001). CONCLUSIONS: The detection of GC-like structures by light microscopy in pSS diagnostic salivary biopsies is proposed as a highly predictive and easy-to-obtain marker for NHL development. This allows for risk stratification of patients and the possibility to initiate preventive B-cell-directed therapy.

Objectives: The oral cavity commonly displays mucosal lichenoid lesions and salivary gland dysfunction, which are considered different chronic Graft-versus-Host Disease (cGVHD) patho-physiology's. However, diagnostics of salivary gland (sg-)cGVHD are limited. The objectives of the current study are to evaluate the minor salivary gland (MSG) histo-immunopathological profiles post allogenic hematopoietic cell transplantation based on sg-cGVHD criteria. Design: Histopathology was characterized according to two published grading strategies. Firstly, the National Institute of Health (NIH) assessed peri-ductal/acinar infiltration, exocytosis, damage, and fibrosis, and a points-based grading scheme was established (0-16 points, Grade (G) 0 to IV). Second, a modified Sjo center dot gren's Syndrome focus-score with parenchymal damage was also adapted, (0-10 points, Score 0 to 2). 146 MSG biopsies from 79 patients were compared, using the his-topathological specific criteria for sg-cGVHD pathology. Quantitative immunohistochemistry for T-cells (CD4, CD8), B-cells (CD19, CD20), monocytic cells (CD68) and dendritic cells (CD1a) were also assessed. Results: The large-scale cohort validated the use of both grading schemes. GIII-GIV and score 2 signified a histopathological diagnosis of "likely" sg-cGVHD. Immunopathological severity was associated with increased T-cells (CD4 and CD8) and monocytic (CD68) infiltrate, with minimal involvement of B-cells (CD19 and CD20), and Langerhans cells (CD1a). Conclu-sions: Both schemes were verified as being suitable for histological grading to improve assess-ment and diagnosis of sg-cGVHD. The NIH cGVHD grading appears to be more beneficial for research purposes, including final diagnostics of "no/inactive", "possible" or "likely" cGVHD. The study highlights the intricacies of sg-cGVHD pathology; and the need for standardized assessment to improve patient management associated to sg-cGVHD.

Visual grading of chromogenically stained immunohistochemical (IHC) samples is subjective, time consuming, and predisposed to considerable inter- and intra-observer variations. The open-source digital analysis software, CellProfiler has been extensively used for fluorescently stained cells/tissues; however, chromogenic IHC staining is routinely used in both pathological and research diagnostics. The current investigation aimed to compare CellProfiler quantitative chromogenic IHC analyses against the gold standard manual counting. Oral mucosal biopsies from patients with chronic graft-versus-host disease were stained for CD4. Digitized images were manually counted and subjected to image analysis in CellProfiler. Inter-observer and inter-platform agreements were assessed by scatterplots with linear regression and Bland-Altman plots. Validation comparisons between the manual counters demonstrated strong intra-observer concordance (r(2) = 0.979), particularly when cell numbers were less than 100. Scatterplots and Bland-Altman plots demonstrated strong agreement between the manual counters and CellProfiler, with the number of positively stained cells robustly correlating (r(2) = 0.938). Furthermore, CellProfiler allowed the determination of multiple variables simultaneously, such as area stained and masking to remove any nonstained tissue and white gaps, which also demonstrated reliable agreement (r(2) = >0.9). CellProfiler demonstrated versatility with the ability to assess large numbers of images and allowed additional parameters to be quantified. CellProfiler allowed rapid high processing capacity of chromogenically stained chronic inflammatory tissue that was reliable, accurate, and reproducible and highlights potential applications in research diagnostics.

Objective Chronic graft-versus-host disease (cGVHD) is the main cause of late non-relapse mortality following hematopoietic cell transplantation. Oral mucosal (om-) cGVHD is common, but diagnosis and assessment rely on clinical interpretation and patient-reported symptoms. We investigated immunohistopathological profiles with respect to om-cGVHD severity disease duration. Material and methods Ninety-four transplant patients and 15 healthy controls (n = 212 biopsies) were investigated by quantitative immunohistochemistry for T cells (CD4, CD8, and CD5), B cells (CD19 and CD20), macrophages (CD68), and Langerhans cells (CD1a). Results We found significant increases in T (CD4, CD8) and monocytic (CD68) cells in om-cGVHD, and a notable absence of B (CD19 and CD20) cells. Histopathological activity correlated with increased CD4, CD8 and CD68. However, CD4 was associated with mild om-cGVHD, whereas CD8 and CD68 were found to be elevated in severe om-cGVHD. CD8 and CD68 levels were raised at disease onset, but during late phase, the predominant CD68 population was accompanied by CD4. Conclusion Oral cGVHD is a heterogenous clinical disorder, but our knowledge of the underlying biology remains limited. We highlight the importance of CD4, CD8 and CD68 immune profiling, together with histological grading for the staging of oral cGVHD, to broaden our understanding of the biology and individual disease course.

Graft-versus-host disease (GVHD) can manifest as acute or chronic complications in patients after hematopoietic cell transplantation (HCT). Oral chronic GVHD (cGVHD) occurs in approximately 70% of HCT recipients and includes lichenoid-like mucosal reactions, restricted mouth opening, and salivary gland dysfunction. However, the underlying histopathological presentation remains to be validated in large cohorts. We characterized the histopathological features of oral mucosal cGVHD and devised a scoring model in a large patient cohort (n = 112). Oral mucosal biopsy sections (n = 303) with and without oral cGVHD were identified from archived and current HCT recipients with additional healthy controls. Histological screening was performed on hematoxylin and eosin-stained and periodic acid-Schiff-stained sections. A points-based grading tool (0 to 19, grade 0 to IV) was established based on intraepithelial lymphocytes and band-like inflammatory infiltrate, atrophic epithelium with basal cell liquefaction degeneration, including apoptosis, as well as separation of epithelium and pseudo-rete ridges. Validation involved 62 biopsy specimens, including post-HCT (n = 47) and healthy (n = 15) specimens. Remaining biopsy specimens (n = 199) were blindly graded by 3 observers. Histological severity was correlated with clinical diagnostic and distinctive features, demonstrating a spectrum of individual patient severity, including frequent signs of subclinical GVHD in healthy mucosa. However, oral cGVHD presented with significantly higher (P < .001) scores compared with HCT controls, with moderate to high positive likelihood ratios for inflammatory infiltrate, exocytosis, and basal membrane alterations. The grade II-IV biopsy specimens demonstrated a histopathological diagnosis of active mucosal lichenoid-like cGVHD, highlighting the importance of correlating clinical presentation with the dynamic histopathological processes for improved patient stratification. In addition, this tool could be used for assessing treatments, pathological processes, and immune cellular content to provide further insight into this debilitating disease.

PURPOSE: To estimate and compare the costs of maxillary sinus augmentation performed with autologous bone graft either from the iliac crest or from local bone harvested from the mandibula. To evaluate post-operative health-related quality-of-life parameters for patients subjected to sinus augmentation and iliac bone surgery. MATERIAL AND METHODS: The hospital records of 14 patients subjected to sinus augmentation with iliac autograft, and 14 patients treated with local autograft, were analysed with regard to costs related to surgery, hospitalization and sick leave. Post-operative health parameters were assessed with a questionnaire. RESULTS: Mean hospital costs, administration excluded, for sinus augmentation with iliac autograft was €3447. Policlinic treatment alternatives e.g. local bone autograft with or without bone substitutes, rendered costs of approximately 42% thereof. The loss of production for a worker was 41% of the total cost (€9285). With regard to health-related quality-of-life and post-operative morbidity, most of the patients had recovered 14 days after the iliac graft surgery. CONCLUSION: The cost for a sinus augmentation with iliac surgery exceeds that of a policlinic procedure manifold. Provided that a policlinic operation with local bone, with or without bone substitute, renders an adequate end result, the economic gain would be substantial and post-operative morbidity would be greatly reduced.

OBJECTIVES: To investigate the capacity of Cerament, an injectable bone substitute, to guide bone generation from a cortical surface. MATERIALS AND METHOD: Cerament was applied to the cortical surface of rat tibiae and investigated histologically after 3, 6 and 12 weeks, using a procedure similar to that performed in sham-operated rats. RESULTS: In both groups, the thickness of the bone cortex increased significantly from 473 + or - 58 microm (mean + or - SD) at day 0 to 1193 + or - 255 microm (Cerament) and 942 + or - 323 microm (sham) after 3 weeks. In the Cerament group, the new bone thickness remained constant (1258 + or - 288 microm) until the end of the experiment at 12 weeks, while the sham group demonstrated a return to initial cortical thickness (591 + or - 73 microm) at 12 weeks. The newly formed bone in the Cerament group was highly trabecular after 3 weeks but attained a normal trabecular structure of the cortex after 12 weeks. CONCLUSION: Cerament may guide bone generation from an intact cortical bone surface. Although bone remodeling speed may differ between rats and humans, our study indicates that Cerament may become a useful alternative to autologous bone, both to fill defects and to increase bone volume by cortical augmentation.

The purpose was to investigate whether a new biphasic and injectable ceramic bone substitute Cerament that rapidly remodels to bone, may contribute to the retention of titanium implant screws during the healing period, and to analyze the pattern of bone formation around titanium implants.Titanium screws were implanted in rat tibiae and embedded with or without Cerament on the cortical surface. Torsional resistance was measured after 1 day, and after 6 and 12 weeks. Implant areas without bone substitute were analyzed histologically for comparison. The torsional resistance increased over time as the screws were osseointegrated. There was no difference in resistance between screws embedded in the bone substitute and control screws. The bone apposition was more pronounced on the proximal side of the screw than on the distal side. Cerament is capable of conducting bone growth from a cortical bone surface. The newly formed bone in this application does not significantly add to the osseointegrative strength of the implant screw, as measured by torque resistance, during the first 12 weeks.

This project focuses on students’ proficiency to learn in a problem-based curriculum at the Faculty of Odontology at Malmö University. We have developed a series of metacognitive workshops designed to make students more aware of the structure of a fruitful problem-solving rationale. A play exemplifying a condensed low-achieving tutorial was performed live by students, followed by discussions. In other workshops, the students analyzed tutorial reports with reference to the problem-solving structure and also tried to write new cases from given curricular goals. The students exposed to the exercises displayed a higher metacognitive awareness than students not exposed and they also felt that their tutorial work had improved. In conclusion, to enhance learning, it is desirable to boost students’ metacognitive awareness and it is also possible to do so.

The purpose of this project was to create a web based course with the following characteristics. It should provide a flexible and free learning environment where students' problem-solving skills and meta-cognitive awareness were developed. Problem based learning (PBL) was chosen as the pedagogical concept where collaboration was mixed with individual contributions, thus challenging and testing different competencies of the students. To further stimulate interaction, several modes of communication were provided at the web site. Assessment was formative. Facilitators feedback was clearly/firmly scheduled and kept low in order to create independent and self-reliant students and to avoid investing unreasonable resources. Contact with experts were possible throughout the course and the course was concluded with an online seminar with opportunities to pose questions to the experts. The web site and its functions were designed to be easy to use and available with simple technology. In conclusion this course model functioned fairly well; the students were overall satisfied and we think that we accomplished, to a certain degree, our purposes. In coming courses, we intend to stimulate more discussions in order to further develop group collaboration, and to firmly hold on to the demands on equipment to be able to attend the course. The course may well serve as a model for other web based PBL-courses.