Danish post-marketing pharmacosurveillance of spontaneous Oral Adverse Drug Reactions 2009-2019.

Post-marketing pharmacosurveillance is important to reduce harm to patients from marketed drugs. Oral adverse drug reactions (OADRs) are seldom reported and only few OADRs are listed scarcely in summary of product characteristics (SmPC) of drugs. OBJECTIVE: Structured search for OADRs in the Danish Medicines Agencies database from January 2009 to July 2019. RESULTS: Forty-eight percent of OADRs were categorized as "serious" where oro-facial swelling was reported 1041 times, medication-related osteonecrosis of the jaw (MRONJ) 607 times and para- or hypoaesthesia 329 times. Four-hundred-eighty OADRs in 343 cases were related to biologic or biosimilar drugs where 73% affected the jawbone as MRONJ. Physician reported 44%, dentists 19% and citizens 10% of OADRs. CONCLUSIONS: Health care professionals had a sporadic reporting pattern that seemed to be influenced by the debate in the community and in professional circles but also by the information in the SmPC of the drugs. The results indicate some reporting stimulation of OADRs in relation to Gardasil 4, Septanest, Eltroxin and MRONJ. Eventually the knowledge of OADRs increases but there is a risk of skewed information if reporting is not systematic, reliable and consistent. All healthcare professionals must be educated in spotting and reporting all suspected adverse drug reactions.

Salivary gland involvement and oral health in patients with coeliac disease.

Coeliac disease (CD) is a chronic immune-mediated enteropathy triggered by ingestion of gluten. The aim of this study was to investigate if the salivary glands as a component of the mucosal immune system are involved in CD, leading to sialadenitis and salivary gland dysfunction and associated oral manifestations. Twenty patients with CD aged 49.2 (SD 15.5 years) and 20 age- and gender-matched healthy controls underwent an interview regarding general and oral health, serological analysis, a clinical oral examination including bitewing radiographs, Candida smear, assessment of salivary mutans streptococci and lactobacilli levels, unstimulated and chewing-stimulated whole and parotid saliva flow rates, analysis of secretory IgA, and a labial salivary gland biopsy. Xerostomia, mucosal lesions, dry/cracked lips and focal lymphocytic sialadenitis were more prevalent and extensive in patients with CD than in healthy controls. Moreover, the patients had less gingival inflammation and higher whole saliva flow rates than the healthy controls, but did not differ regarding dental health and levels of cariogenic bacteria and Candida. The major salivary gland function appears unaffected, contributing to maintenance of a balanced microbiota and oral health in CD patients. Xerostomia and labial dryness may be related to minor salivary gland inflammation and subsequent impaired mucosal lubrication.

Gluten-free diet modulates inflammation in salivary glands and pancreatic islets.

OBJECTIVES: A lifelong gluten-free (GF) diet ameliorates autoimmune diabetes in non-obese diabetic (NOD) mice and most likely in humans. Besides diabetes, NOD mice develop focal sialadenitis, as seen in Sjögren's syndrome (SS). In humans, type 1 diabetes (T1D) is also linked to SS. Here, we investigated whether a lifelong GF diet influences the immune cell infiltration in the salivary glands and pancreatic islets in NOD mice. METHODS: NOD mice were fed a lifelong (i.e. 13 weeks) GF or gluten-containing standard (STD) diet. Insulitis and sialadenitis were scored on H&E-stained paraffin-embedded sections of pancreas and submandibular glands. Immune cell specificity and distribution were investigated immunohistochemically. RESULTS: There were fewer CD68+ and CD4+ cells in submandibular gland areas with focal sialadenitis as well as reduced insulitis and fewer VEGFR2+ cells in pancreatic islets in mice on GF versus STD diet. The degree of sialadenitis was not significantly lower in GF mice, but sialadenitis and insulitis correlated strongly. Lung weight was lower in GF mice. CONCLUSION: In NOD mice, a lifelong GF diet reduces infiltration of monocytes/macrophages and T cells in salivary glands and inflammation in pancreatic islets, possibly by reducing VEGFR2, indicating that the linked autoimmune diseases, T1D and SS, may be alleviated by a GF diet.

Oral symptoms and salivary findings in oral lichen planus, oral lichenoid lesions and stomatitis.

BACKGROUND: To examine if patients with oral lichen planus, oral lichenoid lesions and generalised stomatitis and concomitant contact allergy have more frequent and severe xerostomia, lower unstimulated and chewing-stimulated saliva and citric-acid-stimulated parotid saliva flow rates, and higher salivary concentration of total protein and sIgA than cases without contact allergy and healthy controls. METHODS: Forty-nine patients (42 women, aged 61.0 ± 10.3 years) and 29 healthy age- and gender-matched subjects underwent a standardised questionnaire on general and oral health, assessment of xerostomia, clinical examination, sialometry, mucosal biopsy and contact allergy testing. RESULTS: Nineteen patients had oral lichen planus, 19 patients had oral lichenoid lesions and 11 patients had generalised stomatitis. 38.8% had contact allergy. Xerostomia was significantly more common and severe in patients (46.9%) than in healthy controls, whereas the saliva flow rates did not differ. The patients had higher sIgA levels in unstimulated and chewing-stimulated saliva than the healthy controls. The total protein concentration in saliva was lower in the unstimulated saliva samples whereas it was higher in the chewing stimulated saliva samples from patients when compared to healthy controls. The differences were not significant and they were irrespective of the presence of contact allergy. CONCLUSION: Xerostomia is prevalent in patients with oral lichen planus, lichenoid lesions and generalised stomatitis, but not associated with salivary gland hypofunction, numbers of systemic diseases or medications, contact allergy, age, or gender. Salivary sIgA levels were higher in patients than in healthy controls, but did not differ between patient groups. The total salivary protein concentration was lower in unstimulated saliva samples and higher in chewing-stimulated saliva samples in patients than in healthy controls, but did not differ between patient groups. Our findings do not aid in the discrimination between OLP and OLL and these conditions with or without contact allergic reactions.

The prognostic value of histopathology on lingual nerve neurosensory recovery after micro-neurosurgery.

OBJECTIVE: Micro-neurosurgical repair is considered in permanent nerve damage but the outcome is unpredictable. We examined if histopathologic parameters of traumatic neuromas have a prognostic value for recovery in relation to lingual nerve micro-neurosurgery. MATERIALS AND METHODS: Retrospective case study on neurosensory recovery after micro-neurosurgery. Outcome variables were as follows: pain perception, two-point discrimination, and sum score of perception, before and 12 months after micro-neurosurgery. Predictive histopathology variables included size, nerve tissue, and inflammation. Statistics are as follows: logistic and correlation analyses (P < 0.05). RESULTS: Sixty-five patients with lingual nerve damage were included in the study. Improved two-point discrimination was associated with small size of resected tissue (P = 0.0275). No normal appearing distal nerve tissue was associated with improved sum score of perception (P = 0.0185), higher final sum score of perception value (P = 0.0475) and final pain perception (P = 0.0324). Foreign body reaction was associated with no final pain perception (P = 0.0492). CONCLUSIONS: Small size, absence of distal nerve tissue, and no foreign body reaction were associated with improvement of the neurosensory functions. CLINICAL RELEVANCE: Histological parameters of the traumatic neuromas in routine preparation appeared to have some prognostic value for neurosensory functions as improvement of the neurosensory functions was associated with small size of resected tissue, no distal normal appearing nerve tissue, and no foreign body reaction.

Single cell migration in oral squamous cell carcinoma - possible evidence of epithelial-mesenchymal transition in vivo.

BACKGROUND: The invasion of cancer cells into the surrounding normal tissue is one of the defining features of cancer. While the phenomena of tumour budding, epithelial-mesenchymal transition and the presence of myofibroblasts have independently been shown to be related to a poor prognosis of oral carcinomas, their relationship has not been examined in detail. METHODS: Paraffin-embedded tissues from 28 patients with oral squamous cell carcinomas were stained with antibodies to cytokeratin, α-SMA, vimentin, E-cadherin, N-cadherin and Twist and evaluated for their expression in relation to invasive cancer cells and the surrounding tumour stroma. RESULTS AND CONCLUSIONS: A direct, histological relationship between invading, budding tumour cells and myofibroblasts was occasionally seen but was not a general feature. Most of the budding tumour cells at the invasive front had a decreased expression of E-cadherin, but we did not find that this was associated with a consistent or clear increase in either N-cadherin or vimentin. We therefore suggest that the budding of tumour cells is not dependent upon either myofibroblasts or a complete epithelial-mesenchymal transition and that these phenomena most likely represent separate processes in tumour progression.

Glandular Odontogenic Cyst: a Case Report and Literature Review.

Background: The glandular odontogenic cyst is now a well-known entity comprising < 0.5% of all odontogenic cysts with a recent review tabulating about 200 cases in the English literature. Glandular odontogenic cyst shows epithelial features that simulate salivary gland or glandular differentiation. The importance of glandular odontogenic cyst relates to the fact that it has a high recurrence rate and shares overlapping histologic features with central mucoepidermoid carcinoma. The purpose of this paper is to describe the clinical, radiological, and histopathological features of a case of glandular odontogenic cyst with the course of treatment and 9-years follow-up, followed by a review of the literature. Methods: A 63-year-old male was referred for further investigation of a mandibular radiolucency observed by his general dental practitioner. The main complaint was a murmuring sensation in the lower jaw right side. Radiological examination revealed a well-defined, unilocular, radiolucent lesion, involving the right mandible with 17 and 68 mm in mediolaterally and anteroposterior dimension, respectively. Results: A total enucleation of the cystic lesion and surgical extraction of tooth #46, #47 and #48, was performed under local anaesthesia. Histopathologic examination revealed a glandular odontogenic cyst. Conclusions: Glandular odontogenic cyst shows no pathognomonic clinico-radiographic characteristics, and therefore in many cases it resembles a wide spectrum of lesions. Diagnosis can be extremely difficult due to histopathological similarities with dentigerous cyst, lateral periodontal cyst and central mucoepidermoid carcinoma. Therefore a careful histopathological examination and a long-term follow-up (preferably seven years) are required to rule out recurrences.

Saliva and plasma TIMP-1 in patients with colorectal cancer: a prospective study.

BACKGROUND AND AIMS: A prospective cross-sectional study was designed to test if total levels of TIMP-1 in saliva and plasma correlated with the diagnosis of colorectal cancer (CRC) in a population with symptoms consistent with this disease. MATERIALS AND METHODS: Stimulated whole saliva and blood samples were collected from 161 individuals referred to colonoscopy with symptoms associated with CRC. The results of the examination, as well as previous and/or current other diseases were recorded. In a blinded study, the authors used an in-house TIMP-1 ELISA previously validated for use in saliva and plasma to determine total levels of TIMP-1. RESULTS: Fifty-six of the patients (35%) were diagnosed with CRC. Plasma TIMP-1 levels were significantly elevated in CRC patients compared with patients with other, non-malignant diseases and individuals without disease. Significant differences in saliva TIMP-1 levels between CRC patients and individuals without CRC could not be demonstrated. In addition, no correlation was found between levels of TIMP-1 in plasma and saliva. CONCLUSION: Total levels of TIMP-1 in saliva do not reflect the presence of CRC, and TIMP-1 saliva measurements thus cannot substitute plasma TIMP-1 measurements in detection of CRC.

Reimplantation of cultivated human bone cells from the posterior maxilla for sinus floor augmentation. Histological results from a randomized controlled clinical trial.

OBJECTIVES: The aim of the present randomized clinical study was to evaluate histologically whether the addition of cultivated, autogenous bone cells to a composite graft of deproteinized bovine bone mineral (DBBM) and autogenous bone (AB) for sinus floor augmentation (SFA) enhance bone formation compared with what achieved after SFA with DBBM + AB alone. MATERIAL AND METHODS: Twenty patients with remaining posterior maxillary alveolar crest height of less than 3 mm received SFA after randomization either with an DBBM and AB composite in a 1 : 1 ratio or with DBBM + AB supplemented with autogenous bone cells, which were cultivated from a bone biopsy harvested earlier from the tuberosity area. Four months after SFA, two cylindrical biopsies were taken from the augmented sinuses concomitantly with the implant site preparation by means of a trephine bur. An additional biopsy was taken from the tuberosity area. Bone density at the augmented sinus and the tuberosity area and the height of augmentation were estimated on non-decalcified histological sections prepared from the biopsies. A relative bone density index (RBD) was also calculated by dividing bone density at the augmented sinus with bone density at the tuberosity area. RESULTS: All patients but one could receive two implants after SFA; in one patient, only one implant could be placed. All implants were osseointegrated and could be loaded. Median bone density in the sinus was 30% and 25% in the cell seeded and no-cells added DBBM + AB groups, respectively. Bone augmentation height averaged 6.0 and 5.4 mm and RBD averaged 0.48 and 0.73 in the cell seeded and no-cells added DBBM + AB groups, respectively. None of the differences between groups was statistically significant. CONCLUSIONS: Cultivated autogenous bone cell seeded to a DBBM + AB composite did not significantly improve bone formation (density and height) after SFA, compared with what was achieved with DBBM + AB alone. Both approaches resulted into enough bone to support implant placement and osseointegration.

Peripheral ameloblastic fibro-odontoma or peripheral developing complex odontoma: report of a case.

BACKGROUND. Peripheral (extraosseous) odontogenic tumors are rare. CASE REPORT. This report describes a case which illustrates the clinical and histopathological features of a lesion in an 8-year-old, healthy Caucasian girl that on purely morphological grounds would seem to be an ameloblastic fibro-odontoma, but may represent a case of a peripheral developing complex odontoma. CONCLUSION. Conservative surgical enucleation of the lesion was followed by unbcomplicated healing and no recurrence was seen.

Value of multilevel sectioning of labial salivary gland biopsies in the diagnosis of Sjögren's syndrome.

OBJECTIVES: The objective of this study was to examine the diagnostic value of cutting labial salivary gland (LSG) biopsies at 2 levels in the histological evaluation for Sjögren's syndrome (SS). STUDY DESIGN: This retrospective study included LSG biopsy specimens from 112 consecutive patients evaluated for SS from 2007 to 2019. Three observers, blinded with regard to patient data, independently scored the degree of focal lymphocytic infiltration (foci) and calculated the focus score in specimens cut at 2 levels 60 µm apart. RESULTS: Unblinded analysis revealed that the LSG specimens derived from 107 women and 5 men, aged 49.2 ± 22.3 years. Seventy-six patients had SS (70 primary SS and 6 secondary SS) according to the American-European Consensus Group and American College of Rheumatology/European League Against Rheumatism criteria. The average number of LSGs was 5.0 ± 1.4 and the focus scoring area was 16.1 ± 7.6 mm2. Compared to baseline, the average number of foci (4.4 vs 5.1, P < .001), focus score (1.7 vs 1.9, P = .01), and cases with focus score >1.0 (61 vs 74%; P = .03) were higher in the second level. Subsequently, an additional 11 cases of SS were confirmed (14%), and 8 non-SS cases were reclassified as SS (22%). CONCLUSIONS: Histological assessment of an additional section level improves the diagnostic accuracy of the labial salivary gland biopsy to detect histopathological changes consistent with the diagnosis of SS.

Adjuvant chemotherapy in breast cancer patients induces temporary salivary gland hypofunction.

It is an open question if chemotherapy (CT) per se imposes adverse effects on salivary gland function. The aim of the present study was to investigate effects of CT on salivary function in breast cancer patients during and after adjuvant CT. Forty-five breast cancer patients, eligible for adjuvant CT with CEF or CMF (cyclophosphamide, epirubicin or methotrexate, 5-fluorouracil) were followed before, during, six months and one year after CT. Findings were compared to those in a control group of 31 breast cancer patients not receiving CT. Flow rates and compositions of unstimulated and stimulated whole saliva as well as stimulated parotid saliva (UWS, SWS and SPS) were measured. Feeling of oral dryness and saliva-related complaints were registered. UWS and SWS flow rates decreased during CT (p<0.001 and p<0.01). UWS remained lower six months after, but reached baseline level within one year. SPS flow rate was not significantly affected, suggesting that the decrease in whole saliva production is accounted for by decreased acinar saliva formation by the submandibular glands. Twenty patients (44%) suffered from hyposalivation (UWS < or = 0.1 ml/min and/or SWS < or = 0.5 ml/min) during CT. Xerostomia scores rose during CT and stayed elevated one year after treatment. CT also induced compositional changes by slightly increasing salivary sodium and chloride concentrations as well as decreasing inorganic phosphate concentrations in spite of lower or unchanged flow rates, implying that ductal modification mechanisms are affected. UWS and SWS total protein output and UWS secretory IgA output decreased in response to CT. Thus, the results suggest that acinar and ductal cell functions are affected by adjuvant CT. These adverse drug reactions are temporary, as salivary findings generally returned to baseline values within one year following treatment.

NUT carcinoma presenting in the palate - a case report.

NUT carcinomas (NC) are rare and aggressive tumours characterized by chromosomal rearrangements of the gene encoding for nuclear protein of the testis (NUT) located on chromosome 15q14. This article presents a case of a 60-year-old woman diagnosed with NC presenting as a fast growing primary tumour in the right palate. Further evaluation revealed a tumour mass in the lungs and widespread metastases. A review of the literature did not reveal earlier cases presenting in the palate. In order to improve early diagnosis it is suggested to perform immunohistochemical testing for NUT in all poorly differentiated carcinomas without glandular differentiation arising in the chest, and head and neck (Clin Cancer Res, 18, 2012, 5773).

Diagnostic validity of periapical radiography and CBCT for assessing periapical lesions that persist after endodontic surgery.

OBJECTIVES: Traditionally, healing after surgical endodontic retreatment (SER); i.e. apicectomy with or without a retrograde filling, is assessed in periapical radiographs (PR). Recently, the use of cone beam CT (CBCT) has increased within endodontics. Generally, CBCT detects more periapical lesions than PR, but basic research on the true nature of these lesions is missing. The objective was to assess the diagnostic validity of PR and CBCT for determining inflammation in SER cases that were re-operated (SER-R) due to unsuccessful healing, using histology of the periapical lesion as reference for inflammation. METHODS: Records from 149 patients, receiving SER 2004-10, were screened. In total 108 patients (119 teeth) were recalled for clinical follow-up examination, PR and CBCT, of which 74 patients (83 teeth) participated. Three observers assessed PR and CBCT as "successful healing" or "unsuccessful healing" using Rud and Molven's criteria. SER-R was offered to all non-healed teeth with expected favourable prognosis for subsequent functional retention. During SER-R, biopsy was performed and histopathology verified whether or not inflammation was present. RESULTS: All re-operated cases were assessed non-healed in CBCT while 11 of these were assessed successfully healed in PR. Nineteen biopsies were examined. Histopathologic diagnosis revealed 42% (teeth = 8) without periapical inflammation, 16% (teeth = 3) with mild inflammation and 42% (teeth = 8) with moderate to intense inflammation. A correct diagnosis was obtained in 58% with CBCT (true positives) and 63% with PR (true positives+true negatives). CONCLUSIONS: Of the re-operated teeth, 42% had no periapical inflammatory lesion, and hence no benefit from SER-R. Not all lesions observed in CBCT represented periapical inflammatory lesions.

Serum cytokine profile and clinicopathological findings in oral lichen planus, oral lichenoid lesions and stomatitis.

The objective of this study was to examine if clinical and histopathological variables in patients with oral lichen planus (OLP), oral lichenoid lesions (OLL), and generalized stomatitis display different cytokine profiles and if concomitant contact allergy influences this profile. Forty-nine patients and 29 healthy age- and gender-matched subjects were included. Demographic and clinical data immunohistochemical findings in mucosal specimens, results of contact allergy testing, and serum levels of tumor necrosis factor-α, interferon-γ, interleukin (IL)-6, IL-10, IL-12p40, and IL-12p70 were analyzed and compared between groups. Nineteen patients had OLP, primarily with ulcerative lesions on the buccal mucosa, 19 patients had OLL, and 11 patients had generalized stomatitis. All patients had oral symptoms, mainly stinging and burning. Nineteen patients and 10 healthy subjects had contact allergies, primarily to fragrance ingredients. Patient groups did not differ with regard to oral symptoms, clinical pattern of the lesions, or contact allergy. Serum cytokine levels did not differ between the different patient groups and were not related to histopathological findings. The patients had higher levels of IL-6 than the healthy subjects. Interferon-γ, IL-12p40, and IL-12p70 were below detection limit. Our findings indicate that OLP, OLL, and generalized stomatitis cannot be discriminated by means of the selected serum cytokines, and that the presence of concomitant contact allergy does not influence the cytokine expression.

Elevated p16ink4a Expression in Human Labial Salivary Glands as a Potential Correlate of Cognitive Aging in Late Midlife.

BACKGROUND: The cell-cycle inhibitor and tumor suppressor cyclin dependent kinase inhibitor, p16ink4a, is one of the two gene products of the ink4a/ARF (cdkn2a) locus on chromosome 9q21. Up-regulation of p16ink4a has been linked to cellular senescence, and findings from studies on different mammalian tissues suggest that p16ink4a may be a biomarker of organismal versus chronological age. OBJECTIVE: The aim of this study was to examine the immunolocalization pattern of p16ink4a in human labial salivary gland (LSG) tissue, and to analyze whether its expression level in LSGs is a peripheral correlate of cognitive decline in late midlife. METHODS: The present study was a part of a study of causes and predictors of cognitive decline in middle-aged men in a Danish birth cohort. It is based on data from 181 male participants from the Danish Metropolit birth cohort, born in 1953, who were examined for age-associated alterations in cognition, dental health, and morphological and autonomic innervation characteristics of the LSGs. The participants were allocated to two groups based on the relative change in cognitive performance from young adulthood to late midlife. LSG biopsies were analyzed by qRT-PCR for the expression level of p16ink4a. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections of LSGs. RESULTS: p16ink4a immunoreactivity was observed in LSG ductal, myoepithelial, and stromal cells, but not in acinar cells. The mean relative expression of p16ink4a in LSGs was higher in the group of participants with decline in cognitive performance. A logistic regression analysis revealed that the relative p16 expression was predictive of the participant's group assignment. A negative correlation was found between relative p16ink4a expression and the participant's standardized regression residuals from early adulthood to late midlife cognitive performance scores. CONCLUSIONS: p16ink4a expression in human LSGs may constitute a potential peripheral correlate of cognitive decline. Human labial salivary glands seem suitable for studies on organismal as opposed to chronological age.

Histo-blood group ABO antigen in oral potentially malignant lesions and squamous cell carcinoma--genotypic and phenotypic characterization.

Loss of histo-blood group A/B antigens is frequent in oral cancer. It is unclear whether this alteration is due to loss of the chromosomal region encoding the genes. The aim was to investigate genotypic alterations in the ABO locus in oral potentially malignant lesions and carcinomas. Seventy-three cases which expressed A/B antigen in normal epithelium by immunohistochemical (IHC) staining were investigated. Both tumour and normal cells were collected from paraffin-embedded tissue by laser microdissection. DNA was extracted and analysed by PCR coupled with restricted digestion analysis in order to establish the ABO genotype. Total and patchy loss of A/B antigen expression was found in 24/32 carcinomas, 6/7 leukoplakias with severe dysplasia, 12/17 leukoplakias with mild and moderate dysplasia, and 6/17 leukoplakias without dysplasia. Specific A/B allele loss was found in 8/24 cases with carcinoma and 3/24 cases with mild and moderate dysplasia by genotyping analysis. O allele loss was found in 10 cases involving all four groups. In patients with heterozygous genotypes, A/B allelic loss by genotyping analysis was always followed by loss of A/B antigen expression by IHC staining. Loss of A/B antigen expression in tissues which had intact ABO alleles was, however, found and may be explained by other genetic and epigenetic changes.

Comparison of nonexposed and exposed bisphosphonate-induced osteonecrosis of the jaws: a retrospective analysis from the Copenhagen cohort and a proposal for an updated classification system.

OBJECTIVE: Nonexposed osteonecrosis of the jaws (NE-ONJ) does not fit into the current definition of osteonecrosis, which requires exposed bone. A modification of the classification of bisphosphonate-induced osteonecrosis of the jaws (ONJ) is proposed. This study aimed to test proposed criteria for NE-ONJ and compare NE-ONJ with exposed ONJ (E-ONJ) in a retrospective analysis. STUDY DESIGN: In 102 patients with E-ONJ diagnosed according to Ruggiero et al. (2006, 2009), criteria for NE-ONJ were developed. Subgroups of NE-ONJ and E-ONJ were tested against each other using nonparametric and parametric statistics. RESULTS: Among 102 patients with ONJ, 14 had NE-ONJ and 88 had E-ONJ. NE-ONJ and E-ONJ were similar in all important data (P > .05) except bone exposure. CONCLUSIONS: NE-ONJ belongs to the same disease condition as E-ONJ. NE-ONJ may be otherwise classified as ONJ stage 1, 2, or 3 and is different from ONJ stage 0. We propose to include the criteria for NE-ONJ into the classification.

Associations between xerostomia, histopathological alterations, and autonomic innervation of labial salivary glands in men in late midlife.

OBJECTIVE: One aim of the present study was to investigate whether symptoms of oral dryness (xerostomia) during daytime, assessed in a study group of middle-aged male positive and negative outliers in cognition scores, were associated with age-related degenerative changes in human labial salivary glands and with quantitative measures of the glandular autonomic innervation. Another aim was to study the relation between the autonomic innervation and loss of secretory acinar cells in these glands. METHODS: Labial salivary gland biopsies were taken from the lower lip from 190 men, born in 1953 and members of the Danish Metropolit birth cohort, who were examined for age-related changes in cognitive function and dental health as part of the Copenhagen University Center for Healthy Aging clinical neuroscience project. The glands were routinely processed and semi-quantitatively analyzed for inflammation, acinar atrophy, fibrosis, and adipocyte infiltration. Sections of labial salivary gland tissue were stained with the panneuronal marker PGP 9.5. In a subsample of 51 participants, the autonomic innervation of the glands was analyzed quantitatively by use of stereology. RESULTS: Labial salivary gland tissue samples from 33% of all participants displayed moderate to severe acinar atrophy and fibrosis (31%). Xerostomia was not significantly associated with structural changes of labial salivary glands, but in the subsample it was inversely related to the total nerve length in the glandular connective tissue. Acinar atrophy and fibrosis were negatively correlated with the parenchymal innervation and positively related to diffuse inflammation. CONCLUSIONS: The results from the present study indicate that aspects of the autonomic innervation of labial salivary glands may play a role in the occurrence of xerostomia which in the present study group was not significantly associated with degenerative changes in these glands. The findings further indicate that the integrity of labial salivary gland acini is related to the parenchymal autonomic innervation, whereas inflammatory processes may compromise it by alternative mechanisms.

[Dental materials can cause oral allergic reactions]. / Dentalmaterialer kan udløse orale allergiske reaktioner.

A large number of materials used in the diagnosis, treatment and prevention of dental, periodontal and oral mucosal diseases may induce acute or chronic reactions in the oral cavity including allergic reactions. Clinically, it may be difficult to discriminate oral mucosal changes caused by dental materials from changes related to oral mucosal diseases. Diagnosis and management of allergic reactions in the oral mucosa may therefore be a major challenge. The purpose of this paper is to draw attention to commonly used dental materials, which can trigger typical, but also atypical, symptoms and clinical signs of an allergic reaction.