Safety and Efficacy of Mesenchymal Stem Cells for Radiation-Induced Xerostomia: A Randomized, Placebo-Controlled Phase 1/2 Trial (MESRIX).

BACKGROUND: Salivary gland hypofunction and xerostomia are major complications to head and neck radiotherapy. This trial assessed the safety and efficacy of adipose tissue-derived mesenchymal stem cell (ASC) therapy for radiation-induced xerostomia. PATIENT AND METHODS: This randomized, placebo-controlled phase 1/2 trial included 30 patients, randomized in a 1:1 ratio to receive ultrasound-guided transplantation of ASCs or placebo to the submandibular glands. Patients had previously received radiotherapy for a T1-2, N0-2A, human papillomavirus-positive, oropharyngeal squamous cell carcinoma. The primary outcome was the change in unstimulated whole salivary flow rate, measured before and after the intervention. All assessments were performed one month prior (baseline) and one and four months following ASC or placebo administration. RESULTS: No adverse events were detected. Unstimulated whole salivary flow rates significantly increased in the ASC-arm at one (33%; P = .048) and four months (50%; P = .003), but not in the placebo-arm (P = .6 and P = .8), compared to baseline. The ASC-arm symptom scores significantly decreased on the xerostomia and VAS questionnaires, in the domains of thirst (-22%, P = .035) and difficulties in eating solid foods (-2%, P = .008) after four months compared to baseline. The ASC-arm showed significantly improved salivary gland functions of inorganic element secretion and absorption, at baseline and four months, compared to the placebo-arm. Core-needle biopsies showed increases in serous gland tissue and decreases in adipose and connective tissues in the ASC-arm compared to the placebo-arm (P = .04 and P = .02, respectively). MRIs showed no significant differences between groups in gland size or intensity (P < .05). CONCLUSIONS: ASC therapy for radiation-induced hypofunction and xerostomia was safe and significantly improved salivary gland functions and patient-reported outcomes. These results should encourage further exploratory and confirmatory trials.

First-in-man mesenchymal stem cells for radiation-induced xerostomia (MESRIX): study protocol for a randomized controlled trial.

BACKGROUND: Salivary gland hypofunction and xerostomia are major complications following radiotherapy for head and neck cancer and may lead to debilitating oral disorders and impaired quality of life. Currently, only symptomatic treatment is available. However, mesenchymal stem cell (MSC) therapy has shown promising results in preclinical studies. Objectives are to assess safety and efficacy in a first-in-man trial on adipose-derived MSC therapy (ASC) for radiation-induced xerostomia. METHODS: This is a single-center, phase I/II, randomized, placebo-controlled, double-blinded clinical trial. A total of 30 patients are randomized in a 1:1 ratio to receive ultrasound-guided, administered ASC or placebo to the submandibular glands. The primary outcome is change in unstimulated whole salivary flow rate. The secondary outcomes are safety, efficacy, change in quality of life, qualitative and quantitative measurements of saliva, as well as submandibular gland size, vascularization, fibrosis, and secretory tissue evaluation based on contrast-induced magnetic resonance imaging (MRI) and core-needle samples. The assessments are performed at baseline (1 month prior to treatment) and 1 and 4 months following investigational intervention. DISCUSSION: The trial is the first attempt to evaluate the safety and efficacy of adipose-derived MSCs (ASCs) in patients with radiation-induced xerostomia. The results may provide evidence for the effectiveness of ASC in patients with salivary gland hypofunction and xerostomia and deliver valuable information for the design of subsequent trials. TRIAL REGISTRATION: EudraCT, Identifier: 2014-004349-29. Registered on 1 April 2015. ClinicalTrials.gov, Identifier: NCT02513238 . First received on 2 July 2015. The trial is prospectively registered.

Incidence of sialolithiasis in Denmark: a nationwide population-based register study.

Sialolithiasis is a frequent disorder affecting the salivary glands. The incidence rate (IR) has been reported to be 2.9-5.5 per 100,000 person-years, but all previous studies have been based on selected hospital data. In this study, we conducted a population-based study evaluating the IR of sialolithiasis and the IR variation according to age, gender and geography in Denmark. We included data from hospitals as well as from private ear, nose and throat (ENT) clinics. The study was based on registry data on all sialolithiasis cases in Denmark between 2003 and 2009 extracted from the Danish National Patient Registry (hospital cohort) and the Danish Regions Centre for Healthcare Statistics (private ENT clinic cohort). To validate the diagnosis, the proportion of visually confirmed cases was estimated based on patient records from subsamples of the two cohorts. The IR was 7.27 and 14.10 per 100,000 person-years based on visually confirmed cases only and on all cases, respectively. The highest IR was observed among 60- to 70-year-olds, in the North Denmark region and among females. In the validation subsamples, 35% of assumed sialoliths were visually confirmed in the private ENT clinic cohort and 59% in the hospital cohort. In this first population-based study of IR on sialolithiasis, we found a substantially higher IR. With respect to both visually confirmed cases and all cases, this is higher than previously reported from studies based on selected hospital data.

Comparative analysis of bacterial profiles in unstimulated and stimulated saliva samples.

BACKGROUND AND OBJECTIVE: The microbial profiles of stimulated saliva samples have been shown to differentiate between patients with periodontitis, patients with dental caries, and orally healthy individuals. Saliva was stimulated to allow for easy and rapid collection; however, microbial composition may not reflect the more natural, unstimulated state. The purpose of this study was to validate whether stimulated saliva is an adequate surrogate for unstimulated saliva in determining salivary microbiomes. DESIGN: Unstimulated (n=20) and stimulated (n=20) saliva samples were collected from 20 orally and systemically healthy, non-smoking participants. Salivary bacterial profiles were analyzed by means of the Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS), and statistical analysis was performed using Mann-Whitney test with Benjamini-Hochberg's correction for multiple comparison, cluster analysis, principal component analysis, and correspondence analysis. RESULTS: From a total of 40 saliva samples, 496 probe targets were identified with a mean number of targets per sample of 203 (range: 146-303), and a mean number of probe targets of 206 and 200 in unstimulated and stimulated saliva samples, respectively (p=0.62). Based on all statistical methods used for this study, the microbial profiles of unstimulated and stimulated saliva samples collected from the same person were not statistically significantly different. CONCLUSIONS: Analysis of bacterial salivary profiles in unstimulated and stimulated saliva samples collected from the same individual showed comparable results. Thus, the results verify that stimulated saliva is an adequate surrogate of unstimulated saliva for microbiome-related studies.

Does drinking water influence hospital-admitted sialolithiasis on an epidemiological level in Denmark?

OBJECTIVES: Sialolithiasis, or salivary stones, is not a rare disease of the major salivary glands. However, the aetiology and incidence remain largely unknown. Since sialoliths are comprised mainly of calcium phosphate salts, we hypothesise that drinking water calcium levels and other elements in drinking water could play a role in sialolithiasis. Owing to substantial intermunicipality differences in drinking water composition, Denmark constitutes a unique environment for testing such relations. DESIGN: An epidemiological study based on patient data extracted from the National Patient Registry and drinking water data from the Geological Survey of Denmark and Greenland retrieved as weighted data on all major drinking water constituents for each of the 3364 waterworks in Denmark. All patient cases with International Statistical Classification of Diseases 10th Revision (ICD-10) codes for sialolithiasis registered between the years 2000 and 2010 were included in the study (n=3014) and related to the drinking water composition on a municipality level (n=98). PRIMARY AND SECONDARY OUTCOME MEASURES: Multiple regression analysis using iterative search and testing among all demographic and drinking water variables with sialolithiasis incidence as the outcome in search of possible relations among the variables tested. RESULTS: The nationwide incidence of hospital-admitted sialolithiasis was 5.5 cases per 100,000 citizens per year in Denmark. Strong relations were found between the incidence of sialolithiasis and the drinking water concentration of calcium, magnesium and hydrogen carbonate, however, in separate models (p<0.001). Analyses also confirmed correlations between drinking water calcium and magnesium and their concentration in saliva whereas this was not the case for hydrogen carbonate. CONCLUSIONS: Differences in drinking water calcium and magnesium may play a role in the incidence of sialolithiasis. These findings are of interest because many countries have started large-scale desalination programmes of drinking water.

Root caries, root surface restorations and lifestyle factors in adult Danes.

AIM: To investigate selected lifestyle factors in relation to active caries and restored root surface lesions in adults. MATERIALS AND METHODS: Based on clinical examinations and questionnaires, data on root caries, socioeconomic status, body mass index, dietary habits, alcohol consumption, tobacco use and oral hygiene routines were collected from 4369 adults aged 21-89 who took part in a survey covering 13 municipalities across Denmark. Uni- and multivariate logistic regression analyses were applied to analyse the relationship between the independent lifestyle variables and active caries and restored root surface lesions, respectively. RESULTS: The prevalence of active root caries was 4%, while 26% displayed restored root surfaces. The sugar intake was not related to root caries. A multivariate logistic regression analysis revealed that, in subjects aged 45 or over, smoking and wearing dentures were significantly associated with presence of active root caries (p<0.01). The intake of 15 drinks or more per week was associated with higher odds of root surface restorations compared with no alcohol intake (OR=1.7; p<0.001). CONCLUSIONS: Lifestyle factors such as tobacco use and alcohol consumption, as well as wearing dentures, were significantly associated with the occurrence of untreated caries and restored root surface lesions, especially in persons over 45. Thus, such lifestyle factors should be taken into consideration, identifying persons with a need of preventive dental services. In addition, oral health education should focus on the possible risks of smoking and a high alcohol intake.

Mesenchymal stem cell therapy for salivary gland dysfunction and xerostomia: a systematic review of preclinical studies.

The most severe forms of xerostomia and salivary gland dysfunction, as well as a severely reduced quality of life, are seen in Sjögren syndrome (SS) and after radiotherapy for head and neck cancer. For both conditions, no effective regenerative therapies yet exist. Thus, the aim of this article was to assess, through systematic review, the potential benefit of mesenchymal stem cell (MSC) therapy in radiation-induced and SS-related salivary gland dysfunction and xerostomia. We searched PubMed/MEDLINE, Embase, Web of Science, the Cochrane Database of Systematic Reviews, the World Health Organization Clinical Trials Registry Platform, and Google Scholar. We identified 6 separate study comparisons eligible for inclusion. Owing to the limited number of studies, we conclude that more randomized, adequately powered clinical trials are needed to validate the potential beneficial effect of MSCs on salivary gland dysfunction and xerostomia. Nonetheless, the preliminary studies identified in the present review were encouraging for further research.

Saliva in relation to dental erosion before and after radiotherapy.

OBJECTIVE: Low saliva flow and abnormal saliva composition are common conditions after radiotherapy for oral cavity and pharyngeal cancer. Both conditions increase the susceptibility to dental caries and erosion, which may be further accelerated by changes in food preferences. The aim of this study was to determine changes in saliva flow and susceptibility to erosive challenges in pharyngeal cancer patients before and after radiotherapy to the head and neck. MATERIALS AND METHODS: The erosive potential of sucking acidic candies with and without calcium was determined in nine patients (50-68 years) before and after receiving a radiation dose of 66 Gy to the head and neck area. The erosive potential was evaluated from saliva degree of saturation with respect to hydroxyapatite (HAp) and by dissolution of HAp in candy-stimulated saliva. RESULTS: Sucking acidic candies increased saliva flow rates ≈ 17-fold before as well as after radiotherapy (p < 0.001). However, significantly lower unstimulated (p < 0.05) and stimulated (p < 0.01) saliva flow rates were obtained after radiotherapy. Also, saliva became more under-saturated with respect to HAp during (p < 0.01) and in a period after sucking the candies (p < 0.01). HAp dissolution was significantly lower with the candy containing calcium compared with the control candy, both before and after radiotherapy (p < 0.001 and p < 0.05). CONCLUSIONS: Radiotherapy to the head and neck area significantly reduced saliva flow and altered saliva composition in a way that may increase the susceptibility to dental disease. However, saliva could be stimulated by acidic candies, which could be made nearly non-erosive even in irradiated patients.

Effect of chewing gums containing the probiotic bacterium Lactobacillus reuteri on oral malodour.

OBJECTIVE: To evaluate the effect of chewing gums containing probiotic bacteria on oral malodour. The null hypothesis was that no difference would be displayed compared with placebo gums. MATERIALS AND METHODS: Twenty-five healthy young adults with self-reported malodorous morning breath completed this randomized double-blind placebo-controlled cross-over trial. The design included run-in and wash-out periods interspersed by two intervention periods of 14 days each. The subjects were instructed to chew one gum in the morning and one in the evening containing either two strains of probiotic lactobacilli (L. reuteri DSM 17938 and L. reuteri ATCC PTA 5289) or placebo. The outcome measures were (i) organoleptic scores (0-5) by a certified test panel, (ii) concentration of volatile sulphur compounds (VSC) measured with a Halimeter and (iii) concentration of VSC after a cysteine rinse. Registrations were made at baseline and after each intervention period. Differences between the groups were assessed by non-parametric paired statistics and chi-square test. RESULTS: The median organoleptic score was similar (score 2) in both groups at baseline. After 14 days of treatment, the organoleptic scores were significantly lower in the probiotic group compared with the placebo group (p < 0.05). Assessments of the VSC levels displayed no significant differences between the groups, either before or after rinsing with L-cysteine. No adverse effects were registered. CONCLUSION: The results demonstrated that probiotic chewing gums may have some beneficial effect on oral malodour assessed by organoleptic scores. The results indicate that the probiotic gum may affect bacteria that produce malodourous compounds other than VSCs.

Amount and type of alcohol consumption and missing teeth among community-dwelling older adults: findings from the Copenhagen Oral Health Senior study.

OBJECTIVES: To study if an association between total weekly intake of alcohol, type-specific weekly alcohol intake, alcoholic beverage preference, and the number of teeth among older people exists. METHODS: A cross-sectional study including a total of 783 community-dwelling men and women aged 65-95 years who were interviewed about alcohol drinking habits and underwent a clinical oral and dental examination. Multiple regression analyses were applied for studying the association between total weekly alcohol consumption, beverage-specific alcohol consumption, beverage preference (defined as the highest intake of one beverage type compared with two other types), and the number of remaining teeth (≤ 20 versus >20 remaining teeth). RESULTS: The odds ratio (OR) of having a low number of teeth decreased with the total intake of alcohol in women, with ORs for a low number of teeth of 0.40 [95 percent confidence interval (CI) 0.22-0.76] in women drinking 1-14 drinks per week and 0.34 (95 percent CI 0.16-0.74) in women with an intake of more than 14 drinks per week compared with abstainers. Similar relations could also be obtained for type-specific alcohol intake of wine and for wine and spirits preference among women. Men who preferred beer showed a decreased risk for a low number of teeth compared with men with other alcohol preferences. CONCLUSION: In this study, alcohol consumption, wine drinking, and wine and spirits preference among women were associated with a higher number of teeth compared with abstainers. Among men, those who preferred beer also had a higher number of teeth.

The Copenhagen Oral Health Senior Cohort: design, population and dental health.

BACKGROUND: In order to study the way old age influence oral health, the Copenhagen Oral Health Senior Cohort (COHS) has been established. OBJECTIVES: To describe the design, measurement procedures, and baseline values for COHS including spatial distribution of restorations and dental caries as well as reasons for non-participation. MATERIALS AND METHODS: Seven hundred and eighty-three individuals aged 65 years or older, from a total of 1918 invited elderly people, underwent an interview regarding oral health-related behaviour and a clinical oral examination including measurement of unstimulated whole saliva flow rate. RESULTS: Twelve percent of the COHS was edentulous. The number of dental restorations was higher for women compared to men; however, men had more caries than women. Coronal caries was most frequent on mesial and distal surfaces and on the maxillary incisors and canines; root caries was most frequent on labial surfaces and evenly distributed within the dentition. Only 41% of all invited elderly people accepted the invitation, with old age and poor health being the primary reasons for non-participation. CONCLUSION: The baseline values for COHS show that a substantial proportion of the participants had retained a natural dentition and that dental caries was prevalent with the anterior maxillary teeth being most affected.

MUC1 and the simple mucin-type antigens: Tn and Sialyl-Tn are differently expressed in salivary gland acini and ducts from the submandibular gland, the vestibular folds, and the soft palate.

OBJECTIVE AND DESIGN: Autopsies of the submandibular gland, the vestibular folds and the soft palate from 65-87 old humans were examined to record the immunohistochemical expression of MUC1 and the simple mucin-type antigens Tn and Sialyl-Tn. RESULTS: (1) The serous acini in the submucosal glands from the larynx and the soft palate expressed MUC1-associated glycans that were not detectable in the serous acini from the submandibular gland. (2) Virtually all the submucosal acini at oral site of the soft palate are mucous, and in contrast to mucous acini in the vestibular folds and submandibular gland, the palatinal acini in the submucosa underneath the oral mucosa showed a well-defined cytoplasmic reaction with anti-MUC1 antibodies as wells as with anti-Tn. (3) Both the mucous acini and the ducts at the oral site of the soft palate showed reaction for Sialyl-Tn while in the vestibular folds and in the submandibular gland expression for this carbohydrate was observed only in the acini. (4) The staining obtained after incubation with the Tn antibodies showed no cross localization with the staining obtained after incubation with an anti-A blood group antibody. (5) All the autopsies showed reaction in the glands after incubation with the MUC1 antibodies while some autopsies reacted with the anti-Tn antibodies and/or with the anti-Sialyl-Tn antibodies and others did not. CONCLUSION: The mucin expression in the acini and ducts from the upper human aerodigestive tract strongly depended on the location of the glandular tissue.

Erosive potential of calcium-modified acidic candies in irradiated dry mouth patients.

PURPOSE: Patients who have received irradiation therapy on the head and neck area are known to suffer from reduced saliva flow and may therefore use acidic candies to relieve symptoms of dry mouth. However, such acidic candies have erosive potential even among healthy individuals. Therefore, the aim of the present study was to determine if calcium-modified acidic candies have reduced erosive potential in irradiated cancer patients. MATERIALS AND METHODS: Nineteen cancer patients (26 to 70 years) ipsilaterally irradiated on the head and neck area sucked control and calcium-modified acidic candies, while their whole saliva was collected into a closed system. The erosive potential of both candies was evaluated from saliva degree of saturation with respect to hydroxyapatite and by dissolution of hydroxyapatite (HAp) directly in candy-stimulated saliva. The results were compared to normative data that were previously obtained on 20 healthy test persons (21 to 29 years). RESULTS: No significant difference was obtained in the saliva flow rates between control and calcium-modified candy. However, the saliva became significantly less undersaturated with respect to HAp when sucking calcium-modified compared to control candy (P < 0.001) and more undersaturated for both candies in ipsilaterally irradiated cancer patients compared to normative data (P < 0.001). HAp dissolution was found to be significantly lower in patients sucking the modified candy compared to the control candy (P < 0.01) and, surprisingly, slightly lower in patients compared to normative data. CONCLUSIONS: Modified acidic candy with calcium has reduced erosive potential in patients irradiated on the head and neck area and could therefore be used as a favourable stimulant for relief of dry mouth.

Erosive potential of saliva stimulating tablets with and without fluoride in irradiated head and neck cancer patients.

BACKGROUND: Patients irradiated in the head and neck region often suffer from severe dry mouth and use acidic saliva stimulating products, which may cause erosion of teeth. PURPOSE: To determine saliva stimulating effects and erosive potential (EP) of acidic saliva stimulating tablets (Xerodent) with and without fluoride in irradiated head and neck cancer patients. MATERIALS AND METHOD: Nineteen irradiated patients (median age 57 years) sucked Xerodent tablets with and without fluoride. Saliva collections were divided into three 10-min sessions in the sequence: unstimulated whole saliva, Xerodent stimulated saliva without fluoride, and with fluoride. Saliva pH was determined without loss of CO(2) and in combination with inorganic measures used to calculate the degree of saturation of hydroxyapatite (HAp) and fluorapatite (FAp). EP was determined directly in all saliva samples by monitored dissolution of HAp crystals. RESULTS: Saliva flow rates increased significantly (15-fold) when sucking both tablets (p<0.001). Major changes in saliva composition caused undersaturation of HAp in some samples. However, no dissolution of HAp occurred in the saliva obtained with any of the two tablets. This was most likely due to the limited drop in pH resulting in saliva that was still supersaturated with respect to FAp. CONCLUSION: Both Xerodent with and without fluoride were evaluated as non-erosive, however, for additional caries protection the fluoride variant is preferable.

Surgical risk factors and maxillary nerve function after Le Fort I osteotomy.

PURPOSE: Data on intraoperative risk factors for long-term postoperative complications after Le Fort I osteotomy (LFO) are limited. The aim of this study was to describe prospectively the overall postoperative changes in maxillary nerve function after LFO, and to correlate these changes with a number of possible intraoperative risk factors. PATIENTS AND METHODS: Twelve men and 13 women (mean +/- standard deviation: aged 25+/-10 years) participated in 4 sessions: 1 before LFO (baseline), and the rest at 3, 6, and 12 months after LFO. At each session, somatosensory sensitivity was assessed for the skin, oral mucosa, and teeth, using quantitative sensory tests at either 1 cutaneous point or on a 5 x 5 point matrix reproduced on the skin. In addition, all patients were asked to report their perceived differences in somatosensory sensitivity and their overall satisfaction with the LFO. RESULTS: The thresholds of tactile stimuli on the gingiva and palate were increased 12 months after LFO (P< .001). Significant increases in 2-point discrimination detection thresholds (P< .01) and increased sensitivity to heat (P< .01) and cold (P< .001) in the infraorbital region were also recorded 12 months after LFO. Correspondingly, self-reported complaints of changed sensation under the eyes (P< .01), upper lip (P< .01), gingiva (P< .001), palate (P< .01), and teeth (P< .01) were reported during the entire postoperative period. Intraoperative risk factors were identified and correlated with postoperative changes in somatosensory sensitivity. Segmentation of the maxilla was associated with an increase in tactile thresholds at the palate and gingiva (P< .05), as were self-reported complaints involving the palate and gingiva (P< .001), whereas maxillary impaction was related to lower-tooth pulp pain thresholds when compared with maxillary lowering (P< .01). All patients expressed satisfaction with LFO, despite signs of somatosensory disturbances in up to 64% of patients. CONCLUSION: Numerous changes in postoperative somatosensory function are to be expected after LFO. In most patients, these changes are minor, and some are dependent on intraoperative procedures. Nonetheless, all patients reported satisfaction with the surgical results, and would recommend the procedure to others.

Salivary changes and dental erosion in bulimia nervosa.

OBJECTIVE: Our aim was to study if bulimia nervosa (BN) has an impact on salivary gland function and if such changes are related to dental erosion. STUDY DESIGN: Twenty women with BN and twenty age- and gender-matched controls participated. Flow rate and composition of whole and glandular saliva, as well as feeling of oral dryness were measured. Dental erosion was measured on casts. RESULTS: Compared with control subjects, unstimulated whole saliva (UWS) flow rate was reduced in persons with BN, primarily owing to intake of medication (P = .007). No major compositional salivary changes were found. In the BN group, the dental erosion score was highest and complaints of oral dryness were more frequent. CONCLUSIONS: The BN persons had impaired UWS, mainly owing to medication; increased feeling of oral dryness; and more dental erosion. Dental erosion was related to the duration of eating disorder, whereas no effect of vomiting frequency or intake of acidic drinks on reduced UWS was observed.

Risk factors affecting somatosensory function after sagittal split osteotomy.

PURPOSE: The aim of this study was to evaluate potential individual and intraoperative risk factors associated with bilateral sagittal split osteotomy (BSSO) and to correlate the findings with postoperative changes in somatosensory function. PATIENTS AND METHODS: A total of 18 men and 29 women (mean age, 31 +/- 10 years) scheduled for BSSO participated in 1 session before BSSO and 5 sessions after BSSO (at 2 and 14 days and 3, 6, and 12 months). At each session, subjective oral sensation was scored and quantitative sensory tests were performed. RESULTS: The results showed that complete exposure and free dissection of the inferior alveolar nerve during BSSO increased self-reported changes in lower lip sensation and lower lip tactile threshold after BSSO (P < .01). Long surgical movements reduced self-perceived jaw-opening function and impaired 2-point discrimination (P < .05). Significant correlations were noted between preoperative values for somatosensory function and changes in these variables after BSSO. Patients with low sensory thresholds before BSSO experienced more impairment than those patients with higher preoperative sensory thresholds. CONCLUSION: These findings imply that somatosensory function after BSSO is dependent on both intraoperative risk factors and preoperative sensation levels.

Whole saliva in X-linked hypohidrotic ectodermal dysplasia.

BACKGROUND: X-linked hypohidrotic ectodermal dysplasia (HED) is the most common type of ectodermal dysplasia. Identification of female carriers of X-linked HED can be difficult because of varying degrees of clinical symptoms due to the X-chromosome inactivation. This is the first study about whole saliva flow and composition in males affected by HED and female carriers all confirmed by molecular genetic analysis. HYPOTHESIS AND AIM: As salivary glands derive from ectoderm, we hypothesized that whole saliva flow and composition are altered in males affected by HED and female carriers. DESIGN: Saliva flow and composition were examined in a group of affected males and in a group of female carriers, all confirmed by molecular genetic analysis, and compared with healthy male and female controls. RESULTS: Affected males and female carriers had reduced whole saliva flow and saliva with high concentrations of most inorganic salivary constituents as well as total protein. However, affected males and female carriers seemed to have reduced amylase activity and concentration relative to their total protein concentration. CONCLUSION: Saliva flow and composition may be used as part of a comprehensive clinical examination to identify potential female carriers of HED.

Anomalies of tooth formation in hypohidrotic ectodermal dysplasia.

OBJECTIVE: The X-linked hypohidrotic ectodermal dysplasia (HED) is the most common type of ectodermal dysplasia. The clinical identification of possible heterozygous females can be difficult because of the varying degrees of clinical signs caused by X-chromosome inactivation. This study is the first to elaborate on anomalies of tooth formation found in a group of hemizygous males and heterozygous females with known ED1 mutations. These tooth anomalies may be used as dental biomarkers for heterozygous females, enabling an earlier diagnosis, and therefore, better treatment and genetic counselling. METHODS: Anomalies of tooth formation were examined using panoramic radiographs, dental casts and oral photographs in hemizygous males and heterozygous females who were identified by molecular genetic analysis. The results were compared to existing controls and normative data. RESULTS: All affected males had multiple missing permanent teeth and tooth malformations. The heterozygous females had a significantly higher frequency of agenesis of permanent teeth compared to normative data. The heterozygous females had an increased prevalence of tooth malformations and reduced tooth size, especially in the mesiodistal dimension. CONCLUSIONS: We conclude that observed anomalies of tooth formation may be used as dental biomarkers in the clinical identification of potentially heterozygous females.

Treatment of gustatory sweating with low-dose botulinum toxin A: a case report.

UNLABELLED: Frey's syndrome, gustatory sweating in the preauricular area, is an unpleasant phenomenon occurring during meals after surgery on the parotid gland. Recently, botulinum toxin A (BTX) has been shown to reduce the symptoms, but the variation in the reported doses is large. OBJECTIVE: To quantify the effect of treatment with low-dose BTX in a case of Frey's syndrome over a period of 6 months. MATERIAL AND METHODS: A 56-year-old woman was treated with 10 U Botox given as 20 single, intracutaneous injections of 0.5 U, one for each cm(2), 3 years after resection of the parotid gland. Before treatment and repeatedly during the 6-month period, the sweating was rated subjectively on a 100-mm visual analog scale (VAS) and by a severity index, and objectively by assessment of the extent of the involved skin area using Minor's iodine-starch test, staining the area of sweating dark. RESULTS: The treatment decreased the involved area from 20 to 5 cm(2) and the VAS ratings from 98 to 8 mm. The index showed that treatment affected the sweating intensity, not the frequency. After the 6-month period the patient was still satisfied, but the involved skin area had increased; however, not entirely to pretreatment values. CONCLUSIONS: The effect of BTX injections for gustatory sweating obtained in this case was comparable to results reported using higher doses. Low doses of BTX can therefore be used in the treatment of Frey's syndrome, but studies to clarify the dose-response relationship, in terms of both time-course and obtained effect, are needed.